MX2008009528A

MX2008009528A - Ligands that bind il-4 and/or il-13

Info

Publication number: MX2008009528A
Application number: MXMX/A/2008/009528A
Authority: MX
Inventors: Holmes Steve; M Tomlinson Ian; Sepp Armin; D Drew Philip; M T De Wildt Rudolf; Pupecka Malgorzata; Allart Stoop Adriaan; De Silva Inusha; J Dimech Caroline
Original assignee: De Silva Inusha; M T De Wildt Rudolf; J Dimech Caroline; Domantis Limited; D Drew Philip; Holmes Steve; Pupecka Malgorzata; Sepp Armin; Stoop Adrian Allart; Tomlinson Ian
Priority date: 2006-01-24
Filing date: 2008-07-24
Publication date: 2008-10-03

Abstract

Disclosed are ligands that have binding specificity for interleukin-4 (IL-4), for interleukin-13 (IL-13), or for IL-4 and IL-13. Also disclosed are methods of using these ligands. In particular, the use of these ligands for treating allergic asthma is described.

Description

LIGAN TWO THAT LINK IL-4 AND / OR IL-13 Related Request The present application claims the benefit of US Provisional Application No. 60 / 761,708, filed January 24, 2006. The total teachings of the aforementioned application are incorporated herein by reference. Background of the Invention Interleukin-4 (IL-4) is a pleiotropic cytokine that has a broad spectrum of biological effects on B cells and T cells and many non-lymphoid cells including monocytes, endothelial cells and fibroblasts. For example, IL-4 stimulates the proliferation of various cell lines dependent on IL-2-and IL-3, induces the expression of higher class II histocompatibility complex molecules in resting B cells, and increases the secretion of IgG4 and I g E using human B cells. IL-4 is associated with a Th2-type immune response and is produced through and promotes the differentiation of Th2 cells. IL-4 has been implicated in a number of disorders, such as allergy and asthma. Interleukin-13 (IL-13) is a pleiotropic cytokine that induces the immunoglobulin isotype that alternates to IgG4 and IgE, CD23 activation, VCAM-1 expression and directly activates eosinophils and mast cells, for example. IL- 13 it is produced mainly through Th2 cells and inhibits the production of inflammatory cytokines (IL-1, IL-6, TNF, IL-8) by monocytes stimulated with LPS. IL-13 is closely related to IL-4 with which it shares 20 to 25% sequence similarity at the amino acid level. (Minty and associates, Nature, 363 (6417): 248-50 (1993)). Although many activities of IL-13 are similar to those of IL-4, IL-13 does not have growth promotion effects on activated T cells or T cell clones as IL-4 does. (Zurawski and associates, EMBO J. 12: 2663 (1993)). Cell surface receptors and receptor complexes bind to IL-4 and / or IL-13 with different affinities. The major components of the receptor and receptor complexes that bind to IL-4 and / or IL-13 are IL-4Ra, IL-13Ra1 and IL-13Ra2. These chains are expressed on the surface of cells as monomers or heterodimers of IL-4Ra / IL-13Ra1 or IL-4Ra / IL-13Ra2. The monomer IL-4ra binds to IL-4, but not to IL-13. The monomers IL-13Ra1 and IL-13Ra2 bind to IL-13, but do not bind to IL-4. The IL-4Ra / IL-13R a1 and IL-4Ra / IL-13Ra2 heterodimers bind both IL-4 and IL-13. Th2 immune responses, promote the production of antibodies and humoral immunity, and are developed to combat extracellular pathogens. Th2 cells are transmitters of production (humoral immunity) and produce IL-4, IL-5, IL-6, IL-9, IL-10 and IL-13 (Tanaka, and associates, Cytokine Regulation of Humoral Immunity, 251-272, Snapper, ed., John Wiley and Sons, New York (1996)). Th2 type immune responses are characterized by the generation of certain cytokines (eg, IL-4, IL-13) and specific types of antibodies (I g E, lgG4) and are typical of allergic reactions, which can result in symptoms of watery eyes and asthmatic symptoms, such as inflammation of the airways and contraction of airway muscle cells found in the lungs. Both IL-4 and IL-13 are therapeutically important proteins based on their biological functions. IL-4 has been shown to have the ability to inhibit autoimmune diseases and IL-4 and IL-13 have both shown the potential to improve anti-tumor immune responses. Since both cytokines are involved in pathogenesis and allergic diseases, inhibitors of these cytokines may provide therapeutic benefits. However, inhibiting only IL-4 or IL-13 using conventional agents may not provide the desired therapeutic results because many of the activities and functions of these cytokines are similar. Accordingly, there is a need for improved agents that inhibit IL-4, inhibit IL-13, and simple agents that inhibit both IL-4 and IL-13. Brief Description of the Invention The present invention relates to ligands that have binding specificity for IL-4 (e.g., human IL-4), ligands that have binding specificity for IL-13 (e.g., human IL-3), and to ligands that have binding specificity for IL-4 and IL -13 (e.g., human IL-4 and human IL-3). For example, the ligands may comprise a polypeptide domain having a binding site with binding specificity for IL-4, a polypeptide domain that has a binding site with binding specificity for IL-13, or comprises a binding domain. polypeptide having a binding site with binding specificity for IL-4 and a polypeptide domain having a binding site with binding specificity for IL-13. In one aspect, the present invention relates to a ligand that has binding specificity for IL-4 or for IL-13. Said ligands comprise a portion of protein having a binding site with binding specificity for IL-4 and a portion of protein having a binding site with binding specificity for IL-13. The portion of the protein having a binding site with binding specificity for IL-4 and the protein portion having a binding site with binding specificity for IL-13 can be any suitable binding moiety. The protein portions can be a peptide portion, polypeptide portion or protein portion. For example, portions of protein can be provided through an antibody fragment that it has a binding site with binding specificity for IL-4 or IL-13, such as a single immunoglobulin variable domain that has binding specificity for IL-4 or IL-13. The ligand may comprise a portion of a protein having a binding site with binding specificity for IL-4 competing to bind IL-4 with IL-4Ra, an IL-4 binding portion of IL-4Ra or an antibody of anti-IL-4 domain (dAb). In some embodiments, a ligand comprises a portion of a protein that has a binding site with binding specificity for IL-4 (eg, a single immunoglobulin variable domain) that competes to bind IL-4 with an anti-IL dAb. -4 selected from the group consisting of the anti-IL-4 dAbs described in the present invention (e.g., DOM9-15 (SEQ ID NO.175), DOM9-17 (SEQ ID NO: 176), DOM9-23 ( SEQ ID NO: 177), DOM9-24 (SEQ ID NO: 178), DOM9-25 (SEQ ID NO-179), DOM9-27 (SEQ ID NO: 180), DOM9-28 (SEQ ID NO: 181) , DOM9-29 (SEQ ID NO: 182), DOM9-30 (SEQ ID NO: 183), DOM9-31 (SEQ ID NO: 184), DOM9-32 (SEQ ID NO: 185), DOM9-33 (SEQ ID NO: 186), DOM9-50 (SEQ ID NO: 187), DOM9-57 (SEQ ID NO: 188), DOM9-59 (SEQ ID NO: 189), DOM9-63 (SEQ ID NO: 190), DOM9-67 (SEQ ID NO: 191), DOM9-68 (SEQ ID NO: 192), DOM9-70 (SEQ ID NO: 193), DOM9-79 (SEQ ID NO: 194), DOM9-82 (SEQ ID NO: 195), DOM9-86 (SEQ ID NO: 196), DOM9-94 (SEQ ID NO: 197), DOM9-108 (SEQ ID NO: 198), DOM9-112 (SEQ ID NO: 199), DOM9-112-1 (SEQ ID NO: 200), DOM9-112-2 (SEQ ID NO: 201), DOM9-112-3 (SEQ ID NO: 202), DOM9-112-4 (SEQ ID NO: 203) ), DOM9-112-5 (SEQ ID NO: 204), DOM9-112-6 (SEQ ID NO: 205), DOM9-132-7 (SEQ ID NO: 206), DOM9-112-8 (SEQ ID NO. : 207). DOM9-112-9 (SEQ ID NO: 208), DOM9-112-10 (SEQ ID NO: 209), DOM9-112-11 (SEQ ID NO: 210), DOM9-112-12 (SEQ ID N0: 211) ), DOM9-112-13 (SEQ ID NO: 212), DOM9-112-14 (SEQ ID NO: 213), DOM9-112-15 (SEQ ID NO: 214), DOM9-112-16 (SEQ ID NO. : 215), DOM9-112-17 (SEQ ID NO: 216), DOM9-112-18 (SEQ ID NO: 217), DOM9-312-19 (SEQ ID NO: 218), DOM9-112-20 (SEQ ID NO: 219), DOM9-112-21 (SEQ ID NO: 220), DOM9-112-22 (SEQ ID NO: 221), DOM9-112-23 (SEQ ID NO: 222), DOM9-112-25 (SEQ ID NO: 223), DOM9-112-81 (SEQ ID NO: 224), DOM9-112-82 (SEQ ID NO: 225), DOM9-112-83 (SEQ ID NO: 226), DOM9-112 -84 (SEQ ID NO: 227), DOM9-112-85 (SEQ ID NO: 228). DOM9-112-86 (SEQ ID NO: 229), DOM9-112-87 (SEQ ID NO: 230), DOM9-112-88 (SEQ ID NO: 231), DOM9-112-89 (SEQ ID NO: 232) ), DOM9-112-90 (SEQ ID NO: 233), DOM9-112-91 (SEQ ID NO: 234), DOM9-112-92 (SEQ ID ??: 235), DOM9-112-93 (SEQ ID NO: 236), DOM9-112-94 (SEQ ID NO: 237), DOM9-112-95 (SEQ ID NO: 238), DOM9-112-96 (SEQ ID NO: 239), DOM9- 112-97 ( SEQ ID NO: 240), DOM9-112-98 (SEQ ID NO: 241), DOM9-112-99 (SEQ ID NO: 242), DOM9-112-100 (SEQ ID NO: 243), DOM9-112- 101 (SEQ ID NO: 244), DOM9-112-102 (SEQ ID NO: 245), DOM9-112-103 (SEQ ID NO: 246), DOM9-112-104 (SEQ ID N0.247), DOM9-112-105 (SEQ ID NO: 248), DOM9-112-106 (SEQ ID NO: 249), DOM9-112-107 (SEQ ID NO-.250), DOM9-112-108 (SEQ ID NO: 251), DOM9-112-109 (SEQ ID NO: 252), DOM9-112-110 (SEQ ID NO: 253), DOM9- 112-111 (SEQ ID NO: 254), DOM9-112-112 (SEQ ID NO: 255), DOM9-112-113 (SEQ ID NO: 256), DOM9-112-114 (SEQ ID NO: 257), DOM9-112-115 (SEQ ID NO: 258), DOM9-112-116 (SEQ ID NO: 259), DOM9-112-117 (SEQ ID NO: 260), DOM9-112-118 (SEQ ID NO: 261) ), DOM9-112-119 (SEQ ID NO: 262), DOM9-112-120 (SEQ ID NO: 263), DOM9-112-121 (SEQ ID NO: 264), DOM9-112-122 (SEQ ID NO. : 265), DOM9-112-123 (SEQ ID NO: 266), DOM9-112-124 (SEQ ID NO: 267), DOM9-112-125 (SEQ ID NO: 268), DOM9-112-126 (SEQ ID NO: 269), DOM9-112-127 (SEQ ID NO: 270), DOM9-112-128 (SEQ ID NO: 271), DOM9-112-134 (SEQ ID NO: 272), DOM9-112-135 (SEQ ID NO: 273), DOM9-112-136 (SEQ ID NO: 274), DOM9-112-137 (SEQ ID NO: 275), DOM9-112-138 (SEQ ID NO: 276), DOM9-112 -140 (SEQ ID NO: 277), DOM9-112-141 (SEQ ID NO: 278), DOM9-112-142 (SEQ ID NO. : 279), DOM9-112-143 (SEQ ID NO: 280), DOM9-112-144 (SEQ ID NO: 281), DOM9-112-145 (SEQ ID NO: 282), DOM9-112-146 (SEQ ID NO: 283), DOM9-112-147 (SEQ ID NO: 284), DOM9-112-348 (SEQ ID NO: 285), DOM9-112-149 (SEQ ID NO: 286), DOM9-112-150 (SEQ ID NO: 287), DOM9-112-151 (SEQ ID NO: 288), DOM9-112-152 (SEQ ID NO: 289), DOM9-112-153 (SEQ ID NO: 290), DOM9-112 -154 (SEQ ID NO: 291), DOM9-112-155 (SEQ ID NO: 292), DOM9-112-156 (SEQ ID NO: 293), DOM9-112-157 (SEQ ID NO: 294), DOM9-112-158 (SEQ ID NO: 295), D0M9-112 -159 (SEQ ID NO.296), DOM9-U2-160 (SEQ ID NO: 297), DOM9-112-161 (SEQ ID NO: 298), DOM9-112-162 (SEQ ID NO: 299), DOM9 -112-163 (SEQ ID NO: 300), DOM9-112-164 (SEQ ID NO: 301), DOM9-112-165 (SEQ ID NO: 302), DOM9-112-166 (SEQ ID NO: 303) , DO 9-112-167 (SEQ ID NO: 304), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-169 (SEQ ID NO: 306), DOM9-112-170 (SEQ ID NO. : 307), DOM9-112-171 (SEQ ID NO: 308), DOM9-112-172 (SEQ ID NO: 309), DOM9-112-173 (SEQ ID NO: 310), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-175 (SEQ ID NO: 312), DOM9-112-76 (SEQ ID NO.313), DOM9-112-177 (SEQ ID NO: 314), DOM9-112-178 (SEQ ID NO: 315), DOM9-112-179 (SEQ ID NO: 316), DOM9-112-180 (SEQ ID NO: 317), DOM9-112-181 (SEQ ID NO: 318), DOM9-112 -182 (SEQ ID NO: 319), DOM9-112-183 (SEQ ID NO: 320), DOM9-112-184 (SEQ ID NO: 321), DOM9-112-185 (SEQ ID NO.322), DOM9 -112-186 (SEQ ID NO: 323), DOM9-112-187 (SEQ ID NO: 324), DOM9-112-188 (SEQ ID N O: 325), DOM9-112-189 (SEQ ID NO: 326), DOM9-112-190 (SEQ ID NO: 327), DOM9-12-191 (SEQ ID NO: 328), DOM9-112-192 ( SEQ ID NO: 329), DOM9-112-193 (SEQ ID NO: 330), DOM9-112-194 (SEQ ID NO: 331), DOM9-112-195 (SEQ ID NO.-332), DOM9-112 -196 (SEQ ID NO: 333), DOM9-112-197 (SEQ ID NO: 334), DOM9-112-398 (SEQ ID NO: 335), DOM9-112-199 (SEQ ID NO: 336), DOM9 -112-200 (SEQ ID NO: 337), DOM9-112- 201 (SEQ ID NO: 338), DOM9-112-202 (SEQ ID NO: 339), DOM9-120 (SEQ ID NO: 340), DOM9-121 (SEQ ID NO: 341), DOM9-122 (SEQ ID NO: 342), DOM9-123 (SEQ ID NO: 343), DOM9-124 (SEQ ID NO: 344), DOM9-125 (SEQ ID NO: 345), DOM9-128 (SEQ ID NO.346), DOM9 - 134 (SEQ ID NO: 347), DOM9-136 (SEQ ID NO: 348) D0M9 -26 (SEQ ID NO: 500), DOM9 -35 (SEQ ID NO: 501) D0M9 -36 (SEQ ID NO: 502 ), DOM9 -37 (SEQ ID NO: 503) DOM9 -38 (SEQ ID NO: 504), DOM9 -39 (SEQ ID NO: 505) DOM9 -40 (SEQ ID NO: 506), OD 9-41 (SEQ ID NO: 507) DOM9 -43 (SEQ ID NO: 508), DOM9 -44 (SEQ ID NO: 509), DOM9-44-500 (SEQ ID NO: 510), DOM9-44-501 (SEQ ID NO: 511), DOM9-44-502 (SEQ ID NO: 512), DOM9-44-503 ( SEQ ID NO: 513), DOM9-44-504 (SEQ ID NO: 514), DOM9-44-505 (SEQ ID NO: 515), DOM9-44-506 (SEQ ID NO: 516), DOM9-44- 507 (SEQ ID NO: 537), DOM9-44-509 (SEQ ID NO: 518), DOM9-44-510 (SEQ ID NO: 519), DOM9-44-511 (SEQ ID NO: 520), DOM9- 44-512 (SEQ ID NO.521), DOM9-44-513 (SEQ ID NO.522), DOM9-44-514 (SEQ ID NO.523), DOM9-44-5 5 (SEQ ID NO: 524), DOM9-44-516 (SEQ ID NO: 525), DOM9-44-517 (SEQ ID NO: 526), DOM9-44-518 (SEQ ID NO: 527), DOM9-44-519 (SEQ ID NO: 528) ), DOM9-44-520 (SEQ ID NO: 529), DOM9-44-521 (SEQ ID NO: 530), DOM9-44-522 (SEQ ID NO: 531), DOM9-44-523 (SEQ ID NO. : 532), DOM9-44-524 (SEQ ID NO: 533), DOM9-44-525 (SEQ ID NO: 534), DOM9-44-526 (SEQ ID NO: 535), DOM9-44-527 (SEQ ID NO: 536), DOM9-44-528 (SEQ ID NO: 537), DOM9-44-529 (SEQ ID NO: 538), D0M9-44-530 (SEQ ID N0: 539), DOM9-44-531 (SEQ ID NO: 540), DOM9-44 -532 (SEQ ID NO: 541), DOM9-44-533 (SEQ ID N0: 542), D0M9-44-534 (SEQ ID N0: 543), DOM9-44-535 (SEQ ID N0: 544), D0M9 -44-536 (SEQ ID NO: 545), DOM9-44-537 (SEQ ID NO: 546), D0M9-44-538 (SEQ ID NO: 547), DOM9-44-539 (SEQ ID NO: 548) , DOM9-44-540 (SEQ ID NO: 549), DOM9-44-541 (SEQ ID NO.550), DOM9-44-542 (SEQ ID NO: 551), DOM9-44-543 (SEQ ID NO: 552), DOM9-44-544 (SEQ ID NO: 553), DOM9-44-545 (SEQ ID NO: 554), DOM9-44-546 (SEQ ID NO: 555), DOM9-44-547 (SEQ ID NO: 556), DOM9-44-548 (SEQ ID NO: 557), DOM9-44-549 (SEQ ID NO: 558), DOM9-44-550 (SEQ ID NO: 559), DOM9-44-551 ( SEQ ID NO: 560), DOM9-44-552 (SEQ ID NO: 561), DOM9-44-553 (SEQ ID NO: 562), DOM9-44-554 (SEQ ID NO: 563), DOM9-44- 555 (SEQ ID NO: 564), DOM9-44-556 (SEQ ID NO: 565), DOM9-44-557 (SEQ ID NO: 566), DOM9-44-558 (SEQ ID NO: 567), DOM9- 44-559 (SEQ ID NO: 568), DOM9-44-560 (SEQ ID NO: 569), DOM9-44-561 (SEQ ID NO: 570), DOM9-44-562 (SEQ ID NO: 571) ), DOM9-44-563 (SEQ ID NO: 572), DOM9-44-564 (SEQ ID NO: 573), DOM9-44-565 (SEQ ID NO: 574), DOM9-44-566 (SEQ ID NO. : 575), DOM9-44-625 (SEQ ID NO: 576); DOM9-44-626 (SEQ ID NO: 577), DOM9-44-627 (SEQ ID NO: 578), DOM9-44-628 (SEQ ID NO: 579), DOM9-44-629 (SEQ ID NO: 580) ), DOM9-44-630 (SEQ ID NO: 581), DOM9-44-63I (SEQ ID NO: 582), DOM9-44-632 (SEQ ID NO: 583), DOM9-44-633 (SEQ ID NO: 584), DOM9-44-634 (SEQ ID NO: 585), DOM9-44-636 (SEQ ID NO: 586), D0M9-44 -637 (SEQ ID NO: 587), DOM9-44-639 (SEQ ID NO: 588), DOM9-44-640 (SEQ ID NO: 589), DOM9-44-641 (SEQ ID NO: 590), DOM9 -44-642 (SEQ ID NO: 591), DOM9-44-643 (SEQ ID NO: 592), DOM9-44-644 (SEQ ID NO: 593), DOM9-45 (SEQ ID NO: 594), DOM9 -46 (SEQ ID NO: 595), DOM9-47 (SEQ ID NO: 596), DOM9-48 (SEQ ID NO: 597), DOM9-143 (SEQ ID NO: 598), DOM9-144 (SEQ ID NO : 599), DOM9-146 (SEQ ID NO: 600), DOM9-152 (SEQ ID NO; 601), DOM9-155 (SEQ ID NO: 602), DOM9-155-001 (SEQ ID NO.603), DOM9-155-3 (SEQ ID NO: 604), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-8 (SEQ ID NO: 606), DOM9-155-9 (SEQ ID NO: 607) ), DOM9-155-11 (SEQ ID NO: 608), DOM9-155-I3 (SEQ ID NO: 609), DOM9-155-14 (SEQ ID NO: 610), DOM9-155-17 (SEQ ID N0) : 611), DOM9-155-19 (SEQ ID NO: 612), DOM9-155-20 (SEQ ID NO: 613), DOM9-155-22 (SEQ ID NO: 614), DOM9-155-23 (SEQ ID NO: 615), DOM9-155-24 (SEQ ID NO: 616), DOM9-155-25 (SEQ ID NO: 617), DOM9-155-26 (SEQ ID NO: 61 8), DOM9-155-27 (SEQ ID NO; 619), DOM9-155-28 (SEQ ID NO: 620), DOM9-155-29 (SEQ ID NO: 621), DOM9-155-30 (SEQ ID NO: 622), DOM9-155-31 (SEQ ID NO: 623), DOM9-155-32 (SEQ ID NO: 624), DOM9-155-33 (SEQ ID NO: 625), DOM9-155-34 ( SEQ ID NO: 626), DOM9-155-35 (SEQ ID NO: 627), DOM9-155-36 (SEQ ID NO: 625), DOM9-155-37 (SEQ ID NO: 629), DOM9-155- 38 (SEQ ID NO: Ó30), D0M9-155-39 (SEQ ID NO: 631), DOM9-155-41 (SEQ ID NO: 632), DOM9-155-42 (SEQ ID NO: 633), DOM9-155-43 (SEQ ID NO: 634), DOM9-155-44 (SEQ ID NO: 635), DOM9-155-45 (SEQ ID NO: 636), DOM9-155-46 (SEQ ID NO.637), DOM9-155 -47 (SEQ ID NO.638), DOM9-155-48 (SEQ ID NO: 639), DOM9-155-49 (SEQ ID NO: 640), DOM9-155-50 (SEQ ID NO: 641); DOM9-155-51 (SEQ ID NO: 642), DOM9-155-52 (SEQ ID NO: 643), DOM9-155-53 (SEQ ID NO: 644), DOM9-158 (SEQ ID NO: 645), DOM9-160 (SEQ ID NO: 646), DOM9-161 (SEQ ID NO: 647), DOM9-162 (SEQ ID NO: 648), DOM9-163 (SEQ ID NO: 649) and DOM9-164 (SEQ ID NO: 650)). In additional embodiments, a ligand comprises a portion of a protein that has a binding site with binding specificity for IL-4 (eg, a single immunoglobulin variable domain) that competes to bind IL-4 with an anti-IL dAb. -4 selected from the group consisting of DOM9-15 (SEQ ID NO: 175), DOM9-17 (SEQ ID NO: 176), DOM9-23 (SEQ ID NO: 177), DOM9-24 (SEQ ID NO: 178) ), DOM9-25 (SEQ ID NO: 179), DOM9-27 (SEQ ID NO: 180), DOM9-28 (SEQ ID NO: 181), DOM9-29 (SEQ ID NO: 182), DOM9-30 ( SEQ ID NO: 183), DOM9-31 (SEQ ID NO: 184), DOM9-32 (SEQ ID NO: 185), DOM9-33 (SEQ ID NO: 186), DOM9-50 (SEQ ID NO: 187) , DOM9-57 (SEQ ID NO: 188), DOM9-59 (SEQ ID NO: 189), DOM9-63 (SEQ ID NO: 190), DOM9-67 (SEQ ID NO: 191), DOM9-68 (SEQ ID NO: 192), DOM9-70 (SEQ ID NO: 193), DOM9-79 (SEQ ID NO: 194), DOM9-82 (SEQ ID NO: 195), DOM9-86 (SEQ ID N0: 196), DOM9-94 (SEQ ID NO: 197), DOM9-108 (SEQ ID NO: 198), DOM9-112 (SEQ ID NO: 199), DOM9-112-1 (SEQ ID NO: 200), DOM9-112-2 (SEQ ID NO: 201), DOM9- 112-3 (SEQ ID NO: 202), DOM9-112-4 (SEQ ID NO: 203), DOM9-112-5 (SEQ ID NO: 204), DOM9-112-6 (SEQ ID NO: 205), DOM9-112-7 (SEQ ID NO.206), DOM9-112-8 (SEQ ID NO: 207), DOM9-112-9 (SEQ ID NO: 208), DOM9-112-10 (SEQ ID NO: 209) ), DOM9-112-11 (SEQ ID NO: 210), DOM9-112-12 (SEQ ID NO: 211), DOM9-112-13 (SEQ ID NO: 212), DOM9-112-14 (SEQ ID NO. : 213), DOM9-112-15 (SEQ ID NO: 214), DOM9-112-16 (SEQ ID NO: 215), DOM9-112-17 (SEQ ID NO: 216), DOM9-112-18 (SEQ ID NO: 217), DOM9-112-19 (SEQ ID NO: 218), DOM9-112-20 (SEQ ID NO: 219), DOM9-112-21 (SEQ ID NO: 220), DOM9-112-22 (SEQ ID NO: 221), DOM9-112-23 (SEQ ID NO: 222), DOM9-112-25 (SEQ ID NO: 223), DOM9-112-81 (SEQ ID NO: 224), DOM9-112 -82 (SEQ ID NO: 225), DOM9-112-83 (SEQ ID NO: 226), DOM9-112-84 (SEQ ID NO: 227), DOM9-112-85 (SEQ ID NO: 228), DOM9 - 112-86 (SEQ ID NO: 229), DOM9-112-87 (SEQ ID NO: 230), DO 9-112-88 (SEQ ID NO: 231), DOM9-112-89 (SEQ ID NO: 232) , DOM9-112-90 (SEQ ID NO: 233), DOM9-112-91 (SEQ ID NO: 234), DOM9-112-92 (SEQ ID NO: 235), DOM9-312-93 (SEQ ID NO: 236), DOM9-112-94 (SEQ ID NO: 237), DOM9-112-95 (SEQ ID NO: 238), DOM9-112-96 (SEQ ID NO: 239), DOM9-112-97 (SEQ ID NO: 240), DOM9-112-98 (SEQ ID NO: 241), DOM9-112-99 (SEQ ID NO: 242), DOM9-112-100 (SEQ ID NO: 243), DOM9-112-101 (SEQ ID NO: 244) ), D0M9-1132-102 (SEQ ID NO: 245), DOM9-112-103 (SEQ ID NO: 246), DOM9-312-104 (SEQ ID NO: 247), DOM9-112-105 (SEQ ID NO. : 248), DOM9-312-106 (SEQ ID NO: 249), DOM9-112-107 (SEQ ID NO: 250), DOM9-112-108 (SEQ ID NO: 251), DOM9-112-109 (SEQ ID NO: 252), DOM9-112-110 (SEQ ID NO: 253), DOM9-112-111 (SEQ ID NO: 254), DOM9-112-112 (SEQ ID NO: 255), DOM9-112-113 (SEQ ID NO: 256), DOM9-112-1 14 (SEQ ID NO: 257), DOM9-112-115 (SEQ ID NO: 258), DOM9-112-116 (SEQ ID NO: 259), DOM9- 112-117 (SEQ ID NO: 260), DOM9-112-118 (SEQ ID NO: 261), DOM9412-119 (SEQ ID NO.262), DOM9-112420 (SEQ ID NO: 263), DOM9-112- 121 (SEQ ID NO: 264), DOM9-112-122 (SEQ ID N0.265), DOM9-112-123 (SEQ ID NO: 266), DOM9-112-124 (SEQ ID NO: 267), DOM9- 112-125 (SEQ ID NO: 268), DOM9-332-126 (SEQ ID NO: 269), DOM9-112-127 (SEQ ID NO: 270), DOM9-112-128 (SEQ ID NO: 271), DOM9-112-134 (SEQ ID NO: 272), DOM9-112-135 (SEQ ID NO.273), DOM9-112- 136 (SEQ ID NO: 274), DOM9-112-137 (SEQ ID NO.275), DOM9-112-138 (SEQ ID NO: 276), DOM9-112-140 (SEQ ID NO: 277), DOM9- 112-141 (SEQ ID NO: 278), DOM9-112-142 (SEQ ID NO: 279), DOM9-112-143 (SEQ ID NO: 280), DOM9-112-144 (SEQ ID NO: 281), DOM9-112-145 (SEQ ID NO: 282), DOM9-112-146 (SEQ ID NO: 283), DOM9-112-147 (SEQ ID NO: 284), DOM9-112-148 (SEQ ID NO: 285) ), DOM9-112-149 (SEQ ID NO: 286), DOM9-112-150 (SEQ ID NO: 287), DOM9-112-151 (SEQ ID NO: 288), DOM9-112-152 (SEQ ID NO: 289), DOM9-112-153 ( SEQ ID NO.290), DOM9-112-154 (SEQ ID NO: 291), DOM9-112-155 (SEQ ID NO: 292), DOM9-112-156 (SEQ ID NO: 293), D0M9-112- 157 (SEQ ID NO.294), DOM9-112-158 (SEQ ID NO: 295), DOM9-112-159 (SEQ ID NO: 296), DOM9-112-160 (SEQ ID NO: 297), DOM9- 112-161 (SEQ ID NO: 298), DOM9-3 12-162 (SEQ ID NO: 299), DOM9-112-163 (SEQ ID NO: 300), DOM9-112-164 (SEQ ID NO: 301) , DOM9-112-165 (SEQ ID NO.302), DOM9-112-166 (SEQ ID NO: 303), DOM9-112-167 (SEQ ID NO: 304), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-169 (SEQ ID NO: 306), DOM9-112-170 (SEQ ID NO: 307), DOM9-112-171 (SEQ ID NO: 308), DOM9-112-172 (SEQ ID NO: 309), DOM9-112-173 (SEQ ID NO: 310), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-175 (SEQ ID NO: 312), DOM9-112-176 ( SEQ ID NO.313), DOM9-112-177 (SEQ ID NO: 314), DOM9-112-178 (SEQ ID NO: 315). DOM9-112-179 (SEQ ID NO: 316), DOM9-112-180 (SEQ ID NO: 317), DOM9-112-181 (SEQ ID NO: 318), DOM9-112-182 (SEQ ID NO: 319) ), DOM9-112-183 (SEQ ID NO: 320), DOM9-112-184 (SEQ ID NO: 321), DOM9-112-185 (SEQ ID NO: 322), DOM9-112-186 (SEQ ID NO. .-323), DOM9-112-187 (SEQ ID NO: 324), DOM9-112-188 (SEQ ID NO: 325), DOM9-112-189 (SEQ ID NO.326), DOM9-112-190 ( SEQ ID NO: 327), DOM9-112-191 (SEQ ID NO.328), DOM9-112-I92 (SEQ ID NO: 329), DOM9-112-193 (SEQ ID NO: 330): DOM9-112- 194 (SEQ ID NO: 333), DOM9-112-195 (SEQ ID NO: 332), DOM9-112-196 (SEQ ID NO: 333), DOM9-112-197 (SEQ ID NO.-334), DOM9-112-198 (SEQ ID NO: 335), DOM9- 112-199 (SEQ ID ??: 33d), DOM9-112-200 (SEQ ID NO: 337), DOM9-112 -201 (SEQ ID NO: 338), DOM9-112-202 (SEQ ID NO:: 339), DOM9-120 (SEQ ID NO.-340), DOM9- 121 (SEQ ID NO: 341), DOM9- |122 (SEQ ID NO: 342), DOM9- 123 (SEQ ID NO: 343), DOM9- -124 (SEQ ID NO.344), DOM9- 125 (SEQ ID NO: 345), DOM9- -128 (SEQ ID NO: 346), DOM9- 134 (SEQ ID NO: 347), DOM9- -136 (SEQ ID NO: 348), DOM.9 I-26 (SEQ ID NO: 500), DOM9 -35 (SEQ ID NO: 501), DOM9 -36 (SEQ ID NO: 502), DOM9 -37 (SEQ ID NO: 503), DOM9 -38 (SEQ ID DO NOT. 504), DOM9 -39 (SEQ ID NO: 505), DOM9 -40 (SEQ ID NO: 506), DOM9 -41 (SEQ ID NO: 507), DOM9 -43 (SEQ ID NO: 508), DOM9-44 (SEQ ID NO: 509), DOM9-44-500 (SEQ ID NO: 510), DOM9-44-501 (SEQ ID NO: 511), DOM9-44-502 (SEQ ID NO: 512), DOM9-44-503 (SEQ ID NO: 513), DOM9-44-504 (SEQ ID NO: 514), DOM9-44-505 (SEQ ID NO: 515), DOM9-44-506 ( SEQ ID NO: 516), DOM9-44-507 (SEQ ID NO: 517), DOM9-44-509 (SEQ ID NO: 518), DOM9-44-510 (SEQ ID NO: 519), DOM9-44- 511 (SEQ ID NO: 520), DOM9-44-512 (SEQ ID NO: 521), DOM9-44-513 (SEQ ID NO: 522), DOM9-44-514 (SEQ ID NO: 523), DOM9- 44-515 (SEQ ID NO: 524), DOM9-44-516 (SEQ ID NO: 525), DOM9-44-517 (SEQ ID NO: 526), DOM9-44-518 (SEQ ID NO: 527), DOM9-44-519 (SEQ ID NO: 528), DOM9-44-520 (SEQ ID NO.529), DOM9-44-521 (SEQ ID NO.530), DOM9-44-522 (SEQ ID NO: 531), DOM9-44-523 (SEQ ID NO: 532), DOM9-44-524 (SEQ ID NO: 533), DOM9-44-525 (SEQ ID NO: 534) ), DOM9-44-526 (SEQ ID NO: 535), DOM9-44-527 (SEQ ID NO: 536), DOM9-44-528 (SEQ ID NO: 537), DO 9-44-529 (SEQ ID NO: 538), DOM9-44-530 (SEQ ID NO: 539), DOM9-44-531 (SEQ ID NO: 540), DOM9-44-532 (SEQ ID NO: 541), DOM9-44-533 ( SEQ ID NO: 542), DOM9-44-534 (SEQ ID NO: 543), DOM9-44-535 (SEQ ID NO: 544), DOM9-44-536 (SEQ ID NO: 545), DOM9-44- 537 (SEQ ID: 546), DOM9-44-538 (SEQ ID NO: 547), DOM9-44-539 (SEQ ID 1? 0: 548), DOM9-44-540 (SEQ ID NO: 549), DOM9 -44-541 (SEQ ID NO: 550), DOM9-44-542 (SEQ ID NO: 551), DOM9-44-543 (SEQ ID NO: 552), DOM9-44-544 (SEQ ID NO: 553) , DOM9-44-545 (SEQ ID NO.554), DOM9-44-546 (SEQ ID NO: 555), DOM9-44-547 (SEQ ID NO: 556), DOM9-44-548 (SEQ ID NO: 557), DOM9-44-549 (SEQ ID NO: 558), DOM9-44-550 (SEQ ID NO: 559), DOM9-44-551 (SEQ ID NO: 560), DOM9-44-552 (SEQ ID NO: 561), DOM9-44-553 (SEQ ID NO: 562), DOM9-44-554 (SEQ ID NO: 563), DOM9-44-555 (SEQ ID NO: 564), DOM9-44-556 ( SEQ ID NO.565), DOM9-44-557 (SEQ ID NO: 566), DOM9-44-558 (SEQ ID NO: 567), DOM9-44-559 (SEQ ID NO: 568), DOM9-44- 560 (SEQ ID NO: 569), DOM9-44-561 (SEQ ID NO: 570), DOM9-44-562 (SEQ ID NO: 571), DOM9-44-563 (SEQ ID NO: 572), DOM9- 44-564 (SEQ ID NO: 573), DOM9-44-565 (SEQ ID NO: 574), DOM9-44-566 (SEQ ID NO: 575), DOM9-44-625 (SEQ ID NO: 576), DOM9-44-626 (SEQ ID NO.577), DOM9-44-627 (SEQ ID NO: 578), DOM9-44-628 (SEQ ID NO: 579), DOM9-44-629 (SEQ ID NO: 580) ), DOM9-44-630 (SEQ ID NO: 581), DOM9-44-631 (SEQ ID NO: 582), DO 9-44-632 (SEQ ID NO: 583), DOM9-44-633 (SEQ ID NO: 584), DOM9-44-634 (SEQ ID NO: 585), DOM9-44-636 (SEQ ID NO: 586), DOM9-44-637 (SEQ ID NO: 587), DOM9-44-639 ( SEQ ID NO: 588), DOM9-44-640 (SEQ ID NO: 589), DOM9-44-64 (SEQ ID NO.590), DOM9-44-642 (SEQ ID NO: 591), DOM9-44 -643 (SEQ ID NO.592), DOM9-44-644 (SEQ ID NO.593), DOM9-45 (SEQ ID NO: 594), DOM9-46 (SEQ ID NO: 595), DOM9-47 (SEQ. ID NO: 596), DOM9-48 (SEQ ID NO: 597), DOM9-143 (SEQ ID NO: 598), DOM9-144 (SEQ ID UO: 599)} DOM9-146 (SEQ ID NO: 600), DOM9-152 (SEQ ID NO: 601), DOM9-155 (SEQ ID NO: 602), DOM9-155-001 (SEQ ID NO: 603), DOM9-155- 3 (SEQ ID NO: 604), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-8 (SEQ ID NO: 606), DOM9-155-9 (SEQ ID NO: 607), DOM9- 155-11 (SEQ ID NO: 608), DOM9-155-13 (SEQ ID NO: 609), DOM9-155-14 (SEQ ID NO: 610), DOM9-155-17 (SEQ ID NO: 6l 1) , DOM9-155-19 (SEQ ID NO: 612), DOM9-155-20 (SEQ ID NO: 613), DOM9-155-22 (SEQ ID NO: 614), DOM9-155-23 (SEQ ID NO: 615), DOM9-155-24 (SEQ ID NO: 616), DOM9-155-25 (SEQ ID NO: 617), DOM9-156-26 (SEQ ID NO: 618), DOM9-155-27 (SEQ ID NO: 619), DOM9-155-28 (SEQ ID NO: 620), DOM9-155-29 (SEQ ID NO: 621), DOM9-155-30 (SEQ ID NO: 622), DOM9-155-31 ( SEQ ID NO: 623), DOM9-155- 32 (SEQ ID NO: 624), DOM9-155-33 (SEQ ID NO: 625), DOM9-155-34 (SEQ ID NO: 626), DOM9-155-35 (SEQ ID NO: 627), DOM9- 155-36 (SEQ ID NO: 628), D0M9-155-37 (SEQ ID NO: 629), DOM9-155-38 (SEQ ID NO: 630), DOM9-155-39 (SEQ ID NO: 631), DOM9-155-41 (SEQ ID NO.632), DOM9-55-42 (SEQ ID NO: 633), DOM9-155-43 (SEQ ID NO: 634), DOM9-155-44 (SEQ ID NO: 635) ), DOM9-155-45 (SEQ ID NO: 636), DOM9-155-46 (SEQ ID NO: 637), DOM9-155-47 (SEQ ID N0.638), DOM9-155-48 (SEQ ID NO. : 639), DOM9-155-49 (SEQ ID NO: 640), DOM9-155-50 (SEQ ID NO.641), DOM9- 155-51 (SEQ ID NO: 642), DOM9-155-52 (SEQ ID NO: 643), DOM9-155-53 (SEQ ID NO: 644), DOM9-158 (SEQ ID NO: 645), DOM9-160 (SEQ ID NO: 646), DOM9-161 (SEQ ID NO: 647 ), DOM9-162 (SEQ ID NO: 648), DOM9-163 (SEQ ID NO: 649) and DOM9-164 (SEQ ID NO: 650). In addition, in other embodiments, the ligand may comprise a portion of a protein that has a binding site with binding specificity for IL-13 that competes to bind IL-13 with IL-13Ra1, an IL-13 binding portion of IL -13Ra1, IL-13Ra2, an IL-13 binding part of IL-13Ra2 or an anti-IL-13 domain antibody (dAb). The ligand may comprise a portion of a protein having a binding site with binding specificity for IL-13 (eg, a single immunoglobulin variable domain) that competes to bind IL-13 with an anti-IL-domain antibody. 13 (dAb) selected from the anti-IL-13 dAbs described herein (e.g., DOM10-53 (SEQ ID NO: 967), DOM10-53-1 (SEQ ID N0: 968), DOM10-53-2 (SEQ ID N0: 969) ), DOM10-53-3 (SEQ ID NO: 970), DOM10-53-4 (SEQ ID NO: 971), DOM 10-53-5 (SEQ ID N0: 972), DOM10-53-6 (SEQ ID N0.973), DOM10-53-7 (SEQ ID NO: 974), DOM10-53-8 (SEQ ID NO: 975), DOM10-53-9 (SEQ ID N0: 976), DOM10-53-10 ( SEQ ID NO: 977), DOM10-53-11 (SEQ ID N0: 978), DOM10-53-12 (SEQ ID NO: 979), DOM 10-5343 (SEQ ID NO: 980), DOM 10-53- 14 (SEQ ID NO: 981), DOM10-53-15 (SEQ ID NO: 982), DOM10-53-16 (SEQ ID NO: 983), DOM10-53-17 (SEQ ID NO: 984), DOM10- 53-18 (SEQ ID NO: 985), DOM10-53-19 (SEQ ID NO: 986), DOM10-53-20 (SEQ ID NO: 987), DOM10-53-21 (SEQ ID NO.988), DOM10-53-122 (SEQ ID NO: 989), DOM10-53-123 (SEQ ID NO: 990), DOM10-53-24 (SEQ ID NO: 991), DOM10-53-25 (SEQ ID NO: 992) ), DOM10-53-26 (SEQ ID NO: 993), DOM10-53-27 (SEQ ID NO: 994), DOM10-53-28 (SEQ ID NO: 995), DOM10-53-29 (SEQ ID NO. : 996), DOM10-53-30 (SEQ ID NO: 997), DOM10-53-31 (SEQ ID NO: 998), DOM10-53-3 2 (SEQ ID NO: 1999), DOM10-53-43 (SEQ ID NO: 1000), DOM10-53-44 (SEQ ID NO: 1001), DOM10-53-45 (SEQ ID NO: 1002), DOM10- 53-46 (SEQ ID NO.1003), DOM10-53-47 (SEQ ID NO: 1004), DOM10-53-48 (SEQ ID NO: 1005), DOM10-53-49 (SEQ ID NO: 1006), DOM10-53-50 (SEQ ID NO.1007), DOM10-53-51 (SEQ ID NO: 1008), DOM10-53-52 (SEQ ID NO.1009), DOM10-53-53 (SEQ ID NO: 1010) ), DOM10-53-54 (SEQ ID NO: 1011) ,. DOM10-53-55 (SEQ ID NO: 1012), DOM10-53-56 (SEQ ID NO: 1013), DOM 10-53-57 (SEQ ID NO: 1014), DOM10-53-59 (SEQ 1DNO: 1015) ), DOM10-53-60 (SEQ ID NO: 1016), DOM10-53-61 (SEQ ID NO 017), DOM10-53-62 (SEQ ID NO: 1018), DOM10-53-63 (SEQ ID NO: 1019), DOM10-53-64 (SEQ ID NO: 1020), DOM10-53-65 (SEQ ID NO: 1021), DOM10-53-66 (SEQ ID NO: 1022), DOM 10-53-67 (SEQ. ID NO: 1023), DOM10-53-68 (SEQ ID NO: 1024), DOM10-53-69 (SEQ ID NO: 1025), DOM10-53-70 (SEQ ID NO: 1026), DOM10-53-71 (SEQ ID NO: 1027), DOM10-53-72 (SEQ ID NO: 1028), DOM10-53-73 (SEQ ID NO: 1029), DOM10-53-74 (SEQ ID: 1030), DOM10-53 -75 (SEQ ID NO: 1031), DOM10-53-76 (SEQ ID NO: 1032), DOM10-53-77 (SEQ ID NO: 1033), DOM10-53-78 (SEQ ID NO: 1034), DOM10 -53-79 (SEQ ID NO: 1035), DOM10-53-80 (SEQ ID NO: 1036), DOM10-53-81 (SEQ ID NO: 1037), DOM10-53-82 (SEQ ID NO: 1038) , DOM10-53-83 (SEQ ID NO: 1039), DOM10-53-84 (SEQ ID NO: 1040), DOM10-53-55 (SEQ ID NO: 1041), DOM10-53-86 (SEQ ID NO: 1042), DOM10-53-87 (SEQ ID NO: 1043), DOM10-53-88 (SEQ ID NO: 1044), DOM10-53-8 9 (SEQ ID NO: 1045), DOM10-53-91 (SEQ ID NO: 1046), DOM10-53-92 (SEQ ID NO: 1047), DOM10-53-93 (SEQ ID NO: 1048), DOM10- 53-94 (SEQ ID NO: 1049), DOM10-53-95 (SEQ ID NO: 1050), DOM10-53-96 (SEQ ID NO: 1051), DOM10-53-97 (SEQ ID NO: 1052), DOM10-53-98 (SEQ ID NO: 1053), DOM10-53-99 (SEQ ID NO: 1054), DOM10-53-100 (SEQ ID NO: 1055), DOM10-53-103 (SEQ BD NO: 1056), DOM10-53-105 (SEQ ID NO: 1057), DOM10-53-106 (SEQ ID NO: 1058), DOM10-53-108 (SEQ ID NO: 1059), DOM10-53 -110 (SEQ ID NO: 1060), DOM10-53-111 (SEQ ID NO.1061), DOM10-53-112 (SEQ ID NO: 10632), DOM10-53-114 (SEQ ID NO: 1063), DOM10 -53-1 15 (SEQ ID NO: 1064), DOM10-53-116 (SEQ ID NO: 1065), DOM10-53-117 (SEQ ID NO: 1066), DOM10-53-119 (SEQ ID NO: 1067) ), DOM10-53-320 (SEQ ID NO: 1068), DOM10-53-122 (SEQ ID NO: 1069), DOM10-53-201 (SEQ ID NO: 1070), DOM10-53-2Q3 (SEQ ID NO. : 1071), DOM10-53-204 (SEQ ID NO: 1072), DOM10-53-205 (SEQ ID NO: 1073), DOM10-53-206 (SEQ ID NO: 1074), DOM10-53-207 (SEQ ID NO: 1075), DOM10-53-208 (SEQ ID NO: 1076), DOM 10-53-209 (SEQ ID NO: 1077), DOM10-53-210 (SEQ ID NO: 1078), DOM10-53- 211 (SEQ ID NO: 1079), DOM10-53-213 (SEQ ID NO: 1080), DOM10-53-214 (SEQ ID NO: 1081), DOM10-53-215 (SEQ ID NO: 1082), DOM10- 53-216 (SEQ ID NO: 1083), DOM10-53-217 (SEQ ID NO: 1084), DOM 10-53-1218 (SEQ ID NO: 1085), DOM10-53-219 (SEQ ID NO: 1086) , DOM10-53-220 (SEQ ID NO: 1087), DOM10-53-221 (SE Q ID NO: 1088), DOM10-53-222 (SEQ ID NO: 1089), DOM10-53-223 (SEQ ID NO: 1090), DOM10-53-224 (SEQ ID NO: 1091), DOM10-53- 225 (SEQ ID NO: 1092), DOM10-53-226 (SEQ ID NO: 1093), DOM10-53-227 (SEQ ID NO: 1094), DOM10-53-228 (SEQ ID NO: 1095), DOM10- 53-229 (SEQ ID NO: 1096), DOM 10-53-230 (SEQ ID NO: 1097), DOM10-53-231 (SEQ ID NO: 1098), DOM10-53-232 (SEQ ID NO: 1099) , DOM10- 53-233 (SEQ ID NO: 1300), DOM10-53-234 (SEQ ID NO: 1101), DOM10-53-235 (SEQ ID NO: 1102), DOM10-53-236 (SEQ ID NO: 1103), DOM10-53-237 (SEQ ID NO: 1104), DOM10-53-238 (SEQ ID NO: 1105), DOM10-53-239 (SEQ ID NO: 1106), DOM10-53-240 (SEQ ID NO: 1107), DOM10-53-241 (SEQ ID NO: 1108), DOM10-53-242 (SEQ ID NO: 1109), DOM10-53-243 (SEQ ID NO: 1110), DOM10-53-244 (SEQ ID NO: 1111), DOM10-53-245 (SEQ ID NO: 1112), DOM10-53-246 (SEQ ID NO: 1113), DOM10-53-247 (SEQ ID NO: 1114), DOM10-53-248 ( SEQ ID NO: 1115), DOM10-53-249 (SEQ ID NO: 1116), DOM10-53-250 (SEQ ID NO.-1117), DOM10-53-251 (SEQ ID NO.H18), DOM10-53 -252 (SEQ ID NO: 1119), DOM10-53-253 (SEQ ID NO: 1120), DOM10-53-254 (SEQ ID NO: 1121), DOM10-53-255 (SEQ ID NO: 1122), DOM10 -53-256 (SEQ ID NO: 1123), DOM10-53-257 (SEQ ID NO: 1124), DOM10-53-258 (SEQ ID NO: 1125), DOM10-53-259 (SEQ ID NO: 1126) , DOM10-53-260 (SEQ ID NO: 1127), DOM10-53-261 (SEQ ID NO: 1128), DOM10-53-262 (SEQ ID NO: 1129), DOM10-53-263 (SEQ ID NO: 1130), DOM10-53-264 (SEQ ID NO: 1131), DOM10-53-265 ( SEQ ID NO: 1132), DOM10-53-266 (SEQ ID NO: 1133), DOM10-53-267 (SEQ ID NO: 1134), DOM10-53-268 (SEQ ID NO: 1135), DOM10-53- 269 (SEQ ID NO: 1136), DOM10-53-270 (SEQ ID NO: 1137), DOM10-53-271 (SEQ ID NO: 1138), DOM10-53-272 (SEQ ID NO: 1139), DOM 0 -53-273 (SEQ ID NO: 1140), DOM10-53-274 (SEQ ID NO: 1141), DOM10-53-275 (SEQ ID NO: 1142), DOM10-53-276 (SEQ ID NO: 1143) , DOM10-53-277 (SEQ ID NO: 1144), DOM10-53-278 (SEQ ID NO: 1145), DOM10-53-279 (SEQ ID NO: 1146), DOM10-53-280 (SEQ ID NO: 1147) ), DOM10-53-281 (SEQ ID NO: 1148), DOM10-53-282 (SEQ ID NO: 1149), DOM10-53-283 (SEQ ID NO: 1150), DOM 10-53-284 (SEQ ID NO: 1151), DOM10-53-285 (SEQ ID NO: 1152), DOM10-53-286 (SEQ ID NO: 1153), DOM10-53-287 (SEQ ID NO: 1154), DOM10-53-288 ( SEQ ID NO: 1155), DOM10-53-289 (SEQ ID NO: 1156), DOM10-53-290 (SEQ ID NO: 1157), DOM10-53-291 (SEQ ID NO: 1158), DOM10-53- 292 (SEQ ID NO: 1159), DOM10-53-293 (SEQ ID NO: 1160), DOM10-53-294 (SEQ ID NO: 1161), DOM10-53-295 (SEQ ID NO: 1162), DOM10- 53-296 (SEQ ID NO: 1163), DOM10-53-297 (SEQ ID NO: 1164), DOM10-53-298 (SEQ ID NO: 1165), DOM10-53-299 (SEQ ID NO: 1166), DOM10-53-300 (SEQ ID NO: 1167), DOMÍO-53-301 (SEQ ID NO: 1168), DOM10-53-302 (SEQ ID NO: 1169), DOM10-53-303 (SEQ ID NO: 1170) ), DOM10-53-304 (SEQ ID NO: 1171), DOM10-53-305 (SEQ ID NO: 1172), DOM10-53-306 (SEQ ID NO: 1173), DOM10-53-307 (SEQ ID NO. : 1174), DOM10-53-308 (SEQ ID NO: 1175), DOM10 -53-309 (SEQ ID NO: 1176), DOM10-53-310 (SEQ ID NO: 1177), DOM10-53-311 (SEQ ID NO: 1178), DOM10-53-312 (SEQ ID NO: 1179) , DOM 10-53-314 (SEQ ID NO: 1180), DOM10-53-315 (SEQ ID NO: 1181), DOM10-53-316 (SEQ ID NO: 1182), DOM10-53-317 (SEQ ID NO. : 1183), DOM10-53-318 (SEQ ID NO: 1184), DOM10-53-319 (SEQ ID NO: 1185), DOM10-53-320 (SEQ ID NO: 1186), DOM 10-53-321 ( SEQ ID NO: 1187), DOM10-53-322 (SEQ ID NO: 1188), DOM10-53-323 (SEQ ID NO: 1189), DOM 10-53-324 (SEQ ID NO: 1190), DOM10-53-325 (SEQ ID NO: 1191), DOM10-53-326 (SEQ ID NO: 1192), DOM10-53-327 (SEQ ID NO: 1193), DOM10-53-328 (SEQ ID NO: 1194), DOM10-53 -329 (SEQ ID NO: 1195), DOM10-53-330 (SEQ ID NO 196), DOM10-53-331 (SEQ ID NO: 1197), DOM10-53-333 (SEQ ID NO: 1198), DOM10- 53-334 (SEQ ID NO: 1199), DOM10-53-336 (SEQ ID NO: 1200), DOM10-53-337 (SEQ ID NO: 1201), DOM10-53-338 (SEQ ID NO: 1202), DOM10-53-339 (SEQ ID NO: 1203), DOM 0-53-340 (SEQ ID NO: 1204), DOM10-53-341 (SEQ ID NO: 1205), DOM10-53-342 (SEQ ID NO: 1206), DOM10-53-343 (SEQ ID NO: 1207), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-345 (SEQ ID NO: 1209), DOM10-53-346 (SEQ ID NO: 1210), DOM 10-53-347 (SEQ ID NO: 1211), DOM10-53-348 (SEQ ID NO: 1212), DOM10-53-349 (SEQ ID NO: 1213), DOM10-53-350 (SEQ ID NO: 1214), DOM10-53-351 (SEQ ID NO: 1215), DOM10-53-352 (SEQ ID NO: 1216), DOM10-53-353 (SEQ ID NO: 1217), DOM10-53 -354 (SEQ ID NO: 1218), DOM10-53-355 (SEQ ID NO: 121 9), DOM10-53-356 (SEQ ID NO: 1220), DOM10-53-357 (SEQ ID NO: 1221), DOM10-53-358 (SEQ ID NO: 1222), DOM10-53-359 (SEQ ID NO: 1223), DOM10-53-360 (SEQ ID NO: 1224), DOM10-53-361 (SEQ ID NO: 1225), DOM10-53-362 (SEQ ID NO: 1226), DOM10-53-363 ( SEQ ID NO: 1227), DOM10-53-364 (SEQ ID NO: 1228), DOM10-53-365 (SEQ ID NO: 1229), DOM10-53-366 (SEQ ID NO: 1230), DOM10-53- 367 (SEQ ID NO: 1231), DOM 10-53-368 (SEQ ID NO: 1232), DOM10-53-369 (SEQ ID NO: 1233), DOM10-53-370 (SEQ ID NO: 1234), DOM10- 53-371 (SEQ ID NO: 1235), DOM10-53-372 (SEQ ID NO: 1236), DOM10-53-373 (SEQ ID NO: 1237), DOM10-53-374 (SEQ ID NO: 1238), DOM 10-53-375 (SEQ ID NO: 1239), DOM10-53-376 (SEQ ID NO: 1240), DOM10-53-377 (SEQ ID NO: 1241), DOM10-53-378 (SEQ ID NO: 1242), DOM10-53-379 (SEQ ID NO: 1243); DOM10-53-380 (SEQ ID NO: 1244), DOM10-53-381 (SEQ ID NO: 1,245), DOM10-53-382 (SEQ ID NO: 1246), DOM10-53-383 (SEQ ID NO: 1247) ), DOM10-53-384 (SEQ ID NO: 1248), DOM10-53-385 (SEQ ID NO: 1249), DOM10-53-386 (SEQ ID NO: 1250), DOM10-53-387 (SEQ ID NO. : 1251), DOM10-53-388 (SEQ ID NO: 1252), DOM10-53-389 (SEQ ID NO: 1253), DOM10-53-390 (SEQ ID NO: 1254), DOM10-53-391 (SEQ. ID NO: 1255), DOM10-53-392 (SEQ ID NO: 1256), DOM] 0-53-393 (SEQ ID NO: 1257), DOM10-53-394 (SEQ ID NO: 1258), DOM10-53 -395 (SEQ ID NO: 1259), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-400 (SEQ ID NO: 1261), DOM10-53-401 (SEQ ID NO: 1262), DOM20 -53-402 (SEQ ID NO: 1263), DOM10-53-403 (SEQ ID NO: 1264), DOM10-53-404 (SEQ ID NO: 1265), DOM10-53-405 (SEQ ID NO: 1266) , DOM10-53-406 (SEQ ID NO: 1267), DOM10-53-407 (SEQ ID NO: 1268), DOM10-53-408 (SEQ ID NO: 1269), DOM10-53-409 (SEQ ID NO: 1270), DOM10-53-410 (SEQ ID NO: 1271), DOM10-53-411 (SEQ ID NO: 1272), DOMIO-53-412 (SEQ ID NO: 1273), DOM10-53-413 (SEQ ID NO: 1274), DOM10- 53-414 (SEQ ID NO: 1275), DOM10-53-415 (SEQ ID NO: 1276), DOM10-53-416 (SEQ ID NO: 1277), DOM10-53-417 (SEQ ID NO: 1278), DOM 10-53-418 (SEQ ID NO: 1279), DOM10-53-419 (SEQ ID NO: 1280), DOM10-53-420 (SEQ ID NO: 1281), DOM10-53-421 (SEQ ID NO: 1282), DOM10-268 (SEQ ID NO: 1508), DOM10-169 (SEQ ID NO: 15G9), DOM10-176 (SEQ ID NO: 1510), DOM10-176-1 (SEQ ID NO: 1511), DOM10 -176- 2 (SEQ ID NO: 1512), DOM10-173 (SEQ ID NO: 1513), DOM10-176-4 (SEQ ID NO: 1514), DOM 10-176-5 (SEQ ID NO: 1515), DOM10-176-6 (SEQ ID NO: 1516), DOM10-176-23 (SEQ ID NO: 1517), DOM10-176-24 (SEQ ID NO: 1518), DOM10- 176-25 (SEQ ID NO: 1519) ), DOM10-176-26 (SEQ ID NO: 1520), DOM10-176-27 (SEQ ID NO: 1521), DOM10-176-28 (SEQ ID NO: 1522), DOM10-176-29 (SEQ ID N0) : I523), DOM10-176-30 (SEQ ID NO: 1524), DOM10-176-31 (SEQ ID NO: 1525), DOM10-176-32 (SEQ ID NO: 1526), DOM10-176-33 (SEQ. ID NO: 1527), DOM10-176-34 (SEQ ID NO: 1528), DOM 10- 176-35 (SEQ ID NO: 1529), DOM10-176-36 (SEQ ID NO: 1530), DOM10-176- 37 (SEQ ID NO: 1531), DOM10-176-38 (SEQ ID NO: 1 532), DOM10-176-39 (SEQ ID NO: 1533), DOM10-176-40 (SEQ ID NO: 1534), DOM 10- 176- 101 (SEQ ID NO: 1535), DOM 10- 176-102 ( SEQ ID NO: 1536), DOM 10-176-103 (SEQ ID NO: 1537), DOM10-176-104 (SEQ ID NO: 1538), DOM10-176-105 (SEQ ID NO: 1539), DO M 10 - 176- 106 (SEQ ID NO: 1540), DOM10-176-107 (SEQ ID NO: 1541), DOM 10- 176- 108 (SEQ ID NO: 1542), DOM 10-176-109 (SEQ ID NO: 1543), DOM 10- 176- 110 (SEQ ID NO: 1544), DOM10-176-111 (SEQ ID NO: 1545), DOM10-176-112 (SEQ ID NO: 1546), DOM10-176-1 13 (SEQ ID NO: 1547), DOM 10 -176-114 (SEQ ID NO: 1548), DOM 10-176-115 (SEQ ID NO: 1549), DOM10-176-1 6 (SEQ ID NO: 1550), DOM10-176-117 (SEQ ID NO: 1551), DOM 10-76-500 (SEQ ID NO: 1552), DOM10-176-501 (SEQ ID NO: 1553), DOM10-176-502 (SEQ ID NO: 1554), DOM 10-176-503 ( SEQ ID NO: 1555), DOM10-176-504 (SEQ ID NO: 1556), DOM10-176-505 (SEQ ID NO: 1557), DOM10-176-506 (SEQ ID NO: 1558), DOM 10- 176 -507 (SEQ ID NO: 1559), DOM10-176-508 (SEQ ID NO: 1560), DO M 10- 176-509 (SEQ ID NO: 1561), DOM10-176-510 (SEQ ID NO: 1562) , DOM 10-176-511 (SEQ ID NO: 1563), DOM 10-176-512 (SEQ ID NO: 1564), DOM10-176-513 (SEQ ID NO: 1565), DO M 10- 176-514 ( SEQ ID NO: 1566), DOM10-176-515 (SEQ ID NO: 1567), DOM 10- 176-516 (SEQ ID NO: 1568), DOM10-176-517 (SEQ ID NO: 1569), DOM 10- 176-518 (SEQ ID NO: 1570), DOM 10-176-519 (SEQ ID NO: 1571), DOM10-176-520 (SEQ ID NO: 1572), DOM 10-176-521 (SEQ ID NO: 1573 ), DOM10-176-522 (SEQ ID NO: 1574), DOM 10- 176-523 (SEQ ID NO: 1575), DOM 10-176-524 (SEQ ID NO: 1576), DOM10-176-525 (SEQ ID NO: 1577), DOM 10- 176-526 (SEQ ID NO: 1578), DOM10-176-527 (SEQ ID NO: 1579), DOM10-176-528 (SEQ ID NO: 1580), DOM10-176-529 (SEQ ID NO: 1581), DOM 10-176-530 (SEQ ID NO: 1582), DOM 10- 176-531 (SEQ ID NO: 1583), DOM10-176-532 (SEQ ID NO: 1584), DOM10-176-533 (SEQ ID NO: 1585), DOM10- 176-534 (SEQ ID NO: 1586), OJ M 10-176-535 (SEQ ID NO: 1587), DOM10-176-536 (SEQ ID N0: 1588), D0M10-176-537 (SEQ ID N0: 1589), DOM 10-176-538 (SEQ ID NO: 1590), DOM 10- 176-539 (SEQ ID NO. : 1591), DOM 10- 176-540 (SEQ ID NO: 1592), DOM10-176-541 (SEQ ID NO: 1593), DOM 10-176-542 (SEQ ID NO: 1594), DOM10-176-543 (SEQ ID NO: 1595), DOM 10-176-544 (SEQ ID NO: 1596), DOM 10- 176-545 (SEQ ID NO: 1597), DOM10-176-546 (SEQ ID NO: 1598), DOM 10- 176-547 (SEQ ID NO: 1599), DOM10-176-548 (SEQ ID NO: 1600), DOM 10-176-549 (SEQ ID NO: 1601), DOM10-176-550 (SEQ ID NO: 1602), DOM10-176-551 (SEQ ID NO: 1603), DOM10-176-552 (SEQ ID NO: 1604), DOM 10-176-553 (SEQ ID NO: 1605), DOM 10- 176-554 ( SEQ ID NO: 1606), DOM10-176-555 (SEQ ID NO: 1607), DOM 10-176-556 (SEQ ID NO: 1608), DOM10-176-557 (SEQ ID NO: 1609), DOM 10- 176-558 (SEQ ID NO: 1610), DOM10-176-559 (SEQ ID NO: 1611), DOM 10- 176-560 (SEQ ID NO: 1612), DOM10-176-561 (SEQ ID NO: 1613) , DOM10-176-562 (SEQ ID NO: 1614), DOM 10-376-563 (SEQ ID NO: 1615), DOM10-176-564 (SEQ ID NO: 1616), DOM 10-I76-565 (SEQ ID NO: 1617), OJ M 10- 176-566 (S EQ ID NO: 1618), DOM 10-176-567 (SEQ ID NO: 1619), DOM 10-76-568 (SEQ ID NO: 1620), DOM10-176-569 (SEQ ID NO: 1621), DOM 10 -176-570 (SEQ ID NO: 1622), DOM10-176-571 (SEQ ID NO: 1623), DOM 10-176-572 (SEQ ID NO: 1624), DOM10-176-573 (SEQ ID NO: 1625 ), DOM 10-176-574 (SEQ ID NO: 1626), DOM10-176-575 (SEQ ID NO: 1627), DOM10-176-576 (SEQ ID NO: 1628), DOM 10-176-577 (SEQ. ID NO: 1629), DOM10-176-578 (SEQ ID NO: 1630), DOM 10-176-579 (SEQ ID NO: 1631), DOM 10-176-580 (SEQ ID NO: 1632), DOM 10-176-581 (SEQ ID NO: 1633), DOM10-176-582 (SEQ ID NO: 1634), DOM10-176- 583 (SEQ ID NO: 1635), DOM10-176-584 (SEQ ID NO: 1636), DOM10-76-585 (SEQ ID NO: 1637), DOM10-76-586 (SEQ ID NO: 1638), DOM 10 -? 76-587 (SEQ ID NO: 1639), DOM 10-176-588 (SEQ ID NO: 1640), DOM 10-176-589 (SEQ ID NO: 1641), DOM10-176-590 (SEQ ID NO. : 1642), DOM 10- 176-591 (SEQ ID NO: 1643), DOM10-176-592 (SEQ ID NO: 1644), DOM 10- 176-593 (SEQ ID NO: 1645), DOM 10- 176- 594 (SEQ ID NO: 1646), DOM 10- 176-595 (SEQ ID NO: 1647), DOM 10-176-596 (SEQ ID NO: 3648), DOM10476-597 (SEQ ID NO: 1649), DO M 10- 176-598 (SEQ ID NO: 1650), DOM 10-176-599 (SEQ ID NO: 1651), DOM 10- 176-600 (SEQ ID NO: 1652), DOM10-176-601 (SEQ ID NO. : 1653), DOM10-176-602 (SEQ ID NO: 1654), DOM 10-176-603 (SEQ ID NO: 1655), DOM10-176-604 (SEQ ID NO: 1656), DOM 10-376-605 (SEQ ID NO: 1657), DOM 10-176-606 (SEQ ID NO: 1658), DOM10-176-607 (SEQ ID NO: 1659), DOM 10-176-608 (SEQ ID NO: 1660), DOM10 -176-609 (SEQ ID NO: 1661), DOM10- 176-610 (SEQ ID NO: 1662), DOM10-176-611 (SEQ ID NO: 1663), DOM 10-176-612 (SEQ ID NO: 1664), DOM10-176-613 (SEQ ID NO: 1665) , DOM10-176-614 (SEQ ID NO: 1666), DOM10-76-615 (SEQ ID NO: 1667), DOM10-176-616 (SEQ ID NO: 1668), DOM 30-176-617 (SEQ ID NO. : 1669), DOM10-176-618 (SEQ ID NO: 1670), DOM10-176-619 (SEQ ID NO: 1671), DOM 10-176-620 (SEQ ID NO: 1672), DOM10-176-621 ( SEQ ID NO: 1673), OJ M 10- 176-622 (SEQ ID NO: 1674), DOM10-176-623 (SEQ ID N0: 1675), DOM 10-176-624 (SEQ ID NO: 1676). DOM 10-176-625 (SEQ ID NO: 1677), DOM 10- 176-626 (SEQ ID NO: 1678), DOM10-176-627 (SEQ ID NO: 1679), DOM10-176-628 (SEQ ID NO. : 1680), DOM 10- 176-629 (SEQ ID NO: 26SJ) h DOM10-176-630 (SEQ ID NO: 1682), DOM 10-176-631 (SEQ ID NO: 1683), DOM 10- 176- 632 (SEQ ID NO: 1684), DOM 10-176-633 (SEQ ID NO: 1685), DOM 10-176-634 (SEQ ID NO: 1686), DOM10-176-635 (SEQ ID NO: 1687), DOM 0176-636 (SEQ ID NO: 1688), DOM10-176-637 (SEQ ID NO: 1689), DOM10-176-638 (SEQ ID NO: 1690), DOM 10-176-639 (SEQ ID NO. -A691), DOM 10- 176-640 (SEQ ID NO: 1692), DOM10-176-641 (SEQ ID NO: 1693), DOM10-176-643 (SEQ ID NO: 1694), DOM 10- 176-644 (SEQ ID NO: 1695), DOM10-176-645 (SEQ EJ NO: 1696), DOM 10- 176-646 (SEQ ID NO: 1697), DOM 10-176-647 (SEQ ID NO: 1698), DOM 10- 176-648 (SEQ ID NO: 1699), DOM10-176-649 (SEQ ID NO: 1700), DOM10-276-650 (SEQ ID NO: 1701), DOM 10- 176-651 (SEQ ID NO: 1702), DOM10-176-652 (SEQ ID NO: 1703), DOM 10-76-653 (SEQ ID NO: 1704), DOM 10-176-654 (SEQ ID NO: 1705), DOM 10-176-655 (SEQ ID NO: 1706), DOM 10- 176-656 (SEQ ID NO: 1707), DOM10-176-657 (SEQ ID NO: 1708), DOM 10-176-658 (SEQ ID NO: 1709), DOM10-176-659 (SEQ ID NO: 1730), DO M 10- 176-660 (SEQ ID NO: 1711), DOM10-176-661 (SEQ ID NO: 1712), DO M 10- 176-662 (SEQ ID NO: 1713), DOM 10-176-663 (SEQ ID NO: 1714), DOM10-176-664 (SEQ ID NO: 1715), DOM 10-176-665 (SEQ ID NO: 1716), DOM10-176-666 (SEQ ID NO: 1717), DOM10-176-667 (SEQ ID NO: 1718), DOM 10-176-668 (SEQ ID NO: 1719), DOM 10-176-669 (SEQ ID NO: 1720), DOM 10- 176-670 (SEQ ID NO: 1721), DOM10-176 -671 (SEQ ID NO: 1722), DOM 10- 176-672 (SEQ ID NO: 1723), DOM10-176-673 (SEQ ID NO: 1724), DOM 10-176-674 (SEQ ID NO: 1725) , DOM 10-176-675 (SEQ ID NO: 1726), DOM10-253 (SEQ ID NO: 1727), DOM10-255 (SEQ ID NO: 1728), DOM10-272 (SEQ ID NO: 1729), DOM10- 307 (SEQ ID NO: 1730), DOM10-319 (SEQ ID NO: 1731) and DOM10-319-1 (SEQ ID NO: 1732)). The ligand may also comprise a portion of the protein having a binding site with binding specificity for IL-13 (e.g., a single immunoglobulin variable domain) competing to bind IL-13 with an anti-IL domain antibody. -13 (dAb) selected from the group consisting of DOM10-236 (SEQ ID NO 2129) DOM10-238 (SEQ ID NO: 2130), DOM10-241 (SEQ ID NO 2131) DOM10-245 (SEQ ID NO: 2132) , DOM10 -249 (SEQ ID NO 2133) DOM10-250 (SEQ ID NO: 2134), DOM10 -251 (SEQ ID NO 2135) DOM10-254 (SEQ ID NO: 2136), DOM10-256 (SEQ ID NO 2137) DOM10-259 (SEQ ID NO: 2138), DOM10-260 (SEQ ID NO 2139) DOM10-261 (SEQ ID NO: 2140), DOM10-263 (SEQ ID NO 2141) DOM10-264 (SEQ ID NO: 2142) , DOM10 -273 (SEQ ID NO 2143) DOM10-278 (SEQ ID NO: 2144), DOM10 -279 (SEQ ID NO 2145) DOM10-281 (SEQ ID NO: 2146), DOM10-282 (SEQ ID NO 2147) DOM10-283 (SEQ ID NO: 2148), DOM10-400 (SEQ ID NO 2149) DOM10-401 (SEQ ID NO.2150), DOM10 -402 (SEQ ID NO 2151) DOM10- 404 (SEQ ID NO: 2152) DOM10- | 406 (SEQ ID NO: 2153) > DOM10-407 (SEQ ID NO 2154) DOM10- • 409 (SEQ ID NO 2155), DOM10-410 (SEQ ID NO 2156) DOM10- | 414 (SEQ ID NO 2157), DOM10-415 (SEQ ID NO 2158) DOM10 - | 416 (SEQ ID NO 2159), DOM10-418 (SEQ ID NO 2160) DOM10- | 420 (SEQ ID NO 2161), DOM10-4222 (SEQ ID NO 2162) DOM10-4213 (SEQ ID NO 2163), DOM10 424 (SEQ ID NO 2164) DOM10-425 (SEQ ID NO 2165), DOM10-426 (SEQ ID NO: 2166), DOM10-427 (SEQ 1 BNO: 2167); DOM10- 428 (SEQ ID NO 2168) DOM10- 429 (SEQ ID NO 2169), DOM10-430 (SEQ ID NO 2170) DOM10- 431 (SEQ ID NO 2171), DOM10-432 (SEQ ID NO 2172) DOM10- 433 (SEQ ID NO 2173), DOM10-467 (SEQ ID NO 2174) DOM10-468 (SEQ ID NO 2175), DOM10-469 (SEQ ID NO 2176) DOM10-470 (SEQ ID NO 2177), DOM10-234 (SEQ. ID NO 2178), DOM10-235 (SEQ ID NO 2179), DOM10-237 (SEQ ID NO 2180) DOM10-239 (SEQ ID NO 2181), DOM10-240 (SEQ ID NO 2182) DOM10-242 (SEQ ID NO. 2183), DOM10-243 (SEQ ID NO: 2184), DOM10-244 (SEQ ID NO 2185), DOM10-246 (SEQ ID NO: 2186), DOM10-247 (SEQ ID NO 2187), DOM10-248 (SEQ. ID NO: 2188), DOM 30-252 (SEQ ID NO: 2189) DOM10-257 (SEQ ID NO: 2190), DOM10-258 (SEQ ID NO: 2191) DOM10-262 (SEQ ID NO: 2192), DOM10-265 (SEQ ID NO: 2193) DOM10-266 (SEQ ID NO: 2194), DOM10-274 (SEQ ID NO: 2195) DOM30-275 (SEQ ID NO: 2196), DOM10-276 (SEQ ID NO: 2197) DOM10-277 (SEQ ID NO: 2198), DOM10-280 (SEQ ID NO: 2199) DOM10-403 (SEQ ID NO: 2200), DOM10-405 (SEQ ID NO: 2201) DOM10 -408 (SEQ ID NO: 2202), DOM10-41 1 (SEQ ID NO: 2203), DOM10 -412 (SEQ ID NO 2204), DOM10- | 413 (SEQ ID NO: 2205), DOM10 -417 (SEQ ID! MO: 2206) DOM10 -419 (SEQ ID NO: 2207), DOM10 -472 (SEQ ID NO 2208), DOM10- | 203 (SEQ ID NO: 2209), DOM10 -205 (SEQ ID NO 2210), DOM10- |208 (SEQ ID NO: 2211), DOM10 -218 (SEQ ID NO 2212), DOM10- |219 (SEQ ID NO: 2213), DOM10 -220 (SEQ ID NO 2214), DOM10- |225 (SEQ ID NO: 2215), DOM10 -228 (SEQ ID NO 2236), DOM10-229 (SEQ ID NO: 2217), DOM10 -230 (SEQ ID NO 2218), DOM10-231 (SEQ ID NO: 2219), DOM10 -268 (SEQ ID NO 2220), DOM10-201 (SEQ ID NO: 2221), DO 10-202 (SEQ ID NO 2222), DOM10-204 (SEQ ID NO.-2223), DOM10 -206 (SEQ ID NO 2224), DOM10-207 (SEQ ID NO: 2225), DOM10 -209 (SEQ ID NO 2226), DOM10-210 (SEQ ID NO: 2227), DOM10 -211 (SEQ ID NO 2228), DOM10-213 (SEQ ID NO: 2229), DOM10 -214 (SEQ ID NO 2230), DOM10-215 (SEQ ID NO.-2231), DOM10 -216 (SEQ ID NO 2232), DOM10-217 (SEQ ID NO: 2233), DOM10 -221 (SEQ ID NO 2234), DOM10-222 (SEQ ID NO: 2235), DOM10-224 (SEQ ID NO 2236), DOM10-227 (SEQ ID NO: 2237), DOM10 -232 (SEQ ID NO 2238), DOM10-267 (SEQ ID NO: 2239), DOM10 -270 (SEQ ID NO: 2240), DOM 10-275-1 (SEQ ID NO: 2241), DOM 10-276-2 (SEQ ID NO: 2242), DOM10-276-3 (SEQ ID NO: 2243), DOM10-275-3 (SEQ ID NO: 2244), DOM] 0-277 -2 (SEQ ID NO: 2245), DOM10-277-3 (SEQ ID NO: 2246), DOM10-273-1 (SEQ ID 1S! 0: 2247), DOM10-273-2 (SEQ ID NO: 2248) , DOM10-275-2 (SEQ ID NO: 2249), DOM10-275-4 (SEQ ID NO: 2250), DOM10-276-1 (SEQ ID NO: 2251), DOM10-276-4 (SEQ ID NO: 2252), DOM10-277-1 (SEQ ID NO: 2253), DOM10-275-13 ( SEQ ID NO: 2254), DOM10-275-15 (SEQ ID NO: 2255), DOM10-275-20 (SEQ ID NO: 2256), DOM10-275-8 (SEQ ID NO: 2257), DOM10-276- 13 (SEQ ID NO: 2258), DOM10-276-14 (SEQ ID NO: 2259), DOM10-276-15 (SEQ ID NO: 2260), DOM10-276-17 (SEQ IDM): 2261), DOM10-276-7 (SEQ ID NO: 2262), DOM10-276-8 ( SEQ ID NO: 2263), DOM10-275-11 (SEQ ID NO: 2264), DOM10-275-12 (SEQ ID NO: 2265), DOM10-275-14 (SEQ ID NO: 2266), DOM10-275- 16 (SEQ ID NO: 2267), DOM10-275-17 (SEQ ID NO: 2268), DOM10-275-5 (SEQ ID NO: 2269), DOM10- 275-6 (SEQ ID NO: 2270), DOM10- 275-7 (SEQ ID NO: 2271), DOM10-275-9 (SEQ ID NO: 2272), DOM10-276-10 (SEQ ID NO: 2273), DOM10-276-11 (SEQ ID NO: 2274), DOM10-276-12 (SEQ ID NO: 2275), DOM10-276-16 (SEQ ID NO: 2276), DOM10-276-5 (SEQ ID NO: 2277), DOM10-276-6 (SEQ ID NO: 2278) ), DOM10-276-9 (SEQ ID NO: 2279), DOM10-212 (SEQ ID NO: 2280), DOM10-53-424 (SEQ ID NO: 2281), DOM10-53-425 (SEQ ID NO: 2282) ), DOM10-53-426 (SEQ ID NO: 2283), DOM10-53-422 (SEQ ID NO: 2284), DOM10-53423 (SEQ ID NO: 2285), DOM10-53-613 (SEQ ID NO: 2286) ), DOM10-53-517 (SEQ ID NO: 2287), DOM10-53-519 (SEQ ID NO: 2288), DOM10-53-520 (SEQ ID NO: 2289), DOM10-53-521 (SEQ ID NO. : 2290), DOM10-53-522 (SEQ ID NO: 2291), DOM10- 53-526 (SEQ ID NO: 2292), DOM10-53-527 (SEQ ID NO: 2293), DOM10-53-528 (SEQ ID NO: 2294), DOM 10-53-518 (SEQ ID NO: 2295), DOM10-53-523 (SEQ ID NO: 2296), DOM10-53-524 (SEQ ID NO: 2297), DOM10-53-525 (SEQ ID NO: 2298), DOM10-53-601 (SEQ ID NO: 2299), DOM10-53-602 (SEQ ID NO: 2300), DOM10-53-605 (SEQ ID NO: 2301), DOM10-53 -606 (SEQ ID NO: 2302), DOM10-53-607 (SEQ ID NO: 2303), DOM10-53-608 (SEQ ID NO: 2304), DOM10-53-609 (SEQ ID NO: 2305), DOM10 -53-610 (SEQ ID NO: 2306), DOM10-53-611 (SEQ ID NO: 2307), DOM10-53-612 (SEQ ID NO: 2308), DOM 10-53-603 (SEQ ID NO: 2309) ), DOM10-53-604 (SEQ ID NO: 2310), DOM10-53-429 (SEQ ID NO: 2311), DOM10-53-432 (SEQ ID NO: 2312), DOM10-53-433 (SEQ ID NO. : 2313), DOM10-53-435 (SEQ ID NO: 2314), DOM10-53-430 (SEQ ID NO: 2315), DOM10-53-431 (SEQ ID NO: 2316), DOM10-53-434 (SEQ. ID NO: 2317), DOM10-53-436 (SEQ ID NO: 2318); DOM10-53-437 (SEQ ID NO: 2319), DOM10-53-438 (SEQ ID NO: 2320), DOM10-53-440 (SEQ ID NO: 2321), DOM10-53-439 (SEQ ID NO: 2322) ), DOM10-53-441 (SEQ ID NO: 2323), DOM10-53-442 (SEQ ID NO: 2324), DOM10-53-443 (SEQ ID NO: 2325), DOM10-53-444 (SEQ ID NO. : 2326), DOM10-53-445 (SEQ ID NO: 2327). DOM10-53-446 (SEQ ID NO: 2328), DOM10-53-447 (SEQ ID NO: 2329), DOM10-53-449 (SEQ ID NO: 2330), DOM10-53-448 (SEQ ID NO: 2331) ), DOM10-53-450 (SEQ ID NO: 2332), DOM10-53-451 (SEQ ID NO: 2333), DOM10-53-452 (SEQ ID NO: 2334), DOM10-53-453 (SEQ ID NO. : 2335), DOM10-53-454 (SEQ ID NO: 2336), DOM10-53-455 (SEQ ID NO: 2337), DOM 10-53-456 (SEQ ID NO: 2338), DOM 10-53-457 (SEQ ID NO: 2339), DOM10-53-458 (SEQ ID NO: 2340), DOM10-53-459 (SEQ ID NO: 2341), DOM10- 53-461 (SEQ ID NO: 2342), DOM10-53-462 (SEQ ID NO: 2343), DOM 10-53-465 (SEQ ID NO: 2344), DOM10-53-466 (SEQ ID NO: 2345) , DOM10-53-467 (SEQ ID NO: 2346), DOM10-53-468 (SEQ ID NO: 2347), DOM10-53-460 (SEQ ID NO: 2348), DOM10-53-463 (SEQ ID NO: 2349), DOM10-53-464 (SEQ ID NO: 2350), DOM10-53-469 (SEQ ID NO: 2351), DOM10-53-471 (SEQ ID NO: 2352), DOM10-53-470 (SEQ ID NO: 2353), DOM10-53-533 (SEQ ID NO: 2354), DOM10-53-534 (SEQ ID NO: 2355), DOM10-53-535 (SEQ ID NO: 2356), DOM10-53-537 ( SEQ ID NO: 2357), DOM 10-53-538 (SEQ ID NO: 2358), DOM10-53-539 (SEQ ID NO: 2359), DOM10-53-540 (SEQ ID NO: 2360), DOM10-53 -531 (SEQ ID NO: 2361), DOM10-53-532 (SEQ ID NO: 2362), DOM10-53-536 (SEQ ID NO: 2363), DOM10-53-542 (SEQ ID NO: 2364), DOM10 -53-541 (SEQ ID NO: 2365), DOM10-53-473 (SEQ ID NO: 2366), DOM10-53-472 (SEQ ID NO: 2367), DOM10-53-475 (SEQ ID NO: 2368) , DOM10-53-474 (SEQ ID NO: 2369), DOM10-53-543 (SEQ ID NO: 2370), DOM10-53-544 (SEQ ID NO: 2371), DOM10-53-545 (SEQ ID NO: 2372), DOM10-53-548 (SEQ ID NO: 2373), DOM10-53-546 (SEQ ID NO: 2374), DOM10-53-549 (SEQ ID NO: 2375), DOM10-53-547 (SEQ ID NO: 2376), DOMAIN-53-550 (SEQ ID NO: 2377), DOM10-53 -551 (SEQ ID NO: 2378), DOM10-53-560 (SEQ ID NO: 2379), DOM10-53-565 (SEQ ID NO: 2380), DOM10-53-559 (SEQ ID NO: 2381), DOM10 - 53-561 (SEQ ID NO: 2382), DOM10-53-562 (SEQ ID NO: 2383), DOM10-53-563 (SEQ ID NO: 2384), DOM10-53-564 (SEQ ID NO: 2385), DOM10-53-566 (SEQ ID NO: 2386), DOM10-53-554 (SEQ ID NO: 2387), DOM10-53-552 (SEQ ID NO: 2388), DOM10-53-553 (SEQ ID NO: 2389) ), DOM 10-53-558 (SEQ ID NO: 2390), DOM10-53-556 (SEQ ID NO: 2391) and DOM10-53-557 (SEQ ID NO: 2392). In particular embodiments, the ligand having binding specificity for IL-4 and for IL-13 comprises a portion of protein having a binding site with binding specificity for IL-4 competing to bind IL-4 with an antibody of anti-IL-4 domain (dAb) selected from the group consisting of DOM9-112-155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 ( SEQ ID NO: 606), DOM9-155-25 (SEQ ID NO: 617), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112- 202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433) (DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512), and comprises in addition a protein portion having a binding site with binding specificity for IL-13 which competes to bind IL-13 with an anti-IL-13 domain antibody (dAb) selected from the group consisting of DOM10-176- 535 (SEQ ID NO: 1587), D OM10-53-223 (SEQ ID NO: 1090), DOM10-53-234 (SEQ ID NO: 1101), DOM 10-53-316 (SEQ ID NO: 1182), DOM 10-53-339 (SEQ ID NO: 1203), DOM10-53- 344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241). The ligand having binding specificity for IL-4 and IL-13 can inhibit the binding of IL-4 to IL-4R, inhibit IL-4 activity, and / or inhibit IL-4 activity without substantially inhibiting the activity of IL-4. Link from IL-4 to IL-4R. Preferably, the ligand (e.g., single immunoglobulin variable domain) binding to IL-4 inhibits the binding of IL-4 to an IL-4 receptor (e.g., IL-4Ra) with an inhibition concentration of 50 (IC50). what is = 10 μ ?, < 1 μ ?, < 100 nM, < 10 nM, < 1 nM, < 500 pM, < 300 pM, < 100 pM, or < 10 pM. The IC50 is determined using preferably an in vitro receptor binding assay, such as the assay described herein.

It is also preferred that the ligand (e.g., single immunoglobulin variable domain) that binds to an IL-4 receptor, inhibits the functions induced by IL-4 in a suitable in vitro assay with a neutralization dose of 50 (ND50) which is < 10 μ ?, < 1 μ ?, < 100 nM, < 10 nM, < 1 nM, < 500 pM, < 300 pM, < 100 pM, or < 10 pM. For example; the ligand that binds to an IL-4 receptor can inhibit the IL-4-induced proliferation of TF-1 cells (Accession to ATCC No. CRL-2003) in an in vitro assay, such as the assay described herein.

It is also preferred that the ligand (e.g., single immunoglobulin variable domain) that binds to an IL-4 receptor inhibit the proliferation induced by house dust mites (HDM) of mononuclear peripheral blood mononuclear cells (PBMC) in at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90% in a suitable in vitro assay, such as the assay described here where 4 x 10 6 cells / ml were stimulated with 20-50 ug / ml HDM and 100 nM anti-IL-4 dAbs were added. A ligand (e.g., single immunoglobulin variable domain) that does not substantially inhibit the binding of IL-4 to an IL-4 receptor (e.g., IL-4Ra) does not significantly inhibit the binding of IL-4 to an IL-4 receptor. 4 in the receiver link described here. For example, said ligand can inhibit the binding of IL-4 to an IL-4 receptor at the receptor link described herein with IC50 of about 1 mM or greater or inhibits the binding by no more than about 20%, no more about 15%, no more than about 10%, or no more than about 5%.

The ligand having binding specificity for IL-4 and IL-13 can inhibit the binding of IL-13 to IL-13Ra1 and / or IL-13Ra2, inhibit the activity of IL-13, and / or inhibit the activity of IL-13 without substantially inhibit the binding of IL-13 to IL-13Ra1 and / or IL-13Ra2. Preferably, the ligand (e.g., single immunoglobulin variable domain) that binds IL-13 inhibits the binding of IL-13 to an IL-13 receptor (e.g., IL-13Ra1, IL-13Ra2) at an inhibitory concentration. (IC50) which is < 10 μ ?, < 1 μ ?, < 100 nM, < 10 nM, < 1 nM, < 500 pM, < 300 pM, < 100 pM, 0 < 10 pM. The IC50 is determined using preferably the in vitro receptor binding assay, such as the assay described herein. It is also preferred that the ligand (e.g., single immunoglobulin variable domain) binding to the IL-13 receptor inhibits the functions induced by IL-13 in a suitable in vitro assay with a neutralization dose 50 (ND50) which is < 10 μ ?, < 1 μ ?, < 100 nM, < 10 nM, < 1 mVL < 500 pM? < 300 pM, < 100 pM, < 10 pM, < 1 pM < 500 fM, < 300 fM, < 100 fM, < 10 fM, For example, the ligand binding to an IL-13 receptor can inhibit the proliferation induced by IL-13 of TF-1 cells (ATCC Access No. CRL-2003) in an in vitro assay, such as the assay here described in which the TF-1 cells were mixed with a final concentration of 5 ng / ml of IL-13.

It is also preferred that the ligand binding to the IL-13 receptor inhibit IL-13 induced B cell proliferation by at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90% in an in vitro assay, such as the assay described herein where 1 x 10 s B cells were incubated with 10 or 100 nM anti-IL-13 dAbs. A ligand (e.g., single immunoglobulin variable domain) that does not substantially inhibit the binding of IL-13 to an IL-13 receptor (e.g., IL-13Ra1, IL-13Ra2) does not significantly inhibit the binding of IL-13 to an IL-13 receptor in the sandwich binding assay or sandwich ELISA assay described herein. For example, said ligand can inhibit the assay of IL-13 to an IL-13 receptor in the receptor binding assay described herein with an IC 50 of about 1 mM or greater or inhibit the binding no more than about 20%, no more about 15%, no more than about 10%, or no more than about 5%. In more particular embodiments, the ligand having binding specificity for IL-4 and for IL-13 comprises a single immunoglobulin variable domain with binding specificity for IL-4 and a single immunoglobulin variable domain with binding specificity for! L -13, wherein the variable domain of simple immunoglobulin with binding specificity for IL-4 competes to bind IL-4 with an antibody of domain IL-4 (dAb) selected from the group dAbs anti-IL-4 described herein. In more particular modalities, the ligand having binding specificity for IL-4 and for IL-13 comprises a single immunoglobulin variable domain with binding specificity for IL-4 and a single immunoglobulin variable domain with binding specificity for IL-13 > wherein the variable domain of simple immunoglobulin with binding specificity for IL-13 competes to bind IL-13 with an anti-IL-13 domain antibody (dAb) selected from the group consisting of anti-IL-13 dAbs described herein . The ligand having binding specificity for IL-4 and IL-13 may contain a protein binding portion (eg, single immunoglobulin variable domain) with binding specificity for IL-4 that binds IL-4 with an affinity ( KD) which is between about 100 nM and about 1 pM, as determined by surface plasmon resonance. The ligand having binding specificity for IL-4 and IL-13 may contain a protein binding portion (eg, single immunoglobulin variable domain) with binding specificity for IL-13 binds IL-13 with an affinity (KD) ) which is between about 100 nM and about 1 pM, as determined by surface plasmon resonance. The ligand having binding specificity for IL-4 and IL-13 can bind to IL-13 with an affinity (KD) that is between about 100 nM and about 1 pM, as determined by plasmon resonance of surface. The ligand having binding specificity for IL-4 and IL-13 can bind to IL-13 with affinity (KD) which is between about 100 nM and about 1 pM, as determined by surface plasmon resonance. The ligand having binding specificity for IL-4 and IL-13 may comprise a single immunoglobulin variable domain with binding specificity for IL-4 and a single immunoglobulin variable domain with binding specificity for IL-13, wherein Variable domains of single immunoglobulin are selected from the group consisting of a human VH and a human VL. In some embodiments, the ligand having binding specificity for IL-4 and IL-13 can be an IgG type format comprising two variable domains of single immunoglobulin with binding specificity for IL-4, and two variable domains of single immunoglobulin with binding specificity for IL-13. In some embodiments, the ligand having binding specificity for IL-4 and for IL-13 may comprise an antibody region of Fe. In some embodiments, the ligand having binding specificity for IL-4 and IL-13 may comprise a constant region IgG. The present invention relates to a ligand that has binding specificity for IL-4 comprising a single immunoglobulin variable domain with binding specificity for IL-4, wherein the variable domain of single immunoglobulin with binding specificity for IL-4 competes to bind IL-4 with an antibody of IL-4 domain (dAb) selected from the group consisting of the anti-IL-4 dAbs described herein. For example, a single immunoglobulin variable domain with binding specificity for IL-4 may comprise an amino acid sequence having at least about 85% amino acid sequence identity with the amino acid sequence of a dAb selected from the group consisting of in the anti-IL-4 dAbs described herein. The ligand having binding specificity for IL-4 can inhibit the binding of IL-4 to IL-4R, inhibit IL-4 activity and / or inhibit IL-4 activity without substantially inhibiting the binding of IL-4. to IL-4R. Preferably, the ligand (e.g., single immunoglobulin variable domain) that binds IL-4 inhibits the binding of IL-4 to an IL-4 receptor (e.g., IL-4Ra) with an inhibition concentration of 50 (IC 50) which is < 10 μ ?, < 1 μ ?, < 100 nM, < 10 nM, < 1 nM, < 500 pM, < 300 pM, < 100 pM, or < 10 pM. The IC50 preferably using an in vitro receptor binding assay, such as the assay described herein.

It is also preferred that the ligand (e.g., single immunoglobulin variable domain) binding to the IL-4 receptor inhibits the functions induced by IL-4 in a suitable in vitro assay with a neutralization dose 50 (ND50) which is < 10 μ ?, < 1 μ ?, < 100 nM, < 10 nM, < 1 nM, < 500 pM, < 300 pM, < 100 pM, or < 10 pM. For example, the ligand ligand binding to the IL-4 receptor can inhibit IL-4-induced proliferation of TF-1 cells (Accession ATCC No. CRL-2003) in an in vitro assay, such as the assay described herein. It is also preferred that the ligand (e.g., single immunoglobulin variable domain) binding to the IL-4 receptor inhibit the proliferation induced by house dust (HDM) of peripheral blood mononuclear cells (PBMC) in at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90% in a suitable in vitro assay, such as the assay described herein where 4 x 10 6 cells / ml were stimulated with 20-50 ug / ml HDM and 100 nM anti-IL-4 dAbs were added. A ligand (e.g., single immunoglobulin variable domain) that does not substantially inhibit the binding of IL-4 to an IL-4 receptor (e.g., IL-4Ra) does not significantly inhibit the binding of IL-4 in an IL-4 receptor. 4 in the receptor binding assay described here. For example, said ligand can inhibit the assay of IL-4 to an IL-4 receptor in the receptor binding assay described herein with IC 50 of about 1 mM or greater or inhibits the binding by no more than about 20%, not more than about 15%, no more than about 10%, or no more than about 5%. The ligand having binding specificity for IL-4 may contain a single immunoglobulin variable domain with binding specificity for IL-4 that binds IL-4 with affinity (KD) that is between about 100 nM and about 1 pM, such as it is determined by surface plasmon resonance. The ligand having binding specificity for IL-4 can bind to IL-4 with an affinity (KD) that is between about 100 nM and about 1 pM, as determined by surface plasmon resonance. The ligand having binding specificity for IL-4 may comprise a single immunoglobulin variable domain with binding specificity for IL-4 which is selected from the group consisting of human VH and human VL. In some embodiments, the ligand having binding specificity for IL-4 is an IgG type format comprising at least two immunoglobulin variable domains simple with binding specificity for IL-4. In some embodiments, the ligand having binding specificity for IL-4 comprises an antibody region of Fe. In some embodiments, the ligand having binding specificity for IL-4 comprises an IgG constant region. The present invention also relates to a ligand having binding specificity for IL-13 comprising a single immunoglobulin variable domain with binding specificity for IL-13, wherein the variable domain of single immunoglobulin with binding specificity for IL- 13 competes to bind IL-13 with an anti-IL-13 domain antibody (dAb) selected from the group consisting of anti-IL-13 dAbs described herein. For example, the variable domain of simple immunoglobulin with binding specificity for IL-13 may comprise an amino acid sequence having at least about 85% amino acid sequence identity with the amino acid sequence of a dAb selected from the group consisting of in the anti-IL-13 dAbs described herein. The ligand having binding specificity for IL-13 can inhibit the binding of IL-13 to IL-13Ra1 and / or IL-13Ra2, inhibit IL-13 activity, and / or inhibit IL-13 activity without substantially inhibit the binding of IL-13Ra1 and / or IL-13Ra2 to IL-13. Preferably, the ligand (e.g., single immunoglobulin variable domain) that binds IL-13 inhibits the binding of IL-13 to an IL-13 receptor (e.g., IL-13Ra1, IL-13Ra2) at an inhibitory concentration. (IC50) which is < 10 μ ?, < 1 μ ?, < 100 rM, < 10 nM. < 1 nM, < 500 pM, < 300 pM, < 100 pM, 0 < 10 pM. The IC50 is determined using preferably an in vitro receptor binding assay, such as the assay described herein. It is also preferred that the ligand (e.g., single immunoglobulin variable domain) that binds to the IL-13 receptor inhibits the functions induced by IL-13 in a suitable in vitro assay with a neutralization dose 50 (ND50) which is < 10 μ ?, < 1 μ ?, < 100 nM, < 10 nM, < 1 nM. < 500 pM, < 300 pM, < 100 pM, < 10 pM, < 1 pM < 500 fM, < 300 fM, < 100 fM, < 10 fM. For example, the ligand that binds to the IL-13 receptor can inhibit the proliferation induced by IL-13 of TF-1 cells (ATCC Accession No. CRL-2003) in an in vitro assay, such as the assay described herein wherein the TF-1 cells were mixed with a final concentration of 5 ng / ml of IL-13.

It is also preferred that the ligand binding to an IL-13 receptor inhibits B-cell proliferation induced by IL-13 by at least about 70%, at least about 80%, or at least about 90% in an in vitro assay, such as the assay described herein where 1 x 10 5 B cells were incubated with 10 or 100 nM anti-IL-13 dAbs. A ligand (e.g., single immunoglobulin variable domain) that does not substantially inhibit the binding of IL-13 to an IL-13 receptor (e.g., IL-l3Ra1, IL-13Ra2) does not significantly inhibit the binding of IL-13 to an IL-13 receptor in the sandwich binding assay or sandwich ELISA assay described herein. For example, said ligand must inhibit the assay of IL-13 to an IL-13 receptor in the receptor binding assay described herein with an IC50 of about 1 mM or greater or inhibit the binding no more than about 20%, no more about 15%, no more than about 10%, or no more than about 5%. The ligand having binding specificity for IL-13 may contain a single immunoglobulin variable domain with binding specificity for IL-13 binds IL-13 with an affinity (KD) that is between about 100 nM and about 1 pM, such as it is determined by surface plasmon resonance. The ligand having binding specificity for IL-13 can bind IL-13 with an affinity (KD) that is between about 300 nM and about 1 pM, as determined by surface plasmon resonance.

The ligand having binding specificity for IL-13 may comprise a single immunoglobulin variable domain with binding specificity for IL-13 which is selected from the group consisting of a human VH and a human VL- In some embodiments, the ligand which has binding specificity for IL-13 is an IgG type format comprising at least two variable domains of single immunoglobulin with binding specificity for IL-13. In some embodiments, the ligand having binding specificity for IL-13 comprises an antibody region of Fe. In some embodiments, the ligand having binding specificity for IL-13 comprises an IgG constant region. The present invention also relates to a ligand (e.g., fusion protein) having binding specificity for IL-4 and IL-13, comprising a single immunoglobulin variable domain with binding specificity for IL-4, wherein the variable domain of simple immunoglobulin with binding specificity for IL-4 competes to bind IL-4 with an IL-4 domain antibody (dAb) selected from the group consisting of the anti-IL-4 dAbs described herein and comprises a variable domain of simple immunoglobulin with binding specificity for IL-13 where the variable domain of simple immunoglobulin with binding specificity for IL-13 competes to bind IL-13 with an anti-IL-13 domain (dAb) antibody selected from the group consisting of anti-IL-13 dAbs described herein. For example, the ligand (e.g., fusion protein) comprising a single immunoglobulin variable domain with binding specificity for IL-4 may comprise an amino acid sequence having at least 85% amino acid sequence identity with the sequence of amino acid of a dAb selected from the group consisting of the anti-IL-4 dAbs described herein. In another example, the ligand (e.g., fusion protein) comprising the variable domain of single immunoglobulin with binding specificity for IL-13 may comprise an amino acid sequence having at least 85% amino acid sequence identity with the amino acid sequence of a dAb selected from the group consisting of anti-IL-13 dAbs described herein. In some embodiments, the ligand (e.g., fusion protein) comprising a single immunoglobulin variable domain with binding specificity for IL-4 and a single immunoglobulin variable domain with binding specificity for IL-3 further comprising a portion of link. The present invention relates to a ligand that comprises a portion of the protein having a binding site with binding specificity for IL-4, wherein the protein portion comprising an amino acid sequence that is equal to the amino acid sequence of CDR3 of an anti-IL-4 dAb here described. In some embodiments, the ligand comprises a portion of a protein having a binding site with binding specificity for IL-4, wherein the protein portion has an amino acid sequence that is equal to the amino acid sequence of CDR3 of a dAb. anti-IL-4 described herein, and also comprises an amino acid sequence that is the same to the amino acid sequence of CDR1 and / or CDR2 of an anti-IL-4 dAb described herein. In other embodiments, a ligand comprises a single immunoglobulin variable domain that binds IL-4, wherein the variable domain of single immunoglobulin binding IL-4 differs from the amino acid sequence of an anti-IL-4 dAb described herein in no. more than 25 amino acid positions and has a CDR1 sequence that has at least 50% identity with the CDR1 sequence of the anti-IL-4 dAbs described herein. In other embodiments, a ligand comprises a single immunoglobulin variable domain that binds IL-4, wherein the amino acid sequence of the single immunoglobulin variable domain that binds IL-4 differs from the amino acid sequence of an anti-IL-dAb. 4 described here and no more than 25 amino acid positions and has a CDR2 sequence that has at least 50% identity with the CDR2 sequence of the anti-IL-4 dAbs described herein. In other embodiments, a ligand comprises a single immunoglobulin variable domain that binds IL-4, wherein the amino acid sequence of the single immunoglobulin variable domain that binds IL-4 differs from the amino acid sequence of an anti-IL-4 dAb. described herein and not more than 25 amino acid positions and has a CDR3 sequence that has at least 50% identity with the CDR3 sequence of the anti-IL-4 dAbs described herein. In other embodiments, a ligand comprises a single immunoglobulin variable domain that binds IL-4, wherein the amino acid sequence of the single immunoglobulin variable domain that binds IL-4 differs from the amino acid sequence of an anti-IL-4 dAb. described herein and not more than 25 amino acid positions and has a CDR1 sequence and a CDR2 sequence having at least 50% identity of the CDR1 and CDR2 sequences, respectively, of the anti-IL-4 dAbs described herein. In other embodiments, a ligand comprises a single immunoglobulin variable domain that binds IL-4, wherein the amino acid sequence of the single immunoglobulin variable domain that binds IL-4 differs from the amino acid sequence of an anti-IL-4 dAb. here described and no more than amino acid positions and has a CDR2 sequence and a CDR3 sequence having at least 50% identity of the CDR2 or CDR3 sequences, respectively, of the anti-IL-4 dAbs described herein. In other embodiments, the ligand comprises a single immunoglobulin variable domain that binds IL-4, wherein the amino acid sequence of the single immunoglobulin variable domain that binds IL-4 differs from the amino acid sequence of an anti-IL-4 dAb. described herein and not more than 25 amino acid positions and has a CDR1 sequence and a CDR3 sequence having at least 50% identity with the CDR1 or CDR3 sequences, respectively of the anti-IL-4 dAbs described herein. In other embodiments, the ligand comprises a single immunoglobulin variable domain that binds IL-4, wherein the amino acid sequence of the single immunoglobulin variable domain that binds IL-4 differs from the amino acid sequence of an anti-IL-4 dAb. described herein and not more than 25 amino acid positions and has a CDR1 sequence, a CDR2 sequence and a CDR3 sequence that has at least 50% identity with the CDR1, CDR2 or CDR3 sequences, respectively, of the anti-HIV dAbs. IL-4 described here. In another embodiment, the present invention is a ligand comprising a single immunoglobulin variable domain that binds IL-4, wherein the variable domain of Simple immunoglobulin binding IL-4 has a CDR2 sequence that has at least 50% identity with the CDR2 sequences of an anti-IL-4 dAb described herein. In another embodiment, the present invention is a ligand comprising a variable domain of single immunoglobulin that binds IL-4, wherein the variable domain of single immunoglobulin binding IL-4 has a CDR3 sequence having at least 50% identity with the CDR3 sequences of an anti-IL-4 dAb described herein. In another embodiment, the present invention is a ligand comprising a single immunoglobulin variable domain that binds IL-4, wherein the variable domain of single immunoglobulin binding IL-4 has a CDR1 sequence and a CDR2 sequence having at least one 50% identity with the CDR1 and CDR2 sequences, respectively, of an anti-IL-4 dAb described herein. In another embodiment, the present invention is a ligand comprising a single immunoglobulin variable domain that binds IL-4, wherein the variable domain of single immunoglobulin binding IL-4 has a CDR2 sequence and a CDR3 sequence having at least 50% identity with the CDR2 and CDR3 sequences, respectively, of an anti-IL-4 dAb described herein. In another embodiment, the present invention is the ligand comprising a single immunoglobulin variable domain that binds IL-4, wherein the variable domain of single immunoglobulin that binds IL-4 has a CDR1 sequence and a CDR3 sequence that has at least 50% identity with the CDR1 and CDR3 sequences, respectively, of an anti-HIV antibody. IL-4 described here. In another embodiment, the present invention is the ligand comprising a single immunoglobulin variable domain that binds IL-4, wherein the variable domain of single immunoglobulin binding IL-4 has a sequence CDR1, CDR2, and a sequence of CDR3 having at least 50% identity with the CDR1, CDR2 and CDR3 sequences respectively, of an anti-IL-4 dAb described herein. In some embodiments, the ligand comprises a portion of a protein that has a binding site that binds to IL-13, wherein the protein portion comprises an amino acid sequence that is equal to the amino acid sequence of CDR3 of an anti-DNA. IL-13 described here. In other embodiments, the ligand comprises a portion of a protein having a binding site that binds IL-13, wherein the protein portion comprises an amino acid sequence that is equal to the amino acid sequence of CDR3 of an anti-IL dAb. -13 described herein and has an amino acid sequence that is equal to the amino acid sequence of CDR1 and / or CDR2 of an anti-IL-13 dAb described herein. In other embodiments, the ligand comprises a domain single immunoglobulin variable binding IL-13, wherein the amino acid sequence of the variable domain of single immunoglobulin binding IL-13, differs from the amino acid sequence of an anti-IL-13 dAb described herein and no more than 25 positions of amino acids and has a CDR1 sequence that has at least 50% identity with the CDR1 sequences of the anti-IL-13 dAbs described herein. In other embodiments, the ligand comprises a single immunoglobulin variable domain that binds IL-13, wherein the amino acid sequence of the single immunoglobulin variable domain that binds IL-13 differs from the amino acid sequence of an anti-IL-13 dAb. described herein and not more than 25 amino acid positions and has a CDR2 sequence that has at least 50% identity with the CDR2 sequences of the anti-IL-13 dAbs described herein. In other embodiments, the ligand comprises a single immunoglobulin variable domain that binds IL-13, wherein the amino acid sequence of the single immunoglobulin variable domain that binds IL-13 differs from the amino acid sequence of an anti-IL-13 dAb. described herein and not more than 25 amino acid positions and has a CDR3 sequence that has at least 50% identity with the CDR3 sequences of the anti-IL-13 dAbs described herein. In other embodiments, the ligand comprises a single immunoglobulin variable domain that binds IL-13, wherein the amino acid sequence of the single immunoglobulin variable domain linking IL-13 differs from the amino acid sequence of an anti-IL-13 dAb described herein and no more than 25 amino acid positions and has a CDR1 sequence and a CDR2 sequence that has at least 50% identity with the CDR1 and CDR2 sequences, respectively, of the anti-IL-13 dAbs described herein. In other embodiments, the ligand comprises a single immunoglobulin variable domain that binds IL-13, wherein the amino acid sequence of the single immunoglobulin variable domain that binds IL-13 differs from the amino acid sequence of an anti-IL-13 dAb. described herein and not more than 25 amino acid positions and has a CDR2 sequence and a CDR3 sequence having at least 50% identity of the CDR2 and CDR3 sequences, respectively, of the anti-IL-13 dAbs described herein. In other embodiments, the ligand comprises a single immunoglobulin variable domain that binds to IL-13, wherein the amino acid sequence of the variable domain of single immunoglobulin binding to IL-13 differs from the amino acid sequence of an anti-IL dAb. -13 described herein and no more than 25 amino acid positions and has a CDR1 sequence and a CDR3 sequence having at least 50% identity with the CDR1 and CDR3 sequences, respectively, of the anti-IL-13 dAbs described herein .

In other embodiments, the ligand comprises a single immunoglobulin variable domain that binds to IL-13, wherein the amino acid sequence of the variable domain of single immunoglobulin binding to IL-13 differs from the amino acid sequence of an anti-IL dAb. -13 described herein and no more than 25 amino acid positions and has a CDR1 sequence, CDR2 sequence and a CDR3 sequence having at least 50% identity of the CDR1, CDR2 and CDR3 sequences, respectively, of the anti-DNA dAbs. IL-13 described here. In another embodiment, the present invention is a ligand comprising a variable domain of single immunoglobulin binding to IL-13, wherein the variable domain of single immunoglobulin comprises a sequence of CDR2 having at least 50% identity with the sequence CDR2 of an anti-IL-13 dAb described herein. In another embodiment, the present invention is a ligand comprising a variable domain of single immunoglobulin binding to IL-13, wherein the variable domain of single immunoglobulin comprises a sequence of CDR3 having at least 50% identity with the sequence CDR3 of an anti-IL-13 dAb described herein. In another embodiment, the present invention is a ligand comprising a single immunoglobulin variable domain that binds to IL-13, wherein the single immunoglobulin variable domain comprises a CDR1 sequence and a CDR2 sequence having at least 50% identity with the CDR1 and CDR2 sequences, respectively, of an anti-IL-13 dAb described herein. In another embodiment, the present invention is a ligand comprising a single immunoglobulin variable domain that binds to IL-13, wherein the single immunoglobulin variable domain comprises a CDR2 sequence and a CDR3 sequence having at least 50% identity. with the CDR2 and CDR3 sequences, respectively, of an anti-IL-13 dAb described herein. In another embodiment, the present invention is a ligand comprising a single immunoglobulin variable domain that binds to IL-13, wherein the single immunoglobulin variable domain comprises a CDR1 sequence and a CDR3 sequence having at least 50% identity. with the CDR1 and CDR3 sequences, respectively, of an anti-IL-13 dAb described herein. In another embodiment, the present invention is a ligand comprising a single immunoglobulin variable domain that binds to IL-13, wherein the variable domain of single immunoglobulin comprises a sequence CDR1, CDR2, and a CDR3 sequence having at least 50 % identity with the CDR1, CDR2, and CDR3 sequences, respectively, of an anti-IL-13 dAb described herein. In other modalities, any of the ligands here described further comprises a half-life extension portion, such as a polyalkylene glycol moiety, serum albumin or a fragment thereof, a transfer receptor or a transfer link portion thereof, or a portion comprising a binding site of a polypeptide that increases the half-life in vivo. In some embodiments, the half-life extension portion is a portion comprising a binding site for a polypeptide that increases the in vivo half-life selected from the group consisting of an affibody, an SpA domain, an LDL class A receptor domain. , an EGF domain, and an avimer. In other embodiments, the half-life extension portion is a polyethylene glycol portion. In other embodiments, the half-life extension portion is an antibody or an antibody fragment (e.g., a single immunoglobulin variable domain) that comprises a binding site for serum albumin or neonatal Fe receptor. The present invention is to a ligand of the present invention for use in therapy or diagnosis, and to the use of a ligand of the present invention for the manufacture of a medicament for the treatment, prevention or suppression of a disease described herein (e.g., allergic disease, transmitted by Th2, asthma, cancer). The present invention also relates to a ligand of the same for use in the treatment, suppression or prevention of a Th2 type immune response. The present invention also relates to therapeutic methods comprising administering a therapeutically effective amount of a ligand of the present invention to a subject in need thereof. In one embodiment, the present invention relates to a method for inhibiting a Th2 type immune response, wherein the method comprises administering a subject in need thereof a therapeutically effective amount of a ligand of the present invention. In other embodiments, the present invention relates to a method for treating asthma, wherein the method comprises administering a subject in need thereof, a therapeutically effective amount of a ligand of the present invention. In other embodiments, the present invention relates to a method for treating cancer, wherein the method comprises administering a subject in need thereof a therapeutically effective amount of a ligand of the present invention. The present invention also relates to the use of any of the ligands of the present invention for the manufacture of a medicament for the simultaneous administration of an anti-IL-4 treatment and an anti-IL-treatment. 13. In other modalities, the present invention relates to a method for administering to a subject an anti-IL-4 treatment and an anti-IL-13 treatment, characterized in that it comprises the simultaneous administration of an anti-IL-4 treatment and an anti-IL treatment. -13, administering to the subject a therapeutically effective amount of a ligand having binding specificity for IL-4 and IL-13. The present invention relates to a composition (e.g., pharmaceutical composition) comprising a ligand of the present invention and a physiologically acceptable carrier. In some embodiments, the composition comprises a vehicle for intravenous, intramuscular, intraperitoneal, intra-arterial, intrathecal, intra-articular, subcutaneous, pulmonary, intranasal, vaginal, or rectal administration. The present invention also relates to a drug delivery apparatus comprising the composition (e.g., pharmaceutical composition) of the present invention. In some embodiments, the drug delivery apparatus comprises a plurality of therapeutically effective doses of a ligand. In other embodiments, the drug delivery apparatus is selected from the group consisting of a parenteral delivery apparatus, an intravenous delivery device, an intramuscular delivery device, an intraperitoneal delivery device, a transdermal delivery device, a pulmonary delivery apparatus, an intra-arterial delivery apparatus, an intrathecal delivery apparatus, an intra-articular delivery apparatus, a subcutaneous delivery apparatus, an intranasal delivery apparatus, a vaginal delivery apparatus, a rectal delivery apparatus , a syringe, a transdermal delivery device, a capsule, a tablet, a nebulizer, an inhaler, an atomizer, an aerosol, a nebulizer, a dry powder inhaler, a metered dose inhaler, a metered dose sprayer, a Metered dose nebulizer, a metered dose atomizer and a catheter. The present invention also relates to an isolated or recombinant nucleic acid encoding any of the ligands of the present invention. In other embodiments, the present invention relates to a vector comprising the recombinant nucleic acid of the present invention. The present invention also relates to a host cell comprising the recombinant nucleic acid of the present invention or the vector of the present invention. The present invention also relates to a method for producing a ligand, characterized in that it comprises maintaining a host cell of the present invention under conditions suitable for the expression of a nucleic acid or vector of the present invention, whereby the ligand is produced. In other embodiments, the method for producing a ligand further comprises isolating the ligand.

The present invention also relates to a method for inhibiting the proliferation of peripheral blood mononuclear cells (PBMC) in an allergen-sensitive subject, wherein the method comprises administering to a subject a pharmaceutical composition comprising any of the ligands of the present invention. invention. In some embodiments, the allergen is selected from house dust mites, cat allergen, grass allergen, mud allergen and pollen allergen. The present invention also relates to a method for inhibiting the proliferation of B cells in a subject, wherein the method comprises administering to the subject a pharmaceutical composition comprising a ligand of the present invention. The present invention also relates to a pharmaceutical composition for treating preventing or suppressing a disease described herein (e.g., Th2-transmitted disease, allergic disease, asthma, cancer), wherein the composition comprises as an active ingredient a ligand such as herein It is described. The present invention also relates to a ligand having binding specificity for IL-4 and IL-13, comprising a portion of a protein having a binding site with binding specificity for IL-4, and a portion of protein that has a binding site with binding specificity for IL-13, where the portion of protein having specificity Linkage for IL-4 does not compete to bind with any of the anti-IL-4 dAbs described herein. The present invention also relates to a ligand having binding specificity for IL-4 and IL-13 comprising a portion of protein having a binding site with binding specificity for IL-4, and a portion of protein having a binding site with binding specificity for IL-13, wherein the protein portion having binding specificity for IL-13, does not compete to bind with any of the anti-IL-13 dAbs described herein. The present invention also relates to a ligand having binding specificity for IL-4 and IL-13, wherein the ligand is a fusion protein comprising a single immunoglobulin variable domain with binding specificity for IL-4 and a variable domain of simple immunoglobulin with binding specificity for IL-13, wherein the variable domain of simple immunoglobulin with binding specificity for IL-4 competes to bind IL-4 with an antibody of domain IL-4 (dAb) selected from group consisting of DOM9-112-210 and DOM9-155-78, and the single immunoglobulin variable domain with binding specificity for IL-13 competes to bind IL-13 with an anti-IL-13 domain antibody (dAb ) selected from the group consisting of DOM10-208, DOM10-212, DOM10-213, DO M 10-215, DOM10-224, DOM10-270, DOM10-416, DOM10-236, DOM10-273, DOM10-275, DOM10-276 and DOM10-277. In some embodiments, the present invention relates to a ligand having binding specificity for IL-4, comprising a single immunoglobulin variable domain with binding specificity for human IL-4 and a non-human IL-4. In preferred embodiments, non-human IL-4 is selected from IL-4 resus and IL-4 cynomolgus. It is also preferred that the binding affinity of the variable domain of single immunoglobulin for non-human IL-4 and the binding affinity for human IL-4, differ by a factor not greater than 10, 50, 100, 500 or 1000. In some embodiments, the present invention relates to a ligand having binding specificity for IL-13, comprising a single immunoglobulin variable domain with binding specificity for human IL-13 and a non-human IL-13. In preferred embodiments, non-human IL-13 is selected from IL-13 resus and IL-13 cynomolgus. It is also preferred that the binding affinity of the variable domain of single immunoglobulin for non-human IL-13 and binding affinity for human IL-13 differ by a factor not greater than 10, 50, 100, 500 or 1000. In other embodiments , the present invention relates to a ligand having binding specificity for IL-4 and IL-13, comprising a variable domain of simple immunoglobulin with binding specificity for IL-4 and a variable domain of simple immunoglobulin with binding specificity for IL-13, wherein the variable domain of simple immunoglobulin with binding specificity for IL-4 binds to human IL-4 and non-human IL-4 and the variable domain of simple immunoglobulin with binding specificity for IL-13 binds to human IL-13 and non-human IL-13. In preferred embodiments, human IL-4 is selected from IL-4 resus and IL-4 cynomolgus and non-human IL-13 is selected from IL-13 resus and IL-13 cynomolgus. It is also preferred that the binding affinity of the variable domain of single immunoglobulin for non-human IL-4 and binding affinity for human IL-4 differ by a factor not greater than 10, 50, 100, 500 or 1000, and affinity of the variable domain of simple immunoglobulin for non-human IL-13 and binding affinity for human IL-13 differ by a factor not greater than 10, 50, 100, 500 or 1000. Brief Description of the Drawings Figures 1A a 1U, illustrates several nucleotide sequences encoding human VH domain antibodies. { Homo sapiens) (dAbs) that bind specifically to human IL-4. The nucleotide sequences presented are SEQ ID NOS: 1-174. Figures 2A to 2J illustrate the amino acid sequences of the dAbs encoded via the nucleic acid sequences shown in Figures 1A to 1U. The amino acid sequences presented are SEQ ID NOS: 175-348.

Figures 3A to 3S illustrate several nucleotide sequences encoding human VK domain antibodies (Homo sapiens) (dAbs) that specifically bind to human IL-4. The nucleotide sequences presented are SEQ ID NOS: 349-499. Figures 4A to 4H illustrate the amino acid sequences of the dAbs encoded via the nucleic acid sequences shown in Figures 3A to 3S. The amino acid sequences presented are SEQ ID NOS: 500-650. Figures 5A to 5Z, 5AA to 5MM, illustrate various nucleotide sequences encoding human VH domain antibodies (Homo sapiens) (dAbs) that specifically bind to human IL-13. The nucleotide sequences presented are SEQ ID NOS: 651-966. Figures 6A to 6Q illustrate the amino acid sequences of the dAbs encoded through the nucleic acid sequences shown in Figures 5A to 5Z, 5AA to 5MM. The amino acid sequences presented are SEQ ID NOS: 967-1282. Figures 7A to 7Z, 7AA to 7BB, illustrate various nucleotide sequences encoding human VK domain antibodies (Homo sapiens) (dAbs) that specifically bind human IL-13. The nucleotide sequences presented are SEQ ID NOS: 1283-1507. Figures 8A to 8L, illustrate the sequences of amino acids of the dAbs encoded through the nucleic acid sequences shown in Figures 7A to 7Z, 7AA, 7BB. The amino acid sequences presented are SEQ ID NOS: 1508-1732. Figure 9A is an alignment of the amino acid sequences of the six VKS that bind rat serum albumin (RSA). The aligned amino acid sequences are from VKS designated as DOM7r-1 (SEQ ID NO: 1736), DOM7r-3 (SEQ ID NO: 1737), DOM7r-4 (SEQ ID NO: 1738), DOM7r-5 (SEQ ID NO. : 1739), DOM7r-7 (SEQ ID NO: 1740), and DOM7r-8 (SEQ ID NO: 1741). Figure 9B is an alignment of the amino acid sequences of six VKs that bind human serum albumin (HSA). The aligned amino acid sequences are from VKs designated DOM7h-2 (SEQ ID NO: 1742), DOM7h-3 (SEQ ID NO: 1743), DOM7h-4 (SEQ ID NO: 1744), DOM7h-6 (SEQ ID NO: 1745), DOM7h-1 (SEQ ID NO: 1746) and DOM7h-7 (SEQ ID NO: 1747). Figure 9C is an alignment of the amino acid sequences of seven VHs that bind human serum albumin and a consensus sequence (SEQ ID NO: 1755). The aligned sequences are from designated VHs DOM7h-22 (SEQ ID NO: 1748), DOM7h-23 (SEQ ID NO: 1749), DOM7h-24 (SEQ ID NO: 1750), DOM7h-25 (SEQ ID NO: 1751) , DOM7h-26 (SEQ ID NO: 1752), DOM7h-21 (SEQ ID NO: 1753) and DOM7h-27 (SEQ ID NO: 1754). Figure 9D is an alignment of the amino acid sequences of three VKS that bind human serum albumin and rat serum albumin. The aligned amino acid sequences are from the VKS designated DOM7h-8 (SEQ ID NO: 1756), DOM7r-13 (SEQ ID NO: 1757) and DOM7r-14 (SEQ ID NO: 1758). Figure 10 is an illustration of the amino acid sequences of VKS that bind rat serum albumin (RSA). The illustrated sequences are from VKS designated DOM7r-15 (SEQ ID NO: 1759), DOM7r-16 (SEQ ID NO: 1760), DOM7r-17 (SEQ ID NO: 1761), DOM7r-18 (SEQ ID NO: 1762) , DOM7r-19 (SEQ ID NO: 1763). Figures 11A to 11B are an illustration of the amino acid sequences of the amino acid sequences of VHs that bind rat serum albumin (RSA). The illustrated sequences are from the designated VHs DOM7r-20 (SEQ ID NO: 1764), DOM7r-21 (SEQ ID NO: 1765), DOM7r-22 (SEQ ID NO: 1766), DOM7r-23 (SEQ ID NO: 1767) ), DOM7r-24 (SEQ ID NO: 1768), DOM7r-25 (SEQ ID NO: 1769), DOM7r-26 (SEQ ID NO: 1770), DOM7r-27 (SEQ ID NO: 1771), DOM7r-28 ( SEQ ID NO: 1772), DOM7r-29 (SEQ ID NO: 1773), DOM7r-30 (SEQ ID NO: 1774), DOM7r-31 (SEQ ID NO: 1775), DOM7r-32 (SEQ ID NO.-1776 ) and DOM7r-33 (SEQ ID NO: 1777). Figure 12 illustrates the amino acid sequences of various Camelid VHHS that bind to mouse serum albumin which are described in WO 2004/041862. Sequence A (SEQ ID NO: 1778), Sequence B (SEQ ID NO: 1779), Sequence C (SEQ ID NO: 1780), Sequence D (SEQ ID NO: 1781), Sequence E (SEQ ID NO: 1782) , Sequence F (SEQ ID NO: 1783), Sequence G (SEQ ID NO: 1784), Sequence H (SEQ ID NO: 1785), Sequence I (SEQ ID NO: 1786), Sequence J (SEQ ID NO: 1787) , Sequence K (SEQ ID NO: 1788), Sequence L (SEQ ID NO: 1789), Sequence M (SEQ ID NO: 1790), Sequence N (SEQ ID NO: 1791), Sequence O (SEQ ID NO: 1792) , Sequence P (SEQ ID NO: 1793), and Sequence Q (SEQ ID NO: 1794). Figure 13 is a sensorgram that shows some of the dAbs that link IL-4 (DOM9-112-22, DOM9-44 and DOM9-155-1) that link to different IL-4 epitopes. IL-4 was immobilized on a surface plasmon resonance chip and a first anti-IL-4 dAb was flown over the surface and a second dAb was subsequently flowed over the surface. This figure shows that DOM9-155-1 did not bind to IL-4 after it linked DOM9-44. Similarly, DOM9-44 did not bind after it linked DOM9-155-1. However, the third and fourth peaks show that DOM9-112-22 bound to IL-4 after DOM9-44 was linked and also after DOM9-155-1 was linked, which shows that these dAbs bind to different epitopes in the IL-4 antigen.

Figure 14A, is a graph showing the effect of 100 nM anti-IL-4 dAb (DOM9-44-502) on a proliferation induced by domestic dust acarid (HDM) of peripheral blood mononuclear cells (PBMC) from twelve individual donors in an in vitro assay. Cell proliferation was evaluated by measuring the incorporation of 3 [H] trimidine. The addition of anti-IL-4 dAb inhibited allergen-induced proliferation of PBMC obtained from ten of the twelve donors. The average inhibition was 38%. Figure 14B, is a graph showing the effect of 100 nM anti-IL-4 dAb (DOM9-155-11) on a proliferation induced by domestic dust acarid (HDM) of PBMC from twelve individual donors in an in vitro assay. Cell proliferation was evaluated by measuring 3 [H] trimidine incorporation. The addition of anti-IL-4 dAb inhibited the allergen-induced proliferation of PBMC obtained from ten of the twelve donors. The average inhibition was 34%. Figure 15 is a graph showing the effect of anti-IL-13 dAbs DOM10-53-338 and DOM 10-176-535 on B-cell proliferation induced by IL-13. Cell proliferation was evaluated by measuring incorporation of 3 [H] trimidine. Both dAbs showed an average inhibition of 80% at a concentration of 10nM and an average inhibition of 100% at a concentration of 100 nM. Figure 16A is a graph showing the effect of a double specific ligand of extended half-life format that binds IL-4 and IL-13 (PEGylated DOM9-112 (AST) DOM10-53-343) on the IL-4 binding in an IL-4 receptor binding assay. The strength of the anti-IL-4 arm of the specific double ligand (PEGylated DOM9-112 (AST) DOM 10-53-343) was 13 nM. The monomer dAb DOM9-112 power was 3.5 nM. The graph shows that the potency of the specific double ligand (PEGylated DOM9-112 (AST) DOM 10-53-343) was only reduced in light form compared to dAb. Figure 16B is a graph showing the effect of a double-ligand specific for extended half-life format that binds IL-4 and IL-13 (PEGylated DOM9-112 (AST) DOM10-53-343) on an IL- link 13 in an IL-13 receptor binding assay. The strength of the anti-IL-13 arm of the double specific ligand was 310 pM and the potency of the monomer dAb DOM10-53-343 was 230 pM. The graph shows that the potency of the double specific ligand was approximately equal to that of the dAb monomer. Figure 17A is a graph showing the effect of the double specific ligand (DOM9-112 (ASTKGPS) DOM10-53-344) on an IL-4 bond in the IL-4 receptor ligand assay. The strength of the anti-IL-4 arm of the double specific ligand and the monomer dAb DOM9-112 was approximately 1 nM. The graph shows that the potency of the double specific ligand was approximately equal to that of the dAb monomer.

Figure 17B is a graph showing the effect of the double specific ligand (DOM9-112 (ASTKGPS) DOM10-53-344) on the IL-13 binding in the IL-13 receptor binding assay. The strength of the anti-IL-13 arm of the double specific ligand was 120 pM. The potency of monomer dAb DOM 10-53-344 was 40 pM. The graph shows that the potency of the double specific ligand was only reduced in light form compared to the dAb monomer. Figure 18A is a graph showing the effect of a double specific IgG type format that binds IL-4 and IL-13 (IgG: 9-44-502 x 10-176-535) on the IL-4 link in the IL-4 receptor binding assay. The monomer dAb DOM9-44-502 power was 4 nM and the power of the double specific IgG type format was 13 nM. The graph shows that the potency of the monomer anti-IL-4 dAb DOM9-44-502 was reduced 3 to 4 times when formatted in an IgG type format. Figure 18B is a graph showing the effect of a double specific IgG type format that binds IL-4 and IL-13 (IgG: 9-44-502 x 10-176-535) on an IL-13 link in ELISA sandwich assay IL-13. The power for both the specific IgG type format and for the DOM10-176-535 dAb monomer was 1 nM. Figures 19A to 19Z, 19AA to 19ZZ, 19AAA to 19HHH, illustrate various nucleotide sequences encoding human domain antibodies (Homo sapiens) (dAbs) that specifically bind IL-13 and nucleotide sequences of several primers. The nucleotide sequences presented are SEQ ID NOS: 1804-2128. Figures 20A to 20Z, 20AA to 20CC, illustrate the amino acid sequences of the dAbs encoded by the nucleic acid sequences shown in Figures 19A to 19Z, 19AA to 19ZZ, 19AAA to 19HHH. The amino acid sequences presented are SEQ ID NOS: 2129-2392. Figures 21A to 21E illustrate various nucleotide sequences encoding human domain antibodies. { JHomo sapiens) (dAbs) that specifically bind IL-4. The nucleotide sequences presented are SEQ ID NOS: 2393-2425. Figures 22A to 22C illustrate the amino acid sequences of the dAbs encoded via the nucleic acid sequences shown in Figures 21A to 21E. The amino acid sequences presented are SEQ ID NOS: 2426-2455 and SEQ ID NOS: 1733-1735. Detailed Description of the Invention Within the present specification, modalities have been described in a form that allows a clear and concise specification to be written, although it is intended and it will be appreciated that the modalities may be combined or separated in various ways without departing from the present invention.

As used in the present invention, the term "ligand" refers to a compound comprising at least a portion of peptide, polypeptide or protein having a binding site with binding specificity for a desired endogenous target compound (e.g. , IL-4, IL-13). Ligands according to the present invention preferably comprise immunoglobulin variable domains having different binding specificities, and do not contain pairs of variable domains that together form a binding site for a target compound (eg, they do not comprise a variable domain of Immunoglobulin heavy chain and an immunoglobulin light chain variable domain that together form a binding site for IL-4 or IL-13). Preferably each domain having a binding site that has binding specificity for a target is a single immunoglobulin variable domain (eg, single immunoglobulin heavy chain variable domain (eg, VH, VHH), light chain variable domain of simple immunoglobulin (e.g., VL)) having binding specificity for a desired objective (e.g., IL-4, IL-13). Each polypeptide domain having a binding site that has binding specificity for a target (eg, IL-4, IL-13) may also comprise one or more complementarity determining regions (CDRs) of an antibody or fragment of antibody (for example, a domain single immunoglobulin variable) having binding specificity for a desired target (eg, IL-4, IL-13) in a suitable format, so that the binding domain has binding specificity for the target. For example, CDRs can be grafted onto a suitable protein scaffold or scaffold, such as an affibody, an SpA scaffold, an LDL class A receptor domain, or an EGF domain. In addition, the ligand may be bivalent (heterobivalent) or multivalent (heteromultivalent), as described herein. Therefore, "ligands" include polypeptides comprising two dAbs, wherein each dAb binds to a different target (e.g., IL-4, IL-13). The ligands also include polypeptides comprising at least two dAbs that bind to different targets (or CDRs of dAbs) in a suitable format, such as an antibody format (e.g., IgG, scFv, Fab, Fab ', F type format). (ab ') 2) or a suitable scaffold or protein skeleton, such as an affibrant, a SpA scaffold, an LDL class A receptor domain, an EGF domain, avimer and multispecific ligands as described herein. The polypeptide domain having a binding site that has binding specificity for a target (eg, IL-4, IL-13) can also be a protein domain comprising a binding site for a desired target, e.g. , a protein domain that is selected from an affibody, an SpA domain, an LDL class A receptor domain, an avimer (see for example, US Patent Application Publication Nos. 2005/0053973, 2005/0089932, 2005/0164301). If desired, a "ligand" may further comprise one or more additional portions, which may each be independently a peptide, polypeptide or protein portion or a portion without a peptide (eg, a polyalkylene glycol, a lipid, a carbohydrate). For example, the ligand may further comprise a portion extending the half-life, as described herein, (eg, a portion of polyalkylene glycol, a portion comprising albumin, a fragmentate albumin or an albumin variant, a portion comprising transferrin , a fragment of transferrin or variant of transferrin, a portion that binds to albumin, a procion that binds to the neonatal receptor Fe. As used in the present invention the term "target" refers to a biological molecule (eg, peptide, polypeptide, protein, lipid, carbohydrate) to which a polypeptide domain having a binding site can bind. The objective may be for example, an intracellular target (eg, an intracellular protein target) a soluble target (eg, a secreted protein, such as IL-4, IL-3) or a cell surface target (e.g. , a membrane protein, a receptor protein). Preferably, the target is IL-4 or IL-13. The phrase "single immunoglobulin variable domain" is refers to a variable region of antibody (VH, VHH, V1) that binds specifically to a target, antigen or epitope independently of other V domains; however, as the term is used in the present invention, a single immunoglobulin variable domain can be presented in one format (eg, hetero-multimer) with other variable regions or variable domains, where the other regions or domains are not. required for antigen binding through the variable domain of single immunoglobulin (eg, wherein the variable domain of single immunoglobulin binds antigen independently of the additional variable domains). Each "single immunoglobulin variable domain" comprises not only an isolated single antibody variable domain polypeptide, but also larger polypeptides comprising one or more monomers of a single antibody variable domain polypeptide sequence. A "domain antibody" or "dAb" is the same as a "single immunoglobulin variable domain" polypeptide as the term is used in the present invention. A single immunoglobulin variable domain polypeptide is preferably a mammalian immunoglobulin variable domain polypeptide, more preferably human, and includes variable domains of simple rodent immunoglobulin (e.g., as described in WO 00/29004). whose contents are incorporated in its entirety to the present invention as reference) and dHebs VHH of camelid. As used in the present invention, camelid dAbs are single immunoglobulin variable domain polypeptides which are derived from species including camel, llama, alpaca, dromedary and guanaco, and comprise heavy chain antibodies naturally devoid of light chain ( VHH) - Similar dAbs can be obtained from single chain antibodies from other species, such as a nurse shark. Preferred ligands comprise at least two different single immunoglobulin variable domain polypeptides or at least different dAbs. The variable domains of simple immunoglobulin (dAbs) described herein contain regions of complementarity determination (CDR1, CDR2 and CDR3). The locations of CDRs and structure regions (FR) and a numbering system have been defined by Kabat and associates (Kabat, EA and associates., Sequences of Proteins of Immunological Interest, Fifth Edition, US Department of Health and Human Services, US Government Printing Office (1991) The amino acid sequences of the CDRs (CDR1, CDR2, CDR3) of the dAbs VH and VK described herein will be readily appreciated by those skilled in the art, based on the amino acid numbering system Well-known Kabat and the definition of the CDRs, in accordance with the Kabat numbering CDR1 VL (VK Ó \?) is from position 24 to 34, CDR2 VL is from position 50 to 56, CDR3 VL is from position 89 to 97 and CDR1 VH is from position 31 to 35, CDR2 VH is from position 50 to 65 and CDR3 VH is from position 95 to 102. The heavy chain CDR-H3 have varying lengths, inserts are listed between residues H100 and H101 with letters up to K (for example, H100 , H100A ... H100K, H101). The residue 103 which is the start of FR4, is almost always a W. As used in the present invention, the term "interleukin-4" (IL-4) refers to endogenous mammalian IL-4 proteins or naturally occurring proteins already have an amino acid sequence that is the same as the corresponding naturally occurring or endogenous mammalian IL-4 protein (e.g., recombinant proteins, synthetic proteins (e.g., produced using organic chemistry methods synthetic)). Accordingly, as defined in the present invention, the term includes mature IL-4 protein, polymorphic or allelic variants and other isoforms of an IL-4 and modified or unmodified forms of the foregoing (eg, lipidated, glycosylated) . Endogenous or naturally occurring IL-4 includes wild-type proteins such as mature IL-4, polymorphic or allelic variants and other isoforms and mutant forms that occur naturally in mammals (e.g., human, non-human primates). These proteins can be coated or isolated from a source that naturally produces, for example, IL-4. These proteins and proteins having the same amino acid sequence as the corresponding naturally occurring or endogenous IL-4 are referred to by the name of the corresponding mammal. For example, when the corresponding mammal is a human, the protein is designated as human IL-4. Several mutant IL-4 proteins are known in the art, such as those described in WO 03/038041. As used in the present invention, the term "interleukin-13" (IL-13) refers to endogenous or naturally occurring mammalian IL-13 proteins and to proteins that have an amino acid sequence that is the same as that of naturally occurring mammalian IL-13 protein or endogenous, corresponding (eg, recombinant proteins, synthetic proteins (eg, produced using synthetic organic chemistry methods)). Accordingly, as defined in the present invention, the term includes mature IL-13 protein, polymorphic or allelic variants, and other isoforms of an IL-13 (e.g., produced by alternative division processes or other cellular processes), and modified or unmodified forms of the foregoing (for example, lipidated, glycosylated). Endogenous or naturally occurring IL-13 includes natural proteins such as mature IL-13, polymorphic or allelic variants and other isoforms and mutant forms that occur naturally in mammals (eg, human, non-human primates). For example, as used in the present invention, IL-13 comprises the human IL-13 variant in which Arg at position 110 of mature IL-13 is replaced with Gln (position 100 of mature IL-13 corresponding to position 130 of the precursor protein) which is associated with asthma (atopic or non-atopic asthma) and other variants of IL-13. (Heinzmann et al., Hum Mol Genet, 9: 549-559 (2000)). Said proteins can be recovered or isolated from a source that naturally produces IL-13, for example. These proteins and proteins that have the same amino acid sequence to endogenous or naturally occurring, corresponding IL-13 are referred to by the name of the corresponding mammal. For example, when the corresponding mammal is a human, the protein is designated as human IL-13. Various mutant IL-13 proteins are known in the art, such as those described in WO 03/035847. The terms "affinity" and "avidity" are terms in the art that describe the strength of a bonding interaction. With respect to the ligands of the present invention, avidity refers to the overall resistance of the link between the targets (eg, first cell surface target and second cell surface target) in the cell and the ligand. Avidity is greater than the sum of the individual affinities of the individual goals. As used in the present invention, the term "toxin portion" refers to a portion comprising a toxin. A toxin is an agent that has detrimental effects, or alters cellular physiology (eg, causes cell necrosis, apoptosis or inhibits cell division). As used in the present invention, the term "dose" refers to the amount of ligand administered to a subject at a time (unit dose), or in two or more administrations during a defined time interval. For example, the dose may refer to the amount of ligand (eg, ligand comprising a variable domain of single immunoglobulin binding to IL-4 and a variable domain of single immunoglobulin binding to IL-13) administered to a subject in the course of one day (24 hours) (daily dose), two days, one week, two weeks, three weeks or one or more months (for example, through a single administration or through two or more administrations). The interval between doses can be any desired amount of time. As used in the present invention, the term "complementarity" refers to when two immunoglobulin domains belong to families of structures that form pairs or cognate groups or are derived from said families and retain their characteristic. For example, a VH domain and a VL domain of an antibody are complementary; two domains VH are not complementary, and two VL domains are not complementary. The complementarity domains can be found in other members of the immunoglobulin superfamily, such as the Va and Vp domains (o and 5) of the T cell receptor. Domains that are artificial, such as domains based on protein scaffolds that do not link epitopes unless constructed to perform this function, are non-complementary. Similarly, the base (for example) domains of an immunoglobulin domain and a fibronectin domain are not complementary. As used in the present invention, the term "immunoglobulin" refers to a family of polypeptides that retains the immunoglobulin fold characteristic of antibody molecules, which contain two β-sheets and typically, a conserved disulfide bond. Members of the immunoglobulin superfamily are involved in many aspects of cellular and non-cellular interactions in vivo, including broad roles in the immune system (e.g., antibodies, T-cell receptor molecules and the like), involvement in cell adhesion ( for example, ICAM molecules) and intracellular signaling (e.g., receptor molecules, such as PDGF receptor). The present invention applies to all molecules of the immunoglobulin superfamily that possess binding domains. Preferably, the present invention relates to antibodies As used in the present invention, the term "domain" refers to a bent protein structure that retains its tertiary structure independently of the rest of the protein. Generally, domains are responsible for the functional properties other than proteins, in many cases they can be added, deleted or transferred to other proteins without the loss of function of the rest of the protein and / or the domain. By the term simple antibody variable domain is meant a bent polypeptide domain comprising characteristic sequences of antibody variable domains. Accordingly, it includes entire variable domains of antibodies and modified variable domains, for example, where one or more loops have been replaced by sequences that are not characteristic of variable domains of antibody or variable domains of antibody that have been truncated or comprise N-extents. or C-terminal, as well as bent fragments of variable domains that retain at least in part the binding activity and specificity of the total length domain. Therefore, each ligand comprises at least two different domains. The term "repertoire" is a collection of various variants, for example, polypeptide variants that differ in their primary sequence. A library comprising a repertoire of polypeptides, preferably comprises less 1000 members. The term "library" refers to a mixture of heterogeneous polypeptides or nucleic acids. The library is composed of members, each of which has a simple polypeptide or nucleic acid sequence. For this purpose, the library is synonymous with repertoire. The differences in sequence among library members are responsible for the diversity found in the library. The library can take the form of a simple mixture of polypeptides or nucleic acids, or it can be in the form of organisms or cells, for example, cells of bacteria, viruses, animals or plants and the like, transformed with a library of nucleic acids. Preferably, each individual organism or cell contains only one or a limited number of members of the library. In a convenient way, the nucleic acids are incorporated into expression vectors, in order to allow the expression of the polypeptides encoded by the nucleic acids. In a preferred aspect, therefore, a library can take the form of a population of host organisms, each organism containing one or more copies of an expression vector that contains a single member of the library in the form of a nucleic acid that can be expressed to produce its corresponding polypeptide member. Therefore, the population of host organisms has the potential to code a large repertoire of genetically diverse polypeptide variants. As used in the present invention, an antibody refers to IgG, IgM, IgA, IgD or IgE or a fragment (such as Fab, F (ab ') 2, Fv, disulfide-linked Fv, scFv, multispecific antibody of closed conformation, disulfide-linked scFv, diabody) either derived from any species that naturally produces an antibody, or created by recombinant DNA technology; either serum isolate, B cells, hybridomas, transfectomas, bacteria or yeast. As described in the present invention, a "antigen" is a molecule that is linked through a binding domain according to the present invention. Normally, the antigens are linked by antibody ligands and have the ability to raise an antibody response in vivo. It can be a polypeptide, protein, nucleic acid or other molecule. Generally, the specific double ligands according to the present invention are selected for objective specificity against two particular targets (e.g., antigens). In the case of antibodies and conventional fragments thereof, the binding site of the antibody defined by the variable loops (L1, L2, L3 and H1, H2, H3) have the ability to bind to the antigen. An "epitope" is a structure unit linked in a conventional manner by an immunoglobulin VH / VL pair. The epitopes define the minimum binding site of an antibody, and therefore they represent the specificity goal of an antibody. In the case of a single domain antibody, an epitope represents the structure unit linked by a variable domain in the isolation. The term "universal structure" refers to a sequence of antibody structure corresponding to the regions of an antibody conserved in the sequence as defined in the Kabat publication ("Sequences of Proteins of Immunological Interest" US Department of Health and Human Services) or which correspond to the repertoire or structure of human germline immunoglobulin as defined in the publication of Chothia and Lesk, (1987) J. Mol. Biol. 196: 910-917. The present invention provides the use of a simple structure, or a group of such structures, which have been found to allow the derivation of virtually any binding specificity through variation in the hypervariable regions alone. The phrase "half-life" refers to the time taken by serum concentration of the ligand to reduce 50% in vivo, for example, due to degradation of the ligand and / or clearance or sequestration of the specific double ligand through the natural mechanisms. The ligands of the present invention are stabilized in vivo and their half-life is increased through binding to the molecules that resist degradation and / or clearance or sequestration. Normally, these molecules are naturally occurring proteins that by themselves have a long half-life in vivo. The half-life of a ligand is increased if its functional activity persists in vivo, over a longer period than a similar ligand which is not specific for the molecule that increases the half-life. Therefore a specific ligand for HSA and two target molecules are compared to the same ligand where specificity with HSA is not found, and does not bind to HSA but binds to another molecule. For example, you can link to a third objective in the cell. Normally, the half-life is increased by 10%, 20%, 30%, 40%, 50% or more. Increments within the range of 2x, 3x, 4x, 5x, 10x, 20, 30x, 40x, 50x or more of half-life are also possible. As an alternative, or additionally, increments in a range of up to 30x, 40x, 50x, 60x, 70x, 80x, 90x, 100x, 150x of the half-life are possible. As referred to in the present invention, the term "competes" means that the binding of a first target to its cognate target binding domain is inhibited when a second object is linked to its target cognate binding domain. For example, the link can be inhibited in spherical form, for example, by physically blocking a binding domain or by altering the structure or environment of a binding domain, so that its affinity or avidity for a target is reduced. .

As used in the present invention, the terms "low stringency", "medium stringency", "high stringency" or "very high stringency conditions" describe nucleic acid hybridization and washing conditions. The guide for carrying out the hybridization reactions can be found in the publication of Current Protocols in Molecular Biology, John Wiley & Sons, N.Y. (1989), 6.3.1-6.3.6, which is incorporated in its entirety to the present invention as a reference. Aqueous and non-aqueous methods are described in said reference, and any of them can be used. The specific hybridization conditions referred to herein are as follows: (1) low stringency hybridization conditions in sodium chloride / 6X sodium citrate (SSC) at a temperature of about 45C, followed by two washes in 0.2X SSC , 0.1% SDS at a temperature of at least 50C (the temperature of the washings can be increased to 55C for conditions of low stringency); (2) medium stringency hybridization conditions in 6X SSC at a temperature of approximately 45C, followed by one or more washes in 0.2X SSC, 0.1% SDS at a temperature of 60C; (3) high stringency hybridization conditions in 6X SSC at a temperature of about 45C, followed by one or more washes in 0.2X SSC, 0.1% SDS at a temperature of 65C; and preferably (4) very high stringency hybridization conditions are 0.5M sodium phosphate, 7% SDS at a temperature of 65C, followed by one or more washed in 0.2X SSC, 1% SDS at a temperature of 65C. The conditions of very high stringency (4) are the preferred conditions and those that should be used unless otherwise specified. Similar or homologous sequences (eg, at least about 70% sequence identity) to the sequences described herein are also part of the present invention. In some embodiments, the sequence identity at the amino acid level can be about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or greater. At the level of nucleic acid, the sequence identity can be about 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97% , 98%, 99% or greater. Alternatively, there is a substantial identity when the nucleic acid segments will hybridize under selective hybridization conditions (e.g., very high stringency hybridization conditions), with the complement of the strand. The nucleic acids can be present in whole cells, in a used cell or in a partially purified or substantially pure form. The calculations of "homology" or "sequence identity" or "similarity" between two sequences (the terms are used interchangeably in the present invention) are carried out as indicated below. The sequences are aligned for optimal comparison purposes (for example, they can be introduce gaps in one or both of a first or second amino acid or nucleic acid sequence for optimal alignment and the non-homologous sequences can be ignored for comparison purposes). In a preferred embodiment, the length of an aligned reference sequence for comparison purposes is at least 30%, preferably at least 40%, more preferably at least 50%, even more preferably at least 60%, and even more preferably at least 70%, 80%, 90%, 100% of the length of the reference sequence. The amino acid or nucleotide residues at the amino acid positions or corresponding nucleotide positions are subsequently compared. When a position in the first sequence is occupied by the same amino acid or nucleotide residue as the corresponding position in the second sequence, then the molecules are identical in that position (as the amino acid "homology" term is used in the present invention). or nucleic acid is equivalent to "identity" of amino acid or nucleic acid). The percent identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps, and the length of each gap, which needs to be introduced for the optimal alignment of the two sequences. The alignments and the homology, similarity or identity of amino acid and nucleotide sequence, as defined in the present invention, are preferably prepared and determined using the algorithm of the BLAST2 Sequences, using default parameters (Tatusova, TA and associates., FEMS Microbiol Lett, 174: 187-188 ( 1999)). As an alternative, the BLAST algorithm (version 2.0) is used for sequence alignment, with parameters adjusted with default values. BLAST (Basic Local Alignment Search Tool) is the heuristic search algorithm used by the blastp, blastn, blastx, tblastn and tblastx programs; these programs add significance to their discoveries using the statistical methods of Karlin and Altschul, 1990, Proc. Nati Acad. Sci. USA 87 (6): 2264-8. Unless defined otherwise, all the techniques and scientific terms used have the same meaning as commonly understood by one skilled in the art (eg, in cell culture techniques, molecular genetics, nucleic acid chemistry, hybridization techniques and biochemistry). Standard techniques are used for molecular genetic and biochemical methods (see generally, the Sambrook and associates publication., Molecular Cloning: A Laboratory Manual, 2nd edition (1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY and Ausubel and associates., Short Protocols in Molecular Biology (1999) 4th Edition, John Wiley &Sons, Inc., which are incorporated to the present invention as reference) and chemical methods. The present invention relates to ligands that have binding specificity for IL-4 (e.g., human IL-4), ligands that have binding specificity for IL-13 (e.g., human IL-13), and to ligands that have specificity of binding for IL-4 and IL-13 (for example human IL-4 and human IL-13). For example, the ligand may comprise a polypeptide domain having a binding site with binding specificity for IL-4, a polypeptide domain that has a binding site with binding specificity for IL-13, or comprises a binding domain. polypeptide having a binding site with binding specificity for IL-4 and a polypeptide domain having a binding site with binding specificity for IL-13. The present invention also relates to ligands that are cross-reactive with human IL-4 and a non-human IL-4 (e.g., IL-4 resus, IL-4 cynomolgus), ligands that cross-react with human IL-13 and a non-human IL-13 (e.g., IL-13 resus, IL-13 cynomolgus), and ligands that have binding specificity for human IL-4, human IL-13, non-human IL-4, and non-human IL-13 (for example, IL-4 resus, IL-13 resus, IL-4 cynomolgus and IL-13 cynomolgus). The ligands of the present invention provide various advantages. For example, as described herein, the ligand can be custom-made to have a half-life in desired serum in vivo. The domain antibodies are much smaller than conventional antibodies, and can be administered to achieve better tissue penetration than conventional antibodies. Therefore, dAbs and ligands comprising a dAb provide advantages over conventional antibodies when administered to treat a disease, such as a Th2-transmitted disease, asthma, allergic diseases, cancer (e.g., renal cell cancer). . For example, asthma (eg, allergic asthma) can be IgE-transmitted or non-IgE-transmitted, and ligands that have binding specificity for IL-4, IL-13 or IL-4 and IL-13 can be administered to treat Asthma transmitted both by IgE and not transmitted by IgE. Similarly, due to the overlap and similarity in the biological activity of IL-4 and IL-13, therapy with agents that bind and inhibit only one of these cytokines may not produce the desired effects in all circumstances. Accordingly, ligands that have binding specificity for IL-4 and IL-13 can be administered to a patient (e.g., a patient with an allergic disease (e.g., allergic asthma)) to provide superior therapy using an agent simple therapeutic In some embodiments, the ligand that has binding specificity for IL-4 and comprises one (at least one) variable domain of simple immunoglobulin with binding specificity for IL-4. In other embodiments, the ligand has binding specificity for IL-13 and comprises one (at least one) variable domain of single immunoglobulin with binding specificity for IL-13. In certain embodiments, the ligand has binding specificity for IL-4 and IL-13, and comprises a (at least one) variable domain of simple immunoglobulin with binding specificity for IL-4 and a (at least one) variable domain of simple immunoglobulin with binding specificity for IL-13. The ligand of the present invention can be formatted as described in the present invention. For example, the ligand of the present invention can be formatted to tailor the serum half-life in vivo. If desired, the ligand may further comprise a toxin or a toxin moiety as described herein. In some embodiments, the ligand comprises an active surface toxin, such as a free radical generator (eg, toxin containing setenium) or a radionuclide. In other embodiments, the toxin or toxin portion is a polypeptide domain (eg, a dAb) that has a binding site with binding specificity for an intracellular target. In particular embodiments, the ligand is an IgG-like format that has binding specificity for IL-4 and IL-13 (e.g., human IL-4 and human IL-13).

In one aspect, the present invention relates to a ligand having binding specificity for interleukin-4 (IL-4) and interleukin-13 (IL-13) comprising a portion of protein having a binding site with specificity of link for IL-4; and a portion of protein having a binding site with binding specificity for IL-13. The ligand having binding specificity for IL-4 and IL-13 of this aspect of the present invention, may be further characterized through one or a combination of the following: (1) provided that said portion of the protein that has a binding site with binding specificity for IL-4, is not an IL-4 receptor or an IL-4 binding portion thereof, and the protein portion that has a binding site with binding specificity for IL- 13 is not an IL-13 receptor or IL-13 link part thereof; (2) provided that the binding site with binding specificity for IL-4 and the binding site with binding specificity for IL-13 each consist of a single amino acid chain; (3) provided that neither the binding site with binding specificity for IL-4, nor the linkage site with binding specificity for IL-13 comprises an immunoglobulin heavy chain variable domain and an immunoglobulin light chain variable domain.; and (4) provided that the protein portion having a binding site with binding specificity for IL-4 is not an antibody binding to IL-4 or an antigen binding fragment thereof. comprising an immunoglobulin heavy chain variable and an immunoglobulin light chain variable domain that together form a binding site for IL-4, and that portion of the protein having a binding site with binding specificity for IL-3 is not an antibody binding to IL-13 or an antigen binding fragment thereof comprising an immunoglobulin heavy chain variable domain and an immunoglobulin light chain variable domain that together form a binding site for IL-13. In one aspect, the present invention relates to a ligand having binding specificity for IL-4, comprising a portion of protein having a binding site with binding specificity for IL-4. The ligand having binding specificity for IL-4 of this aspect of the present invention may be further characterized through any one or any combination of the following: (1) provided the protein portion having a linkage site with binding specificity for IL-4, is not an antibody binding to IL-4 or an antigen binding fragment thereof comprising an immunoglobulin heavy chain variable domain and an immunoglobulin light chain variable domain that together form a liaison site for IL-4; (2) provided that the portion of protein that has a binding site with specificity of linkage for IL-4 is not an IL-4 receptor or an IL-4 binding part thereof; (3) as long as the binding site with binding specificity for IL-4 consists of a single amino acid chain; and (4) provided that the binding site for binding specificity for IL-4 does not consist of an immunoglobulin heavy chain variable domain and an immunoglobulin light chain variable domain. In one aspect, the present invention relates to a ligand having binding specificity for IL-13, comprising a portion of a protein having a binding site with binding specificity for IL-13. The ligand having binding specificity for IL-13 of this aspect of the present invention may be further characterized by any one or any combination of the following: (1) provided that the portion of the protein having a linkage with binding specificity for IL-13 is not an antibody binding to IL-13 or an antigen binding fragment thereof comprising an immunoglobulin heavy chain variable domain and an immunoglobulin light chain variable domain which together form a link site for IL-13; (2) provided that the protein portion having a binding site with binding specificity for IL-13 is not an IL-13 receptor or an IL-13 binding moiety thereof; (3) as long as the binding site with binding specificity for IL-13 consists of an amino acid chain simple; and (4) provided that the binding site for binding specificity for IL-13 does not consist of an immunoglobulin heavy chain variable domain and an immunoglobulin light chain variable domain. Ligand Formats The ligand of the present invention can be formatted as a monospecific, specific dual or multispecific ligand as described herein. See also WO 03/002609, the full teachings of which are incorporated herein by reference, with respect to ligand formatting. Said specific double ligands comprise variable domains of single immunoglobulin having different binding specificities. Said specific double ligands may comprise combinations of heavy and light chain domains. For example, the double specific ligand may comprise a VH domain and a VL domain, which may be linked together in the form of a scFv (e.g., using a suitable linker such as Gly4Ser), or formatted into a bispecific antibody or fragment. of antigen binding thereof (eg, F (ab ') 2, Fab', Fab fragment). The specific dual ligands do not comprise complementary VH / VL pairs that form a binding site of two standard antigen antibodies that bind to epitopes or antigens in joint operation. Rather, the dual-format ligands they may comprise a complementary pair VH / VL, wherein the V domains have different binding specificities. The ligand (e.g., monospecific, specific dual ligands) may comprise one or more VH or VL domains, if desired. A joint region domain may also be included if desired. Such combinations of domains can, for example, mimic natural antibodies, such as IgG or IgM, or fragments thereof such as Fv, scFv, Fab or F (ab ') 2 molecules. Other structures, such as a single arm of a IgG molecule comprising VH, VL, CH1 and CL domains are considered. The ligand may comprise a heavy chain constant region of an immunoglobulin (eg, IgG (eg, IgG1, IgG2, IgG3, IgG4) IgM, IgA, IgD or IgE) or part thereof (eg, Fe part) and / or a light chain constant region (eg, CX, CK). For example, the ligand may comprise CH1 of IgG1 (eg, human IgG1), CH1 and CH2 of IgG1 (eg, human IgG1), CH1, CH2 and CH3 of IgG1 (eg, IgG1 human), CH2 and CH3 of IgG1. (for example, human IgG1), or CH1 and CH3 of IgG1 (for example, human IgG1). In one example, a specific double ligand of the present invention comprises only two variable domains, although several ligands can be incorporated together in the same protein, for example, two of said ligands can be incorporated into an IgG or a multimeric immunoglobulin, such as IgM. Alternatively, in another embodiment, a plurality of specific double ligands are combined to form a multimer. For example, two different double specific ligands are combined to create a tetra-specific molecule. Those skilled in the art will appreciate that the light and heavy variable regions of a specific double ligand of the present invention may be in the same polypeptide chain, or alternatively, in different polypeptide chains. In the case where the variable regions are in different polypeptide chains, then they can be linked through a linker, generally a flexible linker (such as a polypeptide chain), a chemical linking group or any other method known in the art. technique. Ligands can be formatted as bi-or multi-specific antibodies or antibody fragments or structures without bi-or multi-specific antibodies. Suitable formats include, any polypeptide structure in which the antibody variable domain or one or more of the CDRs thereof, can be incorporated to thereby confer specificity of binding for antigens in the structure. A variety of suitable antibody formats are known in the art, such as bispecific IgG type formats (e.g., chimeric antibodies, humanized antibodies, human antibodies, single chain antibodies, heavy chain heterodimers and / or antibody light chains, antigen binding fragments of any of the foregoing (eg, Fv fragment (e.g., single chain Fv (scFv), disulfide linked Fv), a Fab fragment, a Fab 'fragment, an F (ab') 2 fragment, a simple variable domain (e.g., VH, VL, VHH), a dAb, and modified versions of any of the foregoing (e.g., modified through adhesion) covalent of polyalkylene glycol (eg, polyethylene glycol, polypropylene glycol, polybutylene glycol) or other suitable polymer.) See PCT publication / GB03 / 002804, filed June 30, 2003, which was designated in the United States, (WO 2004/081026 ) with respect to PEGylation of single variable domains and dAbs, suitable methods for preparing them, increased in vivo half-life of the PEGylated single variable domains and dAb monomers and multimers, suitable PEGs, hydrodynamic sizes Preferred PEGs, and preferred hydrodynamic sizes of PEGylated single variable domains and dAb monomers and multimers. The total teachings of PCT / GB03 / 002804 (WO 2004/081026), including the parts referred to above, are incorporated by reference into the present invention. The ligand can be formatted using a suitable linker such as (Gly4Ser) n, where n = from 1 to 8, (eg, 1, 2, 3, 4, 5, 6 or 7). If desired, the ligands, including dAb monomers, dimers and trimers can be linked to an Fe antibody region, comprising one or both of the CH2 and CH3 domains, and optionally a hinge region. For example, vectors encoding ligands linked as a single nucleotide sequence to an Fe region can be used to prepare said polypeptides. It is also possible to combine and / or form ligands in dAb monomers also multi-ligand structures without antibodies that form multivalent complexes, which bind target molecules with the same antigen, thus providing a higher avidity. For example, natural bacterial receptors such as SpA can be used as scaffolds for the grafting of CDRs to generate ligands that specifically bind to one or more epitopes. The details of this procedure are described in U.S. Patent No. US 5,831,012. Other suitable scaffolds include those that are based on fibronectin and affibodies. Details of suitable procedures are described in WO 98/58965. Other suitable scaffolds include lipocalin and CTLA4, as described in the publication by van den Beuken et al., J. Mol. Biol. 310: 591-601 (2001), and scaffolds, such as those described in WO 00/69907 (Medical Research Council), which are based for example on the ring structure of bacterial GroEL or other polypeptides chaperones. Protein scaffolds can be combined; for example, CDRs can be grafted onto a CTLA4 scaffold and used together with the immunoglobulin VH or VL domains to form a ligand. Similarly, fibronectin, lipocalin and other scaffolds can be combined. A variety of suitable methods for preparing any desired format are known in the art. For example, antibody chains and formats (eg, monospecific, bispecific, trispecific or tetraespecific IgG formats, chimeric antibodies, humanized antibodies, human antibodies, single chain antibodies, homodimers and heavy chain heterodimers and / or chains). light antibodies) can be prepared by expressing suitable expression constructs and / or suitable cell cultures (eg, hybridomas, heterohybridomas, recombinant host cells containing recombinant constructs encoding the format). In addition, formats such as antibody antigen binding fragments or antibody chains (e.g., bispecific binding fragments, such as Fv fragment (e.g., single chain Fv (scFv), Fv linked with disulfide), a fragment Fab, a Fab 'fragment, an F (ab') 2 fragment, can be prepared by expressing suitable expression constructs or by enzymatic digestion of antibodies, using for example, papain or pepsin. The ligand can be formatted as a multispecific ligand, for example, as described in WO 03/002609, the entire teachings of which are incorporated herein by reference. Said multispecific ligand possesses more than one epitope binding specificity. Generally, the multi-specific ligand comprises two or more epitope-binding domains, such as dAbs or non-antibody protein domain comprising a binding site for an epitope, eg, an affibody, an SpA domain, a receptor domain LDL class A, an EGF domain, an avimer. The multispecific ligands can be formatted additionally as described in the present invention. In some modalities, the ligand is a type format IgG Said formats have structures of four conventional chains of an IgG molecule (2 heavy chains and two light chains), where one or more of the variable regions (VH and / or VL) have been replaced with a dAb or variable domain of simple immunoglobulin of a desired specificity. Preferably, each of the variable regions (2 VH regions and 2 VL regions) are replaced with a dAb or a single immunoglobulin variable domain. The dAb (s) or variable immunoglobulin domain (s) that are included in an IgG type format can have the same specificity or different specificities. In some embodiments, the IgG type format is tetravalent and may have one, two, three or four specificities. The IgG type format can be bispecific and comprise, for example, a first and a second dAb having the same specificity, a third dAb with a different specificity and a fourth dAb with a different specificity to the first, second and third dAbs; or tetraespecific and comprise four dAbs that each have different specificity. The IgG type format can be monospecific and comprise 4 dAbs that have the specificity for IL-4 or for IL-13. The IgG type format can be bispecific and comprise, for example, 3 dAbs having specificity for IL-4 and another dAb having specificity for IL-13, or bispecific and comprising, for example, two dAbs having specificity for IL-4. and two dAbs that have specificity for IL-13. The IgG type format can be bispecific and comprise, for example, 3 dAbs that have specificity for IL-13 and another dAb that has specificity for IL-14. When the IgG type format contains two or more dAbs that link to II-4, the dAbs can bind to the same epitopes or different epitopes. For example, the IgG type format may comprise two, three or four dAbs having binding specificity for IL-4 that binds to the same epitopes or different epitopes on IL-4. Similarly, when the IgG type format contains two or more dAbs that link IL-13, dAbs can bind to the same epitopes or different epitopes. For example, the IgG type format can comprise two, three or four dAbs having binding specificity for IL-13 that binds to the same epitopes or different epitopes on IL-13. In one example, the IgG type format is a tetravalent IgG ligand that has binding specificity for IL-4 or IL-13 comprising two heavy chains and two light chains, wherein the heavy chains comprise the constant region of a heavy chain of immunoglobulin and a single immunoglobulin variable domain having binding specificity for IL-4 or IL-13; and the light chains comprise the constant region of an immunoglobulin light chain and a single immunoglobulin variable domain having binding specificity for IL-4 or IL-13. The IgG-like format of this example may be further characterized through the provision that when the heavy chains comprise a single immunoglobulin variable domain having binding specificity for IL-4, the light chains comprise an immunoglobulin variable domain simple that has binding specificity for IL-13; and when the heavy chains comprise a single immunoglobulin variable domain having binding specificity for IL-13, the light chains comprise a single immunoglobulin variable domain having binding specificity for IL-4. Antigen binding fragments of the IgG type formats (eg, Fab, F (ab ') 2> Fab', Fv, scFv) can be prepared. In addition, a particular constant region or Fe part (eg, constant region or Fe part of an IgG, such as IgG1 (eg, CH1, CH2 and CH3; CH2 and CH3)), variant or part thereof can be selected in order to tailor the effector function. For example, if the activation function of complement and / or antibody dependent cellular cytotoxicity (DAC) is desired, the ligand can be an IgG type format. If desired, the IgG type format can comprise a mutated constant region (heavy chain constant region IgG variant) to minimize binding to Fe receptors and / or the ability to fix the complement (see for example, Winter and associates publication). ., GB 2,209,757 B, Morrison and associates, WO89 / 07142, Morgan et al., WO 94/29351, December 22, 1994). The ligands of the present invention can be formatted as a fusion protein containing a first variable domain of single immunoglobulin that is fused directly (for example, via a peptide bond) or through a suitable linker (amino acid, peptide, polypeptide) to a second variable domain of simple immunoglobulin. If desired, said format may further comprise, for example, one or more immunoglobulin domains (e.g. constant, part Fe) and / or half-life extension portion as described in the present invention. For example, the ligand may comprise a first single immunoglobulin variable domain that is directly fused to a second variable domain of single immunoglobulin that is directly fused to a single immunoglobulin variable domain that binds to serum albumin. In one example, the ligand comprises a first variable domain of single immunoglobulin, a second variable domain of single immunoglobulin and one part Fe or a constant region of immunoglobulin. The first and second variable domains of single immunoglobulin each may have binding specificity for IL-4 or IL-13. Accordingly, this type of ligand may contain two binding sites (be bivalent), wherein each binding site binds to IL-4, linking each binding site to IL-13 or where the binding site binds to IL- 4 and a link site links to IL-13. For example, the ligands may have the structure V domain-V domain-constant region IgG or the Fe part of domain V-domain V-IgG. Generally targeting the polypeptide domains having a binding site with binding specificity for a target, and whether the ligand comprises a linker is a matter of design choice. However, some orientations, with or without linkers, can provide better link characteristics than others. All orientations (e.g., dAb1 -linker-dAb2; dAb2-linker-dAbl) are encompassed by the present invention, and ligands that contain an orientation that provides desired link characteristics can be easily identified by classification. Extended Medium Life Formats The dAb ligands and monomers described herein can be formatted to extend their serum half life in vivo. The increased in vivo half-life is useful in in vivo applications of immunoglobulins, especially antibodies and most antibody fragments, especially small size such as dAbs. These fragments (Fvs, Fvs linked with disulfide, Fabs, scFvs, dAbs) are rapidly cleared from the body, which may increase clinical applications. A ligand can be formatted as a binding fragment of larger antigens of an antibody or as an antibody (eg, formatted as a Fab, Fab ', F (ab) 2, F (ab') 2, IgG, scFv) which has a larger hydrodynamic size. The ligands can also be formatted to have a larger hydrodynamic size, for example, by adhesion of a polyalkylene glycol group (eg, polyethylene glycol (PEG) group, polypropylene glycol, polybutylene glycol), serum albumin, transferin, transfer or at least the transfer part of transferin, an antibody region Fe, or by conjugation to an antibody domain. In some embodiments, the ligand (e.g., monomer dAb) is PEGylated. Preferably the PEGylated ligand (e.g., monomer dAb) binds IL-4 and / or IL-4 with substantially the same affinity or avidity as the same ligand that is not PEGylated. For example, the ligand may be a PEGylated ligand comprising a dAb that binds IL-4 or IL-4 with an avidity that differs from the avidity of the ligand in a PEGylated form by no more than a factor of about 1000, preferably no more of a factor of about 100, more preferably not more than a factor of about 10, or with avidity affinity substantially unchanged with respect to the PEGylated form. See Publication, PCT / GB03 / 002804, filed on June 30, 2003, which is designated in the United States (WO 2004/081026) with respect to simple variable domains PEGylated and dAbs, suitable methods to prepare them, life increased in vivo media of the PEGylated single variable domains and dAb monomers and multimers, suitable PEGs, preferred hydrodynamic sizes of PEGs, and preferred hydrodynamic sizes of PEGylated single variable domains and dAb monomers and multimers. The total teachings of PCT / GB03 / 002804 (WO 2004/081026), including the parts referred to above, are incorporated herein by reference. The hydrodynamic size of the ligands (e.g., monomers and dAb multimers) of the present invention can be determined using methods that are known in the art. For example, gel filtration chromatography can be used to determine the hydrodynamic size of a ligand. Suitable gel filtration matrices for determining the hydrodynamic sizes of ligands, such as cross-linked agarose matrices, are well known and readily available. The size of a ligand format (e.g., the size of a PEG portion adhered to a dAb monomer) may vary depending on the desired application. For example, when the ligand is projected to leave the circulation and enter the peripheral tissues, it is desirable to keep the hydrodynamic size of the ligand low to facilitate emptying of the bloodstream. Alternatively, when it is desired to have a ligand that remains in the systemic circulation for a longer period of time, the size of the ligand can be increased, for example by formatting as an Ig-like protein or through the addition of a PEG-30 portion. at 60 kDa (eg, PEG of 30 to PEG 40 kDa, such as the addition of two PEG 20 kDa). The size of the ligand format can be tailored to achieve a desired in vivo serum half life, for example to control exposure to a toxin and / or reduce the side effects of toxic agents. The hydrodynamic size of the ligand (e.g., monomer dAb) and its serum half-life can also be increased by conjugate or binding the ligand to a binding domain (e.g., antibody or antibody fragment) that binds to an antigen or epitope that increases the half-life in vivo, as described in the present invention. For example, the ligand (e.g., the dAb monomer) can be conjugated or bound to an anti-serum albumin or anti-neonatal Fe antibody or antibody fragment, e.g., an anti-SA or anti-neonatal receptor dAb Fe, Fab, Fab 'or scFv, or an anti-SA antibody or an anti-neonatal Fe receptor affinity. Suitable examples of albumin, albumin fragments or albumin variants for use in a ligand according to the present invention are described in WO 2005/077042A2, which is incorporated herein by reference in its entirety. In particular, the following variants of albumin, albumin or albumin fragments can be used in the present invention: SEQ ID NO: 1 as described in WO 2005 / 077042A2, (this sequence is explicitly incorporated in the present invention as reference); • Fragment of albumin or albumin variant that comprises or consists of amino acids 1-387 of SEQ ID NO: 1 in Publication WO 2005 / 077042A2; • Albumin, or fragment or variant thereof, comprising an amino acid sequence selected from the group consisting of: (a) amino acids 54 to 61 of SEQ ID NO: 1 in Publication WO 2005 / 077042A2; (b) amino acids 76 to 89 of SEQ ID NO: 1 in the Publication WO 2005 / 077042A2; (c) amino acids 92 to 100 of SEQ ID NO: 1 in Publication WO 2005 / 077042A2; (d) amino acids 170 to 176 of SEQ ID NO: 1 in Publication WO 2005/077042 A2; (e) amino acids 247 to 252 of SEQ ID NO: 1 in Publication WO 2005 / 077042A2; (f) amino acids 266 to 277 of SEQ ID NO: 1 in Publication WO 2005 / 077042A2; (g) amino acids 280 to 288 of SEQ ID NO: 1 in Publication WO 2005 / 077042A2; (h) amino acids 362 to 368 of SEQ ID NO: 1 in Publication WO 2005 / 077042A2; (i) amino acids 439 to 447 of SEQ ID NO: 1 in Publication WO 2005 / 077042A2 O) amino acids 462 to 475 of SEQ ID NO: 1 in Publication WO 2005/077042 A2; (k) amino acids 478 to 486 of SEQ ID NO: 1 in Publication WO 2005 / 077042A2; and (I) amino acids 560 to 566 of SEQ ID NO: 1 in Publication WO 2005 / 077042A2. Additional examples of albumin, fragments and analogs for use in a ligand according to the present invention are described in Publication WO 03/076567A2, which is incorporated in its entirety to the present invention as a reference. In particular, the following albumin, fragments or variants can be used in the present invention: • Human serum albumin as described in Publication WO 03/076567 A2, for example, in Figure 3 (this information of sequence is explicitly incorporated by reference in the present invention); • Human serum albumin (HA) consisting of a single non-glycosylated polypeptide chain of 585 amino acids with a formula molecular weight of 66,500 (see Meloun Publication, and associates, FEBS Letters 55: 136 (1975); Behrens, and associates, Fed. Proc. 34: 591 (1975); Lawn, et al., Nucleic Acids Research P: 6102-6114 (1981); Minghetti, et al., J. Biol. Chem. 261: 6747 (1986)); · Polymorphic or analogous variant or fragment of albumin as described in the Publication of Weitkamp, and associates, Ann. Hum. Genet 37: 219 (1973); • A fragment or variant of albumin as described in EP 322094, for example, HA (1-373., HA (1-388), HA (1-389), HA (1-369), and HA (1 -419) and fragments between 1-369 and 1-419 • A fragment or variant of albumin as described in EP 399666, for example, HA (1-177) and HA (1-200) and fragments between HA ( IX), where X is any number from 178 to 199.

Wherein one (one or more) half-life extension portion (eg, albumin, transferin and fragments and analogs thereof) is used in the ligands of the present invention, it can be conjugated to ligands using any suitable method such as by direct fusion to the target binding portion (eg, dAb or antibody fragment), using for example a simple nucleotide portion encoding a fusion protein, wherein the fusion protein is encoded as a single polypeptide chain with a half-life extension portion located at N or C terminal in the cell surface target binding portions. Alternatively, conjugation can be accomplished using a peptide linker between portions, a peptide linker as described in Publication WO 03/076567A2 or WO 2004/003019 (these linker descriptions are incorporated herein by reference for provide examples to be used in it). Typically, a polypeptide that improves the serum half-life in vivo is a polypeptide that occurs naturally in vivo and that resists degradation or elimination by endogenous mechanisms that remove unwanted material from the organism (e.g., human). For example, a polypeptide that increases the half-life in vivo can be selected from proteins from the extracellular matrix, proteins found in the blood, proteins found in the blood-brain barrier or a neural tissue, proteins located in the kidney, liver, lung, heart, skin or bones, tension proteins, specific proteins of the disease, or proteins involved in the Fe transport. Suitable polypeptides that increase the half-life in vivo include, for example, receptor-ligand-specific neuropharmaceutical fusion proteins of transferrin receptor (see US Patent No. 5,977,307, which teachings are incorporated in the present invention as reference, brain capillary endothelial cell receptor, transferin, transferrin receptor (eg, soluble transferin receptor), insulin, insulin-like growth factor-1 receptor (IGF 1), insulin-like growth factor-2 receptor (IGF) 2), insulin receptor, blood coagulation factor X, 1-antitrypsin and HNF 1a, the appropriate polypeptides that increase so the serum half-life also includes alpha-1 glycoprotein (orosomucoid; AAG), alpha-1 antichymotrypsin (ACT), alpha-1 microglobulin (HC protein, AIM), anti-thrombin III (AT III), apolipoprotein A-1 (Apo A-1), apolipoprotein B (Apo B), ceruloplasmin (Cp), complement component C3 (C3), complement component C4 (C4), esterase inhibitor C1 (C1 INH), C-reactive protein (CRP), ferritin (FER), hemopexin (HPX), lipoprotein (Lp) (a)), handy binding protein (MBP), myoglobin (Myo), prealbumin (transthyretin; PAL), retinol binding protein (RBP), and rheumatoid factor (RF). Suitable proteins of the extracellular matrix include, for example, collagen and laminites, integrins and fibronectin. Collagens are the important proteins of the extracellular matrix. Approximately 15 types of collagen molecules are currently known, found in different parts of the body, for example, type I collagen (which covers 90% of the body's collagen) found in bones, skin, tendons, ligaments, cornea, internal organs, or type II collagen found in cartilage, vertebral discs, cord noto and vitreous humor of the eyes. Suitable proteins in the blood include, for example, plasma protein (e.g., fibrin, α-2 macroglobulin, serum albumin, fibrinogen (e.g., fibrinogen A, fibrinogen B), serum A amyloid protein, haptoglobin, profilin , ubiquitin, uteroglobulin and β-2 microglobulin), enzymes, enzyme inhibitors (eg, plasminogen, lysozyme, cystatin C, alpha-1-antitrypsin and pancreatic trypsin inhibitor), immune system proteins such as immunoglobulin proteins (eg, example, IgA, IgD, IgE, IgG, IgM, immunoglobulin light chains (kappa / lambda)), transport proteins (e.g., retinol binding protein, a-1 microglobulin), defensins (e.g. beta-defensin) 1, neutrophil defensin 1, defensin 2 neutrophil and neutrophil defensin 3) and the like. Suitable proteins encintrated in the blood-brain or neural tissue barrier include, for example, melanocortin receptor, myelin, ascorbate transporter and the like. Polypeptides that increase serum half-life in vivo also include proteins located in the kidney (eg, polycystin, type IV collagen, organic anion transporter, Heymann's antigen), protein located in the liver (eg, alcohol dehydrogenase) , G250), proteins located in the lung (for example, secretion component that binds to IgA), proteins located in the heart (for example, HSP 27, which is associated with dilated cardiomyopathy), proteins located in the skin (for example , keratin), bone specific proteins such as morphogenic proteins (BMPs), which are a subgroup of the transforming growth factor superfamily of ß -reflecting proteins that demonstrate ostreogénica activity (eg, BMP-2, BMP-4). , BMP-5, BMP-6, BMP-7, BMP-8), tumor-specific proteins (e.g., tropoblast antigen, herceptin receptor, estrogen receptor, cathepsins (e.g., cathepsin B, which can be found in the liver and spleen)). Suitable disease-specific proteins include, for example, antigens expressed only in activated T cells, including LAG-3 (lymphocyte activation gene), osteoprotegerin ligands (OPGL, Nature 402, 304-309 (1999)), OX40 (a member of the TNF receptor family expressed in activated T cells and specifically activated in cells that produce human type I T cell leukemia virus (HTLV-1), see Immunol Publication 165 (l): 263-70 (2000)). Suitable disease-specific proteins also include, for example, metalloproteases (associated with arthritis / breast cancer) including drosophila CG6512, human paraplegina, human FtsH, human AFG3L 2, murine ftsH; and angiogenic growth factor, including acid fibroblast growth factor (FGF-1), basic fibroblast growth factor (FGF-2), vascular endothelial growth factor / vascular permeability factor (IL-4 / VPF), factor- a transforming growth (TGF a), tumor necrosis factor-alpha (TNF-a), angiogenin, interleukin-3 (IL-3), interleukin-8 (IL-8), platelet-derived endothelial growth factor (PD-ECGF), placental growth factor (P1GF), growth factor-BB derived from midline platelets (PDGF), and fractalcin. Suitable polypeptides that increase serum half life in vivo also include strain proteins such as heat shock proteins (HSPs). HSPs are usually found intracellularly. When they are in extracellular form, it is an indicator that the cell it has died and its contents are spilled. This unscheduled cell death (necrosis) occurs when as a result of trauma, disease or injury, extracellular HSPs are activated in response to the immune system. The binding to extracellular HSP can result in localization of the compositions of the present invention in a diseased site. Suitable proteins involved in Fe transport include, for example, Brambell receptor (also known as FcRB). This Fe receptor has two functions, both of which are potentially useful for administration. The functions are (1) transport of IgG from the mother to the child through the placenta (2) protection of IgG in terms of degradation, prolonging its half-life in this way. The receptor is considered to recycle IgG from the endosomes. (See Publication by Holliger and associates, Nat Biotechnol 15 (7): 632-6 (1997).) Methods for analysis and pharmacokinetic determination of half-life of ligand will be familiar to those skilled in the art. Publication by Kenneth, A. and associates: Chemical Stability of Pharmaceuticals: A Handbook for Pharmacists and in Peters and Associates, Pharmacokinetc analysis: A Practical Approach (1996). Reference is also made to the Publication of "Pharmacokinetics", M Gibaldi &; D Perron, published by Marcel Dekker, 2nd Revision (1982), which describes parameters pharmacokinetics such as half-lives alpha t and beta t and urea under the curve (AUC). Ligands Containing a Portion of Toxin or Toxin The present invention also relates to ligands comprising a toxin or toxin portion. Portions of suitable toxins comprise a toxin (e.g., active surface toxin, cytotoxin). The toxin or toxin portion can be linked or conjugated to the ligand using any suitable method. For example, toxin or toxin portion can be covalently bound to the ligand directly or through the appropriate linker. Suitable linkers can include non-dissociable or dissociable linkers, for example, pH-releasable linkers comprising a dissociation site for a cellular enzyme (eg, cellular esterases, cellular proteases such as cathepsin B). Said dissociable linkers can be used to prepare a ligand that can release a toxin or toxin portion after the ligand is internalized. A variety of methods can be used to bind or conjugate a portion of toxin or toxin to a ligand. The particular method selected will depend on the toxin or toxin portion and the ligand that will be bound conjugate. If desired, linkers containing terminal functional groups can be used to link the ligand and the toxin or toxin portion. Generally, conjugation is achieved by reacting the toxin portion with toxin containing a reactive functional group (or modified to contain a reactive functional group) as a linker or directly with a ligand. The covalent bonds formed by reacting a toxin to toxin portion containing (or modifying to contain) a chemical moiety or functional group which, under suitable conditions, can react with a second chemical group thereby forming a covalent bond. If desired, a suitable reactive chemical group can be added to a ligand or a linker using any suitable method. (See, for example, Hermanson Publication, GT, Bioconjugate Techniques, Academic Press: San Diego, CA.) Many combinations of reactive chemical groups suitable in the art are known, for example an amine group can react with an electrophilic group. such as tosylate, mesylate, halo (chloro, bromo, fluoro, iodo), N-hydroxysuccinimidylester (NHS), and the like.The thiols can react with maleimide, iodoacetyl, a cri I or I i I, pyridyl disulfides, thiol of 5-thiol-2-nitrobenzoic acid (TNB-thiol), and the like: A functional group of aldehyde molecules containing amine or hydrazide can be coupled, and an azide group can react with a trivalent phosphorus group to form ligatures of amidate phosphorus or imide phosphorus Suitable methods for introducing molecule activation groups are known in the art (see for example, Publication of Hermanson, G. T., Bioconjugate Techniques, Academic Press: San Diego, CA (1996)). Portions of suitable toxins include, for example, a maytansinoid (eg, maytansinol, eg, DM1, DM4), a taxane, a calicamycin, a duocarmycin, or derivatives thereof. The maytansinoid may be, for example, maytansinol or a maytansinol analogue. Examples of maytansinol analogs include those having a modified aromatic ring (eg, C-19-dechloro, C-20-demethoxy, C-20-acyloxy) and those having modifications in other positions (eg, C- 9-CH, C-14-alkoxymethyl, C-14-hydroxymethyl or acyloxymethyl, C-15-hydroxy / acyloxy, C-15-methoxy, C-18-N-demethyl, 4,5-deoxy). Maytansinol and maytansinol analogues are described, for example, in US Patent Nos. 5,208,020 and 6,333,410, the contents of which are incorporated herein by reference. Maitansinol can be coupled to antibodies and antibody fragments using, for example, an N-succinimidyl proprionate 3- (2-pyridyldithio) (also known as pentanoate N-succinimidyl 4- (2-pyridyldithio) or SPP), 4-succinimidyl -oxycarbonyl-a- (2-pyridyldithio) -toluene (SMPT), N-succinimidyl-3- (2-pyridyldithio) butyrate (SDPB), 2-iminothiolane, or S-acetyl-succinic anhydride. The taxane can be, for example, a taxol, taxoter, or novel taxane (see for example, Publication WO 01/38318). Calicheamycin can be, for example, a bromo complex calicheamicin (eg, an alpha, beta or gamma bromo complex), a complex iodine calicheamicin (eg, alpha, beta or gamma iodine complex), or analogs and imitations thereof. Bromo complex calicheamicins include H-BR.12-BR, 13-BR, 14-BR, J1-BR, J2-BR and K1-BR. Complex-iodine calicheamicins include 11-1, 12-1, 13-1, J1-I, J2-I, L1-I and K1-BR. Calicheamicin and mutants, analogs and mimetics are described for example in U.S. Patent Nos. 4,970,198; 5,264,586; 5,550,246; 5,712,374, and 5,714,586, the contents of which are incorporated herein by reference. Duocarmycin analogs (eg, KW-2189, DC88, DC89 CBI-TMI, and derivatives thereof) are described, for example, in U.S. Patent No. 5,070,092, U.S. Patent No. 5,187,186, U.S. Patent No. 5,641,780, US Patent No. 5,641,780, US Patent No. 4,923,990, and US Patent No. 5,101,038, the contents of which are incorporated herein by reference. Examples of other toxins include, but are not limited to antimetabolites (e.g., methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouracil decarbazine), alkylating agents (e.g., mechlorethamine, thioepa chlorambucil, CC- 1065 (see US Patent Nos. 5,475,092, 5,585,499, 5,846,545), melphalan, carmustine (BSNU) and lomustine (CCNU), cyclophosphamide, busulfan, dibromomannitol, streptozotocin, mitomycin C, and cis-dichlorodiamine (II) platinum (DDP) cisplatin), anthracyclines (eg, daunorubicin (mainly daunomycin) and doxorubicin), antibiotics (eg, dactinomycin) (mainly actinomycin), bleomycin, mithramycin, mitomycin, puromycin anthramycin (AMC)), duocarmycin and analogs or derivatives thereof, agents and anti-mitotics (e.g., vincristine, vinblastine, taxol, auristatins (e.g., auristatin E ) and maytansinoids, and analogs or homologs thereof The toxin may also be a surface active toxin, such as a toxin that is a free radical generator (eg, portions of selenium containing toxin) or a portion containing Radionuclide Portions containing suitable radionuclides include, for example, portions containing radioactive iodine (131l or 25l), yttrium (90Y), lutetium (177Lu), actinium (225Ac), praseodim io, astatine (21 At), rhenium (186 Re), bismuth (212Bi 213Bi), indium (111ln), technetium (99mTc), phosphorus (32P), rhodium (188Rh), sulfur (35S), carbon (14C), tritium (3H), chromium (51Cr), chlorine (36CI), cobalt (57Co or 58Co), iron (59Fe), selenium (75Se), or gallium (67Ga). The toxin can be a protein, polypeptide or peptide, from bacterial sources, for example, diphtheria toxin, pseudomonas exotoxin (PE) and plant proteins, for example the ricin A chain (RTA), the proteins that deactivate ribosome (RIPs) gelonin, antiviral protein of plant "pokeweed", saporin, and dodecandron are contemplated to be used as toxins. Antisense nucleic acid compounds designed to bind disable, promote degradation or prevent the production of mRNA responsible for generating a particular target protein can also be used as a toxin. The anti-sense compounds include single or double-stranded RNA or DNA, oligonucleotides or their analogs that can hybridize specifically to mRNA species and prevent transcription and / or RNA processing of mRNA species and / or the translation of encoded polypeptide and thereby effect a reduction in the amount of the respective polypeptide. Ching, and associates, Proc. Nati Acad. Sci. E.U.A. 86: 10006-10010 (1989); Broder, and associates, Ann. Int. Med. 113: 604-618 (1990); Loreau, and associates, FEBS Letters 214: 53-56 (1990); Useful antisense therapeutics include for example: Vegli ™ (VasGene) and OGX-011 (Oncogenix). Toxins can also be photoactive agents. Suitable photoactive agents include porphyrin-based materials such as porfimer sodium, green porphyrins, E6 chlorin, the hematoporphyrin derivative itself, phthalocyanines, ethiopurpurines, texaprin, and the like. The toxin may be an antibody or an antibody fragment that binds to an intracellular target (e.g. an intrabody), such as a dAb that binds to an intracellular target. Said antibodies or antibody fragments (dAbs) can be directed to defined or objective subcellular compartments. For example, antibodies or antibody fragments (dAbs) can bind to an intracellular target selected from erbB2, IL-4, BCR-ABL, p21Ras, Caspase3, Caspase7, Bcl-2, p53, cyclin E, ATF-1 / CREB, HPV16 E7, HP1, collagenase type IV, cathepsin L as well as others described in the Publications of Kontermann, RE, Methods, 34: 163-170 (2004), incorporated herein by reference to Polypeptide Domains that bind IL-4 La present invention provides polypeptide domains (e.g., single immunoglobulin variable domains, dAb monomers) that have a binding site with binding specificity for IL-4. In preferred embodiments, the polypeptide domain (e.g., dAb) binds IL-4 with an affinity of (KD; KD-K0ff (kd / Kon (ka)) from 300 nM to 1 pM (e.g., 3 x 10"7 to 5 x 10" 12M), preferably 50 nM to 1 pM, more preferably 5 nM to 1 pM and most preferably 1 nM to 1 pM, for example a KD of 1 x 10"7 M or less, preferably 1 x 10"8 M or less, more preferably 1 x 10" 9 M or less, conveniently 1 x 10"10 M or less and more preferably 1 x 10" 11 M or less; and / or a range constant of Koff of 5 x 10"1 s" 1 to 1 x 10"7 s" 1, preferably 1 x 10 * s "1 to 1 x 10" 6 s "1, more preferably 5 x 10" 3 s "1 to 1 x 10" s "1, for example 5 x 10" 1 s "or less, preferably 1 x 10" 2 s "1 or less, conveniently 1 x 10" 3 s "p less, more preferably 1 x 10" 4 s "1 or less, even more preferably 1 x 10" 5 s "1 or less, and most preferably 1 x 10" 6 s "1 or less as determined by surface plasmon resonance In some embodiments, the domain of polypeptide having a binding site with binding specificity for IL-4 competes to bind IL-4 with a dAb selected from the group consisting of DOM9-15 (SEQ ID NO: 175), DOM9-17 (SEQ ID NO. : 176), DOM9-23 (SEQ ID NO: 177), DOM9-24 (SEQ ID NO: 178), DOM9-25 (SEQ ID NO: 179), DOM9-27 (SEQ ID NO: 180), DOM9- 28 (SEQ ID NO: 181), DOM9-29 (SEQ ID NO: 182), DOM9-30 (SEQ ID NO: 183), DOM9-31 (SEQ ID NO: 184), DOM9-32 (SEQ ID NO: 185), DOM9-33 (SEQ ID NO: 186), DOM9-50 (SEQ ID NO: 187), DOM9-57 (SEQ ID NO: 188), DOM9-59 (SEQ ID NO: 189), DOM9-63 (SEQ ID NO.190), DOM9-67 (SEQ ID NO: 191), DOM9-68 (SEQ ID NO: 192), DOM9-70 (SEQ ID NO: 193), D OM9-79 (SEQ ID NO: 194), DOM9-82 (SEQ ID NO: 195), DOM9-86 (SEQ ID NO: 196), DOM9-94 (SEQ ID NO: 197), DOM9-108 (SEQ ID NO: 198), DOM9-112 (SEQ ID NO: 199), DOM9-112-1 (SEQ ID NO: 200), DOM9-112-2 (SEQ ID NO: 201), DOM9-112-3 (SEQ ID NO: 202), DOM9-112-4 (SEQ ID NO: 203), DOM9-112-5 (SEQ ID NO: 204), DOM9-112-6 (SEQ ID NO: 205), DOM9-112-7 ( SEQ ID NO: 206), DOM9-112-8 (SEQ ID NO: 207), D0M9-112-9 (SEQ ID NO: 208), DOM9-112-10 (SEQ ID NO: 209), D0M9-112-11 (SEQ ID NO: 210), DOM9-112-12 ( SEQ ID NO: 2111), DOM9-112-13 (SEQ ID NO: 212), DOM9-112-14 (SEQ ID NO: 213), DOM9-112-15 (SEQ ID NO: 214), DOM9-112- 16 (SEQ ID NO: 215), DOM9-112-17 (SEQ ID NO: 216), D0M9-112-18 (SEQ ID NO: 217), DOM9-112-19 (SEQ ID NO: 218), DOM9- 112-20 (SEQ ID NO: 219), DOM9-112-21 (SEQ ID NO: 220), DOM9-112-22 (SEQ ID NO.221), DOM9-112-23 (SEQ ID NO: 222), DOM9-112-25 (SEQ ID NO: 223), DOM9-112-81 (SEQ ID NO: 224), DOM9-112-82 (SEQ ID NO: 225), DOM9-112-83 (SEQ ID NO: 226) ); DOM9-112-84 (SEQ ID NO: 227), DOM9-112-85 (SEQ ID NO: 228), DOM9-112-86 (SEQ ID NO: 229), DOM9-112-87 (SEQ ID NO: 230) ), DOM9-112-88 (SEQ ID NO: 231), DOM9-112-89 (SEQ ID NO: 232), DOM9-112-90 (SEQ ID NO: 233), DOM9-112-91 (SEQ ID NO. : 234), DOM9-112-92 (SEQ ID NO: 235), DOM9-112-93 (SEQ ID NO: 236), DOM9-112-94 (SEQ ID NO: 237), DOM9- 112-95 (SEQ ID NO: 238), DOM9-3 12-96 (SEQ ID NO: 239), DOM9-112-97 (SEQ ID NO: 240), DOM9-112-98 (SEQ ID NO: 241), DOM9-112- 99 (SEQ ID NO.242), DOM9-112-100 (SEQ ID NO.243), DOM9-112-101 (SEQ ID NO: 244), DOM9-1132-102 (SEQ ID NO: 245), DOM9- 112-103 (SEQ ID NO: 246), DOM9-112-104 (SEQ ID NO: 247), DOM9-112-105 (SEQ ID NO: 248), DOM9-112-106 (SEQ ID NO: 249), DOM9-112-107 (SEQ ID NO: 250), DOM9-112-108 (SEQ ID NO: 251), DOM9-112-109 (SEQ ID NO: 252), DOM9-112-110 (SEQ ID NO.253), DOM9-132-111 (SEQ ID NO: 254), DOM9-112-112 (SEQ ID NO: 255), DOM9-112-113 (SEQ ID NO: 256), DOM9-112-114 ( SEQ ID NO: 257), DOM9-112-115 (SEQ ID NO: 258), DOM9-112-116 (SEQ ID NO.259), DOM9-112-117 (SEQ ID NO: 260), DOM9-112- 118 (SEQ ID NO: 261), DOM9-112-119 (SEQ ID NO: 262), DOM9-112-120 (SEQ ID NO: 263), DOM9-112-321 (SEQ ID NO: 264), DOM9- 112-122 (SEQ ID NO: 265), DOM9-112-123 (SEQ ID NO: 266), DOM9-112-124 (SEQ ID NO: 267), DOM9-112-125 (SEQ ID NO: 268), DOM9-112-126 (SEQ ID NO: 269), DOM9-112-127 (SEQ ID NO.270), DOM9-112-128 (SEQ ED NO: 271), DOM9-112-134 (SEQ ID NO: 272) ), DOM9-112-135 (SEQ ID NO: 273), DOM9-112-136 (SEQ ID NO: 274), DOM9-112-137 (SEQ ID NO: 275), DOM9-112-138 (SEQ ID NO. : 276), DOM9-112-140 (SEQ ID NO: 277), DOM9-112-141 (SEQ ID NO: 278), DOM9-112-142 (SEQ ID NO: 279), DOM9-112-143 (SEQ ID NO: 280); DOM9-112-144 (SEQ ID NO: 281), DOM9-112-145 (SEQ ID NO: 282), DOM9-112-146 (SEQ ID NO: 283), DOM9-112-147 (SEQ ID NO: 284) ), DOM9-112-148 (SEQ ID NO: 285), DOM9-112-149 (SEQ ID NO: 286), DOM9-112-150 (SEQ ID NO: 287), DOM9-112-151 (SEQ ID NO. : 288), DOM9-112-152 (SEQ ID NO: 289), DOM9-112-153 (SEQ ID NO: 290), DOM9-112-154 (SEQ ID NO: 291), DOM9-112-155 (SEQ ID NO: 292), DOM9-112-156 (SEQ ID NO: 293), DOM9-112-157 (SEQ ID NO: 294), DOM9-112-158 (SEQ ID NO: 295), DOM9-112-159 (SEQ ID NO: 296), DOM9-112-160 (SEQ ID NO: 297), DOM9-112-161 (SEQ ID NO: 298), DOM9-112-162 (SEQ.

ID NO: 299), D0M9-112-163 (SEQ ID NO: 300), D0M9-1 2-164 (SEQ ID NO: 301), DOM9-112-165 (SEQ ID NO.302), DOM9-112- 166 (SEQ ID NO: 303), DOM9-112-167 (SEQ ID NO: 304), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-169 (SEQ ID NO.306), DOM9- 112-170 (SEQ ID NO: 307), DOM9-112-171 (SEQ ID NO: 308), DOM9-112-172 (SEQ ID NO: 309), DOM9-112-173 (SEQ ID NO: 310), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-175 (SEQ ID NO: 312), DOM9-112-176 (SEQ ID NO: 313), DOM9-112-177 (SEQ ID NO: 314) ), DOM9-112-178 (SEQ ID NO: 315), DOM9-112-179 (SEQ ID NO: 316); DOM9-112-180 (SEQ ID NO.317), DOM9-112-181 (SEQ ID NO: 318), DOM9-112-182 (SEQ ID NO: 319), DOM9-112-183 (SEQ ID NO: 320 ), DOM9-112-184 (SEQ ID NO: 321), DOM9-112-185 (SEQ ID NO: 322), DOM9-112-186 (SEQ ID NO: 323); DOM9-112-187 (SEQ ID NO: 324), DOM9-112-188 (SEQ ID NO: 325), DOM9-112-189 (SEQ ID NO: 326), DOM9-112-190 (SEQ ID NO: 327) ), DOM9-112-191 (SEQ ID NO: 328), DOM9-112-192 (SEQ ID NO.329), DOM9-112-193 (SEQ ID NO: 330), DOM9-112-194 (SEQ ID NO. : 331), DOM9-112-195 (SEQ ID NO: 332), DOM9-112-196 (SEQ ID NO.333), DOM9-112497 (SEQ ID NO: 334), DOM9-112-198 (SEQ ID NO. : 335), DOM9-112-199 (SEQ ID NO: 33), DOM9-112-200 (SEQ ID NO: 337); DO 9-112-201 (SEQ ID NO: 338), DOM9-112-202 (SEQ ID NO: 339), DOM9-120 (SEQ ID NO: 340), DOM9-121 (SEQ ID NO: 341), DOM9 -122 (SEQ ID NO: 342), DOM9-123 (SEQ ID NO: 343), DOM9-124 (SEQ ID NO: 344), DOM9-125 (SEQ ID NO: 345), DOM9-128 (SEQ ID NO: 346), DOM9-134 (SEQ ID NO: 347), DOM9-136 (SEQ ID NO: 348), DOM9-26 (SEQ ID NO: 500), DOM9-35 (SEQ ID NO: 501), DOM9-36 (SEQ ID NO: 502), D0M9-37 (SEQ ID NO: 503), DOM9-38 (SEQ ID NO: 504), DOM9-39 (SEQ ID NO: 505), DOM9 -40 (SEQ ID NO: 506), DOM9-41 (SEQ ID NO: 507), DOM9-43 (SEQ ID NO: 508), DOM9-44 (SEQ ID NO: 509), DOM9-44-500 (SEQ. ID NO: 510), DOM9-44-501 (SEQ ID NO: 511), DOM9-44-502 (SEQ ID NO: 512), DOM9-44-503 (SEQ ID NO: 513), DOM9-44-504 (SEQ ID NO: 514), DOM9-44-505 (SEQ ID NO: 515), DOM9-44-506 (SEQ ID NO: 516), DOM9-44-507 (SEQ ID NO: 517), DOM9-44 -509 (SEQ ID NO: 518), DOM9-44-510 (SEQ ID NO: 519), DOM9-44-511 (SEQ ID NO: 520), DOM9-44-512 (SEQ ID NO: 521), DOM9 -44-513 (SEQ ID NO: 522), DOM9-44-514 (SEQ ID NO: 523), DOM9-44-515 (SEQ ID NO.524), DOM9-44-516 (SEQ ID NO: 525) , DOM9-44-517 (SEQ ID NO: 526), DOM9-44-518 (SEQ ID NO: 527), DOM9-44-519 (SEQ ID NO: 528), DOM9-44-520 (SEQ ID NO. 529), DOM9-44-521 (SEQ ID NO: 530), DOM9-44-522 (SEQ ID NO: 531), DOM9-44-523 (SEQ ID NO: 532), DOM9- 44-524 (SEQ ID NO: 533), DOM9-44-525 (SEQ ID NO: 534), DOM9-44-526 (SEQ ID NO: 535), DOM9-44-527 (SEQ ID NO: 536), DOM9-44-528 (SEQ ID NO: 537), DOM9-44-529 (SEQ ID NO: 538), DOM9-44-530 (SEQ ID NO: 539), DOM9-44-531 (SEQ ID NO: 540) ), DOM9-44-532 (SEQ ID NO: 541), DOM9-44-533 (SEQ ID NO: 542), DOM9-44-534 (SEQ ID NO: 543), DOM9-44-535 (SEQ.

ID NO: 544), DOM9-44-536 (SEQ ID NO: 545), DOM9-44-537 (SEQ ID NO: S46), DOM9-44-538 (SEQ ID NO: 547), DOM9-44-539 (SEQ ID NO: 548), DOM9-44-540 (SEQ ID NO: 549), D0M9-44-541 (SEQ ID NO: 550), DOM9-44-542 (SEQ ID NO.551), DOM9-44 -543 (SEQ ID NO: 552), DOM9-44-544 (SEQ ID NO: 553), DOM9-44-545 (SEQ ID NO: 554), DOM9-44-546 (SEQ ID NO: 555), DOM9 -44-547 (SEQ ID NO: 556), DOM9-44-548 (SEQ ID NO.557), DOM9-44-549 (SEQ ID NO: 558), DOM9-44-550 (SEQ ID NO: 559) , DOM9-44-551 (SEQ ID NO: 560), DOM9-44-552 (SEQ ID NO: 561), DOM9-44-553 (SEQ ID NO: 562), DOM9-44-554 (SEQ ID NO: 563), DOM9-44-555 (SEQ ID NO: 564), DOM9-44-556 (SEQ ID NO: 565), DOM9-44-557 (SEQ ID NO: 566), DOM9-44-558 (SEQ ID NO: 567), DOM9-44-559 (SEQ ID NO: 568), DOM9-44-560 (SEQ ID NO: 569), DOM9-44-561 (SEQ ID ??: 570), DOM9-44-562 (SEQ ID NO: 571), DOM9-44-563 (SEQ ID NO: 572), DOM9-44-564 (SEQ ID NO: 573), DOM9-44-565 (SEQ ID NO: 574); DOM9-44-566 (SEQ ID NO: 575), DOM9-44-625 (SEQ ID NO: 576), DOM9-44-626 (SEQ ID NO: 577), DOM9-44-627 (SEQ ID NO: 578) ), DOM9-44-628 (SEQ ID NO: 579), DOM9-44-629 (SEQ ID NO: 580), DOM9-44-630 (SEQ ID NO: 581), DOM9-44-631 (SEQ ID NO. : 582), DOM9-44-632 (SEQ ID NO: 583), DOM9-44-633 (SEQ ID NO: 584), DOM9-44-634 (SEQ ID NO: 585), DOM9-44-636 (SEQ ID NO: 586), DOM9-44-637 (SEQ ID NO: 587), DOM9-44-639 (SEQ ID NO: 588), DOM9-44-640 (SEQ ID NO: 589), DOM9-44-641 (I KNOW THAT ID NO: 590), DOM9-44-642 (SEQ ID NO: 591), DOM9-44-643 (SEQ ID NO: 592), DOM9-44-644 (SEQ ID NO.593), DOM9-45 (SEQ. ID NO.594), DOM9-46 (SEQ ID NO: 595), DOM9-47 (SEQ ID NO: 596), DOM9-48 (SEQ ID NO: 597), DOM9-143 (SEQ ID NO: 598), DOM9-144 (SEQ ID NO: 599), DOM9-146 (SEQ ID NO: 600), DOM9-152 (SEQ ID NO: 601), DOM9-155 (SEQ ID NO: 602), DOM9-155-001 ( SEQ ID NO: 603), DOM9-155-3 (SEQ ID NO: 604), DOM9-155-5 (SEQ ID NO.605), DOM9-155-8 (SEQ ID NO.606), OD 9-155 -9 (SEQ ID NO: 607), DOM9-155-11 (SEQ ID NO: 608), DOM9-155-13 (SEQ ID NO: 609), DOM9-155-14 (SEQ ID NO: 610), DOM9 -155-17 (SEQ ID NO: 611), DOM9-155-19 (SEQ ID NO: 612), DOM9-155-20 (SEQ ID NO: 613), DOM9-155-22 (SEQ ID NO: 614) , DOM9-155-23 (SEQ ID NO: 615), DOM9-155-24 (SEQ ID NO: 616), DOM9-155-25 (SEQ ID NO: 617), DOM9-155-26 (SEQ ID NO: 618), DOM9-155-27 (SEQ ID NO: 619), DOM9-155-28 (SEQ ID NO: 620), DOM9-155-29 (SEQ ID NO: 621), DOM9-155-30 (SEQ ID NO: 622), DOM9-155-31 (SEQ ID NO.623), DOM9-155-32 (SEQ ID NO: 624), DOM9-155-33 (SEQ ID NO: 625), DOM9- 155-34 (SEQ ID NO: 626), DOM9-55-35 (SEQ ID NO: 627), DOM9-155-36 (SEQ ID NO: 628), DOM9-155-37 (SEQ ID NO: 629), DOM9-155-38 (SEQ ID NO: 630), DOM9-155-39 (SEQ ID NO: 631), DOM9-155-41 (SEQ ID NO: 632), DOM9-155-42 (SEQ ID NO.633) ), DOM9-155-43 (SEQ ID NO: 634), DOM9-155-44 (SEQ ID NO: 635), DOM9-155-45 (SEQ ID NO: 636), DOM9-155-46 (SEQ ID NO. : o37), DOM9-155-47 (SEQ ID NO: 638), DOM9-155-48 (SEQ ID NO: 639), DOM9-155-49 (SEQ ID NO: 640), DOM9-155-50 (SEQ ID NO: 641) ), DOM9-155-51 (SEQ ID NO: 642), DOM9-155-52 (SEQ ID NO: 643), DOM9-155-53 (SEQ ID NO: 644), DOM9-158 (SEQ ID NO: 645) ), DOM9-160 (SEQ ID NO: 646), DOM9-161 (SEQ ID NO: 647), DOM9-162 (SEQ ID NO: 648), DOM9-163 (SEQ ID NO: 649) and DOM9-164 ( SEQ ID NO: 650). In some embodiments, the polypeptide domain having a binding site with binding specificity for IL-4 competes to bind IL-4 with a dAb selected from the group consisting of DOM9-155-77 (SEQ ID NO: 2426) , DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-204 (SEQ ID NO.2428), DOM9-112-205 (SEQ ID NO.2429), DOM9-112-206 (SEQ ID NO: 2430), DOM9-112-207 (SEQ ID NO: 2431), DOM9-H 2-208 (SEQ ID NO: 2432), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ. ID NO: 2434), DOM9-112-211 (SEQ ID NO: 2435), DOM9-112-212 (SEQ ID NO.2436), DOM9-112-213 (SEQ ID NO: 2437), DOM9-112-214 (SEQ ID NO: 2438), DOM9-112-215 (SEQ ID NO: 2439), DOM9-112-216 (SEQ ID NO: 2440), DOM9-112-217 (SEQ ID NO: 2441), DOM9-112 -218 (SEQ ID NO: 2442), DOM9-112-219 (SEQ ID NO: 2443), DOM9-112-220 (SEQ ID NO: 2444), DOM9-112-221 (SEQ ID NO: 2445), DOM9 -112-222 (SEQ ID NO: 2446), DOM9-112-223 (SEQ ID NO: 2447), DOM9-112-224 (SEQ ID NO: 2448), DOM9-112-225 (SEQ ID NO: 2449) , DOM9-112-226 (SEQ ID NO: 2450), DOM9-112-227 (SEQ ID NO: 2451), DOM9-112-228 (SEQ ID NO: 2452), D0M9-112-229 (SEQ ID NO: 2453), DOM9-112-230 (SEQ ID NO: 2454), DOM9-112-231 (SEQ ID NO: 2455) ), DOM9-112-233 (SEQ ID NO: 1734), DOM9-112-232 (SEQ ID NO: 1733) and DOM9-112-234 (SEQ ID NO: 1735). In some embodiments, the polypeptide domain having a binding site with binding specificity for IL-4 (e.g., a dAb) comprises an amino acid sequence having at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at less about 97%, at least about 98%, or at least about 99% amino acid sequence identity with the amino acid sequence or a dAb selected from the group consisting of DOM9-15 (SEQ ID.

NO: 175), DOM9 -17 (SEQ ID NO: 176), DOM9-23 (SEQ ID NO: 177), DOM9- • 24 (SEQ ID NO: 178), DOM9 -25 (SEQ ID NO: 179), DOM9-27 (SEQ ID NO: 180), DOM9 -28 (SEQ ID NO: 181), DOM9- 29 (SEQ ID NO: 182), DOM9 -30 (SEQ ID NO: 183), DOM9-31 (SEQ ID NO: 184), DOM9 -32 (SEQ ID NO: 185), DOM9-33 (SEQ ID NO: 186), DOM9 -50 (SEQ ID NO: 187), DOM9-57 (SEQ ID NO: 188), DOM9 -59 (SEQ ID NO: 189), DOM9-63 (SEQ ID NO: 190), DOM9 -67 (SEQ ID N0: 191), DOM9-68 (SEQ ID NO: 192), DOM9-70 (SEQ ID NO: 193), DOM9-79 (SEQ ID NO: 194), DOM9-82 (SEQ ID NO: 195), DOM9 -86 (SEQ ID NO: 196), DOM9-94 (SEQ ID NO: 197), DOM9-108 (SEQ ID NO: 198), D0M9-1 12 (SEQ ID NO: 199), DOM9-112-1 ( SEQ ID NO: 200), DOM9-112-2 (SEQ ID NO: 201), DOM9-112-3 (SEQ ID NO: 202), D0M9-112-4 (SEQ ID NO: 203), DOM9-112- 5 (SEQ ID NO.204), DOM9-112-6 (SEQ ID NO: 205), DOM9-112-7 (SEQ ID NO: 206), DOM9-112-8 (SEQ ID NO: 207), DOM9- 112-9 (SEQ ID NO: 208), DOM9-112-10 (SEQ ID NO.209), DOM9-112-11 (SEQ ID NO: 210), DOM9-112-12 (SEQ ID NO: 211), DOM9-112-13 (SEQ ID NO: 212), DOM9-112-14 (SEQ ID NO: 213), DOM9-112-15 (SEQ ID NO: 214), DOM9-112-16 (SEQ ID NO: 215) ), DOM9-112-17 (SEQ ID NO: 216), DOM9-112-18 (SEQ ID NO: 217), DOM9-112-19 (SEQ ID NO: 218), DOM9-112-20 (SEQ ID NO. : 219), DOM9-112-21 (SEQ ID NO: 220), DOM9-112-22 (SEQ ID NO: 221), DOM9-112-23 (SEQ ID NO: 222), DOM9-112-25 (SEQ ID NO.223), DOM9-112-81 (SEQ ID NO: 224), DOM9-112-82 (SEQ ID NO: 225), DOM9-112-83 (SEQ ID NO: 22), DOM9- 112-84 (SEQ ID NO: 227), DOM9-112-85 (SEQ ID NO: 228), DOM9-112-86 (SEQ ID NO: 229), DOM9-112-87 (SEQ ID NO: 230), DOM9-112 -88 (SEQ ID NO.-231), DOM9-112-89 (SEQ ID NO: 232), DOM9-112-90 (SEQ ID NO: 233), DOM9-112-91 (SEQ ID NO: 234), DOM9-112-92 (SEQ ID NO: 235), DOM9-112-93 (SEQ ID NO: 236), DOM9-112-94 (SEQ ID NO: 237), DOM9-112-95 (SEQ ID NO: 238) ), DOM9- 112-96 (SEQ ID NO.239), DOM9-112-97 (SEQ ID NO: 240), DOM9-112-98 (SEQ ID NO: 241), DOM9-112-99 (SEQ ID NO: 242), DOM9-112-100 (SEQ JD NO: 243), DOM9-112-101 (SEQ ID NO.244), DOM9-1 132-102 (SEQ ID NO.245), DOM9-112-103 (SEQ ID NO: 246), DOM9-112-104 (SEQ ID NO: 247), DOM9-112-105 (SEQ ID NO: 248), DOM9-112-106 (SEQ ID NO: 249), DOM9-112-107 (SEQ ID NO.250), DOM9-112-108 (SEQ ID NO.251), DOM9-112-109 (SEQ ID NO: 252), DOM9-112-110 (SEQ ID NO: 253), DOM9-112-1 11 (SEQ ID NO: 254), DOM9-112-112 (SEQ ID NO: 255), DOM9-112-113 (SEQ ID NO: 256), DOM9-112-114 (SEQ ID NO: 257), DOM9-112 -115 (SEQ ID NO: 258), DOM9-112-116 (SEQ ID NO: 259), DOM9-112-117 (SEQ ID NO: 260), DOM9-112-118 (SEQ ID NO: 261), DOM9 -112-119 (SEQ ID NO: 262), DOM9-112-120 (SEQ ID NO: 263), DOM9-112-121 (SEQ ID NO: 264), DOM9-112-122 (SEQ ID NO: 265) , DOM9-112-123 (SEQ ID NO: 266), DOM9-112-124 (SEQ ID NO: 267), DOM9-112-125 (SEQ ID NO: 268), DOM9-112-126 (SEQ ID NO: 269), DOM9-112-127 (SEQ ID NO: 270), DOM9-112-128 (SEQ ID NO: 271), DOM9-112-134 (SE Q ID NO: 272), DOM9-112-135 (SEQ ID NO: 273), DOM9-112-136 (SEQ ID NO: 274), DOM9-112-137 (SEQ ID NO: 275); DOM9-112-138 (SEQ ID NO: 276), DOM9-112-140 (SEQ ID NO: 277), DOM9-112-141 (SEQ ID NO: 278), DOM9-112-142 (SEQ ID NO: 279) ), DOM9-112-143 (SEQ ID NO: 280), DOM9-112-144 (SEQ ID NO: 281), DOM9-112-145 (SEQ ID NO: 282), DOM9-112-146 (SEQ ID NO. : 283), DOM9-112-147 (SEQ ID NO: 284), D0M9-112-148 (SEQ ID NO: 285), DOM9-112-149 (SEQ ID NO: 286), DOM9-112-150 (SEQ ID NO: 287), DOM9-112-151 (SEQ ID NO: 288), DOM9-112-152 (SEQ ID NO: 289), DOM9-112-153 (SEQ ID NO: 290), DOM9-112-154 (SEQ ID NO: 291), DOM9-112 -155 (SEQ ID NO: 292), DOM9-112-156 (SEQ ID NO: 293), DOM9-112-157 (SEQ ID NO: 294), DOM9-112-158 (SEQ ID NO: 295), DOM9 -112-159 (SEQ ID NO: 296), DOM9-112-160 (SEQ ID NO: 297), DOM9-112-161 (SEQ ID NO: 298), DOM9-112-162 (SEQ 1DNO: 299), DOM9-112-163 (SEQ ID NO: 300), DOM9-112-164 (SEQ ID NO: 301), DOM9-112-165 (SEQ ID NO.302), DOM9-112-166 (SEQ ID NO.303) ), DOM9-112-167 (SEQ ID NO: 304), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-169 (SEQ ID NO: 306), DOM9-112-170 (SEQ ID NO. .307), DOM9-112-171 (SEQ ID NO: 308). DOM9-112-172 (SEQ ID NO: 309), DOM9-112-173 (SEQ ID NO: 310), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-175 (SEQ ID NO: 312) ), DOM9-112-176 (SEQ ID NO: 313), DOM9-112-177 (SEQ ID NO: 314), DOM9-112-178 (SEQ ID NO: 315), DOM9-112-179 (SEQ ID NO. : 316), DOM9-112-180 (SEQ ID NO: 317), DOM9-112-181 (SEQ ID NO: 318); DOM9-112-182 (SEQ ID NO: 319), DOM9-112-183 (SEQ ID NO: 320), DOM9-112-184 (SEQ ID NO: 321), DOM9-112-185 (SEQ ID NO: 322) ), DOM9-112-186 (SEQ ID NO.323), DOM9-112-187 (SEQ ID NO.324), DOM9-112-188 (SEQ ID NO: 325), DOM9-112-189 (SEQ ID NO. : 326), DOM9-112-190 (SEQ ID NO: 327), DOM9-112-191 (SEQ ID NO: 328), DOM9-112-192 (SEQ ID NO: 329), DOM9-112-193 (SEQ ID NO: 330), DOM9-112-194 (SEQ ID NO: 331), DOM9-112-195 (SEQ ID NO: 332), DOM9-112-196 (SEQ ID NO: 333), DOM9-112 -197 (SEQ ID NO.334), DOM9-112-198 (SEQ ID NO: 335), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9 -112-201 (SEQ ID NO: 338), DOM9-112-202 (SEQ ID NO: 339), DOM9-120 (SEQ ID NO: 340), DOM9-121 (SEQ ID NO: 341), DOM9- -122 (SEQ ID NO: 342), DOM9- 123 (SEQ ID NO: 343), DOM9- |124 (SEQ ID NO: 344), DOM9- 125 (SEQ ID NO: 345), DOM9- -128 (SEQ ID NO.346), DOM9- 134 (SEQ ID NO: 347), DOM9 -136 (SEQ ID NO: 348), DOM9 -26 (SEQ ID NO: 500), DOM9 -35 (SEQ ID NO.501), DOM9 -36 (SEQ ID NO: 502), DOM9 -37 (SEQ ID NO: 503), DOM9 -38 (SEQ ID NO: 504), DOM9 -39 (SEQ JD NO: 505), DOM9 -40 (SEQ ID NO: 506), DOM9 -41 (SEQ ID NO: 507), DOM9 -43 (SEQ ID NO: 508), DOM9-44 (SEQ ID NO: 509), DOM9-44 -500 (SEQ ID NO.510), DOM9-44-501 (SEQ ID NO: 511), DOM9 -44- 502 (SEQ ID NO: 512), DOM9-44-503 (SEQ ID NO: 513), DOM9-44-504 (SEQ ID NO: 514), DOM9-44-505 (SEQ ID NO: 515), DOM9-44-506 (SEQ ID NO: 516), DOM9-44-507 (SEQ ID NO: 517), DOM9-44-509 (SEQ ID NO: 518), DOM9-44-S10 (SEQ ID NO: 519), DOM9-44 -511 (SEQ ID NO: 520), DOM9-44-512 (SEQ ID NO: 521), DOM9-44-513 (SEQ ID NO: 522), DOM9-44-514 (SEQ ID NO: 523), DOM9 -44-515 (SEQ ID NO: 524), DOM9-44-5 6 (SEQ ID NO: 525), DOM9-44-517 (SEQ ID NO: 526), DOM9-44-518 (SEQ ID NO: 527) ), DOM9-44-519 (SEQ ID NO: 528), DOM9- 44-520 (SEQ ID NO: 529), DOM9-44-521 (SEQ ID NO: 530), DOM9-44-522 (SEQ ID NO: 531), DOM9-44-523 (SEQ ID NO: 532), DOM9-44-524 (SEQ ID NO: 533), DOM9-44-525 (SEQ ID NO: 534), DOM9-44-526 (SEQ ID NO: 535), DOM9-44-527 (SEQ ID NO.536) ), DOM9-44-528 (SEQ ID NO: 537), DOM9-44-529 (SEQ ID NO: 538), DOM9-44-530 (SEQ ID NO: 539), DOM9-44-531 (SEQ ID NO. : 540), DOM9-44-532 (SEQ ID NO: 541), DOM9-44-533 (SEQ ID NO: 542), DOM9-44-534 (SEQ ID NO: 543), DOM9-44-535 (SEQ ID NO.544), DOM9-44-536 (SEQ ID NO: 545), DOM9-44-537 (SEQ ID NO: 546), DOM9-44-538 (SEQ ID NO: 547), DOM9-44-539 (SEQ ID NO: 548), DOM9-44-540 (SEQ ID NO: 549), DOM9-44-541 (SEQ ID NO: 550), DOM9-44-542 (SEQ ID NO: 551), DOM9-44 -543 (SEQ ID NO: 552), DOM9-44-544 (SEQ ID NO: 553), DOM9-44-545 (SEQ ID NO: 554), DOM9-44-546 (SEQ ID NO: 555), DOM9 -44-547 (SEQ ID NO: 556), DOM9-44-548 (SEQ ID NO: 557), DOM9-44-549 (SEQ ID NO: 558), DOM9-44-550 (SEQ ID NO: 559) , DOM9-44-551 (SEQ ID NO: 560), DOM9-44-552 (SEQ ID NO: 561), DOM9-44-553 (SEQ ID NO: 562), DOM9-44-554 (SEQ ID NO: 563), DOM9-44-555 (SEQ ID NO: 564), DOM9-44-556 (SEQ ID NO: 565), DOM9-44-557 (SEQ ID NO: 566), DOM9-44-558 ( SEQ ID NO: 567), DOM9-44-559 (SEQ ID NO: 568), DOM9-44-560 (SEQ ID NO: 569), DOM9-44-561 (SEQ ID NO: 570), DOM9-44- 562 (SEQ ID NO.571), DOM9-44-563 (SEQ ID NO: 572), DOM9-44-564 (SEQ ID NO: 573), DOM9-44-565 (SEQ ID NO: 574), DOM9-44-566 (SEQ ID NO: 575), DOM9-44-625 (SEQ ID NO: 576), DOM9-44-626 (SEQ ID NO: 577), DOM9-44-627 (SEQ ID NO: 578) ), DOM9-44-628 (SEQ ID NO: 579), DOM9-44-629 (SEQ ID NO: 580), DOM9-44-630 (SEQ ID NO: 581), DOM9-44-631 (SEQ ID NO. : 582), DOM9-44-632 (SEQ ID NO: 583), D0M9-44-633 (SEQ ID NO: 584), DOM9-44-634 (SEQ ID NO: 585), DOM9-44-636 (SEQ ID NO: 586), DOM9-44-637 (SEQ ID NO: 587), DOM9-44-639 (SEQ ID NO: 588), DOM9-44-640 (SEQ ID NO: 589), DOM9-44-641 (SEQ ID NO: 590), DOM9-44-642 (SEQ ID NO.591), DOM9-44-643 (SEQ ID NO: 592), DOM9-44-644 (SEQ ID NO: 593), DOM9-45 (SEQ ID NO: 594), DOM9-46 (SEQ ID NO: 595), DOM9-47 (SEQ ID NO: 596), DOM9-48 (SEQ ID NO: 597), DOM9-143 (SEQ ID NO: 598) ), DO 9-144 (SEQ ID NO: 599), DOM9-146 (SEQ ID NO: 600), DOM9-152 (SEQ ID NO: 601), DOM9-155 (SEQ ID NO: 602), DOM9-155 -001 (SEQ ID NO: 603), DOM9-155-3 (SEQ ID NO: 604), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-8 (SEQ ID NO: 606), DOM9 -155-9 (SEQ ID NO: 607), DOM9-155-11 (SEQ ID NO: 608), DOM9-155-13 (SEQ ID NO: 609), DOM9-155-14 (SEQ ID NO: 610), DOM9-155-17 (SEQ ID NO: 611), DOM9-155-19 (SEQ ID NO: 612); DOM9-155-20 (SEQ ID NO.613), DOM9-152-22 (SEQ ID NO: 614), DOM9-155-23 (SEQ ID NO: 615), DOM9-155-24 (SEQ ID NO: 616) ), DOM9-155-25 (SEQ ID NO: 617), DOM9-I55-26 (SEQ ID NO: 618), DOM9-155-27 (SEQ ID NO: 619), DOM9-155-28 (SEQ ID NO. : 620), DOM9-155-29 (SEQ ID NO: 621), DOM9-155-30 (SEQ ID NO: 622), D0M9-155-31 (SEQ ID NO: 623), D0M9-155-32 (SEQ ID NO.624), DOM9-155-33 (SEQ ID NO: 625), DOM9-155-34 (SEQ ID NO: 626), DOM9-155-35 (SEQ ID NO: 627), DOM9-155-36 (SEQ ID NO: 628), DOM9-155-37 (SEQ ID NO: 629), DOM9-155 -38 (SEQ ID NO.630), DOM9-155-39 (SEQ ID NO: 631), DOM9-155-41 (SEQ 1DNO: 632), DOM9-155-42 (SEQ ID NO: 633), DOM9- 155-43 (SEQ ID NO: 634), DOM9-155-44 (SEQ ID NO.635), DOM9-155-45 (SEQ ID NO: 636), DOM9-155-46 (SEQ ID NO: 637), DOM9-155-47 (SEQ ID NO: 638), DOM9-155-48 (SEQ ID NO: 639), DOM9-155-49 (SEQ ID NO: 640), DOM9-155-50 (SEQ ID NO: 641) ), DOM9-155-51 (SEQ ID NO: 642), DOM9-155-52 (SEQ ID NO: 643), DOM9-155-53 (SEQ ID NO: 644), DOM9-158 (SEQ ID NO: 645) ), DOM9-160 (SEQ ID NO: 646), DOM9-161 (SEQ ID NO.647), DOM9-162 (SEQ ID NO: 648), DOM9-163 (SEQ ID NO: 649) and DOM9-164 ( SEQ ID NO: 650). In some embodiments, the polypeptide domain having a binding site with binding specificity for IL-4 (e.g., a dAb) comprises an amino acid sequence having at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at less approximately 97%, at least about 98%, or at least about 99% amino acid sequence identity with the amino acid sequence or a dAb selected from the group consisting of DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-204 (SEQ ID NO: 2428), DOM9-112-205 (SEQ ID NO: 2429), DOM9-112-206 (SEQ ID NO: 2430) ), DOM9-112-207 (SEQ ID NO: 2431), DOM9-112-208 (SEQ ID NO: 2432), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO. : 2434), DOM9-112-211 (SEQ ID NO: 2435), DOM9-112-212 (SEQ ID NO: 2436), DOM9-112-213 (SEQ ID NO: 2437), DOM9-112-214 (SEQ ID NO: 2438), DOM9-112-215 (SEQ ID NO: 2439), DOM9-112-216 (SEQ ID NO: 2440), DOM9-112-217 (SEQ ID NO: 2441), DOM9-112-218 (SEQ ID NO: 2442), DOM9-112-219 (SEQ ID NO: 2443), DOM9-112-220 (SEQ ID NO: 2444), DOM9-112-221 (SEQ ID NO: 2445), DOM9-112 -222 (SEQ ID NO: 2446), DOM9-112-223 (SEQ ID NO: 2447), DOM9-112-224 (SEQ ID NO: 2448), DOM9-112-225 (SEQ ID NO: 2449), DOM9 -112-226 (SEQ ID NO: 2450), DOM9-112-227 (SEQ ID NO: 2451), D OM9-112-228 (SEQ ID NO: 2452), DOM9-112-229 (SEQ ID NO: 2453), DOM9-112-230 (SEQ ID NO: 2454), DOM9-112-231 (SEQ ID NO: 2455) ), DOM9-112-233 (SEQ ID NO: 1734), DOM9-112-232 (SEQ ID NO: 1733) and DOM9-112-234 (SEQ ID NO: 1735). In preferred embodiments, the polypeptide domain having a binding site with binding specificity for IL-4 comprises an amino acid sequence having at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at less about 96%, at least about 97%, at least about 98%, or at least about 99% amino acid sequence identity with the amino acid sequence or a dAb selected from the group consisting of DOM9-112 -155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9 -112-200 (SEQ ID NO: 337), DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617) , DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512). For example, the polypeptide domain having a binding site with binding specificity for IL-4 may comprise DOM9-112-155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9 -112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO.337), DOM9-44-502 (SEQ ID NO: 512) , DOM9-155-5 (SEQ ID NO: 605, DOM9-155-25 (SEQ ID NO: 617), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427 ), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9- 112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512). In some embodiments, the polypeptide domain having a binding site with binding specificity for IL-4 competes with any of the dAbs described herein for binding to IL-4. Preferably, the polypeptide domain having a binding site with binding specificity for IL-4 is a single immunoglobulin variable domain. The polypeptide domain having a binding site with binding specificity for IL-4 can comprise any variable domain of single immunoglobulin, and preferably comprises a human variable domain or a variable domain comprising regions of human structure. In certain embodiments, the polypeptide domain having a binding site with binding specificity for IL-4, comprises a universal structure, as described herein. The universal structure can be a VL (VA or VK) structure, such as a structure comprising the structure amino acid sequences encoded by the immunoglobulin gene segment DPK1, DPK2, DPK3, DPK4, DPK5, DPK6, DPK7, DPK8, DPK9, DPK10, DPK12, DPK13, DPK15, DPK16, DPK18, DPK19, DPK20, DPK21, DPK22, DPK23, DPK24, DPK25, DPK26 or human germline DPK 28. If desired, the VL structure may further comprise the amino acid sequence of the structure encoded by the gel segment of JKi immunoglobulin, JK2, JK3, JK4, or human germline JK5. In other embodiments the universal structure may be a VH structure, such as a structure comprising the amino acid sequences encoded by the immunoglobulin gene segment DP4, DP7, DP8, DP9, DP10, DP31, DP33, DP38, DP45, DP46, DP47, DP49, DP50, DP51, DP53, DP54, DP65, DP66, DP67, DP68 or DP69 of human germ line. If desired, the VH structure may further comprise the amino acid sequence of the structure encoded by the immunoglobulin gene segment JH1 > JH2, Jh3, Jh4, JH4b, JH5 and JH6 of the human germ line. In certain embodiments, the polypeptide domain having a binding site with binding specificity for IL-4 comprises one or more regions comprising an amino acid sequence that is equal to the amino acid sequence of a corresponding structure region encoded by a human germline antibody gene segment, or the amino acid sequences of one or more structure regions collectively comprise differences of up to 5 amino acids relative to the amino acid sequence of the region of the corresponding structure encoded by the segment of human germline antibody gene. In other embodiments, the amino acid sequences of FW1, FW2, FW3 and FW4 of the polypeptide domain having a linkage site with binding specificity for IL-4, are equal to the amino acid sequences of corresponding structure regions encoded by a human germline antibody gene segment, or the amino acid sequences of FW1, FW2, FW3 and FW4 which collectively contain differences of up to 10 amino acids relative to the amino acid sequences of the corresponding structure regions encoded by the human germline antibody gene segment. In other embodiments, the polypeptide domain having a binding site with binding specificity for IL-4 comprises FW1, FW2 and FW3 regions, and the amino acid sequence of the FW1, FW2 and FW3 regions are the same as the amino acid sequences. of the corresponding structure regions encoded by the human germline antibody gene segments. In particular embodiments, the polypeptide domain having a binding site with binding specificity for IL-4 comprises the DPK9 VL structure, or a VH structure selected from the group consisting of DP47, DP45 and DP38. The polypeptide domain having a binding site with binding specificity for IL-4 may comprise a binding site of a generic ligand, such as a protein A, protein L and protein G. The ligand of the present invention (e.g. , ligand having binding specificity for IL-4 and 1L-13, the ligand having binding specificity for IL-4) may comprise a binding portion without immunoglobulin having binding specificity for IL-4 and preferably inhibiting an IL function -4 (eg, receptor binding) wherein the non-immunoglobulin binding portion comprises one, two or three of the CDRs of a VH, VL, or VHH that binds IL-4 and a suitable scaffold. In certain embodiments, the non-immunoglobulin binding portion comprises CDR3 but not CDR1 or CDR2 of a VH, VL or VHH that binds IL-4 and a suitable scaffold. In other embodiments, the non-immunoglobulin binding portion comprises CDR1 and CDR2, but not CDR3 of a VH, VL or VHH that binds IL-4 and a suitable scaffold. In other embodiments, the non-immunoglobulin binding portion comprises CDR1, CDR2 and CDR3 of a VH, VL or VHH that binds to IL-4 and a suitable scaffold. Preferably, the CDRs or CDRs of the ligand of these embodiments are a CDR or CDRs of an anti-IL-4 dAb described herein. Preferably, the binding portion without immunoglobulin comprises one, two or three of the CDRs of one of the anti-IL-4 dAbs described herein. In other embodiments, the ligand (e.g., ligand having binding specificity for IL-4 and IL-13, the ligand having binding specificity for IL-4) comprises only CDR3 of a VH, VL or VHH that binds IL -4. The domain without immunoglobulin can comprising an amino acid sequence having one or more regions having sequence identity with one, two or three of the CDRs of an anti-IL-4 dAb described herein. For example, the domain without immunoglobulin can have an amino acid sequence containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90% sequence identity with CDR1, CDR2 and / or CDR3 of an anti-IL-4 dAb described herein. Even more preferably, the binding portion without immunoglobulin comprises one, two or three of the CDRs of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155- 25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9- 112-199 (SEQ ID NO: 336), and DOM9-112-200 (SEQ ID NO: 337). In certain embodiments, the polypeptide domain having a binding site with binding specificity for IL-4 is substantially resistant to aggregation. For example, in some embodiments, less than about 10%, less than about 9%, less than about 8%, less than about 7%, less than about 6%, less than about 5%, less than about 4%, less of about 3%, less than about 2% or less than about 1% of the polypeptide domain having a binding site with binding specificity for IL-4 is added when a solution of 1-5 mg / ml, 5-10 mg / ml, 10-20 mg / ml 20-50 mg / ml, 50-100 mg / ml, 100-200 mg / ml or 200-500 mg / ml ligand or dAb in a solvent that is routinely used for drug formulation such as saline, buffered saline, citrated buffered saline, water, an emulsion and any These solvents with an acceptable excipient such as those approved by the FDA, are maintained at a temperature of about 22 ° C, 22-25 ° C, 25-30 ° C, 30-37 ° C, 37-40 ° C, 40 - 50 ° C, 50-60 ° C, 60-70 ° C, 70-80 ° C, 15-20 ° C, 10-15 ° C, 5-1O0C, 2-5 ° C, 0-2 ° C , -10 ° C to 0 ° C, -20 ° C to -10 ° C, -40 ° C to -20 ° C, -60 ° C to -40 ° C, or -80 ° C to -60 ° C , for an approximate period of time, for example, 10 minutes, 1 hour, 8 hours, 24 hours, 2 days, 3 days, 4 days, 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months , 4 months, 6 months, 1 year, or 2 years. Aggregation can be evaluated using any suitable method such as microscopy, evaluating the turbidity of a solution by visual inspection or spectroscopy or any other suitable method. Preferably, the aggregation is evaluated by dynamic light scattering. Polypeptide domains that have a binding site with binding specificity for IL-4 that are resistant to aggregation provide several advantages. For example, said polypeptide domains having a binding site with Binding specificity for IL-4 can be easily produced at high yields in the form of soluble proteins by expression, using a suitable biological production system such as E. coli, and can be formulated and / or stored at higher concentrations than conventional polypeptides, and with less aggregation and loss of activity. In addition, the polypeptide domain having a binding site with binding specificity for IL-4 that is resistant to aggregation can be produced more economically than other antigen-binding polypeptides or epitopes (eg, conventional antibodies). For example, generally the preparation of antigen or epitope-binding polypeptides projected for in vivo applications include processes (e.g., gel filtration) that remove aggregated polypeptides. Failure to eliminate such aggregates may result in a preparation that is not suitable for in vivo applications, due, for example, to the fact that aggregates of a polypeptide binding antigens that are projected to act as an antagonist, may work as an agonist inducing the cross-linking or agglomeration of the target antigen. Protein aggregates can also reduce the efficacy of the therapeutic polypeptide by inducing an immune response to the subject to which they are administered. In contrast, the polypeptide domain resistant to Aggregation that has a binding specific binding site for IL-4 of the present invention, can be prepared for in vivo applications without the need to include process steps that eliminate aggregates, and can be used in in vivo applications without the above-mentioned disadvantages caused by the polypeptide aggregates. In some embodiments, the polypeptide domain having a binding site with binding specificity for IL-4, reversibly unfolds when heated to a temperature (Ts) and cooled to a temperature (Te), where Ts is greater than the melting temperature (Tm) of the polypeptide domain having a binding site with binding specificity for IL-4, and Te is less than the fusion temperature of the polypeptide domain having a binding site with specificity Link for IL-4. For example, a polypeptide domain having a binding site with binding specificity for IL-4 can be reversibly split when heated to a temperature of 80 ° C and cooled to approximately room temperature. A polypeptide that unfolds in a reversible manner loses its function when it unfolds, although it regains its function when it is doubled again. Said polypeptides are distinguished from the polypeptides that are added when they are unfolded or that are re-folded in an inadequate manner (poorly folded polypeptides) ie they do not regain the function.

The cleavage and redoubling of polypeptide can be evaluated, for example by direct or indirect directing of the polypeptide structure using any suitable method. For example, the polypeptide structure can be detected by circular dichroism (CD) (e.g., remote UV CD, near UV CD), fluorescence (e.g., tryptophan side chain fluorescence), susceptibility to proteolysis, nuclear magnetic resonance ( NMR), or by detecting or measuring a polypeptide function that depends on the appropriate fold (e.g. ligand to target ligand, binding to a generic ligand). In one example, cleavage of the polypeptide is evaluated using a functional assay in which the loss of binding function (e.g. binding of a generic and / or targeting ligand, binding to a substrate) indicates that the polypeptide is unfolded. The degree of cleavage and redoubling of a polypeptide domain having a binding site with binding specificity for IL-4 can be determined using a cleavage or denaturation curve. A splitting curve can be produced by plotting the temperature as the ordinate and the relative concentration of the folded polypeptide as the abscissa. The relative concentration of the bent polypeptide domain having a binding site with binding specificity for IL-4 can be determined directly and indirectly using any suitable method (eg, example, CD, fluorescence, binding assay). For example, a polypeptide domain having a binding site with binding specificity for IL-4 can be prepared and the ellipticity of the solution determined by CD. The ellipticity value obtained represents a relative concentration of bent ligand (e.g., monomer dAb) of 100%. The polypeptide domain having a binding site with binding specificity for IL-4, in the solution is subsequently split up by increasing the temperature of the solution in increments and the ellipticity is determined in appropriate increments (for example, after each increase in a degree in temperature). The polypeptide domain having a binding site with binding specificity for IL-4, in the solution, is subsequently redoubled by reducing the temperature of the solution in increments and the ellipticity is determined in appropriate increments. The data can be plotted to produce a splitting curve and a bending curve. The doubling and redoubling curves have a characteristic sigmoid shape that includes a part in which the polypeptide domain having a binding site with binding specificity for IL-4 molecules is doubled, a doubling / doubling transition in which the polypeptide domain having a binding site with binding specificity for IL-4 molecules are split into various degrees, and a part in which the domain of polypeptide having a binding site with binding specificity for IL-4, is split. The intercept of the y-axis of the redoubling curve is the relative amount of the redoubled polypeptide domain having a binding site with binding specificity for recovered IL-4. A recovery of at least about 50%, or at least about 60%, or at least about 70%, or at least about 75%, or at least about 80%, or at least about 85%, or at least about 90%, or at least about 95%, is indicative that the dAb ligand or monomer is reversibly split. In a preferred embodiment, the ability to revert the unfolding of a polypeptide domain having a binding site with binding specificity for IL-4, is determined by preparing a polypeptide domain having a binding site with binding specificity for a IL-4 solution, and that traces bending curves and double bending. The polypeptide domain having a binding site with binding specificity for an IL-4 solution, can be prepared in any suitable solvent, such as an aqueous buffer having a suitable pH to allow the polypeptide domain having a site of linkage with binding specificity for IL-4, dissolves (for example, a pH that is approximately 3 units up below the point isoelectric (pl)). The polypeptide domain having a binding site with binding specificity for an IL-4 solution is sufficiently concentrated to allow splitting and / or bending to be detected. For example, the ligand solution or the dAb monomer may be approximately 0.1 μ? to approximately 100 μ ?, or preferably approximately 1 μ? up to approximately 10 μ ?. If the melting temperature (Tm) of a polypeptide domain having a binding site with binding specificity for IL-4 is known, the solution can be heated to approximately ten degrees below the Tm (Tm-10) and evaluated bending by ellipticity or fluorescence (eg, distant-UV CD scan from 200 nm to 250 nm, fixed length CD at 235 nm or 225 nm, fluorescent emission spectrum from tryptophan at 300 to 450 nm with excitation at 298 nm) to provide a 100% relative bent dAb ligand or monomer. The solution is then heated to ten degrees above Tm (Tm + 10) in predetermined increments (e.g., increments of about 0.1 to about 1 degree), and the ellipticity or fluorescence is determined at each increment. Subsequently, the polypeptide domain having a binding site with binding specificity for IL-4 is redoubled by cooling at least Tm-10 in predetermined increments and an ellipticity or fluorescence determined at each increment. If the melting temperature of a polypeptide domain having a binding site with binding specificity for IL-4 is not known, the solution can be split by increasing heating at a temperature from about 25 ° C to about 100 ° C and subsequently redoubling by cooling the increase at a temperature of at least about 25 ° C, and ellipticity or fluorescence at each increase in heating and cooling will be determined. The obtained data can be processed to produce a splitting curve and a redoubling curve, where the intercept of the y-axis of the roll-up curve is the relative amount of redoubled protein recovered. In some embodiments, the polypeptide domain having a binding site with binding specificity for IL-4 does not comprise a Camelid immunoglobulin variable domain, or one or more structure amino acids that are unique to the encoded immunoglobulin variable domains by Camelid germline antibody gene segments. Preferably, the polypeptide domain having a binding site with binding specificity for VEG is secreted in an amount of at least about 0.5 mg / L when expressed in E. coli or Pichia species (eg, P. pastoris ). In other preferred embodiments, the polypeptide domain having a binding site with binding specificity for IL-4, is secreted in an amount of at least about 0.75 mg / L, at least about 1 mg / L, at least about 4 mg / L, at least about 5 mg / L, at least about 10 mg / L, at least about 15 mg / L, at less about 20 mg / l, at least about 25 mg / l, at least about 30 mg / l, at least about 35 mg / l, at least about 40 mg / l, at least about 45 mg / l, or at least about 50 mg / l, or at least about 100 mg / l, or at least about 200 mg / l, or at least about 300 mg / l, or at least about 400 mg / l, or at least about 500 mg / l , or at least about 600 mg / l, or at least about 700 mg / l, or at least about 800 mg / l, at least about 900 mg / l, or at least about Ig / l when expressed in species E. coli or in Pichia (for example, P. pastoris). In other preferred embodiments, a polypeptide domain having a binding site with binding specificity for IL-4, is secreted in an amount of at least about 1 mg / L to at least about Ig / I, at least about 1 mg / l to at least about 750 mg / l, at least about 100 mg / l to at least about 1 g / l, at least about 200 mg / l to at least about 1 g / l, at least about 300 mg / l up to at least about 1 g / l, at least about 400 mg / l to at least about 1 g / l, at least about 500 mg / l to at least about Ig / I, at least about 600 mg / l to at least about 1 g / l , at least about 700 mg / l to at least about 1 g / l, at least about 800 mg / l to at least about Ig / I, or at least about 900 mg / l to at least about Ig / I when it is expressed in E. coli or Pichia species (for example, P. pastoris). Although a polypeptide domain having a binding site with binding specificity for IL-4, described herein can be secretable when expressed in E. coli species or in Pichia species (eg, P. pastoris), they can be produced using any suitable method, such as synthetic chemical methods or biological production methods that do not employ E. coli or Pichia species. IL-13 Linking Polypeptide Domain The present invention provides polypeptide domains (e.g., dAb) that have a binding site with binding specificity for IL-13. In preferred embodiments, the polypeptide domain (e.g., dAb) binds IL-13 with an affinity (KD; KD = Koff (kd) / Kon (ka)) from 300 nM to 1 pM (e.g., 3 x 10"7 to 5 x 10" 12M), preferably 100 nM to 1 pM, or 50 nM to 10 pM, more preferably 10 nM to 100 pM and most preferably approximately 1 nM, for example and KD of 1 X 10"7 M or less, preferably 1 x 10" 8 M or less, more preferably about 1 x 10"9 M or less, 1 x 10" 10 M or less or 1 x 10"11 M or less and / or a constant of rank K0ff of 5 x 10"1 s" 1 to 1 x 0"7 s" 1 preferably 1 x 10"2 s" 1 to 1 x 10"6 s" 1, more preferably 5 x 10"3 s" 1 to 1 x 1 O "5 s" 1, for example 5 x 10"1 s" 1 or less, preferably 1 x 102 s "1 or less, conveniently 1 x 103 s" 1 or less, more preferably 1 x 10 ~ 4 s "1 or less, still more preferably 1 x 10" 5 s "1 or less, and most preferably 1 x 10" 6 s "1 or less as determined by plasmon resonance of surface. In some embodiments, a polypeptide domain having a binding site with binding specificity for IL-13 competes to bind IL-13 with a dAb selected from the group consisting of DOM10-53 (SEQ ID NO: 967), DOM10-53-1 (SEQ ID NO: 968), DOM 10-53-2 (SEQ ID NO: 969), DOM10-53-3 (SEQ ID NO: 970), DOM10-53-4 (SEQ ID NO: 971), DOM10-53-5 (SEQ ID NO: 972), DOM10-53-6 (SEQ ID NO: 973), DOM 10-53-7 (SEQ ID NO: 974), DOM10-53-8 (SEQ. ID NO: 975), DOM 10-53-9 (SEQ ID NO: 976), DOM10-53-10 (SEQ ID NO: 977), DOM10-53-11 (SEQ ID NO: 978), DOM10-53- 12 (SEQ ID NO: 979), DOM10-53-13 (SEQ ID NO: 980), DOM10-53-14 (SEQ ID NO: 981), DOM10-53-15 (SEQ ID NO: 982), DOM10- 53-16 (SEQ ID NO: 983), DOM10-53-17 (SEQ ID NO: 984), DOM10-53-18 (SEQ ID NO: 985), DOM10-53-19 (SEQ ID NO: 986), DOM10-53-20 (SEQ ID NO: 987), DOM 10-53-21 (SEQ ID NO: 988), DOM10-53-122 (SEQ ID NO: 989), DOM10-53-123 (SEQ ID NO: 990), DOM10-53- 24 (SEQ ID NO: 991), DOM 10-53-25 (SEQ ID NO: 992), DOM10-53-26 (SEQ ID NO: 993), DOM10-53-27 (SEQ ID NO: 994), DOM10 -53-28 (SEQ ID NO: 995), DOM10-53-29 (SEQ ID NO: 996), DOM10-53-30 (SEQ ID NO: 997), DOM10-53-31 (SEQ ID NO: 998) , DOM10-53-32 (SEQ ID NO: 999), DOM10-53-43 (SEQ ID NO.1000), DOM10-53-44 (SEQ ID NO: 1001), DOM10-53-45 (SEQ ID NO: 1002), DOM30-53-46 (SEQ ID NO: 1003). DOM10-53-47 (SEQ ID NO: 1004), DOM10-53-48 (SEQ ID NO: 1005), DOM10-53-49 (SEQ ID NO.1006), DOM10-53-50 (SEQ ID NO: 1007) ), DOM10-53-51 (SEQ ID NO: 1008), DOM10-53-52 (SEQ ID NO: 1009), DOM10-53-53 (SEQ ID NO: 1010), DOM10-53-54 (SEQ ID NO. : 1011), DOM10-53-55 (SEQ ID NO: 1012), DOM10-53-56 (SEQ ID NO: 1013), DOM10-53-57 (SEQ ID NO: 1014), DOM10-53-59 (SEQ ID NO: 1015), DOM10-53-60 (SEQ ID NO: 1016), DOM10-53-61 (SEQ ID NO: 1017), DOM10-53-62 (SEQ ID NO: 1018), DOM10-53-63 (SEQ ID NO: 1019), DOM10-53-64 (SEQ ID NO: 1020), DOM 10-53-65 (SEQ ID NO: 1021), DOM10-53-66 (SEQ ID NO: 1022), DOM10- 53-67 (SEQ ID NO: 1023), DOM10-53-68 (SEQ ID NO: 1024), DOM10-53-69 (SEQ ID NO: 1025), DOM10-53-70 (SEQ ID NO: 1026), DOM10-53-71 (SEQ ID NO: 1027), DOM10-53-72 (SEQ ID NO: 1028), DOM10-53-73 (SEQ ID NO: 1029), DOM10-53-74 (SEQ ID NO: 1030) ), DOM10-53-75 (SEQ ID NO: 1031), DOM10-53-76 (SEQ ID NO: 1032), DOM10-53-77 (SEQ ID NO: 1033), DOM10-53-78 (SEQ ID NO: 1034), DOM10-53-79 (SEQ ID NO: 1035) DOM10-53-80 (SEQ. ID NO: 1036), DOM10-53-81 (SEQ ID NO: 1037), DOM10-53-82 (SEQ ID NO: 1038), DOM10-53-83 (SEQ ID NO: 1039), DOM10-53-84 (SEQ ID NO: 1040), DOM10-53-85 (SEQ ID NO: 1041), D0M10-53-86 (SEQ ID NO: 1042), DOM10-53-87 (SEQ ID NO: 1043), DOM10-53 -88 (SEQ ID NO: 1044), DOM10-53-89 (SEQ ID NO: 1045), DOM10-53-91 (SEQ ID NO: 1046), DOM10-53-92 (SEQ ID NO: 1047), DOM10 -53-93 (SEQ ID NO: 1048), DOM10-53-94 (SEQ ID NO: 1049), DOM10-53-95 (SEQ ID NO: 1050), DOM10-53-96 (SEQ ID NO: 1051) , DOM10-53-97 (SEQ ID NO: 1052), DOM10-53-98 (SEQ ID NO: 1053), DOM 10-53-99 (SEQ ID NO.1054), DOM10-53-100 (SEQ ID NO. : 1055), DOM10-53-103 (SEQ ID NO: 1056), DOM10-53-105 (SEQ ID NO: 1057), DOM10-53-106 (SEQ ID NO: 1058), DOM10-53-108 (SEQ. ID NO: 1059), DOM10-53-110 (SEQ ID NO: 1060), DOM10-53-111 (SEQ ID NO: 1061), DOM10-53-112 (SEQ ID NO: 1062), DOM10-53-314 (SEQ ID NO: 1063), DOM10-53-115 (SEQ ID NO: 1064), DOM10-53-116 (SEQ ID NO: 1065), DOM10-53-117 (SEQ ID NO: 1066), DOM10-53-119 (SEQ ID NO: 1067), DOM 10-53-120 (SEQ ID NO: 1068), DOM10-53-122 (SEQ ID NO: 1069), DOM10-53-201 (SEQ ID NO: 1070), DOM10-53-203 (SEQ ID NO: 1071), DOM10-53-204 (SEQ ID NO: 1072), DOM10-53 -205 (SEQ ID NO: 1073), DOM 10-53-206 (SEQ ID NO: 1074), DOM10-53-207 (SEQ ID NO: 1075), DOM10-53-208 (SEQ ID NO: 1G76), DOM10- 53-209 (SEQ ID NO: 1077), DOM10-53-210 (SEQ ID NO: 1078), DOM10-53-211 (SEQ ID NO: 1079), DOM10-53-213 (SEQ ID NO: 1080), DOM10-53-214 (SEQ ID NO: 1081), DOM10-53-215 (SEQ ID NO: 1082), DOM10-53-216 (SEQ ID NO: 1083), DOM10-53-217 (SEQ ID NO: 1084) ), DOM 10-53-1218 (SEQ ID NO: 1085), DOM10-53-219 (SEQ ID NO: 1086), DOM10-53-220 (SEQ ID NO: 1087), DOM10-53-221 (SEQ ID NO: 1088), DOM10-53-222 (SEQ ID NO: 1089), DOM 10-53-223 (SEQ ID NO: 1090), DOM10-53-224 (SEQ ID NO: 1091), DOM10-53-225 (SEQ ID NO: 1092), DOM10-53-226 (SEQ ID NO: 1093), DOM10-53-227 (SEQ ID NO: 3094), DOM10-53-228 (SEQ ID NO: 1095), DOM10-53 -229 (SEQ ID NO: 1096), DOM 10-53-230 (SEQ ID NO: 1097), DOM10-53-231 (SEQ ID NO: 1098), DOM10-53-232 (SEQ ID NO: 1099), DOM10-53-233 (SEQ ID NO: 1100), DOM10-53-234 (SEQ ID NO: 1101), DOM10-53-235 (SEQ ID NO: 1102), DOM10-53-236 (SEQ ID NO 103) , DOM10-53-237 (SEQ ID NO: 1104), DOM10-53-238 (SEQ ID NO: 1105), DOM10-53-239 (SEQ ID NO: 1106), DOM10-53-240 (SEQ ID NO: 1107), DOM10-53-241 (SEQ ID NO: 1108), DOM10-53-2 42 (SEQ ID NO: 1109), DOM10-53-243 (SEQ ID NO: 11 10), DOM10-53-244 (SEQ ID NO: 111 I), DOM10-53-245 (SEQ ID NO 112), DOM10 -53-246 (SEQ ID NO: 1113), DOM10-53-247 (SEQ ID NO: 1114), DOM10-53-248 (SEQ ID NO: 1115), DOM10-53-249 (SEQ ID NO: 1116) , DOM10-53-250 (SEQ ID NO: 1117), DOM10-53-251 (SEQ ID NO: 1118), DOM10-53-252 (SEQ ID NO: 1119), DOM10-53-253 (SEQ ID NO: 1120), DOM10-53-254 (SEQ ID NO: 1121), DOM10-53-255 (SEQ ID NO: 1122), DOM10-53-256 (SEQ ID NO: 1123), DOM10-53-257 (SEQ ID NO: 1124) ), DOM10-53-258 (SEQ ID NO: 1125), DOM10-53-259 (SEQ ID NO: 1126), DOM10-53-260 (SEQ ID NO: 1127), DOM10-53-261 (SEQ ID NO. : 1328), DOM10-53-262 (SEQ ID NO: 1129), DOM10-53-263 (SEQ ID NO: 1130), DOM10-53-264 (SEQ ID NO: 1131), DOM10-53-265 (SEQ. ID NO: 1132), DOM10-53-266 (SEQ ID NO: 1133), DOM10-53-267 (SEQ ID NO: 1134), DOM10-53-268 (SEQ ID NO: 1135), DOM10-53-269 (SEQ ID NO: 1136), DOM10-53-270 (SEQ ID NO: 1137), DOM10-53-271 (SEQ ID NO: 1138), DOM10-53-272 (SEQ ID NO: 1139), DOM10-53 -273 (SEQ ID NO: 1140), DOM10-53-274 (SEQ ID NO: 1143), DOM10-53-275 (SEQ ID NO: 1142), DOM10-53-276 (SEQ ID NO 143), DOM10- 53-277 (SEQ ID NO: 1144), DOM10-53-278 (SEQ ID NO: 1145), DOM10-53-279 (SEQ ID NO: 1146), DOM10-53-280 (SEQ ID NO: 1147), DOM10-53-281 (SEQ ID NO: 1148), DOM10-53-282 (SEQ ID NO: U49), DOM10-53-283 (SEQ ID NO: 1150), DOM10-53-284 (SEQ ID NO: 1151) ), DOM10-53-285 (SEQ ID NO: 1152), DOM10-53-2 86 (SEQ ID NO: 1153), DOM10-53-287 (SEQ ID NO: 1154), DOM10-53-288 (SEQ ID NO: 1155), DOM10-53-289 (SEQ ID NO: 1156), DOM10- 53-290 (SEQ ID NO: 1157), DOM10-53-291 (SEQ ID NO: 1158), DOM10-53-292 (SEQ ID NO: 11S9), DOM10-53-293 (SEQ ID NO: 1160), DOM10-53-294 (SEQ ID NO: 1161), DOM10-53-295 (SEQ ID NO: 1162), DOM10-53-296 (SEQ ID NO: 1163), DOM10-53-297 (SEQ ID NO: 1164), DOM10-53-298 (SEQ ID NO: 1165), DOM 10-53-299 (SEQ ID NO: 1166), DOM10-53-300 (SEQ ID NO: 1167), DOM10-53-301 (SEQ ID NO: 1168), DOM10-53-302 (SEQ ID NO: 1169), DOM10-53-303 (SEQ ID NO: 1170), DOM10-53-304 (SEQ ID NO: 1171), DOM10-53 -305 (SEQ ID NO: 1172), DOM10-53-306 (SEQ ID NO: 1173), DOM10-53-307 (SEQ ID NO: 1174), DOM10-53-308 (SEQ ID NO: 1175), DOM10 -53-309 (SEQ ID NO: 1176), DOM10-53-310 (SEQ ID NO: 11787), DOM10-53-311 (SEQ ID NO: 1178), DOM10-53-312 (SEQ ID NO: 1179) , DOM10-53-314 (SEQ ID NO: 1180), DOM10-53-315 (SEQ ID NO: 1181), DOM10-53-316 (SEQ ID NO: 1182), DOM10-53-317 (SEQ ID NO: 1183), DOM10-53-318 (SEQ ID NO: 1184), DOM10-53-319 (SEQ ID NO: 1185), DOM10-53-320 (SEQ ID NO: 1186), DOM 10-53-321 (SEQ. ID NO: 1187), DOM10-53-322 (SEQ ID NO: 1188), DOM10-53-323 (SEQ ID NO: 1189), DOM10-53-324 (SEQ ID NO: 1190), DOM10-53-325 (SEQ ID ?? -? 1911 DOM10-53-326 (SEQ ID NO: 1192), DOM10-53-327 (SEQ ID NO: 1193), DOM10-53-328 (SEQ ID NO: 1194), DOM10-53 -329 (SEQ ID NO: 1195), DOM10-53-330 (SEQ ID NO: 11 96), DOM10-53-331 (SEQ ID NO: 1197), DOM10-53-333 (SEQ ID NO: 1198), DOM10-53-334 (SEQ ID NO: 1199), DOM10-53-336 (SEQ ID NO: 1200), DOM10-53-337 (SEQ ID NO: 1201), DOM 10-53-338 (SEQ ID NO: 1202), DOM10-53-339 (SEQ ID NO: 1203), DOM10-53-340 (SEQ ID NO: 1204), DOM10-53-341 (SEQ ID NO-1205), DOM30-53-342 (SEQ ID NO: 1206), DOM10-53-343 (SEQ ID NO: 1207), DOM10-53 -344 (SEQ ID NO: 1208), DOM10-53-345 (SEQ ID NO: 1209), DOM10-53-346 (SEQ ID NO: 1210), DOM10-53-347 (SEQ ID N0: 121 1), DOM10- 53-348 (SEQ ID NO: 1212), DOM10-53-349 (SEQ ID NO: 1213), DOM10-53-350 (SEQ ID NO: 1214), DOM 10-53-351 (SEQ ID NO: 1215) , DOM10-53-352 (SEQ ID NO: 1216), DOM10-53-353 (SEQ ID NO: 1217), DOM10-53-354 (SEQ ID NO: 1218), DOM10-53-355 (SEQ ID NO: 1219), DOM10-53-356 (SEQ ID NO: 1220), DOM10-53-357 (SEQ ID NO: 1221), DOM10-53-358 (SEQ ID NO: 1222), DOM10-53-359 (SEQ ID NO: 1223), DOM10-53-360 (SEQ ID NO: 1224), DOM10-53-361 (SEQ ID NO: 1225), DOM10-53-362 (SEQ ID NO.1226), DOM 10-53-363 (SEQ ID NO: 1227), DOM 10-53-364 (SEQ ID NO: 1228), DOM10-53-365 (SEQ ID NO: 1229), DOM10-53-366 (SEQ ID NO: 1230), DOM10- 53-367 (SEQ ID NO: 1231), DOM10-53-368 (SEQ ID NO: 1232), DOM10-53-369 (SEQ ID NO: 1233), DOM10-53-370 (SEQ ID NO: 1234), DOM10-53-371 (SEQ ID NO: 1235), DOM10-53-372 (SEQ ID NO: 1236), DOM10-53-373 (SEQ ID NO: 1237), DOM10-53-374 (SEQ ID NO: 1238) ), DOM10-53-375 (SEQ ID NO: 1239), DOM10-53-376 (SEQ ID NO: 1240), DOM10-53-377 (SEQ ID NO: 1241), DOM10-53-378 (SEQ ID NO: 1242), DOM10-53-379 (SEQ ID NO: 1243), DOM10-53-380 (SEQ ID NO: 1244), DOM10-53-381 (SEQ ID NO: 1245), DOM10-53-382 (SEQ ID NO: 1246), DOM10-53-383 (SEQ ID NO: 1247), DOM10-53 -384 (SEQ ID NO: 1248), DOM10-53-355 (SEQ ID NO: 1249), DOM10-53-386 (SEQ ID NO: 1250), DOM10-53-387 (SEQ ID NO: 1251), DOM10 - 53-388 (SEQ ID NO: 1252), DOM 10-53-389 (SEQ ID NO: 1253), DOM10-53-390 (SEQ ID NO: 1254), DOM 10-53-391 (SEQ ID NO: 1255 ), DOM 10-53-392 (SEQ ID NO: 1256), DOM10-53-393 (SEQ ID NO: 1257), DOM10-53-394 (SEQ ID NO: 1258), DOM10-53-395 (SEQ ID NO: 1259), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-400 (SEQ ID NO: 1261), DOM10-53-401 (SEQ ID NO: 1262), DOM10-53-402 ( SEQ ID NO: 1263), DOM10-53-403 (SEQ ID NO: 1264), DOM10-53-404 (SEQ ID NO: 1265), DOM10-53-405 (SEQ ID NO: 1266), DOM10-53- 406 (SEQ ID NO'.1267), DOM10-53-407 (SEQ ID NO: 1268), DOM10-53-408 (SEQ ID NO: 1269), DOM10-53-409 (SEQ ID NO: 1270), DOM10 -53-410 (SEQ ID NO: 1271), DOM10-53-411 (SEQ ID NO: 1272), DOM10-53-412 (SEQ ID NO: 1273), DOM10-53-413 (SEQ ID NO: 1274) , DOM10-53-414 (SEQ ID NO: 1275), DOM10-53-415 (SEQ ID NO: 1276), DOM10-53-416 (SEQ ID NO: 1277), DOM10-53-417 (SEQ ID NO: 1278), DOM10-53-418 (SEQ ID NO: 1279), DOM10-53-419 (SEQ ID NO: 1280), DOM10-53-420 (SEQ ID NO: 1281), DOM10-53-421 (SEQ ID NO: 1282), DOM10-168 (SEQ ID NO: 1508), DOM10-169 (SE Q ID NO: 1509), DOM10-176 (SEQ ID NO: 1510), DOM10-176-1 (SEQ ID NO: 1511), DOM10-176-2 (SEQ ID NO: 1532), DOM10-173 (SEQ ID NO: 1513), DOM10-176-4 (SEQ ID NO: 1514), DOM10-176-5 (SEQ ID NO: 1515), DOM10-176-6 (SEQ ID NO: 1516), DOM10-176-23 ( SEQ ID NO: 1517), DOM10-176-24 (SEQ ID NO: 1518), DOM10-176-25 (SEQ ID NO: 1519), DOM10-176-26 (SEQ ID NO: 1520), DOM10-176- 27 (SEQ ID NO: 1521), DOM10-176-28 (SEQ ID NO: 1522), DOM10-176-29 (SEQ ID NO: 1523), DOM10-176-30 (SEQ ID NO: 1524), DOMJ 0- 176-31 (SEQ ID NO: 1525), DOM10-176-32 (SEQ ID NO: 1526), DOM10476-33 (SEQ ID NO: 1527), DOM10-176-34 (SEQ ID NO: 1528), DOM 10 -176-35 (SEQ ID NO: 1529), DOM10-176-36 (SEQ ID NO: 1530), DOM10-176-37 (SEQ ID NO: 1531), DOM10-176-38 (SEQ ID NO: 1532) , DOM10-176-39 (SEQ ID NO: 1533), DOM10-176-40 (SEQ ID NO: 1534), DOM 10- 176- 101 (SEQ ID NO: 1535), DOM10-176-102 (SEQ ID NO. : 1536), DOM10-176-103 (SEQ ID NO: 1537), DOM 10-176-104 (SEQ ID NO: 1538), DOM10-176-105 (SEQ ID NO: 1539), DOM10-176-106 ( SEQ ID NO: 1540), DOM10-176-107 (SEQ ID NO: 1541), DOM 10-176-108 (SEQ ID NO: 1542), DOM 10-176-109 (SEQ ID NO: 1543), DOM10- 176-110 (SEQ ID NO: 1544), DOM 10-176-111 (SEQ ID NO: 1545), DOM1G-176-112 (SEQ ID NO: 1546), DOM 10-176-113 (SEQ ID NO: 1547) ), DO M 10-176-114 (SEQ ID NO: 154S), DOM 10-176-115 (SEQ ID NO: 1549), DOM 10-176-116 (SEQ ID NO: 1550), DOM10-176-117 (SEQ ID NO: 1551), DOM 10-17 6-500 (SEQ ID NO: 1552), DOM10-176-501 (SEQ ID NO: 1553), DOM 10- 176-502 (SEQ ID NO: 1554), DOM 10-176-503 (SEQ ID NO: 1555 ): DOM 10- 176-504 (SEQ ID NO: 1556), DOM 10-176-505 (SEQ ID NO: 1557), DOM10-176-506 (SEQ ID NO: 1558), DO M 10- 176-507 (SEQ ID NO: 1559), DOM10-176-508 (SEQ ID NO: 1560), DOM 10- 176-509 (SEQ ID NO: 1561), DOM 10- 176-510 (SEQ ID NO: 1562), DOM10 -176-511 (SEQ ID NO: 1563), DOM10-176-512 (SEQ ID NO: 1564), DOM10- 176-513 (SEQ ID NO: 1565), DOM 1 O- 176-514 (SEQ ID NO: 1566), DOM10-176-515 (SEQ ID NO: 1567), DOM 10-176-516 (SEQ ID NO: 1568), DOM10-176-517 (SEQ ID NO: 1569), DOM10-176-518 (SEQ ID NO: 1570), DOM10-176-519 (SEQ ID NO: 1571), DOM10-176-520 (SEQ ID NO: 1572), DOM 10-176-521 (SEQ ID NO: 1573), DOM10-176-522 (SEQ ID NO: 1574), DOM 10-176-523 (SEQ ID NO: 1575), DOM 10- 176 -524 (SEQ ID NO: 1576)) DOM 10- 176-525 (SEQ ID NO: 1577), DOM 10- 176-526 (SEQ ID NO: 1578), DOM10-176-527 (SEQ ID NO: 1579) , DOM 10- 176-528 (SEQ ID NO: 1580), DOM10-176-529 (SEQ ID NO: 1581), DOM 10- 176-530 (SEQ ID NO: 1582), DOM 10- 176-531 (SEQ. ID NO: 1583), DOM 10- 176-532 (SEQ ID NO: 1584), DOM 10-176-533 (SEQ ID NO: 1585), DOM10-176-534 (SEQ ID NO: 1586), DOM30-76 -535 (SEQ ID NO: 1587), DOM10-176-536 (SEQ ID NO: 1588), DOM 10-176-537 (SEQ ID NO: 1589), DOM 10- 176-538 (SEQ ID NO: 1590) , DOM10-176-539 (SEQ ID NO: 1591), DOM 10-176-540 (SEQ ID NO: 1592), DOM10-176-541 (SEQ ID NO: 1593), DOM 10-176-542 (SEQ ID NO: 1594), DOM10-176-543 (SEQ ID NO: 1595), DOM 10-176-544 (SEQ ID NO: 1596), DOM 10-176-545 (SEQ ID NO: 1597), DOM 10-176-546 (SEQ ID NO: 1598), DOM 10 176-547 (SEQ ID NO: 1599), DOM10-176-548 (SEQ ID NO: 1 600), DOM 10-176-549 (SEQ ID NO: 1601), DOM10-176-550 (SEQ ID NO: 1602), DOM10-176-551 (SEQ ID NO: 1603), DOM 10-176-552 (SEQ ID NO: 1604), DOM10-176-553 (SEQ ID NO: 1605), DOM10-176-554 (SEQ. ID NO: 1606), DOM10-176-555 (SEQ ID NO: 1607), DOM 10- 176-556 (SEQ ID NO: 1608), DOM 1 O- 176-557 (SEQ ID NO: 1609), DOM 10-176-558 (SEQ ID NO: 1610), DOM 10-176-559 (SEQ ID NO: 1611), DOM10- 176-560 (SEQ ID NO: 1612), DOM10-176-561 (SEQ ID NO: 1613), DOM10-176-562 (SEQ ID NO: 1614), DOM 10- 176-563 (SEQ ID NO: 1615) , DOM 10-176-564 (SEQ ID NO: 1616), DOM 10-176-565 (SEQ ID NO: 1617), DOM 10-176-566 (SEQ ID NO: 1618), DOM10-176-567 (SEQ. ID NO: 1619), DOM 10- 176-568 (SEQ ID NO.3620), DOM10-176-569 (SEQ ID NO: 1621), DOM 10- 176-570 (SEQ ID NO: 1622), DOM 10- 176-571 (SEQ ID NO: 1623), DOM 10-176-572 (SEQ ID NO: 1624), DOM 10-176-573 (SEQ ID NO: 1625), DOM10-176-574 (SEQ ID NO: 1626 ), DOM 10- 176-575 (SEQ ID NO: 1627), DOM10-176-576 (SEQ ID NO: 1628), DOM 10- 176-577 (SEQ ID NO: 1629), DOM 10-176-578 ( SEQ ID NO: 1630), DOM 10- 176-579 (SEQ ID NO: 1631), DOM 10-176-5S0 (SEQ ID NO: 1632), DOM10-176-581 (SEQ ID NO: 1633), DOM 10 176-582 (SEQ ID NO: 1634), DOM10-176-583 (SEQ ID NO: 1635), DOM 10- 176-584 (SEQ ID NO: 1636), DOM 10-176-585 (SEQ ID NO: 1637), DOM 10- 176-586 (SEQ ID NO: 163 8), DOM10-176-587 (SEQ ID NO: 1639), DOM10-176-588 (SEQ ID NO: 1640), DOM 10- 176-589 (SEQ ID NO: 1641), DOM10-176-590 (SEQ. ID NO: 1642), DOM 10- 176-591 (SEQ ID NO: 1643), DOM 10- 176-592 (SEQ ID NO: 1644), OD M 10- 176-593 (SEQ ID NO: 1645), DOM10 -176-594 (SEQ ID NO: 1646), DOM10-176-595 (SEQ ID NO: 1647), DOM 10- 176-596 (SEQ ID NO: 1648), DOM10-176-597 (SEQ ID NO: 1649 ), DOM 10-176-598 (SEQ ID NO: 1650), DOM 10-176-599 (SEQ ID NO: 1651), DOM 10-176-600 (SEQ ID NO: 1652), D0M10-176-601 (SEQ ID NO: 1653), DOM10-176-602 (SEQ ID NO: 1654), DOM 10-176-603 (SEQ ID NO: 1655), DOM10- 176-604 (SEQ ID NO: 1656), DOM 10-176-605 (SEQ ID NO: 1657), DOM 10-176-606 (SEQ ID NO: 1658), DOM 10-176-607 (SEQ ID NO: 1659), DOM 10-376-608 (SEQ ID NO: 1660), DOM10-176-609 (SEQ ID NO: 1661), DOM10-176-610 (SEQ ID NO: 1662), DOM10-176-611 (SEQ. ID NO: 1663), DOM10-176-612 (SEQ ID NO: 1664), DOM 10- 176-613 (SEQ ID NO: 1665), DO M 10- 176-614 (SEQ ID NO: 1666), DOM10- 176-615 (SEQ ID NO: 1667), DOM10-176-616 (SEQ ID NO: 1668), DOM10-176-617 (SEQ ID NO: 1669), DOM10-176-618 (SEQ ID NO: 1670), DOM 10-76-619 (SEQ ID NO 671), DOM10-176-620 (SEQ ID NO: 1672), DOM 10-176-621 (SEQ ID NO: 1673), DOM 10- 176-622 (SEQ ID NO. : 1674), DOM10-176-623 (SEQ ID NO: 1675), DOM 10-176-624 (SEQ ID NO: 1676), DOM10-176-625 (SEQ ID NO: 1677), DOM 10- 176-626 (SEQ ID NO: 1678), DOM 10-176-627 (SEQ ID NO: 1679), DOM 10-76-628 (SEQ ID NO: 1680), DO M 10- 176-629 (SEQ ID NO: 1681) , DOM10-176-630 (SEQ ID NO: 1682), D OM10-176-631 (SEQ ID NO: 1683), DOM10-176-632 (SEQ ID NO: 1684), DOM 10- 176-633 (SEQ ID NO: 1685), DOM 10-176-634 (SEQ ID NO. : 1686), DOM 10- 176-635 (SEQ ID NO: 1687), DOM10-176-636 (SEQ ID NO: 1688), DOM30-176-637 (SEQ ID NO: 1689), DOM10-] 76-638 (SEQ ID NO: 1690), DOM10-176-639 (SEQ ID NO: 1691), DOM 10- 176-640 (SEQ ID NO: 1692), DOM 10- 176-641 (SEQ ID NO: 1693), DOM 10- 176-643 (SEQ ID NO: 1694), DOM10-176-644 (SEQ ID NO: 1695), DOM10- 176-645 (SEQ ID NO: 1696), DOM 1 O- 176-646 (SEQ ID NO: 1697), DOM10-176-647 (SEQ ID NO: 1698), DOM10-176-648 (SEQ ID NO: 1699) ), DOM 10- 176-649 (SEQ ID NO: 1700), DOM 10-176-650 (SEQ ID NO: 1701), DOM 10- 176-651 (SEQ ID NO: 1702), DOM10-176-652 ( SEQ ID NO: 1703), DOM 10-176-653 (SEQ ID NO: 1704), DOM10-176-654 (SEQ ID NO: 1705), DOM 10-176-655 (SEQ ID NO: 1706), DOM 10 176-656 (SEQ ID NO: 1707), DOM 10-176-657 (SEQ ID NO: 1708), DOM 10-176-658 (SEQ ID NO: 1709), DOM10-176-659 (SEQ ID NO: 1710), DOM 10-76-660 (SEQ ID NO: 1711), DOM10-176-661 (SEQ ID NO: 1712), DOM 10- 176-662 (SEQ ID NO: 1713), DOM 10-176-663 (SEQ ID NO: 1714), DOM 10- 176-664 (SEQ ID NO: 1715). DOM10-176-665 (SEQ ID NO: 1716), DOM10-176-666 (SEQ ID NO: 1717), DOM 10- 176-667 (SEQ ID NO: 1718), DOM10-176-668 (SEQ ID NO: 1719), DOM10-176-669 (SEQ ID NO: 1720), DOM 10-176-670 (SEQ ID NO: 1721), DOM10-176-671 (SEQ ID NO: 1722), DO M 10- 176-672 (SEQ ID NO: 1723), DOM10-176-673 (SEQ ID NO: 1724), DOM 10- 176-674 (SEQ ID NO: 1725), DOM10-176-675 (SEQ ID NO: 1726), DOM10- 253 (SEQ ID NO: 1727), DOM10-255 (SEQ ID NO: 1728), DOM10-272 (SEQ ID NO: 1729), DOM10-307 (SEQ ID NO: 1730), DOM10-319 (SEQ ID NO: 1731) and DOM10-319-1 (SEQ ID NO: 1732). In some embodiments, a polypeptide domain having a binding site with binding specificity for IL-13 competes to bind IL-13 with a dAb selected from the group consisting of DOM10-236 (SEQ ID NO: 2129), DOM10 -238 (SEQ ID NO: 2130) DOM10 -241 (SEQ ID NO: 2131) DOM10 -245 (SEQ ID NO | 2132) DOM10 -249 (SEQ ID NO | 2133) DO 10 -250 (SEQ ID NO 2134) DOM10 -251 (SEQ ID NO 2135) DOM10 -254 (SEQ ID NO 2136) DOM10 -256 (SEQ ID NO 2137) DOM10 -259 (SEQ ID NO 2138) DOM10 -260 (SEQ ID NO • 2139) DOM10 -261 (SEQ ID NO 2140) DOM10 -263 (SEQ ID NO 2141) DOM10 -264 (SEQ ID NO 2142) DOM10 -273 (SEQ ID NO 2143) DOM10 -278 (SEQ ID NO 2144) DOM10 -279 (SEQ ID NO 2145) DOM10 -281 (SEQ ID NO 2146) DOM10 -282 (SEQ ID NO 2147) DOM10 -283 (SEQ ID NO 2148) DOM10 -400 (SEQ ID NO 2149) DOM10 -401 (SEQ ID NO 2150) DOM10 -402 (SEQ ID NO 2151) DOM10 -404 (SEQ ID NO 2152) DOM10 -406 (SEQ ID NO 2153) DOM10 -407 (SEQ ID NO 2154) DOM10 -409 (SEQ ID NO 2155) DOM10 -410 (SEQ ID NO 2156) DOM10 -414 (SEQ ID NO 2157) DOM10 -415 (SEQ ID NO 2158) DOM10 -416 (SEQ ID NO 2159), DOM10 -418 (SEQ ID NO 2160) DOM10 -420 (SEQ ID NO 2161) DOM10 -422 (SEQ ID NO 2162) DOM10 -423 (SEQ ID NO 2163) DOM10 -424 (SEQ ID NO 2164) DOM10 -425 (SEQ ID NO 2165), DOM10 -426 (SEQ ID NO 2166) DOM10 -427 (SEQ ID NO 2167), DOM10 -428 (SEQ ID NO 2168) DOM10 -429 (SEQ ID NO 2169), DOM10 -430 (SEQ ID NO 2170), DOM10 -431 (SEQ ID NO 2171), DOM10- -432 (SEQ ID NO: 2172), DOM10 -433 (SEQ ID NO 2173), DOM10 -467 (SEQ ID NO: 2174), DOM10 -468 (SEQ ID No. 2175), DOM10- -469 (SEQ ID NO: 2176), DOM10-470 (SEQ ID NO: 2177), DOM10- |234 (SEQ ID NO: 2178), DOM10- |235 (SEQ ID NO: 2179), DOM10- -237 (SEQ ID NO: 2180) DOM10 -239 (SEQ ID NO: 2181) DOM10 -240 (SEQ ID NO: 2182) DOM10 -242 (SEQ ID NO: 2183) DOM10 -243 (SEQ ID NO: 2184) DOM10 -244 (SEQ ID NO • 2185) DOM10 -246 (SEQ ID NO: 2186) DOM10 -247 (SEQ ID NO 2187) DOM10 -248 (SEQ ID NO: 2188) DOM10 -252 (SEQ ID NO 2189) DOM10 -257 (SEQ ID NO: 2190), DOM10 -258 (SEQ ID NO: 2191) DOM10 -262 (SEQ ID NO 2192) DOM10 -265 (SEQ ID NO 2193) DOM10 -266 (SEQ ID NO 2194) DOM10 -274 (SEQ ID NO 2195) DOM10 -275 (SEQ ID NO 2196) DOM10 -276 (SEQ ID NO 2197) DOM10 -277 (SEQ ID NO 2198) DOM10 -280 (SEQ ID NO 2199) DOM10 -403 (SEQ ID NO 2200) DOM10 -405 (SEQ ID NO 2201) DOM10 -408 (SEQ ID NO 2202) DOM10 -411 (SEQ ID NO 2203) DOM10 -412 (SEQ ID NO 2204) DOM10 -413 (SEQ ID NO 2205) DOM10 -417 (SEQ ID NO 2206) DOM10 -419 (SEQ ID NO 2207) DOM10 -472 (SEQ ID NO 2208) DOM10 -203 (SEQ ID NO 2209) DOM10 -205 (SEQ ID NO 2210) DOM10 -208 (SEQ ID NO 2211) DOM10 -218 (SEQ ID NO 2212), DOM10 -219 (SEQ ID NO 2213), DOM10-220 (SEQ ID NO 2214), DOM10-225 (SEQ ID NO 2215), DOM30- -228 (SEQ ID NO 2216), DOM10 -229 (SEQ ID NO 2217), DOM10-230 (SEQ ID NO 2218), DOM10-231 (SEQ ID NO: 2219), DOM10-268 (SEQ ID NO 2220), DOM10- -201 (SEQ ID NO 2221), DOM10- |202 (SEQ ID NO 2222), DOM10- -204 (SEQ ID NO: 2223), DOM10- -206 (SEQ ID NO: 2224), DOM10- |207 (SEQ ID NO: 2225), DOM10- |209 (SEQ ID NO: 2226), DOM10- |210 (SEQ ID NO: 2227), DOM10- |211 (SEQ ID NO: 2228). DOM10- |213 (SEQ ID NO: 2229), DOM10- • 214 (SEQ ID NO: 2230), DOM10-215 (SEQ ID NO: 2231), DOM10-216 (SEQ ID NO: 2232), DOM10-217 (SEQ ID NO: 2233), DOM10-221 (SEQ ID NO: 2234) ), DOM10-223 (SEQ ID NO: 2235), DOM10-224 (SEQ ID NO: 2236), DOM10-227 (SEQ ID NO: 2237), DOM10-232 (SEQ ID NO: 2238), DOM10-267 ( SEQ ID NO: 2239), DOM10-270 (SEQ ID NO: 2240), DOM10-275-1 (SEQ ID NO: 2241), DOM10-276-2 (SEQ ID NO: 2242), DOM10-276-3 ( SEQ ID NO: 2243), DOM 10-275-3 (SEQ ID NO: 2244), DOM10-277-2 (SEQ ID NO: 2245), DOM10-277-3 (SEQ ID NO: 2246), DOM 10- 273-1 (SEQ ID NO: 2247), DOM10-273-2 (SEQ ID NO: 2248), DOM10-275-2 (SEQ ID NO: 2249), DOM10-275-4 (SEQ ID NO: 2250), DOM10-276-1 (SEQ ID NO: 2251), DOM10-276-4 (SEQ ID NO: 2252), DOM10-277-1 (SEQ ID NO: 2253), DOM10-275-13 (SEQ ID NO: 2254) ), DOM10-275-15 (SEQ ID NO: 2255), DOM10-275-20 (SEQ ID NO: 2256), DOM10-275-8 (SEQ ID NO: 2257), DOM10-276-13 (SEQ ID NO. : 2258), DOM10-276-14 (SEQ ID NO: 2259), DOM10-276-15 (SEQ ID NO: 2260), DOM 10-276-17 (SEQ ID NO: 2261), DOM10-276-7 ( SEQ ID NO: 2262), DOM10-276-8 (SEQ ID NO: 2263), DO M10-275-11 (SEQ ID NO: 2264), DOM10-275-12 (SEQ ID NO: 2265), DOM10-275-14 (SEQ ID NO: 2266), DOM10-275-16 (SEQ ID NO: 2267) ), DOM10-275-17 (SEQ ID NO: 2268), DOM10-275-5 (SEQ ID NO: 2269), DOM10-275-6 (SEQ ID NO: 2270), DOM10-275-7 (SEQ ID NO. : 2271), DOM10-275-9 (SEQ ID NO: 2272), DOM10-276-10 (SEQ ID NO: 2273), DOM10-276-11 (SEQ ID NO: 2274), DOM10-276-12 (SEQ. ID NO: 2275), DOM10- 276-16 (SEQ ID NO: 2276), DOM 10-276-5 (SEQ ID NO: 2277), DOM10-276-6 (SEQ ID NO: 2278), DOM10-276-9 (SEQ ID NO: 2279) , DOM10-212 (SEQ ID NO: 2280), DOM10-53-424 (SEQ ID NO: 2281), DOM 0-53-425 (SEQ ID NO: 2282), DOM10-53-426 (SEQ ID NO: 2283) ), DOM10-53-422 (SEQ ID NO: 2284), DOM10-53-423 (SEQ ID NO: 2285), DOM10-53-613 (SEQ ID NO: 2286); DOM10-53-517 (SEQ ID NO: 2287), DOM10-53-519 (SEQ ID NO: 2288), DOM10-53-520 (SEQ ID NO: 2289), DOM1G-53-521 (SEQ ID NO: 2290) ): DOM10-53-522 (SEQ ID NO: 2291), DOM10-53-526 (SEQ ID NO: 2292), DOM10-53-527 (SEQ ID NO: 2293), DOM10-53-528 (SEQ ID NO. : 2294), DOM10-53-518 (SEQ ID NO: 2295), DOM 10-53-523 (SEQ ID NO: 2296), DOM10-53-524 (SEQ ID NO: 2297), DOM10-53-525 ( SEQ ID NO: 2298), DOM10-53-601 (SEQ ID NO: 2299), DOM10-53-602 (SEQ ID NO: 2300), DOM10-53-605 (SEQ ID NO: 2301), DOM10-53- 606 (SEQ ID NO: 2302), DOM10-53-607 (SEQ ID NO: 2303), DOM10-53-608 (SEQ ID NO: 2304), DOM10-53-609 (SEQ ID NO: 2305), DOM10-53-610 (SEQ ID NO: 2306), DOM10-53-611 (SEQ ID NO: 2307), DOM10-53-612 (SEQ ID NO: 2308), DOM10-53-603 (SEQ ID NO: 2309), DOM10-53-604 (SEQ ID NO: 2310), DOM50-53-429 (SEQ ID NO: 2311), DOM10-53-432 (SEQ ID NO: 2312), DOM10-53-433 (SEQ ID NO: 2313), DOM10-53-435 ( SEQ ID NO: 2314), DOM10-53-430 (SEQ ID NO: 2315), DOM10-53-431 (SEQ ID NO: 2316), DOM10-53-434 (SEQ ID NO: 2317), DOM10-53- 436 (SEQ ID NO: 2318), DOM10-53-437 (SEQ ID NO: 2319), DOM10- 53-438 (SEQ ID NO: 2320), DOM10-53-440 (SEQ ID NO: 2321), DOM10-53-439 (SEQ ID NO: 2322), DOM10-53-441 (SEQ ID NO.-2323) , DOM10-53-442 (SEQ ID NO: 2324), DOM 10-53-443 (SEQ ID NO: 2325), DOM10-53-444 (SEQ ID NO: 2326), DOM10-53-445 (SEQ ID NO. : 2327), DOM10-53-446 (SEQ ID NO: 2328), DOM10-53-447 (SEQ ID NO: 2329), DOM10-53-449 (SEQ ID NO: 2330), DOM10-53-448 (SEQ. ID NO: 2331), DOM10-53-450 (SEQ ID NO: 2332), DOM10-53-451 (SEQ ID NO: 2333), DOM10-53-452 (SEQ ID NO: 2334), DOM10-53-453 (SEQ ID NO: 2335), DOM10-53-454 (SEQ ID NO: 2336), DOM10-53-455 (SEQ ID NO: 2337), DOM10-53-456 (SEQ ID NO: 2338), DOM10-53 -457 (SEQ ID NO: 2339), DOM10-53-458 (SEQ ID NO: 2340), DOM10-53-459 (SEQ ID NO: 2341), DOM10-53-461 (SEQ ID NO: 2342), DOM10 -53-462 (SEQ ID NO: 2343), DOM10-53-465 (SEQ ID NO: 2344), DOM10-53-466 (SEQ ID NO: 2345), DOM 10-53-467 (SEQ ID NO: 2346) ), DOM10-53-468 (SEQ ID NO: 2347), DOM10-53-460 (SEQ ID NO: 2348), DOM10-53-463 (SEQ ID NO: 2349), DOM10-53-464 (SEQ ID NO. : 2350), DOM10-53-469 (SEQ ID NO: 2351), DOM10-53-47 1 (SEQ ID NO: 2352), DOM10-53-470 (SEQ ID NO: 2353), DOM10-53-533 (SEQ ID NO: 2354), DOM10-53-534 (SEQ ID NO: 2355), DOM10- 53-535 (SEQ ID NO: 2356), DOM10-53-537 (SEQ ID NO: 2357), DOM10-53-538 (SEQ ID NO: 2358), DOM10-53-539 (SEQ ID NO: 2359), DOM10-53-540 (SEQ ID NO: 2360), DOM10-53-531 (SEQ ID NO: 2361), DOM10-53-532 (SEQ ID NO: 2362), DOM10-53-536 (SEQ ID NO: 2363) ), DOM10-53-542 (SEQ ID NO: 2364), DOM 10-53-541 (SEQ ID NO: 2365), DOM10-53-473 (SEQ ID NO: 2366), DOM10-53-472 (SEQ ID NO: 2367), DOM10-53-475 (SEQ ID NO: 2368), DOM10-53-474 (SEQ ID NO: 2369), DOM10-53-543 (SEQ ID NO: 2370), DOM10-53-544 (SEQ ID NO: 2371), DOM 10-53-545 (SEQ ID NO: 2372), DOM10-53-548 (SEQ ID NO: 2373), DOM10-53-546 (SEQ ID NO: 2374), DOM10-53-549 (SEQ ID NO: 2375), DOM10-53-547 (SEQ ID NO: 2376), DOM10-53-550 (SEQ ID NO: 2377), DOM10-53-551 (SEQ ID NO: 2378), DOM10-53 -S60 (SEQ ID NO: 2379), DOM10-53-565 (SEQ ID NO: 2380), DOM10-53-559 (SEQ ID NO: 2381), DOM10-53-561 (SEQ ID NO: 2382), DOM10 -53-562 (SEQ ID NO: 2383), DOM10-53-563 (SEQ ID NO: 2384), DOM10-53-564 (SEQ ID NO: 2385), DOM10-53-566 (SEQ ID NO: 2386) , DOM10-53-554 (SEQ ID NO.2387), DOM10-53-552 (SEQ ID NO: 2388), DOM10-53-553 (SEQ ID NO: 2389), DOM10-53-558 (SEQ ID NO: 2390), DOM10-53-556 (SEQ ID NO: 2391) and DOM10-53-557 (SEQ ID NO: 2392). In some embodiments, the polypeptide domain having a binding site with binding specificity for IL-13 (e.g., a dAb) comprising an amino acid sequence having at least about 80%, at least about 85% , at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% amino acid sequence identity with the amino acid sequence or a dAb selected from the group consisting of at DOM10-53 (SEQ ID NO: 967), DOM 10-53-1 (SEQ ID NO: 968), DOM10-53-2 (SEQ ID NO: 969); DOM10-53-3 (SEQ ID NO: 970), DOM10-53-4 (SEQ ID NO: 971), DOM10-53-5 (SEQ ID NO: 972), DOM10-53-6 (SEQ ID NO: 973) ), DOM 10-53-7 (SEQ ID NO: 974), DOM 10-53-8 (SEQ ID NO: 975), DOM10-53-9 (SEQ ID NO: 976), DOM10-53-10 (SEQ. ID NO: 977), DOM10-53-11 (SEQ ID NO'.978), DOM10-53-12 (SEQ ID NO: 979), DOM10-53-13 (SEQ ID NO: 980), DOM10-53- 14 (SEQ ID NO: 981), DOM10-53-15 (SEQ ID NO: 982), DOM10-53-16 (SEQ ID NO: 983), DOM10-53-17 (SEQ ID NO: 984), DOM10- 53-18 (SEQ ID NO: 985), DOM10-53-19 (SEQ ID NO: 986), DOM10-53-20 (SEQ ID NO: 987), DOM10-53-21 (SEQ ID NO: 988), DOM10-53-122 (SEQ ID NO: 989), DOM10-53-123 (SEQ ID NO: 990), DOM10-53-24 (SEQ ID NO: 991), DOM10-53-25 (SEQ ID NO: 992) ), DOM10-53-26 (SEQ ID NO: 993), DOM10-53-27 (SEQ ID NO: 994), DOM10-53-28 (SEQ ID NO: 995), DOM10-53-29 (SEQ ID NO. : 996), DOM10-53-30 (SEQ ID NO: 997), DOM10-53-3 1 (SEQ ID NO: 99S), DOM10-53-32 (SEQ ID NO: 1999), DOM10-53-43 ( SEQ ID NO: 1000), DOM10-53-44 (SEQ ID NOilOOI), DOM10-53-45 (SEQ ID NO: 1002), DOM10-53-46 (SEQ ID NO: 1003), DOM10-5 3-47 (SEQ ID NO: 1004), DOM10- 53-48 (SEQ ID NO: 1005), DOM 10-53-49 (SEQ ID NO: 1006), DOM10-53-50 (SEQ ID NO: 1007), DOM10-53-51 (SEQ ID NO: 1008) , DOM10-53-52 (SEQ ID NO: 1009), DOM 10-53-53 (SEQ ID NO: 1010), DOM 10-53-54 (SEQ ID NO: 1011), DOM10-53-55 (SEQ ID NO: 1012), DOM10-53-56 (SEQ ID NO: 1013), DOM10-53-57 (SEQ ID NO: 1014), DOM10-53-59 (SEQ ID NO: 1015), DOM10-53-60 ( SEQ ID NO: 1016), DOM10-53-61 (SEQ ID NO: 1017), DOM10-53-62 (SEQ ID NO: 1018), DOM10-53-63 (SEQ ID NO: 1019), DOM10-53- 64 (SEQ ID NO: 1020), DOM10-53-65 (SEQ ID NO: 1021), DOM10-53-66 (SEQ ID NO: 1022), DOM10-53-67 (SEQ ID NO: 1023), DOM10- 53-68 (SEQ ID NO: 1024), DOM10-53-69 (SEQ ID NO: 1025), DOM10-53-70 (SEQ ID NO: 1026), DOM10-53-71 (SEQ ID NO: 1027), DOM10-53-72 (SEQ ID NO: 1028), DOM10-53-73 (SEQ ID NO: 1029), DOM10-53-74 (SEQ ID NO: 1030), DOM10-53-75 (SEQ ID NO: 1031) ), DOM10-53-76 (SEQ ID NO: 1032), DOM10-53-77 (SEQ ID NO: 1033), DOM10-53-78 (SEQ ID NO: 1034), DOM10-53-79 (SEQ ID NO. : 1035), DOM10-53-80 (SEQ ID NO: 1036), DOM10-53-81 (SEQ ID NO: 1037), DOM10-53-82 ( SEQ ID NO: 1038), DOM10-53-83 (SEQ ID NO: 1039), DOM10-53-84 (SEQ ID NO: 1040), DOM10-53-85 (SEQ ID NO: 1041), DOM10-53- 86 (SEQ ID NO: 1042), DOM10-53-87 (SEQ ID NO: 1043), DOM10-53-88 (SEQ ID NO: 1044), DOM10-53-89 (SEQ ID NO: 1045), DOM10- 53-91 (SEQ ID NO: 1046), DOM10-53-92 (SEQ ID NO: 1047), DOM10-53-93 (SEQ ID NO: 1048), DOM10-53-94 (SEQ ID NO: 1049), DOM10- 53-95 (SEQ ID NO: 1050), DOM10-53-96 (SEQ ID NO: 1051), DOM10-53-97 (SEQ ID NO: 1052), DOM10-53-98 (SEQ ID NO: 1053), DOM 10-53-99 (SEQ ID NO: 1054), DOM10-53-100 (SEQ ID NO: 1055), DOM 10-53-103 (SEQ ID NO: 1056), DOM10-53-105 (SEQ ID NO. : 1057), DOM10-53-106 (SEQ ID NO: 1058), DOM10-53-108 (SEQ ID NO: 1059), DOM10-53-110 (SEQ ID NO: 1060), DOM10-53-11 1 ( SEQ ID NO: 1061), DOM10-53-112 (SEQ ID NO: 10632), DOM10-53-114 (SEQ ID NO: 1063), DOM10-53-115 (SEQ ID NO: 1064), DOM 10-53 -116 (SEQ ID NO: 1065), DOM10-53-117 (SEQ ID NO: 1066), DOM10-53-119 (SEQ ID NO: 1067), DOM10-53-120 (SEQ ID NO: 1068): DOM10 -53-122 (SEQ ID NO: 1069), DOM10-53-201 (SEQ ID NO: 1070), DOM10-53-203 (SEQ ID NO: 1071), DOM10-53-204 (SEQ ID NO: 1072) , DOM10-53-205 (SEQ ID NO: 1073), DOM10-53-206 (SEQ ID NO: 1074), DOM10-53-207 (SEQ ID NO: 1075), DOM10-53-208 (SEQ ID NO: 1076), DOM10-53-209 (SEQ ID NO: 1077), DOM10-53-210 (SEQ ID NO: 1078), DOM10-53-211 (SEQ ID NO: 1079), DOM10-53-213 (SEQ ID NO: 1080), DOM10-53-214 (SEQ ID NO: 1081), DOM10-53-215 ( SEQ ID NO: 1082), DOM10-53-216 (SEQ ID NO: 1083), DOM10-53-217 (SEQ ID NO: 1084), DOM10-53-1218 (SEQ ID NO: 1085), DOM10-53- 219 (SEQ ID NO: 1086), DOM10-53-220 (SEQ ID NO: 3087), DOM10-53-221 (SEQ ID NO: 1088), DOM10-53-222 (SEQ ID NO: 1089), DOM10- 53-223 (SEQ ID NO: 1090), DOM10-53-224 (SEQ ID NO: 1091), DOM10-53-225 (SEQ ID NO: 1092), DOM10-53-226 (SEQ ID NO: 1093), DOM10-53-227 (SEQ ID NO: 1094), DOM10-53-228 (SEQ ID NO: 1095), DOM10-53-229 (SEQ ID NO: 1096), DOM10-53-230 (SEQ ID N0: 1) 097), DOM10-53-231 (SEQ ID NO: 1098), DOM10-53-232 (SEQ ID NO: 1099), DOM10-53-233 (SEQ ID NO: 1100), DOM10-53-234 (SEQ ID NO: 1101), DOM10-53-235 (SEQ ID NO: 1102), DOM10-53-236 (SEQ ID NO: 1103), DOM10-53-237 (SEQ ID NO: 1104), DOM10-53-238 ( SEQ ID NO: 1105), DOM10-53-239 (SEQ ID NO: 1106), DOM10-53-240 (SEQ ID NO: 1107), DOM10-53-241 (SEQ ID NO: 1108), DOM10-53- 242 (SEQ ID NO: 1109), DOM 10-53-243 (SEQ ID NO: 1110), DOM10-53-244 (SEQ ID ??:? III), DOM10-53-245 (SEQ ID NO: 1112) , DOM10-53-246 (SEQ ID NO: 1113), DOM10-53-247 (SEQ ID NO: 1114), DOM10-53-248 (SEQ ID NO: 1115), DOM10-53-249 (SEQ ID NO: 1116), DOM10-53-250 (SEQ ID NO: 1117), DOM10-53-251 (SEQ ID NO: 1118), DOM10-53-252 (SEQ ID NO: 1119), DOM10-53-253 (SEQ ID NO: 1120), DOM 10-53-254 (SEQ ID NO: 1121), DOM10-53-255 (SEQ ID NO: 1122), DOM10-53-256 (SEQ ID NO: 1123), DOM10-53-257 (SEQ ID NO: 1124), DOM10-53-258 (SEQ ID NO: 1125), DO M10-53-259 (SEQ ID NO: 1126), DOM10-53-260 (SEQ ID NO: 1127), DOM10-53-261 (SEQ ID NO: 1128), DOM10-53-262 (SEQ ID NO: 1129) ), DOM10-53-263 (SEQ ID NO: 1130), DOM10-53-264 (SEQ ID NO 131), DOM10-53-265 (SEQ ID NO 132), DOM 10-53-266 (SEQ ID NO: 1133), DOM10-53-267 (SEQ ID NO: 1134), DOM10-53-268 (SEQ ID NO: 1135), DOM10-53-269 (SEQ ID NO: 1136), DOM10-53-270 (SEQ ID NO: 1137), DOM10-53-271 (SEQ ID N0: 1138), DOM10-53-272 (SEQ ID NO 139), DOM 10-53-273 (SEQ ID NO: 1140), DOM10-53-274 ( SEQ ID NO: 1141), DOM10-53-275 (SEQ ID NO: 1142), DOM10-53-276 (SEQ ID N0: 1 143), DOM10-53-277 (SEQ ID NO: 1144), DOM10-53 -278 (SEQ ID NO: 1145), DOM10-53-279 (SEQ ID NO: 1146), DOM10-53-280 (SEQ ID NO: 1147), DOM10-53-285 (SEQ ID N0: 1148), DOM10 -53-282 (SEQ ID NO: 1149), DOM10-53-283 (SEQ ID NO: 1150), DOM10-53-284 (SEQ ID N0: 1151), DOM10-53-285 (SEQ ID NO: 1152) , DOM10-53-286 (SEQ ID NO: 1153), DOM10-53-287 (SEQ ID NO: 1154), DOM10-53-288 (SEQ ID NO: 1155), DOM10-53-289 (SEQ ID NO: 1156), DOM10-53-290 (SEQ ID NO: 1157), DOM10-53-291 (SEQ ID NO: J 158), DOM10-53-292 (SEQ ID NO: 1159), DOM10-53-293 (SEQ. ID NO: 1160), DOM10-53-294 (SEQ ID NO.i 161), DOM10-53-295 (SEQ ID NO: 1162), DOM10-53-296 (SEQ ID NO: 1363), DOM10-53- 297 (SEQ ID NO: 1164), DOM10-53-298 (SEQ ID NO: 1165), DOM10-53-299 (SEQ ID NO: 1166), DOM10-53-300 (SEQ ID NO: 1167), DOM10- 53-301 (SEQ ID NO: 1168), DOM10-53-302 (SEQ ID NO: 1 169), DOM10-53-303 (SEQ ID NO: 1170), DOM10-53-304 (SEQ ID NO: 1171), DOM10-53-305 (SEQ ID NO: 1172), DOM 10-53-306 (SEQ. ID NO: 1173), DOM10-53-307 (SEQ ID NO: 1174), DOM10-53-308 (SEQ ID NO: 1175), DOM10-53-309 (SEQ ID NO.i 176), DOM10-53- 310 (SEQ ID NO: 11787), DOM10-53-311 (SEQ ID NO: 1178), DOM10-53-312 (SEQ ID NO: 1179), DOM10-53-314 (SEQ ID NO: 1180), DOM10- 53-315 (SEQ ID NO: 1181), DOM10-53-316 (SEQ ID NO: 1182), DOM10-53-317 (SEQ ID NO: 1183), DOM10-53-318 (SEQ ID NO: 1184), DOM10-53 -319 (SEQ ID NO: 1 I 8S), DOM10-53-320 (SEQ ID NO: 1186), DOM10-S3-321 (SEQ ID NO: 1187), DOM10-53-322 (SEQ ID NO: 1188) , DOM10-53-323 (SEQ 3D NO: 1189), DOM10-53-324 (SEQ ID NO: 1190), DOM 10-53-325 (SEQ ID NO: 1191), DOM10-53-326 (SEQ ID NO. : 1192), DOM10-53-327 (SEQ ID NO: 1193), DOM 10-53-328 (SEQ ID NO: 1194), DOM10-53-329 (SEQ ID NO: 1195), DOM10-53-330 ( SEQ ID NO: 1196), DOM10-53-331 (SEQ ID NO: 1197), DOM 10-53-333 (SEQ ID NO: 1198), DOM10-53-334 (SEQ ID NO: 1199), DOM10-53 -336 (SEQ ID NO: 1200), DOM10-53-337 (SEQ ID NO: 1 201), DOM10-53-338 (SEQ ID NO: 1202), DOM10-53-339 (SEQ ID NO: 1203), DOM10-53-340 (SEQ ID NO: 1204), DOM10-53-341 (SEQ ID NO: 1205), DOM10-53-342 (SEQ ID NO: 1206), DOM10-53-343 (SEQ ID NO: 1207) ), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-345 (SEQ ID NO: 1209), DOM10-53-346 (SEQ ID NO: 1210), DOM10-53-347 (SEQ ID NO. : 1211), DOM10-53-348 (SEQ ID NO: 1212), DOM10-53-349 (S EQ ID NO: 1213), DOM10-53-350 (SEQ ID NO: 1214), DOM10-53-351 (SEQ ID NO: 1215), DOM10-53-352 (SEQ ID NO: 1216), DOM10-53- 353 (SEQ ID NO: 1217), DOM10-53-354 (SEQ ID NO: 1218), DOM10-53-355 (SEQ ID NO: 1219), DOM10-53-356 (SEQ ID NO: 1220), DOM10- 53-357 (SEQ ID NO: 1221), DOM10-53-358 (SEQ ID NO: 1222), DOM10-53-359 (SEQ ID NO: 1223), DOM10-53-360 (SEQ ID NO: 1224), DOM10- 53-361 (SEQ ID NO: 1225), DOM10-53-362 (SEQ ID NO: 1226), D0M10-53-363 (SEQ ID NO: 1227), DOM 10-53-364 (SEQ ID NO: 1228) , DOM10-53-365 (SEQ ID NO: 1229), DOM10-53-366 (SEQ ID NO: 1230), DOM10-53-367 (SEQ ID NO: 1231), DOM10-53-368 (SEQ ID NO: 1232), DOM10-53-369 (SEQ ID NO: 1233), DOM10-53-370 (SEQ ID NO: 1234), DOM10-53-371 (SEQ ID NO: 1235), DOM10-53-372 (SEQ ID NO: 1236), DOM10-53-373 (SEQ ID NO: 1237), DOM10-53-374 (SEQ ID NO: 1238), DOM10-53-375 (SEQ ID NO: 1239), DOM10-53-376 ( SEQ ID NO: 1240), DOM10-53-377 (SEQ ID NO: 1241), DOM10-53-378 (SEQ ID NO.-1242), DOM10-53-379 (SEQ ID NO: 1243), DOM10-53 -380 (SEQ ID NO: 1244), DOM 10-53-381 (SEQ ID NO: 1245), DOM10-53-382 (SEQ ID NO: 1246), DOM10-53-383 (SEQ ID NO: 1247), DOM10-53-384 (SEQ ID NO: 1248), DOM10-53-385 (SEQ ID NO: 1249), DOM10-53-386 (SEQ ID NO: 1250), DOM10-53-387 (SEQ ID NO: 3251) ), DOM10-53-388 (SEQ ID NO: 1252), DOM10-53-389 (SEQ ID NO: 1253), DOM10-53-390 (SEQ ID NO: 1254), DOM10-53-391 (SEQ ID NO. : 1255), DOM10-53-392 (SEQ ID NO: 1256), DOM10-53-39 3 (SEQ ID NO: 1257), DOM10-53-394 (SEQ ID NO: 1258), DOM10-53-395 (SEQ ID NO: 1259), DOM10-53-396 (SEQ ID NO: 1260), DOM10- 53-400 (SEQ ID NO: 1261), DOM10-53-401 (SEQ ID NO: 1262), DOM10-53-402 (SEQ ID NO: 1263), DOM10-53-403 (SEQ ID NO: 1264), DOM 10-53-404 (SEQ ID NO: 1265), DOM10-53-405 (SEQ ID NO: 1266), DOM10-53-406 (SEQ ID NO: 1267), DOM10-53-407 (SEQ ID NO: 1268), DOM10-53-408 (SEQ ID NO: 1269), DOM10-53-409 (SEQ ID NO: 1270), DOM10-53-410 (SEQ ID NO 271), DOM10-53-411 (SEQ ID N0: 1272) , DOM10-53-412 (SEQ ID N0: 1273), DOM10-53-413 (SEQ ID N0: 1274), DOM10-53-414 (SEQ ID NO: 1275), DOM10-53-415 (SEQ ID NO: 127ó), D0M10-53-416 (SEQ ID NO: 1277), DOM10-53-417 (SEQ ID N0: 1278), DOM10-53-418 (SEQ ID NO: 1279), DOM10-53-419 (SEQ ID NO.1280), DOM10-53-420 (SEQ ID NO: 1281), DOM10-53-421 (SEQ ID NO: 1282); DOM10-168 (SEQ ID NO: 1508), DOM10-169 (SEQ ID NO: 1509), DOM10-176 (SEQ ID NO: 1510), DOM10-176-1 (SEQ ID NO: 1511), DOM10-176- 2 (SEQ ID NO: 1512), DOM10-173 (SEQ ID NO: 1513), DOM10-176-4 (SEQ ID NO: 1514), DOM10-176-5 (SEQ ID NO: 1515), DOM10-176- 6 (SEQ ID NO: 1516), DOM10-176-23 (SEQ ID NO: 1517), DOM10-176-24 (SEQ ID NO: 1518), DOM10-176-25 (SEQ ID NO: 1519), DOM10- 176-26 (SEQ ID NO: 1520), DOM10-176-27 (SEQ ID NO: 1521), DOM 10-176-28 (SEQ ID NO: 1522), DOM10-176-29 (SEQ ID NO: 1523) , DOM10-176-30 (SEQ ID NO: 1524), DOM10-176-31 (SEQ ID NO: 1525), DOM10-176-32 (SEQ ID NO: 1526), DOM10-176-33 (SEQ ID NO: 1 527), DOM10-176-34 (SEQ ID NO: 1528), DOM10-176-35 (SEQ ID NO: 1529), DOM 10- 176-36 (SEQ ID NO: 1530), DOM10-176-37 ( SEQ ID NO: 1531), DOM10-176-38 (SEQ ID NO: 1532), DOM10-176-39 (SEQ ID NO: 1533), DOM10-176-40 (SEQ ID NO: 1534), DOM10-176- 101 (SEQ ID NO: 1535), OJ M 10-176-102 (SEQ ID NO: 1536), OJ M 10-176-103 (SEQ ID NO: 1537), DOM10- 176-104 (SEQ ID NO: 1538), DOM 10-176-105 (SEQ ID NO: 1539), DOM10-176-106 (SEQ ID NO: 1540), DOM10-176-107 (SEQ ID NO: 1541) , DOM10-176-108 (SEQ ID NO: 1542), DOM 10-176-109 (SEQ ID NO: 1543), DOM 10-176-110 (SEQ ID NO: 1544), DOM10-176-111 (SEQ ID NO: 1545) i DOM10-176-1 12 (SEQ ID NO: 1546), DOM10-176-3 (SEQ ID NO: 1547), DOM 10-176-114 (SEQ ID NO: 1548), DOM 10- 176 - 115 (SEQ ID NO: 1549), DOM10-176-116 (SEQ ID NO: 1 550), DOM10-176-117 (SEQ ID NO: 1551), DOM 10-176-500 (SEQ ID NO: 1552) , DOM10-176-501 (SEQ ID NO: 1553), DOM 10- 176-502 (SEQ ID NO: 1554), DOM10-176-503 (SEQ ID NO: 1555), DOM 10- 176-504 (SEQ ID NO: 1556), DOM10-176-505 (SEQ ID NO: 1557), DOM 10-176-506 (SEQ ID NO: 1558), DOM10-176-507 (SEQ ID NO: 1559), DOM 10- 176- 508 (SEQ ID NO: 1560), DOM10-176-509 (SEQ ID NO: 1561), DOM10-176-510 (SEQ ID NO: 1562), DOM10-176-511 (SEQ ID NO.1563), DOM10- 176-512 (SEQ ID NO: 1564), DOM 10-176-513 (SEQ ID NO: 1565), DOM10-176-514 (SEQ ID NO: 1566), DOM 10-175-515 (SEQ ID NO: 1567) ), DOM 10-176-516 (SEQ ID N O: 1568), DOM10-176-517 (SEQ ID NO: 1569), DOM10-176-518 (SEQ ID NO: 1570), DOM10-176-519 (SEQ ID NO: 1571), DOM 10-76-520 (SEQ ID NO: 1572), DOM10-176-521 (SEQ ID NO: 1573), DOM 10- 176-522 (SEQ ID NO: 1574), DOM 10-176-523 (SEQ ID NO: 1575), DOM10 -176-524 (SEQ ID NO: 1576), DOM 10-176-525 (SEQ ID NO: 1577), DOM10-176-526 (SEQ ID NO: 1578), DOM 10-176-527 (SEQ ID NO: 1579), DOM 10-176-528 (SEQ ID NO: 1580), OJ M 10- 176-529 (SEQ ID NO: 1581), D0M10-176-530 (SEQ ID NO: 1582), DOM10-176-531 (SEQ ID NO: 1583), DOM 10- 176-532 (SEQ ID NO: 1584), DOM10- 176-533 (SEQ ID NO: 1585), DOM 10-176-534 (SEQ ID NO: 1586), DOM 10-176-535 (SEQ ID NO: 1587), DOM 10-176-536 (SEQ ID NO: 1588), DOM10-176-537 (SEQ ID NO: 1589), DOM10-176-538 (SEQ ID NO: 1590), DOM 10-176-539 (SEQ ID NO: 1591), DOM10-176-540 (SEQ. ID NO: 1592), DOM10-176-541 (SEQ ID NO: 1593), DOM 10-76-542 (SEQ ID NO: 1594), DOM10-176-543 (SEQ ID NO: 1595), DOM 10-176 -544 (SEQ ID NO: 1596), DOM10-176-545 (SEQ ID NO: 1597), DOM 10-176-546 (SEQ ID NO: 1598), DOM10-176-547 (SEQ ID NO: 1599), DOM 10-176-548 (SEQ ID NO: 1600), DOM10-176-549 (SEQ ID NO: 1601), DOM10-176-550 (SEQ ID NO: 1602), DOM10-176-551 (SEQ ID NO: 1603), DOM10-176-552 (SEQ ID NO: 1604), DOM 10- 176-553 (SEQ ID NO: 1605), DOM10-176-554 (SEQ ID NO: 1606), DOM 10- 176-555 ( SEQ ID NO: 1607), DOM 10-176-556 (SEQ ID NO: 1608), DOM 10-176-557 (SEQ ID NO: 1609), DOM 10-176-558 (SEQ ID NO: 1610), DOM10 -176-559 (SEQ ID NO: 1611), OJ 10- 176-560 (SEQ ID NO: 1612), DOM10-176A561 (SEQ ID NO: 1613), DOM 10-176-562 (SEQ ID NO: 1614), DOM 10-176-563 (SEQ ID NO: 1615 ), DOM10-176-564 (SEQ ID NO: 1616), DOM10-176-565 (SEQ ID NO: 1617), DOM10-176-566 (SEQ ID NO: 1618), DOM 10-176-567 (SEQ ID NO: 1619), DOM10-176-568 (SEQ ID NO: 1620), DOM 10-176-569 (SEQ ID NO: 1621), DOM 10-176-570 (SEQ ID NO: 1622), DO M 10- 176-571 (SEQ ID NO: 1623), DOM 10- 176-572 (SEQ ID NO: 1624), DOM10-176-573 (SEQ ID NO: 1625), D0 10-76-574 (SEQ ID NO: 1626), DOM 10-176-575 (SEQ ID NO: 1627), DOM10-176-576 (SEQ ID NO. : 1628), DOM10-176-577 (SEQ ID NO: 1629), DOM10-176-578 (SEQ ID NO: 1630), DOM 10-176-579 (SEQ ID NO: 1631), DOM) 0-176- 580 (SEQ ID NO: 1632), DOM 10- 176-581 (SEQ ID NO: 1633), DOM 10-176-582 (SEQ ID NO: 1634), DOM 10-176-583 (SEQ ID NO: 1635) , DOM 0-176-584 (SEQ ID NO: 1636), DOM10-176-585 (SEQ ID NO: 1637), DOM 10- 176-586 (SEQ ID NO: 1638), DOM10-176-587 (SEQ ID NO: 1639), DOM 10-176-588 (SEQ ID NO: 1640), DOM 10- 176-589 (SEQ ID NO: 1641), DOM 10-176-590 (SEQ ID NO: 1642), DOM10-176 -591 (SEQ ID NO: 1643), DOM10-176-592 (SEQ ID NO: 1644), DOM 10-176-593 (SEQ ID NO: 1645), DOM10-176-594 (SEQ ID NO: 1646), DOM 10-176-595 (SEQ ID NO: 1647), DOM 10-176-596 (SEQ ID NO: 1648), DOM10-176-597 (SEQ ID NO: 1649), DOM 10-176-598 (SEQ ID. NO: 1650), DOM10-176-599 (SEQ ID NO: 1651), DOM 10-? 76-600 (SEQ ID NO: 1652), DOM10-176-601 (SEQ ID NO: 1653), DOM 10-176-602 (SEQ ID NO: 1654), DOM 10-176-603 (SEQ ID NO: 1655 ), DOM 10- 176-604 (SEQ ID NO: 1656), DOM 10-176-605 (SEQ ID NO: 1657), DOM10-176-606 (SEQ ID NO: 1658), DOM 10- 176-607 ( SEQ ID NO: 1659), DOM10-176-608 (SEQ ID NO: 1660), DO M 10- 176-609 (SEQ ID NO: 1661), DOM 10- 176-610 (SEQ ID NO: 1662), DOM10 -176-611 (SEQ ID NO: 3663), DOM10-176-612 (SEQ ID NO: 1664), DOM10-176-613 (SEQ ID NO: 1665), DOM 10-176-614 (SEQ ID NO: 1666) ), DOM10-176-615 (SEQ ID NO: 1667), DOM10-176-616 (SEQ ID NO: 1668), DOM 1 O- 176-617 (SEQ ID NO: 1669), D0M10-176-618 (SEQ ID NO: 1670), D0M10-176-6 9 (SEQ ID NO: 1671), DOM10-176 -620 (SEQ ID NO: 3672), DOM 10-176-621 (SEQ ID NO: 1673), DOM10-176-622 (SEQ ID NO: 1674), DOM 10-176-623 (SEQ ID NO: 1675) , DOM 10-376-624 (SEQ ID NO: 1676), DOM 10- 176-625 (SEQ ID NO: 1677), DOM 10- 176-626 (SEQ ID NO: 1678), DOM10-176-627 (SEQ. ID NO: 1679), DOM 10-176-628 (SEQ ID NO: 1680), DOM10-176-629 (SEQ ID NO: 1681); DOM 10-176-630 (SEQ ID NO: 1682), DOM 10- 176-631 (SEQ ID NO: 1683), DOM10-176-632 (SEQ ID NO: 1684), DOM30-176-633 (SEQ ID NO. : 1685), DOM10-376-634 (SEQ ID NO: 1686), DOM 10-176-635 (SEQ ID NO: 1687), DOM10-176-636 (SEQ ID NO: 1688), DOM 10- 176-637 (SEQ ID NO: 1689), DOM 10- 176-638 (SEQ ID NO: 1690), DOM 10-176-639 (SEQ ID NO: 1691), DOM 10-176-640 (SEQ ID NO: 1692); DOM10-176-641 (SEQ ID NO: 1693), DOM 10-176-643 (SEQ ID NO: 1694), DOM10-176-644 (SEQ ID NO: 1695), DOM 10-176-645 (SEQ ID NO. : 1696), DOM 10- 176-646 (SEQ ID NO: 1697), DOM 10-176-647 (SEQ ID NO: 1698), DOM 10-176-648 (SEQ ID NO: 1699), DOM10-176- 649 (SEQ ID NO: 1700), DOM 10-176-650 (SEQ ID NO: 1701), DOM10-176-651 (SEQ ID NO: 1702), DOM 10-176-652 (SEQ ID NO: 1703), DOM10-176-653 (SEQ ID NO: 1704), DOM 10-176-654 (SEQ ID NO: 1705), DOM10-176-655 (SEQ ID NO: 1706), DOM10-176-656 (SEQ ID NO: 1707), DOM 10-176-657 (SEQ ID NO: 1708), DOM10-176-658 (SEQ ID NO: 1709), DOM 10- 176-659 (SEQ ID NO 710), DOM10-176-660 (SEQ. ID -NO: 1711), DOM 10- 176-661 (SEQ ID N0.1712), DOM 1 O-176-662 (SEQ ID NO: 1713), DOM10-176-663 (SEQ ID NO: 1714), DOM 10-76-664 (SEQ ID NO: 1715), DOM10-176-665 (SEQ ID NO: 1716), DOM 10-176-666 (SEQ ID NO 717), DOM10-176-667 (SEQ ID NO: 1718), DOM 10-176-668 (SEQ ID NO: 1719), DOM 10-176-669 (SEQ ID NO: 1720), DOM10-176-670 (SEQ ID NO: 1721), DOM10-176-671 (SEQ ID NO: 1722), DOM10-176-672 (SEQ. ID NO: 1723), DOM 10- 176-673 (SEQ ID NO: 1724), DOM 10- 176-674 (SEQ ID NO: 1725), DOM 10-176-675 (SEQ ID NO: 1726), DOM10- 253 (SEQ ID NO: 1727), DOM10-255 (SEQ ID NO: 1728), DOM10-272 (SEQ ID NO: 172.9), DOM10-307 (SEQ ID NO: 1730), DOM10-319 (SEQ ID NO: 1731) and DOM10-319-1 (SEQ ID NO: 1732). In some embodiments, the polypeptide domain having a binding site with binding specificity for IL-13 (e.g., a dAb) comprises an amino acid sequence having at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at less about 97%, at least about 98%, or at least about 99% amino acid sequence identity with the amino acid sequence or a dAb selected from the group consisting of DOM10-236 (SEQ ID.

NO: 2129 DOM10-238 (SEQ ID NO: 2130 DOM10-241 (SEQ ID NO: 2131 DOM10-245 (SEQ ID NO: 2132 DOM10-249 (SEQ ID NO: 2133 DOM10-250 (SEQ ID NO: 2134 DOM10- 251 (SEQ ID NO: 2135 DOM10-254 (SEQ ID NO: 2136 DOM10-256 (SEQ ID NO: 2137 DOM10-259 (SEQ ID NO: 2138 DOM10-260 (SEQ ID NO: 2139 DOM10-261 (SEQ ID NO. : 21.40 DOM10-263 (SEQ ID NO: 2141 DOM10-264 (SEQ ID NO: 2142 DOM10-273 (SEQ ID NO: 2143 DOM10-278 (SEQ ID NO: 2144 DOM10-279 (SEQ ID NO: 2145 DOM10-281 (SEQ ID NO: 2146 DOM10-282 (SEQ ID NO: 2147 DOM10-283 (SEQ ID NO: 2148 DOM10-400 (SEQ ID NO: 2149 DOM10-401 (SEQ ID NO: 2150 DOM10-402 (SEQ ID NO: 2151 DOM10-404 (SEQ ID NO.2152 DOM10-406 (SEQ ID NO: 2153 DOM10-407 (SEQ ID NO: 2154 DOM10-409 (SEQ ID NO: 2155 DOM10-410 (SEQ ID NO: 2156 DOM10-414 ( SEQ ID NO: 2157 DOM10-415 (SEQ ID NO: 2158 DOM10-416 (SEQ ID NO: 2159 DOM10-418 (SEQ ID NO: 2160 DOM10-420 (SEQ ID NO: 2161 DOM10-422 (SEQ ID NO: 2162 DOM10-423 (SEQ ID NO: 2163 DOM10-424 (SEQ ID NO: 2164 DOM10-425 (SEQ ID NO: 2165 DOM10-426 (SEQ ID NO: 2166 DOM10-427 (SEQ ID NO: 2167 DOM 10-428 (SEQ ID NO: 2168 DOM10-429 (SEQ ID NO: 2169 DOM10-430 (SEQ ID NO: 2170 DOM10-431 (SEQ ID NO: 2171 DOM10-432 (SEQ ID NO: 2172 DOM10-433 (SEQ. ID NO: 2173 DOM10-467 (SEQ ID NO: 2174 DOM10-468 (SEQ ID NO: 2175 DOM10-469 (SEQ ID NO: 2176 DOM10-470 (SEQ ID NO: 2177 DOM10-234 (SEQ ID NO: 2178 DOM10 -235 (SEQ ID NO: 2179 DOM10-237 (SEQ ID NO: 2180 DOM10-239 (SEQ ID NO: 2181 DOM10-240 (SEQ ID NO: 2182 DOM10-242 (SEQ ID NO: 2183 DOM10-243 (SEQ ID NO: 2184 DOM10- 244 (SEQ ID NO: 2185 DOM10-246 (SEQ ID NO: 2186 DOM10-247 (SEQ ID NO: 2187 DOM10-248 (SEQ ID NO: 2188 DOM10-252 (SEQ ID NO: 2189 DOM10-257 (SEQ ID NO : 2190 DOM10-258 (SEQ ID NO: 2191 DOM10-262 (SEQ ID NO: 2192 DOM10-265 (SEQ ID NO: 2193 DOM10-266 (SEQ ID NO: 2194 DOM10-274 (SEQ ID NO: 2195 DOM10-275 (SEQ ID NO: 2196 DOM10-276 (SEQ ID NO: 2197 DOM10-277 (SEQ ID NO: 2198 DOM30-280 (SEQ ID NO: 2199 DOM10-403 (SEQ ID NO: 2200 DOM10-405 (SEQ ID NO: 2201 DOM10-408 (SEQ ID NO: 2202 DOM10-411 (SEQ ID NO: 2203 DOM10-412 (SEQ ID NO: 2204 DOM10-413 (SEQ ID NO: 2205 DOM10-417 (SEQ ID NO: 2206 DOM10-419 ( SEQ ID NO: 2207 DOM10-472 (SEQ ID NO: 2208 DOM10-203 (SEQ ID NO: 2209 DOM10-205 (SEQ ID NO: 2210 DOM10-208 (SEQ ID NO: 2211 DOM10-218 (SEQ ID NO: 2212 DOM10-219 (SEQ ID NO: 2213 DOM10-220 (SEQ ID NO: 2214 DOM10-225 (SEQ ID NO: 2215 DOM10-228 (SEQ ID NO: 2216 DOM10-229 (SEQ ID NO: 2217 DOM1 0-230 (SEQ ID NO: 2218 DOM10-23I (SEQ ID NO: 2219 DOM10-268 (SEQ ID NO: 2220 DOM10-201 (SEQ ID NO.2221 DOM10-202 (SEQ ID NO: 2222 DOM10-204 (SEQ ID NO: 2223 DOM10-206 (SEQ ID NO: 2224 DOM10-207 (SEQ ID NO: 2225 DOM10-209 (SEQ ID NO: 2226 DOM10-210 (SEQ ID NO: 2227 DOM10-211 (SEQ ID NO: 2228 DOM1Q -213 (SEQ ID NO: 2229), DOM10-214 (SEQ ID NO: 2230), DOM10-215 (SEQ ID NO: 2231), DOM10-216 (SEQ ID NO.2232), DOM10-217 (SEQ ID NO: 2233), DOM10 -221 (SEQ ID NO: 2234), DOM10-223 (SEQ ID NO: 2235), DOM10-224 (SEQ ID NO: 2236), DOM10-227 (SEQ ID NO: 2237), DOM10-232 (SEQ ID NO. : 2238), DOM10-267 (SEQ ID NO: 2239), DOM10-270 (SEQ ID NO: 2240), DOM10-275-1 (SEQ ID NO: 2241), DOM10-276-2 (SEQ ID NO: 2242) ), DOM 10-276-3 (SEQ ID NO: 2243), DOM10-275-3 (SEQ ID NO: 2244), DOM10-277-2 (SEQ ID NO: 2245), DOM10-277-3 (SEQ ID NO: 224), DOM10-273-1 (SEQ ID NO: 2247), DOM10-273-2 (SEQ ID: 224d), DOM10-27S-2 (SEQ ID NO: 2249), DOM 10-275- 4 (SEQ ID NO: 2250), DOM10-276-1 (SEQ ID NO: 2251), DOM10-276-4 (SEQ ID NO: 2252), DOM10-277-1 (SEQ ID NO: 2253), DOM10- 275-33 (SEQ ID NO: 2254), DOM10-27545 (SEQ ID NO: 2255), DOM10-275-20 (SEQ ID NO: 2256), DOM 0-275-8 (SEQ ID NO: 2257), DOM10 -276-13 (SEQ ID NO: 2258), DOM10-276-14 (SEQ ID NO: 2259), DOM10-276-15 (SEQ ID NO: 2260), DOM10-276-17 (SEQ ID NO: 2261) , DOM10-276-7 (SEQ ID NO: 2262), DOM10-276-8 ( SEQ ID NO: 2263), DOM10-275-11 (SEQ ID NO: 2264), DOM10-275-12 (SEQ ID NO: 2265), DOM10-275-14 (SEQ ID NO: 2266), DOM10-275- 16 (SEQ ID NO: 2267), DOM10-275-17 (SEQ ID NO: 2268), DOM10-275-5 (SEQ ID NO: 2269), DOM10-275-6 (SEQ ID NO: 2270), DOM10- 275-7 (SEQ ID NO: 2271), DOM10-275-9 (SEQ ID NO: 2272), DOM10-276-10 (SEQ ID NO: 2273), DOM10-276-1 1 (SEQ ID NO: 2274) , DOM10- 276-12 (SEQ ID NO: 2275), DOM10-276-16 (SEQ ID NO: 2276), DOM10-276-5 (SEQ ID NO: 2277), DOM10-276-6 (SEQ ID NO: 2278), DOM10-276-9 (SEQ ID NO: 2279), DOM10-212 (SEQ ID NO: 2280), DOM10-53-424 (SEQ ID NO: 2281), DOM10-53-425 (SEQ ID NO: 2282), DOM10-53-426 (SEQ ID NO: 2283), DOM10-53-422 (SEQ ID NO: 2284), DOM10-53-423 (SEQ ID NO: 2285), DOM10-53-613 (SEQ ID NO: 22S6) ); DOM10-53-517 (SEQ ID NO: 2287), DOM 10-53-519 (SEQ ID NO: 2288), DOM10-53-520 (SEQ ID NO: 2289), DOM10-53-521 (SEQ ID NO: 2290), DOM10-53-522 (SEQ ID NO.2291), DOM 10-53-526 (SEQ ID NO: 2292), DOM10-53-527 (SEQ ID NO: 2293), DOM10-53-528 (SEQ. ID NO: 2294), DOM10-53-538 (SEQ ID NO: 2295), DOM10-53-523 (SEQ ID NO: 2296), DOM 10-53-524 (SEQ ID NO: 2297), DOM10-53- 525 (SEQ ID NO: 2298), DOM10-53-601 (SEQ ID NO: 2299), DOM10-53-602 (SEQ ID NO: 2300), DOM10-53-605 (SEQ ID NO: 2301), DOM10- 53-606 (SEQ ID NO: 2302), DOM10-53-607 (SEQ ID NO: 2303), DOM10-53-608 (SEQ ID NO: 2304), DOM10-53-609 (SEQ ID NO: 2305), DOM10-53-610 (SEQ ID NO: 230), DOM10-53-611 (SEQ ID NO: 2307), DOM10-53-612 (SEQ ID NO: 2308), DOM10-53-603 (SEQ ID NO: 2309) ), DOM10-53-604 (SEQ ID NO: 2310), DOM10-53-429 (SEQ ID NO: 2311), DOM10-53-432 (SEQ ID NO: 2312), DOM10-53-433 (SEQ ID NO. : 2313), DOM10-53-435 (SEQ ID NO: 2314), DOM10-53-430 (SEQ ID NO: 2315), DOM10-53-431 (SEQ ID NO: 2316), DOM10-53-434 (SEQ. ID NO: 2317), DOM10-53-436 (SEQ ID NO: 2318), DOM1 0- 53-437 (SEQ ID NO: 2319), DOM10-53-438 (SEQ ID NO: 2320), DOM10-53-440 (SEQ ID NO: 2321), DOM 10-53-439 (SEQ ID NO: 2322) , DOM10-53-441 (SEQ ID NO: 2323), DOM30-53-442 (SEQ ID NO: 2324), DOM 10-53-443 (SEQ ID NO: 2325), DOM10-53-444 (SEQ ID NO. : 2326), DOM 10-53-445 (SEQ ID NO: 2327), DOM10-53-446 (SEQ ID NO: 2328), DOM10-53-447 (SEQ ID NO: 2329), DOM10-53-449 ( SEQ ID NO: 2330), DON410-53-448 (SEQ ID NO: 2331), DOM10-53-450 (SEQ ID NO: 2332), DOM10-53-451 (SEQ ID NO: 2333), DOM10-53- 452 (SEQ ID NO: 2334), DOM10-53-453 (SEQ ID NO: 2335), DOM10-53-454 (SEQ ID NO: 2336), DOM10-53-455 (SEQ ID NO: 2337), DOM10- 53-456 (SEQ ID NO: 2338), DOM10-53-457 (SEQ ID NO: 2339), DOM10-53-458 (SEQ ID NO: 2340), DOM10-53-459 (SEQ ID NO: 2341), DOM10-53-461 (SEQ ID NO: 2342), DOM10-53-462 (SEQ ID NO: 2343), DOM10-53-465 (SEQ ID NO: 2344), DOM10-53-466 (SEQ ID NO: 2345) ), DOM10-53-467 (SEQ ID NO: 2346), DOM10-53-468 (SEQ ID NO: 2347), DOM10-53-460 (SEQ ID NO: 2348), DOM10-53-463 (SEQ ID NO. : 2349), DOM10-53-464 (SEQ ID NO: 2350), DOM10-53- 469 (SEQ ID NO: 2351), DOM10-53-471 (SEQ ID NO: 2352), DOM10-53-470 (SEQ ID NO: 2353), DOM10-53-533 (SEQ ID NO: 2354), DOM10- 53-534 (SEQ ID NO: 2355), DOM10-53-535 (SEQ ID NO: 2356), DOM10-53-537 (SEQ ID NO: 2357), DOM10-53-538 (SEQ ID NO: 2358), DOM10-53-539 (SEQ ID NO: 2359), DOM10-53-540 (SEQ ID NO: 2360), DOM10-53-531 (SEQ ID NO: 2361), DOM10-53-532 (SEQ ID NO: 2362) ), DOM10- 53-536 (SEQ ID NO: 2363), DOM 10-53-542 (SEQ ID NO: 2364), DOM10-53-541 (SEQ ID NO: 2365), DOM10-53-473 (SEQ ID NO: 2366) , DOM10-53-472 (SEQ ID NO: 2367), DOM10-53-475 (SEQ ID NO: 2368), DOM 10-53-474 (SEQ ID NO: 2369), DOM10-53-543 (SEQ ID NO. : 2370), DOM10-53-544 (SEQ ID NO: 2371), DOM10-53-545 (SEQ ID NO: 2372), DOM10-53-548 (SEQ ID NO: 2373), DOM10-53-546 (SEQ ID NO: 2374), DOM10-53-549 (SEQ ID NO: 2375), DOM10-53-547 (SEQ ID NO: 2376), DOM10-53-550 (SEQ ID NO: 2377), DOM 10-53- 551 (SEQ ID NO: 2378), DOM10-53-560 (SEQ ID NO: 2379), DOM10-53-565 (SEQ ID NO: 2380), DOM10-53-559 (SEQ ID NO: 23S1), DOM10- 53-561 (SEQ ID NO: 2382), DOM10-53-562 (SEQ ID NO: 2383), DOM10-53-563 (SEQ ID NO: 2384), DOM10-53-564 (SEQ ID NO: 2385), DOM10-53-566 (SEQ ID NO: 2386), DOM10-53-554 (SEQ ID NO: 2387), DOM10-53-552 (SEQ ID NO: 2388), DOM10-53-553 (SEQ ID NO: 2389) ), DOM10-53-558 (SEQ ID NO: 2390), DOM10-53-556 (SEQ ID NO: 2391) and DOM10-53-557 (SEQ ID NO: 2392).

In preferred embodiments, the polypeptide domain having a binding site with binding specificity for IL-13 (e.g., a dAb) comprises an amino acid sequence having at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at less about 98%, or at least about 99% amino acid sequence identity with the amino acid sequence of DOM-10-53 (SEQ ID NO: 967) or DOM10-176-535 (SEQ ID NO: 1587) . For example, the polypeptide domain having a binding site with binding specificity for IL-13 may comprise the amino acid sequence of DOM10-176-535 (SEQ ID NO: 1587), DOM10-53-223 (SEQ ID NO. : 1090), DOM 10-53-234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO: 1182), DOM10-53-339 (SEQ ID NO: 1203), DOM 10-53-344 (SEQ ID NO: 1208), DOM 10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241). In some embodiments, the polypeptide domain having a binding site with binding specificity for IL-13 competes with any of the dAbs described herein for binding to IL-13. Preferably the polypeptide domain having a binding site with binding specificity for IL-13 is a single immunoglobulin variable domain. The polypeptide domain having a binding site with binding specificity for IL-13 can comprise any variable domain of single immunoglobulin, and preferably comprises a human variable domain or a variable domain comprising regions of human structure. In certain embodiments, the polypeptide domain that has a binding site with binding specificity for IL-13, comprises a universal structure, as described herein. The ligand of the present invention (e.g., the ligand having binding specificity for IL-4 and IL-13, the ligand having binding specificity for IL-13) may comprise a binding portion without immunoglobulin having specificity of linkage for IL-13 and inhibits an IL-13 function (eg, receptor binding), wherein the non-immunoglobulin binding portion comprises one, two or three of the CDRs of a VH, VL or VHH that binds to IL -13 and a suitable scaffolding. In certain embodiments, the non-immunoglobulin binding portion comprises CDR3 but not CDR1 or CDR2 of a VH, Vj, or VHH that binds to IL-13 and a suitable scaffold. In other embodiments, the non-immunoglobulin binding portion comprises CDR1 and CDR2, but not CDR3 of a VH, VL, or VHH that binds to IL-13 and a suitable scaffold. In other embodiments, the non-immunoglobulin binding portion comprises CDR1, CDR2 and CDR3 of a VH, VL or VHH that binds to IL-13 and a suitable scaffold. Preferably, the CDR or CDRs of the ligand of these embodiments is a CDR or CDRs of an anti-IL-13 dAb described herein. Preferably, the binding portion without immunoglobulin comprises one, two or three of the CDRs of one of the anti-IL-13 dAbs described herein. In other embodiments, the ligand (e.g., the ligand that has binding specificity for IL-4 and IL-13, the ligand that has binding specificity for IL-13) comprises only CDR3 of a VH, VL or VHH that binds to IL-13. The domain without immunoglobulin may comprise an amino acid sequence having one or more regions having one, two or three sequence identity of the CDRs of an anti-IL-13 dAb described herein. For example, the domain without immunoglobulin can have an amino acid sequence containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90% sequence identity with CDR1, CDR2 and / or CDR3 of an anti-L 13 dAb described herein. Even more preferably, the binding portion without immunoglobulin comprises one, two or three of the CDRs of DOM 10-176-535 (SEQ ID NO: 1587), DOM10-53-223 (SEQ ID NO: 1090), DOM10-53 -234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO: 1182), DOM 10-53-339 (SEQ ID NO: 1203), DOM 10-53-344 (SEQ ID NO: 1208) and DOM10-53-396 (SEQ ID NO: 1260). In certain embodiments, a polypeptide domain having a binding site with binding specificity for IL-13 resists aggregation, reversibly unfolds, comprises a region of structure and / or is secreted as described above for the domain of polypeptide having a binding site with binding specificity for IL-4. DAb Monomers that Link to Serum Albumin The ligands of the present invention may further comprise a dAb monomer that binds serum albumin (SA) with a Kd of 1 nM to 500 μ? (for example, x 10"9 to 5 x 10" 4), preferably 100 nM to 10 μ ?. Preferably, for a ligand comprising an anti-SA dAb, the linkage (e.g., Kd and / or Koff as measured by resonance to surface plasmon, e.g. using BiaCore) of the ligand to its target (s) is 1 to 100000 times (preferably 100 to 100000, more preferably 1000 to 100000, or 10000 to 100000 times) stronger than SA passes. Preferably, serum albumin is human serum albumin (HSA). In one embodiment, the first dAb (or dAb monomer) links SA (e.g., HSA) with a Kd of about 50, preferably 70, and more preferably 100, 150 or 200 nM. In certain embodiments, the dAb monomer binding SA resists aggregation, reversibly unfolded and / or comprises a structure region as described above for dAb monomers that bind IL-14. In particular embodiments, the antigen binding fragment of an antibody binding serum albumin is a dAb that binds human serum albumin. In certain embodiments, dAb binds human serum albumin and competes to bind albumin with a dAb selected from the group consisting of DOM7r-1 (SEQ ID NO: 1736), DOM7r-3 (SEQ ID NO: 1737), DOM7r-4 ( SEQ ID NO: 1738), DOM7r-5 (SEQ ID NO 1739) DOM7r -7 (SEQ ID NO: 1740), DOM7r -8 (SEQ ID NO 1741) DOM7h -2 (SEQ ID NO: 1742), DOM7h -3 (SEQ ID NO 1743) DOM7h -4 (SEQ ID NO: 1744), DOM7h -6 (SEQ ID NO 1745) DOM7h -1 (SEQ ID NO: "1746), DOM7h -7 (SEQ ID NO 1747) DOM7h -22 (SEQ ID NO: 1748), DOM7h- 23 (SEQ ID NO 1749) DOM7h -24 (SEQ ID NO: 1750), DOM7h- 25 (SEQ ID NO 1751) DOM7h -26 (SEQ ID NO: 1752), DOM7h- 21 (SEQ ID NO 1753) DOM7h -27 (SEQ ID NO: 1754), DOM7h -8 (SEQ ID NO 1756) DOM7r-13 (SEQ ID NO: 1757), DOM7M4 (SEQ ID NO 1758) DOM7r-15 (SEQ ID NO: 1759), DOM7r-16 (SEQ ID NO 1760) DOM7r- 17 (SEQ ID NO: 1761), DOM7r- 18 (SEQ ID NO 1762) DOM7r- 19 (SEQ ID NO: 1763), DOM7r- |20 (SEQ ID NO 1764) DOM7r- 21 (SEQ ID NO: 1765), DOM7r- 22 (SEQ ID NO 1766) DOM7r-23 (SEQ ID NO: 1767), DOM7r- 24 (SEQ ID NO 1768) DOM7r- 25 (SEQ ID NO: 1769), DOM7r- 26 (SEQ ID NO 1770) DOM7r- 27 (SEQ ID NO: 1771), DOM7r- 28 (SEQ ID DO NOT. 1772) DOM7r- 29 (SEQ ID NO: 1773), DOM7r- 30 (SEQ ID NO: 1774) DOM7r- 31 (SEQ ID NO: 1775), DOM7r- 32 (SEQ ID NO: 1776) and DOM7r-33 (SEQ ID NO: 1777). In certain embodiments, the dAb binds to human serum albumin and comprises an amino acid sequence having at least about 80%, or at least about 85%, or at least about 90%, or at least about 95% , or at least about 96%, or at least about 97%, or at least about 98%, or at least about 99% amino acid sequence identity with the amino acid sequence of a dAb selected from the group consisting of DOM7r -1 (SEQ ID.

NO 1736), DOM7r -3 (SEQ ID NO: 1737), DOM7r -4 (SEQ ID NO 1738), DOM7r -5 (SEQ ID NO: 1739), DOM7r -7 (SEQ ID NO 1740), DOM7r -8 (SEQ ID NO 1741), DOM7h -2 (SEQ ID NO 1742), DOM7h -3 (SEQ ID NO: 1743), DOM7h -4 (SEQ ID NO 1744), DOM7h -6 (SEQ ID NO • 1745), DOM7h -1 (SEQ ID NO 1746), DOM7h - 7 (SEQ ID NO 1747), DOM7h- -22 (SEQ ID NO 1748), DOM7h -23 (SEQ ID NO: 1749), DOM7h- |24 (SEQ ID NO 1750), DOM7h -25 (SEQ ID NO: 1751), DOM7h- |26 (SEQ ID NO 1752), DOM7h -21 (SEQ ID NO: 1753), DOM7h- 27 (SEQ ID NO 1754), DOM7h -8 (SEQ ID NO: 1756), DOM7r- 13 (SEQ ID NO 1757), DOM7r-14 (SEQ ID NO: 1758), DOM7r-15 (SEQ ID NO1759), DOM7r-16 (SEQ ID NO: 1760), DOM7r- 17 (SEQ ID DO NOT. 1761), DOM7r- 18 (SEQ ID NO: 1762), DOM7r- 19 (SEQ ID NO: 1763), DOM7r-20 (SEQ ID NO: 1764), DOM7r- 21 (SEQ ID NO: 1765), DOM7r-22 (SEQ ID NO: 1766), DOM7r-23 (SEQ ID NO: 1767), DGM7r-24 (SEQ ID NO: 1768), DOM7r-25 (SEQ ID NO: 1769), DOM7r- -26 (SEQ ID NO 1770), DOM7r- 27 (SEQ ID NO: 1771), DOM7r-28 (SEQ ID NO: 1772), DOM7r-29 (SEQ ID NO: 1773), DOM7r- 30 (SEQ ID NO: 1774), DOM7r- 31 (SEQ ID NO: 1775), DOM7r- 32 (SEQ ID NO: 1776), and DOM7r -33 (SEQ ID NO: 1777).

For example, a dAb binding to human serum albumin may comprise an amino acid sequence having at least about 90%, or at least about 95%, or at least about 96%, or at least about 97% , or at least about 98%, or at least about 99% amino acid sequence identity with DOM7h-2 (SEQ ID NO: 1742), DOM7h-3 (SEQ ID NO: 1743), DOM7h-4 (SEQ ID NO: 1744), DOM7h-6 (SEQ ID NO: 1745), DOM7h-1 (SEQ ID NO: 1746), DOM7h-7 (SEQ ID NO: 1747), DOM7h-8 (SEQ ID NO: 1756), DOM7r-13 (SBQ ID NO: 1757), DOM7r-14 (SEQ ID NO: 1758), DOM7h-22 (SEQ ID NO: 1748), DOM7h-23 (SEQ ID NO: 1749), DOM7h-24 (SEQ ID NO: 1750), DOM7h-25 (SEQ ID NO: 1751), DOM7h-26 (SEQ ID NO: 1752), DOM7h-21 (SEQ ID NO: 1753), and DOM7h-27 (SEQ ID NO: 1754). The amino acid sequence identity is determined using preferably a suitable sequence alignment algorithm and default parameters, such as BLAST P (Karlin and Altschul, Proc, Nati. Acad. Sci. USA, 87 (6): 2264-2268 ( 1990)). In more particular embodiments, dAb is a VK dAb that binds to human serum albumin and has an amino acid sequence selected from the group consisting of DOM7h-2 (SEQ ID NO: 1742), DOM7h-3 (SEQ ID NO: 1743 ), DOM7h-4 (SEQ ID NO: 1744), DOM7h-6 (SEQ ID NO: 1745), DOM7h-1 (SEQ ID NO: 1746), DOM7h-7 (SEQ ID NO: 1747), DOM7h-8 (SEQ ID NO: 1756), DOM7r-13 (SEQ ID NO: 1757), and DOM7r-14 (SEQ ID NO: 1758), or a VH dAb having an amino acid sequence selected from the group consisting of: DOM7h-22 (SEQ ID NO: 1748), DOM7h-23 (SEQ ID NO: Í749), DOM7h-24 (SEQ ID NO: 1750), DOM7h-25 (SEQ ID NO: 1751), DOM7h-26 (SEQ ID NO: 1752), DOM7h-21 (SEQ ID NO: 1753), DOM7h-27 (SEQ ID NO: 1754). In other embodiments, the fragment that binds to an antigen of an antibody that binds to serum albumin is a dAb that binds to human serum albumin and comprises the CDRs of any of the above amino acid sequences. The Camelid VHH binding to serum albumin includes those described in Publications WO 2004/041862 (Ablynx NV) and in the present invention, such as Sequence A (SEQ ID NO: 1778), Sequence B (SEQ ID NO: 1779), Sequence C (SEQ ID NO: 1780), Sequence D (SEQ ID NO: 1781), Sequence E (SEQ ID NO: 1782), Sequence F (SEQ ID NO: 1783), Sequence G (SEQ ID NO: 1784), Sequence H (SEQ ID NO: 1785), Sequence I (SEQ ID NO: 1786), Sequence J (SEQ ID NO: 1787), Sequence K (SEQ ID NO: 1788), Sequence L (SEQ ID NO: 1789), Sequence M (SEQ D NO: 1790), Sequence N (SEQ ID NO: 1791), Sequence O (SEQ ID NO: 1792), Sequence P (SEQ ID NO: 1793), Sequence Q (SEQ ID NO: 1794). In certain modalities, Camelid VHH binds to serum albumin human and comprises an amino acid sequence having at least about 80%, or at least about 85%, or at least about 90%, or at least about 95%, or at least about 96%, or at least about less about 97%, or at least about 98%, or at least about 99% amino acid sequence identity with any of SEQ ID NOS: 1778-1794. The amino acid sequence identity is determined using preferably a suitable sequence alignment algorithm and default parameters, such as BLAST P (Karlin and Altschul, Proc Nail, Acad. Sci. USA 87 (6): 2264-2268 (1990)). ). In some embodiments, the ligand comprises an anti-serum albumin dAb that competes with any of anti-serum albumin dAb described herein for binding to serum albumin (e.g., human serum albumin). Nucleic Acid Molecules, Vectors and Host Cells The present invention also provides isolated and / or recombinant nucleic acid molecules encoding ligands (dual specific ligands and multi-specific ligands), as described herein. The nucleic acids referred to herein as "isolated" are nucleic acids that have been separated from the nucleic acids of the genomic DNA or cellular RNA from their source of origin (for example, as they exist in cells or in a mixture of nucleic acids such as a library) and include nucleic acids obtained through the methods described herein or other suitable methods, including essentially pure nucleic acids, nucleic acids produced by synthesis chemistry, by combinations and biological and chemical methods, and recombinant nucleic acids which are isolated (see for example Daugherty Publications, BL and associated Nucleic Acids Res., 19 (9): 2471-2476 (1991); Lewis, AP and JS Crowe, Gene,?: 297-302 (1991)). Nucleic acids referred to in the present invention, "recombinants" are nucleic acids that have been produced by recombinant DNA methodology, including nucleic acids that are generated through methods that depend on an artificial recombination method, such as the reaction of polymerase chain (PCR) and / or cloning into a vector using restriction enzymes. In certain embodiments, the isolated and / or recombinant nucleic acid comprises a nucleotide sequence encoding a ligand, as described herein, wherein the ligand comprises an amino acid sequence having at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% amino acid sequence identity with the amino acid sequence of a dAb that binds IL-4 described herein, or a dAb that binds to IL-13 described herein. For example, in some embodiments, the isolated and / or recombinant nucleic acid comprises a nucleotide sequence encoding a ligand having binding specificity for IL-4, as described herein, wherein the ligand comprises an amino acid sequence that has at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% amino acid sequence identity with the amino acid sequence of a selected dAb from the group consisting of DOM9-15 (SEQ ID NO: 175), DOM9-17 (SEQ ID NO: 176), DOM9-23 (SEQ ID NO: 177), DOM9-24 (SEQ ID NO: 178), DOM9 -25 (SEQ ID NO: 179), DOM9-27 (SEQ ID NO: 180), DOM9-28 (SEQ ID NO: 181), DOM9-29 (SEQ ID NO: 1 82), DOM9-30 (SEQ ID NO: 183), DOM9-31 (SEQ ID NO 184) DOM9-32 (SEQ ID NO: 185), DOM9-33 (SEQ ID NO 186), DOM9-50 (SEQ ID NO: 187), DOM9-57 (SEQ ID NO 188), DOM9-59 (SEQ ID NO: 189), DOM9-63 (SEQ ID NO 190), DOM9-67 (SEQ ID NO: 191), DOM9-68 (SEQ ID NO 192), DOM9-70 (SEQ ID NO: 193), DOM9-79 (SEQ ID NO 194), DOM9-82 (SEQ ID NO: 195), DOM9-86 (SEQ ID NO 196), DOM9-94 (SEQ ID NO: 197), DOM9-108 (SEQ ID NO 198), DOM9-112 (SEQ ID NO: 199), DOM9-112-1 (SEQ ID NO 200), DOM9-112 -2 (SEQ ID NO: 201), DOM9-112-3 (SEQ ID NO 202), DOM9-112 -4 (SEQ ID NO: 203), DOM9-112-5 (SEQ ID NO 204), DOM9412-6 (SEQ ID NO: 205), DOM9-112-7 (SEQ ID NO 206), DOM9-112 -8 (SEQ ID NO: 207), DOM9-112-9 (SEQ ID NO 208), DOM9-112 -10 (SEQ ID NO: 209), DOM9-112-11 (SEQ ID NO: 210), DOM9-112-12 (SEQ ID NO: 211), DOM9-112-13 (SEQ ID NO: 212), DOM9-112-14 (SEQ ID N0: 2I3), DOM9-112-15 (SEQ ID N 0: 214), DOM9-112-16 (SEQ ID NO: 215), DOM9-112-17 (SEQ ID NO: 216), DOM9-112-18 (SEQ ID NO: 217), DOM9- 112-19 (SEQ ID NO: 218), DOM9-3 12-20 (SEQ ID NO: 219), DOM9-112-21 (SEQ ID NO: 220), DOM9-112-22 (SEQ ID NO: 221) , DOM9-112-23 (SEQ ID NO: 222), DOM9-112-25 (SEQ ID NO: 223), DOM9-112-81 (SEQ ID NO: 224), DOM9-112-82 (SEQ ID NO: 225), DOM9-112-83 (SEQ ID NO: 226), DOM9-112-84 (SEQ ID NO: 227), DOM9-112-85 (SEQ ID NO: 228), DOM9-112-86 (SEQ ID NO: 229), DOM9-112-87 (SEQ ID NO: 230), DOM9-112-88 (SEQ ID NO: 231), DOM9-112-89 (SEQ ID NO: 232), DOM9-112-90 (SEQ ID NO: 233), DOM9-112-91 (SEQ ID NO: 234), DOM9-112-92 (SEQ ID NO: 235), DOM9-112-93 ( SEQ ID NO: 236), DOM9-112-94 (SEQ ID NO: 237), DOM9-112-95 (SEQ ID NO: 238), DOM9-112-96 (SEQ ID NO: 239), D0M9-112- 97 (SEQ ID NO: 240), DOM9-112-98 (SEQ ID NO: 241), DOM9-112-99 (SEQ ID NO: 242), D0M9-112-100 (SEQ ID NO: 243), DOM9- 112-101 (SEQ ID NO: 244), DOM9-1132-102 (SEQ ID NO: 245), DOM9-112-103 (SEQ ID NO: 246), DOM9-112-104 (SEQ ID NO: 247), DOM9-112-105 (SEQ ID NO: 248), DOM9-112-106 (SEQ ID NO: 249), DOM9-112-107 (SEQ ID NO: 250), DOM9-112-108 (SEQ ID NO: 251) ), DOM9-112-109 (SEQ ID NO: 252), DOM9-112-110 (SEQ ID NO: 253), DOM9-112-111 (SEQ ID NO: 254), DOM9-112-112 (SEQ ID NO. : 255), DOM9-112-113 (SEQ ID NO: 25), DOM9-112-114 (SEQ ID NO: 257), DOM9-112-1 15 (SEQ ID NO: 258), DOM9-112-116 ( SEQ ID NO: 259), DOM9-112-117 (SEQ ID NO: 260), DOM9-112-118 (SEQ ID NO: 261), DOM9-112-119 (SEQ ID NO: 262), DOM9-112- 120 (SEQ ID NO: 263), DOM9-112-121 (SEQ ID NO: 264), DOM9-112-122 (SEQ ID NO: 265), DOM9-112 -123 (SEQ ID NO: 266), DOM9-1 32-124 (SEQ ID NO: 267), DOM9-112-125 (SEQ ID NO: 268), DOM9-112-126 (SEQ ID NO: 269), DOM9-112-127 (SEQ ID NO: 270), DOM9-112-128 (SEQ ID NO: 271), DOM9-112-134 (SEQ ID NO: 272), DOM9-112-135 (SEQ ID NO: 273) ), DOM9-112-136 (SEQ ID NO: 274), DOM9-112-137 (SEQ 10? 0: 275), DOM9-112-138 (SEQ ID NO: 276), DOM9-112-140 (SEQ ID NO: 277), OJ M9- 112- 141 (SEQ ID NO: 278), DOM9-112-142 (SEQ ID NO: 279), DOM9-Y 12-143 (SEQ IDM): 28Q), DOM9-112-144 (SEQ ID NO: 281), DOM9- 112-145 (SEQ ID NO: 282), DOM9-112-146 (SBQ ID NO: 283), DOM9-112-147 (SEQ ID NO: 284), DOM9-112-148 (SEQ ID NG: 285), DOM9-112-149 (SEQ ID NO: 286), DOM9-112-150 (SEQ ID NO: 287), DOM9-112-151 (SEQ ID NO.288), DOM9-112-152 (SEQ ID NO: 289) ), DOM9-112-153 (SEQ ID NO.290), DOM9-112-154 (SEQ ID NO: 291), DOM9-112-155 (SEQ ID NO: 292), DOM9-112-156 (SEQ ID NO. : 293), DOM9-112-157 (SEQ ID NO: 294), DOM9-112-158 (SEQ ID NO: 295), DOM9-112-159 (SEQ ID NO: 296), DOM9-112-160 (SEQ ID NO.297), DOM9-112-161 (SEQ ID NO: 298), DOM9-112-162 (SEQ ID NO: 299), DOM9-112-163 (SEQ ID NO: 300), DOM9-112-164 (SEQ ID NO: 301), DOM9-112-165 (SEQ ID NO: 302), DOM9-112-166 (SEQ ID NO: 303), DOM9-112-167 (SEQ ID NO: 304), DOM9-112 -168 (SEQ ID NO: 305), DOM9-112-169 (SEQ ID NO: 306), DOM9-112-170 (SEQ ID NO: 307), DOM9-112-171 (SEQ ID NO: 308), DOM9 -112-172 (SEQ ID NO: 309), DOM9-112-173 (SEQ ID NO: 310), DOM9-112-174 (SEQ. ID NO: 311), DOM9-112-175 (SEQ ID NO: 312), DOM9-112-176 (SEQ ID NO: 313), DOM9-112-177 (SEQ ID NO: 314), DOM9-112-178 (SEQ ID NO: 315), DOM9-112-179 (SEQ ID NO: 316), DOM9-112-180 (SEQ ID NO: 317), DOM9-112-181 (SEQ ID NO: 318), DOM9-112 -182 (SEQ ID NO: 319), DOM9-112-183 (SEQ ID NO: 320), DOM9-112-184 (SEQ ID NO: 321), DOM9-112-185 (SEQ ID NO: 322), DOM9 -112-186 (SEQ ID NO: 323), DOM9-112- 187 (SEQ ID NO: 324), DOM9-112-188 (SEQ ID NO: 325), DOM9-112-189 (SEQ ID NO.326), DOM9-Y 12-190 (SEQ ID NO: 327), DOM9 -112-191 (SEQ ID NO: 328), DOM9-112-192 (SEQ ID NO: 329), DOM9-112-193 (SEQ ID NO: 330), DOM9-112-194 (SEQ ID NO: 331) , DOM9-112-195 (SEQ ID NO: 332), DOM9-112-196 (SEQ ID NO: 333), DOM9-112-197 (SEQ ID NO: 334), DOM9-112-198 (SEQ ID NO: 335), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-112-201 (SEQ ID NO: 338), DOM9-112-202 (SEQ ID NO: 339), DOM9-120 (SEQ ID NO: 340), DOM9-121 (SEQ ID NO: 341), DOM9-122 (SBQ ID NO: 342), DOM9-123 (SEQ ID NO: 343), DOM9 -124 (SEQ ID NO: 344), DOM9-125 (SEQ ID NO: 345), DOM9-128 (SEQ ID NO: 346), DOM9-134 (SEQ ID NO-, 347), DOM9-136 (SEQ ID NO: 348), DOM9-26 (SEQ ID NO: 500), DOM9-35 (SEQ ID NO: 501), DOM9-36 (SEQ ID NO: 502), DOM9-37 (SEQ ID NO: 503), DOM9 -38 (SEQ ID NO: 504), DOM9-39 (SEQ ID NO: 505), DOM9-40 (SEQ ID NO: 506), DOM9-41 (SEQ ID NO: 507), DOM9-43 (SEQ ID NO. : 508), DOM9-44 (SEQ ID NO: 509), DOM9-44-500 (SEQ ID NO: 510), DOM9-44-501 (SEQ ID NO: 511), DOM9-44-502 (SEQ LDNO: 512), DOM9-44-503 (SEQ ID NO: 513), DOM9-44-504 (SEQ ID NO: 514), DOM9-44- 505 (SEQ ID NO: 515), DOM9-44-506 (SEQ ID NO: 516), DOM9-44-507 (SEQ ID NO: 517), DOM9-44-509 (SEQ ID NO: 518), DOM9- 44-510 (SEQ ID NO: 519), DOM9-44-511 (SEQ ID NO: 520), DOM9-44-512 (SEQ ID NO: 521), DOM9-44-513 (SEQ ID NO: 522), DOM9-44-514 (SEQ ID NO: 523), DOM9-44-515 (SEQ ID NO: 524), DOM9-44-516 (SEQ ID NO: 525), DOM9-44-517 (SEQ ID NO: 526), D03VY9-44-5I8 (SEQ ID NO: 527), DOM9-44-519 (SEQ ID NO: 528), DOM9-44-520 (SEQ ID NO: 529), DOM9-44-521 (SEQ ID NO: 530), DOM9-44 -522 (SEQ ID NO: 531), DOM9-44-523 (SEQ ID NO: 532), DOM9-44-524 (SEQ ID NO: 533), DOM9-44-525 (SEQ ID NO: 534), DOM9 -44-526 (SEQ ID NO: 535), DOM9-44-527 (SEQ ID NO: 536), DOM9-44-528 (SEQ ID NO: 537), DOM9-44-529 (SEQ ID NO: 538) , DOM9-44-530 (SEQ ID NO: 539), DOM9-44-531 (SEQ ID NO.540), DOM9-44-532 (SEQ ID NO: 541), DOM9-44-533 (SEQ ID NO: 542), DOM9-44-534 (SEQ ID NO: 543), DOM9-44-535 (SEQ ID NO: 544), DOM9-44-536 (SEQ ID NO.-545), DOM9-44-537 (SEQ. ID NO: 546), DOM9-44-538 (SEQ ID NO: 547), DOM9-44-539 (SEQ ID NO: 548), DOM9-44-540 (SEQ ID NO: 549), DOM9-44-541 (SEQ ID NO: 550), DOM9-44-542 (SEQ ID NO: 551), DOM9-44-543 (SEQ ID NO: 552), DOM9-44-544 (SEQ ID NO: 553), DOM9-44 -545 (SEQ ID NO: 554), DOM9-44-546 (SEQ ID NO: 555), DOM9-44-547 (SEQ ID NO: 556), DOM9-44-548 (SEQ ID NO: 557), DOM9-44-549 (SEQ ID NO: 558), DOM9-44-550 (SEQ ID NO: 559), DOM9-44-551 (SEQ ID NO: 560), DOM9-44-552 (SEQ ID NO: 561) ), DOM9-44-553 (SEQ ID NO: 562), DOM9-44-554 (SEQ ID NO: 563), DOM9-44-555 (SEQ ID NO: 564), DOM9-44-556 (SEQ ID NO. : 565), DOM9-44-557 (SEQ ID NO: 566), DOM9-44-558 (SEQ ID NO: 567), DOM9-44-559 (SEQ ID NO: 568), DOM9-44-560 (SEQ ID NO: 569), DOM9-44-561 (SEQ ID NO: 570), DOM9-44-562 (SEQ ID NO: 571), DOM9-44-563 (SEQ ID NO: 572), DOM9-44 -564 (SEQ ID NO: 573), DOM9-44-565 (SEQ ID NO: 574), DOM9-44-566 (SEQ ID NO: 575), DOM9-44-625 (SEQ ID NO: 576), DOM9 -44-626 (SEQ ID NO.577), DOM9-44-627 (SEQ ID NO: 578), DOM9-44-628 (SEQ ID NO: 579), DOM9-44-629 (SEQ ID NO: 5S0) , DOM9-44-630 (SEQ ID NO: 581), DOM9-44-631 (SEQ ID NO: 582), DOM9-44-632 (SEQ ID NO: 583), DOM9-44-633 (SEQ ID NO: 584), DOM9-44-634 (SEQ ID NO: 585), DOM9-44-636 (SEQ ID NO: 58), DOM9-44-637 (SEQ ID NO: 587), DOM9-44-639 (SEQ ID NO: 588), DOM9-44-640 (SEQ ID NO: 589), DOM9-44-641 (SEQ ID NO: 590), DOM9-44-642 (SEQ ID NO.591), DOM9-44-643 ( SEQ ID NO.592), DOM9-44-644 (SEQ ID NO: 593), DOM9-45 (SEQ ID NO: 594), DOM9-46 (SEQ ID NO: 595), DOM9-47 (SEQ ID NO: 59ó), DOM9-48 (SEQ ID NO: 597), DOM9-143 (SEQ ID NO: 598), DOM9-144 (SEQ ID NO: 599), DOM9-146 (SEQ ID NO: 600), DOM9-152 (SEQ ID NO: 601), DOM9-155 (SEQ ID NO: 602), DOM9-155-001 (SEQ ID NO: 603), DOM9-155-3 (SEQ ID NO: 60) 4), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-8 (SEQ ID NO: 606), DOM9-155-9 (SEQ ID NO: 607), DOM9-155-11 (SEQ ID NO: 608), DOM9-155-13 (SEQ ID NO: 609), DOM9-155-14 (SEQ ID NO: 610), DOM9-155-17 (SEQ ID NO.611), DOM9-155-19 ( SEQ ID NO: 612), DOM9-155-20 (SEQ ID NO: 613), DOM9-155-22 (SEQ ID NO: 614), DOM9-155-23 (SEQ ID NO: 615); DOM9-155-24 (SEQ ID NO: 616), DOM9-155-25 (SEQ ID NO: 617), DOM9-155-26 (SEQ ID NO: 618), DOM9-155-27 (SEQ ID NO: 619), DOM9-155-28 (SEQ ID NO: 620 ), DOM9-155-29 (SEQ ID NO: 621), DOM9-155-30 (SEQ ID NO: 622), DOM9-I55-31 (SEQ ID NO: 623), DOM9-155-32 (SEQ ID NO. : 624), DOM9-155-33 (SEQ ID NO: 625), D0M9-155-34 (SEQ ID NO: 626), DOM9-155-35 (SEQ ID NO: 627), DOM9-155-36 (SEQ ID NO: 628), DOM9-155-37 (SEQ ID NO: 629), DOM9-155-38 (SEQ ID NO: 630), DOM9-155-39 (SEQ ID NO: 631), DOM9-155-41 (SEQ ID NO: 632), DOM9-155-42 (SEQ ID NO: 633), DOM9-155-43 (SEQ ID NO: 634), DOM9-155-44 (SEQ ID NO: 635), DOM9-155 -45 (SEQ ID NO: 636), DOM9-155-46 (SEQ ID NO: 637), DOM9-155-47 (SEQ ID NO: 638), DOM9-155-48 (SEQ ID NO: 639), DOM9 -155-49 (SEQ ID NO: 640), DOM9-155-50 (SEQ ID NO: 641), DOM9-155-51 (SEQ ID NO: 642), DOM9-155-52 (SEQ ID NO: 643) , DOM9-155-53 (SEQ ID NO: 644), DOM9-158 (SEQ ID NO: 645), DOM9-160 (SEQ ID NO: 646), DOM9-161 (SEQ ID NO: 647), DOM9-162 (SEQ ID NO: 648), DOM9-163 (SEQ ID NO: 649) and DOM9-164 (SEQ ID NO: 650). In some embodiments, the isolated and / or recombinant nucleic acid comprises a nucleotide sequence encoding a ligand having binding specificity for IL-4, as described herein, wherein the ligand comprises an amino acid sequence having at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% amino acid sequence identity with the amino acid sequence of a dAb selected from the group consisting of DOM9-155-77 (SEQ ID NO: 2426) , DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-204 (SEQ ID NO.2428), DOM9-112-205 (SEQ ID NO: 2429), DOM9-112-206 (SEQ ID NO: 2430), DOM9-112-207 (SEQ ID NO: 2431), DOM9-112-208 (SEQ ID NO.2432), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434), DOM9-112-21 1 (SEQ ID NO: 2435), DOM9-112-212 (SEQ ID NO.2436), DOM9-112-213 (SEQ ID NO: 2437), DOM9-112-214 (SEQ ID NO: 2438), DOM9-112-215 (SEQ ID NO: 2439), DOM9-112-216 (SEQ ID NO: 2440), DOM9-112-217 (SEQ ID NO: 2441), DOM9-112 -218 (SEQ ID NO.2442), DOM9-112-219 (SEQ ID NO: 2443 ), DOM9-112-220 (SEQ ID NO.2444), DOM9-112-221 (SEQ ID NO: 2445), DOM9-112-222 (SEQ ID NO: 2446), DOM9-112-223 (SEQ ID NO. : 2447), DOM9-112-224 (SEQ ID * NO: 2448), DOM9-112-225 (SEQ ID NO: 2449), DOM9-112-226 (SEQ ID NO: 2450), DOM9-112-227 ( SEQ ID NO.2451), DOM9-112-228 (SEQ ID NO: 2452), DOM9-112-229 (SEQ ID NO: 2453), DOM9-112-230 (SEQ ID NO: 2454), DOM9-112- 231 (SEQ ID NO: 2455), DOM9-112-233 (SEQ ID NO: 1734), D0M9-112-232 (SEQ ID NO: 1733) and D0M9-112-234 (SEQ ID NO: 1735). In other embodiments, the isolated and / or recombinant nucleic acid comprises a nucleotide sequence encoding a ligand having binding specificity for IL-13, as described herein, wherein the ligand comprises an amino acid sequence having at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% amino acid sequence identity with the amino acid sequence of a dAb selected from the group consisting of at DOM10-53 (SEQ ID NO: 967), DOM 10-53-1 (SEQ ID NO: 968), DOM10-53-2 (SEQ ID NO: 969), DOM10-53-3 (SEQ ID NO: 970) ), DOM10-53-4 (SEQ ID NO: 971), DOM 10-53-5 (SEQ ID NO: 972), DOM10-53-6 (SEQ ID NO: 973), DOM 10-53-7 (SE Q ID NO: 974), DOM10-53-8 (SEQ ID NO: 975), DOM10-53-9 (SEQ ID NO: 976), DOM10-53-10 (SEQ ID NO: 977), DOM10-53- 11 (SEQ ID NO: 978), DOM10-53-12 (SEQ ID NO: 979), DOM10-53-13 (SEQ ID NO: 980), DOM10-53-14 (SEQ ID NO: 981), DOM10- 53-15 (SEQ ID NO: 982), DOM10-53-16 (SEQ ID NO: 983), DOM10-53- 17 (SEQ ID NO: 984), DOM10-53-18 (SEQ ID NO: 985), DOM10-53-19 (SEQ ID NO: 986), DOM10-53-20 (SEQ ID NO: 987), DOM10- 53-21 (SEQ ID NO: 988), DOM 10-53-122 (SEQ ID NO: 989), DOM10-53-123 (SEQ ID NO: 990), DOM10-53-24 (SEQ ID NO: 991) , DOM10-53-25 (SEQ ID NO: 992), DOM10-53-26 (SEQ ID NO: 993), DOM10-53-27 (SEQ ID NO: 994), DOM10-53-28 (SEQ ID NO: 995), DOM10-53-29 (SEQ ID NO: 996), DOM10-53-30 (SEQ ID NO: 997), DOM 10-53-31 (SEQ ID NO: 998), DOM10-53-32 (SEQ. ID NO: 1999) f DOM10-53-43 (SEQ ID NO: 1000), DOM10-53-44 (SEQ ID NO: 1001), DOM10-53-45 (SEQ ID NO: 1002), DOM10-53-46 (SEQ ID NO: 1003), DOM10-53-47 (SEQ ID NO: 1004), DOM10-53-48 (SEQ ID NO: 1005), DOM10-53-49 (SEQ ID NO: 1006), DOM10-53 -50 (SEQ ID NO: 1007), DOM10-53-51 (SEQ ID NO: 1008), DOM10-53-52 (SEQ ID NO: 1009), DOM10-53-53 (SEQ ID NO: 1010), DOM 10-53-54 (SEQ ID NO: 1011), DOM10-53-55 (SEQ ID NO: 1012), DOM10-53-56 (SEQ ID NO: 1013), DOM10-53-57 (SEQ ID NO: 1014) ), DOM10-53-59 (SEQ ID NO: 1015), DOM10-53-60 (SEQ ID NO: 1016), DOM10-53-61 (SEQ ID NO: 1017) , DOM10-53-62 (SEQ ID NO: 1018), DOM10-53-63 (SEQ ID NO: 1019), DOM10-53-64 (SEQ ID NO: 1020), DOM10-53-65 (SEQ ID NO: 1021), DOM10-53-66 (SEQ ID NO: 1022), DOM10-53-67 (SEQ ID NO: 1023), DOM10-53-68 (SEQ ID NO: 1024), DOM10-53-69 (SEQ ID NO: 1025), DOM10-53-70 (SEQ ID NO: 1026), DOM10-53-71 (SEQ ID NO: 1027), DOM10-53-72 (SEQ ID NO: 1028), DOM10-53-73 ( I KNOW THAT ID NO: 1029), DOM 10-53-74 (SEQ ID NO: 1030), DOM10-53-75 (SEQ ID NO.-1031), DOM10-53-76 (SEQ ID NO.1032), DOM10-53 -77 (SEQ ID NO: 1033), DOM 10-53-78 (SEQ ID NO: 1034), DOM10-53-79 (SEQ ID NO: 1035), DOM10-53-80 (SEQ ID NO: 1036), DOM10-53-81 (SEQ ID NO: 1037), DOM10-53-82 (SEQ ID NO: 1038), DOM10-53-83 (SEQ ID NO: 1039), DOM10-53-84 (SEQ ID NO: 1040) ), DOM10-53-85 (SEQ ID NO: 1041), DOM10-53-86 (SEQ ID NO: 1042), DOM10-53-87 (SEQ ID NO: 1043), DOM10-53-88 (SEQ ID NO. : 1044), DOM10-53-89 (SEQ ID NO: 1045), DOM10-53-91 (SEQ ID NO: 1046), DOM 10-53-92 (SEQ ID NO: 1047), DOM10-53-93 ( SEQ ID NO: 1048), DOM10-53-94 (SEQ ID NO: 1049), DOM10-53-95 (SEQ ID NO: 1050), DOM10-53-96 (SEQ ID NO: 1051), DOM10-53- 97 (SEQ ID NO: 1052), DOM10-53-98 (SEQ ID NO: 1053), DOM10-53-99 (SEQ ID NO: 1054), DOM10-53-100 (SEQ ID NO: 1055), DOM10- 53-103 (SEQ ID NO: 1056) DOM10-53-105 (SEQ ID NO: 1057), DOM10-53-106 (SEQ ID NO: 1058), DOM10-53-108 (SEQ ID NO: 1059), DOM10 -53-110 (SEQ ID NO: 1060), DOM10-53-111 (SEQ ID NO: 1061), DOM10-53-112 (SEQ. ID NO: 1062), DOM10-53-114 (SEQ ID NO: 1063), DOM10-53-115 (SEQ ID NO: 1064), DOM10-53-116 (SEQ ID NO: 1065), DOM10-53-117 (SEQ ID NO: 1066), DOM10-53-119 (SEQ ID NO: 1067), DOM10-53-120 (SEQ ID NO: 1068), DOM10-53-122 (SEQ ID NO: 1069), DOM10-53 -201 (SEQ ID NO: 1070), DOM10-53-203 (SEQ ID NO: 1071), DOM10-53-204 (SEQ ID NO: 1072), DOM10-53-205 (SEQ ID NO: 1073), DOM10-53-206 (SEQ ID NO: 1074), DOM 10-53-207 (SEQ ID NO: 1075), DOM10-53-208 (SEQ ID NO: 1076), DOM10-53-209 (SEQ ID NO: 1077), DOM10-53-210 (SEQ ID NO: 1078), DOM10-53-23 1 (SEQ ID NO: 1079), DOM10-53-213 (SEQ ID NO: 1080), DOM10-53-214 (SEQ. ID NO: 1081), DOM10-53-215 (SEQ ID NO: 1082), DOM10-53-216 (SEQ ID NO: 1083), DOM10-53-217 (SEQ ID NO: 1084), DOM10-53-1218 (SEQ ID NO: 1085), DOM10-53-219 (SEQ ID NO: 1086), DOM10-53-220 (SEQ ID NO: 1087), DOM10-53-221 (SEQ ID NO: 1088), DOM 10- 53-222 (SEQ ID NO: 1089), DOM10-53-223 (SEQ ID NO: 1090), DOM10-53-224 (SEQ ID NO: 1091), DOM10-53-225 (SEQ ID NO: 1092), DOM10-53-226 (SEQ ID NO: 1093), DOM10-53-227 (SEQ ID NO: 1094), DOM10-53-228 (SEQ ID NO: 095), DOM10-53-229 (SEQ ID NO: 1096) ), DOM10-53-230 (SEQ ID NO: 1097), DOM10-53-231 (SEQ ID NO: 1098), DOM10-53-232 (SEQ ID NO: 1099), DOM10-53-233 (SEQ ID NO. : 1100), DOM10-53-234 (SEQ ID NO: 1101), DOM10-53-235 (SEQ ID NO: 1102), DOM10-53-236 (SEQ ID NO: 1103), DOM10-53-237 (SEQ. ID NO: 1104), DOM10-53-238 (SEQ ID NO: 1105), DOM 10-53-239 (SEQ ID NO: 1106), DOM10-53-240 (SEQ ID NO: 1107), DOM10-53-241 (SEQ ID NO: 1108), DOM10-53-242 (SEQ ID NO: 1109) ), DOM10-53-243 (SEQ ID NO: 1HO), DOM10-53-244 (SEQ ID NO: 1111), DOM10-53-245 (SEQ ID NO: 1112), DOM10-53-246 (SEQ ID NO. : 1113), DOM10-53-247 (SEQ ID NO: 1114), DOM10-53-248 (SEQ ID NO: 1115), DOM10-53-249 (SEQ ID NO: 1116), DOM10-53-250 (SEQ. ID N0: 1117), DOM10-53-251 (SEQ ID N0: 1118), DOM10-53-252 (SEQ ID N0: 1119), DOM 10-53-253 (SEQ EDNO: 1120), DOM10-53-254 ( SEQ ID NO: 1121), DOM10-53-255 (SEQ ID NO: 1122), DOM10-53-256 (SEQ ID NO: 1123), DOM10-53-257 (SEQ ID NO: 1124), DOM10-53- 258 (SEQ ID NO: 1125), DOM10-53-259 (SEQ ID NO: 1126), DOM10-53-260 (SEQ ID NO: 1127), DOM10-53-261 (SEQ ID NO: 1128), DOM10- 53-262 (SEQ ID NO: 1129), DOM10-53-263 (SEQ ID NO: 1130), DOM10-53-264 (SEQ ID NO: 1131), DOM10-53-265 (SEQ ID NO: 1132), DOM10-53-266 (SEQ ID NO: 1133), DOM10-53-267 (SEQ ID NO: 1134), DOM10-53-26S (SEQ ID NO: 1135), DOM10-53-269 (SEQ ID NO: 1136) ), DOM10-53-270 (SEQ ID NO: 1137), ° DOM10-53-271 (SEQ ID NO: 1138), DOM10-53-272 (SEQ ID NO: 1139), DOM10-53-273 (SEQ ID NO: 1140), DOM10-53-274 (SEQ ID NO: 1141), DOM10-53-275 (SEQ ID NO: 1142), DOM10-53-276 (SEQ ID NO: 1143), DOM10-53-277 ( SEQ ID NO: 1144), DOM10-53-278 (SEQ ID NO: 1145), DOM10-53-279 (SEQ ID NO: 1146), DOM10-53-280 (SEQ ID NO: 1147), DOM10-53- 281 (SEQ ID NO: 1148), DOM10-53-282 (SEQ ID NO: 114 9), DOM10-53-283 (SEQ ID NO: 1150), DOM10-53-284 (SEQ ID NO: 1151), DOM10-53-285 (SEQ ID NO: 1152), DOM 10-53-286 (SEQ. ID NO: 1153), DOM10-53-287 (SEQ ID NO: 1154), DOM10-53-288 (SEQ ID NO: 1155), DOM10-53-289 (SEQ ID NO: 1156), DOM10-53-290 (SEQ ID NO: 1157), DOM10-53-291 (SEQ ID NO: 1158), DOM 10-53-292 (SEQ ID NO: 1159), DOM10-53-293 (SEQ ID NO: 1160), DOM10- 53-294 (SEQ ID N0: 1161), DOM10-53-295 (SEQ ID NO: 1162), DOM10-53-296 (SEQ ID NO: 1163), DOM10-53-297 (SEQ ID NO: 1164), DOM10-53 -298 (SEQ ID NO: 1165), DOM10-53-299 (SEQ ID NO: 1166), DOM 10-53-300 (SEQ ID NO: 1167), DOMIO-53-301 (SEQ ID NO: 1168), DOM10-53-302 (SEQ ID NO: 1169), DOM10A53 ~ 303 (SEQ ID NO: 1170), DOM10-53-304 (SEQ ID NO 171), DOM10-53-305 (SEQ ID NO: 1172), DOM10 -53-306 (SEQ ID NO: 1173), DOM10-53-307 (SEQ ID NO: 1174), DOM10-53-308 (SEQ ID NO: 1175), DOM10-53-309 (SEQ ID NO: 1176) , DOM10-53-310 (SEQ ID NO: 11787), DOM10-53-311 (SEQ ID NO: 1178), DOM 10-53-312 (SEQ ID NO: 1179), DOM10-53-314 (SEQ ID NO. : 1180), DOM10-53-315 (SEQ ID NO: 1181), DOM10-53-316 (SEQ ID NO: 1182), DOM10-53-317 (SEQ ID NO: 1183), DOM10-53-318 (SEQ ID NO: 1184), DOM10-53-319 (SEQ ID NO: 1185), DOM10-53-320 (SEQ ID NO: 1186), DOM10-53-321 (SEQ ID NO: 1187), DOM10-53-322 (SEQ ID NO: 1188), DOM10-53-323 (SEQ ID NO: 1189), DOM10-53-324 (SEQ ID NO: 1190), DOM10-53-325 (SEQ ID NO: 1191), DOM10-53 -326 (SEQ ID NO: 1192), DOM10-53-327 (SEQ I D NO: 1193), DOM10-53-328 (SEQ ID NO: 1194), DOM10-53-329 (SEQ ID NO: 1195), DOM10-53-330 (SEQ ID NO: 1196), DOM10-53-331 (SEQ ID NO: 1197), DOM10-53-333 (SEQ ID NO: 1198), DOM 10-53-334 (SEQ ID NO: 1199), DOM10-53-336 (SEQ "NO: 1200), DOM10-53-337 (SEQ ID NO: 1201), DOM10-53-338 (SEQ ID NO: 1202), DOM10-53-339 (SEQ ID NO: 1203), DOM10-53-340 (SEQ ID NO: 1204) ), DOM10-53-341 (SEQ ID NO: 1205), DOM10-53-342 (SEQ ID NO: 1206), DOM10-53-343 (SEQ ID NO: 1207), DOM10-53-344 (SEQ ID NO: 1208) ), DOM10-53-345 (SEQ ID NO: 1209), DOM10-53-346 (SEQ ID NO: 1210), DOM10-53-347 (SEQ ID N0: 1211), DOM10-53-348 (SEQ ID NO. : 1212), DOM 10-53-349 (SEQ ID NO: 1213), DOM10-53-350 (SEQ ID NO: 1214), DOM10-53-351 (SEQ ID NO: 1215), DOM10-53-352 ( SEQ ID NO: 1216), DOM10-53-353 (SEQ ID NO: 1217), DOM10-53-354 (SEQ ID NO: 1218), DOM10-53-355 (SEQ ID NO: 1219), DOM10-53- 356 (SEQ ID NO: 1220), DOM10-53-357 (SEQ ID NO: 1221), DOM10-53-358 (SEQ ID NO: 1222), DOM10-53-359 (SEQ ID NO: 1223), DOM10- 53-360 (SEQ ID NO: 1224), DOM10-53-361 (SEQ ID NO: 1225), DOM10-53-362 (SEQ ID NO: 1226), DOM10-53-363 (SEQ ID NO: 227) , DOM10-53-364 (SEQ ID NO: 1228), DOM10-53-365 (SEQ ID NO: 1229), DOM10-53-366 (SEQ ID NO: 1230), DOM10-53-367 (SEQ ID NO: 1231), DOM 10-53-368 (SEQ ID NO: 1232), DOM10-53-369 (SEQ ID NO: 1233), DOM10-53-370 (SEQ ID NO: 1234), DOM10-53-371 (SEQ. ID NO.1235), DOM10-53-372 (SEQ ID NO: 1236), DOM1 0-53-373 (SEQ ID NO: 1237), DOM10-53-374 (SEQ ID NO: 1238), DOM10-53-375 (SEQ ID NO: 1239), DOM10-53-376 (SEQ ID NO: 1240 ), DOM10-53-377 (SEQ ID NO: 1241), DOM10-53-378 (SEQ ID NO: 1242), DOM10-53-379 (SEQ ID NO: 1243), DOM10-53-380 (SEQ ID NO. : 1244), DOM10-53-381 (SEQ ID NO: 1245), DOM 10-53-382 (SEQ ID NO: 1246), DOM10-53-383 (SEQ ID NO: 1247), * DOM10-53-384 (SEQ ID NO: 1248), DOM10-53-385 (SEQ ID NO: 1249), DOM 10-53-386 (SEQ ID NO: 1250), DOM 10-53-387 (SEQ ID NO: 1251), DOM10-53 -388 (SEQ ID NO: 1252), DOM10-53-389 (SEQ ID NO: 1253), DOM10-53-390 (SEQ ID NO: 1254), DOM10-53-391 (SEQ ID NO: 1255), DOM10 -53-392 (SEQ ID NO: 1256), DOM10-53-393 (SEQ ID NO: 1257), DOM10-53-394 (SEQ ID NO: 1258), DOM10-53-395 (SEQ ID NO: 1259) , DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-400 (SEQ ID NO: 1261), DOM10-53-401 (SEQ ID NO: 1262), DOM10-53-402 (SEQ ID NO: 1263), DOM 10-53-403 (SEQ ID NO: 1264), DOM10-53-404 (SEQ ID NO: 1265), DOM10-53-405 (SEQ ID NO: 1266), DOM10-53-406 (SEQ. ID NO: 1267), DOM10-53-407 (SEQ ID NO: 1268); DOM10-53-408 (SEQ ID NO: 1269), DOM10-53-409 (SEQ ID NO: 1270), DOM10-53-410 (SEQ ID NO 271), DOM10-53-411 (SEQ ID NO: 1272) , DOM10-53-412 (SEQ ID NO: 1273), DOM10-53-413 (SEQ ID NO: 1274), DOM10-53-414 (SEQ ID NO: 1275), DOM10-53-415 (SEQ ID NO: 1276), DOM10-53-416 (SEQ ID NO: 1277), DOM10-53-417 (SEQ ID NO: 1278), DOM10-53-418 (SEQ ID NO: 1279), DOM10-53-419 (SEQ ID NO: 1280), DOM10-53-420 (SEQ ID NO: 1281), DOM10-53-421 (SEQ ID NO: 1282), DOM10-168 (SEQ ID NO: 1508), DOM10-169 (SEQ ID NO: 1509), DOM10-170 (SEQ ID NO: 1510), DOM10-171 (SEQ ID NO: 1511), DOM10-172 (SEQ ID NO: 1512), DOM10-173 (SEQ ID NO: 1513), DOM10-176 -4 (SEQ ID NO: 1514), DOM10-176-5 (SEQ ID NO: 1515), DOM10-176-6 (SEQ ID NO: 1516), DOM10-176-23 (SEQ ID NO: 1517), DOM10 - 176-24 (SEQ ID NO: 1518), DOM10-176-25 (SEQ ID NO: 1519), DOM10-176-26 (SEQ ID NO: 1520), DOM10-176-27 (SEQ ID NO: 1521), DOM10-176-28 (SEQ ID NO: 1522), DOM10-176-29 (SEQ ID NO: 1523), DOM 1 O- 176-30 (SEQ ID NO: 1524), DOM10-176-31 (SEQ ID NO. : 1S25), DOM 10-176-32 (SEQ ID NO: 1526), DOM10-176-33 (SEQ ID NO: 1527), DOM10-176-34 (SEQ ID NO: 1528), DOM10-176-35 ( SEQ ID NO: 1529), DOM10-176-36 (SEQ ID NO: 1530), DOM10-176-37 (SEQ ID NO: 1531), DOM10-176-38 (SEQ ID NO: 1532), DOM10-176- 39 (SEQ ID NO: 1533), DOM10-176-40 (SEQ ID NO: 1534), DOM10-176-101 (SEQ ID NO: 1535), DOM 10-176-102 (SEQ ID NO: 1536), DOM 10- 176-103 (SEQ ID NO: 1537), DOM 10-176-104 (SEQ ID NO: 1538), DOM10-176-105 (SEQ ID NO.1539), DOM 10- 176-106 (SEQ ID NO. : 1540), DOM10-176-107 (SEQ ID NO: 1541), DOM 10-176-108 (SEQ ID NO: 1542), DOM 10-176-109 (SEQ ID NO: 1543), DOM10-176- 110 (SEQ ID NO: 1544), DOM10-176-111 (SEQ ID NO: 1545), DOM10-176-112 (SEQ ID NO: 1546), DOM 10-176-113 (SEQ ID NO: 1547), DOM10- 176-114 (SEQ ID NO: 1548), DOM10-176-115 ( SEQ ID NO: 1549), DOM 10-176-H6 (SEQ ID NO: 1550), DOM10-176-117 (SEQ ID NO: 1551), DOM 10-175-500 (SEQ ID NO: 1552), DOM10- 176-501 (SEQ ID NO: 1553), DOM 10-176-502 (SEQ ID NO: 1554), DOM10-176-503 (SEQ ID NO: 1555), DOM 10- 176-504 (SEQ ID NO: 1556 ), DOM 10- 176-505 (SEQ ID NO: 1557), DOM10-176-506 (SEQ ID NO: 1558), DOM 10-176-507 (SEQ ID NO: 1559), DOM10-176-508 (SEQ. ID NO: 1560), DOM 10- 176-509 (SEQ ID NO: 1561), DOM10-176-510 (SEQ ID NO: 1562), D0M10-176-511 (SEQ ID N0.1563), DO 10-176-512 (SEQ IDN 0: 1564), DOM10-176-513 (SEQ ID NO: 1565), DOM 10-176-514 (SEQ ID NO: 1566), DOM10-176-515 (SEQ ID NO: 1567), DOM 10-176-516 (SEQ ID NO: 1568), DOM10-176-517 ( SEQ ID NO: 1569), DOM10-176-518 (SEQ ID NO: 1570), DOM10-176-519 (SEQ ID NO: 1571), DOM10-176-520 (SEQ ID NO: 1572), DOM 10- 176 -521 (SEQ ID NO: 1573), DOM10-176-522 (SEQ ID NO: 1574), DOM 10-176-523 (SEQ ID NO: 1575), DOM10-176-524 (SEQ ID NO: 1576), DOM 10- 176-525 (SEQ ID N0.1577), DOM10-176-526 (SEQ ID NO: 1578), DOM 10- 176-527 (SEQ ID NO: 1579), DOM 10-176-528 (SEQ ID NO: 1580), DOM10-176-529 (SEQ ID NO: 1581), DOM 10-176-530 (SEQ ID NO: 1582), DOM10-176-531 (SEQ ID NO: 1583), DOM 10- 176- 532 (SEQ ID NO: 1584), DOM 10- 176-533 (SEQ ID NO: 1585), DOM 10-176-534 (SEQ ID NO: 1586), DOM 10- 176-535 (SEQ ID NO: 1587) , DOM10-176-536 (SEQ ID NO.1588), DOM 10- 176-537 (SEQ ID NO: 1589), DOM10-176-538 (SEQ ID NO.1590), DOM 10-176-539 (SEQ ID NO: 1591), DOM10-176-54 0 (SEQ ID NO: 1592), DOM10-176-541 (SEQ ID NO: 1593), DOM 10- 176-542 (SEQ ID NO: 1594), DOM10-176-543 (SEQ ID NG: 1595), DOM 10-176-544 (SEQ ID NO: 1596), DOM10-176-545 (SEQ ID NO: 1597), DOM 10-176-546 (SEQ ID NO: 1598), DOM 10-176-S47 (SEQ ID NO. : 1599), DOM 10- 176-548 (SEQ ID NO: 1600), DOM10-176-549 (SEQ ID NO: 1601), DOM10-176-550 (SEQ ID NO: 1602), DOM10-176-551 ( SEQ ID NO: 1603), DOM10-176-552 (SEQ ID NO: 1604), DOM 10- 176-553 (SEQ ID NO: 1605), DOM 10-176-554 (SEQ ID NO: 1606), DOM 10- 176-555 (SEQ ID NO: 1607), DOM 10- 176-556 (SEQ ID NO: 1608), DOM10-176 -557 (SEQ ID NO: 1609), DOM 10-376-558 (SEQ ID NO: 1610), DOM10-176-559 (SEQ ID NO: 1611), DO M 10- 176-560 (SEQ EDNO: 1612) , DOM 10- 176-561 (SEQ ID NO: 1613), DOM10-176-562 (SEQ ID NO: 1614), DOM 10- 176-563 (SEQ ID NO: 1615), DOM10-176-564 (SEQ ID NO: 1616), DOM10-176-565 (SEQ ID NO: 1617), DOMI0-176-566 (SEQ ID NO: 1618), DOM 10-I76-567 (SEQ ID NO: 1619), DOM 10-176- 568 (SEQ ID NO: 1620), DOM10-176-569 (SEQ ID NO: 1621), DOM 10-í 76-570 (SEQ ID NO: 1622), DOM10-176-571 (SEQ ID NO: 1623), DOM 10-176-572 (SEQ ID NO: 1624), DOM 10-176-573 (SEQ ID NO: 1625), DOM 10-176-574 (SEQ ID NO: 1626), DOM 10-176-575 (SEQ. ID NO: 1627), DOM10-176-576 (SEQ ID NO: 1628), DOM 10- 176-577 (SEQ ID NO: 1629), DOM10-176-578 (SEQ ID NO: 1630), DOM10-176- 579 (SEQ ID NO: 1631), DOM10-176-580 (SEQ ID NO: 1632), DOM10-176-581 (SEQ ID NO: 1633), DOM 10 ~ I76 ~ 582 (SEQ ID NO: 1634), DOM10 -176-583 (SEQ ID NO: 1635), DOM 10-176-584 (SEQ ID NO: 1636), DOM10-176-585 (SEQ ID NO: 1637), DOM10-176-586 (SEQ ID NO: 1638), DOM 10-176-587 (SEQ ID NO: 1639), DOM10-376-588 (SEQ ID NO: 1640), DOM 10-176-589 (SEQ ID NO: 1641), DOM10-176-590 (SEQ ID NO: 1642), DOM 10-176-591 ( SEQ ID NO: 1643), DOM10-176-592 (SEQ ID NO: 1644), DOM 10- 176-593 (SEQ ID NO: 1645), DOM10-176-594 (SEQ ID NO: 1646), DOM10-176 -595 (SEQ ID NO: 1647), DOM 10-176-596 (SEQ ID NO: 1648), D0M10-176-597 (SEQ ID NO: 1649), DOM 10-176-598 (SEQ ID NO: 1650), DOM10-176-599 (SEQ ID NO.1651), DOM 10-176-600 (SEQ ID NO. : 1652), DOM 10- 176-601 (SEQ ID NO: 1653), DOM10-176-602 (SEQ ID NO: 1654), DOM 10-176-603 (SEQ ID NO: 1655), DOM10-176-604 (SEQ ID NO: 1656), DOM 10-176-605 (SEQ ID NO: 1657), DOM 10-176-606 (SEQ ID NO: 1658), DOM 10- 176-607 (SEQ ID NO: 1659), DOM 10-176-608 (SEQ ID NO: 1660), DOM10-176-609 (SEQ ID NO: 1661), DOM10-176-610 (SEQ ID NO: 1662), DOM10-176-611 (SEQ ID NO: 1663), DOM10-176-612 (SEQ ID NO: 1664), DOM10-176-613 (SEQ ID NO: 1665), DOM 10- 176-614 (SEQ ID NO: 1666), DOM10-176-615 (SEQ. ID NO: 1667), DOM10-176-616 (SEQ ID NO: 1668), DOM 10- 176-617 (SEQ ID NO: 1669), DOM10476-618 (SEQ ID NO: 1670), DO M 10- 176- 619 (SEQ ID NO: 1671), DOM 10-176-620 (SEQ ID NO: 1672), DOM 10-176-621 (SEQ ID NO: 1673), DO M 10- 176-622 (SEQ ID NO: 1674 ), DOM10-176-623 (SEQ ID NO: 1675), DOM 10- 176-624 (SEQ ID NO: 1676), DOM10-176-625 (SEQ ID NO: 1677), DOM 10- 176-626 (SEQ. ID NO: 1678), DOM 10- 176-627 (SEQ ID NO: 1679), DOM10-176-628 (SEQ ID NO: 1680), DOM 10- 176-629 (SEQ ID NO: 1681), DOM10-176-630 (SEQ ID NO: 1682), DOM 10 176-631 (SEQ ID NO: 1683), DOM10-176-632 (SEQ ID NO: 1684), DOM 10-176-633 (SEQ ID NO: 1685), DOM 10-176-634 (SEQ ID NO: 1686), DOM 10- 176-635 (SEQ ID NO: 1687), DOM 10- 176-636 (SEQ ID NO: 1688), DOM10-176-637 (SEQ ID NO: 1689), DOM 10-176-638 (SEQ ID NO: 1690), DOM10-176-639 (SEQ ID NO: 1691), DO M 10- 176-640 (SEQ ID NO: 1692), DOM 1 O- 176-641 (SEQ ID NO: 1693), DOM 10-176-643 (SEQ ID NO: 1694), DOM 10-176-644 (SEQ ID NO: 1695), DOM10- 176-645 (SEQ ID NO: 1696), DOM 10-176-646 (SEQ ID NO: 1697), DOM10-176-647 (SEQ ID NO: 1698), DOM 10- 176-648 (SEQ ID NO: 1699) ), DOM 10-176-649 (SEQ ID NO: 1700), DOM 10-176-650 (SEQ ID NO: 1701), DOM10-176-651 (SEQ ID NO: 1702), DOM10-176-652 (SEQ. ID NO: 1703), DOM 10-176-653 (SEQ ID NO: 1704), DOM10-176-654 (SEQ ID NO: 1705), DOM 10-176-655 (SEQ ID NO: 1706), DOM 10- 176-656 (SEQ ID NO: 1707), DOM 10-176-657 (SEQ ID NO: 1708), DOM 10-176-658 (SEQ ID NO: 1709), DOM10-176-659 (SEQ ID NO: 1710 ), DOM 10-176-660 (SEQ ID NO: 1711), DOM10-176-661 (SEQ ID NO: 1712), DOM 0-176-662 (SEQ ID NO 713), DOM10-176-663 (SEQ ID NO: 1714), DOM 10- 176-664 (SEQ ID NO: 1715), DOM 10-176-665 (SEQ ID N0.1716), DOM10-176-666 (SEQ ID NO: 1717), DOM 10- 176 -667 (SEQ ID NO: 1718), DOM10-176-668 (SEQ ID NO: 1719), DOM 10-176-669 (SEQ ID NO: 1720), DOM 10-176-670 (SEQ ID NO 721), DO M 10- 176-67 (SEQ ID NO: 1722), DOM 10 -176-672 (SEQ ID NO: 1723), DOM10-176-673 (SEQ ID NO: 1724), DOM 10-176-674 (SEQ ID NO: 1725), DOM10-176-675 (SEQ ID NO: 1726) ), DOM10-253 (SEQ ID NO: 1727), DOM10-255 (SEQ ID NO: 1728), DOM10-272 (SEQ ID NO: 1729), DOM10-307 (SEQ ID NO: 1730), DOM10-319 ( SEQ ID NO: 1731) and DOM10-319-1 (SEQ ID NO: 1732. In other embodiments, the isolated and / or recombinant nucleic acid comprises a nucleotide sequence that encodes a ligand having binding specificity for IL-13, as described herein, wherein the ligand comprises an amino acid sequence having at least about 80%, at least about 85%, at least about 90% , at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% amino acid sequence identity with the amino acid sequence of a dAb selected from the group consisting of DOM10 -236 (SEQ ID NO 2129) DOM10 -238 (SEQ ID NO: 2130), DOM10 -241 (SEQ ID NO 2131) DOM10 -245 (SEQ ID NO: 2132), DOM10 -249 (SEQ ID NO 2133) DOM10 -250 (SEQ ID NO: 2134), DOM10 -251 (SEQ ID NO 2135) DOM10 -254 (SEQ ID NO: 2136), DOM10 -256 (SEQ ID NO 2137) DOM10 -259 (SEQ ID NO: 2138), DOM10 -260 (SEQ ID NO 2139) DOM10 -261 (SEQ ID NO: 2140), DOM10 -263 (SEQ ID NO 2141) DOM10 -264 (SEQ ID NO: 2142), DOM10 -273 (SEQ ID NO 2143) DOM10 -278 (SEQ ID NO: 2144), DOM10 -279 (SEQ ID NO 2145) DOM10 -281 (SEQ ID NO: 2146), DOM10 -282 (SEQ ID NO 2147), DOM10 -283 (SEQ ID NO: 2148), DOM10 -400 (SEQ ID NO 2149), DOM10 -401 (SEQ ID NO: 2150), DOM10 -402 (SEQ ID NO 2351), DOM10 -404 (SEQ ID NO: 2152), DOM10 -406 (SEQ ID NO 2153), DOM10 -407 (SEQ ID NO: 2154), DOM10 -409 (SEQ ID NO: 2155) DOM10 -410 (SEQ ID NO: 2156), DOM10 -414 (SEQ ID NO: 2157) DOM10 -415 (SEQ ID NO: 2158), DOM10 -416 (SEQ ID NO: 2159) DOM10 -418 (SEQ ID NO: 2160), DOM10 -420 (SEQ ID NO: 2161) DOM10 -422 (SEQ ID NO: 2162), DOM10 -423 (SEQ ID NO: 2163) DOM10 -424 (SEQ ID NO: 2164), DOM10 -425 (SEQ ID NO: 2165) DOM10 -426 (SEQ ID NO: 2166), DOM10 -427 (SEQ ID NO 2167) DOM10 -428 (SEQ ID NO: 2168), DOM10 -429 (SEQ ID NO 2169) DOM10 -430 (SEQ ID NO: 2170), DOM10 -431 (SEQ ID NO 2171) DOM10 -432 (SEQ ID NO: 2172), DOM10 -433 (SEQ ID NO 2173) DOM10 -467 (SEQ ID NO: 2174), DOM10 -468 (SEQ ID NO 2175) DOM10 -469 (SEQ ID NO: 2176), DOM10 -470 (SEQ ID NO 2177) DOM10 -234 (SEQ ID NO.-2178), DOM10-235 (SEQ ID NO 2179) DOM10 -237 (SEQ ID NO: 2180), DOM10 -239 (SEQ ID NO 2181), OD 10 -240 (SEQ ID NO: 2182), DOM10 -242 (SEQ ID NO 2183) DOM10 -243 (SEQ ID NO: 2184), DOM10 -244 (SEQ ID NO 2185), DOM10 -246 (SEQ ID NO: 2186), DOM10 -247 (SEQ ID NO 2187), DOM10 -248 (SEQ ID NO: 2188), DOM10 -252 (SEQ ID NO 2189), DOM10- -257 (SEQ ID NO: 2190), DOM10- -258 (SEQ ID NO 2191), DOM10- • 262 (SEQ ID NO.-2192), DOM10-265 (SEQ ID NO 2193), DOM10-266 (SEQ ID NO: 2194), DOM10-274 (SEQ ID NO 2195), DOM10-275 (SEQ ID NO: 2196), DOM10-276 (SEQ ID NO 2197), DOM10- |277 (SEQ ID NO: 2198), DOM10- | 280 (SEQ ID NO: 2199), DOM10- | 403 (SEQ ID NO: 2200), DOM10-405 (SEQ ID NO: 2201), DOM10- | 408 (SEQ ID NO: 2202), DOM10- | 411 (SEQ ID NO: 2203), DOM10-412 (SEQ ID NO: 2204), DOM10 -413 (SEQ ID NO 2205) DOM10 -417 (SEQ ID NO: 2206), DOM10 -419 (SEQ ID NO 2207) DOM10 -472 (SEQ ID NO: 2208), DOM10 -203 (SEQ ID NO 2209) DOM10 -205 (SEQ ID NO: 2210), DOM10 -208 (SEQ ID NO 2211) DOM10 -218 (SEQ ID NO: 2212), DOM10 -219 (SEQ ID NO 2213) DOM10 -220 (SEQ ID NO: 2214), DOM10-225 (SEQ ID NO 2215) DOM10 -228 (SEQ ID NO: 2216), DOM10 -229 (SEQ ID NO 2217) DOM10 -230 (SEQ ID NO: 2218), DOM10 -231 (SEQ ID NO 2219) DOM10 -268 (SEQ ID NO: 2220), DOM10 -201 (SEQ ID NO 2221) DOM10 -202 (SEQ ID NO: 2222), DOM10 -204 (SEQ ID NO 2223) DOM10 -206 (SEQ ID NO: 2224), DOM10 -207 (SEQ ID NO 2225) DOM10 -209 (SEQ ID NO: 2226), DOM10 -210 (SEQ ID NO 2227) DOM10 -211 (SEQ ID NO: 2228), DOM10 -213 (SEQ ID NO 2229) DOM10 -214 (SEQ ID NO: 2230), DOM10 -215 (SEQ ID NO 2233) DOM10 -216 (SEQ ID NO: 2232), DOM10 -217 (SEQ ID NO 2233) DOM10 -221 (SEQ ID NO: 2234), DOM10 -223 (SEQ ID NO 2235) DOM10 -224 (SEQ ID NO: 2236), DOM10 -227 (SEQ ID NO 2237) DOM10 -232 (SEQ ID NO: 2238), DOM10 -267 (SEQ ID NO 2239) DOM10 -270 (SEQ ID NO: 2240), DOM10-275- 1 (SEQ ID NO: 2241), DOM10-276 -2 (SEQ ID NO: 2242), DOM 10-276-3 (SEQ ID NO: 2243), DOM10-275-3 (SEQ ID NO: 2244), DOM 10-277-2 (SEQ ID NO: 2245), DOM 10-277-3 (SEQ ID NO: 2246), DOM10-273-1 (SEQ ID NO: 2247), DOM10-273-2 ( SEQ ID NO: 2248), DOM10-275-2 (SEQ ID NO: 2249), DOM10-275-4 (SEQ ID NO: 2250), DOM10-276-1 (SEQ ID NO: 2251), DOM10-276- 4 (SEQ ID NO: 2252), DOM10-277-1 (SEQ ID NO: 2253), DOM 10-275-13 (SEQ ID NO: 2254), DOM10-275-15 (SEQ ID NO: 2255), DOM10-275-20 (SEQ ID NO: 2256); DOM10-275-8 (SEQ ID NO: 2257), DOM 10-276-13 (SEQ ID NO: 2258), DOM10-276-14 (SEQ ID NO: 2259), DOM10-276-15 (SEQ ID NO: 2260), DOM 10-276-17 (SEQ ID NO: 2261), DOM10-276-7 (SEQ ID NO: 2262), DOM10-276-8 (SEQ ID NO: 2263), DOM10-275-11 (SEQ. ID NO: 2264), DOM10-275-12 (SEQ ID NO: 2265), DOM10-275-14 (SEQ ID NO: 2266), DOM10-275-16 (SEQ ID NO: 2267), DOM10-275- 17 (SEQ ID NO: 2268), DOM10-275-5 (SEQ ID NO: 2269), DOM10-275-6 (SEQ ID NO: 2270), DOM10-275-7 (SEQ ID NO: 2271), DOM10- 275-9 (SEQ ID NO: 2272), DOM10-276-10 (SEQ ID NO: 2273), DOM10-276-11 (SEQ ID NO: 2274), DOM10-276-12 (SEQ ID NO: 2275), DOM10-276-16 (SEQ ID NO: 2276), DOM10-276-5 (SEQ ID NO: 2277), DOM10-276-6 (SEQ ID NO: 2278), DOM10-276-9 (SEQ ID NO: 2279) ), DOM10-212 (SEQ ID NO: 2280), DOM10-53-424 (SEQ ID NO: 2281), DOM10-53-425 (SEQ ID NO: 2282), DOM10-53-426 (SEQ ID NO: 2283) ), DOM10-53-422 (SEQ ID NO: 2284), DOM10-53-423 (SEQ ID NO: 2255), DOM10-53-613 (SEQ ID NO: 2286), DOM10-53-517 (SEQ ID NO. : 2287), DOM10-53-519 (SEQ ID NO: 2288), DOM10-53-520 ( SEQ ID NO: 2289), DOM10-53-521 (SEQ ID NO: 2290), DOM10-53-522 (SEQ ID NO: 2291), DOM10-53-526 (SEQ ID NO: 2292), DOM10-53- 527 (SEQ ID NO: 2293), DOM10-53-528 (SEQ ID NO: 2294), DOM10-53-518 (SEQ ID NO: 2295), DOM10-53-523 (SEQ ID "NO: 2296), DOM10 -53-524 (SEQ ID NO: 2297), DOM10-53-525 (SEQ ID NO: 2298), DOM10-53-601 (SEQ ID NO: 2299), DOM10-53-602 (SEQ ID NO: 2300), DOM10-53 -605 (SEQ ID NO: 2301), DOM10-53-606 (SEQ ID NO: 2302), DOM10-53-607 (SEQ ID NO: 2303), DOM10-53-608 (SEQ ID NO: 2304), DOM10 -53-609 (SEQ ID NO: 2305), DOM10-53-610 (SEQ ID NO: 2306), DOM10-53-611 (SEQ ID NO.2307), DOM 10-53-612 (SEQ ID NO: 2308) ), DOM 10-53-603 (SEQ ID NO: 2309), DOM 10-53-604 (SEQ ID NO: 2310), DOM10-53-429 (SEQ ID NO: 2311), DOM10-53-432 (SEQ. ID NO: 2312), DOM10-53-433 (SEQ ID NO: 2313), DOM 10-53-435 (SEQ ID NO: 2314), DOM10-53-430 (SEQ ID NO: 2315), DOM10-53- 431 (SEQ ID NO: 2316), DOM10-53-434 (SEQ ID NO: 2317), DOM10-53-436 (SEQ ID NO: 2318), DOM10-53-437 (SEQ ID NO: 2319), DOM10- 53-438 (SEQ ID NO: 2320), DOM10-53-440 (SEQ ID NO: 2321), DOM10-53-439 (SEQ ID NO: 2322), DOM10-53-441 (SEQ ID NO: 2323), DOM10-53-442 (SEQ ID NO: 2324), DOM10-53-443 (SEQ ID NO: 2325), DOM10-53-444 (SEQ ID NO: 2326), DOM10-53-445 (SEQ ID NO: 2327), DOM10-53-446 (SEQ ID NO: 2328), DOM10-53-447 (SEQ ID NO: 2329), DOM10-53-449 (SEQ ID NO: 2330), DOM10-53-448 (SEQ ID NO: 2331), DOM10-53-450 (SEQ ID NO: 2332), DOM10-53-451 (SEQ ID NO: 2333), DOM10-53-452 (SEQ ID NO: 2334), DOM10-53-453 ( SEQ ID NO: 2335), DOM10-53-454 (SEQ ID NO: 2336), DOM10-53-455 (SEQ ID NO: 2337), DOM10-53-456 (SEQ ID NO: 2338), DOM10-53- 457 (SEQ ID NO: 2339), DOM10-53-458 (SEQ ID NO: 2340), DOM10- 53-459 (SEQ ID NO: 2341), D0M10-53-461 (SEQ ID NO: 2342), DOM10-53-462 (SEQ ID NO: 2343), DOM10-53-465 (SEQ ID NO: 2344), DOM10-53-466 (SEQ ID NO: 2345), DOM10-53-467 (SEQ ID NO: 2346), DOM10-53-468 (SEQ ID NO: 2347), DOM10-53-460 (SEQ ID NO: 2348) ), OD M 10-53-463 (SEQ ID NO: 2349), DOM10-53-464 (SEQ ID NO: 2350), DOM10-53-469 (SEQ ID NO: 2351), DOM10-53-471 (SEQ. ID NO: 2352), DOM10-53-470 (SEQ ID NO: 2353), DOM10-53-533 (SEQ ID NO: 2354), DOM10-53-534 (SEQ ID NO: 2355), DOM10-53-535 (SEQ ID NO: 2356), DOM10-53-537 (SEQ ID NO: 2357), DOM 10-53-538 (SEQ ID NO: 2358), DOM10-53-539 (SEQ ID NO: 2359), DOM10- 53-540 (SEQ ID NO: 23O), DOM10-53-531 (SEQ ID NO: 2361), DOM10-53-532 (SEQ ID NO: 2362), DOM10-53-536 (SEQ ID NO: 2363), DOM10-53-542 (SEQ ID NO: 2364), DOM10-53-541 (SEQ ID NO: 2365), DOM10-53-473 (SEQ ID NO: 2366), DOM10-53-472 (SEQ ID NO: 2367) ), DOM 10-53-475 (SEQ ID NO: 2368), DOM10-53-474 (SEQ ID NO: 2369), DOM10-53-543 (SEQ ID NO: 2370), DOM10-53-544 (SEQ ID NO: 2371), DOM10-53-545 (SEQ ID NO: 2372), DOM10-53- 548 (SEQ ID NO: 2373), DOM 10-53-546 (SEQ ID NO: 2374), DOM10-53-549 (SEQ ID NO: 2375), DOM10-53-547 (SEQ ID NO: 2376), DOM10 -53-550 (SEQ ID NO: 2377), DOM10-53-551 (SEQ ID NO: 2378), DOM10-53-560 (SEQ ID NO: 2379), DOM10-53-565 (SEQ ID NO: 2380) , DOM10-53-559 (SEQ ID NO: 2381), DOM10-53-561 (SEQ ID NO: 2382), DOM10-53-562 (SEQ ID NO: 2383), DOM10-53-563 (SEQ ID NO: 2384), DOM10-53-564 (SEQ ID NO: 2385), DOM10-53-566 (SEQ ID NO: 2386), DOM10-53-554 (SEQ ID NO: 2387), DOM10-53-552 (SEQ ID NO: 2388) ), DOM10-53-553 (SEQ ID NO: 2389), DOM10-53-558 (SEQ ID NO: 2390), DOM10-53-556 (SEQ ID NO: 2391) and DOM10-53-557 (SEQ ID NO. : 2392). In other embodiments, the isolated and / or recombinant nucleic acid encoding a ligand having binding specificity for IL-4, as described herein, wherein the nucleic acid comprises a nucleotide sequence having at least about 80% , at least approximately 85%. at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at at least about 97%, at least about 98%, or at least about 99% sequence identity with nucleotides with a nucleotide sequence encoding an anti-IL-4 dAb selected from the group consisting of DOM9-15 ( SEQ ID NO: 1), DOM9-17 (SEQ ID NO: 2), DOM9-23 (SEQ ID NO: 3), DOM9-24 (SEQ ID NO: 4), DOM9-25 (SEQ ID NO: 5) , DOM9-27 (SEQ ID NO: 6), DOM9-28 (SEQ ID NO: 7), DOM9-29 (SEQ ID NO: 8), DOM9-30 (SEQ ID NO: 9), DOM9-31 (SEQ ID NO: 10), DOM9-32 (SEQ ID NO: 11), DOM9-33 (SEQ ID NO: 12), DOM9-50 (SEQ ID NO: 13), DOM9-57 (SEQ ID NO: 14), DOM9-59 (SEQ ID NO: 15), DOM9-63 (SEQ ID N0: 16), DOM9-67 (SEQ ID NO: 17), DOM9-68 (SEQ ID NO: 18), DOM9-70 (SEQ ID NO: 19), DOM9 -79 (SEQ ID NO: 20), DOM9-82 (SEQ ID NO: 21), DOM9-86 (SEQ ID NO: 22), DOM9-94 (SEQ ID NO: 23), DOM9-108 (SEQ ID NO: 24), DOM9-112 (SEQ ID NO: 25), DOM9-112-1 (SEQ ID NO: 26), DOM9-112 -2 (SEQ ID NO27) DOM9 -112 -3 (SEQ ID NO: 28), DOM9-112-4 (SEQ ID NO-29) DOM9 -112 -5 (SEQ ID NO: 30), DOM9- 112 -6 (SEQ ID No. 31) DOM9-12 -7 (SEQ ID NO: 32), DOM9- 112 -8 (SEQ ID NO: 33) DOM9 -112 -9 (SEQ ID NO: 34), DOM9-112-10 (SEQ ID NO: 35), DOM9-112-11 (SEQ ID NO: 36), DOM9-112-12 (SEQ ID NO37), DOM9-112-13 (SEQ ID NO.38), DOM9- 112-14 (SEQ ID NO 39), DOM9 -112-15 (SEQ ID NO: 40), DOM9-112-16 (SEQ ID NO.41), DOM9-112-17 (SEQ ID NO: 42), DOM9-112-18 (SEQ ID NO.43), DOM9-112 -19 (SEQ ID NO: 44), DOM9-112-20 (SEQ ID NO.45), DOM9-112-21 (SEQ ID NO: 46), DOM9-112-22 (SEQ ID NO.47), DOM9-112-23 (SEQ ID NO: 48), DOM9- 112-25 (SEQ ID NO 49) DOM9 -112 -81 (SEQ ID NO: 50), DOM9- 112 -82 (SEQ ID NO 51), DOM9 -112 -83 (SEQ ID NO: 52), DOM9- 112-84 (SEQ ID NO 53) DOM9 -112 -85 (SEQ ID NO: 54), DOM9- 112-86 (SEQ ID NO 55) DOM9 -112 -87 (SEQ ID NO: 56), DOM9- 112 -88 (SEQ ID NO 57) DOM9 -112 -89 (SEQ ID NO: 58), DOM9- 112 -90 (SEQ ID NO 59) DOM9 -112 -91 (SEQ ID NO: 60), DOM9- 112 -92 (SEQ ID NO 61) DOM9 -112 -93 (SEQ ID NO: 62), DOM9- 112 -94 (SEQ ID NO. 63) DOM9 -112 -95 (SEQ ID NO: 64), DOM9-112-96 (SEQ ID NO. 65) DOM9 -1 2 -97 (SEQ ID NO: 66), DOM9-112-98 (SEQ ID NO: 67), DOM9-112-99 (SEQ ID NO: 68), DOM9-112-100 (SEQ ID NO: 69), DOM9-112-101 (SEQ ID NO: 70) ), DOM9-112-102 (SEQ ID NG: 71), D0M9-112-103 (SEQ ID NO: 72), DOM9-112-104 (SEQ ID NO: 73), DOM9-112-105 (SEQ ID NO. : 74), DOM9-112-106 (SEQ ID NO: 75), DOM9-112-107 (SEQ ID NO: 76), DOM9-112-108 (SEQ ID NO: 77), DOM9-112-109 (SEQ ID NO: 78), DOM9-112-110 (SEQ ID NO: 79), DOM9-112-111 (SEQ ID NO: 80), DOM9-112-112 (SEQ ID NO: 81), DOM9-112-113 (SEQ ID NO: 82), DOM9-112-114 (SEQ ID NO: 83), DOM9-112-115 (SEQ ID NO: 84), DOM9-112-116 (SEQ ID NO: 85), DOM9-112 -117 (SEQ ID NO: 86), DOM9-112-118 (SEQ ID NO: 87), DOM9-112-119 (SEQ ID NO: 88), DOM9-132-120 (SEQ ID NO: 89), DOM9 -112-121 (SEQ ID NO: 90), DOM9-112-122 (SEQ ID NO: 91), DOM9-112-123 (SEQ ID NO: 92), DOM9-112-124 (SEQ ID NO: 93) , DOM9-112-125 (SEQ ID NO: 94), DOM9-112-126 (SEQ ID NO: 95), DOM9-112-127 (SEQ ID NO: 96), DOM9-112-128 (SEQ ID NO: 97), DOM9-112-134 (SEQ ID NO: 98), DOM9-112-135 (SEQ ID NO: 99), DOM9-132-136 (SEQ ID NO: 100), DOM9-112-137 (S EQ ID NO: 101), DOM9-112-138 (SEQ ID NO: 102), "DOM9-112-140 (SEQ ID NO: 103), DOM9-112-141 (SEQ ID NO: 104), DOM9-112 -142 (SEQ ID NO: 105), DOM9-112-143 (SEQ ID NO: 106), DOM9-112-144 (SEQ ID NO: 107), DOM9-112-145 (SEQ ID NO: 108), DOM9 -112-146 (SEQ ID NO: 109), DOM9-112-147 (SEQ ID NO: 110), DOM9-112-148 (SEQ ID NO: 111), DOM9-112-149 (SEQ ID NO: 112) , DOM9-112-150 (SEQ ID NO: 113), DOM9-112-151 (SEQ ID N0114), DOM9-112-152 (SEQ ID NO: 115), DOM9-112-153 (SEQ ID NO: 1 16) , DOM9-112-154 (SEQ ID NO: 117), DOM9-112-155 (SEQ ID NO: 118), DO 9-112-156 (SEQ ID NO: 119), DOM9-112-157 (SEQ ID NO. .120), DOM9-112-158 (SEQ ID NO: 121), DOM9-112-159 (SEQ ID NO: 122), DOM9-112-160 (SEQ ID NO: 123), DOM9-112-161 (SEQ. ID NO: 124), DOM9-112-162 (SEQ ID NO: 125), DOM9-112-163 (SEQ ID NO: 126), DOM9-112-164 (SEQ ID NO: 127), DOM9-112-165 (SEQ ID NO: 128), DOM9-112-166 (SEQ ID NO: 129), DOM9-112-167 (SEQ ID NO: 130), DOM9-112-168 (SEQ ID NO: 131), DOM9-112 -169 (SEQ ID NO: 132), DOM9-112-170 (SEQ ID NO: 133), DOM9-112-171 (SEQ ID NO: 134), DOM9-112-172 (SEQ ID NO: 135), DOM9 -112-173 (SEQ ID NO: 136), DOM9-112-174 (SEQ ID NO: 137), DOM9-112-175 (SEQ ID NO: 138), DOM9-112-176 (SEQ ID NO: 139) , DOM9-112-177 (SEQ ID NO: 140), DOM9-112-178 (SEQ ID NO: 141), DOM9-112-179 (SEQ ID NO: 142), DOM9-112-180 (SEQ ID NO: 143), DOM9-112-181 (SEQ ID NO: 144), DOM9-112-182 (SEQ ID NO: 145), DOM9-112-1 83 (SEQ ID NO: 146), DOM9-112-184 (SEQ ID NO: 147), DOM9-112-185 (SEQ ID NO: 148), DOM9-112-186 (SEQ ID NO: 149), DOM9- 112-387 (SEQ ID NO: 150), DOM9-112-188 (SEQ ID NO: 151), DOM9-112-189 (SEQ ID NO: 152), DOM9-112-190 (SEQ ID NO: 153), DOM9-112-191 (SEQ ID NO: 154), DOM9-112-192 (SEQ ID NO: 155), DOM9-112-193 (SEQ ID NO: 156), DOM9-112-194 (SEQ ID NO: 157 ), DOM9-112-195 (SEQ ID NO: 158), DOM9-112-196 (SEQ ID NO: 159), DOM9-112-197 (SEQ ID NO: 160), DOM9-112-198 (SEQ ID NO: 161), DOM9-112-199 ( SEQ ID NO: 162), DOM9-112-200 (SEQ ID NO: 163), DOM9-112-201 (SEQ ID NO: 164), DOM9-112-202 (SEQ ID NO: 165) DOM9-120 (SEQ ID NO: 166), DOM9-121 (SEQ ID NO: 167), DOM9-122 (SEQ ID NO: 168), DOM9-123 (SEQ ID NO: 169), DOM9-124 (SEQ ID NO: 170), DOM9-125 (SEQ ID NO: 171), DOM9-128 (SEQ ID NO: 172), DOM9- -134 (SEQ ID NO: 173), DOM9- 136 (SEQ ID NO: 174), DOM9 -26 (SEQ ID NO: 349), DOM9- -35 (SEQ ID NO: 350), DOM9 -36 (SEQ ID NO: 351), DOM9-37 (SEQ ID NO: 352), DOM9 -38 (SEQ ID NO: 353), DOM9- -39 (SEQ ID NO: 354), DOM9 -40 (SEQ ID NO: 355), DOM9- -41 (SEQ ID NO: 356), DOM9 -43 (SEQ ID NO:, 357), DOM9- |44 (SEQ ID NO: 358), DOM9-44-500 (SEQ ID NO: 359), DOM9-44-501 (SEQ ID NO: 360), DOM9-44-502 (SEQ ID NO: 361), DOM9-44-503 ( SEQ ID NO: 362), DOM9-44-504 (SEQ ID NO: 363), DOM9-44-505 (SEQ ID NO: 364), DOM9-44-506 (SEQ ID NO: 365), DOM9-44- 507 (SEQ ID NO: 366), DOM9-44-509 (SEQ ID NO: 367), DOM9-44-510 (SEQ ID NO: 36S), DOM9-44-511 (SEQ ID NO: 369); DOM9-44-512 (SEQ ID NO: 370), DOM9-44-513 (SEQ ID NO: 373), DOM9-44-514 (SEQ ID NO: 372), DOM9-44-515 (SEQ ID NO: 373) ), DOM9-44-516 (SEQ ID NO: 374), DOM9-44-517 (SEQ ID NO: 375); DOM9-44-518 (SEQ ID NO: 376), DOM9-44-519 (SEQ ID NO: 377), DOM9-44-520 (SEQ ID NO.378), DOM9-44-521 (SEQ ID NO: 379) ), DOM9-44-522 (SEQ ID NO: 380), DOM9-44-523 (SEQ ID NO: 381), DOM9-44-524 (SEQ ID NO: 382), DOM9-44-525 (SEQ ID NO: 383), DOM9-44-526 ( SEQ ID NO: 384), DOM9-44-527 (SEQ ID NO: 385), DOM9-44-528 (SEQ ID NO: 386), DOM9-44-529 (SEQ ID NO: 387), D0M9-44- 530 (SEQ ID NO: 388), DOM9-44-531 (SEQ ID NO: 389), DOM9-44-532 (SEQ ID NO: 390), DOM9-44-533 (SEQ ID NO: 391), DOM9- 44-534 (SEQ ID NO: 392), DOM9-44-535 (SEQ ID NO: 393), DOM9-44-536 (SEQ ID NO: 394), DOM9-44-537 (SEQ ID NO: 395), DOM9-44-538 (SEQ ID NO: 396), DOM9-44-539 (SEQ ID NO: 397), DOM9-44-540 (SEQ ID NO: 398), DOM9-44-541 (SEQ ID NO: 399) ), DOM9-44-542 (SEQ ID NO: 400), DOM9-44-543 (SEQ ID NO: 401), DOM9-44-544 (SEQ ID NO: 402), DOM9-44-545 (SEQ ID NO. .403), DOM9-44-546 (SEQ ID NO: 404), DOM9-44-547 (SEQ ID NO: 405), DOM9-44-548 (SEQ ID NO.406), DOM9-44-549 (SEQ. ID NO: 407), DOM9-44-550 (SEQ ID NO: 408), DOM9-44-551 (SEQ ID NO: 409), DOM9-44-552 (SEQ ID NO: 410), DOM9-44-553 (SEQ ID NO: 411), DOM9-44-554 (SEQ ID NO: 412), DOM9-44-555 (SEQ ID NO: 413), DOM9-44-556 (SEQ ID NO: 414), OD 9- 44-557 (SEQ ID NO: 415), DOM9-44-558 (SEQ ID NO: 416), DOM9-44-559 (SEQ ID NO: 417), DOM9-44-560 (SEQ ID NO: 418), DOM9-44-561 (SEQ ID NO: 419), DOM9-44-562 (SEQ ID NO: 420), DOM9-44-563 (SEQ ID NO: 421), DOM9-44-564 (SEQ ID NO: 422) ), DOM9-44-565 (SEQ ID NO: 423), DOM9-44-566 (SEQ ID NO: 424), DOM9-44-625 (SEQ ID NO: 425), DOM9-44-626 (SEQ.

ID NO: 426), DOM9-44-627 (SEQ ID NO: 427), DOM9-44-628 (SEQ ID NO.428), DOM9-44-629 (SEQ ID NO: 429), DOM9-44-630 (SEQ ID NO: 430), DOM9-44-631 (SEQ ID NO: 431), DOM9-44-632 (SEQ ID NO: 432), DOM9-44-633 (SEQ ID NO: 433), DOM9-44 -634 (SEQ ID NO: 434), DOM9-44-636 (SEQ ID NO: 435), DOM9-44-637 (SEQ ID NO: 436), DOM9-44-639 (SEQ ID NO: 437), DOM9 -44-640 (SEQ ID NO: 438), DOM9-44-641 (SEQ ID NO: 439), DOM9-44-642 (SEQ ID NO: 440), DOM9-44-643 (SEQ ID NO: 441) , DOM9-44-644 (SEQ ID NO: 442), DOM9-45 (SEQ ID NO.443), DOM9-46 (SEQ ID NO.444), DOM9-47 (SEQ ID NO: 445), DOM9-48 (SEQ ID NO: 446), DOM9-143 (SEQ ID NO: 447), DOM9-144 (SEQ ID NO: 448), DOM9-146 (SEQ ID NO: 449), DOM9-152 (SEQ ID NO: 450 ), DOM9-155 (SEQ ID NO: 451), DOM9-155-001 (SEQ ID NO: 452), DOM9-155-3 (SEQ ID NO: 453), DOM9-155-5 (SEQ ID NO.454) ), DOM9-155-8 (SEQ ID NO: 455), DOM9-155-9 (SEQ ID NO: 456), DOM9-155-11 (SEQ ID NO: 457), DOM9-155-13 (SEQ ID NO. : 458), DOM9-155-14 (SEQ ID NO: 459), DOM9-155-17 (SEQ ID NO.460), DOM9-155-19 (SEQ ID NO: 461), DOM9 -155-20 (SEQ ID NO: 462), DOM9-155-22 (SEQ ID NO: 463), DOM9-155-23 (SEQ ID NO: 464), DOM9-155-24 (SEQ ID NO: 465) , DOM9-155-25 (SEQ ID NO: 466), DOM9-155-26 (SEQ ID NO: 467), DOM9-155-27 (SEQ ID NO: 468), DOM9-155-28 (SEQ ID NO: 469), DOM9-155-29 (SEQ ID NO: 470), DOM9-155-30 (SEQ ID NO: 471), DOM9-155-31 (SEQ ID NO: 472), DOM9-155-32 (SEQ ID NO.473), DOM9- 155-33 (SEQ ID NO: 474), DOM9-155-34 (SEQ ID NO: 475), D0M9-155-35 (SEQ ID NO: 476), DOM9-155-36 (SEQ ID NO: 477), DOM9-155-37 (SEQ ID NO: 478), DOM9-155-38 (SEQ ID NO: 479), D0M9-155-39 (SEQ ID NO: 480), DOM9-155-41 (SEQ ID NO: 481) ), DOM9-155-42 (SEQ ID NO: 482), DOM9-155-43 (SEQ ID NO: 483), D0M9- 155-44 (SEQ ID NO: 484), D0M9-155-45 (SEQ ID NO. : 485), DOM9-155-46 (SEQ ID NO: 486), DOM9-155-47 (SEQ ID NO: 487) DOM9-155-48 (SEQ ID NO: 488), DOM9-155-49 (SEQ ID NO: 489), DOM9-155-50 (SEQ ID NO: 490), DOM9-155-51 (SEQ ID NO: 491), DOM9-155-52 (SEQ ID NO: 492), DOM9-155-53 ( SEQ ID NO: 493), DOM9-158 (SEQ ID NO: 494), DOM9-160 (SEQ ID NO: 495), DOM9-161 (SEQ ID NO: 496), DOM9-162 (SEQ ID NO: 497) , DOM9-163 (SEQ ID NO: 498) and DOM9-164 (SEQ ID NO: 499). Preferably, the nucleotide sequence identity is determined throughout the length of the nucleotide sequence encoding the selected anti-IL-4 dAb. In other embodiments, the isolated and / or recombinant nucleic acid encoding a ligand having binding specificity for IL-4, as described herein, wherein the nucleic acid comprises a nucleotide sequence having at least about 80% , at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% nucleotide sequence identity with a nucleotide sequence that encodes an anti-IL-4 dAb selected from the group consisting of DOM9-155-77 (SEQ ID NO.2393), DOM9-155-78 (SEQ ID NO: 2394), DOM9-112-204 (SEQ ID NO: 2395), DOM9-112-205 (SEQ ID NO: 2396), DOM9-112-206 (SEQ ID NO: 2397), DOM9-112-207 (SEQ ID NO: 2398), DOM9-112-208 (SEQ ID NO: 2399) r DOM9-112-209 (SEQ ID NO: 2400), DOM9-112-210 (SEQ ID NO: 2401), DOM9-112-211 (SEQ ID NO: 2402), DOM9-112-212 ( SEQ ID NO: 2403), DOM9-112-213 (SEQ ID NO: 2404), DOM9-112-214 (SEQ ID NO: 2405), DOM9-112-215 (SEQ ID NO: 2406), DOM9-112- 216 (SEQ ID NO: 2407), DOM9-112-217 (SEQ ID NO: 2408), DOM9-112-218 (SEQ ID NO: 2409), DOM9-112-219 (SEQ ID NO: 2410), DOM9- 112-220 (SEQ ID NO: 2411), DOM9-112-221 (SEQ ID NO.2412), DOM9-112-222 (SEQ ID NO.2413), DOM9-112-223 (SEQ ID NO: 2414), SUN 9-112-224 (SEQ ID NO-, 2415), DOM9-112-225 (SEQ ID NO: 2416), DOM9-112-226 (SEQ ID NO: 2417), DOM9-112-227 (SEQ ID NO: 2418), DOM9-112-228 (SEQ ID NO: 2419), DOM9-112-229 (SEQ ID NO.2420), DOM9-112-230 (SEQ ID NO: 2421), DOM9-112-231 (SEQ ID NO.2422), DOM9-112-233 (SEQ ID NO: 2423), DOM9-112-232 (SEQ ID NO: 2424) and DOM9-112-234 (SEQ ID NO: 2425).

In other embodiments, the isolated and / or recombinant nucleic acid encoding a ligand having binding specificity for IL-13, as described herein, wherein the nucleic acid comprises a nucleotide sequence having at least about 80% , at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%? at least about 97%, at least about 98%, or at least about 99% nucleotide sequence identity with a nucleotide sequence encoding an anti-IL-13 dAb selected from the group consisting of DOM10-53 (SEQ ID NO: 651), DOM10-53-1 (SEQ ID NO: 652), DOM10-53-2 (SEQ ID NO: 653), DOM10-53-3 (SEQ ID NO: 654), DOM10-53 -4 (SEQ ID NO: 655), DOM10-53-5 (SEQ ID NO: 656), DOM 10-53-6 (SEQ ID NO: 657), DOM 10-53-7 (SEQ ID NO: 658) , DOM10-53-8 (SEQ ID NO: 659), DOM 10-53-9 (SEQ ID NO: 660), DOM10-53-10 (SEQ ID NO: 661), DOM10-53-11 (SEQ ID NO. : 662), DOM10-53-12 (SEQ ID NO: 663), DOM10-53-13 (SEQ ID NO: 664), DOM10-53-14 (SEQ ID NO: 665), DOM10-53-15 (SEQ. ID NO: 666), DOM10-53-16 (SEQ ID NO: 667), DOM10-53-17 (SEQ ID NO: 668); DOM10-53-18 (SEQ ID NO: 669), DOM10-53-19 (SEQ ID NO: 670), DOM10-53-20 (SEQ ID NO: 671), DOM10-53-21 (SEQ ID NO: 672), D0M10-53-122 (SEQ ID NO: 673), DOM10-53-123 (SEQ ID NO: 674), DOM10-53-24 (SEQ ID NO: 675), DOM10-53-25 ( SEQ ID NO: 676), DOM 10-53-26"(SEQ ID NO: 677), DOM10-53-27 (SEQ ID NO: 678), DOM10-53-28 (SEQ ID NO: 679), DOM10- 53-29 (SEQ ID NO: 680), DOM10-53-30 (SEQ ID NO: 681), DOM10-53-31 (SEQ ID NO: 682), DOM10-53-32 (SEQ ID NO: 683), DOM10-53-43 (SEQ ID NO: 684), DOM10-53-44 (SEQ ID NO: 685), DOM10-53-45 (SEQ ID NO: 686), DOM10-53-46 (SEQ ID NO: 687) ), DOM10-53-47 (SEQ ID NO: 688), DOM10-53-48 (SEQ ID NO: 689), DOM10-53-49 (SEQ ID NO: 690), DOM10-53-50 (SEQ ID NO. : 691), DOM10-53-51 (SEQ ID NO: 692), DOM10-53-52 (SEQ ID NO: 693), DOM10-53-53 (SEQ ID NO: 694), DOM10-53-54 (SEQ ID NO: 695), DOM10-53-55 (SEQ ID NO: 696), DOM 10-53-56 (SEQ ID NO: 697), DOM10-53-57 (SEQ ID NO: 698), DOM10-53- 59 (SEQ ID NO: 699), DOM10-53-60 (SEQ ID NO: 700), DOM10-S3-61 (SEQ ID NO: 701), DOM10-53-62 (SEQ ID NO: 702), DOM10- 53-63 (SEQ ID NO: 703), DOM10-53-64 (SEQ ID NO: 704), DOM 10-53-65 (SEQ ID NO: 705), DOM10-53-66 (SEQ ID NO: 706), DOM10-53-67 (SEQ ID NO: 707), DOM10-53-68 (SEQ ID NO: 708), DOM10-53-69 (SEQ ID NO: 709), DOM10-53-70 (SEQ ID NO: 710), DOM10-53-71 (SEQ ID NO: 71 1), DOM10-53-72 (SEQ ID NO: 712), DOM10-53-73 (SEQ ID NO: 713), DOM10-53-74 (SEQ ID NO: 714), DOM10-53-75 (SEQ ID NO: 715), DOM10-53-76 (SEQ ID NO: 716), DOM10-53-77 (SEQ ID NO: 717), DOM10-53 -78 (SEQ ID NO: 718), DOM 10-53-79 (SEQ ID NO: 719), DOM10-53-80 (SEQ ID NO: 720), DOM10-S3-81 (SEQ ID NO: 721), DOM10- 53-82 (SEQ ID NO: 722), DOM10-53-83 (SEQ ID NO: 723), DOM10-53-84 (SEQ ID NO: 724), DOM10-53-85 (SEQ ID NO: 725), DOM10-53-86 (SEQ ID NO: 726), DOM 10-53-87 (SEQ ID NO: 727), DOM30-53-88 (SEQ ID NO: 728), DOM10-53-89 (SEQ ID NO: 729), DOM10-53-91 (SEQ ID NO: 730), DOM10-53-92 (SEQ ID NO: 731), DOM10-53-93 (SEQ ID NO: 732), DOM10-53-94 (SEQ ID NO: 733), DOM10-53-95 (SEQ ID NO: 734), DOM10-53-96 (SEQ ID NO: 735), DOM 10-53-97 (SEQ ID NO: 736), DOM10-53-98 (SEQ ID NO: 737), DOM10-53-99 (SEQ ID NO: 738), DOM10-53-100 (SEQ ID NO: 739), DOM10-53-103 (SEQ ID NO: 740), DOM10-53 -105 (SEQ ID NO: 741), DOM10-53-106 (SEQ ID NO: 742), DOM10-53-108 (SEQ ID NO: 743), DOM10-53-110 (SEQ ID NO: 744), DOM10 -53-111 (SEQ ID NO: 745), DOM10-53-112 (SEQ ID NO: 746), DOM10-53-114 (SEQ ID NO.-747), DOMJO-53-115 (SEQ ID NO: 748) ), DOM10-53-116 (SEQ ID NO: 749), DOM10-53-117 (SEQ ID NO: 750), DOM10-53-119 (SEQ ID NO: 751), DOM10-5 3-120 (SEQ ID N0.752), DOM10-53-122 (SEQ ID NO: 753), * DOM10-53-201 (SEQ ID NO: 754), DOM10-53-203 (SEQ ID NO: 755) , DOM10-53-204 (SEQ ID NO: 756), DOM10-53-205 (SEQ ID NO: 757), DOM10-53-206 (SEQ ID NO: 758), DOM10-53-207 (SEQ ID NO: 759), DOM10-53-208 (SEQ ID NO: 760), DOM10-53-209 (SEQ ID NO: 761), DOM10-53-210 (SEQ ID NO: 762), DOM10-53-211 (SEQ ID NO: 763), DOM10-53-213 (SEQ ID NO: 764), DOM10-53-214 (SEQ ID NO: 765), DOM 10-53-215 (SEQ ID NO: 766), DOM10-53-216 (SEQ ID NO: 767), DOM10-53-217 (SEQ ID NO: 768), DOM10-53-218 (SEQ ID NO: 769), DOM10-53-219 (SEQ ID NO: 770), DOM10-53 -220 (SEQ ID NO.771). DOM 10-53-221 (SEQ ID NO: 772), DOM 10-53-222 (SEQ ID NO: 773), DOM30-53-223 (SEQ ID NO: 774) ), DOM10-53-224 (SEQ ID NO: 775), DOM10-53-225 (SEQ ID NO: 776), DOM10-53-226 (SEQ ID NO: 777), DOM10-53-227 (SEQ ID NO. : 778), DOM10-53-228 (SEQ ID NO: 779), DOM10-53-229 (SEQ ID NO: 780), DOM10-53-230 (SEQ ID NO: 781), DOM10-53-231 (SEQ. ID NO: 782), DOM10-53-232 (SEQ ID NO: 783), DOM10-53-233 (SEQ ID NO: 784), DOM10-53-234 (SEQ ID NO: 785), DOM10-53-235 (SEQ ID NO: 786), DOM10-53-236 (SEQ ID NO: 787), DOM10-53-237 (SEQ ID NO: 788), DOM10-53-238 (SEQ ID NO: 789), DOM10-53 -239 (SEQ ID NO: 790), DOM10-53-240 (SEQ ID NO: 791), DOM10-53-241 (SEQ ID NO: 792), DOM10-53-242 (SEQ ID NO: 793), DOM10 -53-243 (SEQ ID NO: 794), DOM10-53-244 (SEQ ID NO: 795), DOM10-53-245 (SEQ ID NO: 796) ), DOM10-53-246 (SEQ ID NO: 797), DOM10-53-247 (SEQ ID NO: 798), DOM10-53-248 (SEQ ID NO: 799), DOM10-53-249 (SEQ ID NO. : 800), DOM10-53-250 (SEQ ID NO: 801), DOM10-53-251 (SEQ ID NO: 802), DOM10-53-252 (SEQ ID NO: 803), DOM10-53-253 (SEQ ID NO: 804), DOM10-53-254 (SEQ ID NO: 805), DOM10-53-255 (SEQ ID NO: 806), DOM10-53-256 (SEQ ID NO: 807), DOM10-53-257 (SEQ ID NO: 808), DOM10-53-258 (SEQ ID NO: 809), DOM10-53-259 (SEQ ID NO: 810), DOM 10-53-260 (SEQ ID NO: 811), DOM10-53-261 (SEQ ID NO: 812), DOM10-53-262 (SEQ ID NO.813), DOM10-53-263 (SEQ ID NO.814), DOM10-53-264 (SEQ ID NO: 815), DOM10-53 -265 (SEQ ID NO: 816), DOM10-53-266 (SEQ ID NO: 817), DOM10-53-267 (SEQ ID NO: 818), DOM10-53-268 (SEQ ID NO: 819), DOM30 -53-269 (SEQ ID NO: 820), DOM10-53-270 (SEQ ID NO: 821), DOM10-53-271 (SEQ ID NO: 822), DOM10-53-272 (SEQ ID NO: 823) , DOM10-53-273 (SEQ ID NO: 824), DOM10-53-274 (SEQ ID NO: 825), DOM10-53-275 (SEQ ID NO: 826), DOM10-53-276 (SEQ ID NO: 827), DOM10-53-277 (SEQ ID NO: 828), DOM10-53-278 (SEQ ID NO: 829), DOM10-53-279 (SEQ ID NO: 830), DOM10-53-280 (SEQ ID NO: 831), DOM10-53-281 (SEQ ID NO: 832), DOM10-53-282 (SEQ ID NO: 833), DOM10-53-283 (SEQ ID NO: 834), 0 DOM10-53-284 (SEQ ID NO: 835), DOM10-53-285 (SEQ ID NO: 836), DOM 10-53-286 (SEQ ID NO: 837), DOM10-53-287 (SEQ ID NO: 838), DOM10- 53-288 (SEQ ID NO: 839), DOM10-53-289 (SEQ ID NO: 840), DOM10-53-290 (SEQ ID NO: 841) , DOM10-53-291 (SEQ ID NO: 842), DOM10-53-292 (SEQ ID NO: 843), DOM 10-53-293 (SEQ ID NO: 844), DOM10-53-294 (SEQ ID NO. : 845), DOM10-53-295 (SEQ ID NO: 846), DOM10-53-296 (SEQ ID NO: 847), DOM10-53-297 (SEQ ID NO: 848), DOM10-53-298 (SEQ ID NO: 849), DOM10-53-299 (SEQ ID NO: 850), DOM10-53-300 (SEQ ID NO: 851), DOM10-53-301 (SEQ ID NO: 852), DOM10-53-302 (SEQ ID NO: 853), DOM10-53-303 (SEQ ID NO: 854), DOM 10-53-304 (SEQ ID NO: 855), DOM 10-53-305 (SEQ ID NO: 856), DOM10-53- 306 (SEQ ID NO: 857), DOM10-53-307 (SEQ ID NO: 858), DOM10-53-308 (SEQ ID NO: 859), DOM10-53-309 (SEQ ID NO: 860), DOM10- 53-310 (SEQ ID NO: 861), DOM10-53-311 (SEQ ID NO: 862), DOM10-53-312 (SEQ ID NO: 863), DOM10-53-3] 4 (SEQ ID NO: 864) ), DOM10-53-315 (SEQ ID NO: 865), DOM10-53-316 (SEQ ID NO: 866), DOM10-53-317 (SEQ ID NO: 867), DOM10-53-318 (SEQ ID NO. : 868) DOM30-53-319 (SEQ ID NO: 869), DOM10-53-320 (SEQ ID NO: 870), DOM10-53-321 (SEQ ID NO: 871), DOM10-53-322 (SEQ ID NO: 872), DOM10-53-323 (SEQ ID NO: 873), DOM10-53-324 (SEQ ID NO: 874), DOM10-53-325 (SEQ ID NO: 875), DOM10-53-326 ( SEQ ID NO: 876), DOM10-53-327 (SEQ ID NO: 877), DOM10-53-328 (SEQ ID NO: 878), DOM10-53-329 (SEQ ID NO: 879), DOM10-53- 330 (SEQ ID NO: 880), DOM10-53-331 (SEQ ID NO: 88'1), DOM10-53-333 (SEQ ID NO: 882), DOM10-53-334 (SEQ ID NO: 883), DOM10-53-336 (SEQ ID NO: 884), DOM10-53-337 (SEQ ID NO: 885), DOM10-53-338 (SEQ ID NO: 886) , DOM10-53-339 (SEQ ID NO: 887), DOM10-53-340 (SEQ ID NO: 588), DOM10-53-341 (SEQ ID NO: 889), DOM10-53-342 (SEQ ID NO: 890), DOM10-53-343 (SEQ ID NO: 891), DOM10-53-344 (SEQ ID NO: 892), DOM10-53-345 (SEQ ID NO: 893), DOM10-53-346 (SEQ ID NO: 894), DOM10-53-347 (SEQ ID NO: 895), DOM10-53-348 (SEQ ID NO: 896), DOM10-53-349 (SEQ ID NO: 897), DOM10-53-350 ( I KNOW THAT ID N0.898), DOM10-53-351 (SEQ ID NO: 899), DOM10-53-352 (SEQ ID NO: 900), DOM10-53-353 (SEQ ID NO: 901), DOM10-53-354 (SEQ ID NO: 902), DOM 10-53-355 (SEQ ID NO: 903), DOM10-53-356 (SEQ ID NO: 904), DOM10-53-357 (SEQ ID NO: 905), DOM10- 53-358 (SEQ ID NO: 906), DOM10-53-359 (SEQ ID NO: 907), DOM10-53-360 (SEQ ID NO: 908), DOM 10-53-361 (SEQ ID NO: 909) , DOM10-53-362 (SEQ ID NO: 910), DOM10-53-363 (SEQ ID NO: 911), DOM10-53-364 (SEQ ID NO: 912), DOM10-53-365 (SEQ ID NO: 913), DOM10-53-366 (SEQ ID NO: 914), DOM10-53-367 (SEQ ID NO: 915), DOM 10-53-368 (SEQ ID NO: 916), DOM10-53-369 (SEQ. ID NO: 917), DOM10-53-370 (SEQ ID NO: 918), DOM10-53-371 (SEQ ID NO: 919), DOM10-53-372 (SEQ ID NO: 920), DOM10-53-373 (SEQ ID NO: 921), DOM10-53-374 (SEQ ID NO: 922), DOM10-53-375 (SEQ ID NO: 923), DOM10-53-376 (SEQ ID NO: 924), DOM10-53 -377 (SEQ ID NO: 925), DOM10-53-378 (SEQ ID NO: 926), DOM10-53-379 (SEQ ID NO: 927), DOM10-53-380 (SEQ ID NO: 928), DOM10 -53-381 (SEQ ID NO: 929), DOM10-53-382 (SEQ ID NO: 930), DOM10-53-383 (SEQ ID NO: 9) 31), DOM10-53-384 (SEQ ID NO: 932), DOM10-53-385 (SEQ ID NO: 933), DOM10-53-386 (SEQ ID NO: 934), DOM10-53-387 (SEQ ID NO: 935), DOM10-53-388 (SEQ ID NO: 936), DOM10-53-389 (SEQ ID NO: 937), DOM10-53-390 (SEQ ID NO: 938), DOM10-53-391 ( SEQ ID NO: 939), DOM10-53-392 (SEQ ID NO: 940), DOM10-53-393 (SEQ ID NO: 941), DOM10-53-394 (SEQ ID NO: 942), DOM10-53 -395 (SEQ ID NO: 943), DOM10-53-396 (SEQ ID NO: 944), DOM10-53-400 (SEQ ID NO: 945), DOM10-53-401 (SEQ ID NO: 946); DOM10-53-402 (SEQ ID NO: 947), DOM 10-53-403 (SEQ ID NO: 948), DOM10-53-404 (SEQ ID NO: 949), DOM10-53-405 (SEQ ID NO: 950), DOM10-53-406 (SEQ ID NO: 951), DOM10-53-407 (SEQ ID NO: 952), DOM10-53-408 (SEQ ID NO: 953), DOM 10-53-409 (SEQ. ID NO: 954), DOM10-53-410 (SEQ ID NO: 955), DOM10-53-411 (SEQ ID NO: 956), DOM10-53-412 (SEQ ID NO: 957), DOM10-53-413 (SEQ ID NO: 958), DOM10-53-414 (SEQ ID NO: 959), DOM10-53-415 (SEQ ID NQ,: 960), DOM10-53-416 (SEQ ID NO: 961), DOM10- 53-417 (SEQ ID NO: 962), DOM10-53-418 (SEQ ID NO: 963), DOM10-53-419 (SEQ ID NO: 964), DOM10-53-420 (SEQ ID NO: 965), DOM10-53-421 (SEQ ID NO: 966), DOM10-168 (SEQ ID NO: 1283), DOM10-169 (SEQ ID NO: 1284), DOM10-176 (SEQ ID NO: 1285), DOM 30-176 -1 (SEQ ID NO: 1286), DOM10-176-2 (SEQ ID NO: 1287), DOM10-176-3 (SEQ ID NO: 1288), DOM10-176-4 (SEQ ID NO: 1289), DOM10 -176-5 (SEQ ID NO: 1290), DOM10-176-6 (SEQ ID NO: 1291), DOM10-176-23 (SEQ ID NO: 1292), DOM10-176-24 (SEQ ID NO: 1293) , DOM10-176-25 (SEQ ID NO: 1294), DOM10-176-26 (SEQ ID NO: 1295), DOM10-17 6-27 (SEQ ID NO: 1296), DOM10-176-28 (SEQ ID NO: 1297), DOM10-176-29 (SEQ ID NO: 1298), DOM10-176-30 (SEQ ID NO: 1299), DOM10-176-31 (SEQ ID NO: 1300), DOM10-176-32 (SEQ ID NO: 130I), DOM10-176-33 (SEQ ID NO: 1302), DOM10-176-34 (SEQ ID NO: 1303) ), DOM10-I76-35 (SEQ ID NO: 1304), DOM10-176-36 (SEQ ID NO: 1305), DOM10-176-37 (SEQ ID NO: 1306), DOM10-176-38 (SEQ ID NO: 1307), DOM10-176 -39 (SEQ ID NO: 1308), DOM10-176-40 (SEQ ID NO: 1309), D0M10-176-101 (SEQ ID NO: 1310), DOM10-176-102 (SEQ ID No. 311), DOM10- 176-103 (SEQ ID NO: 1312), DOM10-176-104 (SEQ ID NO: 1313), DOM 10-176-105 (SEQ ID NO: 1314), DOM10-176-106 (SEQ ID NO: 1315) , DOM10-176-107 (SEQ ID NO: 1316), DOM 10-176-108 (SEQ ID NO: 1317), DOM 10-176-109 (SEQ ID NO: 1318), DOM 10-176-110 (SEQ. ID NO: 1319), DOM10-176-111 (SEQ ID NO: 1320), DOM 10-176-112 (SEQ ID NO: 1321), DOM10-176-113 (SEQ ID NO: 1322), DOM10-176- 114 (SEQ ID NO: 1323), DOM 10-176-115 (SEQ ID NO: 1324), DOM 10-176-116 (SEQ ID NO: 1325); DOM 10-176-117 (SEQ ID NO: 1326), DOM10-176-500 (SEQ ID NO: 1327), DOM10-176-501 (SEQ ID NO: 1328), DOM10-176-502 (SEQ ID NO: 1329), DOM 10- 176-503 (SEQ ID NO: 1330), DOM10-176-504 (SEQ ID NO: 1331), DOM 10-176-505 (SEQ ID NO: 1332), DOM 10- 176-506 (SEQ ID NO: 1333), DOM10-176-507 (SEQ ID NO: 1334), DOM 10-176-508 (SEQ ID NO: 1335), DOM10-176-509 (SEQ ID NO: 1336), DOM 10 176-510 (SEQ ID NO: 1337), DOM 10-176-511 (SEQ ID NO: 1338), DO M 10-176-512 (SEQ ID NO: 1339), DOM 10-176-513 (SEQ ID NO: 1340), DOM10-176-514 (SEQ ID NO: 1341), DOM 10- 176-51 S (SEQ ID NO: 1342), DOM10-176-516 (SEQ ID NO: 1343), DOM10-176- 5 M (SEQ ID NO.-1344), DOM10-176-518 (SEQ ID NO: 1345), DOM 10- 176-519 (SEQ ID NO: 1346), DOM10-176-520 (SEQ ID NO: 1347) , DOM10- 176-521 (SEQ ID NO: 1348), DOM10-176-522 (SEQ ID NO: 1349), DOM10-176-523 (SEQ ID NO: 1350), DOM 10-176-524 (SEQ ID NO: 1351) , DOM10-176-525 (SEQ ID NO: 3352), DOM 10-176-526 (SEQ ID NO: 1353), DOM 10- 176-527 (SEQ ID NO: 1354), DOM10-176-528 (SEQ ID NO: 1355), DOM10-176-529 (SEQ ID NO: 1356), DOM10-176-530 (SEQ ID NO: 1357), DOM 10-176-531 (SEQ ID NO: 1358), DOM10-176-532 (SEQ ID NO: 1359), DOM10-176-533 (SEQ ID NO: 1360), DOM 10-176-534 (SEQ ID NO: 1361), DOM10-176-535 (SEQ ID NO: 1362), DOM 10- 176-536 (SEQ ID NO: 1363), DOM10-176-537 (SEQ ID NO: 1364), DOM10-176-538 (SEQ ID NO: 1365), DOM 10-176-539 (SEQ ID NO: 1366), DOM 10-176-540 (SEQ ID NO: 1367), DOM 10- 176-541 (SEQ ID NO: 1368), DOM10-176-542 (SEQ ID NO: 1369), DOM 10-176-543 (SEQ ID NO: 1370), DOM10-176-544 (SEQ ID NO: 1371), DOM 10- 176-545 (SEQ ID NO: 1372), DOM10-176-546 (SEQ ID NO: 1373), DOM10 -176-547 (SEQ ID NO: 1374), DOM 10-176-548 (SEQ ID NO: 1375), DOM10-176-549 (SEQ ID NO: 1376), DOM 10-176-550 (SEQ ID NO: 1377), DOM10-176-551 (SEQ ID NO: 13 78), DO M 10- 176-552 (SEQ ID NO: 1379), DOM 10- 176-553 (SEQ ID NO: 1380), DOM 10-176-554 (SEQ ID NO: 1381), DOM 10-176 -555 (SEQ ID NO: 1382), DOM10-176-556 (SEQ ID NO: 1383), DOM 10-176-557 (SEQ ID NO: 1384), DOM10-176-558 (SEQ ID NO: 1385), DOM 10-176-559 (SEQ ID NO:] 386), DOM 10-I76-560 (SEQ ID NO: 1387), DOM 10-I76-56I (SEQ ID NO: 1388), DOM 10-176-562 ( SEQ ID NO: 1389), DOM10-176-563 (SEQ ID NO: 1390), DOM 10-176-564 (SEQ ID NO: 1391), DOM10-176-565 (SEQ ID NO: 1392), DOM 10-176-566 (SEQ ID NO: 1393), DOM 10-176-567 (SEQ ID NO: 1394), DOM 10- 176-568 (SEQ ID NO: 1395), DOM 10-176-569 (SEQ ID NO: 1396), DOM10-176-570 (SEQ ID NO: 1397), DOM10-176-571 (SEQ ID NO: 1398), DOM10-176-572 (SEQ ID NO: 1399), DOM 10- 176-573 (SEQ ID NO: 1400), DOM10-176-574 (SEQ ID NO: 1401), DOM10-176-575 (SEQ ID NO: 1402), DOM 10 176-576 (SEQ ID NO: 1403), DOM10-176-577 (SEQ ID NO: 1404), DOM 10-176-578 (SEQ ID NO: 1405), DOM10-176-579 (SEQ ID NO: 1406) ), DOM 10-176-580 (SEQ ID NO: 1407), DOM 10- 176-581 (SEQ ID O.1408), DOM10-176-582 (SEQ ID NO: 1409), DOM10-176-583 (SEQ. ID NO 410), DOM10-176-584 (SEQ ID NO: 1411), DOM 10- 176-585 (SEQ ID NO: 1412), DOM10-176-586 (SEQ ID NO: 1413), DOM 10- 176- 587 (SEQ ID NO: 1414), DOM 10-176-588 (SEQ ID NO: 1415), DOM 10- 176-589 (SEQ ID NO: 1416), DOM 10- 176-590 (SEQ ID NO: 1417) , DOM10-176-591 (SEQ ID NO: 1418), DOM10-176-592 (SEQ ID NO: 1419), DOM10-176-593 (SEQ ID NO: 1420), DOM 10-176-594 (SEQ ID NO. : 1421), DOM 10- 176-595 ( SEQ ID NO: 1422), OD M 10-176-596 (SEQ ID NO: 1423), DOM 10-176-597 (SEQ ID NO: 1424), DOM10-176-598 (SEQ ID NO: 1425), DOM 10-176-599 (SEQ ID NO: 1426), DOM10-176-600 (SEQ ID NO: 1427), DOM 10- 176-601 (SEQ ID NO: 1428), DOM 10-176-602 (SEQ ID NO. : 1429), DOM10-176-603 (SEQ ID NO: 1430), DOM 10- 176-604 (SEQ ID NO: 1431), DOM10-176-605 (SEQ ID NO: 1432), DOM 10-176-606 (SEQ ID NO: 1433), DOM10-176-607 (SEQ ID NO: 1434), DOM 10-176-608 (SEQ ID NO: 1435), D0M10-176-609 (SEQ ID NO: 1436), DOM 10- 176-6 0 (SEQ ID NO: 1437), DOM10-176-611 (SEQ ID NO: 1438), DOM10-176- 612 (SEQ ID NO: 1439), DOM 0-176-613 (SEQ ID NO: 1440), DOM10-176-614 (SEQ ID NO: 1441), J DOM 10-176-615 (SEQ ID NO: 1442) , DOM 10- 176-616 (SEQ ID NO: 1443), DOM10-176-617 (SEQ ID NO: 1444), DOM10-176-618 (SEQ ID NO: 1445), DOM10-176-619 (SEQ ID NO. : 1446), DOM 10-176-620 (SEQ ID NO: 1447), DOM10-176-621 (SEQ ID NO: 1448), DOM 10- 176-622 (SEQ ID NO: 1449), DOM 10-176- 623 (SEQ ID NO: 1450), DOM 10-176-624 (SEQ ID NO: 1451), DOM 10-176-625 (SEQ ID NO: 1452), DOM10-176-626 (SEQ ID NO: 1453), DOM 10- 176-627 (SEQ ID NO: 1454), DOM10-176-628 (SEQ ID NO: 1455), DOM 10- 176-629 (SEQ ID NO: 1456), DOM 10-176-630 (SEQ ID NO: 1457), DOM10-176-631 (SEQ ID NO: 1458), DOM 10-176-632 (SEQ ID NO: 1459), DOM10-176-633 (SEQ ID NO: 1460), DOM 10- 176- 634 (SEQ ID NO: 1461), DOM10-176-635 (SEQ ID NO: 1462), DOM 10-176-636 (SEQ ID NO: 1463), DOM 10-176-637 (SEQ ID NO: 1464), DOM 10-176-638 (SEQ ID NO: 1465), DOM 10- 176-639 (SEQ ID NO: 1466), DOM10-176-640 (SEQ ID NO: 1467), DOM 10- 176-641 (SEQ ID NO: 1468), DOM10-176-643 (SEQ ID NO: 1469) , DOM 10-176-644 (SEQ ID NO: 1470), DOM 10-176-645 (SEQ ID * NO: 1471), DOM 10-176-646 (SEQ ID NO: 1472), DOM 10-176-647 (SEQ ID NO: 1473), DOM10-176-648 (SEQ ID NO: 1474), DOM 10-176-649 (SEQ ID NO: 1475), DOM10-176-650 (SEQ ID NO: 1476), DOM 10 176-651 (SEQ ID NO: 1477), DOM 10-176-652 (SEQ ID NO: 1478), OJ M 10- 176-653 (SEQ ID NO: 1479), DOM 10-176-654 (SEQ ID NO: 1480), DOM10-176-655 (SEQ ID NO: 1481), DOM 10-176-656 (SEQ ID NO: 1482), DOM10 -376-657 (SEQ ID NO: 1483), DOM 10-176-658 (SEQ ID NO: 1484), DOM 10-176-659 (SEQ ID NO: 1485), DOM 10- 176-660 (SEQ ID NO. : 1486), DOM 10-176-661 (SEQ ID NO: 1487), DOM10-176-662 (SEQ ID NO: 1488), DOM 10- 176-663 (SEQ ID NO: 1489), DOM10-176-664 (SEQ ID NO: 1490), DOM 10- 176-665 (SEQ ID NO: 1491), DOM10-176-666 (SEQ IDN 0: 1492), DOM 10- 176-667 (SEQ ID NO: 1493), DOM 10-176-668 (SEQ ID NO: 1494), DOM10-176-669 (SEQ ID NO: 1495), DOM 10-176-670 (SEQ ID NO: 1496), DOM10-176-671 (SEQ ID NO: 1497), DOM 10- 176-672 (SEQ ID NO: 1498), DOM 10-176-673 (SEQ ID NO: 1499), DOM 10-176-674 (SEQ ID NO: 1500), DOM 10-176- 675 (SEQ ID NO: 1501), DOM10-253 (SEQ ID NO: 1502), DOM10-255 (SEQ ID NO: 1503), DOM10-272 (SEQ ID NO: 1504), DOM10-307 (SEQ ID NO: 1505), DOM10-319 (SEQ ID NO: 1506) and DOM10-319-1 (SEQ ID NO: 1507). Preferably, the nucleotide sequence identity is determined over the entire length of the nucleotide sequence encoding the selected anti-IL-13 dAb. In other embodiments, the isolated and / or recombinant nucleic acid encoding a ligand having binding specificity for IL-13, as described herein, wherein the nucleic acid comprises a nucleotide sequence has at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%, of nucleotide sequence identity with a nucleotide sequence encoding an anti-IL-13 dAb selected from the group consisting of DOM10-236 (SEQ ID.

NO: 1804), DOM30 -238 (SEQ ID NO 1805) DOM10 -241 (SEQ ID NO: 1806), DOM10 -245 [SEQ ID NO 1807) DOM10 -249 (SEQ ID NO: 1808), DOM10 -250 [SEQ ID NO 1809) DOM10 -251 (SEQ ID NO: 1810), DOM10 -254 |; SEQ ID NO 1811) DOM10 -256 (SEQ ID NO: 1812), DOM10 -259 |; SEQ ID NO 1813) DOM10 -260 (SEQ ID NO: 1814), DOM10 -261 (SEQ ID NO 1815) DOM10 -263 (SEQ ID NO: 1816), DOM10 -264 (SEQ ID NO 1817) DOM10 -273 (SEQ ID NO: 1818), DOM10 -278 (SEQ ID NO 1819) DOM10 -279 (SEQ ID NO: 1820), DOM10 -281 (SEQ ID NO 1821) DOM10 -282 (SEQ ID NO: 1822), DOM10 -283 (SEQ ID NO 1823) DOM10 -400 (SEQ ID NO: 1824), DOM10 -401 (SEQ ID NO 1825) DOM10 -402 (SEQ ID NO: 1826), DOM10 -404 (SEQ ID NO 1827), DOM10 -406 (SEQ ID NO: 1828), DOM10 -407 (SEQ ID NO 1829), DOM10 -409 (SEQ ID NO: 1830), DOM1C 1-410 (SEQ ID NO: 1831), DOM10 -414 (SEQ ID NO: 1832), DOM10 -415 (SEQ ID NO: 1833), DOM10 -416 (SEQ ID NO: 1834), DOM10 -418 (SEQ ID NO: 1835), DOM10 -420 (SEQ ID NO: 1836), DOM10 -422 (SEQ ID NO: 1837), DOM10 -423 (SEQ ID NO 1838) DOM10 -424 (SEQ ID NO 1839) DOM10 -425 (SEQ ID NO 1840) DOM10 -426 (SEQ ID NO 1841) DOM10 -427 (SEQ ID NO 1842) DOM10 -428 (SEQ ID NO 1843) DOM10 -429 (SEQ ID NO 1844) DOM10 -430 (SEQ ID NO 1845) DOM10 -431 (SEQ ID NO 1846) DOM10 -432 (SEQ ID NO 1847) DOM10 -433 (SEQ ID NO 1848) DOM10 -467 (SEQ ID NO 1849) DOM10 -468 (SEQ ID NO 1850) DOM10 -469 (SEQ ID NO 1851) DOM10 -470 (SEQ ID NO 1852) DOM10 -234 (SEQ ID NO 1853) DOM10 -235 (SEQ ID NO 1854) DOM10 -237 (SEQ ID NO 1855) DOM10 -239 (SEQ ID NO 1856) DOM10 -240 (SEQ ID NO 1857) DOM10 -242 (SEQ ID NO 1858) DOM10 -243 (SEQ ID NO 1859) DO 10 -244 (SEQ ID NO 1860) DOM10 -246 (SEQ ID NO 1861) DOM10 -247 (SEQ ID NO 1862) DOM10 -248 (SEQ ID NO 1863) DOM10 -252 (SEQ ID NO 1864) DOM10 -257 (SEQ ID NO 1865) DOM10 -258 (SEQ ID NO: 1866) DOM10 -262 (SEQ ID NO: 1867), DOM10 -265 (SEQ ID NO: 1868) DOM10 -266 (SEQ ID NO 1869) DO ??? -274 (SEQ ID NO: 1870) DOM10 -275 (SEQ ID NO1871) DOM10 -276 (SEQ ID NO: 1872) DOM10 -277 (SEQ ID NO: 1873), DOM10 -280 (SEQ ID NO: 1874), DOM10 -403 (SEQ ID NO: 1875), DOM10 -405 (SEQ ID NO: 1876), DOM10 -408 (SEQ ID NO: 1877), DOM10 -411 (SEQ ID NO: 1878), DOM10 -412 (SEQ ID NO: 1879), DOM10 -413 (SEQ ID NO: 1880), DOM10 -417 (SEQ ID NO: 1881), DOM10 -419 (SEQ ID NO: 1882), DOM10 -472 (SEQ ID NO: 1883), DOM10 -203 (SEQ ID NO: 1884), DOM10- -205 (SEQ ID NO: 1885), DOM10- -208 (SEQ ID NO: 1886), DOM10 -218 (SEQ ID NO: 1887), DOM10-219 (SEQ ID NO 1888) DOM10 -220 (SEQ ID NO 1889), DOM10-225 (SEQ ID NO 1890) DOM10 -228 (SEQ ID NO 1891), DOM10-229 (SEQ ID NO 1892) DOM10 -230 (SEQ ID NO: 1S93), DOM10-231 (SEQ ID NO 1894) DOM10 -268 (SEQ ID NO 1895), DOM10-201 (SEQ ID NO 1896) DOM10 -202 (SEQ ID NO 1897), DOM10- 204 (SEQ ID NO 1898) DOM10 -206 (SEQ ID NO 1899), DOM10-207 (SEQ ID NO 1900) DOM10 -209 (SEQ ID NO 1901), DOM10-210 (SEQ ID NO 1902) DOM10 -211 (SEQ ID NO 1903), DOM10-213 (SEQ ID NO 1904) DOM10 -214 (SEQ ID NO 1905), DOM10- 215 (SEQ ID NO 1906) DOM10 -216 (SEQ ID NO 1907), DOM10-217 (SEQ ID NO 1908) DOM10 -221 (SEQ ID NO 1909), DOM10-222 (SEQ ID NO 1910) DOM10 -224 (SEQ ID NO 1911), DOM10-227 (SEQ ID NO 1912) DOM10 -232 (SEQ ID NO 1913), DOM10-267 (SEQ ID NO 1914) DOM10 -270 (SEQ ID NO: 1915), DOM10-275 -1 (SEQ ID NO: 1918), DOM10-276-2 (SEQ ID NO: 1919), DOM10-276-3 (SEQ ID NO: 1920), DOM10-275-3 (SEQ ID NO: 1979), DOM10-277-2 (SEQ ID NO: 1980), DOM10-277-3 (SEQ ID NO: 1981), DOM10-273-1 (SEQ ID NO: 1982), DOM10-273-2 (SEQ ID NO: 1983), DOM 10-275-2 (SEQ ID NO: 1984), DOM 10-275-4 (SEQ ID NO: 1985), DOM 10-276 - 1 (SEQ ID NO: 1986), DOM 10-276-4 (SEQ ID NO: 1987), DOM10-277-1 (SEQ ID NO: 1988), DOM10-275-13 (SEQ ID NO: 1989), DOM10-275-15 (SEQ ID NO: 1990), DOM10-275-20 (SEQ ID NO: 1991), DOM10-275-8 (SEQ ID NO: 1992), DOM10-276-13 (SEQ ID NO: 1993) ), DOM10-276-14 (SEQ ID NO: 1994), DOM10-276-15 (SEQ ID NO: 1995), DOM10- 276-17 (SEQ ID NO: 1996), DOM10-276-7 (SEQ ID NO: 1997), DOM10-276-8 (SEQ ID NO: 1998), DOM10-275-11 (SEQ ID NO: 1999), DOM10-275-12 (SEQ ID NO: 2000), DOM10-275-14 (SEQ ID NO: 2001), DOM10-275-16 (SEQ ID NO: 2002), DOM10-275-17 (SEQ ID NO: 2003) ), DOM10: 275-5 (SEQ ID NO: 2004), DOM10-275-6 (SEQ ID NO: 2005), DOM10-275-7 (SEQ ID NO: 2006), DOM10-275-9 (SEQ ID NO. : 2007), DOM10-276-10 (SEQ ID NO: 2008), DOM10-276-11 (SEQ ID NO: 2009), DOM10-276-12 (SEQ ID NO: 2010), DOM10-276-16 (SEQ ID NO: 2011), DOM10-276-5 (SEQ ID NO: 2012), DOM10-276-6 (SEQ ID NO: 2013), DOM10-276-9 (SEQ ID NO: 2014), DOM10-212 (SEQ ID NO: 2016), DOM10-53-424 (SEQ ID NO: 2017), DOM10-53-425 (SEQ ID NO: 2018), DOM10-53-426 (SEQ ID NO: 2019), DOM10-53-422 (SEQ ID NO: 2020), DOM10-53-423 (SEQ ID NO: 2021), DOM10-53-613 (SEQ ID NO: 2022), DOM10-53-517 (SEQ ID NO: 2023), DOM20-53-519 (SEQ ID NO: 2024), DOM10-53-520 (SEQ ID NO: 2025), DOM10-53-521 (SEQ ID NO: 2026), DOM10-53-522 (SEQ ID NO: 2027), DOM10-53-526 (SEQ ID NO: 2028), DOM10-53-527 (SEQ ID NO: 2029), DOM10-53-528 (SEQ ID NO: 2030), DOM10-53-518 (SEQ ID NO: 2031), DO 10-53-523 (SEQ ID NO: 2032), DOM10-53-524 (SEQ ID NO: 2033), DOM10-53-525 (SEQ ID NO: 2034), DOM 10-53-601 (SEQ ID NO: 2035), DOM10-53-602 (SEQ ID NO: 2036), DOM10-53-605 (SEQ ID NO: 2037), DOM10- 53-606 (SEQ ID NO: 2038), DOM10-53-607 (SEQ ID NO: 2039), DOM10-53-608 (SEQ ID NO: 2040), DOM10- 53-609 (SEQ ID NO: 2041), DOM 10-53-610 (SEQ ID NO: 2042), DOM10-53-611 (SEQ ID NO: 2043), DOM10-53-612 (SEQ ID NO: 2044) , DOM10-53-603 (SEQ ID NO: 2045), DOM10-53-604 (SEQ ID NO: 2046), DOMAIN-53-429 (SEQ ID NO: 2047), DOM10-53-432 (SEQ ID NO: 2048), DOM10-53-433 (SEQ ID NO: 2049), DOM10-53-435 (SEQ ID NO: 2050), DOM10-53-430 (SEQ ID NO: 2051), DOM10-53-431 (SEQ ID NO: 2052), DOM10-53-434 (SEQ ID NO: 2053), DOM 10-53-436 (SEQ ID NO: 2054), DOM10-53-437 (SEQ ID NO: 2055), DOM 10-53- 438 (SEQ ID NO: 2056), DOM10-53-440 (SEQ ID NO: 2057), DOM10-53-439 (SEQ ID NO: 2058), DOM10-53-441 (SEQ ID NO: 2059), DOM10- 53-442 (SEQ ID NO: 2060), DOM10-53-443 (SEQ ID NO: 2061), DOM10-53-444 (SEQ ID NO: 2062), DOM10-53-445 (SEQ ID NO: 2063), DOM10-53-446 (SEQ ID NO: 2064), DOM10-53-447 (SEQ ID NO: 2065), DOM10-53-449 (SEQ ID NO: 2066), DOM10-53-448 (SEQ ID NO: 2067) ), DOM30-53-450 (SEQ ID NO: 2068), DOM10-53-451 (SEQ ID NO: 2069), DOM10-53-452 (SEQ ID NO: 2070), DOM10-53-453 (SEQ ID NO. : 2071), DOM10-53-454 (SEQ ID NO: 2072), DOM10-53-4 55 (SEQ ID NO: 2073), DOM10-53-456 (SEQ ID NO: 2074), DOM10-53-457 (SEQ ID NO: 2075), DOM10-53-458 (SEQ ID NO: 2076), DOM10- 53-459 (SEQ ID NO: 2077), DOM10-53-461 (SEQ ID NO: 2078), DOM10-53-462 (SEQ ID NO: 2079), DOM10-53-465 (SEQ ID NO: 2080), DOM10-53-466 (SEQ ID NO: 2081), DOM10-53-467 (SEQ ID NO: 2082), DOM10-53-468 (SEQ ID NO: 2083), DOM10-53-460 (SEQ ID NO: 2084) ), DOM10-53-463 (SEQ ID NO: 2085), DOM 10-53-464 (SEQ ID NO: 2086), DOM10-53-469 (SEQ ID NO: 2087), DOM10-53-471 (SEQ ID NO: 2088), DOM10-53-470 (SEQ ID NO: 2089), DOM10-53-533 (SEQ ID NO: 2090), DOM10-53-534 (SEQ ID NO: 2091), DOM10-53-535 (SEQ ID NO: 2092), DOM10-53-537 (SEQ ID NO: 2093), DOM10-53-538 (SEQ ID NO: 2094), DOM10-53-539 (SEQ ID NO: 2095), DOM10-53-540 ( SEQ ID NO: 2096), DOM10-53-531 (SEQ ID NO: 2097), DOM10-53-532 (SEQ ID NO: 2098), DOM10-53-536 (SEQ ID NO: 2099), DOM10-53- 542 (SEQ ID NO: 2100), DOM10-53-541 (SEQ ID NO: 2101), DOM10-53-473 (SEQ ID NO: 2102), DOM10-53-472 (SEQ ID NO: 2103), DOM10- 53-475 (SEQ ID NO: 2104), DOM10-53-474 (SEQ ID NO: 2105), DOM10-53-543 (SEQ ID NO: 2106), DOM10-53-544 (SEQ ID NO: 107), DOM10-53-545 (SEQ ID NO: 2108), DOM10-53-548 (SEQ ID NO: 2109), DOM10-53-546 (SEQ ID NO: 2110), DOM10-53-549 (SEQ ID NO: 2111) ), DOM10-53-547 (SEQ ID NO: 2112), DOM10-53-550 (SEQ ID NO: 2113), DOM10-53-551 (SEQ ID NQ: 2114), DOM10-53-560 (SEQ ID NO. : 2115), DOM10-53-565 (SEQ ID NO: 2116), DOM10-53 -559 (SEQ ID NO: 2117), DOM10-53-561 (SEQ ID NO: 2118), DOM10-53-562 (SEQ ID NO: 2119), DOM10-53-563 (SEQ ID NO: 2120), DOM ) 0-53-564 (SEQ ID NO: 2121), DOM10-53-566 (SEQ ID NO: 2122), DOM10-53-554 (SEQ ID NO: 2123), DOM10-53-552 (SEQ ID NO: 2124), DOM10-53-553 (SEQ ID NO: 2125), DOM10-53-558 (SEQ ID NO: 2126), DOM10-53-556 (SEQ ID NO: 2127) and DOM10-53-557 (SEQ ID NO: 2128). The present invention also provides a vector comprising a recombinant nucleic acid molecule of the present invention. In certain embodiments, the vector is an expression vector that comprises one or more expression control elements or sequences that are operably linked to the recombinant nucleic acid of the present invention. The present invention also provides a recombinant host cell comprising a recombinant nucleic acid molecule or vector of the present invention. Suitable vectors (e.g., plasmids, phagemids), expression control elements, host cells, and methods for producing recombinant host cells of the present invention are well known in the art, and the examples are further described in the present invention. . The expression vectors may contain a number of components, for example, a replication origin, a selectable marker gene, one or more expression control elements, such as a transcription control element (e.g., promoter, enhancer, terminator ) and / or one or more translation signals, a signal sequence or leader sequence and the like. The elements of expression control and its signal sequence, if found, can be provided by the vector or source. For example, the control sequences of transcription and / or translation of a Cloned nucleic acid encoding an antibody chain can be used to direct expression. A promoter can be provided for expression in a desired host cell. The promoters can be constitutive or inducible. For example, a promoter can be operably linked to a nucleic acid encoding an antibody, an antibody chain or part thereof, so as to direct the transcription of the nucleic acid. A variety of suitable promoters are available for prokaryotic hosts (e.g., lac, tac, T3, T7 promoters for E. coli) and eukaryotes (e.g., early or late promoter of simian virus 40, long-terminal repeat promoter). Rous sarcoma virus, cytomegalovirus promoter, adenovirus late promoter). In addition, expression vectors usually comprise a selectable marker for the selection of host cells carrying the vector, and in the case of a replicable expression vector, an origin of the replicate. Genes encoding products that confer resistance to antibiotics or drugs are common selectable markers and can be used in prokaryotic cells (e.g., lactamase gene (ampicillin resistance), Jet gene for tetracycline resistance) and eukaryotic cells (e.g. neomycin (G418 or geneticin), gpt (mycophenolic acid), ampicillin, or hygromycin resistance genes). The marker genes of Dihydrofolate reductase allow the selection of methotrexate in a variety of hosts. Genes encoding the gene product of auxotrophic host markers (eg, LEU2, URA3, HIS3) are frequently used as selectable markers in yeast. The use of viral vectors (eg, baculovirus) or phage, and vectors that have the ability to integrate into the genome of the host cell, such as retroviral vectors are also contemplated. Well-known expression vectors are well known in the art for expression in mammalian cells and prokaryotic cells (E. coli), insect cells (Drosophiia Schnieder S2 cells, Sf9) and yeast cells (P. methanolica, P. pasioris, S. cerevisiae). Suitable host cells can be prokaryotic, including bacterial cells such as E. coli, B, subtilis and / or other suitable bacteria; eukaryotic cells such as fungal or yeast cells (e.g., Pichiapastoris, Aspergillus sp., Saccharomyces cerevisiae, Schizosaccharomyces pombe, Neurospora crassa), or other lower eukaryotic cells and higher eukaryotic cells, such as those from insects (e.g., Drosophiia Schnieder S2 cells, Sf9 insect cells (WO 94/26087 (O'Connor)), mammals (eg, COS cells, such as COS-1 (ATCC Access No. CRL-1650) and COS-7 (ATCC Access No. CRL-1651), CHO (eg, ATCC Access No. CRL-9096, CHO DG44 (Urlaub, G. and Chasin, LA., Proc. Nati. Acac. Sci USA, 77 (7): 4216-4220 (1980))), 293 (ATCC Access No. CRL- 1573), HeLa (Access ATCC No. CCL-2), CVI (Access ATCC No. CCL-70), WOP (Dailey, L., and associates, J. Virol, 54: 739-749 (1985), 3T3, 293T (Pear, WS, and associates, Proc. Nati. Acad, Sci USA, 90: 8392-8396 (1993)) NSO cells, SP2 / 0, HuT 78 cells and the like, or plants (e.g., tobacco). See, for example, Publication of Ausubel, FM and associates, eds, Current Protocols in Molecular Biology, Greene Publishing Associates and John Wiley &Sons Inc. (1993)) In some embodiments, the host cell is an isolated host cell and it is not part of a multicellular organism (e.g., plant or animal) In preferred embodiments, the host cell is a non-human host cell The present invention also provides a method for producing in ligand (e.g., double specific ligand, ligand multi-specific) of the present i nvention, which comprises maintaining a recombinant host cell comprising a recombinant nucleic acid of the present invention, under conditions suitable for expression of the recombinant nucleic acid, whereby the recombinant nucleic acid is expressed and a ligand is produced. In some embodiments, the method further comprises the ligand. Preparation of ligands based on immunoglobulin Ligands (for example, specific double ligands, multispecific ligands) according to the present invention can be prepared according to previously established techniques, used in the field of antibody engineering, for the preparation of scFv, "phage" antibodies and other constructed antibody molecules. The techniques for antibody preparation are described, for example, in the following reviews and references herein: Winter & Milstein, (1991) Nature 349: 293-299; Pluckthun (1992) Immunological Reviews 13 0: 151-188; Wright and associates, (1992) Crit. Rev. Immunol. 12: 125-168; Holliger, P. & Winter, G. (1993) Curr. Opin. Biotechnol. 4, 446-449; Carter, and associates (1995) J. Hematother. 4, 463-470; Chester, K. A. & Hawkins, R.E. (1995) Trends Biotechnol. 13, 294-300; Hoogenboom, H.R. (1997) Nat. Biotechnol. 15, 125-126; Fearon, D. (1997) Nat. Biotechnol. 15, 618-619; Pluckthun, A. & Pack, P. (1997) Immunotechnology 3, 83-105; Carter, P. & Merchant, A.M. (1997) Curr. Opin. Biotechnol. 8, 449-454; Holliger, P. & Winter, G. (1997) Cancer Immunol. Immunother. 45,128-130. Suitable techniques for selection of variable domains of antibody with desired specificity expand libraries and selection procedures that are known in the art. Natural librarles (Marks and associates (1991) J. Mol. Biol., 222: 581; Vaughan and associates (1996) Nature Biotech., 14: 309) which use V genes collected from human B cells that are known to experts in the technique.

Synthetic libraries (Hoogenboom &Winter (1992) J Mol. Biol, 227: 381; Barbas and associates (1992) Proc. Nati, Acad. Sci USA, 89: 4457; Nissim and associates (1994) EMBO J, 13: 692; Griffiths et al. (1994) EMBO J., 13: 3245; De Kruif et al. (1995) J. Mol. Biol., 248: 97) were prepared by cloning immunoglobulin V genes, typically using PCR. Errors in the PCR process can lead to a high degree of randomization. The VH and / or VL libraries can be screened against target antigens or epitopes separately, in which case a single domain link is directly selected for, or together. Library vector systems A variety of selection systems are known in the art which are suitable for use in the present invention. Examples of such systems are described below. The bacteriophage lambda expression systems can be classified directly as bacteriophage plaques or as colonies of lysogens, both as previously described (Huse et al. (1989) Science, 246: 1275; Cato and Koprowski (1990) Proc. Nati. Acad Sci USA, 87, Mullinax and associates (1990) Proc. Nati Acad. Sci USA, 87: 8095, Persson and associates (1991) Proc. Nati, Acad. Sci USA, 88: 2432), and are of use in the present invention. Although such expression systems can be used to classifying up to 10 different members of a library, they really are not suitable for classifying larger numbers (greater than 106 members). Of particular use in the construction of libraries, are the selection display systems, which allow a nucleic acid to be linked to the polypeptide it expresses. As used in the present invention, a selection deployment system is a system that allows the selection, through suitable deployment means, of the individual members of the library, linking to the generic and / or objective. Selection protocols for isolating desired members of large libraries are known in the art, as typified by phage display techniques. Such systems, in which the various peptide sequences are displayed on the surface of filamentous bacteriophages (Scott and Smith (1990) Science, 249: 386), have proven useful in creating libraries of antibody fragments (and nucleotide sequences). encoding them) for the selection and in vitro amplification of specific antibody fragments that bind to a target antigen (McCafferty et al., WO 92/01047). The nucleotide sequences encoding the variable regions are linked to gene fragments encoding leader sequences that direct them to the periplasmic space of E. coli and as a result, the resulting antibody fragments are displayed on the bacteriophage surface, usually as fusions to bacteriophage coat proteins (e.g., plll or p V 111). Alternatively, antibody fragments in lambda phage capsids (fagebodies) are displayed externally. An advantage of phage-based display systems is that, because they are biological systems, the selected library members can be amplified simply by growing the phage containing the selected library member in bacterial cells. In addition, since the nucleotide sequence is that it encodes the polypeptide library member is contained in a phage or phagemid vector, sequencing, expression and subsequent genetic manipulation is relatively simple. Methods for the construction of bacteriophage antibody display libraries and lambda phage display libraries are well known in the art (McCafferty et al. (1990) Nature, 348: 552; Kang et al. (1991) Proc. Nati. Acad. Sci USA, 88: 4363; Clackson and associates (1991) Nature, 352: 624; Lowman and associates (1991) Biochemistry, 30: 10832; Burton and associates (1991) Proc. Nati, Acad. Sel USA, 88: 10134 Hoogenboom and associates (1991) Nucleic Acids Res., 19: 4133; Chang and associates (1991) J. Immunol, 147: 3610; Breitling and associates (1991) Gene, 104: 147; Marks and associates (1991) supra; Barbas and associates (1992) supra; Hawkins and Winter (1992) J.

Immunol, 22: 867; Marks et al., 1992, J. Biol. Chem., 267: 16007; Lerner et al. (1992) Science, 258: 1313, incorporated herein by reference. A particularly convenient method has been the use of phage-scFv libraries (Huston et al., 1988, Proc. Nati, Acad. Sci USA, 85: 5879-5883; Chaudhary et al. (1990) Proc. Nati Acad. Sci USA, 87 : 1066-1070; McCafferty and associates (1990) supra; Clackson and associates (1991) Nature, 352: 624; Marks and associates (1991) J Mol. Biol, 222: 581; Chiswell and associates (1992) Trends Biotechnol, 10 : 80; Marks and associates (1992) J. Biol. Chem., 267). Several modalities of scFv libraries deployed in bacteriophage coat proteins have already been described. Refinements of phage display methods are also known, for example as described in WO96 / 06213 and WO92 / 01047 (Medical Research Council and associates) and WO97 / 08320 (Morphosys), which are incorporated herein invention as reference. Other systems for generating polypeptide libraries involve the use of cell-free enzymatic machinery for in vitro synthesis of the members of the library. In one method, RNA molecules are selected by alternating turns of selection against a PCR target and amplification (Tuerk and Gold (1990) Science, 249: 505; Ellington and Szostak (1990) Nature, 346: 818). You can use a similar technique to identify DNA sequences which bind to a predetermined human transcription factor (Thiesen and Bach (1990) Nucleic Acids Res., 18: 3203; Beaudry and Joyce (1992) Science, 257: 635; WO92 / 05258 and W092 / 14843). In a similar manner, in vitro translation can be used to synthesize polypeptides as a method for generating large libraries. These methods, which generally comprise stabilized polysome complexes, are described further in WO88 / 08453, WO90 / 05785, WO90 / 07003, WO91 / 02076, WO91 / 05058 and WO92 / 02536. Alternative non-phage display systems, such as those described in W095 / 22625 and W095 / 11922 (Affymax) use polysomes to display polypeptides for selection. A still further category of techniques involves the selection of repertoires in artificial compartments, which allow the ligation of a gene with its gene product. For example, a selection system in which nucleic acids encoding desirable gene products can be selected in microcapsules formed by water-in-oil emulsions is described in publications W099 / 02671, WO00 / 40712 and Tawfik & Griffiths (1998) Nature Biotechnol 16 (7), 652-6. The genetic elements that encode a gene product that has a desired activity are compartmentalized into microcapsules and subsequently transcribed and / or translated to produce those respective gene products (RNA or protein) within the microcapsules. The genetic elements that produce gene products that have desired activity are classified subsequently. This method selects gene products of interest by detecting the desired activity through a variety of means. Construction of Libraries Libraries screened for selection may be constructed using techniques known in the art, for example as set forth above, or may be purchased from commercial sources. Libraries that are useful in the present invention are described, for example, in WO99 / 20749. A vector system is chosen and one or more nucleic acid sequences encoding polypeptides of interest are cloned into the library vector, a diversity between the cloned molecules can be generated by carrying out the mutagenesis before expression; alternatively, the encoded proteins can be expressed and selected, as described above, before further mutagenesis and rounds of selection are carried out. The mutagenesis of nucleic acid sequences encoding structurally optimized polypeptides is carried out by standard molecular methods. Of particular interest is the polymerase chain reaction or PCR (Mullis and Faloona (1987) Methods Enzymol., 155: 335, incorporated into the present invention as reference). PCR that uses multiple cycles of DNA replication catalyzed by DNA-dependent DNA polymerase, thermostable to amplify the target sequence of interest, is well known in the art. The construction of the various antibody libraries has been mentioned in the Winter and Associates publication. (1994) Ann. Rev. Immunology 12, 433-55, and the references therein mentioned. PCR is carried out using template DNA (at least 1fg, more usefully, 1-1000 ng) and at least 25 pMol. of oligonucleotide primers; it may be convenient to use a greater amount of primer when the primer group is highly heterogeneous, since each sequence is represented only by a small fraction of the group molecules, and the amounts become limiting in the subsequent amplification cycles. A typical reaction mixture includes two spots: 2 μl DNA, 25 pmol. of oligonucleotide primer, 2.5 μ? of 10X PCR 1 buffer (Perkin-Elmer, Foster City, CA), 0.4 μ? of 1.25 μ? dNTP, 0.15 μ? (or 2.5 units) of Taq DNA polymerase (Perkin Elmer, Foster City, CA) and deionized water at a total volume of 25 μ ?. The mineral oils are covered and the PCR is carried out using a programmable thermal cycler. The length and temperature of each step of a PCR cycle, as well as cycle numbers, is adjusted according to the stringency requirements in effect. Hardening temperature and timing are determined, both through the efficiency with which the primer is expected to harden to a template and the degree of incompatibility that is tolerated; obviously, when nucleic acid molecules are simultaneously amplified and mutagenized, incompatibility is required, at least in the first round of synthesis. The ability to optimize the stringency of hardening conditions of the primer is also within the knowledge of one skilled in the art. A hardening temperature between 30 ° C and 72 ° C is what is normally used. The initial denaturation of the template molecules normally occurs at a temperature between 92 ° and 99 ° C dur, before 4 minutes, followed by 20-40 cycles consisting of denaturation (94-99 ° C for 15 seconds at 1 minute) , hardening (temperature determined as described above, 1-2 minutes) and extension (72 ° C for 1-5 minutes, depending on the length of the amplified product). The final extension is usually 4 minutes at a temperature of 72 ° C, and can be followed by an indefinite step (0-24 hours) at a temperature of 4 ° C. Combination of simple variable domains The domains useful in the present invention, once selected, can be combined through a variety of methods known in the art, including covalent methods and not covalent. Preferred methods include the use of polypeptide linkers as described in the present invention, for example, in relation to scFV molecules (Bird et al., (1988) Science 242: 423-426). A description of suitable linkers is provided in the publication of Bird and associates. Science 242, 423-426; Hudson et al., Journal Immunol Methods 231 (1999) 177-189; Hudson et al., Proc Nat Acad Sd USA 85, 5879-5883. The linkers are preferably flexible, allowing two simple domains to interact. An example of a linker is a linker (Gly4 Ser) n, where n = 1 to 8, for example, 2, 3, 4, 5 or 7. The linkers used in diabodies, which are less flexible, can also be used (Holliger et al., (1993) Proc Nat Acad Sci USA 90: 6444-6448). In one embodiment, the linker employed is not a region of immunoglobulin articulation. The variable domains can be combined using methods other than linkers. For example, the use of disulfide bridges, provided through naturally occurring or constructed cysteine residues, can be exploited to stabilize VH-VH, VL-VL or VH-VL dimers (Reiter and associates, (1994) Protein Eng 7: 697-704) or by remodeling the interface between the variable domains to improve the "fit" and thus the stability of the interaction (Ridgeway et al., (1996) Protein Eng. 7: 617-621; Zhu et al. associates, (1997) Protein Science 6: 781-788). Other techniques for binding or stabilizing variable immunoglobulin domains, and in particular VH antibody domains, may be employed as appropriate. Characterization of ligands The binding of a specific double ligand to a cell or the binding of each binding domain to each specific target can be tested by methods familiar to those skilled in the art, and including ELISA. In a preferred embodiment of the present invention, the linkage is tested using monoclonal phage ELISA. The phage ELISA assay can be carried out according to any suitable procedure: an exemplary protocol is set forth below. The populations of phages produced in each round of selection can be classified for binding by ELISA to the selected antigen or epitope, to identify "polyclonal" phage antibodies. The phage of simple infected bacterial colonies from these populations can subsequently be classified by ELISA to identify "monoclonal" phage antibodies. It is also desirable to classify soluble antibody fragments for binding to an antigen or epitope, and this can also be carried out by ELISA assay using reagents, for example, against a C- or N-terminal label (see for example the publication of Winter and associates (1994) Ann. Rev. Immunology 12, 433-55 and references there mentioned. The diversity of selected phage monoclonal antibodies can also be evaluated by gel electrophoresis of PCR products (Marks et al., 1991, supra, Nissim et al 1994, supra), by probing (Tomlinson et al., 1992) J. Mol. Biol. 227, 776) or by sequencing the vector DNA. Ligand structure In the case where each variable domain is selected from V-gene repertoires, selected for example using phage display technology as described herein, then these variable domains comprise a region of universal structure, so that they can be recognized by a specific generic double specific ligand, as defined herein. The use of universal structures, generic ligands and the like is described in WO99 / 20749. When V-gene repertoires are used, the variation in the polypeptide sequence is preferably located within the structural circuits of the variable domains. The polypeptide sequences of any variable domain can be altered by DNA shuffling or by mutation in order to increase the interaction of each variable domain with its complementary pair. DNA swabbing is known in the art and is considered, for example in the publication of Stemmer, 1994, Nature 370: 389-391 and in US Patent No. 6,297,053, which are incorporated herein by reference. Other methods of mutagenesis are well known to those skilled in the art. In general, nucleic acid molecules and vector constructs for selection, preparation and formation of specific double ligands can be constructed and manipulated as set forth in standard laboratory manuals, such as Sambrook and associates. (1989) Mol.ecular Cloning: A Laboratory Manual, Cold Spring Harbor, USA. The nucleic acid manipulation used in the present invention is usually carried out in recombinant vectors. As used in the present invention, vector refers to an independent element that is used to introduce heterologous DNA into cells for expression and / or replication thereof. The methods by which these vectors are selected or constructed, and subsequently used, are well known to those skilled in the art. Numerous vectors are publicly available, including bacterial plasmids, bacteriophages, artificial chromosomes and episomal vectors. Said vectors can be used for cloning and simple mutagenesis; as an alternative, a gene expression vector is used. A vector to be used according to the present invention is may be selected to accumulate a coding sequence and polypeptide of a desired size, typically 0.25 kilobase (kb) to 40 kb or more in length. An appropriate host cell is transformed with the vector after in vitro cloning manipulation. Each vector contains various functional components, which generally include a cloning site ("polylinker"), a replication origin and at least one selectable marker gene. If the determined vector is an expression vector, it also has one or more of the following: an enhanced element, promoter, transcription termination sequences and signal sequences, each placed in the vicinity of the cloning site, so that they are linked operatively to the gene encoding a specific double ligand according to the present invention. Both cloning and expression vectors generally contain nucleic acid sequences that allow the vector to replicate in one or more selected host cells. Typically in cloning vectors, this technique is one that allows the vector to replicate independently of the host chromosomal DNA and includes replication origins or replication sequences autonomously. Said sequences are known by a variety of bacteria, yeasts and viruses. The replication origin of plasmid pBR322 is suitable for most Gram-bacteria. negative, and the 2 micron plasmid origin is suitable for yeast, and several viral origins (eg SV40, adenovirus) are useful for cloning vectors in mammalian cells. Generally, replication origin is not needed for expression vectors unless they are used in mammalian cells with the ability to replicate high levels of DNA, such as COS cells. Conveniently, a cloning or expression vector may contain a selection gene also required as a selectable marker. This gene encodes a protein necessary for the survival or growth of transformed host cells grown in a selective culture medium. The host cells not transformed with the vector containing the selection gene will therefore not survive in the culture medium. Typical selection genes encode proteins that contain resistance to antibiotics and other toxins, eg, ampicillin, neomycin, methotrexate or tetracycline, auxotrophic complement deficiencies or delivery in important nutrients not available in the growth medium. Since the vector replication encoding a specific double ligand according to the present invention is most conveniently carried out in E. coli, an E-selected marker. coli, for example, the ß-lactamase gene that confers resistance to antibiotic ampicillin, will be used.

This can be obtained from E. coli plasmids, such as pBR322 or a pUC plasmid such as pUC18 or pUC19. Expression vectors typically contain a promoter that is recognized by the host organism and is operably linked to the coding sequence of interest. Said promoter can be inducible or constitutive. The term "linked in operable form" refers to a juxtaposition wherein the components described are in a relationship that allows them to function in their projected form. A control sequence "operably linked" to a coding sequence is ligated such that expression of the coding sequence is achieved under conditions compatible with the control sequences. Promoters suitable for use with prokaryotic hosts include, for example, the β-lactamase and lactose promoter systems, alkaline phosphatase, the tryptophan (trp) promoter system, and hybrid promoters such as the tac promoter. Promoters for use in bacterial systems will also generally contain a Shine-Delgarno sequence linked operably to the coding sequence. Preferred vectors are expression vectors that allow the expression of a nucleotide sequence corresponding to a polypeptide library member. Therefore, the selection with the first and / or second antigens Epitopes can be carried out by a separate spread and expression of a single clone expressing the member of the polypeptide library or through the use of any selection display system. As described above, the preferred selection deployment system is bacteriophage display. Therefore, phage or phagemid vectors can be used (eg plT1 or plT2) The leader sequences in the present invention include pelB, stll, ompA, phoA, bla and pelA An example of phagemid vectors having an origin of E. coli replication (for double-stranded replication) and also a phage replication origin (for the production of single-stranded DNA) The manipulation and expression of said vectors is well known in the art (Hoogenboom and Winter (1992 ) supra; Nissim et al. (1994) supra.) In summary, the vector contains a β-lactamase gene to confer selectivity in the phagemid and an upstream promoter lac of an expression band consisting of (N to C terminal ) in a pelB leader sequence (directing the expressed polypeptide to the periplasmic space), a multiple cloning site (to clone the nucleotide version of the library member) optionally, one or more peptide tags (for detection) option One or more stop codons TAG and the phage protein plll. Therefore, using various suppressor and non-suppressor strains of E. coli and with the addition of glucose, thio- -D-galactoside iso- propyl (IPTG) or an auxiliary phage, such as VCS M13, the vector has the ability to replicate as a plasmid without expression, produce large quantities of the polypeptide library member alone or produce phages, some of which contain at least one copy of the polypeptide-pl 11 fusion on its surface. The construction of vectors encoding double specific ligands according to the present invention employs conventional ligation techniques. The isolated vectors or DNA fragments are dissociated, tailored and reigated in the desired form to generate the required vector. If desired, the analysis to confirm that the correct sequences are present in the constructed vector can be carried out in a known manner. Suitable methods for constructing expression vectors, preparing in vitro transfections, introducing DNA into host cells, carrying out assays to evaluate expression and function are known to those skilled in the art. The presence of a gene sequence in a sample is detected, or its amplification and / or expression is quantified by conventional methods, such as Southern or Northern analysis, Western spotting, spotting of DNA, RNA or protein, in-hybridization. Situ, immunocytochemistry or sequence analysis of nucleic acid or protein molecules. Those skilled in the art will readily consider how these methods can be modified if desired. Skeletons Skeletons can be based on immunoglobulin molecules or can be of non-immunoglobulin origin, as stated above. Each domain of the specific double ligand can be a different skeleton. Preferred immunoglobulin backbones as used in the present invention, include any of one or more of those selected from the following: an immunoglobulin molecule comprising at least (i) the CL domain (kappa or lambda subclass) of an antibody; or (ii) the CH1 domain of an antibody heavy chain; an immunoglobulin molecule comprising the CH1 and CH2 domains of an antibody heavy chain; an immunoglobulin molecule comprising the CH1, CH2 and CH3 domains of an antibody heavy chain; or any of subgroup (ii) together with the CL domain (kappa or lambda subclass) of an antibody. A joint region domain can also be included. For example, the ligand can screen a heavy chain constant region of an immunoglobulin (e.g., IgG (e.g., IgG 1, IgG2, IgG3, IgG4), IgM, IgA, IgD, or IgE) or a portion thereof (e.g. Fe portion) and a light chain comstant region (e.g. CK CU). For example, the ligand may comprise CH1 of IgG1 (eg, human IgG1), CH1 and CH2 of IgG1 (eg, human IgG1) or CH1, CH2 and CH3 of lgG1 (for example human IgG 1), CH2 and CH3 of lgG1 IgG 1 (for example human IgG 1) or CH1 and CH3 of lgG1 (for example I g G1 human) Such combinations of domains, can for example, natural mimicked antibodies such as IgG or IgM, or fragments thereof, such as Fv, scFv, Fab or F (ab ') 2 molecules. Those skilled in the art will be aware that this list is not intended to be exhaustive. Protein scaffolds Each binding domain comprises a protein scaffold and one or more CDRs that are involved in the specific interaction of the domain with one or more epitopes. Conveniently, an epitope linkage domain according to the present invention comprises three CDRs. Suitable protein scaffolds include any of those selected from the group consisting of the following: those that are based on immunoglobulin domains, those that are based on fibronectin, those that are based on antibodies, those that are based on CTLA4, those that they are based on chaperones such as GroEL, those based on lipocalin and those based on Fe SpA and SpD bacterial receptors. Those skilled in the art will appreciate that this list is not intended to be exhaustive. The binding domains may also comprise a protein scaffold that has a binding site that has binding specificity for a target (for example IL-4, IL-13), but do not contain one or more CDRs (for example, of the dAbs described herein), For example the binding domain may be a protein scaffold that has a binding site that has link specificity for a selected target of an affibody, an SpA domain, based on CTLA4, those based on chaperones, such as GroEL, those based on lipocalin and those based on the receptors of bacteria Fe, SpA and SpD, a class A LDL receptor domain, an avimer (see for example US Patent Application Publication Nos. 2005/0053973, 2005/0089932, 2005/0164301) Scaffolds for use in ligand construction Selection of conformation for chain-principal The members of the immunoglobulin superfamily, all share a similar fold for their polypeptide chain. For example, although the antibodies are highly diverse in terms of their primary sequence, the comparison of sequence and crystallographic structures have revealed that, contrary to what was expected, five of six antibody antigen binding circuits (H1, H2 , L1, L2, L3), adopt a limited number of main-chain conformations, or canonical structures (Chothia and Lesk (1987) J. Mol. Biol., 196: 901; Chothia and associates (1989) Nature, 342: 877). The analysis of circuit lengths and key residues has therefore allowed the anticipation of conformations Main chain of H1, H2, L1, L2 and L3 found in most human antibodies (Chothia et al. (1992) J. Mol. Biol., 227: 799; Tomlinson et al. (1995) EMBO J., 14: 4628; Williams et al. (1996) J. Mol. Biol., 264: 220). Although the H3 region is much more diverse in terms of sequence, length and structure (due to the use of the D segments) it also forms' a limited number of main-chain conformations for short circuit lengths that depend on the length and the presence of particular residues, or types of residues, at key positions in the circuit and antibody structure (Martin et al. (1996) J. Mol. Biol., 263: 800; Shirai et al. (1996) FEBS Letters, 399: 1). The ligand libraries and / or link domains can be designed so that certain lengths of circuits and key residues have been chosen to ensure that the main chain conformation of the members is known. Conveniently, these are actual conformations of molecules of the immunoglobulin superfamily found in nature, to minimize the opportunities for them to be nonfunctional, as described above, the germline V gene segments serve as an adequate basic structure to construct antibodies or T cell receptor libraries; 'other sequences are also used. Variations can occur in a low frequency, so that a small number of functional members may have an altered main-chain conformation, which does not affect their function. The canonical structure theory is also used to evaluate the number of different major-chain conformations encoded by the ligands, to anticipate the main-chain conformation based on double-specific ligand sequences and to choose residues for diversification that does not affect the canonical structure. It is known that in the VK domain, the L1 circuit can adopt one of four canonical structures, the L2 circuit has a simple canonical structure and that 90% of the human VK domains adopt one of four or five canonical structures of the L3 circuit (Tomlinson and associates (1995) supra); therefore in the VK domain alone, different canonical structures can be combined to create a range of different main chain conformations. Because the domain ??, encodes a different range of canonical structures for the L1, L2 and L3 circuits and that the VK and ?? domains can be paired with any VH domain that encodes various canonical structures for the H1 and H2 circuits , the number of combinations of canonical structures observed for these five circuits is very large. This implies that the generation of diversity in the main-chain conformation can be essential for the production of a wide range of link specificities. However, by building an antibody library based on a single known backbone conformation it has been found that, contrary to expectation, the diversity in the main chain conformation is not required to generate sufficient diversity to address substantially all the antigens. More surprisingly, the simple main chain conformation does not need to be a consensus structure-a simple conformation that occurs naturally can be used as the basis of an entire library. Therefore, in a preferred aspect, the ligands of the present invention possess a simple known backbone conformation. The single main chain conformation that is chosen is preferably common among the molecules of the immunoglobulin superfamily type in question. A conformation is common when a significant number of molecules that occur naturally are observed for adoption. Accordingly, in a preferred aspect of the present invention, the natural emergence of the different main chain conformations for each linker circuit of an immunoglobulin domain is considered and a naturally occurring variable domain having the desired combination of Main chain conformations for different circuits. If it is not available, it can be Choose the nearest equivalent. It is preferable that the desired combination of main chain conformations for the different circuits be created by selecting germline gene segments that encode the desired main chain conformations. It is more preferable that the selected germline gene segments are frequently expressed in nature, and most preferably they are the most frequently expressed of all the germline gene segments. In the design of ligands (for example ds-dAbs) or libraries thereof, the incidence of the different main chain conformations for each of the six antigen binding circuits can be considered separately. For H1, H2, L1, L2 and L3, a given conformation that is adopted between 20% and 100% of the antigen binding circuits of naturally occurring molecules is the one chosen. Normally, an incidence is observed above 35% (for example between 35% and 100%) and ideally above 50% or even above 65%. Since the vast majority of H3 circuits do not have canonical structures, it is preferred to select a main chain conformation that is common among circuits that display canonical structures. For each of the circuits, the conformation that is most frequently observed in natural repertoires is selected.

In human antibodies, the most popular canonical structures (CS) for each circuit are the following: H1-CS1 (of expressed repertoire), H2-CS3 (46%), L1-CS2 of VK, (39%), L2 - CS 1 (100%), L3 - CS 1 of VK, (36%) (the calculation assumes a ratio:? Of 70:30, Hood and associates. (1967) Cold Spring Harbor Symp. Quant. Biol, 48 : 133). For H3 circuits that have CDR3 structures one length (Kabat et al. (1991) Sequences of proteins of immunological interest, US Department of Health and Human Services) of seven residues with a salt bridge of residue 94 to residue 101 seems to be the most common. There are at least 16 human antibody sequences in the EMBL data libraries, with a required H3 length and key residues to form this conformation and at least two crystallographic structures in the protein data bank that can be used as a basis for modeling of antibodies (2cgr and 1 tet). The most frequently expressed germline gene segments due to this combination of canonical structures are segment VH 3-23 (DP-47) segment JH JH4b, segment VK 02/012 (DPK9) and segment JK JK1. The segments VH DP45 and DP38 are also suitable. These segments are therefore used in combination as a basis for building a library with the desired simple main chain conformation. As an alternative, instead of choosing the conformation of Simple main chain based on the natural emergence of the different main chain conformations of each link circuits in isolation, the natural emergence of combinations of main chain conformations is used as the basis for choosing the simple main chain conformation. In the case of antibodies, for example, the natural emergence of combinations of canonical structures for either two, three, four, five or for the six antigen binding circuits can be determined. Here it is preferred that the chosen conformation be common in antibodies that occur naturally and it is most preferable that it be observed more frequently in the natural repertoire. Therefore, in human antibodies, for example, when the natural combinations of the five antigen binding circuits H1, H2, L1, L2 and L3 are considered, the most common combination of canonical structures is determined and subsequently combined with training most popular circuit H3, as a basis for choosing the simple main chain conformation. Canonical Sequence Diversification Having selected known backbone conformations, or preferably a single known backbone conformation, double specific ligands (eg ds-dAbs) or libraries can be constructed for use in the present invention, varying each site of link of the molecule in order to generate a repertoire with structural and / or functional diversity. This means that the variants are generated so that they possess sufficient diversity in their structure and / or function so that they have the capacity to provide a range of activities. The desired diversity is usually generated by varying the selected molecule in one or more positions. The positions that will be changed can be chosen randomly or are selected preferentially. The variation can then be achieved either by randomization during which the resident amino acid is replaced by any amino acid or analog thereof, natural or synthetic, producing a very large number of variants or replacing the resident amino acid with one or more of a defined subgroup of amino acids, producing a more limited number of variants. Several methods have been reported to introduce such diversity. PCR prone to errors (Hawkins and associates (1992) J. Mol .. Biol, 226: 889), chemical mutagenesis (Deng and associates (1994) J. Biol. Chem., 269: 9533) or bacterial mutation strains ( Low and associates (1996) J. Mol. Biol., 260: 359) can be used to introduce random mutations into the genes encoding the Molecule. Methods for mutating selected positions are also known in the art and include the use of incompatible oligonucleotides or Degeneration oligonucleotides, with or without the use of PCR. For example, several libraries of synthetic antibodies have been created to direct mutations to the antigen binding circuits. The H3 region of a human tetanus toxoid binding Fab has been randomized to create a range of novel binding specificities (Barbas et al., (1992) Proc. Nati, Acad. Sci. USA, 89: 4457). The random or signaling H3 and L3 regions have been appended to segments of the germline V gene to produce large libraries with unmutated structure regions (Hoogenboom &Winter (1992) J. Mol. Biol., 227: 381; associates (1992) Proc. Nati, Acad. Sci. USA, 89: 4457; Nissim et al. (1994) EMBO J., 13: 692; Griffiths et al. (1994) EMBO J, 13: 3245; De Kruif and associates (1995) J] Mol. Biol., 248: 97). Such amusement has been extended to include some of the other antigen binding circuits (Crameri et al. (1996) Nature Med., 2: 100; Riechmann et al. (1995) Bio / Technology, 13: 475; Morphosys, WO97 / 08320, supra). Since circuit scrambling has the potential to create approximately more than 1015 structures for H3 alone, and a similarly large number of variants for the other five circuits, it is not feasible to use current transformation technology or even use cell-free systems to produce a library that represents all possible combinations. For example, in one of the libraries Larger constructed to date, 6 x 1010 different antibodies, which is only a fraction of the potential diversity of a library of this design, were generated (Griffiths et al. (1994) supra). Preferably, only residues that are directly involved in creating or modifying the desired function of each domain of the double specific ligand molecule are diversified. For many molecules, the function of each domain will be linked to an objective and therefore the diversity must be concentrated in the target binding site, while avoiding residues that are crucial for the general packaging of the molecule or to maintain the conformation. of the main chain chosen. Di canonical sequence versification as applied to antibody domains In the case of antibody-based ligands (e.g. ds-dAbs) the binding site for each target is most often the antigen binding site. Therefore, only the residues at the antigen binding site are preferably varied. These residues are extremely diverse in the repertoire of human antibodies and are known to make contacts in high resolution antibody / antigen complexes. For example, in L2 it is known that positions 50 and 53 are diverse in antibodies that occur naturally and are observed to make contact with the antigen. In contrast, the The conventional method may have been to diversify all the residues in the Complementarity Determination Region (CDR1) as defined in the Kabat and associates publication. (1991, supra), some of the seven residues compared with the two diversified in the library to be used in accordance with the present invention. This represents a significant improvement in terms of functional diversity required to create a range of antigen binding specificities. By nature, the diversity of antibodies is the result of two processes: somatic recombination of germline V, D, and J gene segments to create a primary naive repertoire (called the germinal line and union diversity) and somatic hypermutation of V genes resulting readjustments. Analysis of human antibody sequences have shown that the diversity in the primary repertoire is focused on the center of the antigen binding site, whereas somatic hypermutation disperses the diversity to regions at the periphery of the antigen binding site that are highly conserved in the primary antigen repertoire (see Tomlinson and associates. (1996) J. Mol. Biol., 256: 813). This complementarity has been implicated in a proven way as an efficient strategy to look for space in the sequence, and although apparently only for antibodies, it can easily be applied to others. polypeptide repertoires. The residues that are varied are a subset of those that form the liaison site for the objective. The different subgroups (including overlaps) of residues in the effective link site are diversified at different stages during the selection, if desired. In the case of an antibody repertoire, an initial "naive" repertoire can be created where some, although not all residues in the antigen binding site are diversified. As used within this context, the term "naive" refers to antibody molecules that do not have a predetermined purpose. These molecules resemble those that are encoded by the immunoglobulin genes of an individual who has not undergone immune diversification, as is the case with fetal and newborn individuals whose immune system has not yet been stimulated by a wide variety of immune systems. antigenic stimuli. Subsequently this repertoire is selected against a range of antigens or epitopes. If required, additional diversity can be introduced later outside the diversified region in the initial repertoire. This matured repertoire can be selected for function, specificity or modified affinity. Naive repertoires of binding domains for the construction of dual specific ligands where some or all of the residues at the antigen binding site are varied and are known in the art. (See publications WO 2004/058821, WO 2004/003019 and WO 03/002609). The "primary" library mimics the natural primary repertoire, with a diversity restricted to residues in the center of antigen binding sites that are diverse in the germ line V (germline diversity) or diversified segments during recombination processes (union diversity). The residues that are diversified include but are not limited to H50, H52, H52a,? 53.? 55, H56, H58, H95, H96, H97, H98, L50, L53, L91, L92, L93, L94 and L96. In the "somatic" library, diversity is restricted to residues that are diversified during the recombination process (union diversity) or are mutated in a highly somatic manner. The residues that are diversified include but are not limited to: H31, H33, H35, H95, H96, H97, H98, L30, L31, L32, L34 and L96. All the residues described above as suitable for diversification in these libraries are known to make contacts in one or more antibody-antigen complexes. Since in both libraries, not all residues in the antigen binding site are varied, additional diversity is incorporated during selection, varying the remaining residues, if desired. It will be appreciated by one skilled in the art that any subgroup of any of these residues (or additional residues comprising the antigen binding site) can be used to initial and / or subsequent diversification of the antigen binding site. In the construction of libraries for use in the present invention, the diversification of chosen positions is normally achieved at the level of nucleic acid, by altering the coding sequence that specifies the polypeptide sequence so that the number of possible amino acids can be incorporated ( 20 or a subgroup thereof) in said position. Using the IUPAC nomenclature, the most versatile codon is NNK, which encodes all amino acids as well as the TAG stop codon. The NNK codon is preferably used in order to introduce the required diversity. Other codons that achieve the same ends are also used, including the NNN codon, which leads to the additional stop codons TGA and TAA. A characteristic of the side chain diversity at the antigen binding site of human antibodies is a pronounced tilt that favors certain amino acid residues. If the amino acid composition of the ten most diverse positions in each of the regions VH, VK and ?? is added, more than 76% of the side chain diversity comes only from seven different residues, being these, serine (24%), tyrosine (24%), asparagine (11%), glycine (9%), alanine (7) %), aspartate (6%) and threonine (6%). This inclination towards hydrophilic waste and small waste that provide principal chain flexibility, probably reflect the evolution of surfaces that are predisposed to bind a high range of antigens or epitopes and may help explain the required promiscuity of the antibodies in the primary repertoire. Since it is preferable to mimic this distribution of amino acids, the distribution of amino acids in the positions that will be varied, preferentially mimics that observed in the binding site of the antibodies. Said bias in the substitution of amino acids that allows the selection of certain (not only antibody polypeptides) against a range of target antigens, is easily applied to any polypeptide repertoire. These are various methods to tilt the amino acid distribution in the position that will be varied (including the use of tri-nucleotide mutagenesis, see publication WO97 / 08320), which is the preferred method, due to the ease of synthesis, and use of conventional degeneration codons. By comparing the amino acid profile encoded by all codon combinations of degeneration (with single, double triple and quadruple degeneration in equal proportions in each position) with the use of the natural amino acid it is possible to calculate the most representative codon. The codons (AGT) (AGC) T, (AGT) (AGC) C and (AGT) (AGC) (CT) that is, DVT, DVC and DVY, which respectively use IUPAC nomenclature - are the closest to the desired amino acid profile: they encode 22% serine and 11% tyrosine, asparagine, glycine, alanine, aspartate, threonine and cysteine. Preferably, therefore, the libraries are constructed using either the DVT, DVC or DVY codon in each of the diversified positions. Therapeutic and Diagnostic Compositions and Uses The present invention provides compositions comprising the ligands of the present invention and a pharmaceutically acceptable carrier, diluent or excipient, and therapeutic and diagnostic methods employing the ligands or compositions of the present invention. The ligands according to the method of the present invention can be used in therapeutic and prophylactic in vivo applications, in vivo diagnostic applications and the like. The therapeutic and prophylactic uses of ligands of the present invention involve the administration of ligands according to the present invention to a recipient mammal, such as a human. The ligand linkage is directed with high affinity and / or avidity. In some embodiments, such as IgG-like ligands, the ligands may allow the recruitment of cytotoxic cells to transmit the killing of cancer cells, for example by antibody-dependent cellular cytotoxicity. Substantially pure ligands of at least 90 to 95% homogeneity are preferred for administration to a mammal, and 98 to 99% or more homogeneity is most preferred for pharmaceutical uses, especially when the mammal is a human. Once purified, partially or for homogeneity as desired, the ligands can be used for diagnosis or in therapeutic form (including extracorporeal) or in the development and performance of assay procedures, immunofluorescent stains and the like (Lefkovite and Pernis, (197-). 9 and 1981) Immunological Methods, Volumes I and II, Academic Press, NY). In the present application, the term "prevention" implies the administration of the protective composition before the induction of the disease. The term "deletion" refers to the administration of the composition after an inductive event, although prior to the clinical appearance of the disease. The term "treatment" implies the administration of the protective composition after the symptoms of the disease have manifested. The treatment includes reduction of symptoms associated with the disease, and also to the prevention or delay of the onset of the disease, and also the decrease of the severity or frequency of the symptoms of the disease. For example, the ligands of the present invention will find use normally in the prevention, suppression or treatment of disease states. For example, the ligands can be administered for. treat, suppress or prevent a chronic inflammatory disease, allergic hypersensitivity, cancer, bacterial or viral infection, autoimmune disorders (including but not limited to, Type I diabetes, asthma, multiple sclerosis, rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, spondyloarthropathy (eg, ankylosing spondylitis), systemic lupus erythematosus, inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), myasthenia gravis and Behcet's syndrome, psoriasis, endometriosis and abdominal adhesions (eg, post abdominal surgery). present invention can be used to treat, suppress or prevent a disease, such as an allergic disease, a disease transmitted by Th2, a disease transmitted by IL-13, disease transmitted by IL-4, disease transmitted by IL-4 / IL- 13. Examples of these diseases include Hodgkin's disease, asthma, allergic asthma, atopic dermatitis, allergy atopic, ulcerative colitis, scleroderma, allergic rhinitis, COPD, idiopathic pulmonary fibrosis, rejection of chronic graft, bleomycin-induced pulmonary fibrosis, radiation-induced pulmonary fibrosis, pulmonary granuloma, progressive systemic sclerosis, schistosomiasis, hepatic fibrosis, renal cancer, lymphoma Burkitt, Hodgkin's disease, non-Hodgkin's disease, Sezari syndrome, asthma, septic arthritis, dermatitis herpetiformis, chronic idiopathic urticaria, ulcerative colitis, scleroderma, hypertrophic scarring, Whipple's disease, benign prostatic hyperplasia, a lung disorder in which an IL-4 receptor plays an important role, a condition in which the disruption of the epithelial barrier transmitted by the IL-4 receptor plays an important role, a disorder of the digestive system in which the IL-4 receptor plays an important role, an allergic reaction to a drug, Kawasaki disease, sickle-cell disease, Churg-Strauss syndrome, Grave's disease, eclampsia, Sjogren's syndrome, autoimmune lymphoproliferative syndrome, autoimmune hemolytic anemia, Barrett's esophagus, autoimmune uveitis, tuberculosis, cystic fibrosis, allergic bronchopulmonary mycosis, chronic obstructive pulmonary disease, pneumopathy and bleomycin-induced fibrosis, pulmonary alveolar proteinosis, respiratory distress syndrome in adults, sarcoidosis, hyper IgE syndrome, hypereosinophil syndrome or idiopathic, a disease of autoimmune blisters, pemphigus bulgaris, bullous pemphigus, myasthenia gravis, chronic fatigue syndrome, nephrosis). The term "allergic disease" refers to a pathological condition in which a patient is hypersensitized to, and encompasses an immunological reaction against a substance that is normally non-immunogenic. The disease is usually characterized by the activation of mast cells by IgE, resulting in a inflammatory response (eg, local response, systemic response) that can result in symptoms as benign as from a loose nose to an anaphylactic shock that threatens life, and death. Examples of allergic disease include, but are not limited to, allergic rhinitis, (e.g., hayfever), asthma (e.g., allergic asthma), allergic dermatitis (e.g., eczema), contact dermatitis, allergy, and urticaria. food (hives). As used in the present invention, the "Th2-transmitted disease" refers to a disease in which the pathology is produced (in whole or in part) by an immune response (Th2 type immune response) which is regulated by CD4 + Th2 T lymphocytes, which characteristically produce IL-4, IL-5, IL-10 and IL-13. A Th2 type immune response is associated with the production of certain cytokines (eg, IL-4, IL-13) and certain classes of antibodies (eg, IgE), and is associated with mood immunity. Th2-transmitted diseases are characterized by the presence of high levels of Th2 cytokines (eg, IL-4, IL-13) and / or certain classes of antibodies (eg, IgE) and include, for example, allergic disease ( for example, allergic rhinitis, atopic dermatitis, asthma (eg, atopic asthma), allergic respiratory disease (ADA), anaphylactic shock, conjunctivitis), autoimmune disorders associated with elevated levels of IL-4 and / or IL-13 (e.g., rheumatoid arthritis, host-versus-graft disease, kidney disease (e.g., nephritic syndrome, lupus nephritis)), and infections associated with elevated levels of IL-4 and / or I Lr 13 (eg, viral, parasitic, fungal infection (eg, C. albicans)). Certain cancers are associated with elevated levels of IL-4 and / or IL-13 or associated with cancer cell proliferation induced by IL-4 and / or induced by IL-13 (e.g., B-cell lymphoma, T-cell lymphoma). , multiple myeloma, cancer of the head and neck, breast cancer and ovarian cancer). These cancers can be treated, suppressed or prevented using the ligand of the present invention. Generally, the ligands of the present invention will be used in a purified form together with pharmacologically suitable carriers. Typically, these carriers include aqueous or alcoholic / aqueous solutions, emulsions or suspensions and include saline means and / or buffers. The parenteral vehicles include sodium chloride solution, Ringer's dextrose, dextrose, and sodium chloride and lactated Ringer. Physiologically suitable adjuvants, if necessary to maintain a polypeptide complex in a suspension, can be chosen from thickeners such as carboxymethylcellulose, polyvinylpyrrolidone, gelatin and alginates. Intravenous vehicles include fillers Fluids and nutrients and electrolyte fillers, such as those based on Rlnger dextrose. One can find preservatives and other additives, such as antimicrobials, antioxidants, chelating agents and inert gases (Mack (1982) Remington's Pharmaceutical Sciences, 16th Edition). A variety of suitable formulations can be used, including prolonged release formulations. The ligand of the present invention can be used as compositions administered separately together with other agents. Ligands can be used in combination therapy with existing IL-13 therapeutics (eg, existing IL-13 agents (eg, anti-IL-13Ra1, IL-4/13 Trap, anti-l 1-13) plus IL -4 dAb, existing IL-4 agents (eg, anti-IL-4R, IL-4 Mutein, IL-4/3 Trap) plus IL-13 dAb) and antibodies IL-13 and IL-4 (e.g. WO05 / 0076990 (CAT), WO03 / 092610 (Regeneron), WO00 / 64944 (genetic Inst.) And WO2005 / 062969 (Tanox)). The ligands can be administered and / or formulated together with one or more additional therapeutic or active agents. When a ligand is administered with an additional therapeutic agent, the ligand can be administered before, simultaneously with or subsequent to the administration of the additional agent. Generally, the ligand and the additional agent are administered in a form that provides an overlap of the therapeutic effect. Additional agents that can be administered or formulated with the ligand of the present invention, include for example, various immunotherapeutic drugs, such as cyclosporin, methotrexate, adriamycin or cisplatin, antibiotics, antifungals, anti-viral agents and immunotoxins. For example, when the agonist is administered to prevent, suppress or treat lung inflammation or a respiratory disease (e.g., asthma), it can be administered together with phosphodiesterase inhibitors (e.g., phosphodiesterase 4 inhibitors), bronchodilators (e.g. beta-2 agonists, anticholinergics, theophylline), rapid-acting beta-agonists (eg, albuterol, salbutamol, bambuterol, fenoterol, isoeterin, isoproterenol, levalbuterol, metaproterenol, pirbuterol, terbutaline and telolate), long-acting beta-agonists (eg example, formoterol and salmeterol), fast-acting anticholinergics (e.g., ipratropium bromide and oxitropium bromide), long-acting anticholinergics (e.g., tiotropium), theophylline (e.g., fast acting formulation, long-acting formulation) , inhaled steroids (eg, beclomethasone, beclomethasone, budesonide, flunisolide, fluticasone propionate and triamcinolone), oral steroids (eg, methylprednisolone, prednisolone, prednisolone, and prednisone), rapid-acting beta-agonists combined with anticholinergics (eg, albuterol / salbutamol / ipratopio, and fenoterol / ipratopio), long-acting beta-agonists combined with inhaled steroids (eg, salmeterol / fluticasone and formoterol / budesonide) and mucolytic agents (eg, erdostein, acetylcysteine, bromheksin, carbocysteine, guiafenesin and iodinated glycerol) Other suitable co-therapeutic agents that can be administered with a ligand the present invention for preventing, suppressing or treating asthma (e.g., allergic asthma), include a corticosteroid (e.g., beclomethasone, budesonide, fluticasone), cromoglycate, nedocromil, beta-agonist (e.g., salbutamol, terbutaline, bambuterol, fenoterol , reproterol, tolubuterol, salmeterol, fomtero), zafirlukast, salmeterol, prednisone, prednisolone, theophylline, zileutron, montelukast and leukotriene modifiers The ligands of the present invention can be administered together with a variety of co-therapeutic agents suitable for treating diseases (for example, a disease transmitted with Th2, disease transmitted with IL-4, tra Smitted with IL-13, disease transmitted with IL-4 and IL-13, cancer), including cytokines, analgesics / antipyretics, antiemetics and chemotherapeutics. Cytokines include, without limitation, a lymphokine, tumor necrosis, tumor necrosis factors, cytokine type tumor necrosis factor, lymphotoxin, interferon, macrophage inflammatory protein, monocyte colony stimulation factor, granulocyte, interleukin, (including , without limitation, interleukin-1, interleukin-2, interleukin-6, interleukin-12, interleukin-15, interleukin-18), growth factors, including without limitation (eg, growth hormone, growth factor 1 and 2) insulin type (IGF-1 and IGF-2), granulocyte colony stimulation factor (GCSF), platelet-derived growth factor (PGDF), epidermal growth factor (EGF), and agents for erythropoiesis stimulation, for example , recombinant human erythropoietin (Epoetin alfa), EPO, a hormonal agonist, hormonal antagonists (eg, flutamide, tamoxifen, leuprolide acetate (LUPRON)), and steroids (eg, dexamethasone, retinoid, betamethasone, cortisol, cortisone, prednisone , dehydrotestosterone, glucocorticoid, mineralocorticoid, estrogen, testosterone, progestin). Analgesics / antipyretics may include, without limitation, (eg, aspirin, acetamitophen, ibuprofen, naproxen sodium, buprenorphine hydrochloride, propoxyphene hydrochloride, propoxyphene napsylate, meperidine hydrochloride, hydromorphone hydrochloride, morphine sulfate, oxycodone hydrochloride, codeine phosphate, dihydrocodeine bitartrate, pentazocine hydrochloride, hydrocodone bitartrate, levorphanol tartrate, diflunisal, trolamine salicylate, Nalbuphine hydrochloride, mefenamic acid, butorphanol tartrate, choline salicylate, butalbital, phenyltoloxamine citrate, diphenylhydramine citrate, methotrimeprazine, Cinamedrin hydrochloride, meprobamate and the like). The antiemetics can be administered together to prevent or treat nausea and vomiting, for example, suitable antiemetics including meclizine hydrochloride, nabilone, prochlorperazine, dimenhydrinate, promethazine hydrochloride, thiethylperazine, scopolamine and the like). Chemotherapeutic agents, as the term is used in the present invention, include but are not limited to, for example, antimicrotubule agents (e.g., taxol (paclitaxel)), taxotere (docetaxel); alkylating agents (e.g., cyclophosphamide, carmustine, lomustine and chlorambucil); cytotoxic antibiotics (eg, dactinomycin, doxorubicin, mitomycin-C and bleomycin; antimetabolites (eg, cytarabine, gemcitatin, methotrexate and 5-fluorouracil); antimitotics (eg, vinca alkaloids, vincristine (eg, etoposide, vinblastine and vincristine) )), and others such as cisplatin, dacarbazine, procarbazine and hydroxyurea, and combinations thereof The pharmaceutical compositions may include "cocktails" of various other cytotoxic or other agents, together with the ligands of the present invention, or even combinations of ligands according to the present invention having different specificities, such as ligands selected using different target antigens or epitopes, whether or not they are pooled before administration.

The route of administration of the pharmaceutical compositions according to the present invention can be any suitable route, such as any of the routes known to those skilled in the art. For therapy, including without limitation immunotherapy, the ligand of the present invention can be administered to any patient according to standard techniques. The administration can be any suitable mode, including parenterally, intravenously, intramuscularly, intraperitoneally, transdermally, intrathecally, intraarticularly, via the pulmonary route, or also suitably, by direct infusion (for example, with a catheter). The dosage and frequency of administration will depend on the age, sex and condition of the patient, concurrent administration of other drugs, contraindications and other parameters that will be taken into account by the specialist. Administration may be local (eg, local administration to the lung by pulmonary administration (eg, intranasal administration) or local injection directly into a tumor) or systemic administration as indicated. The ligands of the present invention can be lyophilized for storage and reconstituted in a suitable carrier prior to use. This technique has been shown to be effective with conventional immunoglobulins and lyophilization and reconstitution techniques known in the art. The Those skilled in the art will appreciate that lyophilization and reconstitution can lead to varying degrees of loss of antibody activity (for example, with conventional immunoglobulins, IgM antibodies tend to have greater loss of activity than with IgG antibodies) and such levels of use may have to be adjusted upwards to compensate. The compositions containing the ligands can be administered for prophylactic and / or therapeutic treatments. In certain therapeutic applications, an amount suitable for achieving at least one inhibition, suppression, modulation, partial extermination or some other measurable parameter of a population of selected cells is defined as a "therapeutically effective dose". The amounts needed to achieve this dosage will depend on the severity of the disease and the general state of health of the patient, although they will generally fluctuate from 0.005 to 5.0 mg of ligand per kilogram of body weight, with doses of 0.05 to 2.0 mg / kg / dose being the most commonly used. For example, prophylactic applications, compositions containing the ligands or cocktails thereof of the present invention may also be administered in slightly lower doses or the like, to prevent, inhibit or delay the generation of the disease (e.g. remission or latency, or to avoid the acute phase). Those skilled in the art will have the ability to determine the proper dosage range to treat, suppress or prevent the disease. When a ligand is given to treat, suppress or prevent a disease, it can be administered up to four times a day, twice a week, once a week, once every two weeks, once a month or once every two. months, in a dose, for example, from about 10 Mg kg to about 80 mg / kg, from about 100 Mg / kg to about 80 mg / kg, from about 1 mg / kg to about 80 mg / kg, of about 1 mg / kg to about 70 mg / kg, from about 1 mg / kg to about 60 mg / kg, from about 1 mg / kg to about 50 mg / kg, from about 1 mg / kg to about 40 mg / kg, about 1 mg / kg to about 30 mg / kg, from about 1 mg / kg to about 20 mg / kg, from about 1 mg / kg to about 10 mg / kg, from about 10 Mg / kg to about 10 mg / kg , from about 10 Mg / kg to about 5 mg / kg, of about 1 0 MQ kg to about 2.5 mg / kg, about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg kg, approximately 8 mg / kg, approximately 9 mg / kg or approximately 10 mg / kg. In particular modalities, the Ligand is administered to treat, suppress or prevent a chronic allergic disease once every two weeks or once a month in a dose of about 10 μg / kg to about 10 mg / kg (per axis, about 10 μg kg, approximately 100 μg kg, approximately 1 mg / kg, approximately 2 mg / kg, approximately 3 mg / kg, approximately 4 mg / kg, approximately 5 mg / kg, approximately 6 mg / kg, approximately 7 mg / kg, approximately 8 mg / kg kg, approximately 9 mg / kg or approximately 10 mg / kg,). In particular embodiments, the ligand is administered to treat, suppress or prevent asthma every day, every other day, once a week, once every two weeks or once a month in a dose of about 10 μg / kg to about 10 mg / kg (eg, about 10 μg / kg, about 100 μg / kg, about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, approximately 7 mg / kg, approximately 8 mg / kg, approximately 9 mg / kg or approximately 10 mg / kg). The ligand can be administered in a daily dose or unit dose (eg, to treat, suppress or prevent asthma) in a daily dose or unit dose of about 10 mg, about 9 mg, about 8 mg, about 7 mg, about 6 mg, about 5 mg, about 4 mg, about 3 mg, about 2 mg or about 1 mg. In particular embodiments, the ligand of the present invention is administered in a dose that provides saturation of IL-4 and / or IL-13 or a desired in vivo serum concentration. Those skilled in the art can determine the appropriate dosage to achieve saturation, for example, by grinding a ligand and monitoring the amount of free binding sites in IL-4 and / or IL-13 or the serum concentration of the ligand. Therapeutic regimens involving the administration of a therapeutic agent to achieve target saturation or a serum concentration of the desired agent are common in the art. The treatment or therapy carried out using the compositions described herein are considered as "effective", if one or more symptoms are reduced (for example, by at least 10% or at least one point on a clinical evaluation scale), with relation to the symptoms present before treatment, or in relation to the symptoms in an individual (human or animal model) not treated with said composition or other suitable control. The symptoms will obviously vary depending on the target disease or disorder, but may be measured by one skilled in the art. These symptoms can be measured, for example, by monitoring the level of one or more indicators biochemicals of the disease or disorder (e.g., levels of an enzyme or metabolite correlated with the disease, numbers of affected cells, etc.). monitoring physical manifestations (eg, inflammation, tumor size, etc.), or through an accepted clinical assessment scale, for example, evaluation of Juniper's Asthma Quality of Life Questionnaire (American Thoracic Society's 32), which evaluates quality of life with respect to activity limitations, symptoms, emotional function and exposure to environmental stimuli; Juniper, et al., "Health-related Quality of Life in Modérate Asthma", Chest, 116: 1297-1303 (1999)), the Expanded Disability Status Scale (for multiple sclerosis), the Irvine Inflammatory Bowel Disease Questionnaire (32 point evaluation that assesses quality of life with respect to bowel function, systemic symptoms, social function and emotional state - scores range from 32 to 224, where the highest scores indicate a better quality of life), the Quality of Life Rheumatoid Arthritis Scale, or other clinical evaluation scale accept known in the art. A sustained reduction (for example, a day or more, preferably longer) in the symptoms of the disease or disorder by 10% or one or more points on a given clinical scale indicates that the treatment is "effective". Similarly, prophylaxis carried out using a composition as described herein is "effective" if the generation or severity of one or more of the symptoms are delayed, reduced or eliminated in relation to said symptoms in a similar individual (human or animal model) not treated with the composition. A composition containing ligands according to the present invention, can be used in prophylactic and therapeutic preparations to aid in the alteration, deactivation, extermination or elimination of a population of selected target cells in a mammal. In addition, the ligands and repertoires of polypeptides selected herein, can be used in extracorporeal or in vitro form to effectively and selectively exterminate, eliminate or deplete a population of target cells from a collection of heterogeneous cells. The blood of a mammal can be combined extracorporeally, with the ligands, for example, antibodies, cell surface receptors or binding proteins thereof, whereby the unwanted cells are exterminated or otherwise eliminated from the blood that returns to the mammal, according to standard techniques. EXAMPLES EXAMPLE 1: GENERAL METHODS For primary selections against human IL-13, dAbs Vk and dAbs VH libraries were scoured against biotinylated human IL-13 protein (R & D systems, Minneapolis, US). IL-13 was biotinylated using a five-fold molar excess of EZ-Link reagent Sulfo-NHS-LC-Biotin (Pierce, Rockford, USA). Turn 1 was carried out with magnetic beads coated with streptavidin (Dynal, Norway), and either 100 nM or 20 nM antigen; lap 2 with beads coated with neutravidin and either 20 nM or 4 nM antigen (Henderikx et al., 2002, Selection of antibodies against biotinylated antigens, Antibody Phage Display: Methods and protocols, Ed. O'Brien and Atkin, Humana Press). In the second primary selection, the same phage display libraries dAb VH and Vk were washed with a pan while maintaining the antigen concentration at 100 nM, in a final volume of 1 ml PBS, containing 2% Marvel. In the first and third rounds, 4 mg of M280 Streptavidin Dynabeads beads (Dynal, Norway) were used to capture the antigen-phage complexes. In the second round, 4 mg of M270 Carboxi Dynabeads with Neutravidin beads (Dynal, Norway) were used instead. M270 Carboxy Dynabeads beads (Dynal, Norway) were coated with Neutravidin by standard carbodiiminated chemistry as indicated below. Two thousand ml of Carboxy M-270 Dynabeads beads (30 mg / ml, 2x106 counts / μ?) Were washed twice with 1 ml 0.01 M NaOH, which allows for four minutes between washes. Sodium hydroxide was removed through two washes with water, followed by activation of the carboxy groups with 1 ml of 40 mg / ml of 1-Ethyl-3- [3-dimethylaminopropyl] carbodiimide hydrochloride (EDC) (Sigma, U.K.) for 30 minutes at room temperature, with rotary mixing. EDC-activated beads were washed twice with water and 1 ml of 1 mg / ml Neutravidin (Pierce, USA) in 10 mM of 2-Morpholinoethanesulfonic acid buffer (MES, Sigma, U.K.) pH5 were added to the activated beads. The coupling reaction was allowed to proceed with rotation for 30 minutes at room temperature. After coupling, the beads were captured, the unreacted Neutravidin was removed and the reactive-amine groups not reactivated in the beads were quenched by incubation with 1 ml of 0.05 M tris (hydroxymethyl) aminomethane (Tris) buffer, pH4 for fifteen minutes. minutes at room temperature, the coated and extinguished beads were washed four times in PBS containing 0.1% BSA, resuspended in 1 ml thereof. Sodium azide (Sigma, U.K.) was added at 0.02% for preservation and the beads were stored at a temperature of 4 ° C until they were required. The selection process of phage libraries dAb VH and Vk, is described in the following tables (Table 1 and 2) TABLE 1 The VH domain antibodies were cloned (DOM10-236 (SEQ ID NO 1804) DOM10 -238 (SEQ ID NO: 1805 DOM10-241 (SEQ ID NO 1806) DOM10 -245 (SEQ ID NO: 1807 DOM10-249 (SEQ ID NO 1808) DOM10 -250 (SEQ ID NO: 1809 DOM10-251 (SEQ ID NO 1810) DOM10 -254 (SEQ ID NO: 1811 DOM10-256 (SEQ ID NO 1812) DOM10 -259 (SEQ ID NO: 1813 DOM10-260 (SEQ ID NO 1814) DOM10 -261 (SEQ ID NO: 1815 DOM10-263 (SEQ ID NO 1816) DOM10 -264 (SEQ ID NO: 1817 DOM10-273 (SEQ ID NO 1818) DOM10 -278 (SEQ ID NO: 1819 DOM10-279 (SEQ ID NO 1820) DOM10 -281 (SEQ ID NO: 1821 DOM10-282 (SEQ ID NO 1822) DOM10 -283 (SEQ ID NO: 1823 DOM10-400 (SEQ ID NO 1824) DOM10 -401 (SEQ ID NO: 1825 DOM10-402 (SEQ ID NO 1826) DOM10 -404 (SEQ ID NO: 1827 DOM10-406 (SEQ ID NO: 1828) DOM10 -407 (SEQ ID NO: 1829 DOM10-409 (SEQ ID NO: 1830) DOM10 -410 (SEQ ID NO: 1831 DOM10-414 (SEQ ID NO 1832) DOM10 -415 (SEQ ID NO 1833) DOM10 -416 (SEQ ID NO 1834) DOM10 -418 (SEQ ID NO 1835) DOM10 -420 (SEQ ID NO 1836) DOM10 -422 (SEQ ID NO 1837) DOM10 -423 (SEQ ID NO 1838) DOM10 -424 (SEQ ID NO 1839) DOM10 -425 (SEQ ID NO 1840) DOM10 -426 (SEQ ID NO 1841) DOM10 -427 (SEQ ID NO 1842) DOM10 -428 (SEQ ID NO 1843) DOM10 -429 (SEQ ID NO 1844) DOM10 -430 (SEQ ID NO 1845) DOM10 -431 (SEQ ID NO 1846) DOM10 -432 (SEQ ID NO 1847) DOM10 -433 (SEQ ID NO 1848) DOM10 -467 (SEQ ID NO 1849) DOM10 -468 (SEQ ID NO 1850) DOM10 -469 (SEQ ID NO 1851) DOM10 -470 (SEQ ID NO 1852) DOM10 -234 (SEQ ID NO 1853) DOM10 -235 (SEQ ID NO 1854) DOM10 -237 (SEQ ID NO 1855) DOM10 -239 (SEQ ID NO 1856) DOM10 -240 (SEQ ID NO 1857) DOM10 -242 (SEQ ID NO 1858) DOM10 -243 (SEQ ID NO 1859) DOM10 -244 (SEQ ID NO 1860) DOM10 -246 (SEQ ID NO 1861) DOM10 -247 (SEQ ID NO1862) DOM10 -248 (SEQ ID NO 1863) DOM10 -252 (SEQ ID NO 1864) DOM10 -257 (SEQ ID NO 1865) DOM10 -258 (SEQ ID NO1866) DOM10 -262 (SEQ ID NO 1867) DOM10 -265 (SEQ ID NO-1868) DOM10 -266 (SEQ ID NO: 1869) DOM10 -274 (SEQ ID NO: 1870) DOM10 -275 (SEQ ID NO: 1871) DOM10 -276 (SEQ ID NO: 1872) DOM10 -277 (SEQ ID NO: 1873) DOM10 -280 (SEQ ID NO: 1874) DOM10 -403 (SEQ ID NO: 1875) DOM10 -405 (SEQ ID NO: 1876), DOM10 -408 (SEQ ID NO: 1877), DOM10 -411 (SEQ ID NO: 1878), DOM10 -412 (SEQ ID NO: 1879), DOM10 -413 (SEQ ID NO: 1880), DOM10 -417 (SEQ ID NO: 1881), DOM10- -419 (SEQ ID NO: 1882), DOM10-472 (SEQ ID NO: 1883)) (DOM10-203 (SEQ ID NO: 1884), DOM10 -205 (SEQ ID NO: 1885), DOM10 -208 (SEQ ID NO 1886), DOM10 -218 (SEQ ID NO: 1887), DOM10 -219 (SEQ ID NO 1888), DOM10 -220 (SEQ ID NO: 1889), DOM10-225 (SEQ ID NO 1890), DOM10 -228 (SEQ ID NO: 1891), DOM10 -229 (SEQ ID NO 1892), DOM10 -230 (SEQ ID NO: 1893), DOM10 -231 (SEQ ID NO 1894), DOM10 -268 (SEQ ID NO: 1895), DOM10 -201 (SEQ ID NO 1896), DOM10 -202 (SEQ ID NO: 1897), DOM10 -204 (SEQ ID NO 1898), DOM10 -206 (SEQ ID NO: 1899), DOM10 -207 (SEQ ID NO 1900), DOM10 -209 (SEQ ID NO: 1901), DOM10 -210 (SEQ ID NO 1902), DOM10 -211 (SEQ ID NO: 1903), DOM10 -213 (SEQ ID NO 1904), DOM10 -214 (SEQ ID NO: 1905), DOM10 -215 (SEQ ID NO 1906), DOM10 -216 (SEQ ID NO: 1907), DOM10 -217 (SEQ ID NO 1908), DOM10 -221 (SEQ ID NO: 1909), DOM10 -223 (SEQ ID NO 1910), DOM10 -224 (SEQ ID NO: 1911), DOM10 -227 (SEQ ID NO 1912), DOM10 -232 (SEQ ID NO: 1913), DOM10 -53-425 (SEQ ID NO: 2018)), in an expression vector pDOM5 for classification by ELISA or BIAcore range-out analysis. For primary selections against human IL-4, dAbs VH libraries and dAbs Vk libraries were screened against biotinylated human IL-4 protein (Peprotech, Rocky Hill, USA). IL-4 was biotinylated as described above. Turn 1 was carried out with magnetic beads coated with neutravidin (Dynal, Norway) and 100 nM antigen; the turn 2 with beads coated with streptavidin and 20 nM antigen. Neutravidin-coated beads were prepared by incubating tosyl-activated Dyna beads (Dynal, Norway) in 5 mg / ml biotin binding protein of neutravidin lmmunopure / 0.1 M borate buffer pH 9.5 for 16 hours at a temperature of 37 ° C , followed by incubation in 0.1% (w / v) BSA / PBS for 5 minutes at a temperature of 4 ° C, followed by incubation in 0.1% (w / v) BSA / 0.2 M Tris pH 8.5 for 16 hours at a temperature of 4 ° C. The elution in each step was with 1 mg / ml trypsin-PBS. For affinity maturation selections, the above method was used but with the following modifications: two to four selection rounds were performed using streptavidin-coated beads and descending antigen concentrations (within the range of 1 nM to 50 pM). The phage vector was isolated from the selection productions (laps 2 and 3) by plasmid preparation (Qiagen) and the dAb insert was released by restriction digestion with Sal I and Not I. This insert was ligated into Sal \ INot I cut pDOM5 and was used to transform E. coli strain HB2151 for soluble expression and dAbs classification. pDOM5 is an expression vector based on pUC119 under the control of the LacZ promoter. The expression of the dAbs in the supernatant was ensured by fusion to the universal GAS leader signal peptide at the N-terminus. Also I know it adhered a myc-tag tag at the C-terminal end of the dAbs. After transformation of the E. coli HB2151 cell, the colonies were used to inoculate 50 to 500 ml_ of a Terrific Broth broth medium supplemented with carbenicillin (100 μl per ml_). Induction was carried out with OVERNIGHT EXPRESS ™ SYSTEM 1 (high level protein expression system, Novagen) according to the manufacturer's instructions. The cultures were incubated at a temperature of 30 ° C for 24 to 48 hours with shaking at 250 rpm. After cell pelletization by centrifugation (4,000 rpm for 20 minutes) the supernatants were filtered using a 0.45 μ? T filter. and incubated overnight at a temperature of 4 ° C with Streamline-protein A beads (Amersham Biosciences, binding capacity: 5 mg dAb per ml_ counts) for the VH dAbs, or L-sepharose protein beads ( Affitech, bonding capacity: 2 mg of dAb per ml_ of beads) for the VL dAbs. The beads were then packed in drip columns, washed with 10 column volumes of PBS, and the bound dAbs eluted in 0.1 M glycine-HCl, pH 2.0 or 3.0 for the VH and VL dAbs, respectively. After neutralization with 1 M Tris-HCl, pH 8.0, the samples of the protein were dialyzed in PBS and concentrated in concentrators Vuvaspina 5-kDa (Vivascience) before being stored at a temperature of 4 ° C. The purity of protein by visual analysis after SDS-PAGE on Tris-glycine gel of 12% acrylamide (Invitrogen). Protein concentrations and yields (in mg per L of bacterial culture) were measured at 280 nm, using extinction coefficients from the amino acid compositions. Affinity maturation using phage libraries Maturation was carried out using error-prone mutagenesis, site-directed mutagenesis of multiple residues and simple residue sorting technologies. For error-prone maturation libraries, the plasmid DNA encoding the dAb that will be matured by PCR was amplified using the GENEMORPH® II RANDOM MUTAGENESIS KIT (Stratagene single mutagenesis kit). The product was digested with Sal I and Not I and used in a ligation reaction with the phage cut vector pDOM4. For site-directed mutagenesis and single-residue libraries, PCR reactions were carried out, using degeneration oligonucleotides containing codons NNK or NNS to diversify the positions required in the dAb that will be matured by affinity. Subsequently, PCR assembly was used to generate a diversified insert of total length. The insert was digested with Sal I and Not I and used in a ligation reaction with pDOM4 for mutagenesis of multiple residues and pDOM5 for mutagenesis of single residues. The ligature produced through any method, is subsequently used to transform the E. coli strain TB1 by electroporation and the transformed cells were coated on 2xTY agar containing 15 μg / ml tetracycline, producing libraries with sizes of > 1x107 clones. pDOM4 is a derivative of the phage vector Fd in which the gene signal peptide sequence III is replaced with the surface protein signal peptide anchored with yeast glycolipid (GAS). It also contains a c-myc tag between the leader sequence and gene III, which places gene III back in frame. This leader sequence works well both in phage display vectors and in other prokaryotic expression vectors and can be used universally. Affinity maturation using emulsification Construction of library One pg of template DNA was amplified by PCR either from DOM10-176 (SEQ ID NO: 1285), DOM9-155 (SEQ ID NO: 451) or DOM9-44 (SEQ ID NO. : 358) dAb Vk, using GENEMORPH II for 35 cycles with the primer group OA16 (ATACCATGGGGTCGACGG ACATCCAG; SEQ ID NO: 1797) and OA17n (TTCTTTTGCGGCCGCCCGTTTGATTTCCACC; SEQ ID NO: 1798), followed by restriction digestion with Sali and Notl . The fragments DOM10-176 (SEQ ID NO: 1285), DOM9-155 (SEQ ID NO: 451) and DOM9-44 (SEQ ID NO: 358) were ligated into any of the plE2aA or plE7t3T vectors using T4 DNA ligase. in 20 μ? of volume. They were derived all vectors of the vector plVEx2.2b Nde de Roche. They were amplified 0.5 μ? aliquots of ligation product in the presence of competition DNA in the real-time PCR in a BioRad ini-Opticon thermal cycler to establish that the number of ligation events exceeded 109 per reaction. The libraries were amplified by PCR from the ligation reaction using either SuperTaq and the primers AS11 (TTCGCTATTACGCCAGCTGG; SEQ ID NO: 1799) and AS17 (CAGTCAGGCACCGTGTATG; SEQ ID NO: 1800) (scArc libraries) or pfx platinum and primers AS12 (AAAGGGGGATGTGCTGCAAG; SEQ ID NO.1801) and AS18 (AACAATGCGCTC ATCGTCATC; SEQ ID NO; 1802) (Tus libraries). For libraries of targeted diversification, oligonucleotides containing NNS codons at the indicated positions were used and the dAb was assembled by overlap PCR. The assembly reaction was amplified with PCR with OA16 / 17n oligonucleotides using PfuUltra DNA polymerase and Sall / Notl cloned into the scArc or Tus vi n translation vectors (IVT). 10 pg of template DNA of either dAb VH DOM10-416 (SEQ ID NO: 1834), DOM10-273 (SEQ ID NO: 1818), DOM10-275 (SEQ ID NO: 1871) or DOM10-276 was amplified by PCR. (1872) using Genemorphll for 35 cycles with the primer adjustment AS9 (SEQ ID NO: 1916) and AS65 (SEQ ID NO: 1917), followed by a restriction digestion with I left and Notl. Fragments DOM10-416 (SEQ ID NO: 1834), DOM10-273 (DOM 10-273), DOM10-275 (SEQ ID NO: 1871) or DOM10-276 (SEQ ID NO: 1872) were ligated clean in a vector plE2a2A (SEQ ID NO: 2015), a plE2aA derivative with two Are operators per gene and potentially tetravalent deployment capacity, using T4 DNA ligase in a volume of 20 μ ?. They were amplified 0.5 μ? of aliquots of the ligation product using real-time PCR in a BioRad Mini-Opticon thermal cycler to establish that the number of ligation events exceeded 109 per reaction. Expression and emulsification in vitro The following reaction mixture was used for the in vitro transcription / translation of the PCR fragment library: 1.5 μ? 100 mM of oxidized glutathione, 2 μ? 5 mM of methionine, 0.5 μ? of DNA (5.0 x 108 molecules), 10 μ? H20, 0.25 μ? of 50 mg / ml of 3F10 mAb anti-Ha (used only with scArc), biotinylated antigen in various concentrations and 35 μ? of transcription-translation extract coupled with EcoPro T7. Immediately after mixing, the extract was added to 0.7 ml of light white mineral oil containing 4.5% (v / v) Span-80 and 0.5% (v / v) Triton X-100. The emulsification was carried out by spinning a magnetic stirrer for 5 minutes at 2000 rpm and a 5 ml glass bottle. Microscopic analysis of droplet formation confirmed that the droplets had ~ 2 μ? diameter. The emulsion was incubated for 60 (Tus) to 180 (scArc) minutes at a temperature of 25 ° C to allow the expression and formation of the protein-DNA complex to take place. The PBS / 1% emulsion was broken by adding 0.25 ml of BSA / biotinylated antigen and 0.5 ml of hexane / 20% (v / v) mineral oil, followed by a short vortex and centrifugation for 1 minute at 13,000 rpm . After removal of the oil phase, 1 ml of hexane / mineral oil was added and the procedure was repeated three times. The last extraction was carried out using only hexane. Selection and amplification The selection of linkers was carried out, incubating the extracted aqueous phase for 30 minutes in the presence of 50 - 5 nM of biotinylated antigen (See below for the exact conditions used per turn). If range-out selections are made, this incubation is followed by the addition of an excess of non-biotinylated antigen, or the VH dAb of origin at a concentration of 1 μ ?, and an incubation within the range of 5-100 minutes. . Each emulsion reaction was subsequently divided into 5 deposits of a streptavidin-coated PCR plate (50 μl / reservoir), incubated for 15 minutes at a temperature of 25 ° C, and washed 4 times with PBS / BSA. Fifteen μ? Were added to each deposit PCR mixture containing either primers OA16 / 17n, PfuUltra buffer, dNTPs, 2.5 μm DNA polymerase PfuUltra (Tus) or pairs successive nested primers, dNTPs, KOD polymerase buffer and 2.5 u of KOD polymerase (scArc). PCR was carried out for 25 (scArc) or 30 (Tus) cycles. For Tus selections, the PCR product was cleaned and digested with Sall / Notl. Subsequently, the fragment was ligated into the vector plE737 and amplified as described in the library construction. For scArc, the PCR product was gel purified and used directly for a next round of selection. PEGylation using aldehyde and PEGs activated with NHS Under suitable conditions, the proteins can be PEGylated in specific manner through the N-terminus using PEG-aldehyde (PEG-ALD). This has the advantage that the protein does not require any additional construction to introduce a specific amino acid for modification, such as cysteine when PEG-maleimide is used. Under optimized buffer conditions, it is still possible that part of the protein is modified through the lysine residues when PEG-ALD is used. An alternative method is to use PEGs activated with NHS or SPA, which react in a specific way with the lysine residues of the surface. EXAMPLE 2: IL-4 binding ligands IL-4 receptor binding assay (RBA) A MAXISORP ™ plate was coated overnight (high level protein binding plate, ELISA, Nunc, Denmark) with 0.5 μ9 /? T ?? of recombinant human IL-4R / Fc (R & D Systems, Minneapolis, USA). The deposits were washed three times with 0.1% (v / v) Tween 20 in PBS, followed by three washes with PBS, before blocking with 2% (w / v) BSA in PBS. The plates were washed again before the addition of 10 ng / ml of biotinylated II-4 (R &D Systems) mixed with dilution series of anti-IL-4 or IL-4 dAbs. The IL-4 binding was detected with anti-biotin antibody labeled with peroxidase (Stratech, Soham, UK) and subsequently developed with TBM substrate (KPL, Gaithersburg, USA). The reaction was stopped by the addition of HCl and the absorbance was read at 450 nm. The anti-IL-4 dAb activity caused a decrease in the IL-4 binding to the receptor and consequently, a decrease in absorbance compared to the control of only IL-4. IL-4 Cell Assay Isolated dAbs were tested for their ability to inhibit proliferation induced with IL-4 in cultured TF-1 cells (ATCC catalog No. CRL-2003). In synthesis, 40,000 TF-1 cells were placed in RPMI medium free of phenol red (Gibco, Invitrogen Ltd, Paisley, UK), in the reservoir of a tissue culture microtiter plate and mixed with a final concentration of 1. ng / ml of IL-4 (R &D Systems, Minneapolis, USA) and a dilution of dAb that will be tested. The mixture was incubated for 72 hours at a temperature of 37 ° C 5% C02. Subsequently CELLTITER 96® reagent was added (colorimetric reagent to determine viability, Promega, Madison, USA), and the number of cells per cell was quantified by measuring the absorbance at 490 nm. Anti-IL-4 dAb activity caused a decrease in cell proliferation and an A490 correspondingly lower than IL-4 alone. Competitive BIACORE® with anti-IL-4 dAbs These experiments were carried out on a BIACORE® 3000 instrument, using a SA chip streptavidin coated (Biacore surface plasmon resonance system), coupled with ~ 400 RU of IL- 4 biotinylated (R &D Systems). The materials for analysis were passed over the flow cell coated with antigen, with in-line reference against a blank cell-flow, in the flow range of 30 μ? / Minute in HBS-EP in a run buffer (Biacore) . The first dAb was injected, followed immediately by an injection of the second dAb using the Biacore co-injection function. For this experiment, dAbs DOM9-44 (SEQ ID NO: 358), DOM9-155-1 (SEQ ID NO: 452) and DOM9-112-22 (SEQ ID NO: 47) were used. This competition protocol can generally be used to evaluate the competition of an antibody or test fragment with a known dAb (or other antibody polypeptide) for binding to IL-4. Allergen-induced cell proliferation Blood was collected from allergic donors to household dust aids (HDM). Subsequently, cells were isolated peripheral blood mononuclear cells (PBMC) using a Ficoll gradient. The cells were plated at 4x106 / ml in a 96-well plate and stimulated with HDM at 20-50 ug / ml. Anti-IL-4 dAbs were added in 100 nM at the start of the culture (1.4 ug / ml). The cells were incubated for 5 days, with the addition of thymidine 3 [H] for the final 18 hours. Subsequently the cells were harvested and the proliferation was evaluated by determining the amount of 3H incorporated in the cellular DNA. Selection and primary classification for anti-IL-4 dAbs Primary phage selections were carried out using the dAb VH and Vk libraries and the sub-cloned productions in the soluble expression vector pDOM5. The dAb clones that inhibit the binding of IL-4 to L-4 R were identified by supernatant receptor binding assay (RBA). Subsequently, the clones were expressed, purified by protein A or protein L and tested as a dose response in the RBA to estimate the potency with which the clones inhibited the binding of IL-4 to IL-4R. Table 3 shows the results of anti-IL-4 dAbs DOM9-44 (SEQ ID NO: 358), DOM9-112 (SEQ ID NO: 25) and DOM9-155 (SEQ ID NO: 451) in said RBA test.

TABLE 3 Affinity maturation of anti-IL-4 dAbs DOM9-44 lineage The DOM9-44 lineage was matured by affinity using in vitro expression and emulsification. Libraries were constructed that diversify the CDR2 and CDR3 residues and were used in selections against biotinylated IL-4. Exit clones were expressed, purified and classified in the IL-4 receptor binding assay (RBA). The most potent dAb of this lineage was DOM9-44-502 (SEQ ID NO: 361), which had a power of 5.5 nM in the IL-4 RBA (Table 4) and 4.5 nM in the IL-4 cell assay (Table 5). TABLE 4 TABLE 5 DOM9-155 lineage The DOM9-155 lineage was matured by affinity using in vitro expression and emulsification. The DOM9-155 dAb (SEQ ID NO: 451) was amplified by PCR under error-prone conditions and ligated into the Tus vector, followed by a second PCR to amplify the IVT cartridge. Subsequently the libraries were subjected to turns in sequence of selection against biotinylated IL-4. Ten selection rounds were carried out followed by cloning into the supernatant expression and expression vector overnight. The improved clones were identified by Biacore classification and subsequently used as a template for libraries of CDR1 residue diversification by NNS mutagenesis. Production clones were expressed, purified and tested in the IL-4 receptor binding assay and the IL-4 cell assay. The most potent dAbs of the DOM9-155 lineage identified using these methods were DOM9-155-25 (SEQ ID NO: 466), with an IC50 of 0.86 nM in the RBA (Table 4) and 0.83 nM in the cell assay (Table 5). The additional classification of this production identified two additional dAbs with sub nanomolar powers: DOM9-155-77 (SEQ ID NO: 2393) and DOM9-155-78 (SEQ ID NO: 2394). Lineage DOM9-112 The DOM9-112 lineage was matured by affinity by phage display using an error-prone maturation library, CDR 1 multiple residue diversification libraries and 2 CDR1 and 2 individual residue diversification libraries. phage libraries resulting in selections against biotinylated IL-4. The productions were cloned in pDOM5 vector and expression supernatants were classified for improved range-out compared to the origin. The improved-range dAbs were expressed, purified and tested in the IL-4 receptor (RBA) assay and cell assay. The most potent dAbs identified using these methods were DOM9-112-155 (SEQ ID NO: 118), DOM9-112-168 (SEQ ID NO: 131), DOM9-112-174 (SEQ ID NO: 137), DOM9 -112-199 (SEQ ID NO: 162), DOM9-112-200 (SEQ ID NO: 163), DOM9-112-202 (SEQ ID NO: 165) and DOM9-112-210 (SEQ ID NO: 2401) with IC 50 values within the range of 0.9 to 3 nM, as measured in the RBA IL-4 (Table 4). Epitope Mapping of anti-IL-4 dAbs To determine the epitope specificity of dAbs anti-IL-4, BIACORE® competition experiments (surface plasmon resonance, Biacore) were carried out. DAb DOM9-44 (SEQ ID NO: 358) was injected into the chip coupled with IL-4, followed by injection of dAb DOM9-155-1 (SEQ ID NO: 452) which could not bind to IL-4 after it linked DOM9-44 (SEQ ID NO: 358) (figure 13). Similarly, DOM9-44 (SEQ ID NO: 358) then linked DOM9-155-1 (SEQ ID NO: 452). However, dAb DOM9-112-22 (SEQ ID NO: 47) was able to bind to IL-4 after it linked dAb DOM9-44 (SEQ ID NO: 358) and after it linked dAb 9-155-1 (SEQ ID NO: 452). These results indicate that dAbs DOM9-44 (SEQ ID NO: 358) and DOM9-155-1 (SEQ ID NO: 452) linked to the same epitope and that DOM9-112-22 (SEQ ID NO: 47) linked to a different epitope from DOM9-44 (SEQ ID NO: 358) and DOM9-155-1 (SEQ ID NO: 452). This competition protocol can generally be used to evaluate the competition (and epitope mapping) of an antibody or test fragment with a known dAb (or other antibody polypeptide) to bind to IL-4. Allergic-induced PBMC cell proliferation of all allergic donors showed a dose-dependent proliferation when incubated with HDM (house dust acrid). The addition of the anti-IL-4 dAbs resulted in an inhibition of allergen-induced proliferation in most of the donors. dAb inhibited proliferation of PBMC DOM9-44-502 (SEQ ID NO: 361) of 10 of the 12 donors (Figure 14A), DOM9-155-11 (SEQ ID NO: 457) inhibited PBMC proliferation of 10 of 12 donors (Figure 14B) and DOM9-112-22 (SEQ ID NO: 47) inhibited the proliferation of PBMC from 2 of 2 donors. The average inhibition in all the donor response was 38%, 34% and 23% inhibition for dAb DOM9-44-502 (SEQ ID NO: 361), DOM9-155-11 (SEQ ID NO: 457) and DOM9 -112-22 (SEQ ID NO: 47), respectively. The reason why maximum responses are observed only from 30 to 40%, is most likely due to the fact that this allergen-induced response does not only depend on IL-4, but also depends on other interleukins such as IL-2. B cell proliferation induced by IL-4 Blood was collected from normal blood donors. PBMC were isolated using the Ficoll gradient. Subsequently, B cells were isolated using a negative B cell isolation kit (EasySep Negative isolation kit, Stem Cell Technologies Inc). The purity had an excess of 98% as determined by flow cytometry and staining with CD3, CD4, CD8, CD14, CD14, CD19 and CD23. Subsequently, B cells were coated in 1 x 10 5 cells / reservoir in the presence of IL-4 (10 ng / ml) in plates coated with irradiated CD40L + L cells. The cultures were incubated for 5 days with the addition of 3 [H] thymidine for the final 18 hours.

Anti-IL-4 dAbs were added at the start of culture at 10 nM or 100 nM. Cross reactivity with IL-4 of resus and cinomolgus. A desired requirement of these dAbs may be cross-reactivity with IL-4 resus and cynomolgus. For this purpose, DOM9-112-210 (SEQ ID NO: 2401), DOM9-155-5 (SEQ ID NO: 454), DOM9-155-25 (SEQ ID NO: 466), DOM9-155-77 were tested. (SEQ ID NO: 2393) and DOM9-155-78 (SEQ ID NO: 2394) in the TF-1 cell proliferation assay (see above for a more detailed description) wherein the cells are stimulated with IL-4 human (0.5 ng / ml, Peprotech), IL-4 of resus (0.5 ng / ml, R & D systems) or IL-4 cynomolgus (1: 25000 dilution of supernatant containing IL-4 of locally expressed cinomolgus). A dose response of dAb will determine the ND50 in this preparation. A summary of the values obtained in the table below is provided (Table 6) and demonstrates cross-reactivity. TABLE 6 EXAMPLE 3: Ligands that bind IL-13 sandwich ELISA A MAXISORP plate was coated overnight. (high-level protein binding ELISA plate, Nunc, Denmark) with 2.5 μ? / ??? of coating antibody (Module Set, Bender MedSystems, Vienna, Austria), subsequently washed once with 0.05% (v / v) Tween 20 in PBS before blocking with 0.5% (w / v) BSA 0.05% (v / v) Tween 20 in PBS. The plates were washed again before the addition of 25 pg / ml IL-13 (Bender MedSystems) mixed with a dilution series of DOM10 dAb (eg, an anti-IL-13 dAb) or IL-13. The plates were washed again before the IL-13 binding to the capture antibody which was detected using a detection antibody conjugated with biotin (Module Set, Bender Medsystems), followed by Streptavidin labeled with peroxidase (Module Set, Bender MedSystems). Subsequently the plate was incubated with TMB substrate (KPL, Gaithersburg, USA), and the reaction was stopped by the addition of HCl and the absorbance was read at 450 nm. Anti-IL-13 dAb activity caused a decrease in IL-13 binding and consequently a decrease in absorbance compared only to the IL-13 control. IL-13 receptor binding assay (RBA) using the 8200 cell detection system SPHERO ™ calf anti-human IgG polystyrene particles (H & L) (0.5% w / v) (calf particles) were coated overnight. anti-human, Spherotech, Libertyville, USA) with 20 μg IL-13R alpha 1 / chimera Fe or IL-13R alpha 2 / Chimera Fe (R &D Systems, Minneapolis, USA). Subsequently, the following reagents were combined on an FMAT plate with a light background with the black sides of 384 deposits (Applied Biosystems, Foster City, USA): dilution series of DOM-10 dAb or 0.1% (w / v) BSA in PBS; 0.5 g / ml biotinylated anti-IL-13 antibody (R & D Systems); 0.25 μg / ml of STREPTAVI DI ALEXA FLUOR® 647 conjugate (fluorescent probe, Molecular Probes, Invitrogen Ltd, Paisley, UK); 10 ng / ml recombinant human IL-13 (R & D Systems); and 1:10 dilution of IL-13R2 / Fe coated particles. The plate was incubated for seven hours before being read in the 8200 cell detection system (Applied Biosystems). The binding of IL-13 to the receptor coated particle caused a complex to form, which was detected as a fluorescent event through 8200. The anti-IL-13 dAb activity caused a decrease in the IL-13 binding, and therefore a decrease in fluorescent events compared only with the IL-13 control. IL-13 Cell Assay Isolated dAbs were tested for their ability to inhibit proliferation induced with IL-13 in cultured TF-1 cells (ATCC catalog No. CRL-2003). Briefly, 40,000 TF-1 cells were placed in RPMI-free red phenol medium (Gibco, Invitrogen Ltd, Paisley, UK), in the reservoir of a tissue culture microtitre plate and mixed with a final concentration of 5 ml. ng / ml of IL-13 (R & D Systems, Minneapolis, USA) and a dilution of the dAb that will be tested. The mixture was incubated for 72 hours at a temperature of 37 ° C 5% C02. Subsequently, CELLTITER 96® reagent (colorimetric reagent to determine viability) was added, Promega, Madison, USA), and the number of cells per deposit was quantified by measuring the absorbance at 490 nm. Anti-IL-13 dAb activity caused a decrease in cell proliferation and a lower A490 corresponding to IL-13 alone. BIACORE® range-out classification SA chip coated with streptavidin was coated (Biacore) with approximately 500 RU of biotinylated IL-13 (R &D Systems, Minneapolis, USA). The supernatant containing soluble dAb 1: 5 was diluted in the buffer of the run. 50 to 100 ul of the diluted supernatant (kininject) were injected in a flow rate of 50 ul / minute, followed by a dissociation phase in 5 minutes. The clones with ranges-out improved compared to the origin were identified with the naked eye, or by measurement using the software Bl Aevaluation v4.1 (Biacore). Competition BIACORE® with anti-IL-13 dAbs These experiments were carried out on a BIACORE® 3000 instrument (Biacore surface plasmon resonance instrument), using a SA chip streptavidin coated (Biacore) coupled with ~ 400 RU of biotinylated IL-13 (R &D Systems). The materials for analysis are passed over the antigen-coated cell-flow, with in-line reference against a blank cell-flow, in a flow range of 30 μ? / minute in HBS-EP run buffer (Biacore). The first dAb DOM 10-176-535 (SEQ ID NO: 1362) was injected, followed immediately by the injection of dAb DOM10-53-99 (SEQ ID NO: 738), using the Biacore joint injection function. This competition protocol can generally be used to evaluate the competition of an antibody or test fragment with a known dAb (or other antibody polypeptide) to bind to IL-13. Competition and Epitope Mapping Epitope Mapping of Anti-IL-13 dAbs To determine the epitope specificity of anti-IL-13 dAbs, Biacore competition experiments were carried out. DOM dAb 10-176-535 (SEQ ID NO: 1362) was injected, followed immediately by injection dAb DOM 10-53-99 (SEQ ID NO: 738). The dAb DOM10-53-99 (SEQ ID NO: 738) did not bind to IL-13 to which the dAb DOM 10-176-535 (SEQ ID NO: 1362) had already bound. This indicates that these dAbs linked to the same epitope. This competition protocol can be used in general to evaluate the competition (and epitope mapping) of an antibody or known dAb test fragment (or other antibody polypeptide) to bind to IL-13. The epitopes for a second group of dAbs were determined using a slightly modified BIAcore protocol in where the first dAbs were injected onto an IL-13 surface, subsequently a high affinity binding dAb (DOM10-53-386 (SEQ ID NO: 934),) was injected at a higher concentration (5 μ?) saturating the surface IL-13 and finally the dAbs were injected again. If there is a difference between a link before and after saturation with DOM10-53-386 (SEQ ID NO: 934), the epitopes are at least partially overlapped. Using this experimental preparation, it was determined that dAbs Vk DOM10-212 (SEQ ID NO: 2016), DOM10-270 (SEQ ID NO: 1915), DOM10-213 (SEQ ID NO: 1904) and DOM10-215 (SEQ ID NO: 1906) share the same epitope of DOM 10-53-386 (SEQ ID NO: 934), while DOM10-208 (SEQ ID NO: 1886); and DOM10-224 (SEQ ID NO: 1911) have a different epitope. The same BIAcore preparation was used for the injection of the dAbs Vh DOM10-416 (SEQ ID NO: 1834), DOM10-236 (SEQ ID NO: 1804), DOM10-273 (SEQ ID NO: 1818), DOM10-275 ( SEQ ID NO: 1871), DOM10-276 (SEQ ID NO: 1872) and DOM10-277 (SEQ ID NO: 1873). All of these dAbs were shown to have overlap epitopes at least partially with DOM 10-53-386, (SEQ ID NO: 934). This shows that less dAb binds to DOM 10-53-386 (SEQ ID NO: 934) once it has been injected. B cell proliferation induced by IL-13 Blood was collected from normal blood donors. PBMC was isolated using the Ficoll gradient. Subsequently isolated B cells using a negative B cell isolation kit (EasySep Negative isolation kit, Stem Cell Technologies Inc). The purity had an excess of 98% as determined by flow cytometry and staining with CD3, CD4, CD8, CD14, CD14, CD19 and CD23. Subsequently, B cells were coated in 1 x 10 5 cells / reservoir in the presence of IL-13 (10 ng / ml) in plates coated with irradiated CD40L + L cells. The cultures were incubated for 5 days with the addition of 3 [H] thymidine for the final 18 hours. Anti-IL-13 dAbs were added at the start of the culture at 10 nM or 100 nM. Formatting: Specific site-specific PEGylation of DOM 10-53-343 using PEG-Maleimide The anti-IL-13 dAb DOM 10-53-343 was constructed (SEQ ID NO: 891) with a cysteine in the C-terminus of the protein. The expression and purification of the dAbs was carried out as described above. Cysteine was modified specifically with branched dAb to produce 40K monomeric modified PEG2-MAL protein. Other PEG formats are available such as linear PEG-MAL which can also be used to provide PEGylated monomers, for example, 30K or 40K linear PEG. mPEG-MAL raPEG2-MAL The mPEG-Mal formats can be used to PEG a monomeric dAb. PEGs can have a MW of 500 to 60,000 (for example, 2,000 to 40,000) in size and have either linear or branched nature. Was reduced 1 ml of 160 μ? DOM 10-53-343cys with 5 mM dithiothreitol and left at room temperature for 20 minutes. Subsequently the sample was exchanged with buffer using a PD-10 column (Amersham Pharmacia), to eliminate the reducing agent. The column had previously been equilibrated with 5 mM EDTA, 20 mM BIS-TRIS pH 6.5, 10% glycerol, and the sample was applied and diluted according to the manufacturer's instructions. Subsequently the sample (3.5 ml of ~ 50 μ? DAb) was mixed directly with a three-fold molar excess of 40K PEG-MAL (~ 20 mg). The reaction was allowed to proceed at room temperature for 3 hours. Purification of the monomer cys DOM10-53-343 PEGylated by anion exchange The sample was further purified using anion exchange chromatography (1 ml of Resource Q column) to remove any unreacted PEG and protein. The sample was diluted 3 times in an equilibrium buffer (50 mM TRIS pH 8.0), before being applied to the column which had also been balanced in the same buffer. The PEGylated material was separated from unmodified dAb, running a gradient of linear sodium chloride from 0 to 500 mM, in 50 mM TRIS buffer in a 20 volume column. Fractions containing the PEGylated dAb were only identified using SDS-PAGE and subsequently pooled. N-terminal PEGylation using 30K PEG-ALD The anti-IL dAb 13 DOM10-53-338 (SEQ ID NO: 886) was PEGylated through the N-terminus (a-amino group) using 30K PEG-ALD. The dAb was exchanged with buffer in a 20 mM phosphate buffer pH 6.0 to produce a final protein concentration of 2 mg / ml (-166 μ?). A 5-fold molar excess of PEG-ALD (830 μl of polymer) was added directly to the dAb solution followed by the addition of 2 mM sodium cyanoborohydride to reduce the temporary imine binding to an amine which is stable for hydrolysis. The reaction was allowed to proceed overnight at room temperature, the sample was further purified using anion exchange chromatography as described above.

PEGylation of surface lysine residues using 40K PEG2-NHS The anti-IL dAb 13 DOM 10-53-338 (SEQ ID NO: 886) was PEGylated through surface lysine residues using 40K PEG2-NHS. The dAb was exchanged with buffer in 20 mM phosphate buffer pH 8.0 to produce a final protein concentration of 2 mg / ml (-166 μ?). A 5-fold molar excess of PEG-NHS (830 μl of polymer) was directly added to the dAb solution and the reaction was allowed to proceed at room temperature overnight. The sample was further purified using anion exchange chromatography as described above.

Primary selection and classification of anti-IL-13 s-dAbs Primary phage selections were carried out using the dAb VH and Vk libraries and sub-cloned productions in the soluble expression vector pDOM5. The dAb clones that inhibit the binding of IL-13 to IL-13RI were identified by RBA supernatant. Subsequently the clones were expressed, purified by protein A or protein L and tested as a dose response in the RBA to determine the potency with which the clones inhibited the binding of IL-13 to IL-13RI. Table 7 shows the results of the anti-IL-13 dAbs DOM10-53 (SEQ ID NO: 651) and DOM10-176 (SEQ ID NO: 1285) in said RBA test, where their IC50 values are 150 and 100. nM, respectively, in so much that the rest have IC50 values in a micromolar range. TABLE 7 Affinity maturation of anti-IL-13 dAbs Lineage DOM10-176 Nucleic acid encoding DOM 10-176-535 dAb (SEQ ID NO: 1362) was amplified with PCR under conditions prone to error and ligated into the scArc vector, followed by a second PCR to amplify the IVT cartridge. Subsequently, the libraries were subjected to selection turns in sequences, with antigen concentrations that decreased in stages from 50 to 5 nM. A separate diversification library of positions 52 to 54 on CDR2 of DOM10-176 (SEQ ID NO: 1285) was constructed and used in additional selections. Production clones were expressed as supernatants and were classified for range-out improved as compared to the origin. The improved-range dAbs were expressed, purified and tested in the sandwich ELISA assay IL-13 and cell assay. Mutations from the best identified dAbs were combined both of these selections, creating DOM10-176-535 (SEQ ID NO: 1362). This was the most potent dAb of lineage DOM10-176, with an IC50 value in the RBA within the 0.5 nM range and a 0.77 nM value in the IL-13 cell assay (Tables 8 and 9). TABLE 8 Lineage DOM10-53 The DOM10-53 lineage was matured by affinity by phage display using a maturation library error-prone, multiple residue diversification libraries of CDR 1, 2 and 3 and libraries of individual residue diversification of CDR1, 2 and 3. The resulting phage libraries were used in selections against biotinylated IL-13. The productions were cloned in the pDOM5 vector and the expression supernatants were classified for out-of-range ranges compared with the origin. The improved-range dAbs were expressed, purified and tested in the sandwich ELISA assay IL-13 and cell assay. The most potent dAbs identified using these methods were DOM 10-53-223 (SEQ ID NO: 774), DOM10-53-234 (SEQ ID NO: 785), DOM10-53-3 6 (SEQ ID NO: 866), DOM10-53-339 (SEQ ID NO: 887), 'DOM 10-53-344 (SEQ ID NO: 892) and DOM 10-53-396 (SEQ ID NO: 944), with power values as estimated in the sandwich ELISA assay IL-13 and cell assay IL-13 within the range of 100 pM to 40 pM (Tables 8 and 9). Inhibition of IL-13 binding to IL-13Ra2 The anti-IL-3 dAbs were tested for their ability to inhibit the binding of IL-13 to IL13Ra2 in a competition assay. Table 10 shows that both DOM10-53-316 (SEQ ID NO: 866) and DOM 10-176-535 (SEQ ID NO: 1362) had the ability to inhibit the binding of IL-13 to IL13Ra2 with IC50 values of 2. nM and 8 nM respectively.

TABLE 10 Link to IL-13 variant (R130Q) The genetic variants of IL-13 had been associated with an increased risk of asthma (Heinzmann et al., Hum Mol Genet. (2000) 9549-59) and bronchial hyperresponse (Howard and associates., Am. J. Resp. Cell Molec. Biol (2001) 377-384). Therefore, it was determined that if the anti-IL-13 dAbs have the ability to bind variant IL-13 (R130Q), the proliferation assay TF-1 with IL-13 variant (R130Q) is carried out, and increase in dAb. Table 11 shows that both DOM 10-53-316 (SEQ ID NO: 866) and DOM10-176-535 (SEQ ID NO: 1362) had the ability to inhibit TF-1 proliferation induced by IL-13 variant with ND50 values of approximately 0.5 nM and 8 nM respectively. TABLE 11 Cross reactivity with IL-13 of resus and cinomolgus.

A desired requirement of these dAbs may be cross-reactivity with IL-13 resus and cynomolgus. For this purpose, DOM 10-53-344 (SEQ ID NO: 892) and DOM 10-53-434 (SEQ ID NO: 2053) were tested in the TF-1 cell proliferation assay (see above for a description with greater detail) where the cells were stimulated with human IL-13 (5 ng / ml, Peprotech), IL-13 of resus (5 ng / ml, R & D systems) or IL-13 cynomolgus (dilution 1: 4000 of supernatant containing IL-13 of cinomolgus expressed locally). A response to the dose of dAb will determine the ND50 in this preparation. A summary of the values obtained is given in the table below (Table 12) and demonstrates cross-reactivity. TABLE 12 Lineages DOM10-416, DOM10-273, DOM10-275 and DOM 10-276. Error-prone PCR libraries were prepared from dAbs VH DOM10-416 (SEQ ID NO: 1834), DOM10-236 (SEQ ID NO: 1804), DOM10-273 (SEQ ID NO: 1818), DOM10-275 (SEQ ID NO. : 1871), DOM10-276 (SEQ ID NO: 187234) and DOM10-277 (SEQ ID NO: 1873) and quantified as described above. The challenge of the ligation mixture was used as a template for the second PCR reaction catalyzed with regular Taq polymerase (SuperTaq, HT Biotechnology Ltd, Cambridge, UK) with primers AS11 and AS17 to amplify the IVT cartridge. DOM10-275 (SEQ ID NO: 1871) and DOM10-276 (SEQ ID NO: 1872) were kept separate during the affinity maturation reaction, DOM10-273 (SEQ ID NO: 1818) and DOM10-416 (SEQ. ID NO: 1834). The libraries were subsequently subjected to ten rounds of selection. In the first four rounds of selection, the concentration of antigens was 75 nM, in the next two rounds 60 mM, followed by two rounds in 45 nM and. two final laps at 30 nM. The selection production was cloned into a pDOM5 expression vector and the culture supernatants were cultivated by surface plasmon resonance in BIAcore 1000. A number of clones with improved properties were identified. Surprisingly, the improved clones were characterized mostly not by prone to error PCR mutations, but by recombination events between the clones. DOM10-275-1 (SEQ ID NO: 1918) comprises CDR1 and CDR2 of DOM10-275 (SEQ ID NO: 1871) and CDR3 of DOM10-273 (SEQ ID NO: 1818). DOM10-276-2 (SEQ ID NO: 1919) comprises CDR1 and CDR3 of DOM10-276 (SEQ ID NO: 1872) and CDR2 of DOM10-416 (SEQ ID NO: 1834). DOM10-276-2 (SEQ ID NO: 1919) comprises CDR1 and CDR2 of DOM10-416 (SEQ ID NO: 1834) and CDR3 of DOM10-276 (SEQ ID NO: 1872). Clones from the PCR library selection prone to error are described as DOM10-275-1 (SEQ ID NO: 1918), DOM10-276-2 (SEQ ID NO: 1919), DOM10-276-3 (SEQ ID NO: 1920), DOM10-275- 3 (SEQ ID NO: 1979), DOM10-277-2 (SEQ ID NO: 1980), DOM10-277-3 (SEQ ID NO: 1981), DOM10-273-1 (SEQ ID NO: 1982), DOM 10 -273-2 (SEQ ID NO: 1983), DOM10-275-2 (SEQ ID NO: 1984), DOM10-275-4 (SEQ ID NO: 1985), DOM 10-276-1 (SEQ ID NO: 1986) ), DOM10-276-4 (SEQ ID NO: 1987) and DOM10-277-1 (SEQ ID NO: 1988). TABLE 13 Directed diversification libraries of dAbs VH DOM10-273, DOM10-275 and DOM10-276. The VH domain antibodies DOM10-273 (SEQ ID NO: 1818), DOM10-275 (SEQ ID NO: 1871) or DOM10-276 (1872) they were also matured by affinity by diversification at positions 52, 54, 55, 57 and 59 of CDR2 and positions 101, 102 and 104 of CDR3. In both CDRs, two directed positions were randomized in all possible combinations. The libraries that direct the same PCR in the clones of respective origin were assembled and recombined in structures three by SOE PCR, giving rise to a recombinant library with four residues randomized by gene, two in CDR2 and two in CDR3, in all combinations possible surrounding their respective CDR1 regions (diversity calculated at the 3x107 nucleotide level of different clones), that is, three libraries in total. The same was repeated by pooling the 5 'and 3' PCR fragments of all the clones of origin before the SOE PCR step, creating a library of approximately 108 theoretical diversity. Finally, the 5 'fragment of library group DOM10-275 encoding CDR1 and CDR2 was recombined with the 3' group of the CDR3 libraries of DOM10-273. Directed diversification library 1. The CDR2 region of dAb VH DOM10-273 (SEQ ID NO: 1818) in the pDOM5 vector was diversified into ten PCR regions using 10 pg of template DNA polymerase and SuperTaq. The following primers were used: AS818 (SEQ ID NO: 1921), AS819 (SEQ ID NO: 1922), AS820 (SEQ ID NO: 1923), AS821 (SEQ ID NO: 1924), AS822 (SEQ ID NO: 1925) , AS823 (SEQ ID NO: 1926), AS824 (SEQ ID NO: 1927), AS825 (SEQ ID NO: 1928), AS826 (SEQ ID NO: 1929), AS827 (SEQ ID NO: 1930), AS828 (SEQ ID NO: 1931), for running PCR amplification reactions using AS339 (SEQ ID NO: 1951) as the reverse primer. The reaction products were combined and purified with 2% Gel-E (Invitrogen, USA), forming Fragment Group 1. Fragment Group 1 was subsequently extended with SOE PCR with the PCR reaction product formed from the amplification of the same vector construct with the forward primer AS9 (SEQ ID NO: 1916) and the reverse primer AS829 (SEQ ID NO: 1932). The SOE PCR comprised 15 cycles of amplification with SuperTaq DNA polymerase in a hardening step at a temperature of 50 ° C. The formation of the SOE product was verified by gel electrophoresis and an aliquot of the 5 μl reaction was further amplified. with primers AS639 (SEQ ID NO: 1952) and AS65 (TTGTAAAACGACGGCCAGTG; SEQ ID NO: 1917). The CDR3 region of DOM10-273 VH dAb in the pDOM5 vector was diversified into three PCR reactions using 10 pg of the Super Taq DNA template and polymerase. The following forward primers: AS830 (SEQ ID NO: 1933), AS831 (SEQ ID NO: 1934) and AS832 (SEQ ID NO: 1935) were combined with AS339 (CAGGAAACAGCTATGACCATG; SEQ ID NO: 1951). The reaction products were pooled and purified in 2% E-Gel (Invitrogen, USA), forming a Fragment Group 2. The Fragment 2 group was subsequently extended by SOE PCR with the PCR reaction product formed from the amplification of the same vector construction with the forward primer AS9 (SEQ ID NO: 1916) and the reverse primer AS833 (SEQ ID NO: 1936). The SOE PCR comprised 15 cycles of amplification with SuperTaq DNA polymerase in a hardening step at a temperature of 50 ° C. The formation of the SOE product was purified by gel electrophoresis and an aliquot of the 5 μm reaction was further amplified. with the primers AS339 (SEQ ID NO: 1951) and AS65 (SEQ ID NO: 1917). The recombination reaction of the libraries focused with CDR2 and CDR3 of DOM10-273 (SEQ ID NO: 1818), based on Groups of Fragments 1 and 2, was carried out in the region of structure 3. Fragments were generated that carry CDR2 library by PCR amplification from Fragment Group 1 with the primers AS639 (SEQ ID NO: 1952) and AS660 (SEQ ID NO: 1976). The fragment carrying the CDR3 library was generated, by PCR amplification of Fragment 2 Group with the primers AS659 (SEQ ID NO: 1975) and AS65 (SEQ ID NO: 1917). The SOE reaction was carried out as indicated above, except that the extended product was reamplified with the primers AS297 (SEQ ID NO: 1977) and AS298 (SEQ ID NO: 1978). The amplification reaction product was gel purified, cut with enzymes Sal I and Not I, was re-purified in 2% E-Gels and subsequently ligated into a Sal l / Not l-cut plE2a2A vector. Directed diversification library 2. The CDR2 region of DOM10-275 VH dAb in the pDOM5 vector was diversified into ten PCR reactions using 10 pg of the SuperTaq DNA template and polymerase. All of the following forward primers were used: AS836 (SEQ ID NO: 1939), AS837 (SEQ ID NO: 1940), AS838 (SEQ ID NO: 1941), AS839 (SEQ ID NO: 1942), AS840 (SEQ ID NO: 1943), AS841 (SEQ ID NO: 1944), AS842 (SEQ ID NO: 1945), AS843 (SEQ ID NO: 1946), AS844 (SEQ ID NO: 1947), AS845 (SEQ ID NO: 1948) AS846 (SEQ ID NO: 1949), for running PCR amplification reactions using AS339 (SEQ ID NO: 1951) in the reverse primer. The reaction products were pooled and purified with 2% E-Gel (Invitrogen, USA), forming a Fragment Group 3. The Fragment Group of 3 was subsequently extended by SOE PCR, as described above, with the PCR reaction product formed from the amplification of the same vector construct with the forward primer AS9 (SEQ ID NO: 1916) and the reverse primer AS847 (SEQ ID NO: 1950). The formation of the SOE product was verified by gel electrophoresis and an aliquot of the 5 μl reaction was further amplified. with the primers AS65 (SEQ ID NO: 1917) and AS639 (SEQ ID NO: 1952). The CDR3 region of DOM10-273 VH dAb in the vector pD0M5 was diversified into three PCR reactions using 10 pg of the SuperTaq DNA template and polymerase. The following forward primers were combined: AS848 (SEQ ID NO: 1953), AS849 (SEQ ID NO: 1954) and AS850 (SEQ ID NO: 1955) each with AS339 (SEQ ID NO: 1951). The reaction products were pooled and purified with 2% E-gel in (Invitrogen, USA), forming a Fragment Group 4. The Fragment 4 group was subsequently extended by SOE PCR with the PCR reaction product formed from of the amplification of the same vector construct with the forward primer AS9 (SEQ ID NO: 1916) and the reverse primer AS851 (ATAAGCTTTCGCACAGTAATATAC; SEQ ID NO: 1956). SOE product formation was verified by gel electrophoresis and a 5 pl aliquot of the reaction was amplified in addition with the primers AS339 (SEQ ID NO: 1951) and AS65 (SEQ ID NO: 1917). The recombination reaction of libraries focused with CDR2 and CDR3 of DOM10-275, based on Fragment Groups 3 and 4, was carried out in structure 3 of the dAb molecule. Fragments carrying the CDR2 library were generated by PCR amplification from Fragment Group 3 with the primers AS639 (SEQ ID NO: 1952) and AS660 (SEQ ID NO: 1976). The fragment carrying the CDR3 library was generated by PCR amplification of the Fragment 4 group with the AS659 primers (SEQ ID NO: 1975) and AS65 (SEQ ID NO: 1917). The SOE reaction was carried out as indicated above, except that the extended product was reamplified with the primers AS297 (SEQ ID NO: 1977) and AS298 (SEQ ID NO: 1978). The product of the amplification reaction was gel-purified, cut with enzymes Sal I and Not I, re-purified in 2% gels-E and subsequently ligated into the vector Sal l / Not l-cut plE2a2. Directed diversification library 3. The CDR2 region of DOM10-276 VH dAb in pDOM5 was diversified into 10 PCR reactions using 10 pg of the SuperTaq DNA template and polymerase. All of the following forward primers were used: AS854 (SEQ ID NO: 1959), AS855 SEQ ID NO: 1960), AS856 (SEQ ID NO: 1961), AS857 (SEQ ID NO: 1962), AS858 (SEQ ID NO: 1963) ), AS859 (SEQ ID NO: 1964), AS860 (SEQ ID NO: 1965), AS861 (SEQ ID NO: 1966), AS862 (SEQ ID NO: 1967), AS863 (SEQ ID NO: 1968) AS864 (SEQ ID NO: 1969) to run PCR amplification reactions using AS339 (SEQ ID NO: 1951) as the reverse primer. The reaction products were pooled and purified with 2% E-gel in (Invitrogen, USA), forming Fragment Group 5. Fragment Group 5 was subsequently extended by SOE PCR, as described above, with the PCR reaction product formed from the amplification of the same vector construct with the forward primer AS9 (SEQ ID NO: 1916) and the reverse primer AS865 (SEQ ID NO: 1970). The SOE product formation was verified by gel electrophoresis and an aliquot of the 5 μ reaction. it was further amplified with the primers AS65 (SEQ ID NO: 1917) and AS639 (SEQ ID NO: 1952). The CDR3 region of DOM10-273 VH dAb of the pDOM5 vector was diversified into three PCR reactions using 10 pg of the SuperTaq DNA template and polymerase. Each of the following forward primers AS866 (SEQ ID NO: 1971), AS867 (SEQ ID NO: 1972) and AS868 (SEQ ID NO: 1973) was combined with AS339 (SEQ ID NO: 1951). The reaction products were pooled and purified with 2% E-gel (Invitrogen, USA), forming Fragment Group 6. Fragment Group 6 was subsequently extended by SOE PCR with the PCR reaction product formed from the amplification of the same vector construct with the forward primer AS9 (SEQ ID NO: 1916) and the reverse primer AS869 (ATAAGCTTTCGCACAGTAATATAC; SEQ ID NO: 1974). The SOE product formation was verified by gel electrophoresis and an aliquot of the 5 μl reaction was further amplified. with the primers AS339 (SEQ ID NO: 1951) and AS65 (SEQ ID NO: 1917). The recombination reaction of the CDR2 and CDR3 focused libraries of DOM10-276, based on Fragment Groups 5 and 6, was carried out in structure 3 of the dAb molecule. The CDR2 library carrying the fragments were generated by PCR amplification of the Fragment group 3 with the primers AS639 (SEQ ID NO: 1952) and AS660 (SEQ ID NO: 1976). The fragment carrying the CDR3 library was generated by PCR amplification of the Fragment 4 group with the primers AS659 (SEQ ID NO: 1975) and AS65 (SEQ ID NO: 1917). The SOE reaction was carried out as above, except that the extended product was amplified again with the primers AS297 (SEQ ID NO: 1977) and AS298 (SEQ ID NO: 1978). The amplification reaction was purified with gel, cut with enzymes Sal I and Not I, re-purified in 2% gels-E and subsequently ligated into a vector Sal l / Not l-cut plE2a2 A. The library of directed diversification 4. The recombination reaction of all the libraries focused with CDR2 and CDR3 was carried out through the three dAbs VH DOM10-273 (SEQ ID NO: 1818), DOM10-275 (SEQ ID NO: 1871) and DOM10-276 (SEQ ID NO: 1872) in structure 3 of the dAb molecule. The CDR2- library carrying the fragments was generated by PCR amplification of the libraries elaborated from Fragment Groups 1, 3 and 5 with primers AS639 (SEQ ID NO: 1952) and AS660 (SEQ ID NO: 1976). The fragment carrying the CDR-3 library was generated by PCR amplification of the libraries elaborated from Fragment Groups 2, 4 and 6 with the primers AS659 (SEQ ID NO: 1975) and AS65 (SEQ ID NO: 1917). The SOE reaction was carried out as indicated above, except that the Extended product was amplified again with the primers AS297 (SEQ ID NO: 1977) and AS298 (SEQ ID NO: 1978). The amplification reaction product was gel purified, cut with enzymes Sal I and Not I, re-purified in 2% gels-E and subsequently ligated into a Sal l / Not l-cut vector plE2a2 A. Library Directed Diversification The recombination reaction of the entire CDR2- focused library of DOM10-273, (SEQ ID NO: 1818) with the focused CDR3- library of DOM10-273, was carried out in structure 3 of the dAb molecule . Fragments carrying the CDR-2 library were generated by PCR amplification of the library made from Fragment Group 3 using the primers AS639 (SEQ ID NO: 1952) and AS660 (SEQ ID NO: 1976). The fragment carrying the CDR-3 library was generated by PCR amplification of libraries made from Fragment 2 Groups using the primers AS659 (SEQ ID NO: 1975) and AS65 (SEQ ID NO: 1917). The SOE reaction was carried out as indicated above, except that the extended product was amplified again with the primers AS297 (SEQ ID NO: 1977) and AS298 (SEQ ID NO: 1978). The amplification reaction product was gel purified, cut with Sal I and Not I enzymes, re-purified in 2% Gel-E and subsequently ligated into a Sal l / Not l-cut vector plE2a2 A. of diversification libraries directed from Lineages DOM10-273 DOM10-275 and DOM10-276. Directed diversification libraries of lineages DOM10-273 (SEQ ID NO: 1818), DOM10-275 (SEQ ID NO: 1871) and DOM10-276 (SEQ ID NO: 1872) were ligated and quantified as described above for PCR libraries prone to error. Subsequently, the libraries underwent ten rounds of selection. In the first round of selection, the concentration of antigens was 40 nM, in the second round 20 nM, followed by eight rounds in 10 nM. The competitor dAb DOM10-275-1 (SEQ ID NO: 1918) was applied at a concentration μ? starting from the fourth round of selection for 10, 20, 20, 30, 50, 90 and 90 minutes, after a 15-minute equilibrium with the antigen. The selection output was cloned into the expression vector pDOM5 and the culture supernatants were sorted by surface plasmon resonance in BIAcore 1000. A number of clones were identified (eg, DOM10-275-13 (SEQ ID NO: 1989 ), DOM10-275-15 (SEQ ID NO: 1990), DOM10-275-20 (SEQ ID NO: 1991), DOM10-275-8 (SEQ ID NO: 1992), DOM10-276-13 (SEQ ID NO. : 1993), DOM10-276-14 (SEQ ID NO: 1994), DOM10-276-15 (SEQ ID NO: 1995), DOM10-276-17 (SEQ ID NO: 1996), DOM10-276-7 (SEQ ID NO: 1997), DOM10-276-8 (SEQ ID NO: 1998), DOM10-275-11 (SEQ ID NO: 1999), DOM10-275-12 (SEQ ID NO: 2000), DOM10-275-14 (SEQ ID NO: 2001), DOM10-275-16 (SEQ ID NO: 2002), DOM10-275-17 (SEQ ID NO: 2003), DOM10-275-5 (SEQ ID NO: 2004), DOM 10-275-6 (SEQ ID NO: 2005), DOM10- 275-7 (SEQ ID NO: 2006), DOM10-275-9 (SEQ ID NO: 2007), DOM10- 276-10 (SEQ ID NO: 2008), DOM 10-276-11 (SEQ ID NO: 2009), DOM10-276-12 (SEQ ID NO: 2010), DOM10-276-16 (SEQ ID NO: 2011) , DOM10-276-5 (SEQ ID NO: 2012), DOM10- 276-6 (SEQ ID NO: 2013), DOM10-276-9 (SEQ ID NO: 2014)). TABLE 14 Epitope Mapping of Anti-IL-13 dAbs To determine the epitope specificity of the anti-IL-13 dAbs, Biacore competition experiments were carried out. DOM 10-176-535 (SEQ ID NO: 1362) was injected dAb followed immediately by injection of dAb DOM10-53-99 (SEQ ID NO: 738). dAb DOM10-53-99 (SEQ ID NO: 738) did not bind to IL-13 which had already bound to dAb DOM 10 176-535 (SEQ ID NO: 1362). This indicates that these dAbs linked to the same epitope. This competition protocol can generally be used to evaluate the competition (and mapping of epitope) of a test fragment antibody with a known dAb (or other antibody polypeptide) to bind to IL-13. B Cell Proliferation Assay It has previously been shown that CD40L has the ability to activate cells responsive to IL-13. In fact all the donors tested in this study showed a dose-dependent proliferation when their B cells were incubated with irradiated CD40L * L cells and increasing concentrations of IL-13. They were used as negative controls, B cells alone or L cells transfected with CD40L. Addition of anti-IL-13 dAbs DOM10-53-338 (SEQ ID NO: 886) and DOM 10 176-535 (SEQ ID NO: 1362) resulted in an inhibition of IL-13 induced proliferation of B cells. of all donors (FIG.15). With both of dAbs DOM 10-53-338 (SEQ ID NO: 886) and DOM10-176-535 (SEQ ID NO: 1362) the average inhibition was 80% and 100% at concentrations of 10 nM and 100 nM respectively. Complete inhibition of B cell proliferation was also observed with 3 Mg / ml of 13 mAb anti-IL positive control (R & amp; amp;; D). Dabs that did not bind to IL-13 failed to inhibit this B-cell proliferation. PEGylated Monomer The anti-IL13 dAb DOM 10-53-338 (SEQ ID NO: 886) was PEGylated by the N-terminus using a PEG portion of 30K aldehyde or through surface lysines using the portion activated with 40K PEG2-NHS. The anti-L dAbs L13 DO 10-53-343 (SEQ ID N0.891) were also cloned with a cysteine at the C-terminus of the protein. This molecule was PEGylated via the C-term using PEG-Maleimide with a branched 40K PEG2-MAL portion. To determine the effect of PEGylation, PEGylated DOM 10-53-338 dAbs were tested for their ability to inhibit IL-13 binding in the IL-13 receptor binding assay and inhibit induced TF-1 cell proliferation. through IL-13. The potency of both DOM 10-53-338 PEGylated 30K dAb and as of DOM10-53-338 40K PEGylated dAb was maintained in the IL-13 receptor binding assay (Table 15) and in the TF-cell proliferation assay 1 induced by IL-13 (Table 15). To determine the effect of C-terminal PEGylation, PEGylated DOM10-53-343 dAbs (40K PEG2-MAL) were tested for their ability to inhibit IL-13 binding to the IL-13 receptor binding assay (Table 15 ). The potency of the C-terminal PEGylated DOM10-53-343 dAb was slightly improved compared to the DOM 10-53-343 native dAb in the IL-13 receptor binding assay.

TABLE 15 Biophysical properties of anti-IL-13 dAbs In order to develop a product for pulmonary delivery, it is desired that the molecule has good biophysical properties. Poor chemical stability and physical stability can reduce biological activity. Proteins delivered in pulmonary form can be exposed to additional stress, for example by sharing forces and using increased temperatures in the nebulization apparatus. Lungs can metabolize part of the dose given and in some indications of disease, high levels of proteases can be found that can affect biological activity. For this purpose, the state of the solution was investigated by means of Multi Angle Ligth Scattering (MALS) dispersion and the melting temperature as determined by differential scanning calorimetry (DSC) of the molecules. of lineage DOM10-53. SEC-MALLS (multiple angle LASER light scattering) The properties in the solution of dAb proteins were determined through an initial separation SEC (size exclusion chromatography; TSKgel G200073000SWXL, Tosoh Biosciences, Germany; BioSep-SEC-S200073000, Phenomenex, CA, USA) and subsequently in an on-line detection of proteinaceous material eluted by UV (Abs280nm), RI (refractive index) and light scattering (laser at 685nm). The proteins had an initial concentration of 0.5-1mg / mL, as determined by absorbance at 280nm, and were visually inspected for impurities by SDS-PAGE. The homogenity of the samples that are injected normally was > 90% They injected 100μ? in the SEC column. The separation of the SEC protein was carried out at 0.5mL / min for 45 minutes. PBS (saline buffered with phosphate ± 10% EtOH) was used as the mobile phase. The ASTRA software (Wyatt Inc, CA, USA) integrated the signals of the three detectors and allowed the determination of the molecular masses in kDa of proteins from 'the first physical principles'. The self-association of proteins can be determined reliably as shown by orthogonal methods (eg, AUC) with respect to characteristic dAbs. The inter-run variations and the data quality were evaluated running a positive control of a known solution state with each sample batch. For some DOM10-53 clones, a reliable solution status can not be assigned due to molecules bound in a-specific form to the column matrix or can not be resolved using the size exclusion column. For those cases where the status of the solution was reliable (eg, DOM10-53 (SEQ ID NO: 651), DOM10-53-531 (SEQ ID NO: 2097), and DOM 10-53-612 (SEQ ID NO: 2044)) it was shown that the molecule DOM10-53 (SEQ ID NO: 651) is mostly a monomer in solution. DSC. { differential scanning calorimetry) Protein was dilated overnight in PBS buffer (phosphate buffered saline), were diluted and filtered to produce a concentration of 0.5 mg / ml in PBS, as determined by 280 nm absorbance. A PBS buffer was used as a reference for all samples. DSC was carried out using a capillary cell microcalorimeter VP-DSC (Microcal, MA, USA), in a heating range of 180 ° C / hour. Normally the typical scan was from 25 ° to 90 ° C for both the reference buffer and the protein sample. After each reference buffer and sample pair, the capillary cell was cleaned with a 1% Deconen water solution followed by PBS. Resultant data traces were analyzed using the Origin 7 Microcal software. The DSC trace was obtained from the damper reference was subtracted from the sample line. The precise molar concentration of the sample was entered into the routine of data analysis to produce values of appTm, and enthalpy (??) and enthalpy van't Hoff (???). The data was normally adjusted to a non-2 model. The DSC experiments showed that some of the DOM10-53 molecules (eg, 10-53-472 (SEQ ID NO: 2103) and 10-53-474 (SEQ ID NO: 2105)) have high melting temperatures compared to others (for example 10-53-344 and 10-53-434), so much that they maintain their power. Said properties indicate an increased stability and are useful for pulmonary delivery. TABLE 16 Determination of the Pharmacokinetics of an Anti-IL 13 dAb delivered through the pulmonary administration route.

Test Substance DOM10-53-613 (SEQ ID NO: 2022) binds human IL-13, but not murine IL-13. DOM10-53-613 (in 1.2 mg / ml) with an HA label for detection was diluted in 20mM sodium citrate pH6.0. 100mM NaCl. It was tempered from storage temperature at 37 ° C before administration. DOM10-53-613 (in 1.2 mg / ml) was administered to 8-week-old male BALB / c mice. The animals were lightly anesthetized and allowed to drip gently on the nostrils 50 μ? or relevant dAb vehicle. The animals were kept in a vertical position for a few seconds while they were allowed to breathe spontaneously in the solution before being allowed to recover and returned to their cage. Subsequently, the mice were exterminated at the following time points in 10 minutes, 1 hour, 2 hours, 4 hours, 8 hours and 16 hours. Serum homogenates, lung priming and lung homogenate were collected from each mouse at each time point. Three mice were sampled at each time point. ELISA to detect HA tagged dAbs A maxisorp (Nunc) 96-well assay plate was coated overnight at a temperature of 4 ° C with 100 μl per deposit of polyclonal calf anti-HA antibody antibody (Abcam) in 2 g / ml in carbonate buffer. The deposits were washed 3 times with 0.05% Tween / PBS and 3 times with PBS. Was 200μ added? by depositing 2% BSA in PBS to block the plate. The tanks were washed and then 100 μ? of standard or sample of dAb labeled with HA. The tanks were washed and then 100 μl Protein A - HRP (1: 5000 dilution, Amersham) was added to each tank. The plates were developed with a solution of 100 μl SureBlue 1-Component TMB Micro Well Peroxidase (KPL, Gaithersburg, USA) added to each reservoir, and the plate was left at room temperature until a suitable signal was developed. The reaction was stopped by the addition of HCl and the absorbance was read at 450 nm. Data were plotted in GraphPad and subsequently adjusted in WinNonLin using a model without a compartment. Results The levels DOM10-53-613 (SEQ ID NO: 2022) in BAL showed that the dAbs were delivered efficiently in the lumen of the lung. A maximum level of 19 pg / ml (~ 7 pg in 0.4 ml) can be detected in BAL in 1 hour. This means that at least 12% (7 pg of 60 pg of total supplied) of the dose delivered was delivered into the lumen of the lung. It is probable that not all the material can be recovered using the washing procedure and this value is underestimated. The levels in the BAL are maximum in 1 hour and the dAbs are cleared with t1 / 2 of 4.4 hours, giving as result reduced concentrations by 10 times at 16 hours. The levels DOM10-53-613 (SEQ ID NO: 2022) in the lung showed maximum levels in 2 hours of 3.4 pg / ml. This means that approximately 5 to 6% of the dose delivered was present in the lung tissue. The decrease in levels in the lung shows a pattern similar to BAL. There was a maximum level in 10 minutes followed by a clearance range with you 2 of approximately 4.7 hours, resulting in reduced concentrations greater than 10 times in 16 hours. DOM serum levels 10-53-613 (SEQ ID NO: 2022) were detected. The serum levels were in a maximum of 4 hours. In 4 hours a maximum level of 0.73 pg / ml was detected in the serum. This means that -1% (0.7 μg of 60 μg supplied) of the supplied material was detected in the serum.

TABLE 17 EXAMPLE 4: Ligands that bind IL-4 and IL-3 A. Fusion proteins Cloning and dimer production of double anti-IL-4 and anti-IL-13 specificity. Nucleic acids encoding the anti-IL-4 dAb DOM9-112 and anti-IL-13 dAb DOM10-53 343 (SEQ ID NO: 891) were cloned into a construct that encoded a fusion protein in line with a Cysteine C- terminal. The amino acid sequence AST was present between two dAbs, this sequence is the natural CH sequence found in natural antibodies. The construct was cloned into the vector Pichia pastoris pPICZa (Invitrogen). Electrocompetent cells (X-33 or KM71H) were transformed with the construction and the transformers were selected in 100 pg / ml Zeocin. 500ml cultures were grown in a BMGY medium at a temperature of 30 ° C, 250 rpm for 24 hours until the OD6oo reached -15-20. Subsequently the cells were turned and resuspended in BMMY medium (containing 0.5% (v / v) methanol) to induce protein expression. The cultures were maintained at a temperature of 30 ° C with agitation at 250 rpm. At 24-hour intervals, the cultures were fed with the next increase in methanol concentration; 1%, 1.5% and 2% (v / v) using a 50% methanol solution.

Subsequently, the cultures were harvested by centrifugation and the supernatant containing the expressed protein was stored at a temperature of 4 ° C until it was required. The protein was purified from the supernatant using a PrA current line using the standard purification protocol. It was found that the protein purified with PrA contains both dimer and monomer species. Accordingly, chromatofocusing was used to separate the two proteins. A Mono P 5/20 column (GE Healthcare) was used for the separation, using a pH gradient of 6 to 4. The poly-buffers used were as described by the manufacturer to elaborate a pH range of 6 to 4. The sample was applied in a pH6 and subsequently the pH gradient was generated using 100% buffer B in a run of 35 column volumes in 1ml / min. Fractions containing dimer were identified using SDS-PAGE and pooled for PEGylation. Subsequently the protein was PEGylated using 40K PEG2-MAL using the method described above. This material was purified using anion exchange chromatography to obtain a purity of > 95% The resulting dual specific ligand potency (DOM9-112 (AST) DOM10-53-344 PEGylated) was determined in an IL-4 RBA (FIG 16A) and an IL-13 RBA (FIG 16B). The potency of the ligand's anti-IL-4 arm Specific dual (13 nM) was reduced slightly compared to the DOM9-112 dAb monomer power (3.5 nM), while the anti-IL-3 arm power remained (310 pM for the dual specific ligand vs. 230 pM for monomer dAb). The anti-IL-4 and anti-IL-13 dAbs DOM9-112 (SEQ ID NO: 25) and DOM10-53-344 (SEQ ID NO: 892) were also cloned as a fusion in line with the amino acid sequence ASTKGPS (SEQ ID NO: 1803) present between the two dAbs, this sequence is the beginning of the CH sequence found in natural antibodies. The resulting purified double specific ligand potency (DOM9-112 (ASTKGPS) DOM 10-53-344) was determined in an IL-4 RBA (FIG.17A) and a sandwich ELISA assay IL-13 (FIG.17B). The potency of the anti-IL-4 arm was maintained (~ 1nM) whereas the potency of the anti-IL-13 arm was only slightly reduced compared to the dAb monomer (40 pM for the monomer dAb vs 120 pM for the specific ligand dual). Additional dual address in online mergers for IL-4 and IL-13. To further understand the behavior of dAbs double address line merges linking to IL4 and IL13, a series of new online mergers and online merging libraries was built. The DOM10-53 lineage was matured by affinity using phage display, using libraries that diversify triplet residues of FR1, CDR1, CDR2 and CDR3. The libraries were cloned into a phage vector and deployed as a fusion protein for the gene3 protein as an in-line fusion (linker dAb1, dAb2) with DAb 1 being DOM9-112-210 (SEQ ID NO: 2401), being the amino acid residue linker ASTKGPS (SEQ ID NO: 1803) and dAb2 being the DOM10-53 library. The method of selection, subcloning and expression in E coli and the classification method were carried out essentially as described above, except that in-line fusion constructs were used in place of simple dAbs. Productions were cloned into the vector pDpM5 and expression supernatants were classified for enhanced expression by binding to a Biacore chip coated with protein A. Online fusions were expressed in line with improved expression levels, purified and tested in an ELISA sandwich assay IL -13 and a cellular assay. A number of variants were selected (including DOM9-112-210-ASTKGPS-DOM10-53-566). The most potent clones were DOM 10-53-531 (SEQ ID NO: 2097) and DOM 10-53-546 (SEQ ID NO: 2110) (see Table 18). Different protein preparations were made from these clones, and these were tested in a sandwich assay of IL-4 RBA and IL-13 as described above.

TABLE 18 Additional online mergers were built using SOE PCR of the DNA fragments encoding a dAb linker which is either ASTKGPS (SEQ ID NO: 1803), if the first dAb was a Vh, or TVAAPS (SEQ ID NO: 2459) if the first dAb was a Vk. This PCR product was digested with SAII / Notl and ligated into the E coli expression vector pDOM5. After transformation to MACH1 cells (Invitrogen), the clones were checked with sequence and in-line fusions were expressed. Expression was performed by growing E. coli in 2TY supplemented with Onex medium (Novagen) for 2 nights at a temperature of 30 ° C, the cells were centrifuged and the supernatant was incubated with either Protein-L or Protein-A resin. After elution from the resin, the quantity quality of the fusion product of the line produced in SDS-PAGE was verified. The vast majority of the product formed had the molecular mass of an on-line fusion with only one monomer free limited. Accordingly, no additional purification steps were required and the material could be tested directly. Using the method described above, the following in-line fusions IL-4 / IL-13 were expressed, purified and characterized: DOM9- 112 -210 - ASTKGPS - DOM10 -208 DOM9- 112 -210 - ASTKGPS - DOM10 -212 DOM9- 112 -210 - ASTKGPS - DOM10 -213 DOM9- 112 -210 - ASTKGPS - DOM10 -215 DOM9- 112 -210 - ASTKGPS - DOM10-224 DOM9- 112 -210 - ASTKGPS - DOM10 -270 DOM9- 112 -210 - ASTKGPS - DOM10 -416 DOM9- 112 -210 - ASTKGPS - DOM10 -236 DOM9- 112 -210 - ASTKGPS - DOM10 -273 DOM9- 112 -210 - ASTKGPS - DOM10 -275 DOM9- 12 -210 - ASTKGPS - DOM10 -276 DOM9- 112 - 210 - ASTKGPS - DOM10 -277 DOM10-208 TVAAPS - DOM9-155-78 DOM10-212 TVAAPS - DOM9-155-78 DOM10-213 TVAAPS - DOM9-155-78 DOM10-215 TVAAPS - DOM9-155-78 DOM10-224 TVAAPS - DOM9-155-78 DOM10-270 TVAAPS - DOM9-155-78 DOM10-416 TVAAPS - DOM9-155-78 DOM10 -236 - TVAAPS - D0M9- 155 -78 DOM10 -273 - TVAAPS - D0M9- 155 -78 DOM10 -275 - TVAAPS - DOM9- 155 -78 DOM10 -276 - TVAAPS - DOM9- 155 -78 DOM10 -277 - TVAAPS - D0M9- 155-78 Once purified, the expression levels (mg / l) were determined and tested in the activities in an RBA for the IL-4 binding and in a sandwich ELISA assay for binding to IL13. The table below (Table 19) summarizes the data of these online mergers: TABLE 19 In addition, an affinity-matured variant of DOM10-275 (SEQ ID NO: 2196), ie DOM 10-275-1 (SEQ ID NO: 2241), was specifically chosen to pair with both DOM9-112-210 ( SEQ ID NO: 2434) and DOM9-155-78 (SEQ ID NO: 2427). These online mergers were constructed and expressed as described above. further, to make tests on the IL-4 RBA and IL-13 and the aforementioned sandwich ELISA assay, these on-line fusions were also tested for functionality in a TF-1 cell proliferation assay. In these assays the dAb was previously inced in a fixed amount of either IL-4 or IL-13, this mixture was added to the TF-1 cells and the cells were inced for 72 hours. After this incion, the level of cell proliferation was determined. The results of this trial are summarized below (Table 20) and demonstrate that both arms of the online fusion were active in the cell assay. TABLE 20 B. Formats Type IgG Cloning, expression in the form of specific IgG The IgG-like formats that bound IL-4 and IL-13 were expressed using pDOM30. This vector is based on the Invitrogen backbone pBudCE4.1 and has been modified to comprise a codon-optimized heavy chain cartridge under the control of the CMV promoter and a codon-optimized light chain cartridge under the control of the EF1-alpha promoter. dAbs were cloned into the heavy chain cartridge using the BamHI and XhoI restriction sites, and into the light chain cartridge using the SalI and BsiWI restriction sites. This strategy resulted in N-terms of native heavy and light chain and the following constant-variable domain unions. The IgG expression constructs were transformed into chemically competent Machi cells (Invitrogen) grown on an LB agar medium with salt content supplemented with 250pg / L Zeocin. For each construct, the plasmid DNA was prepared from 3 or 4 randomly adjusted colonies and the dAb sequences were verified using the CMV-F primers. (CGCAAATGGGCGGTAGGCGTG) (SEQ ID NO: 1795) and plG (EFI-alpha) (TGAGTGGGTGGAGACTG) (SEQ ID NO: 1796). The endotoxin-free plasmid DNA was prepared from 500mL of culture using the Qiagen endo-free Megaprep kit for verified clones. The specificity of the format IgG-specific type of anti-L4 and antr-L13 was evaluated in RBA of IL-4 receptor, and sandwich ELISA assay of IL-13. Figure 18 shows that the potency of the monomer dAB anti-IL4 DOM9-44-502 (SEQ ID NO: 361) was 3 to 4 times reduced when formatted in the IgG type format (4nM for monomer dAb versus 13 nM for the IgG type format) while the power of the anti-L 13 dAb DOM10-176-535 (SEQ ID NO: 1362) was 1nM for both the dAb monomer and the IgG type format. Determination of pharmacokinetics of dAbs Anti-l L 13 [3H] - PEGylated and in-line fusions anti-IL4 and anti-l L13. Radiolabelling of dAbs Anti-l L13 PEGylated and in-line fusions anti-IL4 and anti-l L13. The anti-L13 dAbs and the anti-IL4 and anti-IL13 in-line fusions were expressed and pegylated using the N-terminus (group or amino) or C-term using a 40K branched PEG as described above. The protein was radiolabelled with tritium using N-Succinimidyl [2,3-3H] propionate (NSP) in hexane: ethyl acetate (9: 1). 400 pL of NSP was supplied in a flask and the solvent was removed under a gentle stream of nitrogen at a temperature of = 30 ° C. The residue was subsequently suspended again in 100 pL of DMSO. Subsequently, 2.5 mL of branched 40K PEG DOM0910 was added to the NSP / DMSO and the mixture was incubated for 60 minutes at room temperature. After incubation, the The solution was loaded onto a PD10 column that was previously equilibrated with 24mL of phosphate buffered saline (PBS) and the eluate was discarded. Subsequently, the radiolabeled protein was extracted from the PD10 column using 3.5mL of PBS and the eluate was collected. The specific activity of the material was determined (assuming a 100% efficiency of labeling and protein recovery of the PD10 column) and the solution was used immediately or stored at a temperature of approximately 4 ° C until it was required. Working with animals For each molecule, 3 female Spargue-Dawley rats received a single intravenous dose at 1 mg / kg. Subsequently, serial blood samples were collected from the tail vein after 2 minutes, 2 hours, 8 hours, 24 hours, 72 hours and 96 hours. The final blood sample was collected after 120 hours immediately before sacrifice through cardiac puncture under anesthesia. To obtain the serum, blood samples were collected and allowed to coagulate. Once coagulated, the samples were centrifuged at 3000 rpm for 10 mins. The serum was then collected and stored at a temperature of -20 ° C until analysis. Determination of radioactivity The radioactive content of each sample was determined by liquid scintillation counting with automatic extension correction. The serum samples were mixed with PBS before the addition of scintillation fluid. The disintegration ranges of the appropriate blank sample bottles were subtracted from the disintegration ranges of the sample to provide a net dpm of each sample. Total radioactivity below a background level of double was considered below the limit of a reliable measurement. Heavy aliquots were lyophilized in additional form of serum obtained after 2 minutes and 48 and 120 hours after the dose, before determination of radioactivity concentration to determine any contribution to total counts from free tritium. The data were adjusted using a Winonlin adjustment software and the terminal half-life values were determined and are described in Table 21. DOM9-112-210 ASTKGPS DOM10-53-612 with branched PEG 40K N-terminal has a half-life terminal 41 hours, while DOM9-112-210 ASTKGPS with branched 40K C-terminal PEG has a half-life of 32 hours.

Table 21 The teachings of all the patents, applications and references disclosed herein are incorporated herein by reference in their entirety. Although the present invention has been particularly shown and described with references to exemplary embodiments thereof, it will be understood by those skilled in the art that various changes can be made in form and detail without departing from the scope of the present invention. which is comprised in the appended claims.

Claims

CLAIMS 1. A ligand having binding specificity for interleukin-4 (IL-4) and interleukin-13 (IL-13) comprising: a protein portion having a binding site with binding specificity for IL-4; and - a protein portion having a binding site with binding specificity for IL13, as long as the protein portion having a binding site with binding specificity for IL-4 is not an IL-4 receptor or a part of IL-4 linkage thereof, and the protein portion having a binding site with binding specificity for IL-13 is not an IL-13 receptor or an IL-13 linkage portion thereof.
2. The ligand as described in claim 1, characterized in that the portion of the protein having a binding site with binding specificity for IL-4 competes to bind IL-4 with IL-4Ra, an IL-linking part. -4 of IL-4Ra or an anti-IL4 domain antibody (dAb) selected from the group consisting of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9 155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311) , DOM9-12-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9- 112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512).
3. The ligand as described in claim 1, characterized in that the portion of the protein having a binding site with binding specificity for IL-13 competes to bind IL-13 with IL-13Ra1, an IL binding portion. -13 of IL-13Ra1, IL-13Ra2, an IL-13 binding part of IL-13Ra2, or an anti-IL-13 domain antibody (dAb) selected from the group consisting of DOM 10-176-535 (SEQ. ID NO: 1587), DOM10-53-223 (SEQ ID NO: 1090), DOM 10-53-234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO: 1382), DOM 10-53 -339 (SEQ ID NO: 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10 -275-1 (SEQ ID NO: 2241).
4. The ligand as described in claim 1, characterized in that the protein portion having a binding site with binding specificity for IL-4 competes to bind IL-4 with IL-4Ra, an IL-binding portion. -4 of IL-4Ra or an IL-4 domain antibody (dAb) selected from the group consisting of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9 -155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311) , DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID, NO : 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9- 112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512); and the portion of the protein that has a binding site with binding specificity for IL-13 competes to bind IL-13 with IL-13Ra1, an IL-13 binding portion of IL-13Ra1, IL-13Ra2 and a portion of IL-13Ra2 linkage IL-13, or an anti-L-13 domain antibody (dAb) selected from the group consisting of DOM 10-176-535 (SEQ ID NO: 1587), DOM10-53-223 (SEQ ID NO: 1090), DOM 10-53-234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO: 1182), DOM 10-53-339 (SEQ ID NO: 1203), DOM10-53 -344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241).
The ligand as described in any one of claims 1 to 4, characterized in that the protein portion having a binding site with binding specificity for IL-4 is provided through an antibody fragment, and the protein portion having a binding site with binding specificity for IL-13 is provided through an antibody fragment.
6. The ligand as described in the claim 5, characterized in that the antibody fragments are each a single immunoglobulin variable domain.
7. The ligand as described in any of claims 1 to 6, characterized in that the ligand inhibits the binding of IL-4 to IL-4R.
8. The ligand as described in any of claims 1 to 6, characterized in that the ligand inhibits the activity of IL-4.
9. The ligand as described in any of claims 1 to 6, characterized in that the ligand inhibits the activity of IL-4 without substantially inhibiting the binding of IL-4 to IL-4R.
10. The ligand as described in any of claims 1 to 9, characterized in that the ligand inhibits the binding of IL-13 to IL-13Ra1 and / or IL-13Ra2.
11. The ligand as described in any of claims 1 to 9, characterized in that the ligand inhibits the activity of IL-13.
12. The ligand as described in any one of claims 1 to 9, characterized in that ligand inhibits the activity of IL-13 without substantially inhibiting the binding of IL-13 to IL-13Ra1 and / or IL-13Ra2.
13. A ligand having binding specificity for IL-4 and IL-13 comprising a single immunoglobulin variable domain with binding specificity for IL-4 and a single immunoglobulin variable domain with binding specificity for IL-13, in where the variable domain of simple immunoglobulin with binding specificity for IL-4 competes to bind IL-4 with an immunoglobulin variable domain antibody simple anti-L4 (dAb) selected from the group consisting of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 ( SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512); and the variable domain of single immunoglobulin with binding specificity for IL-13 competes to bind IL-13 with an anti-IL-13 domain antibody (dAb) selected from the group consisting of DOM10-176-535 (SEQ ID NO. : 1587), DOM10-53-223 (SEQ ID NO: 1090), DOM 10-53-234 (SEQ ID NO: 1101), DOM 10-53-316 (SEQ ID NO: 1182), DOM 10-53- 339 (SEQ ID NO: 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10- 275-1 (SEQ ID NO: 2241).
14. The ligand as described in claim 13, characterized in that the ligand inhibits the binding of IL-4 to IL-4R.
15. The ligand as described in claim 13, characterized in that the ligand inhibits the activity of IL-4.
16. The ligand as described in claim 13, characterized in that the ligand inhibits the activity of IL-4 substantially inhibiting the binding of IL-4 'to IL-4R.
17. The ligand as described in any of claims 13 to 16, characterized in that the ligand inhibits the binding of IL-13 to IL-13Ra1 and / or IL-13Ra2.
18. The ligand as described in any of claims 13 to 16, characterized in that the ligand inhibits the activity of IL-13.
19. The ligand as described in any of claims 13 to 16, characterized in that the ligand inhibits the activity of IL-13 without substantially inhibiting the binding of IL-13 to IL-13Ra1 and / or IL-13Rct2. .
20. The ligand as described in any of claims 13 to 19, characterized in that each variable domain of single immunoglobulin with binding specificity for IL-4 binds to IL-4 with an affinity (KD) that is between about 100 nM and about 1 pM, as determined by surface plasmon resonance.
21. The ligand as described in any of claims 13 to 20, characterized in that each variable domain of simple immunoglobulin with binding specificity for IL-13, binds to IL-13 with an affinity (KD) that is between about 100 nM and about 1 pM, as determined by surface plasmon resonance.
22. The ligand as described in any of claims 13 to 19, characterized in that the ligand binds to IL-4 with an affinity (KD) that is between about 100 nM and about 1 pM, as determined by resonance of plasmon of surface.
23. The ligand as described in any of claims 13 to 19 and 22, characterized in that the ligand binds to IL-13 with an affinity (KD) that is between about 100 nM and about 1 pM, such as it is determined by surface plasmon resonance.
24. The ligand as described in any of claims 13 to 23, characterized in that the variable domain of simple immunoglobulin with binding specificity for IL-4 and the variable domain of single immunoglobulin with binding specificity for IL- 13 are independently selected from the group consisting of human VH and human VL.
25. The ligand as described in any of claims 13 to 24, characterized in that the ligand is an IgG type format comprising two variable domains of single immunoglobulin with binding specificity for IL-4, and two variable domains of simple immunoglobulin with binding specificity for IL-13.
26. The ligand as described in any one of claims 1 to 25, characterized in that the ligand comprises an antibody region.
27. The ligand as described in any one of claims 1 to 25, characterized in that the ligand comprises an IgG constant region.
28. A ligand having binding specificity for IL-4, characterized in that it comprises a single immunoglobulin variable domain with binding specificity for IL-4, wherein the variable domain of single immunoglobulin with binding specificity for IL-4 competes for binding to IL-4 with an anti-IL-4 domain antibody (dAb) selected from the group consisting of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO-.605) , DOM9-55-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44-502 ( SEQ ID NO: 512).
29. The ligand as described in the claim 28, characterized in that the variable domain of simple immunoglobulin with binding specificity for IL-4 comprises an amino acid sequence having at least about 85% amino acid sequence identity with the amino acid sequence of a dAb selected from the group consisting of DOM9-44-502 (SEQ ID NO.-512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617), DOM9-112- 155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9- 112-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433) DOM9-112-210 (SEQ ID NO: 2434) 'and DOM9-44-502 (SEQ ID NO: 512).
30. The ligand as described in the claim 28 or 29, characterized in that the ligand inhibits the binding of IL-4 to IL-4Ra.
31. The ligand as described in claim 28 or 29, characterized in that the ligand inhibits the activity of IL-4.
32. The ligand as described in claim 28 or 29, characterized in that the ligand inhibits the activity of IL-4 without substantially inhibiting the binding of IL-4 to IL-4Ra.
33. The ligand as described in any of claims 28 to 32, characterized in that the variable domain of simple immunoglobulin with binding specificity for IL-4 binds to IL-4 with an affinity (KD) that is between about 100 nM and about 1 pM, as determined by surface plasmon resonance.
34. The ligand as described in any of claims 28 to 32, characterized in that the ligand binds to IL-4 with an affinity (KD) that is between 100 nM and about 1 pM, as determined by resonance of surface plasmon.
35. The ligand as described in any of claims 28 to 34, characterized in that the variable domain of simple immunoglobulin with binding specificity for IL-4 is selected from the group consisting of human VH and human VL.
36. The ligand as described in any of claims 1 to 35, characterized in that the ligand is an IgG type format.
37. The ligand as described in any of claims 28 to 35, characterized in that the ligand comprises an antibody region of Fe.
38. The ligand as described in any of claims 28 to 35. , characterized in that the ligand comprises a constant region IgG.
39. A ligand having binding specificity for IL-13, comprising a single immunoglobulin variable domain with binding specificity for IL-13 wherein the variable domain of single immunoglobulin with binding specificity for IL-13 competes to bind to IL-13 with an anti-IL-13 domain antibody (dAb) selected from the group consisting of DOM 10-176-535 (SEQ ID NO: 1587), DOM10-53-223 (SEQ ID NO: 1090); DOM10-53-234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO: 1182), DOM10-53-339 (SEQ ID NO: 1203), DOM 10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241).
40. The ligand as described in claim 28, characterized in that the variable domain of simple immunoglobulin with binding specificity for IL-13 comprises an amino acid sequence having at least about 85% amino acid sequence identity with the sequence of amino acid of a dAb selected from the group consisting of DOM10-176-535 (SEQ ID NO: 1587), DOM10-53-223 (SEQ ID NO: 1090); DOM 10-53-234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO: 1182), DOM10-53-339 (SEQ ID NO: 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID O. 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241).
41. The ligand as described in claim 39 or 40, characterized in that the ligand inhibits the binding of IL-13 to IL-13Ra1 and / or IL-13Ra2
42. The ligand as described in claim 39 or 40 , characterized in that the ligand inhibits the activity of IL-13.
43. The ligand as described in the claim 39 or 40, characterized in that the ligand inhibits the activity of IL-13 without substantially inhibiting the binding of IL-13 to IL-13Ra1 and / or IL-13Ra2.
44. The ligand as described in any of claims 39 to 43, characterized in that the variable domain of simple immunoglobulin with binding specificity for IL-13 binds to IL-13 with an affinity (KD) that is between about 100 nM and about 1 pM, as determined by surface plasmon resonance.
45. The ligand as described in any of claims 39 to 43, characterized in that the ligand binds to IL-13 with affinity (KD) that is between 100 nM and about 1 pM, as determined by resonance of plasmon of surface.
46. The ligand as described in any of claims 39 to 45, characterized in that the variable domain of simple immunoglobulin with binding specificity for IL-13 is independently selected from the group consisting of human VH and human VL.
47. The ligand as described in any of claims 39 to 46, characterized in that the ligand is an IgG type format.
48. The ligand as described in any of claims 39 to 46, characterized in that the ligand comprises an antibody region Fe.
49. The ligand as described in any of claims 39 to 46, characterized in that the ligand comprises an IgG constant region.
50. A ligand having binding specificity for IL-4 and IL-13, wherein the ligand is a fusion protein comprising a single immunoglobulin variable domain with binding specificity for IL-4 and a single immunoglobulin variable domain with binding specificity for IL-13, wherein the variable domain of single immunoglobulin with binding specificity for IL-4 competes to bind IL-4 with an anti-IL4 domain antibody (dAb) selected from the group consisting of DOM9 -44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 292) , DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512); and a single immunoglobulin variable domain with binding specificity for IL-13 that competes to bind IL-13 with an anti-L 13 domain antibody (dAb) selected from the group consisting of DOM10-176-535 (SEQ. ID NO: 1587), DOM10-53-223 (SEQ ID NO: 1090), DOM10-53-234 (SEQ ID NO 101), DOM10-53-316 (SEQ ID NO: 1182), DOM10-53-339 ( SEQ ID NO: 1203), DOM 10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275 -1 (SEQ ID NO: 2241).
51. The ligand as described in claim 50, characterized in that the variable domain of simple immunoglobulin with binding specificity for IL-13 comprises an amino acid sequence having at least about 85% sequence identity with the sequence of amino acid of a dAb selected from the group consisting of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617), DOM9 -112-155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336) , DOM9-112-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512).
52. The ligand as described in the claim 50 or 51, characterized in that the variable domain of simple immunoglobulin with binding specificity for IL-13 comprises an amino acid sequence having at least about 85% amino acid sequence identity with the amino acid sequence of dAb selected from the group consisting of DOM 10-176-535 (SEQ ID NO: 1587), DOM 10-53-223 (SEQ ID NO: 1090), DOM10-53-234 (SEQ ID NO: 1101), DOM10-53 -316 (SEQ ID NO: 1182), DOM10-53-339 (SEQ ID NO: 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10 -53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241).
53. The ligand as described in any of claims 50 to 52, characterized in that the portion protein further comprises a binding portion.
54. A ligand having binding specificity for IL-4 comprising a portion of protein having a binding site with binding specificity for IL-4, wherein the protein portion comprises an amino acid sequence having the same sequence of amino acids of the CDR3 of a dAb selected from the group consisting of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617 ), DOM9-112-155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO. : 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512).
55. The ligand as described in claim 54, characterized in that the binding portion comprises in addition an amino acid sequence that is equal to the amino acid sequence of CDR1 and / or CDR2 of a dAb selected from the group consisting of DOM9-44-502 (SEQ ID NO.-512), DOM9-155-5 (SEQ ID. NO: 605), DOM9-55-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 ( SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-1 2-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155 -78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434) and DOM9 -44-502 (SEQ ID NO: 512).
56. A ligand comprising a variable domain of single immunoglobulin in binding to fL-4, wherein the amino acid sequence of the variable domain of single immunoglobulin binding to IL-4, differs from the amino acid sequence of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 292), DOM9-112 -168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9 - 155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433) , DOM 9-112-210 (SEQ ID NO: 2434) or DOM9-44-502 (SEQ ID NO: 512) in no more than 25 amino acid positions and has a CDR1 sequence that has at least 50% identity with the CDR1 sequence of DOM9-44-502 (SEQ ID NO: 512), D0M9-155-5 (SEQ ID NO: 605), D0M9-155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 292), DOM9- 112-68 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID N0: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-155 -77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9 -112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512).
57. A ligand comprising a variable domain of single immunoglobulin that binds to IL-4, wherein the amino acid sequence of the variable domain of single immunoglobulin binding to IL-4, differs from the amino acid sequence of DOM9-44- 502 (SEQ ID NO: 512): DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 292), DOM9- 112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433) ), DOM9-112-210 (SEQ ID NO: 2434) or DOM9-44-502 (SEQ ID NO: 512) in no more than 25 amino acid positions and has a CDR2 sequence that has at least 50% identity with the CDR2 sequence of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ. ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID N0: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-155-77 ( SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112- 210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512).
58. A ligand comprising a variable domain of simple immunoglobulin binding to IL-4, wherein the amino acid sequence of the. variable domain of simple immunoglobulin binding to IL-4, differs from the amino acid sequence of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112 -199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9 -112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512) , in no more than 25 amino acid positions and has the CDR3 sequence that has at least 50% identity with the CDR3 sequence of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), D0M9-112-209 (SEQ ID NO: 2433), DOM9-112-210 ( SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512).
59. A ligand comprising a variable domain of simple immunoglobulin binding to IL-4, wherein the amino acid sequence of the variable domain of single immunoglobulin binding to IL-4 differs from the amino acid sequence of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 292), DOM9-112 -168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9 - 155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433) , DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512), in no more than 25% amino acid and has a CDR1 sequence and a CDR2 sequence that are at least 25% % identity with the CDR1 or CDR2 sequences, respectively of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-55-25 (SEQ ID NO: 617) , DOM9-112-155 (SEQ ID NO: 292), DOM9-12-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO. : 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DO 9-155-77 (SEQ ID NO: 2426), DOM9-155-78 ( SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9- 112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512).
60. A ligand comprising a variable domain of simple immunoglobulin that binds to IL-4, wherein the amino acid sequence of. variable domain of simple immunoglobulin binding to IL-4, differs from the amino acid sequence of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 605), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112 -199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9 -112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512) in no more than 25 amino acid positions and has a CDR2 sequence and a CDR3 sequence having at least 50% identity with the CDR2 or CDR3 sequences, respectively, of DOM9-44-502 (SEQ ID NO: 512), DOM9 -155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 605), DOM9-112-168 (SEQ ID NO: 305) , DOM9-112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9- 155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427) , DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512).
61. A ligand comprising a variable domain of simple immunoglobulin binding to IL-4, wherein the amino acid sequence of the variable domain of single immunoglobulin binding to IL-4 differs from the amino acid sequence of DOM9-44-502 (SEQ ID NO: 512), DOM9-155 -5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 605), DOM9-112-168 (SEQ ID NO: 305), DOM9 -112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-55-77 (SEQ ID NO: 2426) , DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512) in no more than 25 amino acid positions and has a CDR1 sequence and a CDR3 sequence that have at least 50% identity with the CDR1 or CDR3 sequences, respectively DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 292) ), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-11 2-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512).
62. A ligand comprising a variable domain of simple immunoglobulin binding to IL-4, wherein the amino acid sequence of the variable domain of Simple immunoglobulin binding to IL-4, differs from the amino acid sequence of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-199 ( SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112- 202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512) in no more of 25 amino acid positions and have a CDR1 sequence, a CDR2 sequence and a CDR3 sequence having at least 50% identity with the CDR1, CDR2 or CDR3 sequences, respectively of DOM9-44-502 (SEQ ID NO: 512) , DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), 'DOM9-112-174 (SEQ ID NO: 311), DOM9-112499 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO. : 2426), DOM9-155-78 (SEQ ID NO : 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512).
63. A ligand comprising a single immunoglobulin variable domain that binds to IL-4, wherein the variable domain of single immunoglobulin binding to IL-4 comprises a CDR2 sequence having at least 50% identity with the CDR2 sequence of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO.-617), DOM9-112- 155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9- 112-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512).
64. A ligand comprising a single immunoglobulin variable domain that binds to IL-4, wherein the variable domain of single immunoglobulin binding to IL-4 comprises a CDR3 sequence having at least 50% identity to the CDR3 sequence of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 ( SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512).
65. A ligand comprising a variable domain of single immunoglobulin binding to IL-4, wherein the variable domain of single immunoglobulin binding to IL-4 it comprises a CDR1 sequence and a CDR2 sequence having at least 50% identity with the CDR1 and CDR2 sequences, respectively of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605 ), DOM9-155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-274 (SEQ ID NO. : 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9- 155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512).
66. A ligand comprising a single immunoglobulin variable domain that binds to IL-4, wherein the variable domain of single immunoglobulin binding to IL-4 comprises a CDR2 sequence and a CDR3 sequence having at least 50% identity with the sequences CDR2 and CDR3, respectively of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617); DO M 9-112-155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NQ: 311), DOM9-112-199 (SEQ ID NO. : 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512).
67. A ligand comprising a single immunoglobulin variable domain that binds to IL-4, wherein the variable domain of single immunoglobulin binding to IL-4 comprises a CDR2 sequence and a CDR3 sequence having at least 50% identity with the CDR2 and CDR3 sequences, respectively of DOM9-44-502 (SEQ ID NO. : 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO: 617), DOM9-112-155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112 -210 (SEQ ID NO: 2434) and DOM9-44-502 (SEQ ID NO: 512).
68. A ligand comprising a variable domain of single immunoglobulin binding to IL-4, wherein the variable domain of single immunoglobulin binding to IL-4 comprises a CDR1 sequence, a CDR2 sequence and a CDR3 sequence having at least one 50% identity with the CDR1, CDR2 and CDR3 sequences, respectively of DOM9-44-502 (SEQ ID NO: 512), DOM9-155-5 (SEQ ID NO: 605), DOM9-155-25 (SEQ ID NO. : 617), DOM9-112-155 (SEQ ID NO: 292), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-202 (SEQ ID NO: 339), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434) and DOM9-44 -502 (SEQ ID NO: 512).
69. A ligand having binding specificity for IL-13, comprising a portion of a protein having a binding site with binding specificity for IL-13, wherein the protein portion comprises an amino acid sequence having the same amino acid sequence of CDR3 of a dAb selected from the group consisting of DOM 10 176-535 (SEQ ID NO: 1587), DOM10-53-223 (SEQ ID NO: 1090), DOM10-53-234 (SEQ ID NO. : 1101), DOM 10-53-316 (SEQ ID NO: 1182), DOM10-53-339 (SEQ ID NO: 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-396 ( SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM 10-275-1 (SEQ ID NO: 2241).
70. The ligand as described in the claim 69, characterized in that the protein portion further comprises an amino acid sequence that is equal to the amino acid sequence of CDR1 and / or CDR2 of a dAb selected from the group consisting of DOM 10-176-535 (SEQ ID NO: 1587) , DOM10-53-223 (SEQ ID NO: 1090), DOM10-53-234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO: 1182), DOM10-53-339 (SEQ ID NO: 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241).
71. A ligand comprising a variable domain of Simple n-globulin binding to IL-4, wherein the variable domain amino acid sequence of single immunoglobulin binding to IL-13 differs from the amino acid sequence of DOM 10-176-535 (SEQ ID NO: 1587) , DOM 10-53-223 (SEQ ID NO: 1090), DOM10-53-234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO: 1182), DOM10-53-339 (SEQ ID NO. : 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241), in no more than 25 amino acid positions and has a CDR1 sequence that has at least 50% identity with the CDR1 sequence of a dAb selected from the group consisting of DOM 0-176-535 (SEQ ID. NO: 1587), DOM10-53-223 (SEQ ID NO: 1090), DOM10-53-234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO: 1182), DOM10-53-339 ( SEQ ID NO: 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275- 1 (SEQ ID NO: 2241).
72. A ligand comprising a variable domain of a single immunoglobulin binding to IL-13, wherein the amino acid sequence of the variable domain of single immunoglobulin binding to IL-13 differs from the amino acid sequence of DOM 10-176 -535 (SEQ ID NO: 1587), DOM10-53-223 (SEQ ID NO: 1090), DOM10-53-234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO: 1182), DOM10 -53-339 (SEQ ID NO: 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM 10-275-1 (SEQ ID NO: 2241) in no more than 25 amino acid positions and has a CDR2 sequence having at least 50% identity with the CDR2 sequence of DOM10-176-535 (SEQ ID NO: 1587), DOM10-53-223 (SEQ ID NO: 1090), DOM10-53-234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO: 1182), DOM10-53-339 (SEQ ID NO: 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-396 ( SEQ ID NO: 1260), DOM 10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241).
73. A ligand comprising a variable domain of single immunoglobulin binding to IL-13, wherein the amino acid sequence of the variable domain of single immunoglobulin binding to IL-13 differs from the amino acid sequence of DOM 10-176-535 (SEQ ID NO: 1587), DOM10-53-223 (SEQ ID NO: 1090), DOM10-53-234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO: 1182), DOM10-53 -339 (SEQ ID NO: 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10 -275-1 (SEQ ID NO: 2241) in no more than 25 amino acid positions and has a CDR3 sequence that has at least 50% identity with the CDR3 sequence of a dAb selected from the group consisting of DOM10-176- 535 (SEQ ID NO: 1587), DOM10-53-223 (SEQ ID NO: 1090), DOM10-53-234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO: 1182), DOM10-53-339 (SEQ ID NO: 1203), DOM 10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241).
74. A ligand comprising a variable domain of single immunoglobulin binding to IL-13, wherein the amino acid sequence of the variable domain of single immunoglobulin binding to IL-13 differs from the amino acid sequence of DOM10-176-535 ( SEQ ID NO: 1587), DOM 10-53-223 (SEQ ID NO: 1090), DOM 10-53-234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO: 1182), DOM10- 53-339 (SEQ ID NO: 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241) in no more than 25 amino acid positions and has a CDR1 sequence and a CDR2 sequence having at least 50% identity with the CDR1 or CDR2 sequences, respectively of a selected dAb of the group consisting of DOM 10- 176-535 (SEQ ID NO: 1587), DOM10-53-223 (SEQ ID NO: 1090), DOM10-53-234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO: 1182), DOM10-53-339 (SEQ ID NO: 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53 -474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241).
75. A ligand comprising a variable domain of single immunoglobulin binding to IL-13, wherein the amino acid sequence of the variable domain of Simple immuno-globulin binding to IL-13 differs from the amino acid sequence of DOM10-176-535 (SEQ ID NO: 1587), DOM 10-53-223 (SEQ ID NO: 1090), DOM 10-53-234 (SEQ ID NO 101), DOM 10-53-316 (SEQ ID NO: 1182), DOM10-53-339 (SEQ ID NO: 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53 -396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241) in no more than 25 amino acid positions and has a CDR2 sequence and a CDR3 sequence having at least 50% identity with the CDR2 or CDR3 sequences, respectively of a dAb selected from the group consisting of DOM 0-76-535 (SEQ ID NO: 1587), DOM10-53-223 (SEQ ID NO: 1090), DOM10-53-234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO: 1182), DOM10-53-339 (SEQ ID NO: 1203), DOM10-53-344 ( SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241).
76. A ligand comprising a variable domain of single immunoglobulin binding to IL-13, wherein the amino acid sequence of the variable domain of single immunoglobulin binding to IL-13 differs from the amino acid sequence of DOM 10- 176-535 (SEQ ID NO: 1587), DOM10-53-223 (SEQ ID NO: 1090), DOM10-53-234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO: 1182), DOM10-53 -339 (SEQ ID NO: 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241) in no more than 25 amino acid positions and has a CDR1 sequence and a CDR3 sequence having at least 50% identity with the CDR1 or CDR3 sequences respectively , of a dAb selected from the group consisting of DOM10-176-535 (SEQ ID NO: 1587), DOM 10-53-223 (SEQ ID NO: 1090), DOM10-53-234 (SEQ ID NO: 1101), DOM 10-53-316 (SEQ ID NO: 1182), DOM10-53-339 (SEQ ID NO: 1203), DOM 10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO. : 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241).
77. A ligand comprising a single immunoglobulin variable domain that binds to IL-13, wherein the amino acid sequence of the variable domain of single immunoglobulin binding to IL-13 differs from the amino acid sequence of DOM10-176-535 ( SEQ ID NO: 1587), DOM10-53-223 (SEQ ID NO: 1090), DOM10-53-234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO 182), DOM10-53-339 (SEQ ID NO: 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275 -1 (SEQ ID NO: 2241) in no more than 25 amino acid positions and has a CDR1 sequence, a CDR3 sequence and a sequence having at least 50% identity with the CDR1, CDR2 or CDR3 sequences, respectively, dAb selected from the group consisting of DOM 10- 176-535 (SEQ ID NO: 1587), DOM10-53-223 (SEQ ID NO: 1090), DOM10-53-234 (SEQ ID NO: 1101), D0M10-53-316 (SEQ ID NO.H82), DOM10-53-339 (SEQ ID NO: 1203), DOM10-53-344 ( SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241).
78. A ligand comprising a single immunoglobulin variable domain that binds to IL-13, wherein the amino acid sequence of the variable domain of single immunoglobulin binding to IL-13 comprises a CDR2 sequence having at least 50% identity. with the CDR2 sequence of the dAb selected from the group consisting of DOM10-176-535 (SEQ ID NO: 1587), DOM 10-53-223 (SEQ ID NO: 1090), DOM10-53-234 (SEQ ID NO: 1101) ), DOM 10-53-316 (SEQ ID NO: 1182), DOM 10-53-339 (SEQ ID NO: 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ. ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241).
79. A ligand comprising a single immunoglobulin variable domain that binds to IL-13, wherein the variable domain of single immunoglobulin binding to IL-13 comprises a CDR3 sequence having at least 50% identity to the CDR3 sequence of the dAb selected from the group consisting of DOM 10-176-535 (SEQ ID NO: 1587), DOM10-53-223 (SEQ ID NO: 1090), DOM10-53-234 (SEQ ID NO: 1101), DOM10- 53-316 (SEQ ID NO: 1182), DOM10-53-339 (SEQ ID NO: 1203), DOM 10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10- 275-1 (SEQ ID NO: 2241).
80. A ligand comprising a single immunoglobulin variable domain that binds to IL-13, wherein the variable domain of single immunoglobulin binding to IL-4 comprises a CDR1 sequence and a CDR2 sequence having at least 50% identity with the CDR1 and CDR2 sequences, respectively, of a dAb selected from the group consisting of DOM 10-176-535 (SEQ ID NO: 1587), DOM 10-53-223 (SEQ ID NO: 1090), DOM10-53- 234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO: 1182), DOM10-53-339 (SEQ ID NO: 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10- 53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241).
81. A ligand comprising a variable domain of single immunoglobulin binding to IL-13, characterized in that the variable domain of single immunoglobulin binding to IL-13 comprises a CDR2 sequence and a CDR3 sequence having at least 50% identity with the CDR2 and CDR3 sequences, respectively, of a dAb selected from the group consisting of DOM10-176-535 (SEQ ID NO.-1587), DOM10-53-223 (SEQ ID NO.1090), DOM10-53-234 (SEQ ID NO: 1101), DOM10-53-316 (SEQ ID NO: 1182), DOM10-53-339 (SEQ ID NO: 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241).
82. A ligand comprising a variable domain of single immunoglobulin binding to IL-13, characterized in that the variable domain of single immunoglobulin binding to IL-13 comprises a CDR1 sequence and a CDR3 sequence having at least 50% identity with the CDR1 and CDR3 sequences, respectively, of a dAb selected from the group consisting of DOM10-176-535 (SEQ ID NO: 1587), DOM 10-53-223 (SEQ ID NO: 1090), DOM 10-53- 234 (SEQ ID NO: 1101), DOM 10-53-316 (SEQ ID NO: 1182), DOM10-53-339 (SEQ ID NO: 1203), DOM 10-53-344 (SEQ ID NO: 1208), DOM10-53-396 (SEQ ID NO 260), 'DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241).
83. A ligand comprising a variable domain of single immunoglobulin binding to IL-13, characterized in that the variable domain of single immunoglobulin binding to IL-13 comprises a CDR1 sequence and a CDR3 sequence having at least 50% identity with the CDR1 and CDR3 sequences, respectively, in a dAb selected from the group consisting of DOM10-176-535 (SEQ ID NO: 1587), DOM10-53-223 (SEQ ID NO: 1090), DOM10-53-234 ( SEQ ID NO.H01), DOM10-53-316 (SEQ ID NO.1182), DOM10-53-339 (SEQ ID NO: 1203), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53- 396 (SEQ ID NO: 1260), DOM10-53-474 (SEQ ID NO: 2369) and DOM10-275-1 (SEQ ID NO: 2241).
84. The ligand as described in any one of claims 1 to 83, characterized in that the ligand further comprises a half-life extension portion.
85. The ligand as described in the claim 84, characterized in that the half-life extension portion is a polyalkylene glycol moiety, serum albumin or a fragment thereof, a transfer receptor or a linker-transfer part thereof, or a portion comprising a site of linkage for a polypeptide that increases the half-life in vivo.
86. The ligand as described in the claim 85, characterized in that the half-life extension portion is a portion comprising a binding site for a polypeptide that increases the in vivo half-life selected from the group consisting of an antibody, an SpA domain, a class A LDL receptor domain , an EGF domain and an avimer.
87. The ligand as described in claim 85, characterized in that the half-life extension portion is a polyethylene glycol portion.
88. The ligand as described in claim 85, characterized in that the half-life extension portion is an antibody or antibody fragment comprising a binding site for serum albumin or neonatal receptor Fe.
89. The ligand as described in claim 85, characterized in that the antibody or antibody fragment comprising a binding site for serum albumin or neonatal Fe receptor, is an antibody fragment, and the antibody fragment is a variable domain of simple immunoglobulin comprising a binding site for serum albumin.
90. The ligand as described in any one of claims 1 to 89 for use in therapy or diagnosis.
91. The ligand as described in any one of claims 1 to 89 for use in treating, suppressing or preventing an allergic disease.
92. The use of a ligand as described in any one of claims 1 to 89, for the manufacture of a medicament for treating, suppressing or preventing an allergic disease.
93. The ligand as described in any one of claims 1 to 89 for use to treat, suppress or prevent a Th2 type immune response.
94. The use of a ligand as described in any one of claims 1 to 89, for the manufacture of a medicament for treating, suppressing or preventing a Th2 type immune response.
95. The ligand as described in any of claims 1 to 89 for use to treat, suppress or prevent asthma.
96. The use of a ligand as described in any one of claims 1 to 89, for the manufacture of a medicament for treating, suppressing or preventing an asthma disease.
97. The ligand as described in any one of claims 1 to 89 for use in treating, suppressing or preventing cancer.
98. The use of a ligand as described in any of claims 1 to 89, for the manufacture of a medicament for treating, suppressing or preventing cancer.
99. A method for treating an allergic disease comprising administering to a subject in need thereof a therapeutically effective amount of a ligand amount of any one of claims 1 to 89.
100. A method for inhibiting immune response type Th2 comprising administering to a subject in need thereof a therapeutically effective amount of a ligand of any one of claims 1 to 89.
101. A method of treating asthma comprising administering to a subject in need thereof a therapeutically effective amount. of a ligand amount of any one of claims 1 to 89.
102. A method of treating cancer comprising administering to a subject in need thereof a therapeutically effective amount of a ligand amount of any one of claims 1 to 89.
103. The use of a ligand as described in any of claims 1 to 89 for the manufacture of a medicament for the simultaneous administration of an anti-IL-4 treatment and an anti-IL-13 treatment.
104. A method for administering an anti-IL-4 treatment and an anti-IL-13 treatment to a subject, wherein the method comprises the simultaneous administration of an anti-IL-4 treatment and an anti-IL-13 treatment by administering to the subject a therapeutically effective amount of a ligand of any of claims 1 to 27.
105. A a pharmaceutical composition comprising a ligand as described in any one of claims 1 to 89, and a physiologically acceptable carrier.
106. The pharmaceutical composition as described in claim 105, characterized in that the composition comprises a vehicle for intravenous, intramuscular, intraperitoneal, intraarterial, intrathecal, intraarticular or subcutaneous administration.
107. The pharmaceutical composition as described in claim 105, characterized in that the composition comprises a vehicle for pulmonary, intranasal, vaginal or rectal administration.
108. A drug delivery apparatus comprising the pharmaceutical composition as described in claim 105.
109. The drug delivery apparatus as described in claim 108, characterized in that the apparatus comprises a plurality of doses of ligand. Therapeutically effective.
110. The drug delivery apparatus as described in claim 108 or 109, characterized in that the drug delivery apparatus is selected from the group consisting of a parenteral delivery apparatus, an intravenous delivery apparatus, an intravenous delivery device, and intramuscular delivery, an intraperitoneal delivery apparatus, a transdermal delivery apparatus, a pulmonary delivery apparatus, an intraarterial delivery apparatus, an intrathecal delivery apparatus, an intraarticular delivery apparatus, a subcutaneous delivery apparatus, an intranasal delivery apparatus , a vaginal delivery apparatus and a rectal delivery apparatus.
111. The drug delivery apparatus as described in claim 110, characterized in that the apparatus is selected from the group consisting of a syringe, a transdermal delivery device, a capsule, a tablet, a nebulizer, an inhaler, an atomizer, an aerosolizer, a nebulizer, a dry powder inhaler, a metered dose inhaler, a metered dose sprayer, a metered dose sprayer , a metered dose nebulizer, a metered dose sprayer and a catheter.
112. An isolated or recombinant nucleic acid encoding a ligand as described in any one of claims 1 to 89.
113. A vector comprising the recombinant nucleic acid as described in claim 112.
114. A a host cell comprising the recombinant nucleic acid as described in claim 112 or the vector as described in claim 113.
115. A method for producing a ligand, wherein the method comprises maintaining a host cell as described in claim 114, under conditions suitable for expression of nucleic acid or vector, whereby a ligand is produced.
116. The method as described in the claim 115, characterized in that it comprises isolating the ligand.
117. A method for inhibiting the proliferation of peripheral blood mononuclear cells (PBMC) in a subject sensitive to allergens, wherein the method comprises administering to the subject a pharmaceutical composition that comprises a ligand as described in any one of claims 1 to 89.
118. The method as described in claim 117, characterized in that the allergen is selected from house dust acarids, cat allergen, grass, mud allergen and pollen allergen.
119. A method for inhibiting B cell proliferation in a subject, wherein the method comprises administering to the subject a pharmaceutical composition comprising a ligand of any one of claims 1 to 89.
120. A ligand having specificity of linkage for IL-4 and IL-13, comprising a portion of the protein having a binding site with binding specificity for IL-4; and a portion of protein having a binding site with binding specificity for IL-13, wherein the protein portion having binding specificity for IL-4 does not compete to bind with DOM9-15 (SEQ ID NO: 175) , DOM9-17 (SEQ ID NO: 176), DOM9 -23 (SEQ ID NO: 177), DOM9 -24 (SEQ ID NO: 178), DOM9 -25 (SEQ ID NO: 179), DOM9 -27 (SEQ ID NO: 180), DOM9 -28 (SEQ ID NO: 181), DOM9 -29 (SEQ ID NO: 182), DOM9 -30 (SEQ ID NO: 183), DOM9 -31 (SEQ ID NO: 184), DOM9 -32 (SEQ ID NO: 185), DOM9 -33 (SEQ ID NO: 186), DOM9 -50 (SEQ ID NO: 187), DOM9 -57 (SEQ ID NO: 188), DOM9 -59 (SEQ ID NO: 189); DOM9 -63 (SEQ ID NO: 190), DOM9 -67 (SEQ ID ??:? 91), DOM9 -68 (SEQ ID NO: 192), DOM9-70 (SEQ ID NO: 193), DOM9-79 (SEQ ID NO: 194), DOM9-82 (SEQ ID NO: 195), DOM9-86 (SEQ ID NO: 196), DOM9 -94 (SEQ ID NO: 197), DOM9-108 (SEQ ID NO: 198), DOM9-112 (SEQ ID NO: 199), D0M9-112-1 (SEQ ID NO: 200), DOM9-112-2 (SEQ ID NO: 201), DOM9-112-3 (SEQ ID NO: 202), DOM9-112-4 (SEQ ID NO: 203), DOM9-112-5 (SEQ ID NO: 204), DOM9-112 -6 (SEQ ID NO: 205), DOM9-112-7 (SEQ ID NO: 206), DOM9-112-8 (SEQ ID NO: 207), DOM9-112-9 (SEQ ID NO: 208), DOM9 -112-10 (SEQ ID NO: 209), D0M9-112-11 (SEQ ID NO: 210), DOM9-112-12 (SEQ ID NO: 211), DOM9-112-13 (SEQ ID NO: 212) , DOM9-112-14 (SEQ ID NO: 213), DOM9-112-15 (SEQ ID NO: 214), DOM9-112-16 (SEQ ID NO: 215), DOM9-112-17 (SEQ ID NO: 216), DOM9-112-18 (SEQ ID NO: 217), DOM9-112-19 (SEQ ID NO: 218), DOM9-112-20 (SEQ ID NO: 219), DOM9-112-21 (SEQ ID NO: 220), DOM9-112-22 (SEQ ID NO: 221), DOM9-112-23 (SEQ ID NO: 222), DOM9-112-25 (SEQ ID NO: 223), DOM9-112-81 ( SEQ ID NO: 224), DOM9-112-82 (SEQ ID NO: 225), DOM9-112-83 (SEQ ID NO: 226), DOM9-112-84 (SEQ ID NO: 227), DOM9-112- 85 (SEQ ID NO: 228), DOM9-112-86 (SEQ ID NO: 229), DOM9-112-87 (SEQ ID NO: 230), DOM9-112-88 (SEQ ID NO: 231); DOM9-112-89 (SEQ ID NO: 232), DOM9-112-90 (SEQ ID NO: 233), DOM9-112-91 (SEQ ID NO: 234), DOM9-112-92 (SEQ ID NO: 235) ), DOM9-112-93 (SEQ ID NO: 236), DOM9-112-94 (SEQ ID NO: 237), DOM9-112-95 (SEQ ID NO: 238), DOM9-112-96 (SEQ ID NO. : 239), DOM9-112-97 (SEQ ID NO.240), DOM9-112-98 (SEQ ID NO: 241), DOM9-112-99 (SEQ ID NO: 242), DOM9-112-100 (SEQ ID NO: 243) ), DOM9-112-101 (SEQ ID NO: 244), DOM9-1132-102 (SEQ ID NO: 245), DOM9-112-103 (SEQ ID NO: 246), DOM9-112-104 (SEQ ID NO. : 247), DOM9-112-105 (SEQ ID NO: 248), DOM9-112-106 (SEQ ID NO: 249), DOM9-112-107 (SEQ ID NO: 250), DOM9-112-108 (SEQ ID NO: 251), DOM9-112-109 (SEQ ID NO: 252), DOM9-112-110 (SEQ ID NO: 253), DOM9-112-111 (SEQ ID NO: 254), DOM9-112-112 (SEQ ID NO: 255), DOM9-112-113 (SEQ ID NO: 256), DOM9-112-114 (SEQ ID NO: 257), DOM9-112-115 (SEQ ID NO: 258), DOM9-112 -116 (SEQ ID NO: 259), DOM9-112-117 (SEQ ID NO: 260), DOM9-112-118 (SEQ ID NO: 261), DOM9-112-119 (SEQ ID NO: 262), DOM9 -112-120 (SEQ ID NO: 263), DOM9-112-121 (SEQ ID NO: 264), DOM9-112-122 (SEQ ID NO: 265), DOM9-112-123 (SEQ ID NO: 266) , DOM9-112-124 (SEQ ID 110: 267), DOM9-112-125 (SEQ ID NO: 268), DOM9-112-126 (SEQ ID NO: 269), DOM9-112-127 (SEQ ID NO: 270), DOM9-112-128 (SEQ ID NO: 271), DOM9-112-134 (SEQ ID NO: 272), DOM9-112-13 5 (SEQ ID NO: 273), DOM9-112-136 (SEQ ID NO: 274), DOM9-112-137 (SEQ ID NO: 275), DOM9-112-138 (SEQ ID NO: 276), DOM9- 112-140 (SEQ ID NO: 277), DOM9-112-141 (SEQ ID NO: 278), DOM9-112-142 (SEQ ID NO: 279), DOM9-112-143 (SEQ ID NO: 280), DOM9-112-144 (SEQ ID NO: 281), DOM9-112-145 (SEQ ID NO: 282), DOM9-112-146 (SEQ ID NO: 283), DOM9-112-147 (SEQ ID NO: 284) ), DOM9-112-148 (SEQ ID NO: 285), D0M9-112-149 (SEQ ID NO: 286), DOM9-112-150 (SEQ ID NO: 287), D0M9-112-51 (SEQ ID NO: 288), DOM9-112-152 ( SEQ ID NO: 289), DOM9-112-153 (SEQ ID NO: 290), DOM9-112-154 (SEQ ID NO: 291), DOM9-112-155 (SEQ ID NO: 292), DOM9-112- 156 (SEQ ID NO: 293), DOM9-112-157 (SEQ ID NO: 294), DOM9-112-158 (SEQ ID NO: 295), DOM9-112-159 (SEQ ID NO: 296), DOM9- 112-160 (SEQ ID ?? ': 297), DOM9-112-161 (SEQ ID NO: 298), DOM9-112-162 (SEQ ID NO: 299), DOM9-112-163 (SEQ ID NO: 300) ), DOM9-112-164 (SEQ ID NO: 301), DOM9-112-165 (SEQ ID NO: 302), DOM9-112-166 (SEQ ID NO: 303), DOM9-112-167 (SEQ ID NO. : 304), DOM9-112-168 (SEQ ID NO: 305), DOM9-112-169 (SEQ ID NO: 306), DOM9-112-170 (SEQ ID NO: 307), DOM9-112-171 (SEQ ID NO: 308), DOM9-112-172 (SEQ ID NO.309), DOM9-112-173 (SEQ ID NO.310), DOM9-112-174 (SEQ ID NO: 311), DOM9-112-175 (SEQ ID NO: 312), DOM9-112-176 (SEQ ID NO: 313), DOM9-112-177 (SEQ ID NO: 314), DOM9-112-178 (SEQ ID NO: 315), DOM9-112 -179 (SEQ ID NO: 316), DOM9-112-180 (SEQ ID NO: 317), DOM9-112-181 (SEQ ID NO: 318), DOM9-112-182 (SEQ ID NO: 319), DOM9-112-183 (SEQ ID NO: 320), DOM9-112-184 (SEQ ID NO: 321), DOM9-112-185 (SEQ ID NO: 322) ), DOM9-112-186 (SEQ ID NO: 323), DOM9-132-387 (SEQ ID NO: 324), DOM9-112-188 (SEQ ID NO: 325), DOM9-112-189 (SEQ ID NO. : 326), DOM9-112-190 (SEQ ID NO: 327), DOM9-112-191 (SEQ ID NO: 328) DOM9-112-192 (SEQ ID NO: 329), DOM9-112-193 (SEQ ID NO: 330), DOM9-112-194 (SEQ ID NO: 331), D0M9-112-195 (SEQ ID NO: 332), DOM9-112-196 (SEQ ID NO: 333), DOM9-112-197 (SEQ ID NO: 334), DOM9-112-198 (SEQ ID NO: 335), D0M9-112-199 (SEQ ID NO: 336), DOM9-112-200 (SEQ ID NO: 337), DOM9-112-201 (SEQ ID NO: 338), DOM9-112 -202 (SEQ ID NO: 339), DOM9-120 (SEQ ID NO: 340), DOM9-121 (SEQ ID NO: 341), DOM9-122 (SEQ ID NO: 342), DOM9-123 (SEQ ID NO. : 343), DOM9-124 (SEQ ID NO: 344), DOM9-125 (SEQ ID NO: 345), DOM9-128 (SEQ ID NO: 346), DOM9-134 (SEQ ID NO: 347), DOM9- 136 (SEQ ID NO: 348) DOM9-26 (SEQ ID NO: 500), DOM9-35 (SEQ ID NO: 503), DOM9-36 (SEQ ID NO: 502), DOM9-37 (SEQ ID NO: 503) ), DOM9-38 (SEQ ID NO: 504), DOM9-39 (SEQ ID NO: 505), DOM9-40 (SEQ ID NO: 506), DOM9-41 (SEQ ID NO: 507), DOM9-43 ( SEQ ID NO: 508), DOM9-44 (SEQ ID NO: 509), DOM9-44-500 (SEQ ID NO: 510), DOM9-44-501 (SEQ ID NO: 511), DOM9-44-502 ( SEQ ID NO: 512), DOM9-44-503 (SEQ ID NO: 513), DOM9-44-504 (SEQ ID NO: 514), DOM9-44-505 (SEQ ID NO: 515), DOM9-44- 506 (SEQ ID NO: 516), DOM9-44-507 (SEQ ID NO: 517), DOM9-44-509 (SEQ ID NO: 518), DOM9 -44-510 (SEQ ID NO: 519), DOM9-44-511 (SEQ ID NO: 520), DOM9-44-512 (SEQ ID NO: 521), DOM9-44-513 (SEQ ID NO: 522) , DOM9-44-514 (SEQ ID NO: 523), DOM9-44-515 (SEQ ID NO: 524), DOM9-44-516 (SEQ ID NO: 525), DOM9-44-517 (SEQ ID NO: 526), DOM9-44-518 (SEQ ID NO: 527), DOM9-44-519 (SEQ ID NO: 528), DOM9-44-520 (SEQ ID NO: 529), DOM9-44-521 (SEQ ID NO: 530), DOM9-44-522 (SEQ ID NO: 531), DOM9-44-523 (SEQ ID NO: 532), DOM9-44-524 (SEQ ID NO: 533), DOM9-44-525 (SEQ ID NO: 534) ), DOM9-44-526 (SEQ ID NO: 535), DOM9-44-527 (SEQ ID NO: 536), DOM9-44-528 (SEQ ID NO: 537), DOM9-44-529 (SEQ ID NO. : 538), DOM9-44-530 (SEQ ID NO: 539), DOM9-44-531 (SEQ ID NO: 540), DOM9-44-532 (SEQ ID NO: 543), DOM9-44-533 (SEQ ID NO: 542), DOM9-44-534 (SEQ ID NO: 543), DOM9-44-535 (SEQ ID NO: 544), DOM9-44-536 (SEQ ID NO: 545), DOM9-44-537 (SEQ ID NO: 546), DOM9-44-538 (SEQ ID NO: 547), DOM944-539 (SEQ ID NO: 548), DOM9-44-540 (SEQ ID NO: 549), DOM9-44-541 (SEQ ID NO: 550), DOM9-44-542 (SEQ ID NO: 551); DOM9-44-543 (SEQ ID NO: 552), DOM9-44-544 (SEQ ID NO: 553), DOM9-44-545 (SEQ ID NO: 554), DOM9-44-546 (SEQ ID NO: 555) ), DOM9-44-547 (SEQ ID NO: 556), DOM9-44-548 (SEQ ID NO: 557), DOM9-44-549 (SEQ ID NO: 558), DOM9-44-550 (SEQ ID NO. : 559), DOM9-44-551 (SEQ ID NO: 560), DOM9-44-552 (SEQ ID NO: 561), DOM9-44-553 (SEQ ID NO: 562), DOM9-44-554 (SEQ ID NO: 563), DOM9-44-555 (SEQ ID NO: 564), DOM9-44-556 (SEQ ID NO: 565), DOM9-44-557 (SEQ ID NO: 566), DOM9-44-558 (SEQ ID NO: 567), DOM9-44-559 (SEQ ID NO: 568), DOM9-44-560 (SEQ ID NO: 569), DOM9-44-561 (SEQ ID NO: 570), DOM9-44 -562 (SEQ ID NO: 571), DOM9-44-563 (SEQ ID NO: 572), DOM9-44-564 (SEQ ID NO: 573), DOM9-44-565 (SEQ ID NO: 574), DOM9 -44-566 (SEQ ID NO: 575), DOM9-44-625 (SEQ ID NO: 576), DOM9-44-626 (SEQ ID NO: 577), DOM9-44-627 (SEQ ID NO: 578), DOM9-44-628 (SEQ ID NO: 579), DOM9-44-629 (SEQ ID NO: 580) ), DOM9-44-630 (SEQ ID NO: 581), DOM9-44-631 (SEQ ID NO: 582), DOM9-44-632 (SEQ ID NO: 583), DOM9-44-633 (SEQ ID NO. : 584), DOM9-44-634 (SEQ ID NO: 585), DOM9-44-636 (SEQ ID NO: 586), DOM9-44-637 (SEQ ID NO: 587), DOM9-44-639 (SEQ ID NO: 588), DOM9-44-640 (SEQ ID NO: 589), DOM9-44-641 (SEQ ID NO: 590), DOM9-44-642 (SEQ ID NO: 591), DOM9-44-643 (SEQ ID NO: 592), DOM9-44-644 (SEQ ID NO: 593), DOM9-45 (SEQ ID NO: 594), DOM9-46 (SEQ ID NO: 595), DOM9-47 (SEQ ID NO. : 596), DOM9-48 (SEQ ID NO: 597), DOM9-143 (SEQ ID NO: 598), DOM9-144 (SEQ ID NO: 599), DOM9-146 (SEQ ID NO: 600), DOM9- 152 (SEQ ID NO: 601), DOM9-155 (SEQ ID NO: 602), DOM9-155-001 (SEQ ID NO: 603), DOM9-155-3 (SEQ ID NO: 604), DOM9-155- 5 (SEQ ID NO: 605), DOM9-155-8 (SEQ ID NO: 606), DOM9-155-9 (SEQ ID NO: 607), DOM9-155-11 (SEQ ID NO: 608), DOM9- 155-13 (SEQ ID NO: 609), DOM9-155-14 (SEQ ID NO: 610), DOM9-155-17 (SEQ ID NO: 611), DOM9-155-19 (SEQ. ID NO: 612), DOM9-155-20 (SEQ ID NO: 613), DOM9-155-22 (SEQ ID NO: 614), DOM9-155-23 (SEQ ID NO: 615), DOM9-155-24 (SEQ ID NO: 616), DOM9-155-25 (SEQ ID NO: 617), DOM9-155-26 (SEQ ID NO: 618), DOM9-155-27 (SEQ ID NO: 619), DOM9-155 -28 (SEQ ID NO: 620), DOM9-155-29 (SEQ ID NO: 621), DOM9-155-30 (SEQ ID NO: 622), DOM9-155-31 (SEQ ID NO: 623), DOM9 -155- 32 (SEQ ID NO.-624), DOM9-155-33 (SEQ ID NO: 625); DOM9-155-34 (SEQ ID NO: 626), DOM9-155-35 (SEQ ID NO: 627), DOM9-155-36 (SEQ ID NO: 628), DOM9-155-37 (SEQ ID NO: 629) ), DOM9-155-38 (SEQ ID NO: 630), DOM9-155-39 (SEQ ID NO: 631), DOM9-155-41 (SEQ ID NO: 632), DOM9-155-42 (SEQ ID NO. : 633), DOM9-155-43 (SEQ ID NO: 634), DOM9-155-44 (SEQ ID NO: 635), DOM9-155-45 (SEQ ID NO: 636), DOM9-155-46 (SEQ ID NO: 637), DOM9-155-47 (SEQ ID NO: 638), DOM9-155-48 (SEQ ID NO: 639), DOM9-155-49 (SEQ ID NO: 640), DOM9-155-50 (SEQ ID NO: 641), DOM9-155-51 (SEQ ID NO: 642), DOM9-155-52 (SEQ ID NO: 643), DOM9-155-53 (SEQ ID NO: 644), DOM9-158 (SEQ ID NO: 645), DOM9-160 (SEQ ID NO: 646), DOM9-161 (SEQ ID NO: 647), DOM9-162 (SEQ ID NO: 648), DOM9-163 (SEQ ID NO: 649) ) and DOM9-164 (SEQ ID NO: 650).
121. A ligand having binding specificity for IL-4 and IL-13, comprising a portion of protein having a binding site with binding specificity for IL-4, and a portion of protein having a binding site with binding specificity for IL-13, wherein the protein portion having binding specificity for IL-13 does not compete to bind with DOM10-53 (SEQ ID NO: 967), DOM10-53-1 (SEQ ID NO: 968), DOM 10-53-2 (SEQ ID NO: 969), DOM10-53-3 (SEQ ID NO: 970), DOM10-53-4 (SEQ ID NO: 971), DOM10-53-5 (SEQ. ID NO: 972), DOM10-53-6 (SEQ ID NO: 973), DOM10- 53-7 (SEQ ID NO: 974), DOM 10-53-8 (SEQ ID NO: 975), DOM10-53-9 (SEQ ID NO: 976), DOM10-53-10 (SEQ ID NO: 977) , DOM10-53-11 (SEQ ID NO: 978), DOM10-53-12 (SEQ ID NO: 979), DOM10-53-13 (SEQ ID NO: 980), DOM10-53-14 (SEQ ID NO: 981), DOM 10-53-15 (SEQ ID NO: 982), DOM10-53-16 (SEQ ID NO: 983), DOM 10-53-17 (SEQ ID NO: 984), DOM10-53-18 ( SEQ ID NO: 985), DOM10-53-19 (SEQ ID NO: 986), DOM10-53-20 (SEQ ID NO: 987), DOM10-53-21 (SEQ ID NO: 988), DOM10-53- 122 (SEQ ID NO: 989), DOM10-53-123 (SEQ ID NO: 990), DOM10-53-24 (SEQ ID NO: 991), DOM10-53-25 (SEQ ID NO.-992), DOM10 -53-26 (SEQ ID NO: 993), DOM10-53-27 (SEQ ID NO: 994), DOM10-53-28 (SEQ ID NO: 995), DOM10-53-29 (SEQ ID NO: 996) , DOM10-53-30 (SEQ ID NO: 997), DOM10-53-31 (SEQ ID NO: 998), DOM10-53-32 (SEQ ID NO: 1999), DOM10-53-43 (SEQ ID NO: 1000), DOM10-53-44 (SEQ ID NO: 1101), DOM10-53-45 (SEQ ID NO: 1002) 'DOM10-53-46 (SEQ ID NO: 1003), DOM10-53-47 (SEQ ID NO: 1004), DOM10-53-48 (SEQ ID NO: 1005), DOM10-53-49 (SEQ ID NO: 1006), DOM10-53-50 (SEQ ID NO: 1007), DOM10-5 3-51 (SEQ ID NO: 1008), DOM10-53-52 (SEQ ID NO: 1009), DOM10-53-53 (SEQ ID NO: 1010), DOM10-53-54 (SEQ ID NO: 1011), DOM10-53-55 (SEQ ID NO: 1012), DOM10-53-56 (SEQ ID NO: 1013), DOM10-53-57 (SEQ ID NO: 1014), DOM10-53-59 (SEQ ID NO: 1015 ), DOM10-53-60 (SEQ ID NO.-1016), DOM10-53-61 (SEQ ID NO: 1017), DOM10-53-62 (SEQ ID NO: 1018), DOM10-53-63 (SEQ ID NO: 1019), D0M10-53-64 (SEQ ID NO: 1020); DOM10-53-65 (SEQ ID NO: 1021), DOM10-53-66 (SEQ ID NO: 1022), DOM 10-53-67 (SEQ ID NO: 1023), DOM10-53-68 (SEQ ID NO: 1024), DOM10-53-69 (SEQ ID NO: 1025), DOM 10-53-70 (SEQ ID NO: 1026), DOM10-53-71 (SEQ ID NO: 1027), DOM10-53-72 (SEQ. ID NO: 1028), DOM10-53-73 (SEQ ID NO: 1029), DOM 10-53-74 '(SEQ ID NO: 1030), DOM10-53-75 (SEQ ID NO: 1031), DOM10-53 -76 (SEQ ID NO: 1032), DOM10-53-77 (SEQ ID NO: 1033), DOM10-53-78 (SEQ ID NO: 1034), DOM10-53-79 (SEQ ID NO: 1035), DOM10 -53-80 (SEQ ID NO: 1036), DOM10-53-81 (SEQ ID NO: 1037), DOM10-53-82 (SEQ ID NO: 1038), DOM10-53-83 (SEQ ID NO: 1039) , DOM10-53-84 (SEQ ID NO: 1040), DOM10-53-85 (SEQ ID NO: 1041), DOM10-53-86 (SEQ ID NO: 1042), DOM10-53-87 (SEQ ID NO: 1043), DOM10-53-88 (SEQ ID NO: 1044), DOM10-53-89 (SEQ ID NO: 1045), DOM10-53-91 (SEQ ID NO: 1046), DOM10-53-92 (SEQ ID NO: 1047), DOM10-53-93 (SEQ ID NO: 1048), DOM10-53-94 (SEQ ID NO: 1049), DOM10-53-95 (SEQ ID NO: 1050), DOM10-53-96 ( SEQ ID NO: 1051), DOM10-53-97 (SEQ ID NO: 1052), DOM10-53-98 (SEQ ID NO: 1053), DOM1 0-53-99 (SEQ ID NO: 1054), DOM10-53-100 (SEQ ID NO: 1055), DOM10-53-103 (SEQ ID NO: 1056), DOM10-53-105 (SEQ ID NO: 1057) ), DOM10-53-106 (SEQ ID NO: 1058), DOM10-53-108 (SEQ ID NO: 1059), DOM10-53-110 (SEQ ID NO: 1060), DOM10-53-111 (SEQ ID NO. : 1061), DOM10-53-112 (SEQ ID NO: 10632), DOM10-53-114 (SEQ ID NO: 1063), DOM10-53-115 (SEQ ID NO: 1064), DOM10-53-116 (SEQ ID NO: 1065), DOM10-53-317 (SEQ ID NO: 1066), DOM 10-53-119 (SEQ ID NO: 1067), DOM10-53-120 (SEQ ID NO: 1068), DOM10-53-122 (SEQ ID NO: 1069), DOM10-53-201 (SEQ ID NO: 1070), DOM10-53-203 (SEQ ID NO: 1071), DOM10-53 -204 (SEQ ID NO: 1072), DOM10-53-205 (SEQ ID NO: 1073), DOM10-53-206 (SEQ ID NO: 1074), DOM10-53-207 (SEQ ID NO: 1075), DOM10 -53-208 (SEQ ID NO: 1076), DOM10-53-209 (SEQ ID NO: 1077), DOM10-53-210 (SEQ ID NO: 1078), DOM10-53-211 (SEQ ID NO: 1079) , DOM10-53-213 (SEQ ID NO: 1080), DOM10-53-214 (SEQ ID NO: 1081), DOM10-53-215 (SEQ ID NO: 1082), DOM 10-53-216 (SEQ ID NO. : 1083), DOM10-53-217 (SEQ ID NO: 1084), DOM10-53-1218 (SEQ ID NO: 1085), DOM10-53-219 (SEQ ID NO: 1086), DOM10-53-220 (SEQ. ID NO: 1087), DOM 10-53-221 (SEQ ID NO: 1088), DOM10-53-222 (SEQ ID NO: 1089), DOM10-53-223 (SEQ ID NO: 1090), DOM10-53- 224 (SEQ ID NO: 1091), DOM10-53-225 (SEQ ID NO: 1092), DOM10-53-226 (SEQ ID NO: 1093), DOM10-53-227 (SEQ ID NO: 1094), DOM10 -53-228 (SEQ ID NO: 1095), DOM10-53-229 (SEQ ID N OR: 1096), DOM10-53-230 (SEQ ID NO: 1097), DOM10-53-231 (SEQ ID NO: 1098), DOM10-53-232 (SEQ ID NO: 1099), DOM10-53-233 ( SEQ ID NO: 1100), DOM10-53-234 (SEQ ID NO: 1101), DOM10-53-235 (SEQ ID NO: 1102), DOM10-53-236 (SEQ ID NO: 1103), DOM10-53- 237 (SEQ ID NO: 1104), DOM10-53-238 (SEQ ID NO: 1105), DOM10-53-239 (SEQ ID NO: 1106), DOM10-53-240 (SEQ ID NO: 1107), DOM10- 53-241 (SEQ ID NO: 1108), DOM10-53-242 (SEQ ID NO: 1109), DOM10-53-243 (SEQ ID NO: 1110), DOM10-53-244 (SEQ ID NO: 1111), DOM10-53 -245 (SEQ ID N0: 1112), DOM10-53-246 (SEQ ID NO: 1113), DOM10-53-247 (SEQ ID N0: 1114), DO 10-53-248 (SEQ ID NO: 1115), DOM10-53-249 (SEQ ID N0: 1116), DOM10-53-250 (SEQ ID NO: 1117), DOM10-53-251 (SEQ ID NO: 1118), DOM10-53-252 (SEQ ID NO: 1119) ), DOM10-53-253 (SEQ ID NO: 1120), DOM10-53-254 (SEQ ID NO: 1121), DOM10-53-255 (SEQ ID NO: 1122), DOM10-53-256 (SEQ ID NO. : 1123), DOM10-53-257 (SEQ ID NO: 11124), DOM10-53-258 (SEQ ID NO: 1125), DOM10-53-259 (SEQ ID NO: 1126); DOM10-53-260 (SEQ ID NO: 1127), DOM 10-53-261 (SEQ ID NO: 1128), DOM10-53-262 (SEQ ID NO.H29), DOM10-53-263 (SEQ ID NO: 1130), DOM10-53-264 (SEQ ID NO: 1131), DOM10-53-265 (SEQ ID NO: 1132), DOM10-53-266 (SEQ ID NO: 1133), DOM10-53-267 (SEQ ID NO: 1134), DOM10-53-268 (SEQ ID NO: 1135), DOM 10-53-269 (SEQ ID NO: 1136), DOM10-53-270 (SEQ ID NO: 1137), DOM10-53-271 (SEQ ID NO: 1138), DOM10-53-272 (SEQ ID NO: 1139), DOM10-53-273 (SEQ ID NO: 1140), DOM10-53-274 (SEQ ID NO: 1141), DOM10-53 -275 (SEQ ID NO: 1142), DOM10-53-276 (SEQ ID NO: 1143), DOM10-53-277 (SEQ ID NO: 1144), DOM10-53-278 (SEQ ID NO.H45), DOM10 -53-279 (SEQ ID NO: 1146), DOM10-53-280 (SEQ ID NO: 1147), DOM10-53-281 (SEQ ID NO: 1148), DOM 10-53-282 (SEQ ID NO: 1149 ), DOM10-53-283 (SEQ ID NO: 1150), DOM10-53-284 (SEQ ID NO: 1151), DOM10- 53-285 (SEQ ID NO: 1152), DOM10-53-286 (SEQ ID NO: 1153), DOM10-53-287 (SEQ ID NO: 1154), DOM10-53-288 (SEQ ID NO: 1155), DOM10-53-289 (SEQ ID NO: 1156), DOM10-53-290 (SEQ ID NO 157), DOM10-53-291 (SEQ ID NO: 1158), DOM10-53-292 (SEQ ID NO: 1159) , DOM 10-53-293 (SEQ ID NO: 1160), DOM10-53-294 (SEQ ID NO: 1161), DOM10-53-295 (SEQ ID NO: 1162), DOM10-53-296 (SEQ ID NO. : 1163), DOM10-53-297 (SEQ ID NO: 1164), DOM10-53-298 (SEQ ID NO: 1165), DOM10-53-299 (SEQ ID NO: 1166), DOM10-53-300 (SEQ. ID NO: 1167), DOM10-53-301 (SEQ ID NO: 1168), DOM10-53-302 (SEQ ID NO: 1169), DOM10-53-303 (SEQ ID NO: 1170), DOM10-53-304 (SEQ ID NO: 1171), DOM 10-53-305 (SEQ ID NO: 1172), DOM10-53-306 (SEQ ID NO: 1173), DOM10-53-307 (SEQ ID NO: 1174), DOM10- 53-308 (SEQ ID NO: 1175), DOM10-53-309 (SEQ ID NO: 1176), DOM10-53-310 (SEQ ID NO: 11787), DOM10-53-311 (SEQ ID NO: 1178), DOM10-53-312 (SEQ ID NO: 1179), DOM10-53-314 (SEQ ID NO: 1180), DOM10-53-315 (SEQ ID NO: 1181), DOM10-53-316 (SEQ ID NO: 1182) ), DOM10-53-317 (SEQ ID NO: 1183), DOM10-53-318 (SEQ ID NO: 1184), DOM10-53-319 (SEQ ID NO: 1185), DOM10-53-320 (SEQ ID NO: 1186), DOM10-53-321 (SEQ ID NO: 1187), DOM10-53 -322 (SEQ ID NO: 1188), DOM10-53-323 (SEQ ID NO: 1189), DOM10-53-324 (SEQ ID NO: 1190), DOM10-53-325 (SEQ ID NO: 1191), DOM10 -53-326 (SEQ ID NO: 1192), DOM10-53-327 (SEQ ID NO: 1193), DOM10-53-328 (SEQ ID NO: 1194), DOM10-53-329 (SEQ ID NO: 1195) , DOM10-53-330 (SEQ ID NO: 1196), DOM 10-53-331 (SEQ ID NO: 1197), DOM10-53-333 (SEQ ID NO: 1198), DOM10-53-334 (SEQ ID NO: 1199), DOM10-53-336 (SEQ ID NO: 1200), DOM10-53-337 (SEQ ID NO: 1201), DOM10-53-338 (SEQ ID NO: 1202), DOM10-53-339 (SEQ ID NO: 1203), DOM 10-53-340 (SEQ ID NO: 1204), DOM10-53-341 (SEQ ID NO: 1205), DOM10-53-342 (SEQ ID NO: 1206), DOM10-53-343 (SEQ ID NO: 1207), DOM10-53-344 (SEQ ID NO: 1208), DOM10-53-345 (SEQ ID NO: 1209), DOM10-53-346 (SEQ ID NO: 1210), DOM10-53 -347 (SEQ ID NO: 1211), DOM10-53-348 (SEQ ID NO: 1212), DOM10-53-349 (SEQ ID NO: 1213), DOM10-53-350 (SEQ ID NO: 1214), DOM10 -53-351 (SEQ ID NO: 1215), DOM10-53-352 (SEQ ID NO: 1216), DOM10-53-353 (SEQ ID NO: 1217), DOM10-53-354 (SEQ ID NO: 1218) , DOM10-53-355 (SEQ ID NO: 1219), DOM10-53-356 (SEQ ID NO: 1220), DOM10-53-357 (SEQ ID NO: 1221), DOM10-53-358 (SEQ ID NO: 1222), DOM10-53-359 (SEQ ID NO: 1223), DOM10-53-360 (SEQ ID NO: 1224), DOM10-53-361 (SEQ ID NO: 1225), DOM10-53-362 (SEQ ID NO: 1226), DOM10-53-363 (SEQ ID NO: 1227), DOM10- 53-364 (SEQ ID NO.H28), DOM10-53-365 (SEQ ID NO: 1229), DOM10-53-366 (SEQ ID NO: 1230), DOM10-53-367 (SEQ ID NO 231), DOM10 -53-368 (SEQ ID NO: 1232), DOM10-53-369 (SEQ ID NO: 1233), DOM10-53-370 (SEQ ID NO: 1234), DOM10-53-371 (SEQ ID NO: 1235) , DOM10-53-372 (SEQ ID NO: 1236), DOM 10-53-373 (SEQ ID NO: 1237), DOM10-53-374 (SEQ ID NO: 1238), DOM10-53-375 (SEQ ID NO: 1239), DOM10-53-376 (SEQ ID * NO: 1240), DOM 10-53-377 (SEQ ID NO: 1241), DOM 10-53-378 (SEQ ID NO: 1242), DOM10-53 -379 (SEQ ID NO: 1243), DOM10-53-380 (SEQ ID NO: 1244), DOM10-53-381 (SEQ ID NO: 1245), DOM10-53-382 (SEQ ID NO: 1246), DOM 10-53-383 (SEQ ID NO: 1247), DOM10-53-384 (SEQ ID NO: 1248), DOM10-53-385 (SEQ ID NO: 1249), DOM10-53-386 (SEQ ID NO: 1250) ), DOM10-53-387 (SEQ ID NO: 1251), DOM10-53-388 (SEQ ID NO: 1252), DOM10-53-389 (SEQ ID NO: 1253), DOM10-53-390 (SEQ ID NO. : 1254), DOM10-53-391 (SEQ ID NO: 1255), DOM10-53-392 (SEQ ID NO: 1256), DOM10-53-393 (SEQ ID NO: 1257), DOM10-53-394 (SEQ. ID NO: 1258), DOM10-53-395 (SEQ ID NO: 1259), DOM10-53-396 (SEQ ID NO: 1260), DOM10-53-400 (SEQ ID NO: 1261), DOM10-53-401 (SEQ ID NO: 1262), DOM10-53-402 (SEQ ID NO: 1263), DOM10-53-403 (SEQ ID NO: 1264), DOM10-53-404 (SEQ ID NO: 1265), DOM10-53 -405 (SEQ ID NO: 1266), DOM10-53-406 (SEQ ID NO: 1267), DOM10-53-407 (SEQ ID NO: 1268), DOM10-53-408 (SEQ ID NO: 1269), DOM10 -53-409 (SEQ ID NO: 1270), DOM10-53-410 (SEQ ID NO: 1 271), DOM10-53-411 (SEQ ID NO: 1272), DOM10-53-412 (SEQ ID NO: 1273), DOM10-53-413 (SEQ ID NO: 1274), DOM10-53-414 (SEQ ID NO: 1275), DOM10-53-415 (SEQ ID NO: 1276), DOM10-53-416 (SEQ ID NO: 1277), DOM10-53-417 (SEQ ID NO: 1278), DOM10-53-418 ( SEQ ID NO: 1279), DOM10-53-419 (SEQ ID NO: 1280), DOM10-53-420 (SEQ ID NO: 1281), DOM10-53-421 (SEQ ID NO: 1282), DOM10-168 ( I KNOW THAT ID NO: 1508), DOM10-169 (SEQ ID NO: 1509), DOM10-176 (SEQ ID NO: 1510), DOM10-176-1 (SEQ ID N0: 1511), DOM10-176-2 (SEQ ID N0 .1512), DO 10-173 (SEQ ID NO: 1513), DOM10-176-4 (SEQ ID NO: 1514), DOM 10-176-5 (SEQ ID NO: 1515), DOM10-176-6 (SEQ. ID NO: 1516), DOM10-176-23 (SEQ ID NO: 1517), DOM10-176-24 (SEQ ID NO: 1518), DOM10-176-25 (SEQ ID NO: 1519), DOM 10-176- 26 (SEQ ID NO: 1520), DOM10-176-27 (SEQ ID NO: 1521), DOM10-176-28 (SEQ ID NO: 1522), DOM10-176-29 (SEQ ID NO: 1523), DOM10- 176-30 (SEQ ID NO: 1524), DOM10-176-31 (SEQ ID NO: 1525), DOM10-176-32 (SEQ ID NO: 1526), DOM10-176-33 (SEQ ID NO: 1527), DOM10-176-34 (SEQ ID NO: 1528), DOM10-176-35 (SEQ ID NO: 1529), DOM10-176-36 (SEQ ID NO: 1530), DOM10-176-37 (SEQ ID NO: 1531) ), DOM10-176-38 (SEQ ID NO: 1532), DOM10-176-39 (SEQ ID NO: 1533), DOM10-176-40 (SEQ ID NO: 1534), DOM 10- 176- 101 (SEQ ID NO: 1535), DOM 10-176-102 (SEQ ID NO: 1536), DOM10-176-103 (SEQ ID NO: 1537), DOM10-176-104 (SEQ ID NO: 1538), DOM10-176-105 (SEQ ID NO: 1539), DOM 10- 176-106 (SEQ ID NO. : 1540), DOM10-176-107 (SEQ ID NO: 1541), DOM 10- 176-08 (SEQ ID NO: 1542), DOM10-176-109 (SEQ ID NO: 1543), DOM10-176-110 ( SEQ ID NO: 1544), DOM10-176-111 (SEQ ID NO: 1545), DOM10-176-112 (SEQ ID NO: 1546), DOM 10-176-113 (SEQ ID NO: 1547), DOM 10- 176-114 (SEQ ID NO: 1548), DOM 10-176-115 (SEQ ID NO: 1549), DOM 10-176-116 (SEQ ID NO: 1550), DOM10-176-117 (SEQ ID NO: 1551) ), DOM 10-175-500 (SEQ ID NO: 1552), DOM10-176-501 (SEQ ID NO: 1553), DOM 10-176-502 (SEQ ID NO: 1554), DOM 10-176-503 (SEQ ID NO: 1555), DOM 10- 176-504 (SEQ ID NO: 1556), DOM10-176-505 (SEQ ID NO: 1557), DOM10-176-506 (SEQ ID NO: 1558), DOM 10-176-507 (SEQ ID NO: 1559), DOM10-176-508 (SEQ ID NO: 1560), DOM 10-176-509 (SEQ ID NO: 1561), DOM10-176-510 (SEQ ID NO: 1562), DOM 10- 176-511 (SEQ ID NO: 1563), DOM10 -176-512 (SEQ ID NO: 1564), DOM10-176-513 (SEQ ID NO: 1565), DOM10-176-514 (SEQ ID NO: 1566), DOM10-176-515 (SEQ ID NO: 1567) , DOM 10-76-516 (SEQ ID NO: 1568), DOM 10-176-517 (SEQ ID NO: 1569), DOM 10- 176-518 (SEQ ID NO: 1570), DOM 10-176-519 ( SEQ ID NO: 1571), DOM10-176-520 (SEQ ID NO: 1572), DOM 10- 176-521 (SEQ ID NO: 1573), DOM10-176-522 (SEQ ID NO: 1574), DOM 10- 176-523 (SEQ ID NO: 1575), DOM 10-176-524 (SEQ ID NO: 1576), DOM 10- 176-525 (SEQ ID NO: 1577), DOM 10-176-526 (SEQ ID NO: 1578), DOM10-176-527 (SEQ ID NO: 3579), DOM 10-176-528 (SEQ ID NO: 1580), DOM10-176-529 (SEQ ID NO: 1581), DOM 10- 176-530 ( SEQ ID NO: 1582), DOM10-176-531 (S EQ ID NO: 1583), DOM 10-176-532 (SEQ ID NO: 1584), DOM 10-176-533 (SEQ ID NO: 1585), DOM10-176-534 (SEQ ID NO: 1586), DOM 10 176-535 (SEQ ID NO: 1587), DOM10-176-536 (SEQ ID NO: 1588), DOM 10-176-537 (SEQ ID NO: 1589), DOM 10- 176-538 (SEQ ID NO: 1590), DOM10-176-539 (SEQ ID NO: 1591), DOM10-176-540 (SEQ ID NO: 1592), DOM10-176-541 (SEQ ID NO: 1593), DOM 10-176-542 (SEQ. ID NO: 1594), DOM10-176-543 (SEQ ID NO: 1595), DOM 10- 176-544 (SEQ ID NO: 1596), DOM 10-176-545 (SEQ ID NO: 1597), DOM 10-176-546 (SEQ ID NO: 1598), DOM 10-176-547 (SEQ ID NO: 1599), DOM10-176 -548 (SEQ ID NO: 1600), DOM 10-176-549 (SEQ ID NO: 1601), DOM10-176-550 (SEQ ID NO: 1602), DOM 10- 176-551 (SEQ ID NO: 1603) , DOM 10-176-552 (SEQ ID NO: 1604), DOM 10-176-553 (SEQ ID NO: 1605), DOM10-176-554 (SEQ ID NO: 1606), DOM10-176-555 (SEQ ID NO: 1607), DOM 10-176-556 (SEQ ID NO: 1608), DOM10-176-557 (SEQ ID NO: 1609), DOM 10-176-558 (SEQ ID NO: 1610), DOM10-176- 559 (SEQ ID NO: 1611), DOM 10-176-560 (SEQ ID NO: 1612), DOM10-176-561 (SEQ ID NO: 1613). DOM10-176-562 (SEQ ID NO: 1614), DOM 10-176-563 (SEQ ID NO: 615), DOM10-176-564 (SEQ ID NO: 1616), DOM 10-176-565 (SEQ ID NO. : 1617), DOM 10- 176-566 (SEQ ID NO: 1618), DOM 10- 176-567 (SEQ ID NO: 1619), DOM 10-176-568 (SEQ ID NO: 1620), DOM10-376- 569 (SEQ ID NO: 1621), DOM 10-176-570 (SEQ ID NO: 1622), DOM10-176-571 (SEQ ID NO: 1623), DOM 10-176-572 (SEQ ID NO: 1624), DOM 10-176-573 (SEQ ID NO: 1625), DO M 10-176-574 (SEQ ID NO: 1626), DOM 10-176-575 (SEQ ID NO: 1627), DOM10-176-576 (SEQ. ID NO: 1628), DOM 10-176-577 (SEQ ID NO: 1629), DOM10-176-578 (SEQ ID NO: 1630), DOM 10- 176-579 (SEQ ID NO: 1631), DOM 10- 176-580 (SEQ ID NO: 1632), DOM10-176-581 (SEQ ID NO: 1633), DOM 10- 176-582 (SEQ ID NO: 1634), DOM10-176-583 (SEQ ID NO: 1635) , DOM 10-176-584 (SEQ ID NO: 1636), DOM10-176-585 (SEQ ID NO: 1637), DOM 10- 176-586 (SEQ ID NO: 1638), DOM 10- 176-587 (SEQ. ID NO: 1639), DOM 10- 176-588 (SEQ ID NO: 1640), DOM 10-76-589 (SEQ ID NO: 1641), DOM10-176-590 (SEQ ID NO: 1642), DOM 10-176-591 (SEQ ID NO: 1643), DOM10 -176-592 (SEQ ID NO: 1644), DOM 0-176-593 (SEQ ID NO: 1645), DOM 10- 176-594 (SEQ ID NO: 1646), DOM 10-176-595 (SEQ ID NO. : 1647), DOM 10- 176-596 (SEQ ID NO: 1648), DOM10-176-597 (SEQ ID NO: 1649), DOM 10-176-598 (SEQ ID NO: 1650), DOM10-176-599 (SEQ ID NO: 1651), DOM10-176-600 (SEQ ID NO: 1652), DOM10-176-601 (SEQ ID NO: 1653), DOM 10-176-602 (SEQ ID NO: 1654), DOM 10 -176-603 (SEQ ID NO: 1655), DOM10-176-604 (SEQ ID NO: 1656), DOM 10- 176-605 (SEQ ID NO: 1657), DOM10-176-606 (SEQ ID NO: 1658 ), DOM 10- 176-607 (SEQ ID NO: 1659), DOM 10- 176-608 (SEQ ID NO: 1660), DOM 10-176-609 (SEQ ID NO: 1661), DOM10-176-610 ( SEQ ID NO: 1662), DOM10-176-611 (SEQ ID NO: 1663), DOM10-176-612 (SEQ ID NO: 1664), DOM10-176-613 (SEQ ID NO: 1665) f DOM 10- 176 -614 (SEQ ID NO: 1666), DOM 10- 176-615 (SEQ ID NO: 1667), DOM 10-76-616 (SEQ ID NO: 1668), DOM 10- 176-617 (SEQ ID NO: 1669 ), DOM10-176-618 (SEQ ID NO: 1670) , DOM10-176-619 (SEQ ID NO: 1671), DOM10-176-620 (SEQ ID NO: 1672), DOM 10-176-621 (SEQ ID NO: 1673), DOM 10-176-622 (SEQ ID. NO: 1674), DO M 10-766-623 (SEQ ID NO: 1675), DOM 10-176-624 (SEQ ID NO: 1676), DOM10-176-625 (SEQ ID NO: 1677), DOM 10- 176-626 (SEQ ID NO: 1678), DOM10-176-627 (SEQ ID NO: 1679), DOM 10-176-628 (SEQ ID NO: 1680), DOM10-176-629 (SEQ ID NO: 1681) , DOM 10-176-630 (SEQ ID NO: 1682), DOM 10- 176-631 (SEQ ID NO: 1683), DOM10- 176-632 (SEQ ID NO: 1684), DOM 10-176-633 (SEQ ID NO: 1685), DOM10-176-634 (SEQ ID NO: 1686), DOM 10- 176-635 (SEQ ID NO: 1687 ), DOM 10-176-636 (SEQ ID NO: 1688), DOM 10-176-637 (SEQ ID NO: 1689), DOM 10- 176-638 (SEQ ID NO: 1690), DOM10-176-639 ( SEQ ID NO: 1691), DOM 10- 176-640 (SEQ ID NO: 1692), DOM10-176-641 (SEQ ID NO: 1693), DOM 10- 176-643 (SEQ ID NO: 1694), DOM 10 176-644 (SEQ ID NO: 1695), DOM 10- 176-645 (SEQ ID NO: 1696), DOM 10-76-646 (SEQ ID NO: 1697), DOM10-176-647 (SEQ ID NO: 1698), DOM 10-176-648 (SEQ ID NO: 1699), DOM10-176-649 (SEQ ID NO: 1700), DOM10-176-650 (SEQ ID NO: 1701), DOM10-176-651 (SEQ. ID NO: 1702), DOM 10-176-652 (SEQ ID NO: 1703), DOM 0-176-653 (SEQ ID NO: 1704), DOM10-176-654 (SEQ ID NO: 1705), DOM 10- 176-655 (SEQ ID NO: 1706), DOM10-176-656 (SEQ ID NO: 1707), DOM 10-176-657 (SEQ ID NO: 1708), DOM 10-176-658 (SEQ ID NO: 1709 ), DOM 10-176-659 (SEQ ID NO: 1710), DOM10-176-660 (SEQ ID NO: 1711), DOM10-176-661 (SEQ ID NO: 1712), DOM 10-176-662 (SEQ. ID NO: 1713), DOM10-176-663 (SEQ ID NO: 1714), DOM 10-176-664 (SEQ ID NO: 1715), DOM 10-176-665 (SEQ ID NO: 1716), DOM 10- 176-666 (SEQ ID NO: 1717), DO M 10 176-667 (SEQ ID NO: 1718), DOM10-176-668 (SEQ ID NO: 1719), DO M 10- 176-669 (SEQ ID NO: 1720), DOM10-176-670 (SEQ ID NO: 1721), DO M 10- 176-671 (SEQ ID NO: 1722), DOM10-176-672 (SEQ ID NO: 1723), DOM 10-176-673 (SEQ ID NO: 1724), DOM 10-176- 674 (SEQ ID NO: 1725), DOM10-176-675 (SEQ ID NO: 1726), DOM10-253 (SEQ ID NO: 1727), DOM10-255 (SEQ ID NO: 1728), DOM10-272 (SEQ ID NO: 1729), DOM10-307 (SEQ ID NO: 1730), DOM10-319 (SEQ ID NO: 1731) and DOM10-319-1 ( SEQ ID NO: 1732).
122. The ligand as described in claim 120 or 121, provided that the ligand does not comprise an IL-4 trap or an IL-13 trap.
123. A ligand having binding specificity for IL-4 and IL-13, comprising a portion of protein having a binding site with binding specificity for IL-4; and a protein portion having a binding site with binding specificity for IL-13, wherein the protein portion having binding specificity for IL-4 does not compete to bind with DOM9-155-77 (SEQ ID NO: 2426), DOM9-155-78 (SEQ ID NO: 2427), DOM9-112-204 (SEQ ID NO: 2428), DOM9-112-205 (SEQ ID NO: 2429), DOM9-112-206 (SEQ ID NO: 2430), DOM9-112-207 (SEQ ID NO: 2431), DOM9-112-208 (SEQ ID NO: 2432), DOM9-112-209 (SEQ ID NO: 2433), DOM9-112-210 (SEQ ID NO: 2434), DOM9-112-21 (SEQ ID NO: 2435), DOM9-112-212 (SEQ ID NO: 2436), DOM9-112-213 (SEQ ID NO: 2437), DOM9-112 -214 (SEQ ID NO: 2438), DOM9-112-215 (SEQ ID NO: 2439), DOM9-112-216 (SEQ ID NO: 2440), DOM9-112-217 (SEQ ID NO: 2441), DOM9 -112-218 (SEQ ID NO: 2442), DOM9-112-219 (SEQ ID NO: 2443), DOM9-112-220 (SEQ ID NO: 2444), DOM9-112-221 (SEQ ID NO: 2445) , DOM9-112-222 (SEQ ID NO: 2446), DOM9-112-223 (SEQ ID NO: 2447), DOM9- 112-224 (SEQ ID NO: 2448), DOM9-1-12-225 (SEQ ID NO: 2449), DOM9-112-226 (SEQ ID NO: 2450), DOM9-112-227 (SEQ ID NO: 2451) ), DOM9-112-228 (SEQ ID NO: 2452), DOM9-112-229 (SEQ ID NO: 2453), DOM9-112-230 (SEQ ID NO: 2454), DOM9-112-231 (SEQ ID NO. : 2455), DOM9-112-233 (SEQ ID NO: 1734), DOM9-112-232 (SEQ ID NO: 1733) and DOM9-112-234 (SEQ ID NO: 1735).
124. A ligand having binding specificity for IL-4 and IL-13 comprising a portion of the protein having a binding site with binding specificity for IL-4; and a protein portion having a binding site with binding specificity for IL-13, wherein the protein portion having binding specificity for IL-13 does not compete to bind with DOM10-236 (SEQ ID NO: 2129) , DOM10 -238 (SEQ ID NO 2130) DOM10 -241 (SEQ ID NO: 2131), DOM10 -245 (SEQ ID NO 2132) DOM10 -249 (SEQ ID NO: 2133), DOM10 -250 (SEQ ID NO 2134) DOM10 -251 (SEQ ID NO: 2135), DOM10 -254 (SEQ ID NO 2136) DOM10 -256 (SEQ ID NO: 2137), DOM10 -259 (SEQ ID NO 2138) DOM10 -260 (SEQ ID NO: 2139), DOM10 -261 (SEQ ID NO 2140) DOM10 -263 (SEQ ID NO: 2141), DOM10 -264 (SEQ ID NO 2142) DOM10 -273 (SEQ ID NO: 2143), DOM10 -278 (SEQ ID NO 2144) DOM10 -279 (SEQ ID NO: 2145), DOM10 -281 (SEQ ID NO 2146), DOM10 -282 (SEQ ID NO: 2147), DOM10 -283 (SEQ ID NO 2148), DOM10 -400 (SEQ ID NO: 2149), DOM10 -401 (SEQ ID NO 2150), DOM10 -402 (SEQ ID NO: 2151), DOM10 -404 (SEQ ID NO: 2152) DOM10 -406 (SEQ ID NO: 2153), DOM10 -407 (SEQ ID NO: 2154) DOM10 -409 (SEQ ID NO: 2155), DOM10 -410 (SEQ ID NO: 2156) DOM10 -414 (SEQ ID NO: 2157), DOM10 -415 (SEQ ID NO: 2158) DOM10 -416 (SEQ ID NO: 2159), DOM10 -418 (SEQ ID NO 2160) DOM10 -420 (SEQ ID NO: 2161), DOM10 -422 (SEQ ID NO 2162) DOM10 -423 (SEQ ID NO: 2163), DOM10 -424 (SEQ ID NO 2164) DOM10 -425 (SEQ ID NO: 2165), DOM10 -426 (SEQ ID NO 2166) DOM10 -427 (SEQ ID NO: 2167), DOM10 -428 (SEQ ID NO 2168) DOM10 -429 (SEQ ID NO: 2169), DOM10 -430 (SEQ ID NO 2170) DOM10 -431 (SEQ ID NO: 2171), DOM10 -432 (SEQ ID NO 2172) DOM10 -433 (SEQ ID NO: 2173), DOM10 -467 (SEQ ID NO 2174) DOM10 -468 (SEQ ID NO: 2175), DOM10 -469 (SEQ ID NO 2176) DOM10 -470 (SEQ ID NO: 2177), DOM10 -234 (SEQ ID NO 2178) DOM10 -235 (SEQ ID NO: 2179), DOM10 -237 (SEQ ID NO 2180) DOM10 -239 (SEQ ID NO: 2181), DOM10 -240 (SEQ ID NO 2182) DOM10 -242 (SEQ ID NO: 2183), DOM10 -243 (SEQ ID NO 2184), DOM10 -244 (SEQ ID NO: 2185), DOM10 -246 (SEQ ID NO 2186), DOM10 -247 (SEQ ID NO: 2187), DOM10 -248 (SEQ ID NO 2188), DOM10 -252 (SEQ ID NO: 2189), DOM10 -257 (SEQ ID NO 2190), DOM10 -258 (SEQ ID NO: 2191), DOM10 -262 (SEQ ID NO 2192), DOM10 -265 (SEQ ID NO: 2193), DOM10-266 (SEQ ID NO: 2194), DOM10- | 274 (SEQ ID NO: 2195), DOM10- |275 (SEQ ID NO: 2196), DOM10- |276 (SEQ ID NO: 2197), DOM10- | 277 (SEQ ID NO: 2198), DOM10- | 280 (SEQ ID NO: 2199), DOM10- | 403 (SEQ ID NO: 2200), DOM10- | 405 (SEQ ID NO: 2201), DOM10 -408 (SEQ ID NO: 2202) DOM10 -411 |; SEQ ID NO: 2203), DOM10 -412 (SEQ 10? 0: 2204), DOM.10- | 413 (SEQ ID NO.2205), DOM10 -417 (SEQ ID NO • 2206) DOM10 -419 | , SEQ ID NO: 2207), DOM10 -472 (SEQ ID NO: 2208) DOM10 -203 | [SEQ ID NO: 2209), DOM10 -205 (SEQ ID NO 2210) DOM10 -208 | SEQ ID NO: 221), DOM10 -218 (SEQ ID NO 2212) DOM10 -219 (SEQ ID NO: 2213), DOM10 -220 (SEQ ID NO: 2214) DOM10-225 ('SEQ ID NO: 2215), DOM10 -228 (SEQ ID NO 2216) DOM10 -229 (SEQ ID NO: 2217), DOM10 -230 (SEQ ID NO 2218) DOM10 -231 (SEQ ID NO: 2219), DOM10 -268 (SEQ ID NO 2220) DOM10 -201 (SEQ ID NO: 2221), DOM10 -202 (SEQ ID NO 2222) DOM10 -204 (SEQ ID NO: 2223), DOM10 -206 (SEQ ID NO 2224) DOM10 -207 (SEQ ID NO: 2225), DOM10 -209 (SEQ ID NO 2226) DOM10 -210 (SEQ ID NO: 2227), DOM10 -211 (SEQ ID NO 2228) DOM10 -213 (SEQ ID NO: 2229), DOM10 -214 (SEQ ID NO 2230) DOM10 -215 (SEQ ID NO: 2231), DOM10 -216 (SEQ ID NO 2232), DOM10 -217 (SEQ ID NO: 2233), DOM10 -221 (SEQ ID NO 2234), DOM10 -223 (SEQ ID NO: 2235), DOM10-224 (SEQ ID NO 2236), DOM10-227 (SEQ ID NO: 2237), DOM10 -232 (SEQ ID NO 2238), DOM10 -267 (SEQ ID NO: 2239), DOM10 -270 (SEQ ID NO: 2240), DOM10 -275- 1 (SEQ ID NO: 2241), OJ M10-276-2 (SEQ ID NO: 2242), DOM 10-276-3 (SEQ ID NO: 2243), DOM10-275-3 (SEQ ID NO: 2244), DOM10-277- 2 (SEQ ID NO: 2245), DOM10-277-3 (SEQ ID NO: 2246), DOM10-273-1 (SEQ ID NO: 2247), DOM10-273-2 (SEQ ID NO: 2248), DOM10- 275-2 (SEQ ID NO: 2249), DOM10-275-4 (SEQ ID NO: 2250), DOM10-276-1 (SEQ ID NO: 2251), DOM 10-276-4 (SEQ ID NO: 2252), DOM 10-277-1 (SEQ ID NO: 2253), DOM 10-275 -13 (SEQ ID NO: 2254), DOM10-275-15 (SEQ ID NO: 2255), DOM10-275-20 (SEQ ID NO: 2256), DOM10-275-8 (SEQ ID NO: 2257), DOM10 -276-13 (SEQ ID NO: 2258), DOM10-276-14 (SEQ ID NO: 2259), DOM10-276-15 (SEQ ID NO: 2260), DOM10-276-17 (SEQ ID NO: 2261), DOM10-276-7 (SEQ ID NO: 2262), DOM10-276-8 ( SEQ ID NO: 2263), DOM10-275-11 (SEQ ID NO: 2264); DOM10-275-12 (SEQ ID NO: 2265), DOM10-275-14 (SEQ ID NO: 2266), DOM10-275-16 (SEQ ID NO: 2267), DOM10-275-17 (SEQ ID NO: 2268) ), DOM10-275-5 (SEQ ID NO: 2269), DOM10-275-6 (SEQ ID NO: 2270), DOM10-275-7 (SEQ ID NO: 2271), DOM10-275-9 (SEQ ID NO. : 2272), 'DOM10-276-10 (SEQ ID NO: 2273), DOM10-276-11 (SEQ ID NO: 2274), DOM10-276-12 (SEQ ID NO: 2275), DOM10-276-16 ( SEQ ID NO: 2276), DOM10- 276-5 (SEQ ID NO: 2277), DOM10-276-6 (SEQ ID NO: 2278), DOM10-276-9 (SEQ ID NO: 2279), DOM10-212 (SEQ ID NO: 2280), DOM10-53-424 (SEQ ID NO: 2281) , DOM10-53-425 (SEQ ID NO: 2282), DOM10-53-426 (SEQ ID NO: 2283), DOM10-53? 422 (SEQ ID NO: 2284), DOM10-53-423 (SEQ ID NO: 2285), DOM10-53-613 (SEQ ID NO: 2286), DOM10-53-517 (SEQ ID NO: 2287), DOM10-53-519 (SEQ ID NO: 2288), DOM10-53-520 (SEQ ID NO: 2289), DOM10-53-521 (SEQ ID NO: 2290), DOM10-53-522 (SEQ ID NO: 2291), DOM10-53-526 (SEQ ID NO: 2292), DOM10-53-527 ( SEQ ID NO: 2293); DOM10-53-528 (SEQ ID NO: 2294), DOM 10-53-518 (SEQ ID NO: 2295), DOM10-53-523 (SEQ ID NO: 2296), DOM10-53-524 (SEQ ID NO: 2297), DOM10-53-525 (SEQ ID NO: 2298), DOM10-53-601 (SEQ ID NO: 2299), DOM10-53-602 (SEQ ID NO: 2300), DOM10-53-605 (SEQ ID NO: 2301), DOM10-53 -606 (SEQ ID NO: 2302), DOM10-53-607 (SEQ ID NO: 2303), DOM 10-53-608 (SEQ ID NO: 2304), DOM10-53-609 (SEQ ID NO: 2305), DOM10-53-610 (SEQ ID NO: 2306), DOM10-53-611 (SEQ ID NO: 2307), DOM10-53-612 (SEQ ID NO: 2308), DOM10-53-603 (SEQ ID NO: 2309) ), DOM10-53-604 (SEQ ID NO: 2310), DOM10-53-429 (SEQ ID NO: 2311), DOM10-53-432 (SEQ ID NO: 2312), DOM10-53-433 (SEQ ID NO. : 2313), DOM10-53-435 (SEQ ID NO: 2314), DOM10-53-430 (SEQ ID NO: 2315), DOM10-53-431 (SEQ ID NO: 2316), DOM 10-53-434 (SEQ ID NO: 2317), DOM10-53-436 (SEQ ID NO: 2318), DOM10-53-437 (SEQ ID NO: 2319), DOM10-53-438 (SEQ ID NO: 2320), DOM10-53 -440 (SEQ ID NO: 2321), DOM10-53-439 (SEQ ID NO: 2322), DOM10-53-441 (SEQ ID NO: 2323), DOM10-53-442 (SEQ ID NO: 2324), DOM10 -53-443 (SEQ ID NO: 2325), DOM10-53-444 (SEQ ID NO: 2 326), DOM10-53-445 (SEQ ID NO: 2327), DOM10-53-446 (SEQ ID NO: 2328), DOM10-53-447 (SEQ ID NO: 2329), DOM10-53-449 (SEQ ID NO: 2330), DOM10-53-448 (SEQ ID NO.-2331), DOM10-53-450 (SEQ ID NO: 2332), DOM10-53-451 (SEQ ID NO: 2333), DOM10-53-452 (SEQ ID NO: 2334), DOM10-53-453 (SEQ ID NO: 2335), DOM10-53-454 (SEQ ID NO: 2336), DOM10-53-455 (SEQ ID NO: 2337), DOM10-53 -456 (SEQ ID NO: 2338), DOM10-53-457 (SEQ ID NO: 2339), DOM10-53-458 (SEQ ID NO: 2340), DOM10-53-459 (SEQ ID NO: 2341), DOM10-53 -461 (SEQ ID NO: 2342), DOM10-53-462 (SEQ ID NO: 2343), DOM 10-53-465 (SEQ ID NO: 2344), DOM10-53-466 (SEQ ID NO: 2345), DOM10-53-467 (SEQ ID NO: 2346), DOM10-53-468 (SEQ ID NO: 2347), DOM10-53-460 (SEQ ID NO: 2348), DOM10-53-463 (SEQ ID NO: 2349) ) DOM 10-53-464 (SEQ ID NO: 2350), DOM10-53-469 (SEQ ID NO: 2351), DOM10-53-471 (SEQ ID NO: 2352), DOM10-53-470 (SEQ ID NO. : 2353), DOM10-53-533 (SEQ ID NO: 2354), DOM10-53-534 (SEQ ID NO: 2355), DOM10-53-535 (SEQ ID NO: 2356), DOM10-53-537 (SEQ. ID NO: 2357), DOM 10-53-538 (SEQ ID NO: 2358), DOM10-53-539 (SEQ ID NO: 2359), DOM10-53-540 (SEQ ID NO: 2360), DOM10-53- 531 (SEQ ID NO: 2361), DOM10-53-532 (SEQ ID NO: 2362), DOM10-53-536 (SEQ ID NO: 2363), DOM10-53-542 (SEQ ID NO: 2364), DOM10- 53-541 (SEQ ID NO: 2365), DOM10-53-473 (SEQ ID NO: 2366), DOM10-53-472 (SEQ ID NO: 2367), DOM10-53-475 (SEQ ID NO: 2368), DOM10-53-474 (SEQ ID NO: 2369), DOM10-53-543 (SEQ I D NO: 2370), DOM10-53-544 (SEQ ID NO: 2371), DOM10-53-545 (SEQ ID NO: 2372), DOM10-53-548 (SEQ ID NO: 2373), DOM10-53-546 (SEQ ID NO: 2374), DOM10-53-549 (SEQ ID NO: 2375), DOM10-53-547 (SEQ ID NO: 2376), DOM10-53-550 (SEQ ID NO: 2377), DOM10-53 -551 (SEQ ID NO: 2378), DOM10-53-560 (SEQ ID-NO: 2379), DOM10-53-565 (SEQ ID NO: 2380), DOM10-53-559 (SEQ ID NO: 2381), DOM10- 53-561 (SEQ ID NO: 2382), DOM10-53-562 (SEQ ID NO: 2383), DOM10-53-563 (SEQ ID NO: 2384), DOM10-53-564 (SEQ ID NO: 2385), DOM 10-53-566 (SEQ ID NO: 2386), DOM10-53-554 (SEQ ID NO: 2387), DOM10-53-552 (SEQ ID NO: 2388), DOM10-53-553 (SEQ ID NO. : 2389), DOM10-53-558 (SEQ ID NO: 2390), DOM10-53-556 (SEQ ID NO: 2391) and DOM10-53-557 (SEQ ID NO: 2392).
125. A ligand having binding specificity for IL-4 and IL-13, wherein the ligand is a fusion protein comprising a single immunoglobulin variable domain with binding specificity for IL-4 and a single immunoglobulin variable domain with binding specificity for IL-13, wherein; the variable domain of simple immunoglobulin with binding specificity for IL-4 competes to bind IL-4 with an anti-IL4 domain antibody (dAb), selected from the group consisting of DOM9-112-210 and DOM9-155-78; and the variable domain of single immunoglobulin with binding specificity for IL-13 competes to bind IL-13 with an anti-IL-13 domain antibody (dAb) selected from the group consisting of DOM10-208, DOM10-212, DOM10 -213, DOM10-215, DOM10-224, DOM10-270, DOM10-416, DOM10-236, DOM10-273, DOM10-275, DOM10-276 and DOM10-277.
126. A ligand having binding specificity for IL-4, characterized in that it comprises a variable domain of simple immunoglobulin with binding specificity for human IL-4 and non-human IL-4.
127. The ligand as described in claim 126, characterized in that the non-human IL-4 is selected from the group consisting of rhesus IL-4 and cynomolgus IL-4.
128. The ligand as described in claim 126 or 127, characterized in that the binding affinity of the variable domain of single immunoglobulin for non-human IL-4 and the binding affinity for IL-4, differ by a factor no greater than 10.
129. A ligand having binding specificity for IL-13, characterized in that it comprises a single immunoglobulin variable domain with binding specificity for human IL-13 and non-human IL-13.
130. The ligand as described in the claim 129, characterized in that non-human IL-13 is selected from the group consisting of rhesus IL-13 and cynomolgus IL-13.
131. The ligand as described in claim 129 or 130, characterized in that the binding affinity of the IL-13 domain for non-human and the binding affinity for human IL-13 differs by a factor not greater than 10.
132. A ligand having binding specificity for IL-4 and IL-13, characterized in that it comprises the single immunoglobulin variable domain as described in any of claims 126 to 128; and a variable domain of simple immunoglobulin with binding specificity for IL-13.
133. A ligand having binding specificity for IL-4 and IL-13, characterized in that it comprises a single immunoglobulin variable domain with binding specificity for IL-4; and the variable immunoglobulin simple domain as described in any of claims 129 to 131.
134. A ligand having binding specificity for IL-4 and IL-13, characterized in that it comprises a single immunoglobulin variable domain as described in any of claims 126 to 128; and the variable domain of simple immunoglobulin as described in any of claims 129 to 131.