MXPA01006330A

MXPA01006330A - Methods and compositions for inhibiting neoplastic cell growth.

Info

Publication number: MXPA01006330A
Application number: MXPA01006330A
Authority: MX
Inventors: Paul J Godowski
Original assignee: Genentech Inc
Priority date: 1998-12-22
Filing date: 1999-12-02
Publication date: 2002-07-02
Also published as: JP2003529317A; JP2007291116A; ATE432987T1; JP2007222180A; EP1141284A2; KR100499600B1; ATE353339T1; JP4037876B2; WO2000037638A3; JP2005237383A; ES2327785T3; CA2353799A1; JP3993746B2; IL186154A0; JP2005245451A; PT1484338E; KR20010084882A; ES2281704T3; AU768230B2; AU1749900A

Abstract

The present invention concerns methods and compositions for inhibiting neoplastic cell growth. In particular, the present invention concerns antitumor compositions and methods for the treatment of tumors. The invention further concerns screening methods for identifying growth inhibitory, e.g., antitumor compounds. In addition, the present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

Description

METHODS AND COMPOSITIONS TO INHIBIT THE GROWTH OF NEOPLASTIC CELLS FIELD OF THE INVENTION The present invention relates to methods and compositions for inhibiting the growth of neoplastic cells. In particular, the present invention relates to antitumor compositions and methods for the treatment of tumors. The present invention further relates to screening methods for identifying growth inhibitory, e.g., antitumor compounds. BACKGROUND OF THE INVENTION Malignant tumors (cancers) are the second leading cause of death in the United States, after heart disease (Boring et al., CA Cancel J. Clin. 43: 7 (1993)). Cancer is characterized by the increase in an abnormal, or neoplastic, number of cells derived from a normal tissue, which proliferate to form a tumor mass, the invasion of adjacent tissues by these neoplastic tumor cells and the generation of malignant cells that eventually they spread through the blood or lymphatic system to the regional lymph nodes and to distant sites (metastases). In a cancerous state, a cell proliferates REF: 129450 - - under conditions in which normal cells would not grow. Cancer manifests in a variety of ways, characterized by different degrees of invasiveness and aggressiveness. Despite recent advances in cancer therapy, there is a great need for new therapeutic agents capable of inhibiting the growth of neoplastic cells. Accordingly, an object of the present invention is to identify compounds capable of inhibiting the growth of neoplastic cells, such as cancer cells. BRIEF DESCRIPTION OF THE INVENTION A. Modalities The present invention relates to methods and compositions for inhibiting the growth of neoplastic cells, more particularly, the present invention relates to methods and compositions for the treatment of tumors, including cancers, such as cancer. breast, prostate, colon, pulmonary, ovarian, renal and CNS, leukemia, melanoma, etc., in mammalian patients, preferably humans. In one aspect, the present invention relates to compositions of materials useful for the inhibition of growth of neoplastic cells, comprising an effective amount of a polypeptide PR0179, PRO207, PRO320, - - PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866, as defined herein, or an agonist thereof, mixed with a pharmaceutically acceptable carrier. In a preferred embodiment, the composition of the material comprises a growth inhibitory amount of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or an agonist thereof. . In another preferred embodiment, the composition comprises a cytotoxic amount of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866, or an agonist thereof. Optionally, the compositions may contain one or more additional growth inhibitory agents and / or cytotoxic agents and / or other chemotherapeutic agents. In a further aspect, the present invention relates to compositions useful for the treatment of a tumor in a mammal, comprising a therapeutically effective amount of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866, as defined herein, or an agonist thereof. The tumor of preference is a cancer. In another aspect, the present invention relates to - - a method for inhibiting the growth of a tumor cell, comprising exposing the cell to an effective amount of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866, as defined herein, or an agonist thereof. In a particular embodiment, the agonist is an antibody, anti-PR0179, anti-PRO207, anti-PRO320, anti-PR0219, anti-PR0221, anti-PR0224, anti-PR0328, anti-PR0301, anti-PR0526, anti-PR0362 , anti-PR0356, anti-PRO509 or anti-PR0866. In another embodiment, the agonist is a small molecule that mimics the biological activity of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. The method can be performed in vi tro or in vivo. In still another embodiment, the present invention provides an article of manufacture, comprising: (a) a container; (b) a composition comprising an active agent contained in the container, wherein the composition is effective to inhibit the growth of neoplastic cells, eg, the growth of tumor cells and the active agent in the composition is a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 as defined herein, or an agonist thereof; Y - - (c) a fixed label on the container, or an insert in the package, included in the container, with reference to the use of the PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or agonist thereof, for inhibiting the growth of neoplastic cells, wherein the agonist can be an antibody that binds to PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0328, PRO301, PR0526, PR0362 polypeptides , PR0356, PRO509 or PR0866. In a particular embodiment, the agonist is an anti-PR0179 antibody, anti-PR? 207, anti-PRO320, anti-PR0219, anti-PR0221, anti-PR0224, anti-PR0328, anti-PRO301, anti-PR0526, anti- PR0362, anti-PR0356, anti-PRO509 or anti-PR0866. In another embodiment, the agonist is a small molecule that mimics the biological activity of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. Similar articles of manufacture comprise a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 such as those described herein, or an agonist thereof, in an amount that is therapeutically effective for the treatment of tumors, wherein these articles are also within the scope of the present invention. They are also within the scope of the - - present invention articles of manufacture comprising a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0301, PR0526, PR0362, PR0356, PRO509 or PR0866 as defined herein, or an agonist thereof , and another growth inhibitory agent, cytotoxic agent or chemotherapeutic agent. B. Additional Modalities In other embodiments of the present invention, there is provided an isolated nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362 , PR0356, PRO509 or PR0866. In one aspect, the isolated nucleic acid molecule comprises a nucleotide sequence having at least about 80% sequence identity, preferably at least 81% sequence identity, more preferably at least about 82% sequence identity , still more preferably at least about 83% "of sequence identity, still more preferably at least about 84% sequence identity, still more preferably at least about 85% sequence identity, still more preferably at least about 86% sequence identity, still more preferably at least approximately - - 87% sequence identity, still more preferably at least about 88% sequence identity, still more preferably at least about 89% sequence identity, still more preferably at least about 90% sequence identity, still more preferably when less about 91% sequence identity, still more preferably at least about 92% sequence identity, still more preferably at least about 93% sequence identity, still more preferably at least about 94% sequence identity, still more preferably at least about 95% sequence identity, still more preferably at least about 96% sequence identity, still more preferably at least about 97% sequence identity, still more preferably at least about 98% d and sequence identity even more preferably at least about 99% sequence identity with (a) a DNA molecule encoding a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356 , PRO509 or PR0866 having a full length amino acid sequence as described herein, an amino acid sequence that lacks the signal peptide as described herein, a extracellular domain of a transmembrane protein, with or without the signal peptide, as described herein, or any other specifically defined fragment of the full length amino acid sequence as described herein, or (b) the complement of the DNA molecule of part (a). In other aspects, the isolated nucleic acid molecule comprises a nucleotide sequence having at least about 80% sequence identity, preferably at least about 81% sequence identity, more preferably at least about 82% sequence identity , still more preferably at least about 83% sequence identity, still more preferably at least about 84% sequence identity, still more preferably at least about 85% sequence identity, still more preferably at least about 86% identity sequence, still more preferably when at least about 87% sequence identity, still more preferably at least about 88% sequence identity, still more preferably at least about 89% sequence identity, still more preferably at least s about 90% sequence identity, still more preferably at least about - - 91% sequence identity, still more preferably at least about 92% sequence identity, still more preferably at least about 93% sequence identity, still more preferably at least about 94% sequence identity, still more preferably when less about 95% sequence identity, still more preferably at least about 96% sequence identity, still more preferably at least about 97% sequence identity, still more preferably at least about 98% sequence identity even more preferably at least about 99% sequence identity with (a) a DNA molecule comprising the coding sequence of the full-length polypeptide cDNA PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356 , PRO509 or PR0866 as described in present, the coding sequence of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 lacking the signal peptide as described herein, the sequence coding for an extracellular domain of a transmembrane polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866, with or without the signal peptide, such as - - describes in the present, or the coding sequence of any other specifically defined fragment of the full length amino acid sequence as described herein, or (b) the complement of the DNA molecule of part (a). In a further aspect, the present invention relates to an isolated nucleic acid molecule comprising a nucleotide sequence having at least about 80% sequence identity, preferably at least 81% sequence identity, more preferably when less about 82% sequence identity, still more preferably at least about 83% sequence identity, still more preferably at least about 84% sequence identity, still more preferably at least about 85% sequence identity, even more preferably at least about 86% sequence identity, still more preferably at least about 87% sequence identity, still more preferably at least about 88% sequence identity, still more preferably at least about 89% sequence identity, still more preferably at least about 90% sequence identity, still more preferably at least about 91% sequence identity, - - still more preferably at least about 92% sequence identity, still more preferably at least about 93% sequence identity, still more preferably at least about 94% sequence identity, still more preferably at least about 95% sequence identity sequence identity, still more preferably at least about 96% sequence identity, still more preferably at least about 97% sequence identity, still more preferably at least about 98% sequence identity still more preferably at least about 99% of sequence identity with (a) a DNA molecule encoding the same mature polypeptide encoded by any of the human protein cDNAs deposited with the ATCC as described herein, or (b) the complement of the human protein molecule. DNA of subsection (a). Another aspect of the present invention provides an isolated nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0301, PR0526, PR0362, PR0356, PRO509 or PR0866. which has undergone the deletion of the transmembrane domain or has been inactivated from the transmembrane domain, or said sequence is complementary to the coding nucleotide sequence, - - wherein the transmembrane domains of such a polypeptide are described herein. Therefore, the soluble extracellular domains of the polypeptides PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 are contemplated. Another embodiment refers to fragments of a coding sequence of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or to the complement of the 10, which could be used as, for example, hybridization probe for fragments encoding a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 which could optionally be encoded for a polypeptide that 15 comprises a binding site for an anti-PR0179, anti-PRO207, anti-PRO320, anti-PR0219, anti-PR0221, anti-PR0224, anti-pñro328, anti-PRO301, anti-PR0526, anti-PR0362, anti -PR0356, anti-PRO509 or anti-PR0866 or as an antisense oligonucleotide probe. Such acid fragments The nucleic acid is usually at least about 20 nucleotides in length, preferably at least about 30 nucleotides in length, more preferably at least about 40 nucleotides in length, still more preferably at least 25 approximately 50 nucleotides in length, even more ai * -jí- - * - * á-.í * ?? i:.? i- a ** t * Jüte., .. j. - preferably at least about 60 nucleotides in length, still more preferably at least about 70 nucleotides in length, still more preferably at least about 80 nucleotides in length, still more preferably at least about 90 nucleotides in length, still more preferably at least about 100 nucleotides in length, still more preferably at least about 110 nucleotides in length, still more preferably at least about 120 nucleotides in length, still more preferably at least about 130 nucleotides in length, still more preferably at least about 140 nucleotides in length, even more preferably at least about 150 nucleotides in length, still more preferably at least about 160 nucleotides in length, still more preferably when less about 170 nucleotides in length, still more preferably at least, about 180 nucleotides in length, still more preferably at least about 190 nucleotides in length, still more preferably at least about 200 nucleotides in length, still more preferably at least about 250 nucleotides in length length, still more preferably at least about 300 - - nucleotides in length, still more preferably at least about 350 nucleotides in length, still more preferably at least about 400 nucleotides in length, still more preferably when at least about 450 nucleotides in length, still more preferably at least about 500 nucleotides in length , still more preferably at least about 600 nucleotides in length, still more preferably at least about 700 10 nucleotides in length, still more preferably at least approximately 800 nucleotides in length, still more preferably at least approximately 900 nucleotides in length, still more preferably at least approximately 1000 nucleotides in length, in 15 where in this context, the term "approximately" means the length of the nucleotide sequence referred to plus or minus 10% of said length. It should be noted that new fragments of a coding nucleotide sequence can be determined for a PR0179, PRO207, PRO320, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PR0356, PRO509 or PR0866 polypeptides, routinely, by aligning the coding nucleotide sequence for the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, 25 PR0526, PR0362, PR0356, PRO509 or PR0866 with other ÍÁ £. * á, .i *** Á, .i ** ¿¡¡¡¡... eml ** ^. m AfáA »*. *, *. ^ **** s¡? t? *** ** '^ f - ^ jfa ^,. ^ faj - - known nucleotide sequences, using any of a number of known sequence alignment programs and determining which or which nucleotide sequence fragments encoding the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 are novel. All of these nucleotide sequences encoding PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 polypeptides are contemplated herein. Likewise, fragments of polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 encoded by these fragments of nucleotide molecules, preferably those PR0179 polypeptide fragments, are contemplated. , PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 comprising a binding site for an anti-PR0179 antibody, anti-PRO207, anti-PRO320, anti-PR0219, anti -PR0221, anti-PR0224, anti-PR0328, anti-PRO301, anti-PR0526, anti-PR0362, anti-PR0356, anti-PRO509 or anti-PR0866. In another embodiment, the present invention provides an isolated polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 encoded by any of the I AA? JÍJ -i * ¿t-. ** * - * h - - previously isolated nucleic acid sequences identified herein. In a certain aspect, the present invention relates to an isolated polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 81% sequence identity, more preferably at least about 82% sequence identity, still more preferably at least about 83% sequence identity, still more preferably at least about 84% % sequence identity, still more preferably at least about 85% sequence identity, still more preferably at least about 86% sequence identity, still more preferably at least about 87% sequence identity, still more preferably when. less approximately 88% sequence identity, to still more preferably at least about 89% sequence identity, still more preferably at least about 90% sequence identity, still more preferably at least about 91% sequence identity, still more preferably at least about - - 92% sequence identity, still more preferably at least about 93% sequence identity, still more preferably at least about 94% sequence identity, still more preferably at least about 95% sequence identity, still more preferably when at least about 96% sequence identity, still more preferably at least about 97% sequence identity, still more preferably at least about 98% sequence identity, still more preferably at least about 99% sequence identity, with a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 having a full length amino acid sequence as described herein, an amino acid sequence lacking the signal peptide as described herein, an extr domain acellular of a transmembrane protein, with or without the signal peptide, as described herein, or any other specifically defined fragment of the full length amino acid sequence as described herein. In a further aspect, the present invention relates to a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 comprising an amino acid sequence - - having at least one about 80% sequence identity, preferably at least about 81% sequence identity, more preferably at least about 82% sequence identity, still more preferably at least about 83% sequence identity, still more preferably at least about 84% sequence identity, still more preferably at least about 85% sequence identity, still more preferably at least about 86% sequence identity, still more preferably at least about 87% sequence identity, still more preferably at least approximately 88% sequence identity, t still more preferably at least about 89% sequence identity, still more preferably at least about 90% sequence identity, still more preferably at least about 91% sequence identity, still more preferably at least about 92% identity of sequence, still more preferably at least about 93% sequence identity, still more preferably at least about 94% sequence identity, still more preferably at least about 95% sequence identity, still more preferably at least about 96% sequence identity sequence identity, - - still more preferably at least about 97% sequence identity, still more preferably at least about 98% sequence identity, still more preferably at least about 99% sequence identity, with an amino acid sequence encoded by either the 7DNA of human protein deposited in the ATCC as described herein. In a further aspect, the present invention relates to an isolated polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 comprising an amino acid sequence that gives a rating when less about 80% positive, preferably at least about 81% positive, more preferably at least about 82% positive, still more preferably at least 83% positive, still more preferably at least about 84% positive, still more preferably at least. 85% positive, still more preferably at least approximately 86% positive, still more preferably at least approximately 87% positive, still more preferably at least approximately 88% positive, still more preferably at least approximately 89% positive, still more preferably at least fl & aaAa. * Lk ¿i * l ** *? -ie > ~ ** i * i¡ 3? £ á¡ * ^ i¡ *. - - about 90% positive, still more preferably at least about 91% positive, still more preferably at least about 92% positive, still more preferably at least about 93% positive, still more preferably at least about 94% positive, still more preferably at least about 95% positive, still more preferably at least about 96% positive, still more preferably at least about 97% positive, still more preferably at least about 98% positive, still more preferably at least about 99% positive, when compared with the amino acid sequence of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 having a full length amino acid sequence as described herein, an amino acid sequence two lacking the signal peptide as described herein, an extracellular domain of a transmembrane protein, with or without the signal peptide, as described herein, or any other specifically defined fragment of the amino acid sequence of full length as described herein. In a specific aspect, the present invention provides an isolated polypeptide PR0179, PRO207, PRO320, i Ji¿ .s -fe ^ A ^^,. ^ h¿ - - PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 without the N-terminal signal sequence and / or the initial methionine and is encoded by a nucleotide sequence coding for such an amino acid sequence such as described above. Processes for producing these sequences are also described herein, wherein these processes comprise culturing a host cell comprising a vector that includes the appropriate coding nucleic acid molecule, under conditions suitable for the expression of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 and recover PR0179, PRO207, PRO320, PR0219, PR0221, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 polypeptides. of cell culture. Another aspect of the present invention provides a PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0224, PR0328, PRO301, PR0526, PR0.362, PR0356, PRO509 or PR0866 isolated PR0866 polypeptide, which has undergone the deletion of the transmembrane domain or has been inactive its transmembranal domain. The processes for producing these polypeptides are also described herein, wherein said processes comprise culturing a host cell containing a vector comprising the acid molecule - - appropriate coding nucleus, under conditions suitable for the expression of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0362, PR0356, PRO509 or PR0866 polypeptides and recover PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0301, PR0526, PR0362, PR0356, PRO509 or PR0866 from cell culture. In still another embodiment, the present invention relates to agonists of a PR0179 native polypeptide, 10 PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0301, PR0526, PR0362, PR0356, PRO509 or PR0866 as defined herein. In a particular embodiment, the agonist is an anti-PR0179 antibody, anti-PR? 207, anti-PRO320, anti-PR0219, anti-PR0221, anti-PR0224, anti-PR0328, anti-PRO301, anti-PR0526, anti -PR0362, anti-PR0356, anti-PR? 509 or anti-PR0866 or a small molecule. In another embodiment, the present invention relates to a method for identifying agonists of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, 20 PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866, wherein the method comprises contacting the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PR0509 or PR0866 with a candidate molecule and monitor a biological activity 25 mediated by said polypeptide PR0179, PRO207, PRO320, - PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. Preferably, the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 is a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526 , PR0362, PR0356, PRO509 or PR0866 native. In still another embodiment, the present invention relates to a composition comprising a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or an agonist of a PR0179 polypeptide, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 as described herein, or an anti-PR0179 antibody, anti-PRO207, anti-PR? 320, anti- PR0219, anti-PR0221, anti-PR0224, anti-PR0328, anti-PRO301, anti-PR0526, anti-PR0362, anti-PR0356, anti-PRO509 or anti-PR0866, in combination with a vehicle. Optionally, the vehicle is a pharmaceutically acceptable vehicle. Another embodiment of the present invention relates to the use of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or an agonist thereof, as described above, or an anti-PR0179 antibody, anti-PRO207, anti-PRO320, anti-PR0219, anti-PR0221, anti- - - PR0224, anti-PR0328, anti-PRO301, anti-PR0526, anti-PR0362, anti-PR0356, anti-PR? 509 or anti-PR0866, for the preparation of a medicament useful in the treatment of a disorder responsive to PR0179 polypeptide , PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866, to an antagonist thereof or to an anti-PR0179 antibody, anti-PRO207, anti-PR? 320, anti-PR0219 , anti-PR0221, anti-PR0224, anti-PR0328, anti-PRO301, anti-PR0526, anti-PR0362, anti-PR0356, anti-PRO509 or anti-PR0866. In other embodiments of the present invention, the present invention provides vectors comprising DNA encoding any of the polypeptides described herein. Host cells comprising any such vector are also provided. For example, the host cells can be CHO cells, E. coli, yeast or insect cells infected with baculovirus. A process for producing any of the polypeptides described herein is also provided and comprises culturing the host cells, under conditions suitable for expression of the desired polypeptide, and recovering the desired polypeptide from the cell culture. In other embodiments, the present invention provides chimeric molecules that comprise any of the peptides described herein, fused to a heterologous polypeptide or an amino acid sequence. Examples of such chimeric molecules comprise any of the polypeptides described herein fused to an epitope tag sequence or an Fc region of an immunoglobulin. In another embodiment, the present invention provides an antibody that specifically binds to any of the above or described polypeptides. Optionally, the antibody is a monoclonal antibody, a humanized antibody, an antibody fragment or a single chain antibody. In yet other embodiments, the present invention provides oligonucleotide probes useful for the isolation of genomic and cDNA nucleotide sequences, or which serve as antisense probes, wherein these probes can be derived from any of the above or later nucleotide sequences. described in the present. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows the nucleotide sequence (SEQ ID NO: 1) of a cDNA containing a nucleotide sequence encoding the native sequence PR0179, wherein the nucleotide sequence (SEQ ID NO: 1) is a clone designated herein as DNA 16451-1078. They are also presented in bold and underlined letters, the - - positions of the respective start and end codons. Figure 2 shows the amino acid sequence (SEQ ID NO: 2) of a native sequence of PR0179 polypeptide, derived from the coding sequence of SEQ ID NO: 1, shown in Figure 1. Figure 3 shows the nucleotide sequence (SEQ ID NO: 6) of a 7DNAc containing a nucleotide sequence encoding the native PRO207 sequence, wherein the nucleotide sequence (SEQ ID NO: 6) is a clone designated herein as DNA 30879-1152.

The positions of the respective start and end codons are also presented in bold letters and underlined. Figure 4 shows the amino acid sequence (SEQ ID NO: 7) of a native polypeptide sequence PRO207 derived from the coding sequence SEQ ID NO: 6, shown in Figure 3. Figure 5 shows the nucleotide sequence (SEQ ID NO: 9) of a 7DNAc containing a nucleotide sequence coding for the native sequence of PRO320, wherein the nucleotide sequence (SEQ ID NO: 9) is a clone designated herein as DNA 32284-1307.

The positions of the respective start and stop codons are also presented in bold letters and underlined. Figure 6 shows the amino acid sequence (SEQ ID NO: 10) of a native sequence of the PRO320 polypeptide derived from the coding sequence SEQ ID NO: 9, shown in Figure 5. Figure 7 shows the nucleotide sequence (SEQ ID. NO: 14) of a 7DNAc containing a nucleotide sequence encoding the native PR0219 polypeptide, wherein the nucleotide sequence (SEQ ID NO: 14) is a clone designated herein as DNA 32290-1164. The positions of the respective start and end codons are also presented in bold letters and underlined. Figure 8 shows the amino acid sequence (ie 15) of a native sequence of PR0219 polypeptide derived from the coding sequence SEQ ID NO: 14 shown in Figure 7. Figure 9 shows the nucleotide sequence (SEQ ID NO: 19) of a cDNA containing a nucleotide sequence encoding the native PR0221 polypeptide sequence, wherein the nucleotide sequence (SEQ ID NO: 19) is a clone designated herein as DNA 33089-1132. The positions of the respective start and end codons are also presented in bold letters and underlined.

- - Figure 10 shows the amino acid sequence (SEQ ID NO: 20) of a native polypeptide sequence PR0221 derived from the coding sequence SEQ ID NO: 19, shown in Figure 9. Figure 11 shows the nucleotide sequence (SEQ ID NO: 24) of an .ADNc containing a nucleotide sequence encoding the native PR0224 polypeptide sequence, wherein the nucleotide sequence (SEQ ID NO: 24) is a clone designated herein as DNA 33221-1133. The positions of the respective start and end codons are also presented in bold letters and underlined. Figure 12 shows the amino acid sequence (SEQ ID NO: 25) of a native sequence of PR0224 polypeptide derived from the coding sequence SEQ ID NO: 24, shown in Figure 11. Figure 13 shows the nucleotide sequence (SEQ ID NO: 24). NO: 29) of a cDNA containing a nucleotide sequence encoding the native sequence of PR0328 polypeptide, wherein the nucleotide sequence (SEQ ID NO: 29) is a clone designated herein as DNA 40587-1231. The positions of the respective start and end codons are also presented in bold letters and underlined. Figure 14 shows the amino acid sequence tA? lA'i-.Jt - - (SEQ ID NO: 30) of a native sequence of PR0328 polypeptide derived from the coding sequence SEQ ID NO: 29, shown in Figure 13. Figure 15 shows the nucleotide sequence (SEQ ID NO: 34) of an .DNA containing a nucleotide sequence encoding the native PRO301 polypeptide sequence, wherein the nucleotide sequence (SEQ ID NO: 34) is a clone designated herein as DNA 40628-1216. The positions of the respective start and end codons are also presented in bold letters and underlined. Figure 16 shows the amino acid sequence (SEQ ID NO: 35) of a native sequence of the PRO301 polypeptide derived from the coding sequence SEQ ID NO: 34, shown in Figure 15. Figure 17 shows the nucleotide sequence (SEQ ID NO: 42) of a 7DNAc containing a nucleotide sequence encoding the native PR0526 polypeptide sequence, wherein the nucleotide sequence (SEQ ID NO: 42) is a clone designated herein as DNA 44184-1319. The positions of the respective start and end codons are also presented in bold letters and underlined. Figure 18 shows the amino acid sequence (SEQ ID NO: 43) of a native polypeptide sequence - PR0526 derived from the coding sequence SEQ ID NO: 42, shown in Figure 17. Figure 19 shows the nucleotide sequence (SEQ ID NO: 47) of a 7DNAc containing a nucleotide sequence encoding the native PR0362 polypeptide sequence, wherein the nucleotide sequence (SEQ ID NO: 47) is a clone designated herein as DNA 45416-1251. The positions of the respective start and end codons are also presented in bold letters and underlined. Figure 20 shows the amino acid sequence (SEQ ID NO: 48) of a native PR0362 polypeptide sequence derived from the coding sequence SEQ ID NO: 47, shown in Figure 19. Figure 21 shows the nucleotide sequence (SEQ ID NO: 54) of a 7DNAc containing a nucleotide sequence encoding the native sequence of PR0356 polypeptide, wherein the nucleotide sequence (SEQ ID NO: 54) is a clone designated herein as DNA 47470- 1130-P1. The positions of the respective start and end codons are also presented in bold letters and underlined. Figure 22 shows the amino acid sequence (SEQ ID NO: 55) of a native sequence of PR0356 polypeptide derived from the coding sequence SEQ ID NO: 54, Ji yes tAaa,. .-. ^ a r.r-. j. ¿. a.,. - - shown in Figure 21. Figure 23 shows the nucleotide sequence (SEQ ID NO: 59) of a cDNA containing a nucleotide sequence encoding the native PRO509 polypeptide sequence, wherein the nucleotide sequence (SEQ. ID NO: 59) is a clone designated herein as DNA 50148-1068. The positions of the respective start and end codons are also presented in bold letters and underlined. Figure 24 shows the amino acid sequence (SEQ ID NO: 60) of a native sequence of the PRO509 polypeptide derived from the coding sequence SEQ ID NO: 59, shown in Figure 23. Figure 25 shows the nucleotide sequence (SEQ ID NO: 59). NO: 61) of a cDNA containing a nucleotide sequence encoding the native sequence of PR0866 polypeptide, wherein the nucleotide sequence (SEQ ID NO: 61) is a clone designated herein as DNA 53971-1359. The positions of the respective start and end codons are also presented in bold letters and underlined. Figure 26 shows the amino acid sequence (SEQ ID NO: 62) of a native sequence of PR0866 polypeptide derived from the coding sequence SEQ ID NO: 61, shown in Figure 25.

- - DETAILED DESCRIPTION OF THE INVENTION The terms polypeptide or protein "PR0179", "PRO207", "PRO320", "PR0219", "PR0221", "PR0224", "PR0328", "PRO301", "PR0526", "PR0362", "PR0356", "PR0509" or "PR0866" as used herein, encompass the native sequence of the polypeptides PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866 and variants of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866 (which are further defined herein). The polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 can be isolated from a variety of sources, such as human tissue types or other sources, or can be prepared by recombinant and / or synthetic methods. A "native sequence PR0179", a "native sequence PRO207", a "native sequence PRO320", a "native sequence PR0219", a "native sequence PR0221", a "native sequence PR0224", a "native sequence PR0328", a "native sequence PRO301", a "native sequence PR0526", a "native sequence PR0362", a "native sequence PR0356", a "native sequence PRO509" or a "native sequence PR0866" comprises a polypeptide having the same amino acid sequence that the polypeptide | ^ ¿T¿A'í-at ^ ** ^ "^ *. A '' * Jl4j» 'a.a .. ". ,, *. * _ **, ******** .. ".. B" .. Ja, Majaj-¡-IfH '-'- ****** * ~? *** - * -. ~ * - .--- ^ - l-MBL -. .4 «A AAj - - PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 as derived from nature. Such a native sequence of the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 can be isolated from nature or can be produced by recombinant and / or synthetic means. The term "native sequence" PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 specifically encompasses truncated or secreted forms of natural origin (eg, an extracellular domain sequence), variant forms of natural origin (eg, alternatively spliced forms) and allelic variants of natural origin of the polypeptides PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866. In one embodiment of the present invention, the native PR0179 polypeptide sequence, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 is a mature or full-length native sequence of PR0179 polypeptide. , PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866, as shown in Figure 2 (SEQ ID NO: 2), in Figure 4 (SEQ ID NO: 7), in Figure 6 (SEQ ID NO: 10), in Figure 8 (SEQ ID NO: 15), in Figure 10 (SEQ ID NO: 20), - - in Figure 12 (SEQ ID NO: 25), in Figure 14 (SEQ ID NO: 30), in Figure 16 (SEQ ID NO: 35), in Figure 18 (SEQ ID NO: 43), in Figure 20 (SEQ ID NO: 48), in Figure 22 (SEQ ID NO: 55), in Figure 24 (SEQ ID NO: 60) or in Figure 26 (SEQ ID NO: 62), respectively. Likewise, while the polypeptides PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866 described in Figures 2 (SEQ ID NO: 2), Figure 4 (SEQ ID NO: 7), Figure 6 (SEQ ID NO: 10), Figure 8 (SEQ ID NO: 15), Figure 10 (SEQ ID NO: 20), Figure 12 (SEQ ID NO: 25), Figure 14 (SEQ ID NO: 30), Figure 16 (SEQ ID NO: 35), Figure 18 (SEQ ID NO: 43), Figure 20 (SEQ ID NO: 48), Figure 22 (SEQ ID NO: 55), Figure 24 (SEQ. ID NO: 60) or Figure 26 (SEQ ID NO: 62), respectively, is shown to start with a methionine residue designated herein as amino acid position 1, it is conceivable and possible that another methionine residue located either upstream or chain below amino acid position 1 in the. Figure 2 (SEQ ID NO: 2), in Figure 4 (SEQ ID NO: 7), in Figure 6 (SEQ ID NO: 10), in Figure 8 (SEQ ID NO: 15), in Figure 10 (SEQ ID NO: 20), in Figure 12 (SEQ ID NO: 25), in the Figure 14 (SEQ ID NO: 30), in Figure 16 (SEQ ID NO: 35), in Figure 18 (SEQ ID NO: 43), in Figure 20 (SEQ ID NO: 48), in Figure 22 (SEQ ID NO: 55), in Figure 24 IS \ I my? * - ** A ** u * á * -i. *** .i, »< ,:. . ^. ^ t? t ^ a ************* *** ^ á? ***. .? *? J * ?? * * Mt? *? f .... ********* .-. ***.-mxm - - - (SEQ ID NO: 60) or in Figure 26 (SEQ ID NO: 62), respectively, can be used as the starting amino acid residue for the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301 , PR0526, PR0362, PR0356, PRO509 or PR0866. The "extracellular domain" or "DEC" of a polypeptide described herein, refers to a form of the polypeptide that is essentially free of the transmembrane and cytoplasmic domains. Typically, a polypeptide DEC will have less than about 1% of such transmembrane and / or cytoplasmic domains and, preferably, will have less than about 0.5% of such domains. It should be understood that any transmembrane domain identified for the polypeptides of the present invention is identified in accordance with criteria routinely employed in the art to identify that type of hydrophobic domain. The exact boundaries of a transmembrane domain may vary, but most likely not by more than about 5 amino acids at either end of the domain, as initially identified and as shown in the accompanying figures. As such, in one embodiment of the present invention, the extracellular domain of a polypeptide of the present invention comprises amino acids 1 through X of the mature amino acid sequence, wherein X is any iA-ii * ?, to Al * -. * a ** k * .i .. **, .. lAlL *. ,, - - amino acid within 5 amino acids to either side of the boundaries of the extracellular domain / transmembrane domain . The approximate location of the "signal peptides" of the various PRO polypeptides described herein is shown in the accompanying figures. However, it should be noted that the C-terminal boundaries of a signal peptide may vary, but it is very likely that no more than 5 amino acids on either side of the C-terminal boundary of the signal peptide, as initially identified in the present, wherein the C-terminal limit of the signal peptide can be identified with respect to the criteria routinely employed in the art to identify that type of amino acid sequence element (eg, Nielsen et al., Prot. Eng. : 1-6 (1997) and von Heinje et al., Nucí Acids, Res., 14: 4683-4690 (1986) In addition, it is also recognized that, in some cases, the breaking of a signal sequence of a The secreted polypeptide is not completely uniform, obtaining more than one secreted species.These mature polypeptides wherein the signal polypeptide was broken within a limit of no more than about 5 amino acids to either side of the C-terminal boundary of the to as identified herein, and the polynucleotides encoding them, are contemplated herein.

- - The term "PR0179 variant polypeptide" as used herein, means an PR0179 active polypeptide (other than the native PR0179 polypeptide sequence) as defined below, having at least about 80% sequence identity with the amino acid sequence of: (a) residues from 1 to about 17 to 460 of the PR0179 polypeptide shown in Figure 2 (SEQ ID NO: 2), (b) from X to 460 of the PR0179 polypeptide shown in Figure 2 (SEQ. ID NO: 2), wherein X is any amino acid residue from 12 to 21 of Figure 2 (SEQ ID NO: 2), or (c) another fragment specifically derived from the amino acid sequence shown in Figure 2 (SEQ ID NO: 2). The term "variant PRO207 polypeptide" means an active PRO207 polypeptide (other than the native PRO207 polypeptide sequence) as defined below, having at least about 80% amino acid sequence identity with the amino acid sequence of: ( a) waste 1 or. from about 41 to 249 of the PRO207 polypeptide shown in Figure 4 (SEQ ID NO: 7), (b) from X to 249 of the PRO207 polypeptide shown in Figure 4 (SEQ ID NO: 7), wherein X is any residue amino acid from 36 to 45 of Figure 4 (SEQ ID NO: 7) or (c) another fragment derived specifically from the amino acid sequence shown in Figure 4 (SEQ ID - - NO: 7). The term "variant PRO320 polypeptide" means an active PRO320 polypeptide (different from the native PRO320 polypeptide sequence) as defined below, having at least about 80% amino acid sequence identity with the amino acid sequence of: a) the residues of 1 or approximately 22 to 338 of the PRO320 polypeptide shown in Figure 6 (SEQ ID NO: 10), (b) from X to 338 of the PRO320 polypeptide shown in Figure 6 (SEQ ID NO: 10) ), wherein X is any amino acid residue from 17 to 26 of Figure 6 (SEQ ID NO: 10) or (c) another fragment specifically derived from the amino acid sequence shown in Figure 6 (SEQ ID NO: 10). The term "PR0219 variant polypeptide" means an active PR0219 polypeptide (other than the native PR0219 polypeptide sequence) as defined below, having at least about 80% amino acid sequence identity with the amino acid sequence of: ( a) the residues of 1 or approximately 24 to 1005 of the PR0219 polypeptide shown in Figure 8 (SEQ ID NO: 15), (b) from X to 1005 of the PR0219 polypeptide shown in Figure 8 (SEQ ID NO: 15) ), wherein X is any amino acid residue from 19 to 28 of Figure 8 (SEQ ID NO: 15) or (c) another fragment a. * - i?: á * Á Í * .i *? á * ¿? .íi. * - - derived specifically from the amino acid sequence shown in Figure 8 (SEQ ID NO: 15). The term "PR0221 variant polypeptide" means an active PR0221 polypeptide (other than the native PR0221 polypeptide sequence) as defined below, having at least about 80% amino acid sequence identity with the amino acid sequence of: a) the residues of 1 or approximately 34 to 259 of the PR0221 polypeptide shown in Figure 10 (SEQ ID NO: 20), (b) from X to 259 of the PR0221 polypeptide shown in Figure 10 (SEQ ID NO: 20) ), wherein X is any amino acid residue from 29 to 38 of Figure 10 (SEQ ID NO: 20) or (c) of 1 or from about 34 to X of Figure 10 (SEQ ID NO: 20), where X is any amino acid residue from 199 to 208 of Figure 10 (SEQ ID NO: 20) or (d) another fragment specifically derived from the amino acid sequence shown in Figure 10 (SEQ ID NO: 20). The term "PR0224 variant polypeptide" means an active PR0224 polypeptide (different from the native PR0224 polypeptide sequence) as defined below, having at least about 80% amino acid sequence identity with the amino acid sequence of: ( a) residues of 1 or approximately 31 to 282 of PR0224 polypeptide - - shown in Figure 12 (SEQ ID NO: 25), (b) from X to 282 of the polypeptide PR0224 shown in Figure 12 (SEQ ID NO: 25), wherein X is any amino acid residue from 26 to 35 of Figure 12 (SEQ ID NO: 25), (c) of 1 or approximately 31 to X of Figure 12 (SEQ ID NO: 25), where X is any amino acid residue from 226 to 235 of the Figure 12 (SEQ ID NO: 25) or (d) another fragment specifically derived from the amino acid sequence shown in Figure 12 (SEQ ID NO: 25). The term "PR0328 variant polypeptide" means an active PR0328 polypeptide (other than the native PR0328 polypeptide sequence) as defined below, having at least about 80% amino acid sequence identity with the amino acid sequence of: a) the residues of 1 or approximately 23 to 463 of the PR0328 polypeptide shown in Figure 14 (SEQ ID NO: 30), (b) from X to 463 of the PR0328 polypeptide shown in Figure 14 (SEQ ID NO: 30) ), wherein X is any amino acid residue from 18 to 27 of Figure 14 (SEQ ID NO: 30) or (c) another fragment specifically derived from the amino acid sequence shown in Figure 14 (SEQ ID NO: 30) . The term "variant PRO301 polypeptide" means an active PRO301 polypeptide (other than the native PRO301 polypeptide sequence) as defined V s? ••} £ Íaí? Ajt Jk * ßk ** *. * ¿T ?? ** > * - > -a ^ * ** i i A *! - below, which has at least about 80% amino acid sequence identity with the amino acid sequence of: (a) residues 1 or about 28 to 299 of the PRO301 polypeptide shown in Figure 16 (SEQ ID NO: 35), (b) from X to 299 of the PRO301 polypeptide shown in Figure 16 (SEQ ID NO: 35), wherein X is any amino acid residue from 23 to 32 of Figure 16 (SEQ ID NO: 35), (c) of 1 or approximately 28 to X of Figure 16 (SEQ ID NO: 35), where X is any amino acid residue from 230 to 239 of the Figure 16 (SEQ ID NO: 35) or (d) another fragment specifically derived from the amino acid sequence shown in Figure 16 (SEQ ID NO: 35). The term "PR0526 variant polypeptide" means an active PR0526 polypeptide (other than the native PR0526 polypeptide sequence) as defined below, having at least about 80% amino acid sequence identity with the amino acid sequence of: a) the residues of 1 or approximately 27 to 473 of polypeptide PR0526 shown in Figure 18 (SEQ ID NO: 43), (b) from X to 473 of polypeptide PR0526 shown in Figure 18 (SEQ ID NO: 43 ), wherein X is any amino acid residue from 22 to 31 of Figure 18 (SEQ ID NO: 43) or (c) another fragment derived specifically from the amino acid sequence li * Í. * í.Ai * AAlíít * * $ táAA *? S - ^^ ti ^ xt-- ¡i * á * a ***** Sl? * l - - shown in Figure 18 ( SEQ ID NO: 43). The term "PR0362 variant polypeptide" means an active PR0362 polypeptide (other than the native PR0362 polypeptide sequence) as defined below, having at least about 80% amino acid sequence identity with the amino acid sequence of: a) the residues of 1 or about 20 to 321 of the PR0362 polypeptide shown in Figure 20 (SEQ ID NO: 48), (b) from X to 321 of the PR0362 polypeptide shown in Figure 20 (SEQ ID NO: 48) ), wherein X is any amino acid residue from 15 to 24 of Figure 20 (SEQ ID NO: 48), (c) from 1 or about 20 to X of Figure 20 (SEQ ID NO: 48), where X is any amino acid residue from 276 to 285 of Figure 20 (SEQ ID NO: 48) or (d) another fragment specifically derived from the amino acid sequence shown in Figure 20 (SEQ ID NO: 48). The term "PR0356 variant polypeptide" means an active PR0356 polypeptide (other than the native PR0356 polypeptide sequence) as defined below, having at least about 80% amino acid sequence identity with the amino acid sequence of: a) the residues of 1 or approximately 27 to 346 of the polypeptide PR0356 shown in Figure 22 (SEQ ID NO: 55), (b) from X to 346 - - of the polypeptide PR0356 shown in Figure 22 (SEQ ID NO: 55), wherein X is any amino acid residue from 22 to 31 of Figure 22 (SEQ ID NO: 55) or (c) another fragment derived specifically from the amino acid sequence shown in Figure 22 (SEQ ID NO: 55). The term "variant PRO509 polypeptide" means an active PRO509 polypeptide (other than the native PRO509 polypeptide sequence) as defined below, having at least about 80% amino acid sequence identity with the amino acid sequence of: a) the residues of 1 or approximately 37 to 283 of the PRO509 polypeptide shown in Figure 24 (SEQ ID NO: 60), (b) from X to 283 of the PRO509 polypeptide shown in Figure 24 (SEQ ID NO: 60) ), wherein X is any amino acid residue 32 to 41 of Figure 24 (SEQ ID NO: 60), (c) of 1 or about 37 to X of Figure 24 (SEQ ID NO: 60), wherein X is any amino acid residue from 200 to 209 of Figure 24 (SEQ ID NO: 60). or (d) another fragment specifically derived from the amino acid sequence shown in Figure 24 (SEQ ID NO: 60). The term "PR0866 variant polypeptide" means an active PR0866 polypeptide (other than the native PR0866 polypeptide sequence) as defined below, having at least about 80% - - amino acid sequence identity with the amino acid sequence of: (a) of residue 1 or approximately 27 to 331 of polypeptide PR0866 shown in Figure 26 (SEQ ID NO: 62), (b) from X to 331 of PR0866 polypeptide shown 'in Figure 26 (SEQ ID NO: 62), wherein X is any amino acid residue from 22 to 31 of Figure 26 (SEQ ID NO: 62) or (c) another fragment derived specifically from the sequence of amino acids shown in Figure 26 (SEQ ID NO: 62). Such variants of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866 include, for example, polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866 wherein one or more amino acid residues have been aggregated or deleted at the N-terminal or C-terminal end, as well as within one or more internal domains of the native sequence. Typically, a variant of PR0179 will have at least about 80% amino acid sequence identity, preferably at least about 81% amino acid sequence identity, more preferably at least about 82% amino acid sequence identity, still more preferably at least approximately 83% of - - amino acid sequence identity, still more preferably at least about 84% amino acid sequence identity, still more preferably at least about 85% amino acid sequence identity, still more preferably at least about 86% sequence identity of amino acids, still more preferably at least about 87% amino acid sequence identity, still more preferably at least about 88% amino acid sequence identity, still more preferably at least about 89% amino acid sequence identity, even more preferably at least about 90% amino acid sequence identity, still more preferably at least about 91% amino acid sequence identity, still more preferably at least about 92% amino acid sequence identity, to still more preferably at least about 93% amino acid sequence identity, still more preferably at least about 94% amino acid sequence identity, still more preferably at least about 95% amino acid sequence identity, even more - - preferably at least about 96% amino acid sequence identity, still more preferably at least about 97% amino acid sequence identity, still more preferably at least about 98% amino acid sequence identity, still more preferably at least approximately 99% amino acid sequence identity with: (a) residues of 1 or about 17 to 460 of the PR0179 polypeptide shown in Figure 2 (SEQ ID NO: 2), (b) from X to 460 of the polypeptide PR0179 shown in Figure 2 (SEQ ID NO: 2), wherein X is any amino acid residue from 12 to 21 of Figure 2 (SEQ ID NO: 2) or (c) another fragment derived specifically from the amino acid sequence shown in Figure 2 (SEQ ID NO: 2). Typically, a variant of PRO207 will have at least about 80% amino acid sequence identity, preferably at least about 81% amino acid sequence identity, more preferably at least about 82% amino acid sequence identity, even more preferably at least about 83% amino acid sequence identity, still more preferably at least about 84% amino acid sequence identity, even more - - preferably at least about 85% amino acid sequence identity, still more preferably at least about 86% amino acid sequence identity, still more preferably at least about 87% amino acid sequence identity, still more preferably at least about 88% amino acid sequence identity, still more preferably at least about 89% amino acid sequence identity, still more preferably at least about 90% amino acid sequence identity, still more preferably at least about 91% identity of amino acid sequence, still more preferably at least about 92% amino acid sequence identity, still more preferably at least about 93% amino acid sequence identity, still more preferably at least about 94% amino acid sequence identity, still more preferably at least about 95% amino acid sequence identity, still more preferably at least about 96% amino acid sequence identity, still more preferably at least about 97% of - - amino acid sequence identity, still more preferably at least about 98% amino acid sequence identity, still more preferably at least about 99% amino acid sequence identity with: (a) residues of 1 or about 41 to 249 of the PRO207 polypeptide shown in Figure 4 (SEQ ID NO: 7), (b) from X to 249 of the PRO207 polypeptide shown in Figure 4 (SEQ ID NO: 7), wherein X is any amino acid residue from 36 to 45 of Figure 4 (SEQ ID NO: 7) or (c) other derivative fragment specifically of the amino acid sequence shown in Figure 4 (SEQ ID NO: 7). Typically, a variant of PRO320 will have at least about 80% amino acid sequence identity, preferably at least about 81% amino acid sequence identity, more preferably at least about 82% amino acid sequence identity, still more preferably at least about 83% amino acid sequence identity, still more preferably at least about 84% amino acid sequence identity, still more preferably at least about 85% amino acid sequence identity, still more preferably at least about 86% from * ÁA? ¿? *? **? *** t.-... M * á < ?YE*. ., S *! *,* * * TO. ******** . - - amino acid sequence identity, still more preferably at least about 87% amino acid sequence identity, still more preferably at least about 88% amino acid sequence identity, still more preferably at least about 89% sequence identity of amino acids, still more preferably at least about 90% amino acid sequence identity, still more preferably at least about 91% amino acid sequence identity, still more preferably at least about 92% amino acid sequence identity, even more preferably at least about 93% amino acid sequence identity, still more preferably at least about 94% amino acid sequence identity, still more preferably at least about 95% amino acid sequence identity, to still more preferably at least about 96% amino acid sequence identity, still more preferably at least about 97% amino acid sequence identity, still more preferably at least about 98% amino acid sequence identity, even more - - preferably at least about 99% amino acid sequence identity with: (a) residues of 1 or about 22 to 338 of the PRO320 polypeptide shown in Figure 6 (SEQ ID NO: 10), (b) X to 338 of the PRO320 polypeptide shown in Figure 6 (SEQ ID NO: 10), wherein X is any amino acid residue 17 through 26 of Figure 6 (SEQ ID NO: 10) or (c) another fragment specifically derived of the amino acid sequence shown in Figure 6 (SEQ ID NO: 10). Typically, a variant of PR0219 will have at least about 80% amino acid sequence identity, preferably at least about 81% amino acid sequence identity, more preferably at least about 82% amino acid sequence identity, still more preferably at least about 83% amino acid sequence identity, still more preferably at least about 84% amino acid sequence identity, still more preferably at least about 85% amino acid sequence identity, still more preferably at least about 86% amino acid sequence identity, still more preferably at least about 87% amino acid sequence identity, even more - preferably at least about 88% amino acid sequence identity, still more preferably at least about 89% amino acid sequence identity, still more preferably at least about 90% amino acid sequence identity, still more preferably at least about 91% amino acid sequence identity, still more preferably at least about 92% amino acid sequence identity, still more preferably at least about 93% amino acid sequence identity, still more preferably at least about 94% identity of amino acid sequence, still more preferably at least about 95% amino acid sequence identity, still more preferably at least about 96% amino acid sequence identity, still more preferably at least about 97% amino acid sequence identity, still more preferably at least about 98% amino acid sequence identity, still more preferably at least about 99% amino acid sequence identity with: (a) residues of 1 or approximately 24 to 1005 of the polypeptide - - PR0219 shown in Fig8 (SEQ ID NO: 15), (b) from X to 1005 of the PR0219 polypeptide shown in Fig8 (SEQ ID NO: 15), wherein X is any amino acid residue from 19 to 28 of Fig8 (SEQ ID NO: 15) or (c) another fragment specifically derived from the amino acid sequence shown in Fig8 (SEQ ID NO: 15). Typically, a variant of PR0221 will have at least about 80% amino acid sequence identity, preferably at least about 81% amino acid sequence identity, more preferably at least about 82% amino acid sequence identity, still more preferably at least about 83% amino acid sequence identity, still more preferably at least about 84% amino acid sequence identity, still more preferably at least about 85% amino acid sequence identity, still more preferably at least about 86% of amino acid sequence identity, still more preferably at least about 87% amino acid sequence identity, still more preferably at least about 88% amino acid sequence identity, still more preferably at least about you 89% of - - amino acid sequence identity, still more preferably at least about 90% amino acid sequence identity, still more preferably at least about 91% amino acid sequence identity, still more preferably at least about 92% sequence identity of amino acids, still more preferably at least about 93% amino acid sequence identity, still more preferably at least about 94% amino acid sequence identity, still more preferably at least about 95% amino acid sequence identity, even more preferably at least about 96% amino acid sequence identity, still more preferably at least about 97% amino acid sequence identity, still more preferably at least about 98% amino acid sequence identity, to still more preferably at least about 99% amino acid sequence identity with: (a) the residues of 1 or about 34 to 259 of the PR0221 polypeptide shown in Fig10 (SEQ ID NO: 20), (b) X to 259 of the polypeptide PR0221 shown in Fig10 (SEQ ID NO: 20), wherein X is any amino acid residue - - from 29 to 38 of Fig10 (SEQ ID NO: 20), (c) from 1 or from about 34 to X of Fig10 (SEQ ID NO: 20), wherein X is any amino acid residue from 199 to 208 of Fig10 (SEQ ID NO: 20) or (d) another fragment specifically derived of the amino acid sequence shown in Fig10 (SEQ ID NO: 20). Typically, a variant of PR0224 will have at least about 80% amino acid sequence identity, preferably at least about 81% amino acid sequence identity, more preferably at least about 82% amino acid sequence identity, still more preferably at least about 83% amino acid sequence identity, still more preferably at least about 84% amino acid sequence identity, still more preferably at least about 85% amino acid sequence identity, still more preferably at least about 86% of amino acid sequence identity, still more preferably at least about 87% amino acid sequence identity, still more preferably at least about 88% amino acid sequence identity, still more preferably at least about you 89% of * átá¡ * i < *?*?*to* *? nán - - amino acid sequence identity, still more preferably at least about 90% amino acid sequence identity, still more preferably at least about 91% amino acid sequence identity, still more preferably at least about 92% amino acid sequence identity, still more preferably when at least about 93% amino acid sequence identity, still more preferably at least about 94% amino acid sequence identity, still more preferably at least about 95% amino acid sequence identity, still more preferably at least about 96% amino acid sequence identity amino acid sequence identity, still more preferably at least about 97% amino acid sequence identity, still more preferably at least about 98% amino acid sequence identity, still more preferably at least approximately 99% amino acid sequence identity with: (a) the residues of 1 or about 31 to 282 of the polypeptide PR0224 shown in Figure 12 (SEQ ID NO: 25), (b) from X to 282 of the polypeptide PR0224 shown in Figure 12 (SEQ ID NO: 25), wherein X is any amino acid residue - - from 26 to 35 of Figure 12 (SEQ ID NO: 25), (c) of 1 or approximately 31 to X of Figure 12 (SEQ ID NO: 25), where X is any amino acid residue from 226 to 235 of Figure 12 (SEQ ID NO: 25) or (d) another fragment specifically derived from the amino acid sequence shown in Figure 12 (SEQ ID NO: 25). Typically, a variant of PR0328 will have at least about 80% amino acid sequence identity, preferably at least about 81% amino acid sequence identity, more preferably at least about 82% amino acid sequence identity, still more preferably at least about 83% amino acid sequence identity, still more preferably at least about 84% amino acid sequence identity, still more preferably at least about 85% amino acid sequence identity, still more preferably at least about 86% of amino acid sequence identity, still more preferably at least about 87% amino acid sequence identity, still more preferably at least about 88% amino acid sequence identity, still more preferably at least approximately 89% of - - amino acid sequence identity, still more preferably at least about 90% amino acid sequence identity, still more preferably at least about 91% amino acid sequence identity, still more preferably at least about 92% sequence identity of amino acids, still more preferably at least about 93% amino acid sequence identity, still more preferably at least about 94% amino acid sequence identity, still more preferably at least about 95% amino acid sequence identity, even more preferably at least about 96% amino acid sequence identity, still more preferably at least about 97% amino acid sequence identity, still more preferably at least about 98% amino acid sequence identity, to still more preferably at least about 99% amino acid sequence identity with: (a) the residues of 1 or about 23 to 463 of the PR0328 polypeptide shown in Figure 14 (SEQ ID NO: 30), (b) X to 463 of the PR0328 polypeptide shown in Figure 14 (SEQ ID NO: 30), wherein X is any amino acid residue ? *% ******? *** «*** A jan. í? - * > ^ * R * ~ *** > *"OR . - from 18 to 27 of Figure 14 (SEQ ID NO: 30) or (c) another fragment specifically derived from the amino acid sequence shown in Figure 14 (SEQ ID NO: 30). Typically, a variant of PRO301 will have at least about 80% amino acid sequence identity, preferably at least about 81% amino acid sequence identity, more preferably at least about 82% amino acid sequence identity, still more preferably at least about 83% amino acid sequence identity, still more preferably at least about 84% amino acid sequence identity, still more preferably at least about 85% amino acid sequence identity, still more preferably at least about 86% of amino acid sequence identity, still more preferably at least about 87% amino acid sequence identity, still more preferably at least about 88% amino acid sequence identity, still more preferably at least about 89% amino acid sequence identity, still more preferably at least about 90% amino acid sequence identity, even more ,? * é *, .jAA * U * L - - preferably at least about 91% amino acid sequence identity, still more preferably at least about 92% amino acid sequence identity, still more preferably at least about 93% amino acid sequence identity, still more preferably at least about 94% amino acid sequence identity, still more preferably at least about 95% amino acid sequence identity, still more preferably at least about 96% identity of amino acid sequence, still more preferably at least about 97% amino acid sequence identity, still more preferably at least about 98% amino acid sequence identity, still more preferably at least about 99% amino acid sequence identity with: (a) residues of 1 or approximately 28 to 299 of the PRO301 polypeptide shown in Figure 16 (SEQ ID NO: 35), (b) from X to 299 of the PRO301 polypeptide shown in Figure 16 (SEQ ID NO: 35), wherein X is any residue of amino acid 23 to 32 of Figure 16 (SEQ ID NO: 35), (c) of 1 or about 28 to X of Figure 16 (SEQ ID NO: 35), wherein X is any amino acid residue of the 230 - to 239 of Figure 16 (SEQ ID NO: 35) or (d) another fragment specifically derived from the amino acid sequence shown in Figure 16 (SEQ ID NO: 35). Typically, a variant of PR0526 will have at least about 80% amino acid sequence identity, preferably at least about 81% amino acid sequence identity, more preferably at least about 82% amino acid sequence identity, still more preferably at least about 83% amino acid sequence identity, still more preferably at least about 84% amino acid sequence identity, still more preferably at least about 85% amino acid sequence identity, still more preferably at least about 86% of amino acid sequence identity, still more preferably at least about 87% amino acid sequence identity, still more preferably at least about 88% amino acid sequence identity, still more preferably at least about 89% amino acid sequence identity, still more preferably at least about 90% amino acid sequence identity, even more l * iJ á.1 ****** t. **** á ************? *. t.Mt ».a" _. - preferably at least about 91% amino acid sequence identity, still more preferably at least about 92% amino acid sequence identity, still more preferably at least about 93% amino acid sequence identity, still more preferably at least about 94% amino acid sequence identity, still more preferably at least about 95% amino acid sequence identity, still more preferably at least about 96% amino acid sequence identity, still more preferably at least about 97% identity of amino acid sequence, still more preferably at least about 98% amino acid sequence identity, still more preferably at least about 99% amino acid sequence identity with: (a) residues 1 or approximately 27 al 473 of the polypeptide PR0526 shown in Figure 18 (SEQ ID NO: 43), (b) from X to 473 of the polypeptide PR0526 shown in Figure 18 (SEQ ID NO: 43), wherein X is any amino acid residue of the to 31 of Figure 18 (SEQ ID NO: 43) or (c) another fragment specifically derived from the amino acid sequence shown in Figure 18 (SEQ ID NO: 43).

- - Typically, a variant of PR0362 will have at least about 80% amino acid sequence identity, preferably at least about 81% amino acid sequence identity, more preferably at least about 82% amino acid sequence identity, still more preferably at least about 83% amino acid sequence identity, still more preferably at least about 84% sequence identity of amino acids, still more preferably at least about 85% amino acid sequence identity, still more preferably at least about 86% amino acid sequence identity, still more preferably at least about 87% amino acid sequence identity, even more preferably at least about 88% amino acid sequence identity, still more preferably at least about 89% amino acid sequence identity, still more preferably at least about 90% amino acid sequence identity, still more preferably at least about 91% amino acid sequence identity, still more preferably at least about 92% - - amino acid sequence identity, still more preferably at least about 93% amino acid sequence identity, still more preferably at least about 94% amino acid sequence identity, still more preferably at least about 95% amino acid identity amino acid sequence, still more preferably at least about 96% amino acid sequence identity, even more 10 preferably at least about 97% amino acid sequence identity, still more preferably at least about 98% amino acid sequence identity, still more preferably at least about 99% 15 amino acid sequence identity with: (a) the residues of 1 or about 20 to 321 of the polypeptide PR0362 shown in Figure 20 (SEQ ID NO: 48), (b) from X to 321 of the polypeptide PR0362 shown in Figure 20 (SEQ ID NO: 48), where X is any. amino acid residue 20 of 15 to 24 of Figure 20 (SEQ ID NO: 48), (c) of 1 or about 20 to X of Figure 20 (SEQ ID NO: 48), wherein X is any amino acid residue of the 276 to 285 of Figure 20 (SEQ ID NO: 48) or (d) another fragment specifically derived from the amino acid sequence 25 shown in Figure 20 (SEQ ID NO: 48).

- - Typically, a variant of PR0356 will have at least about 80% amino acid sequence identity, preferably at least about 81% amino acid sequence identity, more preferably at least about 82% amino acid sequence identity, still more preferably at least about 83% amino acid sequence identity, still more preferably at least about 84% sequence identity of amino acids, still more preferably at least about 85% amino acid sequence identity, still more preferably at least about 86% amino acid sequence identity, still more preferably at least about 87% amino acid sequence identity, even more preferably at least about 88% amino acid sequence identity, still more preferably at least about 89% amino acid sequence identity, still more preferably at least about 90% amino acid sequence identity, still more preferably at least about 91% amino acid sequence identity, still more preferably at least about 92% handle*,*-. * *? - ÁL I-. **** ** - - amino acid sequence identity, still more preferably at least about 93% amino acid sequence identity, still more preferably at least about 94% amino acid sequence identity, still more preferably at least about 95% sequence identity of amino acids, still more preferably at least about 96% amino acid sequence identity, still more preferably at least about 97% amino acid sequence identity, still more preferably at least about 98% amino acid sequence identity, even more preferably at least about 99% amino acid sequence identity with: (a) residues of 1 or about 27 to 346 of the PR0356 polypeptide shown in Figure 22 (SEQ ID NO: 55), (b) from X to 346 of the PR0356 polypeptide shown in Figure 22 (SEQ ID NO: 55, in d where X is any amino acid residue from 22 to 31 of Figure 22 (SEQ ID NO: 55) or (c) another fragment specifically derived from the amino acid sequence shown in Figure 22 (SEQ ID NO: 55). Normally, a variant of PRO509 will have at least about 80% amino acid sequence identity, preferably at least about - - 81% amino acid sequence identity, more preferably at least about 82% amino acid sequence identity, still more preferably at least about 83% amino acid sequence identity, still more preferably at least about 84% sequence identity of amino acids, still more preferably at least about 85% amino acid sequence identity, still more preferably at least about 86% amino acid sequence identity, still more preferably at least about 87% amino acid sequence identity, even more preferably at least about 88% amino acid sequence identity, still more preferably at least about 89% amino acid sequence identity, still more preferably at least about 90% amino acid sequence identity, still more preferably at least about 91% amino acid sequence identity, still more preferably at least about 92% amino acid sequence identity, still more preferably at least about 93% amino acid sequence identity, even more - - preferably at least about 94% amino acid sequence identity, still more preferably at least about 95% amino acid sequence identity, still more preferably at least about 96% amino acid sequence identity, still more preferably at least about 97% amino acid sequence identity, still more preferably at least about 98% amino acid sequence identity, still more preferably at least about 99% amino acid sequence identity with: (a) the residues of 1 or about 37 to 283 of the PRO509 polypeptide shown in Figure 24 (SEQ ID NO: 60), (b) from X to 283 of the PRO509 polypeptide shown in Figure 24 (SEQ ID NO: 60), wherein X is any residue of amino acid from 32 to 41 of Figure 24 (SEQ ID NO: 60), (c) of 1 or from about 37 to X of Figure 24 (SEQ ID NO: 60), wherein X is any amino acid residue from 200 to 209 of Figure 24 (SEQ ID NO: 60) or (d) another fragment specifically derived from the amino acid sequence shown in Figure 24 (SEQ ID NO: 60). NO: 60). Typically, a variant of PR0866 will have at least about 80% amino acid sequence identity, preferably at least about - - 81% amino acid sequence identity, more preferably at least about 82% amino acid sequence identity, still more preferably at least about 83% amino acid sequence identity, still more preferably at least about 84% sequence identity of amino acids, still more preferably at least about 85% amino acid sequence identity, still more preferably at least about 86% amino acid sequence identity, still more preferably at least about 87% amino acid sequence identity, even more preferably at least about 88% amino acid sequence identity, still more preferably at least about 89% amino acid sequence identity, still more preferably at least about 90% amino acid sequence identity, yet more preferably at least about 91% amino acid sequence identity, still more preferably at least about 92% amino acid sequence identity, still more preferably at least about 93% amino acid sequence identity, even more ili '-i, ***. ¡& *, *** - **. * -.- *, .l.: I .. i. ^. ** - *** ** ....... i. * *. ** * .-, ..... ******* - - preferably at least about 94% amino acid sequence identity, still more preferably at least about 95% amino acid sequence identity, yet more preferably at least about 96% amino acid sequence identity, still more preferably at least about 97% amino acid sequence identity, still more preferably at least about 98% amino acid sequence identity, still more preferably at least about 99% amino acid sequence identity with: (a) the residues of 1 or approximately 27 to 331 of the PR0866 polypeptide shown in Figure 26 (SEQ ID NO: 62), (b) from X to 331 of the PR0866 polypeptide shown in Figure 26 (SEQ ID NO: 62), where X is any amino acid residue from 22 to 31 of Figure 26 (SEQ ID NO: 62) or (c) another fragment derived specifically from the amino acid sequence shown in Figure 26. (SEQ ID NO: 62). The variant polypeptides PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866 do not cover the polypeptide sequence PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866 native. Normally, variant polypeptides - - PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866 have at least 10 amino acids in length, often at least 20 amino acids in length, more often at least 30 amino acids in length, more often at least 40 amino acids in length, more often at least 50 amino acids in length, more often at least 60 amino acids in length, more often at least 70 amino acids in length, more often at least 80 amino acids in length, more often at least 90 amino acids in length, more often at least 100 amino acids in length, more often at least approximately 150 amino acids in length, more often at least approximately 200 amino acids in length, more often at least approximately 250 amino acids in length, more often at least approximately 300 amino acids in length, or more. As will be shown later, Table 1 provides the complete source code for the 7? LIGN-2 sequence comparison computer program. This source code can be routinely compiled for use in a UNIX operating system, to provide the ALIGN-2 sequence comparison computer program.

- - In addition, Tables 2A-2D show hypothetical examples of the use of the method described below to determine% identity of amino acid sequences (Tables 2A-2B) and% nucleic acid sequence identity (Tables 2C-2D ) using the sequence comparison computer program ALIGN-2, wherein the term "PRO" represents the amino acid sequence of a hypothetical polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 of interest, the term "comparison protein" represents the amino acid sequence of a polypeptide against which the "PRO" polypeptide of interest is to be compared, the term ".ADN-PRO" represents a sequence of nucleic acids encoding PR0179-, PRO207-, PRO320-, PR0219-, PR0221-, PR0224-, PR0328-, PRO301-, PR0526-, PR0362-, PR0356-, PRO509- or PR0866- hypothetical of interest, the term " DNA comparison "represents the sequence nucleotides of a nucleic acid molecule against which the nucleic acid molecule ".DNA-PRO" of interest is to be compared, "X", "Y" and "Z" each represent different hypothetical amino acid residues and "N", "L" and "V" each represent different hypothetical nucleotides. tj jt .iL »-Amifc ^ .... í > -.a.J ^ tj - - TABLE 1 * C-C mcreased from 12 lo 15 * Z? S average of EQ * B is average of ND * match wiih stop to M. uop-uop • 0. J (joker) match = 0 «/ define _M -? / • valué of a match ph to uop V _day [26J [261 -. { B C D E F G H 1 J K L M N O P R S T U V W X Y Z »/. { 2.0.-2.0.0.-4. l.-l.-l.0.-1.-2.-1.0._M.1.0.-2.1.1.0.0.-6.0, -3.0). . { 0, 3.-4.3.2, -5.0.1.-2.0.0.-3.-2.2. ~, -l.1.0.0.0.0.-2.-5.0.-3. I). . { -2.-4.15.-5.-5.-4, -3.-3.-2.0.-5.-6, -5.-4._M.-3.-5.-4.0.-2.0. -2.-8.0, 0, -5),. { 0.3, -5.4.3, -6.1.1.-2, 0.0, -4.-3.2. M.-l.2.-1.0.0.0, -2, -7, 0.-4.2} . . { 0.2.-5, 3, 4.-5.0.1.-2.0.0.-3.-2. l ~ M.-I.2.-1, 0.0.0.-2.-7.0.-4.3} . . { -4.-5.-4.-6.-5.9, -5.-2. I.0.-5.2.0. ^ ._ M.-5.-S, ^ ».- 3.-3.0.1.0.0.7.-5). . { I.0.-3, 1.0.-5, 5.-2.-3.0.-2, -4.-3.0._ l.-l, -l.-3. I.0.0, -1.-7, 0.-5.0} . (-1.1.-3.1.1.-2.-2.6.-2.0.0.-2.-2.2, _M.0.3.2.-1.-1.0.-2, -3.0.0.2.}., ( -1.-2, -2, -2.-2.1.-3.-2.5.0, -2.2.2.-2._M.-2.-2.-2, -l.0.0, 4.- 5.0.-1.-2.}., { 0.0.0.0.0.0.0.0.0, 0, 0.0, 0.0, M.0, 0.0, 0.0, 0, 0.0.0.0.0.}. ( -1.0.-5, 0.0.-5.-2.0.-2, 0.5.-3.0.! ~ M.-l.1.3.0.0, 0..2..3.0.-4.0.}.. { -2.3, -6.-4.-3.2.-4.-2.2.0.-3.6.4.-3._M.-3.-2, -3, -3.-i.0.2.-2, 0, -1.-2.}.. { -1, -2.-5.-3.-2.0.-3.-2.2, 0.0, 4.6.-2. ~ M.-2, -l .0.-2.-1.0.2, -4.0.-2, -1) { 0.2.-4.2.1.-4.0.2.-2, 0.1.-3.-2.2, M.- l.1.0.1.0, 0.-2.-4.0.-2.1.}.! J? .J ?. M, _M._M._M, _M, _M, _M, _M._M, _M._M, _M .0, _M._M._M._M._M._M._M._M._M._M._M.}.. { L.-r.-3. "L.-l.-5 ~ l. 0.-2. "? R.-3. ~ 2.-r._M * 6," ?. O "! 1.0.0.-lT-6. O.-sTo), { 0, 1. -5.2.2.-5.-1.3.-2.0.1, -2, -1, 1. * M, 0.4.l.-l.-l.0, -2, -5.0.-4.3.}. { -2, 0, -4.-1.-1.-4, -3.2, -2.0.3.-30.0, "M, 0. I.6.0.-1, 0.-2.2, 0 .-4.0) { 1.0.0.0.0.-3.1.-1.-1.0.0.-3.-2.1. M.1.-1.0.2.1.0.-1.-2.0.-3.0 .}... {1.0, -2.0.0.-3.0, -1.0.0.0, -1, -1.0, M, 0.-1, -1, 1.3.0, 0.-5.0, - 3.0} ,. { 0.0, 0.0.0.0.0.0.0, 0.0, 0.0.0._M.0.0, 0.0.0.0.0.0, 0.0.0} . . { 0, -2, -2.-2.-2, -l.-l.-2. .0.-2.2.2, -27_M, -l, -2.-2, -l.0, 0.4.-6.0.-2.-2} . . { -6.-5, -8.-7, -7, 0.-7.-3.-5.0.-3.-2 -4.-4. ~ M.-6.-5.2.-2.- 5.0.-6.17.0.0.-6). . { 0.0.0.0.0.0.0.0.0, 0.0, 0, 0.0, _M, 0, 0.0, 0.0.0, 0, 0.0.0.0} . . { -3, -3, -4-4, -4.7.-3.0, -1.0.-4.-1, -2, -27 M.-5.-4.-4.-3.-3.0, -2.0. 0.10.-4} . . { 0.1.-5.2.3.-5.0.2, -20.0.-2.-1.1. ~ M, 0.3.0.0.0.0.-2.-6.0.-4.4} >; Page 1 of ay.h L? L_ &J? &? * *? ** i * ti ± * < - *** -. t ***** *, ¿?, * * - # - - f ¿inchide < sidio.h > To ude < aype.h > Merme MAXJM? 16 I * max ju ps ip to dtag * / define MAXGAP 24 / * do not continue to penalae gaps larger tfun this * / define JMPS 1024 / * max jmps in an path * / define MX 4 / * save if there's at least MX-1 bases since last jmp • / define DMAT 3 / * vatue of matching bases * / / define DMIS 0 * penalty for misnuiched bases • / define DINSO 8 / * penalty for a gap * / define DINS1 1 / * penalty per base * / define PINSO 8 / * penalty for a gap * / define PINS1 4 / * penalty for residue • / stniet jmp. { short nfMAXJMPl, / * si »ofjmp (neg for dely) • / uDsigned fhort xtMAXJMP], / • base no oí jmp m seq x * / >;; / • liffltts eq? O 2"16 -l * / struct diag { Int score; / * score ai last jmp * / long offset; / • offset of prev block * / shon ijmp; / * currera jmp index * / strucljmp jp: / • list of jmps * /.}.: struct path { int spe, / • number of Icadtng spaces * sbort n'JMPS | ./ • size of jm (gap) • / int xfJMPSJ, / »Loe of pi? (Last elem before gap) • /.}. • ehar • ofile; / • outp? File yam • / cfaar * namex [21; / • seq temes: getseqsf) * /« toar * prog; / * prog ñame for err rasgs "/ efaar • seqxffl. / • seqs: getseqsO V fat dmax. ! * best diag: n? • / int dir xO; / * final diag • / int dna. / * set if dna: ma? nO * / int endgaps. 1 * - set you petuling end gaps * / int gapx. gapy: / * itrtal gaps m seqs * / int lenO, Icnl; / • seq lens * / int ngapx. ngapy; / * loul size of gaps * / tat smax. / * man score; pwfl "'int * xbm; / * bttmap for mailing • / kmg offset; / • cunera offset in jmp file • / struct diag • dx; / • holds diagonals"' ttroct path PPPI / • holds path for seqs * / cfaar • callocO. * malloc0, *? ndex0, * strepy0; ehar • getseqü. * g_calloc ().

Page 1 of nw.h - / • Needleman- unsch alignrnept program * * usage: progs file if? Le2 * where fiiel and f »le2 are two dna or two proiein sequences * The sequences can be in upper- or lowcr-case an may conuin ambiguity * Any Itnes wnh ';'. '> 'or "< * are ignored * Max file length is 65535 (Acknowledged by unsigned sbon x in the jmp anací) * A sequence wtth 1/3 or more of the elements ACGTU is assumed 10 be DNA * Output 15 m the file" align.ouT • * The program may be created by trnp file m Hmp to hold mfo about unceback. * Original version developed under BSD 43 on a vax 8650 • / ineludc "p h" mchide 'day.h' static dbval (26) -. { 7.14.2.13,0,0.4,11,0.0.12.0.3.15.0.0.0.5.6,8.8,7,9,0.10.0 static _pbval [26] =. { 1.2 | (1 << < CD * - 'A')) | (i < ('N * -, A)). 4, 8.16.32.64. 128, 256. OxFFFFFFF.1 < < 10.1 < < U. I < < 12.1 < < 13.1 < < 14. 1 < < 15. I < < 16.1 < < 17.1 < < 18.1 < < 19, l < < 20. I < < 21.1 < < 22. 1 < < 23. I < < 24.1 < < 25 | (l < «? '-"?')) | .l < «'Q' - 'A")) p »? n (ac. av) mam« u ac. cbar • »Q, prog = av. { 01. ifíac! -3 > . { f? r? uf (s? dep usage:% s ftlel f? le2 \ n *. prog); > nntf (stderr, "wt? ere filel and ñlc2 are two dna or rwo protein sequences. \ n"); fpnittf (s? derr. * Tbe sequences can be tn upper- or lower-case \ t? *) -. fpntf. { stderr. "? ny lincs beginnmg with ',' or * < 'are igporedin *); fpnntf < stderr," Output is "n the file Valign.outVVn"); exiKl):.}.? umex [0) - av (l); namex [l] «av (2]; seqx [0) = getseq (namex [0) > &len0), seqxflj * getseq (namexjli.? lepl); xbm - (dna)? _dbva »• jábval; endgaps - 0; / * 1 to criminal ue endgaps V ofile * •" align.out *. / * output file • / nwO: / * fiH m «he matrix. get the possible jmps • / readjmpsO; / • get «I have current mps • / ppntü; / * pnm suis. alígnmem * cleanup (0). / * unlink any tmp files * / Page 1 of pw.c áüt? * * - ^ ÍÍ? Í ^ Mí,. ***, - ** .. ^ **? *? l * LL? - - / * do the ahgnment. rctum best score- numfj * dna- valúes m Fiich and Smith, PNAS. 80. 1382-1386. 1983 • pro PAM 250 valúes * When scores are equal, we prefer mispuicbes to any gap, prefer * to new gap to exteading an ongoing gap, and prefer to gap in seqx * w to gap tn seq y. • / nw. { cbar * p ?. * py / • seqs and ptrs "I bit • ndely." Dely. / • keep track of dely * / such ndelx. Delx; / • keep tnck of delx * / such * anp, / • for swapping rowO. Ro l • / such mis. / * score fbr each type * / such insO. tnsl; / • insepton penallies • / rtgbter id. / * diagonal index * / register i): / * jmp index * / Rglster • colO. «coll; / • score for curr. last tow • / rcgisttr xx, yy; / * index nuo se? s V dx = »(itnict dug •) g_ealloe (" to gel diags *, lenO + lenl + 1. stzeof (struct diag)), ndeJy - (int *) g_calloc ("to get ndely *. Icnl +!. sbeofOnt)). dely * (int *) g_eallocC" or get del) ", lenl + 1. sizeof (tat)). colO * Cml *) g "ca] loc (" get it olO '. lenl + 1. "leof (int)). coll «• (int ') g calloc (" to get coll *. ten I + 1. azeof (tnt), insO - (dna)? D? NSO: PINSO, insl - «toa) * DINSI: PINSI. smax« -10000; if (endgaps) { For (coK) | 0) * delyJO] = > -msO. Yy • »1. y < = lenl, yy + +) { CoKHyyJ = delyfyyj - coKHyy-IJ - insl. ndeiylyyl * yy. > co »(0J < = 0: / • Watepnan Bull Math Biol 84 • /> ebe for (yy •" = 1, < "lenl; yy + +) delylyy] * > -msO; / * fill in match matpx • / for (px - seqx.O), xx = 1; xx < = ienO, px + +, xx + +) { / • initial ize first enrry m col • / go (endg.? ps) { if < xx - - t) collIOJ = delx = - <? nsO +? nsl): efae coilfO) = > delx - col0 [0J - insl. ndelx = xx} efce { colltOl - 0: delx »-msO; ndelx - 0; > Page 2 of nw.c - - ... nw yy < • = lenl; py + +, y and ++). { if (dna) my + - (xbm { * px-A |? xbm |, py- A '])? DMAT: DMIS. dsc mis + = _d »and [* px-'A'JI, p -? 'l: / • update penalty for the in x seq: * favor new on overgong of the ignore MAXGAP if weighling endgaps • / if (endgaps 11 ndeiy [yy.}. < MAXGAP). { if (coWlyy] - insO > = deiyfyyj). { from lyyj = colOíyyl - (msO + insl): ndely [yy) »1; } e e. { dely { yyl - «= ms); ndely [yyj + +; > } ehe { F (col { Yy) - (msO + insi) > = delylyyl). { delylyyj = 8IO. { yy} - (nsO + insJ) ndely (yy] = 1;.}. Etee ndely [yy) + +; } / updale penalty for the m and seq; * new on / off overgong favor (endgaps |! ndelx < MAXGAP). { if tcotllyy'l - «nsO > = delx). { delx-coil [yy-IJ • (msO + msl); ndelx = 1; } els «. { delx - insl: ndelx + +:} } els «. { go (colllyy-l) - (ipsO + insl) > = delx). { delx - colllyy-1) - (insO + insl); ndelx «1; } ebe ndelx-H-; } / * ptefc tfae maximum score; We're favoring * my over any of the delx over dely Page 3 of nw.c - ... n id - x - yy + lenl - 1; go (mis > • = delx? To my > - delylyy]) colilyyl = mis: else if (delx > - delylyy 1) < colllyyl «delx; ij «• dx [? dl.? pnp: go (dx [id) .jp.n [0) ?? (id 1 1 (ndelí > «= MAXJMP? A xx> dx |? d]. p.x | j] + MX) 1 1 my > dx [jd) .sccre + DINSO)). { dx [? d) .ijmp + +. if (+? -ij> = MAXJMP). { wp? ejmps (id); i) = dx] id].? mp • * 0, dxfidj. offset = offset: offset + = • s eof (struct jmp) + «itol? offset); } } dx [? d]. p.n. { ij] = ndelx: dxtidj. p.xiij] »xx; dx (id) .score »delx. } ebe { coll (yyl = - delylyy]: ij «dx (? d).? jmp: go (dx | ¡d]. pn [0] ?? (id 1 1 (ndelylyy) > - MAXJMP? x > dx | ? d.} .jp.xli) + MX) 1 my> dx [id) seore + DlNSO)). { dxf? d |.? jmp + +; go (+ + ij> = MAXJMP). { wtitejmps (? d); ij «= dx [id].? jmp« 0; dxfid). offset = offset; - * - - sizeof (stn? t jmp) + sizeoffoffset), if (e dgaps) coll (yyJ - =? nsO +? nsl * (lenl-yy): lf (coll [yyl > smax) { smax = colllyy]; dmax * = id,)} } go (endgaps ?? xx < lenO) ooill -1! - "msO +? nsl * { lenO-xx): f (coll [yy-l] > smax) { smax ß colllyy-11: dmax = • id;.}. nnp« »colO: colO = coll: coll = »unp;.}. (void) fpse ((cbar *) ndely) (vnid) freefíchar *) deiy); (void) free ((ehar *) co! 0); (void) frre ( (cbar *) 8] 1); Page 4 of n .c - - * ppm () - only rouiine visible outside ihis module «* stauc: * gctmatO - trace back bes! path. co? n matches- priroO * Pr_ »l» g »0 - pnnt alignmem of descpbed in array pQ- prmi () * durnpblock - du p a block of Imes with numbers. stars: pr_ahgn. { ) * numsO - put or? t a number line - dumpblockO * putltneO - put out to Une (yam. | num). I know that. inu} ) - dumphlockO * stats-0 - -put a line of aars: dumpblockO * stripnameO - sipp any path and prefix from a seqname • / isdude "nw h" define SPC 3 define P_LINE 256 / * maximum outpul lipe • / Define P_SPC 3 I 'space between ñame or num and seq * / extern_day (26) [26); int olen, I * se »output line length • / FILE« fx. / * ouiput file • / printO print. { int Ix. ly, firsigap, lastgap; / * overlap • / iT ((fx = fopen (of? »e." w *)) = = 0) {fpr? ptf (stderr, '% s: can not wpte% s \ n ", prog ofile); cleanupd): í fppni fx, "<ftrst sequence:% s (length"% d) \ n *. pamexJOJ. lepO): fpnntf (fx. "<second sequence% i (length"% d) \ n " , namexfl), lenl): olen - 60, Ix - lenO, and - loyal: firstgap »lastgap * 0. If (dmax < lenl - 1) { / * leading gap mx • / pplOJ.spc = firstgap = lenl • dmax - 1; ly - pp (0J.spc.) ebe if (dmax > lenl - 1) { / * leading gap in and "/ pptlj.spc = firstgap = dmax - (lenl • I); Ix - = ppílj.spe. } if (dmaxO < lenO - I). { / * trailing gap in x * / lastgap - lenO - d axO -I. lx - = sigap,} eise if (dmixO > lenO - 1). { / • trailmg gap m and '/ lastgap - dtnaxO - (lenO -.}.),' Ly - «= lasigap; } ge? mat (, ly, firstgap, lastgap): pr_aJ? gnO.

Page 1 of n prmt.c - * trace back ibc best path. count matches • / statk getmal (lx.l, firstgap.lasigap) getraat tat ix. ly. / • * core "(in s endgaps) * / int firstgap. Lastgap; / • leadipg trailipg overlap • / char outx [32] .double pct .rtpsur nO. Nl .register cbar * í> 0, * pl; / * get total matches, score • /? * il «saO» sral «0; pO - seqx | 0J + ppID - spc.pl« = seqx | l] +? p (0) spc. nO = pp | l |. spc + 1. al - pp [01.spc + l; nm • 0. while (* p0 ?? * pl) { IT (s? zO) { pl + -t-; nl + +; sa ~; > else lf (su!) { P0 + +, n0 + +. sizl-; > < be { ifíxbmfpO- A'l? xbmfpl-?.}.) nm + +. > / • pet homology- * if penalizmg endgaps. base of the shorter seq * else. knock off ovcihangs and take shoner core • / lf (endgaps) Ix - (lenO < lenl)? Iß? . len); tbe Ix - (Ix < ly)? lx "ly.pct - I00. * (double) nm / (double) lx.fppntfífx, - \ n"); fppníf (fr. "<% d matches in an overlap of% ú:% .2í percent similar-ityin * nm. (nm * > < * \ >": "is", lx.pa).

Page2 ofnwprint.c - - fpn fffx. "< gaps first sequence.% d". gapx): ... getmat if (gapx). { . { void) sppntf (outx. "(% d% s% s) \ ngapx. (dna) '" baseVrestdue ". (ngapx = = Yp' •« *); fppntf (x% s ", outx); fppmftfx, *, gaps tn second sequence:% d", gipy); if (í * py). { (void) sppntf (ou? x. * (% d% s% s) ", ngipy, (dna)?" base residue *. (ngapy = * »1)? '" O: fpnntf (fx. "% s \ ouu);.}. if (dna) fpnn «f (fx." \ n <score:% d (maich *% d, rais aich =% d, gap penahy =% d + d per base) n " Smax, DMAT, DMIS, DINSO, DINSI), ebe fpnmf (fx, "\ n < score:% d (Dayhoff PAM 250 matrut, gap penalty =% i +% d per res? due) Vn", smax, P1NS0. PINS1). If (endgaps) fpnmf (fx, '<endgaps penalized. Left endgap:% d% s% s. Nghi endgsp:% d% s% s \ n *. Firsigap. (Dr l? "Base ":" residue ", (ftrstgap« = D? "•" s ". lastgap, (dnap" base "-" residue ", (lasigap = = 1)?": V). ebe f? r? mf (fx , * <endgaps not? enal? zcd \ n "). sta tic nw:. '• matches in cote - for checking •' stßtic Imax; . '• lengihs of stppped file yams * / static Ul2); / • jmp index for a path • / s tlc ncP]; / * number ai stan of current line * sutic «¡121: l * current eiem number - for gapptng * / static« zl2J: sutic char • ps (2J; / * ptr to currem element * / static char •? o (21; '* ptr to next output char slot * / static cbar to ouut? ((22)) [[lP_UNEl;' * ouiput hne • / static char surfP:;]; '* set by s rsO V * print alignment of desenbed in struct path ppf] • / static pr aligpO pr align i tat rm; / * char count * / int mote; register i; Tor (i = 0, Imax - 0, i <2:? -n->. {Nn «= stpppame (namex [i)): if (nn> Imax) Imax» nn. nc. { (J = 1; nifi] - 1: »«! »] - Uli] - 0; psíij» seqxfi.}; Polt] - outfi]; Page 3 of n print.c - - for (nn - ron «0. more - 1; more;). { ... pr allgn for (i «more« = 0: i <2;? + +). { / • • do we have more of thts sequenct? • / if (! * Psli |) continue; more + +: if (PPi) spc). { / * ieaduig space • / • o. { i} + + - '•; pp. { i | .spc-; } ebelf (siz { i]). { / • ina gap * / * po | il + + = '-'; sizfi] -; > ebe { / • we're putting to seq ele em * / • polil - *? S [? L; ifdslowerCpsli])) • pslij =? oupper (*? sli)); / • * are we ai next gap for this seq? • and go (n¡li] - ppl¡j.xlijl¡.}. J). { / • • we need? merge all gaps • at ihis location • / a? l'l * = ppli] .n [»j [?} + +), whüe (p? li] - = pp [?]. x [ij | ij]) sizfi) + = R > li} .nl? jll-t- + l:} fi } + +; } } If (+ + pn * = oil 11 Imore? Nn). { du pblockQ; for (i - 0, i <2; n- +) po [) J = ouili): nn = 0; ) 5 / • • dump a block of lines. including numbers. s rs: pr alignO • / static um iocko dumpblock. { refbter i; for (i - 0; i < 2; i ++) • poly) - - '0-; Page 4 of n print .c - .dumpblock (void) pu? c ('\ n', fx), for (i «0. i < 2.? + -). { if < * ouf] ?? foutfi } ! = - * I j • (? O ('l)' "=" » { If () - =« 0) nurasíi), iT (? »= O ?? • outllj) starsO. put)? ne (?), if (? »-0 A * outllJ) fpnntf (fx. south), if (? = =!) nums (?). } > } 1 * • pul out a number line: dumpbiockQ * statk nums (? X) nums tat ix. / • index m out [] holding seq line • /. { rhnr nl? nelP_LlNE). register '.J. register diar • pn. »Px. py for (pn = • nltne, i = 0, i < lmax + P_SPC.? + +, pn ++) • pn = ', for (i = ncfix]. py »ou); »Py; py- > - + pn ++). { ifCpy - = "IJ * py-" • - *) • pn = '' ebe { if% 10 =. = 011 (i == 1 ?? nc (? x)! = i)) { j = (i <O -i: i.fu- (px • = pn, j.j / = 10, px--) • px -j% 10 + '0'. lf (i < Oí) • px - - '..}. ebe • pn = ",» + +. &. ,,. • - pn =' \ 0. nx] «i; for (pn« = nltne; • pn, pn + +) ( void) p «c (* pn.fx); (void) pu? c ('\ n'. fx).}. /. * * put oui a line (yam { num], seq, (nu) ) du pblockO static pu? l? ne (? x) putline tat tx: {Pag Sofnwprint.c áklA ???. Aí ?? * - - ... putline tat i. regkter char • px: for (px - namex (ix) .i - 0: * px &? "px!» ':': px + +,? + +) (vßid) pu? c (*? x, fx) for (; i &) / * these count from I: * nilJ ts current element (from 1) * nefi «s number to the san of currant line • / for (px«> outlix]; "px; px + + ) (void) putc (* pxA0? 7F. fx), (voitftputcOn'.fx): • put a lme sf surs (seqs always tn out [0J, ou [H) dumpblockO) / s tk sursO stars. { im i. register char * p0. * pl. former. * px. If («» out [0111 («outlO] = -" AA • (poJOl) - = •• ou? [I] 11 (• owllj - = '' ?? '(pollj) - =' return; px »south for (i = Imax + P SPC; i; i-) • px + + - 'fot (p0 • ool (03, pl »or? t [IJ:» pOAA • p).? O ++, pl + +) { IT (tsalpha (* pO) ?? isalphaCpl)) { If (xbm! * P -'A) Axbml »pl-A'D { Ex - •. Wn + *,.}. Ebeiffldn AA íayl'pO-? JI'pl-?] > 0) ex = ''. "be xc ''.}. ebe '', Pageßofnwprint.c - - / • strtp palh or prefix trom pn, retum len. pr_al? gn. { ) • / static sinpnamefn) stripname char «pn, / • file ñame (may be paih) • /. { register char p. * py, py = 0, fi > r (px = pn; * px, px + +) ifCpx == V) py = px + 1, if (py) (void) strcpy (pn.py); return (strlen (pn)); Page 7 of nwpruu.c - - • ctcanupO - cieamip any tmp file • getseq - read m seq. sel dna len rnaxlen "g_calloeü - callocO wuh error checkin • réadj psO - gei ihe good jmps. from tmp file if necessaiy • wTitempsO - wnie to filled array of jmps 10 to tmp file: nwQ tacludt" nw.h "inchide <; sysf? le .h > char • jna e = • / pnp / homgXXXXXX '; . '• unp file for jmps • / FILE • o. tat cieanupO; / • cleanup i p file • / long IseekOl / • • remove any i p file if we blow * / cleanup (deanup tat t; { Lf < Q) (void) ufü? Nk (jname); exiid); > / • • read. return pir to seq, set dna. len axlen • skip line tarting with ';'. < \ or > "• seq m upper or lower case • i char • getseq (file.le") g € tseq char 'file, / • file nam • / char I? Ne [l024], * pseq; regbtcr cbar • p *. * py; tat natge.tlen, FILE • f: If ((fp = fopen (file, V)) - - 0) { err. "% t: can'i read% s \ n", prog. file); while (fgetífline.1024. fp)). { - •; • ¡¡ »L? Ne = - '< '|| «Une - '> ') I continued; for (px = &nt; Une; * px! - 'in'; px + +) IT (? supper (»px) 11? slower (» px))? ien ++,} if ((pseq - malloc ((? uuígned) (tlefl -? - 6))) - = 0). { fprtntf (stdert. "% s: mallocO failed IO gct% d bytes for% s \ n" .prog, lien +6. file); ex? t (l); } pseqfO} - pseqll) »p? e? P] - pseq [3) = '\ 0'; Page 1 of nwsubr.c ± ¿. &? Jbitodh-tt - ** Mi¿ **., * "* &" * _ ***, **., *****, ^,. **, ^, *! ¡^? **** * i¡¡ ** ^ - - ..getseq py - pseq + 4; • len = tlep; tewmd (fp); whüe (fgetsdine, 1024. fp)). { lf («lme = = '.- | | • line - = <' | | * ltnc =« = > •) continue; for (px - hite; »px '- \ n"; px + +) { if (supper (»px)) • py-t- - * -« »px: ebe tr (? slower (* px) ) • py + + * louppir (* px); if (? Ndex { "ATGCUV (py-l))) na? Gc + +; } } • py + + =? O '. • py - • «» •; (void) fclose < fp) -. dna = naigc > (? ien / 3); returntpseq + 4 !; } char • g_calloc (msg. nx, if) g_calloc cbar * msg: I * program. cailing routine • / int nx. iz: / • number and stze of elemems • /. { char • px. • callocO; if ((px = »calloc ((unsigned) nx. (unsigned) sz)) - 0). { if C sg). { fynp? f (stderr, "% s- g_callocO failed * s (p = * d, sz ^ Hd) ^". prog, msg. nx, if), ex ?? (l); } remra (px); / • • get final mps from dxfl or imp file, set pp [], reset dmax: mainO *) readjm? S () readjmps . { regbter i. j. xx: (void) fclose (fj); If ( { Fd = open na e. 0_RDONLY. 0) > < 0). { fjpnntf (stderr. '% * >: can not openO? without * .prog. jname); cleanup { l) -. } } for (i - 0 * •? l - 0, dmaxO «dmax, xx» lenO;; i * +). { while (I). { for 0 ß dx | dmax) .ijmp; j > »O AA dx [dmax) .jp.x (j) > - xx: j-) Pagc2 ofnwsubr.c - - ... readjmps if (j < O A? dx (d ax) offset ?? fj). { (void) lseeWfd. dxldmaxj ffset.0): (void) read (fd. (cbar *)? dxldmax] jp, sizeor (struct mp)): (votes) readffd, (char * > Adx.dmaxJ offseí, siaßrfltdxfdpiaxj.offset)): dxldmaxj .imp = MAXJMP- 1.} ebe broaden } go < ? > = JMPS > . { fprtmffjiderr. "% s: too many gaps m alignmen? n". prog): deanup (l):} if (j> = 0) < SIZ »dx [dmax] jpn (j];] .jp.x (jl, if (siz < 0) { / • pp in second seq • / pplU.nlil] = -se; xx *" siz. / • id «• xx - yy + lenl - 1 • / ppll] -x.il) *> xx - dmax + lenl - 1; / • ignore MAXGAP when doing endgaps • / su« = (-siz <MAXGAP 11 endgaps)? -siz: MAXGAP, »+ +.... Ebe if (your> 0) { / • gap in firsi seq • / pp { 0) .n (i0] < * stz ppl0) .x [? 0) * xx.gapx + +; ngapx • * - = siz: / • ignore MAXGAP when doing endgaps * / sp = (siz <MAXGAP 11 endgaps)? stz: MAXGAP,.} ebe brea;> • reverse the order of jmps • / for (j * 0, i0-; < ¡0; + +, ¡0-) { i - pp [0 |.? 4jl: ppíOJ.nfj) - PPÍ0J.p [? 0J. pp | 0] .n [? 0J = .. '- PPlOl.xW: PPlO) xül - PPl0).? |? 0J, ppl0) .x [») = i.}. for (j «> 0. t¡-; j <? l; j + +.? l-) { '- PPlU-nOJ; PrtU-nÜÍ - PPlIJ.pfíil; ppfl]. nf? l] = .. i - PPUJxW. P ín. Ü) - PPfl] -x [? I |: ppílj.xfil] - i. < lf (fd > -0) (void ) close (fd). * f < G) < (void) unlmkfjname); (j-0; offset - 0; Page 3 of nwsubr.c -sá ÍA., L ??. ÁÁ * l, j¿.l '^^ | - - • wpte a filled jmp struct offset of the prev one (if any) - nwO • wptejmps (? X) writejmps char * mktempü; if (! f!) { if (mktemp (jna? ne) < O). { fprmtffude r. ~% s can not mktempO% S \ n ". prog. jtumc). cleanup (l),.}. if { (fj = fopen wime." w ")) - - 0) { fprmtf ( stdcrr, "% t can not wnte * s \ n". prog. jname). ex ?? (l).}.}. (void) fwr ?? e ((char *)? dxf? x ] .p. sizeof (ßp? ct jmp) .I, fj). (void) fwpte ((char ») Adxl? x.}. .offset, sizeoT (dx |? x] .offset). 1, fj) .

Page4ofn subr.c Aú.Aá * L. *** *** ^ f * nf ^ ¡* f * -t .. **.

- - TABLE 2A PRO XXXXXXXXXXXXXXX (length = 15 amino acids) Protein of Cativation XXXXXYYYYYYY (length = 12 amino acids) % amino acid sequence identity = (the number of amino acid residues that match identically between the two polypeptide sequences as determined by ALIGN-2) divided by (the total number of amino acid residues of the PRO polypeptide) = 5 divided between 15 = 33.3% TABLE 2B PRO XXXXXXXXXX (length = 10 amino acids) Copparation Protein XXXXXYYYYYYZZYZ (length = 15 amino acids) % amino acid sequence identity = (the number of amino acid residues that match identically between the two polypeptide sequences as determined by .ALIGN-2) divided by (the total number of amino acid residues of the PRO polypeptide) = 5 divided by 10 = 50% - - TABLE 2C DNA-PRO NNNNNNNNNNNNNN (length = 14 nucleotides) Comparison AEN NNNNNNLLLLLLLLLL (length = 16 nucleotides) % nucleic acid sequence identity = (the number of nucleotides that match identically between the two nucleic acid sequences as determined by ALIGN-2) divided by (the total number of nucleotides of the DNA-PRO nucleic acid sequence ) = 6 divided by 14 = 42.9% 2D TABLE DNA-PRO NNNNNNNNNNNN (length = 12 nucleotides) AEN of Carparation NNNNLLLW (length = 9 nucleotides) % nucleic acid sequence identity = (the number of nucleotides that match identically between the two nucleic acid sequences as determined by ALIGN-2) divided by (the total number of nucleotides of the DNA-PRO nucleic acid sequence ) = 4 divided by 12 = 33.3% The "Percentage (%) of amino acid sequence identity" with respect to the polypeptide sequences PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, - - PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866 identified herein, is defined as the percentage of amino acid residues in a candidate sequence that are identical to the amino acid residues in a sequence of PR0179, PRO207, PRO320, PR0219, PR0221 , PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866, after aligning the sequences and inserting gaps, if necessary, to achieve the maximum percentage of sequence identity and without considering any conservative substitution as part of the identity of sequence. The alignment for purposes of determining the percentage of amino acid sequence identity, can be carried out in various ways that are within the knowledge of those skilled in the art, for example, using computer software available to the public, such as software BLAST, BLAST-2, ALIGN, ALIGN-2 or Megalign (DNASTAR). Those skilled in the art can determine the appropriate parameters to measure the alignment, including any algorithm necessary to achieve maximum alignment over the full length of the sequences being compared. However, for the purposes of the present, amino acid sequence identity% values are obtained in the manner described below using the .ALIGN-2 sequence comparison computer program, in - - where the complete source code for the ALIGN-2 program is provided in Table 1. The ALIGN-2 sequence comparison computer program was authorized by Genetech, Inc. and the source code shown in Table 1 was presented with user documentation at the Copyright Office of the United States, Washington DC, 20559, where it is registered with the Copy Rights Registration Number Copyright USTXU510087. The ALIGN-2 program is available to the public through Genentech, Inc., South San Francisco, California or can be compiled from the source code provided in Table 1. The ALIGN-2 program must be compiled to be used in a system UNIX operative, preferably UNIX digital VA.OD. All sequence comparison parameters are set by the ALIGN-2 program and do not vary. For purposes of the present, the% amino acid sequence identity of a given amino acid sequence A, with or against a given amino acid sequence B (which alternatively can be considered as a given amino acid sequence A having or comprising a certain% sequence identity of amino acids with or against a given amino acid sequence B), is calculated as follows: 100 times the X / Y fraction .i ** *. * *********** ^^ j - - where X is the number of amino acid residues qualified as identical by the sequence alignment program .ALIGN-2 in the alignment of A and B, and where Y is the total number of amino acid residues in B. It will be noted that when the length of the amino acid sequence A is not equal to the length of the amino acid sequence B, the amino acid sequence identity% of A with with respect to B will not be equal to the% amino acid sequence identity of B with respect to A. As examples of% amino acid sequence identity calculations, Tables 2A-2B demonstrate how to calculate% amino acid sequence identity of the amino acid sequence designated "Comparison Protein" with respect to the amino acid sequence designated "PRO". Unless specifically indicated otherwise, all% amino acid sequence identity values used herein are obtained in the manner described above, using the ALIGN-2 sequence comparison computer program. However,% amino acid sequence identity can also be determined using the NCBI-BLAST2 sequence comparison program (Altschul et al., Nucl ei c Acids Res., 25: 3389-3402 (1997)). The NCBI-BLAST2 sequence comparison program can be downloaded from - - the internet address http: // ww .ncbi .nlm.nhi. gov. The ncbi-blast2 program uses several research parameters, where all the parameters investigated are set to the default values, including, for example, unmask = yes, strand = all, expected occurrences = 10, minimum low complexity length = 15/5 , multi-pass e-value = 0.01, constant for multi-pass = 25, dropoff for final gapped alignment = 25 and scoring matrix = BLOSUM62. In situations where the NCBI-BLAST2 program is used for amino acid sequence comparison, the% amino acid sequence identity given A with or against a given amino acid sequence B (which alternatively can be considered as an amino acid sequence) Given that it has or comprises a certain% identity of amino acid sequence with or against a given amino acid sequence B), it is calculated as follows: 100 times the fraction X / Y where X is the number of amino acid residues qualified as identical by the NCBI-BLAST2 sequence alignment program in the alignment of A and B, and where Y is the total number of amino acid residues in B. It will be evident that when the length of the amino acid sequence A is not equal to the length of the amino acid sequence B, the% sequence identity of t ^ * Á $ ^ áÁÁ £ £ i * á £ * Á! S * «* 2tí ***. * - * * £ Há £ H *** ** - X **** * * * fj» *? ** i * l l3 ** ^ * íl ^ *? * ** tl ^ í * í *** l. i * & & ** *. ** i¡in; í * .. - - amino acids of A with respect to B will not be equal to% amino acid sequence identity of B with respect to A. In addition,% amino acid sequence identity can also be determined using the computer program of sequence comparison WU-BLAST-2 (Altschul et al., Methods in Enzymology, 266: 460-480 (1996)). Most of the search parameters of the WU-BLAST-2 program are set to default values. Those that are not established in the default values, i. e. , the adjustable parameters are established with the following values: overlap span = 1, overlap fraction = 0.125, word threshold (T) = 11 and scoring matrix = BLOSUM62. For purposes of the present, a value of% amino acid sequence identity is determined by dividing (a) the number of identical amino acid residues among the amino acid sequence of the PRO polypeptide of interest having a sequence derived from the native PRO polypeptide and comparing the amino acid sequence of interest (i.e., the sequence against which the PRO polypeptide of interest is being compared, which may be a variant PRO polypeptide) determined by WU-BLAST-2, between (b) the total number of amino acid residues of the PRO polypeptide of interest. For example, in the phrase "a peptide comprising a sequence of ÍA Ju¿j .4jfcjtA *. «A.« L j-i .. ».?. to . . ** **, Aüt, ** íl ** a. * T *. , ** .. *** ^ ^^^ & ^^ * a ^ j ^^^ ¿- - amino acids A having at least 80% amino acid sequence identity with the amino acid sequence B ", the sequence of amino acids A is the comparison amino acid sequence of interest and the amino acid sequence B is the amino acid sequence of the PRO polypeptide of interest The term "variant PR0179 polynucleotide" or "variant nucleic acid sequence PR0179" means an acid molecule nucleic acid encoding an active PR0179 polypeptide as defined below and having at least about 80% nucleic acid sequence identity with: (a) a nucleic acid sequence encoding residues 1 or approximately 17 to 469 of PR0179 polypeptide shown in Figure 2 (SEQ ID No. 2), (b) a nucleic acid sequence encoding amino acids X to 460 of PR0179 polypeptide shown in Figure 2 (SEQ ID No. 2) , where X is any amino acid residue from 12 to 21 of Figure 2 (SEQ ID No. 2), or (c) a nucleic acid sequence encoding another fragment derived specifically from the amino acid sequence shown in Figure 2 (SEQ. ID No. 2). Typically, a variant PR0179 polynucleotide will have at least about 80% nucleic acid sequence identity, preferably at least - about 81% nucleic acid sequence identity, more preferably at least about 82% acid sequence identity nucleic acids, more preferably at least about 83% nucleic acid sequence identity, more preferably at least about 84% nucleic acid sequence identity, more preferably at least about 85% nucleic acid sequence identity, more preferably when at least about 86% nucleic acid sequence identity, more preferably at least about 87% nucleic acid sequence identity, more preferably at least about 88% nucleic acid sequence identity, more preferably at least approximately and 89% nucleic acid sequence identity, more preferably at least about 90% nucleic acid sequence identity, more preferably at least about 91% nucleic acid sequence identity, more preferably at least about 92% identity of nucleic acid sequence, more preferably at least about 93% nucleic acid sequence identity, more •? * Ú ** i * i? I ****? * T, ~ *****, - - preferably at least about 94% nucleic acid sequence identity, more preferably at least about 95% nucleic acid sequence identity, more preferably at least about 96% nucleic acid sequence identity, more preferably at least about 97% nucleic acid sequence identity, more preferably at least about 98% acid sequence identity nucleic acids, more preferably at least about 99% nucleic acid sequence identity with: (a) a nucleic acid sequence encoding the residues of 1 or about 17 to 460 of the PR0179 polypeptide shown in Figure 2 (SEQ ID No. 2), (b) a nucleic acid sequence encoding amino acids X to 460 of PR0179 polypeptide shown in Figure 2 (SEQ ID No. 2), wherein X is any residue amino acid duo from 12 to 21 of Figure 2 (SEQ ID No. 2), or (c) a nucleic acid sequence encoding another fragment specifically derived from the amino acid sequence shown in Figure 2 (SEQ ID No. 2) . The PR0179 polynucleotide variants do not encompass the native PR0179 nucleotide sequence. The term "variant PRO207 polynucleotide" or i.sL? i**? . á * i * iíi * a-? i-. »)., * & - & ' a ^ afe - - "variant PRO207 nucleic acid sequence" means a nucleic acid molecule encoding an active PRO207 polypeptide as defined below and having at least about 80% nucleic acid identity with: (a) a nucleic acid sequence that encodes for the residues of 1 or approximately 41 to 249 of the PRO207 polypeptide shown in Figure 4 (SEQ ID No. 7), (b) a nucleic acid sequence encoding the amino acids of X to 249 of the PRO207 polypeptide shown in Figure 4 (SEQ ID No. 7), wherein X is any amino acid residue from 36 to 45 of Figure 4 (SEQ ID No. 7), or (c) a nucleic acid sequence encoding another fragment specifically derived from the amino acid sequence shown in Figure 4 (SEQ ID No. 7). Typically, a variant PRO207 polynucleotide will have at least about 80% nucleic acid sequence identity, preferably at least about 81% nucleic acid sequence identity, more preferably at least about 82% nucleic acid sequence identity, more preferably at least about 83% nucleic acid sequence identity, more preferably at least about 84% nucleic acid sequence identity, more emá ** íú, á J..ia a? .. L¿ t, ^ - - preferably at least about 85% nucleic acid sequence identity, more preferably at least about 86% nucleic acid sequence identity, more preferably at least about 87% nucleic acid sequence identity, more preferably at least about 88% nucleic acid sequence identity, more preferably at least about 89% nucleic acid sequence identity, more preferably at least about 90% nucleic acid sequence identity, more preferably at least about 91% nucleic acid sequence identity, more preferably at least about 92% nucleic acid sequence identity, more preferably at least about 93% nucleic acid identity identity nucleic acid sequence, more preferably at least approximately 94% nucleic acid sequence identity, more preferably at least about 95% nucleic acid sequence identity, more preferably at least about 96% nucleic acid sequence identity, more preferably at least about 97% ***** * Ú? * Kua *. *. ,! - nucleic acid sequence identity, more preferably at least about 98% nucleic acid sequence identity, more preferably at least about 99% nucleic acid sequence identity with: (a) a nucleic acid sequence coding for the residues of 1 or about 41 to 249 of the PRO207 polypeptide shown in Figure 4 (SEQ ID No. 7), (b) a nucleic acid sequence encoding amino acids from X to 249 of the PRO207 polypeptide shown in Figure 4 (SEQ ID No. 7), wherein X is any amino acid residue from 36 to 45 of Figure 4 ( SEQ ID No. 7), or (c) a nucleic acid sequence encoding another fragment specifically derived from the amino acid sequence shown in Figure 4 (SEQ ID No. 7). The PRO207 polynucleotide variants do not encompass the native PRO207 nucleotide sequence. The term "variant PRO320 polynucleotide" or "variant PRO320 nucleic acid sequence" means a nucleic acid molecule encoding an active PRO320 polypeptide as defined below and having at least about 80% acid sequence identity nucleic acids with: (a) a nucleic acid sequence encoding residues 1 or approximately 22 to 338 of the * i,? **? a.i * i *: i * j, i lii r.

- PRO320 polypeptide shown in Figure 6 (SEQ ID No. 10), (b) a nucleic acid sequence encoding amino acids from X to 338 of the PRO320 polypeptide shown in Figure 6 (SEQ ID No. 10), wherein X is any amino acid residue 17 through 26 of Figure 6 (SEQ ID No. 10), or (c) a nucleic acid sequence encoding another fragment specifically derived from the amino acid sequence shown in Figure 6 (SEQ ID No. 10). Typically, a variant PRO320 polynucleotide will have at least about 80% nucleic acid sequence identity, preferably at least about 81% nucleic acid sequence identity, more preferably at least about 82% nucleic acid sequence identity, more preferably at least about 83% nucleic acid sequence identity, more preferably at least about 84% nucleic acid sequence identity, more preferably at least about 85% nucleic acid sequence identity, more preferably at least about 86% nucleic acid sequence identity, more preferably at least about 87% nucleic acid sequence identity, more preferably at least about 88% nucleic acid sequence identity, more preferably at least about 89% nucleic acid sequence identity, more preferably at least about 90% nucleic acid sequence identity, more preferably at least about 91% nucleic acid sequence identity, more preferably at least about 92% identity nucleic acid sequence, more preferably at least about 93% nucleic acid sequence identity, more preferably at least about 94% nucleic acid sequence identity, more preferably at least about 95% nucleic acid sequence identity, more preferably at least about 96% nucleic acid sequence identity, more preferably at least about 97% nucleic acid sequence identity, more preferably at least about 98% nucleic acid sequence identity, more preferably when about 99% nucleic acid sequence identity with: (a) a nucleic acid sequence encoding residues 1 or about 22 to 338 of the - PRO320 polypeptide shown in Figure 6 (SEQ ID No. 10), (b) a nucleic acid sequence encoding amino acids from X to 338 of the PRO320 polypeptide shown in Figure 6 (SEQ ID No. 10), where X is any amino acid residue 17 through 26 of Figure 6 (SEQ ID No. 10), or (c) a nucleic acid sequence encoding another fragment specifically derived from the amino acid sequence shown in Figure 6 ( SEQ ID No. 10). The PRO320 polynucleotide variants do not encompass the native PRO320 nucleotide sequence. The term "variant PR0219 variant polynucleotide" or "PR0219 variant nucleic acid sequence" means a nucleic acid molecule encoding an active PR0219 polypeptide as defined below and having at least about 80% acid sequence identity nucleic acids with: (a) a nucleic acid sequence encoding the residues of 1 or approximately 24 to 1005 of the polypeptide PR0219 shown in Figure 8 (SEQ ID No. 15), (b) a nucleic acid sequence that encodes for amino acids from X to 1005 of PR0219 polypeptide shown in Figure 8 (SEQ ID No. 15), wherein X is any amino acid residue from 19 to 28 of Figure 8 (SEQ ID No. 15), or ( c) a nucleic acid sequence that encodes another fragment derived specifically from the ^ aJ ^ Sfe * ^ - - amino acid sequence shown in Figure 8 (SEQ ID No. 15). Typically, a variant PR0219 polynucleotide will have at least about 80% nucleic acid sequence identity, preferably at least about 81% nucleic acid sequence identity, more preferably at least about 82% nucleic acid sequence identity, more preferably at least about 83% nucleic acid sequence identity, more preferably at least about 84%! of nucleic acid sequence identity, more preferably at least about 85% nucleic acid sequence identity, more preferably at least about 86% nucleic acid sequence identity, more preferably at least about 87% nucleic acid sequence identity nucleic acids, more preferably at least about 88% nucleic acid sequence identity, more preferably at least about 89% nucleic acid sequence identity, more preferably at least about 90% nucleic acid sequence identity, more preferably at least approximately 91% nucleic acid sequence identity, more iiáí.í **** ** .i -... * .- i * ji, l í ** • &. ***** ***** - - preferably at least about 92% nucleic acid sequence identity, more preferably at least about 93% nucleic acid sequence identity, more preferably at least about 94% identity of nucleic acid sequence, more preferably at least about 95% nucleic acid sequence identity, more preferably at least about 96% nucleic acid sequence identity, more preferably at least about 97% nucleic acid sequence identity , more preferably at least about 98% nucleic acid sequence identity, more preferably at least about 99% nucleic acid sequence identity with: (a) a nucleic acid sequence encoding residues of 1 or approximately 24 to 1005 of the polypeptide PR0219 shown in Figure 8 (SEQ ID N or 15), (b) a nucleic acid sequence encoding amino acids from X to 1005 of PR0219 polypeptide shown in Figure 8 (SEQ ID No. 15), wherein X is any amino acid residue from 19 to 28 of Figure 8 (SEQ ID No. 15), or (c) a nucleic acid sequence encoding another fragment derived specifically from the J? L- É.-i? HiAiA **: *: ** ,. '! ^ - * --- * -. ^ Jk? IdÁü - - amino acid sequence shown in Figure 8 (SEQ ID No. 15). The PR0219 polynucleotide variants do not encompass the native PR0219 nucleotide sequence. The term "variant PR0221 polynucleotide" or "variant PR0221 nucleic acid sequence" means a nucleic acid molecule encoding an active PR0221 polypeptide as defined below and having at least about 80% acid sequence identity nucleic acids with: (a) a nucleic acid sequence encoding the residues of 1 or approximately 34 to 259 of the PR0221 polypeptide shown in Figure 10 (SEQ ID No. 20), (b) a nucleic acid sequence that encodes for amino acids from X to 259 of PR0221 polypeptide shown in Figure 10 (SEQ ID No. 20), wherein X is any amino acid residue from 29 to 38 of Figure 10 (SEQ ID No. 20), (c ) of amino acid 1 or about 34 to X of Figure 10 (SEQ ID No. 20), wherein X is any residue, of amino acid from 199 to 208 of Figure 10 (SEQ ID No. 20), or ( d) a nucleic acid sequence encoding another fragment specifically derived from the amino acid sequence shown in Figure 10 (SEQ ID No. 20). Normally, a variant PR0221 polynucleotide will have at least approximately 80% acid sequence identity , *. FcaKA.i-ÁJ - - nucleics, preferably at least about 81% nucleic acid sequence identity, more preferably at least about 82% nucleic acid sequence identity, more preferably at least about 83% identity nucleic acid sequence, more preferably at least about 84% nucleic acid sequence identity, more preferably at least about 85% nucleic acid sequence identity, more preferably at least about 86% nucleic acid sequence identity, more preferably at least about 87% nucleic acid sequence identity, more preferably at least about 88% nucleic acid sequence identity, more preferably at least about 89% nucleic acid sequence identity, more preferably at least about 90% of nucleic acid sequence identity, more preferably at least about 91% nucleic acid sequence identity, more preferably at least about 92% nucleic acid sequence identity, more preferably at least about 93% - nucleic acid sequence identity, more preferably at least about 94% nucleic acid sequence identity, more preferably at least about 95% nucleic acid sequence identity, more preferably at least about 96% sequence identity nucleic acids, more preferably at least about 97% nucleic acid sequence identity, more preferably at least about 98% nucleic acid sequence identity, more preferably at least about 99% nucleic acid sequence identity with: a) a nucleic acid sequence encoding the residues of 1 or approximately 34 to 259 of the PR0221 polypeptide shown in Figure 10 (SEQ ID No. 20), (b) a nucleic acid sequence encoding the amino acids from X to 259 of polypeptide PR0221 shown in Figure 10 (SEQ ID No. 20), wherein X is any amino acid residue from 29 to 38 of Figure 10 (SEQ ID No. 20), (c) of amino acid 1 or from about 34 to X of Figure 10 (SEQ ID No. 20), wherein X is any amino acid residue from 199 to 208 of Figure 10 (SEQ ID No. 20), or (d) a nucleic acid sequence encoding another fragment - - specifically derived from the amino acid sequence shown in Figure 10 (SEQ ID No. 20). The PR0221 polynucleotide variants do not encompass the native PR0221 nucleotide sequence. The term "variant PR0224 polynucleotide" or "variant PR0224 nucleic acid sequence" means a nucleic acid molecule encoding an active PR0224 polypeptide as defined below and having at least about 80% nucleic acid sequence identity with: (a) a sequence of nucleic acids encoding the residues of 1 or about 31 to 282 of the polypeptide PR0224 shown in Figure 12 (SEQ ID No. 25), (b) a nucleic acid sequence encoding amino acids from X to 282 of PR0224 polypeptide shown in Figure 12 (SEQ ID No. 25), wherein X is any amino acid residue from 26 to 35 of Figure 12 (SEQ ID No. 25), (c) of amino acid 1 or of about 31 to X of Figure 12 (SEQ ID No. 25), wherein X is any amino acid residue from 226 to 235 of Figure 12 (SEQ ID No. 25), or (d) a nucleic acid sequence coding for another fragment derived specifically from the sequence of amino acids shown in Figure 12 (SEQ ID No. 25). Normally, a variant PR0224 polynucleotide will have at least about 80% of - - nucleic acid sequence identity, preferably at least about 81% nucleic acid sequence identity, more preferably at least about 82% nucleic acid sequence identity, more preferably at least about 83% nucleic acid sequence identity, more preferably at least about 84% nucleic acid sequence identity, more preferably at least about 85% nucleic acid sequence identity, more preferably at least about 86% nucleic acid sequence identity, more preferably at least about 87% nucleic acid sequence identity, more preferably at least about 88% nucleic acid sequence identity, more preferably at least about 89% nucleic acid sequence identity, more preferably at least about 90% amino acid sequence identity nucleic acids, more preferably at least about 91% nucleic acid sequence identity, more preferably at least about 92% nucleic acid sequence identity, more preferably at least about 93% i - ** j ** í * á *? íá - *? á *? ti * a *** .-, .- * itta ..---. ,, **. á. ** ,. i -í *. - nucleic acid sequence identity, more preferably at least about 94% nucleic acid sequence identity, more preferably at least about 95% nucleic acid sequence identity, more preferably at least about 96% sequence identity nucleic acids, more preferably at least about 97% nucleic acid sequence identity, more preferably at least about 98% nucleic acid sequence identity, more preferably at least about 99% nucleic acid sequence identity with: a) a nucleic acid sequence encoding the residues of 1 or approximately 31 to 282 of the polypeptide PR0224 shown in Figure 12 (SEQ ID No. 25), (b) a nucleic acid sequence encoding the amino acids from X to 282 of the PR0224 polypeptide shown in Figure 12 (SEQ ID Np. 25), in nde X is any amino acid residue from 26 to 35 of Figure 12 (SEQ ID No. 25), (c) of amino acid 1 or from about 31 to X of Figure 12 (SEQ ID No. 25), where X is any amino acid residue from 226 to 235 of Figure 12 (SEQ ID No. 25), or (d) a nucleic acid sequence encoding another fragment I? * t * Á .. _-, *** ¿JS¡lí * l *. * -: -,? - - specifically derived from the amino acid sequence shown in Figure 12 (SEQ ID No. 25). The PR0224 polynucleotide variants do not encompass the native PR0224 nucleotide sequence. The term "variant PR0328 polynucleotide" or "variant PR0328 nucleic acid sequence" means a nucleic acid molecule encoding an active PR0328 polypeptide as defined below and having at least about 80% nucleic acid sequence identity with: (a) a sequence of nucleic acids encoding the residues of 1 or about 23 to 463 of the PR0328 polypeptide shown in Figure 14 (SEQ ID No. 30), (b) a nucleic acid sequence encoding amino acids from X to 463 of the PR0328 polypeptide shown in Figure 14 (SEQ ID No. 30), wherein X is any amino acid residue from 18 to 27 of Figure 14 (SEQ ID No. 30), or (c) a nucleic acid sequence that encodes another fragment derived specifically from the amino acid sequence shown in Figure 14 (SEQ ID No. 30). Typically, a variant PR0328 polynucleotide will have at least about 80% nucleic acid sequence identity, preferably at least about 81% nucleic acid sequence identity, more preferably at least about - 82% acid sequence identity nucleic acids, more preferably at least about 83% nucleic acid sequence identity, more preferably at least about 84% nucleic acid sequence identity, more preferably at least about 85% nucleic acid sequence identity, more preferably when at least about 86% nucleic acid sequence identity, more preferably at least about 87% nucleic acid sequence identity, more preferably at least about 88% nucleic acid sequence identity, more preferably at least approximately and 89% nucleic acid sequence identity, more preferably at least about 90% nucleic acid sequence identity, more preferably at least about 91% nucleic acid sequence identity, more preferably at least about 92% identity of nucleic acid sequence, more preferably at least about 93% nucleic acid sequence identity, more preferably at least about 94% nucleic acid sequence identity, more ÁÁ.H - - preferably at least about 95% nucleic acid sequence identity, more preferably at least about 96% nucleic acid sequence identity, more preferably at least about 97% nucleic acid sequence identity, plus preferably at least about 98% nucleic acid sequence identity, more preferably at least about 99% nucleic acid sequence identity with: (a) a nucleic acid sequence encoding residues of 1 or approximately 23 to 463 of PR0328 polypeptide shown in Figure 14 (SEQ ID No. 30), (b) a nucleic acid sequence encoding amino acids X to 463 of PR0328 polypeptide shown in Figure 14 (SEQ ID No. 30) , wherein X is any amino acid residue from 18 to 27 of Figure 14 (SEQ ID No. 30), or (c) a nucleic acid sequence encoding for another fragment specifically derived from the amino acid sequence shown in Figure 14 (SEQ ID No. 30). The PR0328 polynucleotide variants do not encompass the native PR0328 nucleotide sequence. The term "variant PRO301 polynucleotide" or "variant PRO301 nucleic acid sequence" means a nucleic acid molecule that encodes a - - active PRO301 polypeptide as defined below and having at least about 80% nucleic acid sequence identity with: (a) a nucleic acid sequence coding for residues of 1 or approximately 28 to 299 of the PRO301 polypeptide shown in Figure 16 (SEQ ID No. 35), (b) a nucleic acid sequence encoding the amino acids of X to 299 of the PRO301 polypeptide shown in Figure 16 (SEQ ID No. 35), wherein X is any amino acid residue from 23 to 32 of Figure 16 (SEQ ID No. 35), (c) of amino acid 1 or from about 28 to X of Figure 16 (SEQ ID No. 35), wherein X is any amino acid residue from 230 to 239 of Figure 16 (SEQ ID No. 35), or (d) a nucleic acid sequence encoding another fragment specifically derived from the amino acid sequence shown in Figure 16 (SEQ ID No. 35). Typically, a variant PRO301 polynucleotide will have at least about 80% nucleic acid sequence identity, preferably at least about 81% nucleic acid sequence identity, more preferably at least about 82% nucleic acid sequence identity, more preferably at least about 83% nucleic acid sequence identity, more preferably at least about 84% •? i - - nucleic acid sequence identity, more preferably at least about 85% nucleic acid sequence identity, more preferably at least about 86% nucleic acid sequence identity, more preferably at least about 87% identity nucleic acid sequence, more preferably at least about 88% nucleic acid sequence identity, more preferably at least about 89% nucleic acid sequence identity, more preferably at least about 90% nucleic acid sequence identity, more preferably at least about 91% nucleic acid sequence identity, more preferably at least about 92% nucleic acid sequence identity, more preferably at least about 93% nucleic acid sequence identity, more preferably when about 94% nucleic acid sequence identity, more preferably at least about 95% nucleic acid sequence identity, more preferably at least about 96% nucleic acid sequence identity, more ? a * i - preferably at least about 97% nucleic acid sequence identity, more preferably at least about 98% nucleic acid sequence identity, more preferably at least about 99% nucleic acid sequence identity with: (a) a nucleic acid sequence encoding the residues of 1 or about 28 to 299 of the PRO301 polypeptide shown in Figure 16 (SEQ ID No. 35), (b) a nucleic acid sequence encoding the amino acids from X to 299 of the PRO301 polypeptide shown in Figure 16 (SEQ ID No. 35), wherein X is any amino acid residue from 23 to 32 of Figure 16 (SEQ ID No. 35), (c) of the amino acid 1 or from about 28 to X of Figure 16 (SEQ ID No. 35), wherein X is any amino acid residue from 230 to 239 of Figure 16 (SEQ ID No. 35), or (d) a sequence of nucleic acids that codes for another fragment specifically derived from the amino acid sequence shown in Figure 16 (SEQ ID No. 35). The PRO301 polynucleotide variants do not encompass the native PRO301 nucleotide sequence. The term "variant PR0526 polynucleotide" or "variant PR0526 nucleic acid sequence" means a nucleic acid molecule that codes for a - active PR0526 polypeptide as defined below and having at least about 80% nucleic acid sequence identity with: (a) a nucleic acid sequence encoding residues 1 or approximately 27 to 473 of PR0526 polypeptide shown in Figure 18 (SEQ ID No. 43), (b) a nucleic acid sequence encoding amino acids from X to 473 of PR0526 polypeptide shown in Figure 18 (SEQ ID No. 43), where X is any amino acid residue from 22 to 31 of Figure 18 (SEQ ID No. 43), or (c) a nucleic acid sequence encoding another fragment specifically derived from the amino acid sequence shown in Figure 18 ( SEQ ID No. 43). Typically, a variant PR0526 polynucleotide will have at least about 80% nucleic acid sequence identity, preferably at least about 81% nucleic acid sequence identity, more preferably at least about 82% nucleic acid sequence identity, more preferably at least about 83% nucleic acid sequence identity, more preferably at least about 84% nucleic acid sequence identity, more preferably at least about 85% nucleic acid sequence identity, plus - - preferably when at least about 86% nucleic acid sequence identity, more preferably at least about 87% nucleic acid sequence identity, more preferably at least about 88% nucleic acid sequence identity, more preferably at least approximately and 89% nucleic acid sequence identity, more preferably at least about 90% nucleic acid sequence identity, more preferably at least about 91% nucleic acid sequence identity, more preferably at least about 92% identity of nucleic acid sequence, more preferably at least about 93% nucleic acid sequence identity, more preferably at least about 94% nucleic acid sequence identity, more preferably at least about 95% nucleic acid sequence identity , more preferably at least about 96% nucleic acid sequence identity, more preferably at least about 97% nucleic acid sequence identity, more preferably at least about 98% MAé & AM * M * i <; **** aa - - nucleic acid sequence identity, more preferably at least about 99% nucleic acid sequence identity with: (a) a nucleic acid sequence encoding residues of 1 or approximately 27 to 473 of PR0526 polypeptide shown in Figure 18 (SEQ ID No. 43), (b) a nucleic acid sequence encoding amino acids X to 473 of PR0526 polypeptide shown in Figure 18 (SEQ ID No. 43) ), wherein X is any amino acid residue from 22 to 31 of Figure 18 (SEQ ID No. 43), or (c) a nucleic acid sequence encoding another fragment specifically derived from the amino acid sequence shown in Figure 18 (SEQ ID No. 43). The PR0526 polynucleotide variants do not encompass the native PR0526 nucleotide sequence. The term "variant PR0362 polynucleotide" or "variant PR0362 nucleic acid sequence" means a nucleic acid molecule encoding an active PR0362 polypeptide as defined below and having at least about 80% acid sequence identity nucleic acids with: (a) a nucleic acid sequence encoding the residues of 1 or about 20 to 321 of the polypeptide PR0362 shown in Figure 20 (SEQ ID No. 48), (b) a nucleic acid sequence that encode ? Ú, ****** A * J ***? ** Á tfat - - for amino acids from X to 321 of polypeptide PR0362 shown in Figure 20 (SEQ ID No. 48), where X is any amino acid residue from 15 to 20 of Figure 20 (SEQ ID No. 48), (c) of amino acid 1 or from about 20 to X of Figure 20 (SEQ ID No. 48), wherein X is any residue of amino acid from 276 to 285 of Figure 20 (SEQ ID No. 48), or (d) a nucleic acid sequence encoding another fragment specifically derived from the amino acid sequence shown in Figure 20 (SEQ ID No. 48) ). Typically, a variant PR0362 polynucleotide will have at least about 80% nucleic acid sequence identity, preferably at least about 81% nucleic acid sequence identity, more preferably at least about 82% nucleic acid sequence identity, more preferably at least about 83% nucleic acid sequence identity, more preferably at least about 84% nucleic acid sequence identity, more preferably at least about 85% nucleic acid sequence identity, more preferably at least about 86% nucleic acid sequence identity, more preferably at least about 87% nucleic acid sequence identity, more i »jj¡ & l A ***** í * Í ** AiA **? * i **** íi ** ?? * ****? ** i ******.! --a ** ».,,» & < ..ja * * _? * iA ** - ** ** ** ** i ** * ^ i ** ^ * e * A **? *? i *? .. * ^, **. .. *** * s *. * t * i * - - preferably at least about 88% nucleic acid sequence identity, more preferably at least about 89% nucleic acid sequence identity, more preferably when at least about 90% nucleic acid sequence identity, more preferably at least about 91% nucleic acid sequence identity, more preferably at least about 92% nucleic acid sequence identity, more preferably at least about 93% nucleic acid sequence identity, more preferably at least about 94% nucleic acid sequence identity, more preferably at least about 95% nucleic acid sequence identity, more preferably at least about 96% acid sequence identity nucleic acids, more preferably at least approximately 97% of the nucleic acid sequence identity, more preferably at least about 98% nucleic acid sequence identity, more preferably at least about 99% nucleic acid sequence identity with: (a) a nucleic acid sequence encoding the nucleic acid sequence IJ-á. * I?, Í. * ** 4 ** i * - - residues of 1 or about 20 to 321 of polypeptide PR0362 shown in Figure 20 (SEQ ID No. 48), (b) a nucleic acid sequence encoding amino acids from X to 321 of PR0362 polypeptide 5 shown in Figure 20 (SEQ ID No. 48), wherein X is any amino acid residue from 15 to 24 of Figure 20 (SEQ ID No 48), (c) of amino acid 1 or about 20 to X of Figure 20 (SEQ ID No. 48), wherein X is any amino acid residue of 276 10 to 285 of Figure 20 (SEQ ID No. 48), or (d) a nucleic acid sequence encoding another fragment specifically derived from the amino acid sequence shown in Figure 20 (SEQ ID No. 48). The PR0362 polynucleotide variants do not encompass the sequence of 15 nucleotides PR0362 native. The term "variant PR0356 polynucleotide" or "variant PR0356 nucleic acid sequence" means a nucleic acid molecule encoding an active PR0356 polypeptide as defined above. 20 and having at least about 80% nucleic acid sequence identity with: (a) a nucleic acid sequence encoding the residues of 1 or about 27 to 346 of the PR0356 polypeptide shown in Figure 22 ( SEQ ID No. 25 55), (b) a nucleic acid sequence encoding - - for the amino acids from X to 346 of the polypeptide PR0356 shown in Figure 22 (SEQ ID No. 55), wherein X is any amino acid residue from 22 to 31 of Figure 22 (SEQ ID No. 55), or (c) a nucleic acid sequence encoding another fragment specifically derived from the amino acid sequence shown in Figure 22 (SEQ ID No. 55). Typically, a variant PR0356 polynucleotide will have at least about 80% nucleic acid sequence identity, preferably at least about 81% nucleic acid sequence identity, more preferably at least about 82% nucleic acid sequence identity, more preferably at least about 83% nucleic acid sequence identity, more preferably at least about 84% nucleic acid sequence identity, more preferably at least about 85% nucleic acid sequence identity, more preferably at least about 86% nucleic acid sequence identity, more preferably at least about 87% nucleic acid sequence identity, more preferably at least about 88% nucleic acid sequence identity, more preferably at least about 89% of - nucleic acid sequence identity, more preferably at least about 90% nucleic acid sequence identity, more preferably at least about 91% nucleic acid sequence identity, more preferably at least about 92% sequence identity of nucleic acids, more preferably at least about 93% nucleic acid sequence identity, more 10 preferably at least about 94% nucleic acid sequence identity, more preferably at least about 95% nucleic acid sequence identity, more preferably at least about 96% 15 nucleic acid sequence identity, more preferably at least about 97% nucleic acid sequence identity, more preferably at least about 98% nucleic acid sequence identity, more Preferably at least about 99% nucleic acid sequence identity with: (a) a nucleic acid sequence encoding the residues of 1 or about 27 to 346 of the PR0356 polypeptide shown in Figure 22 (SEQ ID No. 55), 25 (b) a nucleic acid sequence encoding the - - amino acids from X to 346 of the PR0356 polypeptide shown in Figure 22 (SEQ ID No. 55), wherein X is any amino acid residue from 22 to 31 of Figure 22 (SEQ ID No. 55), or (c ) a nucleic acid sequence encoding another fragment specifically derived from the amino acid sequence shown in Figure 22 (SEQ ID No. 55). The PR0356 polynucleotide variants do not encompass the native PR0356 nucleotide sequence. The term "variant PRO509 polynucleotide" or "variant PRO509 nucleic acid sequence" means a nucleic acid molecule encoding an active PRO509 polypeptide as defined below and having at least about 80% acid sequence identity nucleic acids with: (a) a nucleic acid sequence encoding the residues of 1 or approximately 37 to 283 of the PRO509 polypeptide shown in Figure 24 (SEQ ID No. 60), (b) a nucleic acid sequence that encodes for amino acids from X to 283 the PRO509 polypeptide shown in Figure 24 (SEQ ID No. 60), wherein X is any amino acid residue 32 to 41 of Figure 24 (SEQ ID No. 60), (c) of amino acid 1 or about 37 to X of Figure 24 (SEQ ID No. 60), wherein X is any amino acid residue from 200 to 209 of Figure 24 (SEQ ID No. 60), or (d) a nucleic acid sequence áAl á, IttátA - - coding for another fragment derived specifically from the amino acid sequence shown in Figure 24 (SEQ ID No. 60). Typically, a variant PRO509 polynucleotide will have at least about 80% nucleic acid sequence identity, preferably at least about 81% nucleic acid sequence identity, more preferably at least about 82% nucleic acid sequence identity, more preferably at least about 83% nucleic acid sequence identity, more preferably at least about 84% nucleic acid sequence identity, more preferably at least about 85% nucleic acid sequence identity, more preferably at least about 86% nucleic acid sequence identity, more preferably at least about 87% nucleic acid sequence identity, more preferably at least about 88% nucleic acid sequence identity, more preferably at least about 89 % nucleic acid sequence identity, more preferably at least about 90% nucleic acid sequence identity, more preferably at least about 91% & * iiA.aiá .¿ -i .j-ai.-4. ¿¿, aiá. tea. i *****. **. *. - - nucleic acid sequence identity, more preferably at least about 92% nucleic acid sequence identity, more preferably at least about 93% nucleic acid sequence identity, more preferably at least about 94% sequence identity of nucleic acids, more preferably at least about 95% nucleic acid sequence identity, more preferably at least about 96% nucleic acid sequence identity, more preferably at least about 97% nucleic acid sequence identity, more preferably at least about 98% nucleic acid sequence identity, more preferably at least about 99% nucleic acid sequence identity with: (a) a nucleic acid sequence encoding residues of 1 or approximately 37 to 283 of the PRO509 polypeptide Figure 24 (SEQ ID No. 60), (b) a nucleic acid sequence encoding amino acids from X to 283 of the PRO509 polypeptide shown in Figure 24 (SEQ ID No. 60), wherein X is any amino acid residue 32 to 41 of Figure 24 (SEQ ID No. 60), (c) of amino acid 1 or about - - from 37 to X of Figure 24 (SEQ ID No. 60), wherein X is any amino acid residue from 200 to 209 of Figure 24 (SEQ ID No. 60), or (d) an acid sequence nucleic acid coding for another fragment derived specifically from the amino acid sequence shown in Figure 24 (SEQ ID No. 60). The PRO509 polynucleotide variants do not encompass the native PRO509 nucleotide sequence. The term "variant PR0866 variant polynucleotide" or "variant PR0866 nucleic acid sequence" means a nucleic acid molecule encoding an active PR0866 polypeptide as defined below and having at least about 80% acid sequence identity nucleic acids with: (a) a nucleic acid sequence encoding the residues of 1 or approximately 27 to 331 of the polypeptide PR0866 shown in Figure 26 (SEQ ID No. 62), (b) a nucleic acid sequence that encodes for amino acids from X to 331 of polypeptide PR0866 shown in Figure 26 (SEQ ID No. 62), wherein X is any amino acid residue from 22 to 31 of Figure 26 (SEQ ID No. 62), or ( c) a nucleic acid sequence encoding another fragment specifically derived from the amino acid sequence shown in Figure 26 (SEQ ID No. 62). Normally, a variant PR0866 polynucleotide will have at least about 80% of Ai? .ii.ii? IÍ ** á¡, t¡ ****! * SáA? Ák * ******* *****. ***: & * aát-.a. to? . jBiMMBk.it tafaA »- - nucleic acid sequence identity, preferably at least about 81% nucleic acid sequence identity, more preferably at least about 82% nucleic acid sequence identity, more preferably at least about 83 % nucleic acid sequence identity, more preferably at least about 84% nucleic acid sequence identity, more preferably at least about 85% nucleic acid sequence identity, more preferably at least about 86% sequence identity of nucleic acids, more preferably at least about 87% nucleic acid sequence identity, more preferably at least about 88% nucleic acid sequence identity, more preferably at least about 89% nucleic acid sequence identity, more preferable at least about 90% nucleic acid sequence identity, more preferably at least about 91% nucleic acid sequence identity, more preferably at least about 92% nucleic acid sequence identity, more preferably at least about 93 % from ? i * A ** h * A? áJ ******* x **? * Ja »á- * - - nucleic acid sequence identity, more preferably at least approximately 94% acid sequence identity nucleic acids, more preferably at least about 95% nucleic acid sequence identity, more preferably at least about 96% nucleic acid sequence identity, more preferably at least about 97% nucleic acid sequence identity, more preferably when at least about 98% nucleic acid sequence identity, more preferably at least about 99% nucleic acid sequence identity with: (a) a nucleic acid sequence coding for residues of 1 or approximately 27 to 331 of PR0866 polypeptide shown in Figure 26 (SEQ ID No. 62), (b) a nucleic acid sequence encoding amino acids from X to 331 of the PR0866 polypeptide shown in Figure 26 (SEQ ID No. 62), where X is any amino acid residue from 22 to 31 of Figure 26 (SEQ ID No. 62), or (c) a nucleic acid sequence encoding another fragment specifically derived from the amino acid sequence shown in Figure 26 (SEQ ID No. 62). The PR0866 polynucleotide variants do not encompass the native PR0866 nucleotide sequence. ** Íltí * Á, £. ? Á- * i.? Ll ai.-a.a- - - Typically, the variant polynucleotides PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509, and PR0866, are approximately 30 nucleotides in length, often at least approximately 60 nucleotides in length, plus often at least about 90 nucleotides in length, more often at least about 120 nucleotides in length, more often at least about 150 nucleotides in length, more often at least about 180 nucleotides in length, more often at least about 210 nucleotides in length, more often at least approximately 240 nucleotides in length, more often at least approximately 270 nucleotides in length, more often at least approximately 300 nucleotides in length, more often at least approximately 450 nucleotides in length, more often at least approximately 600 nucleotides in length, more s often at least about 900 nucleotides in length or more. The term "percentage (%) of nucleic acid sequence identity" with respect to the nucleic acid sequences that qualify for PR0179 polypeptides, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866 identified herein, is defined as the percentage of nucleotides, in a candidate sequence, that are identical to the nucleotides of a nucleic acid sequence encoding PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0301, PR0526, PR0362, PR0356, PRO509 and PR0866 polypeptides, after aligning the sequences and inserting gaps, if necessary, to achieve the maximum percentage of sequence identity. Alignment for the purposes of determining the percentage of nucleic acid sequence identity can be carried out in various ways, which are well within the knowledge of those skilled in the art, for example, using computer software available to the public such such as BLAST, BLAST-2, ALIGN, ALIGN-2 or Megalign (DNASTAR). Those skilled in the art can determine the appropriate parameters to measure the alignment, including any algorithm necessary to achieve maximum alignment over the full length of the sequences being compared. However, for the purposes of the present, the nucleic acid sequence identity% values are obtained in the manner described below using the ALIGN-2 sequence comparison computer program, wherein the code The complete source code for the ALIGN-2 program is provided in Table 1. The ALIGN-2 sequence comparison computer program was authorized by - - Genentech, Inc. and the source code shown in Table 1 was presented with user documentation at the Copyright Office of the United States, Washington DC, 20559, where it is registered with the Registration Number of Copyright Rights Copyright USTXU510087. The 7? LIGN-2 program is available to the public through Genentech, Inc., South San Francisco, California or can be compiled from the source code provided in Table 1. The ALIGN-2 program must be compiled for use in a UNIX operating system, preferably UNIX digital VA.OD. All sequence comparison parameters are set by the ALIGN-2 program and do not vary. For the purposes of the present, the% nucleic acid sequence identity of a given C nucleic acid sequence, with or against a nucleic acid sequence D (which alternatively can be considered as a nucleic acid sequence C having or comprises certain% nucleic acid sequence identity with or against a given D nucleic acid sequence), is calculated as follows: 100 times the W / Z fraction where W is the number of nucleotides that qualified as identical matings by the alignment program of sequences ALIGN-2 in the alignment of C and D, and where Z - - is the total number of nucleotides in D. It will be noted that when the length of nucleic acid sequence C is not equal to the length of the nucleic acid sequence D, the% nucleic acid sequence identity of C with respect to D will not be equal to the% nucleic acid sequence identity of D with respect to C. or examples of% nucleic acid sequence identity calculations, Tables 2C-2D demonstrate how to calculate the% nucleic acid sequence identity of the Sequence designated as ".DNA of comparison" with respect to the nucleic acid sequence designated "DNA-PRO". Unless otherwise specifically stated, all values of identity% of The sequence of nucleic acids used herein is obtained in the manner described above using the ALIGN-2 sequence comparison computer program. However, the% nucleic acid sequence identity can also be determined using the 20 NCBI-BLAST2 sequence comparison program (Altschul et al., Nucleic Acids Res., 25: 3389-3402 (1997)). The NCBI-BLAST2 sequence comparison program can be downloaded from the website http: //www.ncbi .nlm.nih.gov. The NCBI-BLAST2 program uses several search parameters, 25 where all the search parameters are - - established in the default values including, for example, unmask = yes, strand = all, expected occurces = 10, minimun low complexity length = 15/5, multip-pass e- value = 0.01, constant for multip-pass = 25, dropoff for 5 final alignment = 25 and scoring matrix = BLOSUM62. In situations where the NCBI-BLAST2 is used for sequence comparisons, the% nucleic acid sequence identity of a given C nucleic acid sequence, with or against a given D-nucleic acid sequence (which can alternatively be consider as a given C nucleic acid sequence having or comprising certain% nucleic acid sequence identity with or against a given D nucleic acid sequence), calculated as follows: 15 100 times the W / Z fraction where W is the number of nucleotides that qualify as identical matings by the alignment program of 20 NCBI-BLAST2 sequences in the alignment of C and D, and where Z is the total number of nucleotides in D. It will be noted that when the length of the C nucleic acid sequence is not equal to the length of the acid sequence D nucleic acid,% acid sequence identity 25 nuclei of C with respect to D will not be equal to% of - - nucleic acid sequence identity of D with respect to C. In addition,% nucleic acid sequence identity values can also be generated using the WU-BLAST-2 computer program (Altschul et al., Methods in Enzumology, 265: 460-480 (1996)). Most of the WU-BLAST-2 search parameters are set to default values. Those that are not values established by default, i.e. the adjustable parameters are established with the following values: overlap span = 1, overlap fraction = 0.125, word threshold (T) = 11, and scoring matrix = BLOSUM62. For purposes of the present, a value of% nucleic acid sequence identity is determined by dividing (a) the number of identical paired nucleotides between the nucleic acid sequence of the nucleic acid molecule encoding the PRO polypeptide of interest having a sequence derived from a nucleic acid encoding the native sequence PRO polypeptide and the comparison nucleic acid molecule of interest (ie, the sequence against which the nucleic acid molecule encoding the PRO peptide of interest is being compared , which may be a variant PRO polynucleotide) as determined in the WU-BLAST-2 program, between (b) the total number of nucleotides of the nucleic acid molecule encoding the PRO polypeptide of interest. For example, the phrase "an isolated nucleic acid molecule comprising a nucleic acid sequence A having at least 80% nucleic acid sequence identity with the nucleic acid sequence B", the nucleic acid sequence A is the comparative nucleic acid molecule of interest and nucleic acid sequence B is the nucleic acid sequence of the nucleic acid molecule encoding the PRO polypeptide of interest. In another embodiment, the variant polynucleotides PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866 are nucleic acid molecules that encode a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 active, respectively, and which are capable of hybridizing, preferably under stringent hybridization and washing conditions, with nucleotide sequences encoding the PR0179 polypeptide of full length shown in Figure 2 (SEQ ID NO: 2), with the nucleotide sequences encoding the full-length PRO207 polypeptide shown in Figure 4 (SEQ ID NO: 7), with the nucleotide sequences coding for the full-length PRO320 polypeptide shown in Figure 6 (SEQ ID ? ** ?., * -. ii:. *.! - * *** ll *. * ** **** &! * & »? * *.? - - NO: 10), with the nucleotide sequences encoding the full length PR0219 polypeptide shown in Figure 8 (SEQ ID NO: 15), with the nucleotide sequences encoding the full length PR0221 polypeptide shown in Figure 10 (SEQ ID NO: 20), with the nucleotide sequences encoding the full-length PR0224 polypeptide shown in Figure 12 (SEQ ID NO: 25), with the nucleotide sequences encoding the full-length PR0328 polypeptide shown in Figure 14 (SEQ ID NO: 30), with the nucleotide sequences encoding the full-length PRO301 polypeptide shown in Figure 16 (SEQ ID NO: 35), with the nucleotide sequences encoding the polypeptide Full length PR0526 shown in Figure 18 (SEQ ID NO: 43), with the nucleotide sequences encoding the full length PR0362 polypeptide shown in Figure 20 (SEQ ID NO: 48), with the nucleotide sequences encoding the full-length PR0356 polypeptide shown in Figure 22 (SEQ ID NO: 55), with the nucleotide sequences encoding the full-length PRO509 polypeptide shown in Figure 24 (SEQ ID NO: 60), with the nucleotide sequences encoding the full length PR0866 polypeptide shown in Figure 26 (SEQ ID NO: 62), - - respectively. The variant polypeptides PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866 can be those that are encoded by a polynucleotide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328 , PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 variant. The term "positives" in the context of amino acid sequence identity comparisons performed in the manner described above, includes amino acid residues in the compared sequences that are not only identical, but also those that have similar properties. The amino acid residues that qualify for a positive value with an amino acid residue of interest, are those that are either identical to the amino acid residue of interest, or are a preferred substitution (as defined in Table 3 below). presented below) of the amino acid residue of interest. For purposes of the present, the value of% of positives of an amino acid sequence A given with or against a given amino acid sequence B (which alternatively can be considered as a given amino acid sequence A having or comprising a certain% of positive with or against a given amino acid sequence B), is calculated as follows: tfc ri * - > seSátáti. **! ** .. * * ÍL *. r * ***, * *. - - 100 times the fraction X / Y where X is the number of amino acid residues that qualify for a positive value as defined above, by the alignment program of sequences ALIGN-2 in the alignment of A and B, and where Y is the total number of residues of amino acid in B. It will be noted that when the length of the amino acid sequence A is not equal to the length of the amino acid sequences B, the% positive of A with respect to B will not be equal to the% of positive of B with with respect to A. The term "isolated" when used to describe the various polypeptides herein, means a polypeptide that has been identified and separated and / or recovered from a component of its natural environment. Preferably, the isolated polypeptide is free of association with any component with which it is naturally associated. The contaminating components of their natural environment are materials that would typically interfere with the diagnostic or therapeutic uses of the polypeptide and could include enzymes, hormones and other protein or non-protein solutes. In preferred embodiments, the polypeptide will be purified (1) to a sufficient degree to obtain at least 15 residues of the N-terminal or internal amino acid sequence, by - - the use of a rotating cup sequencer or (2) up to homogeneity by SDS-PAGE, under reducing or non-reducing conditions, using Coomassie blue staining or, preferably, silver staining. The isolated polypeptide includes the polypeptide itself within the recombinant cells, since at least one component of the natural environment of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 will not be present However, normally the isolated polypeptide will be prepared by at least one purification step. An "isolated" nucleic acid molecule encoding a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or an "isolated" nucleic acid molecule encoding for an anti-PR0179 antibody, anti-PR? 207, anti-PRO320, anti-PR0219, anti-PR0221, anti-PR0224, anti-PR0328, anti-PRO301, anti-PR0526, anti-PR0362, anti-PR0356, anti- PRO509 or anti-PR0866, is a nucleic acid molecule that is identified and separated from at least one contaminating nucleic acid molecule that is normally associated in the natural source of the nucleic acid encoding PR0179-, PRO207-, PRO320-, PR0219- , PR0221-, PR0224-, PR0328-, PRO301-, PR0526-, PR0362-, PR0356-, PRO509- or PR0866- or encoding nucleic acid ? íl * *? * íí¿?,? t '? r? * - h * .. * A *. * t .-., .. * ,. _. ,, ... "- ... - **, i. i. * "- - of anti-PR0179-, anti-PRO207-, anti-PRO320-, anti-PR0219-, anti-P.R0221-, anti-PR0224-, anti-PR0328-, anti-PR0301-, anti-PR0526 -, anti-PR0362-, anti-PR0356-, anti-PRO509- or anti-PR0866-. Preferably, the isolated nucleic acid is free of associations with all the components with which it is associated in nature. A nucleic acid molecule encoding PR0179-, PRO207-, PRO320-, PR0219-, PR0221-, PR0224-, PR0328-, PRO301-, PR0526-, PR0362-, PR0356-, PRO509- or PR0866- or an acid molecule nucleic encoder for anti-PR0179-, anti-PRO207-, anti-PRO320-, anti-PR0219-, anti-PR0221-, anti-PR0224-, anti-PR0328-, anti-PRO301-, anti-PR0526-, anti- PR0362-, anti-PR0356-, anti-PRO509- or anti-PR0866- is different from the way it is found in nature. Therefore, the isolated nucleic acid molecules are distinguished from the nucleic acid molecules encoding PR0179-, PRO207-, PRO320-, PR0219-, PR0221-, PR0224-, PR0328-, PRO301-, PR0526-, PR0362-, PR0356-, PRO509- or PR0866- or nucleic acid molecules encoding anti-PR0179-, anti-PRO207-, anti-PRO320-, anti-PR0219-, anti-PR0221-, anti-PR0224-, anti-PR0328 -, anti-PRO301-, anti-PR0526-, anti-PR0362-, anti-PR0356-, anti-PRO509- or anti-PR0866-, because it exists in natural cells. However, an isolated nucleic acid molecule encoding a PR0179, PRO207, PRO320 polypeptide, - PR0219, PR0221, PR0224, PR0328, PR0301, PR0526, PR0362, PR0356, PRO509 or PR0866 or an isolated nucleic acid molecule that codes for an anti-PR0179 antibody, anti-PRO207, anti-PRO320, anti-PR0219, anti-PR0221 , anti-PR0224, anti-PR0328, anti-PRO301, anti-PR0526, anti-PR0362, anti-PR0356, anti-PR? 509 or anti-PR0866 includes nucleic acid molecules that encode PR0179-, PRO207-, PRO320- , PR0219-, PR0221-, PR0224-, PR0328-, PRO301-, PR0526-, PR0362-, PR0356-, PRO509- or PR0866- or nucleic acid molecules that code for anti-PR0179-, anti-PRO207-, anti- PRO320-, anti-PR0219-, anti-PR0221-, anti-PR0224-, anti-PR0328-, anti-PRO301-, anti-PR0526-, anti-PR0362-, anti-PR0356-, anti-PR? 509- anti-PR0866- contained in cells that ordinarily express polypeptides PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or anti-PR0179 antibodies, anti-PRO207, anti-PRO320, anti-PR0219, anti-PR0221, anti-PR0224, anti i-PR0328, anti-PRO301, anti-PR0526, anti-PR0362, anti-PR0356, anti-PRO509 or anti-PR0866, wherein, for example, the nucleic acid molecule is in a chromosomal location different from that of the cells natural The term "control sequences" refers to DNA sequences necessary for the expression of a coding sequence operably linked in a Lia ** *****. * - A ^ ai. - - particular host organism. The control sequences that are suitable for prokaryotic cells, for example, include a promoter, optionally an operator sequence and a ribosome binding site. Eukaryotic cells are known to use promoters, polyadenylation signals and enhancers. A nucleic acid is "operably linked" when placed in a functional relationship with another nucleic acid sequence. For example, the DNA of a presequence or secretory leader is operably linked to the DNA of a polypeptide if it is expressed as a protein that participates in the secretion of the polypeptide; a promoter or enhancer is operably linked to a coding sequence, if it affects the transcription of said sequence; or a ribosome binding site is operably linked to a coding sequence, if it is positioned in such a way as to facilitate translation. Generally, the term "operably linked" means that the. sequences of .ADN that are being linked, are contiguous and, in the case of a secretory leader, they are contiguous and are within the reading phase. However, the intensifiers do not have to be contiguous. Linkage is achieved by ligating at convenient restriction sites. If such sites do not exist, oligonucleotide-synthetic adapters or linkers are used, in accordance with conventional practice. The term "antibody" is used in the broadest sense and specifically covers, for example, anti-PR0179 monoclonal antibodies, anti-PRO207, anti-PRO320, anti-PR0219, anti-PR0221, anti-PR0224, anti-PR0328, anti -PRO301, anti-PR0526, anti-PR0362, anti-PR0356, anti-PRO509 and anti-PR0866 (including agonist antibodies), anti-PR0179, anti-PRO207, anti-PRO320, anti-PR0219, anti-PR0221 , anti-PR0224, anti-PR0328, anti-PRO301, anti-PR0526, anti-PR0362, anti-PR0356, anti-PRO509 and anti-PR0866 with polyepitopic specificity, anti-PR0179, anti-PRO207, anti-PRO320, anti - PR0219, anti-PR0221, anti-PR0224, anti-PR0328, anti-PRO301, anti-PR0526, anti-PR0362, anti-PR0356, anti-PRO509 and anti-PR0866, single-chain and anti-PR0179 antibody fragments , anti-PRO207, anti-PRO320, anti-PR0219, anti-PR0221, anti-PR0224, anti-PR0328, anti-PRO301, anti-PR0526, anti-PR0362, anti-PR0356, anti-PRO509 and anti-PR0866 (see later) . The term "monoclonal antibody" as used herein, refers to an antibody obtained from a population of substantially homogeneous antibodies, ie, the individual antibodies comprising the population are identical, except for possible mutations of natural origin that could be present ? L. í? iá.aa J. *, * '. iL * \ i, - - in smaller quantities. The "stringency" of the hybridization reactions is easily determined by a person skilled in the art and is generally an empirical calculation, depending on the length of the probe, the temperature of the wash and the salt concentration. In general, longer probes require higher temperatures for proper pairing, while short probes require lower temperatures. Hybridization generally 10 depends on the ability of the denatured .DNA to re-pair when complementary strands are present in an environment below its melting temperature. The higher the desired degree of homology between the probe and the hybridizable sequence, the higher the 15 relative temperature that can be used. As a result, the higher relative temperatures would tend to make the reaction conditions more stringent (strict), while the lower temperatures would be less stringent. For additional details and 20 explanation of the rigor of the hybridization reactions, see Ausubel et al. Current Protocols Molecular Biology, Wiley Interscience Publishers, (1995). The term "stringent conditions" or "highly stringent conditions" as defined herein, 25 can be identified by those who: (1) employ a - - low ionic strength and a high temperature for washing, for example 0.015M sodium chloride / 0.0015M sodium citrate / 0.1% sodium dodecyl sulfate, at 50 ° C; (2) employ during the hybridization a denaturing agent such as formamide, for example, 50% formamide (v / v) with 0.1% bovine serum albumin / 0.1% Ficol / 0.1% polyvinylpyrrolidone / sodium phosphate buffer 50 mM, at pH 6.5, with 750 mM sodium chloride, 75 mM sodium citrate at 42 ° C; or (3) employ 50% formamide, 5 x SSC (0.75M NaCl, 0.075M sodium citrate), 50 mM sodium phosphate (pH 6.8), 0.1% sodium pyrophosphate, 5 x Denhardt's solution, sonicated salmon sperm (50 μg / mL), 0.1% SDS and 10% dextran sulfate, at 42 ° C, washed at 42 ° C in 0.2 x SSC (sodium chloride / sodium citrate) and 50% of formamide at 55 ° C, followed by a highly stringent wash consisting of 0.1 x SSC containing AEDT at 55 ° C. The "moderately strict conditions" can be identified as those described by Sambrook et al. Molecular Cloning: A. Laboratory Manual, New York: Cold Spring Harbor Press, 1989, and include the use of a washing solution and hybridization conditions (eg, temperature, ionic strength and% SDS) less stringent than those previously described . An example of moderately strict conditions is to incubate overnight at 37 ° C in a solution comprising: 20% formamide, 5 x SSC "~? * á ** * J * i,: * ti * ii.i ,. - - (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5 x Denhardt's solution, 10% dextran sulfate and 20 mg / mL 7 'DN of cut and denatured salmon sperm, followed by washes of the filters with 1 x 5 SSC at approximately 37-50 ° C. Those skilled in the art will recognize how to adjust the temperature, ionic strength, etc., as necessary, to accommodate factors such as the length of the probe and the like. The term "marked epitope" when used in The present invention relates to a chimeric polypeptide comprising a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 fused to a "tag polypeptide". The brand polypeptide has enough residues to 15 provide an epitope against which an antibody can be prepared, but is short enough such that it does not interfere with the activity of the polypeptide with which it is fused. The brand polypeptide of preference is also unique, such that the 20 antibodies do not show substantial cross-reactions with other epitopes. Such label polypeptides generally have at least six amino acid residues and typically have between about 8 and 50 amino acid residues (preferably between 25 approximately 10 and 20 amino acid residues).

- - As used herein, the term "immunoadhesin" designates antibody-like molecules that combine the binding specificity of a heterologous protein (an "adhesin") with the effector functions of the constant domains of the immunoglobulins. Structurally, the immunoadhesins comprise a fusion of an amino acid sequence with the desired binding specificity that is different from the site of recognition and binding of antigens that the antibodies present (i.e., is "heterologous") and an immunoglobulin constant domain sequence. The adhesin part of an immunoadhesin molecule is typically a sequence of contiguous amino acids comprising at least the binding site of a receptor or a ligand. The sequence of the immunoglobulin constant domain in the immunoadhesin can be obtained from any immunoglobulin, such as the subtypes IgG-1, IgG-2, IgG-3 or IgG-4, IgA (including IgA-1 and IgA-2), IgE, IgD or IgM. The terms "active" or "activity" for the purposes herein, refer to forms of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 that retain a biological and / or immunological activity of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 of natural or native origin, . A? L. ,, a., aa "- - where the term" biological "activity refers to biological function (whether inhibitory or stimulating) caused by PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526 , PR0362, PR0356, PRO509 or PR0866 of natural or native origin different from the capacity and induce the production of an antibody against an antigenic epitope possessed by a PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362 , PR0356, PRO509 or PR0866 of natural or native origin and an "immunological" activity refers to the ability to induce the production of an antibody against an antigenic epitope possessed by a PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 of natural or native origin. The "biological activity" in the context of an antibody or other agonist that can be identified by the screening assays described herein (eg, a small organic or inorganic molecule, peptide, etc.) is used to refer to the ability of Such molecules induce one or more of the effects listed herein in connection with the definition of a "therapeutically effective amount". In a specific embodiment, "biological activity" is the ability to inhibit the growth of neoplastic cells or their proliferation. A preferred biological activity is inhibition, including Ííi * i l. ** á *? k * - * Á * * l * - * i * * .....-. - - slowing down or completely stopping the growth of a white tumor cell (e.g., cancer). Another preferred biological activity is the cytotoxic activity that results in the death of the white tumor cell (e.g., cancer). Still another preferred biological activity is the induction of apoptosis of a white tumor cell (e.g., cancer). The phrase "immunological activity" means immunological cross-reactivity with at least one epitope of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. The term "immunological cross-reactivity" as used herein, means that the candidate polypeptide is capable of competitively inhibiting the qualitative biological activity of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 having this activity, with ppliclonal antisera directed against PR0179, PRO207, PRO320, PR0219, PR0221, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 known active polypeptides. Such antisera are prepared in the conventional manner by injecting goats or rabbits, for example, subcutaneously, with the known active analogue, mixing in complete Freund's adjuvant, * 1 *? * \ ** i - - followed by an intraperitoneal or subcutaneous reinforcement in Freund's complete adjuvant. The immunological cross-reactivity is preferably "specific", which means that the binding affinity of the immunological cross-reactive molecule (eg, antibody) identified, with the corresponding PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328 polypeptide. , PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866, is significantly greater (preferably at least about 2 times greater, more preferably at least about 4 times greater, even more preferably at least about 6 times greater, more preferably at least about 8 times greater) than the binding affinity of the molecule for another known native polypeptide. The term "tumor" as used herein, refers to any growth and proliferation of neoplastic cells, whether malignant or benign, and to all precancerous or cancerous cells and tissues. The terms "cancer" and "cancerous" refer to or describe the physiological condition, in mammals, which is typically characterized by the uncontrolled growth of cells. Examples of cancer include, but are not limited to, carcinoma, lymphoma, blastoma, sarcoma, and leukemia.

- - More particular examples of such cancers include breast cancer, prostate cancer, colon cancer, squamous cell cancer, small cell lung cancer, non-small cell lung cancer, ovarian cancer, cervical cancer, gastrointestinal cancer, pancreatic cancer, glioblastoma, liver cancer, bladder cancer, hepatoma, colorectal cancer, endometrial carcinoma, salivary gland carcinoma, kidney cancer, vulvar cancer, thyroid cancer, hepatic carcinoma and various types of head and neck cancer. A "treatment" is an intervention performed with the intention of preventing development to alter the pathology of a disorder. Accordingly, the term "treatment" refers to both a therapeutic and prophylactic treatment and preventive measures. Those in need of treatment include subjects already suffering from the disorder as well as subjects in whom the disorder is to be prevented. In the treatment of tumors (e.g., cancer), a therapeutic agent could directly decrease the pathology of tumor cells or make the tumor cells more susceptible to treatment with other therapeutic agents, e.g. radiation and / or chemotherapy. The "pathology of cancer" includes any phenomenon that compromises the well-being of the patient. This - - includes, without limitation, the abnormal or uncontrollable growth of cells, metastasis, interference with the normal functioning of neighboring cells, the release of cytokines or other secretory products to abnormal levels, the suppression or aggravation of the inflammatory or immunological response, etc. An "effective amount" of a polypeptide described herein or an agonist thereof, in reference to the inhibition of growth of neoplastic cells, is an amount capable of inhibiting, to some extent, the growth of target cells. The term includes an amount capable of inducing a growth inhibitory, cytostatic and / or cytotoxic effect and / or apoptosis of target cells. An "effective amount" of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or an agonist thereof, for the purposes of inhibiting the growth of neoplastic cells, it can be determined empirically and in a ruthless manner. A "therapeutically effective amount" in reference to the treatment of tumors, refers to an amount capable of inducing one or more of the following effects: (1) inhibition, to some extent, of tumor growth, including slowing growth and stop it completely; (2) reducing the number of ? iáut't Í v., a, j.t.jntMt ...?. t í * - - tumor cells; (3) reduction of tumor size; (4) the inhibition (i.e., reduction, slow down or completely stop) of the infiltration of tumor cells into peripheral organs; (5) inhibition (ie, reduction, slowing or stopping completely) of the metastasis; (6) the intensification of the antitumor immune response, which could, but does not have to, result in regression or rejection of the tumor; and / or (7) the relief, to some extent, of one or more symptoms associated with the disorder. A "therapeutically effective amount" of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or an agonist thereof, for the purposes of tumor treatment, may be determine empirically and routinely. A "growth inhibitory amount" of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or an agonist thereof, is an amount capable of inhibiting the growth of a cell, especially tumor, eg a cancer cell, either in vi tro or in vivo. A "growth inhibitory amount" of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or an agonist thereof for the purpose of inhibiting growth of iA &d? * AJk &e ** L * í - - neoplastic cells, can be determined empirically and routinely. A "cytotoxic amount" of a PR0179 polypeptide, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or an agonist thereof, is an amount capable of causing the destruction of a cell , especially tumor, eg a cancer cell, either in vi tro or in vivo. A "cytotoxic amount" of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or an agonist thereof for the purposes of inhibiting the growth of neoplastic cells, is it can be determined empirically and routinely. The term "cytotoxic agent" as used herein, refers to a substance that inhibits or prevents the function of cells and / or causes the destruction of cells. The term is intended to include radioactive isotopes (e.g., 131 I, 125 I, 90 Y and 18 d Re), chemotherapeutic agents and toxins such as enzymatically active toxins of bacterial, fungal, plant or animal origin, or fragments thereof. A "chemotherapeutic agent" is a chemical compound useful in the treatment of tumors, e.g. Cancer. Examples of chemotherapeutic agents include - - adriamycin, doxorubicin, epirubicin, 5-fluorouracil, cytosine arabinoside ("Ara-C"), cyclophosphamide, thiotepa, busulfan, cytoxin, taxoids, eg, paclitaxel (Taxol, Bristol-Myers Squibb Oncology, Princeton, NJ) and doxetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, Rnace), toxotere, methotrexate, cis-platinum, melphalan, vinblastine, bleomycin, etoposide, ifosfamide, mitomycin C, mitoxantrone, vincristine, vinorrelbine, carboplatin, teniposide, dauno icine, carminomycin, aminopterin, dactinomycin, mitomycins, esperamycins (see US Patent No. 4,675,187), melphalan and nitrogen mustards. Also included in this definition are hormonal agents that act to regulate or inhibit the hormonal action on tumors, such as tamoxifen and onapristone. The term "growth inhibitory agent" as used herein, refers to a compound or composition that inhibits the growth of a cell, especially tumor, e.g., a cancer cell, either in vi tro or in vivo. Thus, the growth inhibitory agent is one that significantly reduces the percentage of S-phase target cells. Examples of growth inhibitory agents include agents that block the progress of the cell cycle (in a different place than the S phase), such as agents that induce HÜ j p .í - l-1 *.! * .. * i ** .., kMs- * ii.?.

- - Gl arrest and M-phase arrest. Classical M-phase blockers include vincas (vincristine and vinblastine), taxol and topo II inhibitors such as doxorubicin, epirubicin, daunorubicin, etoposide and bleomycin. Agents that stop the Gl phase can also stop the S phase, for example, DNA alkylating agents such as tamoxifen, prednisone, dacarbazine, mechlorethamine, cis-platinum, methotrexate, 5-fluorouracil and Ara-C. Additional information can be found in The Molecular Basis of Cancer, Mendelsohn and Israel, eds. Chapter 1, entitled "Cell Cycle regulation, oncogenes, and antineoplastic drugs" by Murakami et al. , (WB Saunders: Philadelphia, 1995), especially p. 13. The term "cytochrome" is a generic term for proteins released by a population of cells, which act on another cell as intercellular mediators. Examples of such cytokines are lymphokines, monokines and traditional polypeptide hormones. Growth hormone, such as human growth hormone, N-methionyl human growth hormone and bovine growth hormone, are included among the cytokines; the parathyroid hormone; thyroxine; insulin; proinsulin; relaxin; Prorrelaxin; glycoprotein hormones such as follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH) and luteinizing hormone - '* #' - - (LH); liver growth factor; fibroblast growth factor; prolactin; placental lactogen; tumor necrosis factor-a and -β; Mulerian inhibitory substance; peptide associated with murine gonadotropin; inhibin; activin; Vascular endothelial growth factor; integrin; thrombopoietin (TPO); nerve growth factors such as NGF-β; platelet growth factor; Transforming growth factors (FCTs) such as FCT-a and FCT-β; growth factor similar to insulin-I and -II; erythropoietin (EPO); osteoinductive factors; interferons such as interferon-a, -β and - ?; colony stimulating factors (FEC) such as FEC of macrophages (FEC-M); FEC of granulocytes-macrophages (FEC-GM) and FEC of granulocytes (FEC-G); interleukins (IL) such as IL-1, IL-la, IL-2, IL-3, IL-4, IL-5, IL-6, IL-17, IL-8, IL-9, IL-11, IL- 12; a tumor necrosis factor such as TNF-a or TNF-β; and other polypeptide factors including LIF and ligand kit (KL). As used herein, the term cytokine includes proteins of natural origin or from recombinant cell cultures and biologically active equivalents of the native sequence cytokines. The term "prodrug" as used in the ú-.L? * la.hA ^? *!,? .. M *, *, - - present application, refers to a precursor or a derivative form of a pharmaceutically active substance that is less cytotoxic for tumor cells compared to the drug progenitor, and that is capable of being activated or converted enzymatically into the most active progenitor form. See e.g., Wilman, "Prodrugs in Cancer Chemotherapy," Biochemi cal Society Transactions, 14, p. 375-382, 615tn Meetmg Belfast (1986) and Stella et al. , "Prodrugs: A Chemical Approach to Targeted Drug Delivery", Directed Drug Delivery, Borchardt et al. , (ed.), pp. 247-267, Humana Press (1985). Prodrugs of the present invention include, but are not limited to, phosphate-containing prodrugs, thiophosphate-containing prodrugs, glycosylated prodrugs or optionally prodrugs containing substituted phenylacetamide, 5-fluorocytosm and other prodrugs of 5-fluorouridma which may be derivatives in a Prodrug form for use in the present invention, including but not limited to, those chemotherapeutic agents described above. The term "agonist" is used in the broadest sense and includes any molecule that mimics a biological activity of a PR0179, PRO207, PRO320, PR0219, PR0221, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 native polypeptide. described in jJljjM.iUfaA *.? . i? , * t ** í tii é? > ? - - I presented. Suitable agonist molecules specifically include agonist antibodies or antibody fragments, fragments or amino acid sequence variants of the native PR0179, PRO207, PRO320, PR0219, PR0221, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 polypeptides. peptides, small organic molecules, et cetera. Methods for identifying the agonists of a PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0366, PRO509 or PR0866 polypeptide may comprise contacting a tumor cell with a candidate agonist molecule and measuring the inhibition of the growth of the tumor cell. The term "chronic administration" refers to the administration of an agent or agents in a continuous manner, as opposed to an acute mode, to maintain the initial therapeutic effect (activity) for a prolonged period of time. "Intermittent" administration is a treatment that is not performed consecutively without interruption, but which is cyclic in nature. The term "mammal" for the purposes of treatment, refers to any animal classified as a mammal, including humans, domestic and farm animals, zoo animals, sports animals, or pets, such as dogs, cats, cattle, horses, sheep , pigs, goats, rabbits, etc. Preferably, the mammal is Í? *. * * 4-. * Í- * É ** '- ii * i * ¿.. -t .. ****?' *** -? ** ... * .. *, JSk * - * - - a human being. The administration "in combination with" one or more additional therapeutic agents, includes simultaneous (concurrent) administration and consecutive administration, in any order. The term "carrier" as used herein, includes pharmaceutically acceptable carriers, excipients or stabilizers that are not toxic to the cell or to the mammal being exposed thereto, at the doses and concentrations employed. Often the physiologically acceptable carrier is an aqueous pH buffer solution. Examples of physiologically acceptable vehicles include regulatory solutions such as phosphates, citrates and other organic acids; antioxidants including ascorbic acid; low molecular weight polypeptides (less than about 10 residues); proteins such as serum albumin, gelatin or immunoglobulins; hydroflucos polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine or lysine; monosaccharides, disaccharides and other carbohydrates including glucose, mannose or dextrins; chelating agents such as AEDT, sugar alcohols such as mannitol or sorbitol; salt-forming counterions such as sodium; and / or non-ionic surfactants such as TWEEN ™, polyethylene glycol \ * h ** - - - * - * * *** - * - - (PEG) and PLURONICS ™. The "native antibodies" and "native immunoglobulins" are usually heterotetrameric glycoproteins of approximately 150,000 daltons, composed of two identical light chains (L) and two identical heavy (H) chains. Each light chain is linked to a heavy chain by a covalent disulfide bridge, while the number of disulfide bonds varies among the heavy chains of the different immunoglobulin isotypes. Each light and heavy chain also has intrachain chain disulfide bridges at regular spaces. Each chain has at one end a variable domain (VH) followed by a number of constant domains. Each light chain has a variable domain at one end (VL) and a constant domain at its other end; the constant domain of the light chain is aligned with the first constant domain of the heavy chain and the variable domain of the light chain is aligned with the variable domain of the heavy chain. It is thought that some particular amino acid residues form an interface between the variable domains of light chain and heavy chain. The term "variable" refers to the fact that certain portions of the variable domains differ widely in sequence between the antibodies and are used in the binding and in the specificity of each - - particular antibody for its particular antigen. However, the variability is not evenly distributed in the variable domains of the antibodies. This is concentrated in three segments called complementarity determining regions (RDC) or hypervariable regions, both in the variable domains of the light chains and in the variable domains of the heavy chains. The most highly conserved portions of the variable domains are called frame regions (FR). The variable domains of the native heavy and light chains comprise four FR regions, largely adopting a β-sheet configuration, connected by three RDCs, which form connection handles and in some cases are part of the β-sheet structure. The RDCs of each chain are kept close together by the FR regions and, with the RDCs of the other chain, contribute to the formation of the antigen binding site of the antibodies (see Kabat et al., NIH Publ. No. 91-3242, Vol. I, pages 647-669 - (1991)). The constant domains do not participate directly in the binding of an antibody to an antigen, but exhibit several effector functions, such as the participation of the antibody in antibody-dependent cellular toxicity. The term "hypervariable region" as used herein, refers to the - amino acid residues of an antibody that are responsible for antigen binding. The hypervariable region comprises amino acid residues from a "complementarity determining region" or "RDC" (ie, residues 24-34 ((Ll), 50-56 (L2) and 89-97 (L3) of the light chain variable domain and 31-35 (Hl), 50-65 (H2) and 95-102 (H3) in the variable domain of the heavy chain; Kabat et al. , Sequences of Proteins of Immunological Interest, 5tn Ed. Public Health Service, National Institute of Health, Bethesda, MD

[1991]) and / or those residues of a "hypervariable loop" (ie, residues 26-32 (Ll), 50-52 (L2) and 91-96 (L3) in the variable domain of the light chain and 26-32 (Hl), 53-55 (H2) and 96-102 (H3) in the variable domain of the heavy chain Clothia and Lesk, J. Mol. Biol. 196: 901-911

[1987]). The "frame" or "FR" residues are those variable domain residues different from the hypervariable region residues as defined herein. The "antibody fragments" comprise a portion of an intact antibody, preferably the antigen binding region or variable region of the intact antibody Examples of antibody fragments include the Fab, Fab ', F (ab') 2 fragments and Fv; diabodies; linear antibodies (Zapata et al., Protein Eng. 8 (10): 1057-1062

[1995]); single-chain antibody molecules and multispecific antibodies formed from antibody fragments. With papain the antibodies produce two identical antigen binding fragments, called "Fab" fragments, each with a single antigen binding site and a residual "Fc" fragment, a designation that reflects the ability to crystallize easily. Pepsin produces an F (ab ') 2 fragment that has two antigen binding sites and is still capable of binding the antigen.The term "Fv" is the minimum antibody fragment that contains a specific region of antigen. knowledge of the antigen and a binding site. This region consists of a dimer of a heavy chain variable domain and a light chain variable domain in close but non-covalent association. It is in this configuration that the three RDCs of each variable domain interact to define an antigen binding site on the surface of the VH-VL dimer. Collectively, the six RDCs confer antigen binding specificity to the antibody. However, even a single variable domain (or half of an Fv comprising only three RDCs specified by the antigen) has the ability to recognize and bind to its antigen, albeit with a lower affinity than the entire binding site. The Fab fragment also contains the domain - - constant of the light chain and the first constant domain (CHI) of the heavy chain. The Fab fragments differ from the Fab 'fragments by the addition of a few residues at the carboxyl-terminal end of the CHI domain of the heavy chain, including one or more cysteines from the hinge region of the antibody. Fab'-SH is the designation for a Fab 'in which the cysteine residue or residues of the constant domains carry a free thiol group. The F (ab ') 2 antibody fragments were originally produced as pairs of Fab' fragments having the hinge cysteines between them. Other chemical pairs of antibody fragments are also known. The "light chains" of the antibodies (immunoglobulins) of a vertebrate species can be assigned to one of two clearly distinct types, called kappa and lambda, based on the amino acid sequences of their constant domains. Depending on the amino acid sequence of the constant domain of their heavy chains, immunoglobulins can be assigned to different classes. There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG and IgM and several of these can be subdivided into subclasses (isotypes), e.g., IgGl, IgG2, IgG3, igg4, IgAl and IgA2. The term "monoclonal antibody" as used herein, refers to an antibody obtained from a substantially homogeneous population of antibodies, ie, the individual antibodies comprising the population are identical except for possible mutations of natural origin that could be present in smaller quantities. Monoclonal antibodies are highly specific, they are directed against a single antigenic site. In addition, in contrast to conventional (polyclonal) antibody preparations that typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant in the antigen. In addition to their specificity, monoclonal antibodies are advantageous because they are synthesized by hybridoma cultures, which are not contaminated with other immunoglobulins. The "monoclonal" modifier indicates the character of the antibody that is obtained from a substantially homogeneous population of antibodies and that is not constructed as required by the production of the antibody by any particular method. For example, the monoclonal antibodies to be used according to the present invention can be prepared by the hybridoma method, first described by Kohler et al. , Nature, 256: 495

[1975]), or can be prepared by recombinant 7DNA methods (see e.g., the US Patent - No. 4,816,567). "Monoclonal antibodies" can also be isolated from phage antibody libraries using the techniques described in Clackson et al. , Nature, 352: 624-628

[1991] and Marks et al. , J. Mol. Biol. 222: 581-597 (1991), for example. The monoclonal antibodies herein specifically include "chimeric" antibodies (immunoglobulins) in which a portion of the heavy and / or light chain is identical or homologous to the corresponding sequences of antibodies derived from a particular species or belonging to a class or subclass of particular antibody, while the rest of the chain or chains is identical or homologous to the corresponding sequences of antibodies derived from another species or belonging to another class or subclass of antibody, as well as fragments of such antibodies, as long as they exhithe desired biological activity (U.S. Patent No. 4,816,567; Morrison et al., Proc. Nat '1 Acad. Sci. USA. 81: 6851-6855

[1984]). The "humanized" forms of non-human (eg, murine) antibodies are chimeric immunoglobulins, chains or fragments of chimeric immunoglobulins (such as Fv, Fab, Fab ', F (ab') 2 or other antigen-binding subsequences of the antibodies ) containing minimal sequences derived from non-human immunoglobulins. Mostly, humanized antibodies are human immunoglobulins (receptor antibody) in which the residues of a CDR of the receptor are replaced by residues of a CDR of a non-human species (donor antibody) such as murine, rabbit or rat antibodies having the specificity, affinity and capacity desired. In some cases, the Fv FR residues of the human immunoglobulin are replaced by the corresponding non-human residues. In addition, the humanized antibodies may comprise residues that are not found in the recipient antibody or in the imported RDC or in the frame sequence. These modifications are made to further refine and maximize antibody performance. In general, the humanized antibody will substantially comprise all of at least one and typically two variable domains, in which all or substantially all of the RDC regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin sequence. The humanized antibody optimally will also comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. For more details, see Jones et al. , Na ture 321: 522-525 (1986); Reich ann et al. , Nature, . ^ * ^ * ^ - *** ^ ¡& m ^ - - 332: 323-329

[1988]; and Presta, Curr. Op. Struct. Biol, 2: 593-596 (1992). The humanized antibody includes a PRIMATIZED ™ antibody wherein the antigen binding region of the antibody is derived from an antibody produced by immunization of macaque monkeys with the antigen of interest. The "single chain Fv" or "sFv" antibody fragments comprise the VH and VL domains of the antibody, wherein these domains are present in a single polypeptide chain. Preferably, the Fv polypeptide further comprises a polypeptide linker between the VH and VL domains which makes it possible for the sFv to form the desired structure for antigen binding. For a review of sFvs, see Pluckthun in The Pharmacol ogy of Monoclonal Antibodies, Vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994). The term "diabodies" refers to small fragments of antibody with two antigen binding sites, wherein these fragments contain a heavy chain variable domain (VH) connected to a light chain variable domain (VL) in the same chain polypeptide (Vri - VL). By using a linker that is too short to allow pairing between the two domains in the same chain, the domains are forced to 'If *, * -i * 1. ** - .. * * j t¿ - - pair with complementary domains of another chain and create two antigen binding sites. The diabodies are described in greater detail, for example, European Patent EP 404,097; International Publication WO 93/11161 and Hollinger et al. , Proc. Nat '1 Acad. Sci. USES. 90: 6444-6448 (1993). An "isolated" antibody is one that has been identified and separated and / or recovered from a component of its natural environment. The contaminating components of its natural environment are materials that would interfere with the diagnostic or therapeutic uses of the antibody and could include enzymes, hormones and other protein and non-protein solutes. In preferred embodiments, the antibody will be purified (1) to a degree greater than 95% by weight of antibody, determined by the Lowry method and preferably more than 99% by weight, (2) to a sufficient degree to obtain at least 15 residues of the N-terminal or internal amino acid sequences using a rotary cup sequencer or (3) to homogeneity by SDS-HSPA under reducing or non-reducing conditions, using Coomassie blue staining or preferably silver staining. The isolated antibody includes the antibody itself within recombinant cells, since at least one component of the antibody's natural environment will not be present. Without However, normally the isolated antibody will be prepared by at least one purification step. The word "label" when used herein refers to a detectable compound or composition that is conjugated directly or indirectly with the antibody to generate a "labeled" antibody. The label may be detectable by itself (e.g., radioisotopic labels or fluorescent labels) or, in the case of an enzymatic label, could catalyze the chemical alteration of a substrate compound that is detectable. The brand can also be a non-detectable entity, such as a toxin. The term "solid phase" refers to a non-aqueous matrix to which the antibody of the present invention can adhere. Examples of the solid phases encompassed herein, include those formed partially or completely of glass (e.g., glass of controlled porosity), polysaccharides (e.g., agarose), polyacrylamides, polystyrene, polyvinyl alcohol and silicones. In certain embodiments, depending on the context, the solid phase may comprise the wells of a test plate; in other contexts, it is a purification column (e.g., an affinity chromatography column). This term also includes a discontinuous solid phase or discrete particles, such as those - - described in United States Patent No. 4,275,149. A "liposome" is a small vesicle composed of various types of lipids, phospholipids and / or surfactants, which is useful for the distribution of a drug (such as the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301 , PR0526, PR0362, PR0356, PRO509 or PR0866 or an antibody thereto) in a mammal. The components of the liposome are commonly arranged in a bilayer formation, similar to the arrangement of the lipids of the biological membranes. A "small molecule" is defined herein as one having a molecular weight below about 500 daltons. II. Compositions and Methods of the Present Invention A. PRQ179, PRO207, PRO320, PR320, PRQ219, PRQ221, PRQ224, PRQ328, PRO301, PRQ526, PRQ362, PR0356, PRO509, and PRQ866 Full-Length PRQ866 Polypeptides The present invention provides novel isolated and identified nucleotide sequences coding for the polypeptides referred to in the present application as PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866. In particular, cDNAs encoding PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and - PR0866 and have been isolated, in the manner that will be described in greater detail in the Examples presented below. As described in the Examples presented below, the 7DNA clones encoding the PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866 polypeptides have been deposited at the ATCC [with the exception of the clone PRO509, which was not deposited with the ATCC]. The actual nucleotide sequences of the clones can be readily determined by those skilled in the art by sequencing the deposited clones by the use of routine methods. The predicted amino acid sequences can be determined from the nucleotide sequences, using routine techniques. For the PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and pro866 polypeptides and the nucleic acids encoding them described herein, the Applicants have identified what is thought to be the most identifiable reading frame with the sequence information available at that time. B. Variants of PRQ179, PRO207, PRO320, PRQ219, PRQ221, PRQ224, PRQ328, PRO301, PRQ526, PRQ362, PRQ356, PRO509 and PR0866 In addition to the native length sequence - - complete of the polypeptides PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PR0509 and PR0866 described herein, it is contemplated that variants of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866. The variants of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866 can be prepared by introducing appropriate nucleotide changes into the DNA of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 and / or by synthesis of the desired PR0179, PRO207, PRO320, PR0219, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 polypeptide. Those skilled in the art will note that amino acid changes can alter the post-translational processes of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 polypeptides, for example by changing the number or po.sición of glycosylation sites or altering the characteristics of anchoring to the membrane. The variations in the native full length sequence of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or of several domains of PR0179, PRO207, PRO320, ..,.--i i Á...... a a a a a a a a a a a a a a a PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PR0509 or PR0866 described herein, can be made, for example, using any of the conservative and non-conservative mutations techniques and guidelines established, for example, in U.S. Patent No. 5,364,934. The variations may be a substitution, deletion or insertion of one or more codons coding for PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0301, PR0526, PR0362, PR0356, PRO509 or PR0866 which result in a change in the amino acid sequence of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 compared to the native sequence of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328 , PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. Optionally, the variation is by substitution of at least one amino acid for any other amino acid in one or more of the domains of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. The guidelines for determining which amino acid residue can be inserted, replaced or eliminated without adversely affecting the desired activity, can be found by comparing the sequence of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362 , PR0356, PRO509 or PR0866 with that of protein molecules * & ?TO. < íá * '?? ** k? * í & i * Mh ** & *** »* - known homologs and minimizing of amino acid sequence changes in regions of high homology. Amino acid substitutions can result in the replacement of one amino acid with another that has similar structural and / or chemical properties, such as the replacement of a serine with a leucine, i. e. , conservative amino acid replacements. The insertions or deletions, optionally, may be in the range of about 1 to 5 amino acids. The allowed variation can be determined by making insertions, deletions or substitutions systematically in the amino acid sequence and testing the resulting variants with respect to the activity shown in comparison with the full-length or mature native sequence. Herein fragments of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866 polypeptides are provided herein. Such fragments may be truncated at the N-terminal or C-terminal end, or they may be. lack of internal waste, for example, when compared to a full-length native protein. Certain fragments lack amino acid residues that are not essential for the desired biological activity of the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. ííJaii II - ** "- * ** *** **** t -.... ** - 'i ... * ** * *** --.- i... *** lí? ', _? **. ***: ** ** ..,? ...,., -,. ****.., - * - **: - ** *** you ** **. *** I * - - The fragments of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866 can be prepared by any of a number of conventional techniques. The desired peptide fragments can be chemically synthesized. An alternative method includes the generation of fragments PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PR0509 and PR0866 by enzymatic digestion, eg, by a treatment of the protein with an enzyme that is it knows that it breaks proteins at sites defined by particular amino acid residues, or by digesting the 7DNA with appropriate restriction enzymes and isolating the desired fragment. Yet another suitable technique includes isolating and amplifying a DNA fragment encoding a desired polypeptide fragment by a polymerase chain reaction (PCR). Oligonucleotides that define the desired terms of the DNA fragment are used in the 5 'and 3' primers in the PCR. Preferably, the polypeptide fragments PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866 share at least one biological and / or immunological activity with the polypeptides PR0179, PRO207, PRO320 , PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 shown - in Figure 2 (SEQ ID No. 2), Figure 4 (SEQ ID No. 7), Figure 6 (SEQ ID No. 10), Figure 8 (SEQ ID No. 15), Figure 10 (SEQ ID No. 20), Figure 12 (SEQ ID No. 25), Figure 14 (SEQ ID No. 30), Figure 16 (SEQ ID No. 35), Figure 18 (SEQ ID No. 43), Figure 20 (SEQ ID No. 48), Figure 22 (SEQ ID No. 55), Figure 24 (SEQ ID No. 60), or Figure 26 (SEQ ID No. 62), respectively. In particular embodiments, conservative substitutions of interest are shown in Table 3 under the heading of preferred substitutions. If such substitutions result in a change in biological activity, then more substantial changes are introduced, termed example substitutions in Table 3, or which are described below with reference to the amino acid classes, and the products are selected. TABLE 3 Waste Substitutions Example Preferred Original Substitutions Wing (A) val; leu; ile val Arg (R) lys; gln; asn lys Asn (N) gln; his; lys; arg gln Asp (D) glu glu Cys (C) be Gln (Q) asn asn - - Glu E) asp asp Gly G) pro; wing wing His H) asn; gln; lys; arg arg He I) leu; val; met; to; phe; norleucina leu Leu L) norleucine; ile; val; met; to; phe ile Lys K) arg; gln; asn arg Met (M) leu; phe; ile leu Phe F) leu; val; ile; to; tyr leu Pro P) ala ala Ser S) thr thr Thr (T) be be Trp (W) tyr, phe tyr Tyr Y) trp; phe; thr; be phe Val V) ile; leu; met; phe; to; norleucina leu Substantial modifications are made in the function or in the immunological identity of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0366, PRO509 or PR0866 polypeptides, through the selection of substitutions that differ significantly in its effect on maintaining (a) the base structure of the polypeptide in the substitution area, for example, in a leaf or helical conformation, (b) changing the hydrophobicity of the molecule at the target site, or ( c) the bulk of the side chain.

******* - - The residues of natural origin are divided into groups based on the common side chain properties: (1) hydrophobic: norleucine, met, ala, val, leu, ile; (2) neutral hydrophilic: cys, ser, thr; (3) acids: asp, glu; (4) basic: asn, gln, his, lys, arg; (5) residues that influence the orientation of the chain: gly, pro; and (6) aromatics: trp, tyr, phe. Non-conservative substitutions will result in the exchange of a member of one of these classes by another class. Such substituted residues may also be introduced at the conservative substitution sites or, preferably, at the remaining (non-conservative) sites. Variations can be made using methods known in the art such as oligonucleotide-mediated mutagenesis (site-directed) alanine scanning and PCR mutagenesis. Site-directed mutagenesis [Cárter et al. , Acids Res. , I3: .4331 (1986); Zoller et al. , Nucí. Aci ds Res. , 10: 6487 (1987)], cartridge mutagenesis [Wells et al. , Gene, 34: 315 (1985)], mutagenesis of restriction selection [Wells et al. , Philos. Trans. R. Soc. London SerA, 317: 415 (1986)] or other known techniques, can be performed on the cloned DNA to produce DNA variant of PR0179, PRO207, PRO320, - - PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. Amino acid analysis can also be used by scanning to identify one or more amino acids along a contiguous sequence. Among the preferred scanning amino acids are relatively small and neutral amino acids. Such amino acids include alanine, glycine, serine and cysteine. Alanine is typically a preferred amino acid of scanning among this group, because it removes the side chain beyond the beta carbon and is less likely to alter the major conformation of the variant chain [Cunningham and Wells, Science, 244: 1081 -1085 (1989)]. Alanine is also typically preferred, because it is the most common amino acid. In addition, it is frequently found in buried positions and in exposed positions [Creighton, The Proteins, (W.

Freeman & Co. , N.Y.); Chothia, J. Mol. Biol. 150: 1 (1976)]. If the substitution of. Alanine does not produce adequate amounts of a variant, an isoteric amino acid can be used. C. Modifications of PRQ179, PRO207, PRO320, PRQ219, PRQ221, PRQ22, PRQ328, PRO301, PRQ526, PRQ362, PRQ356, PRO509 and PRQ866. The covalent modifications of PR0179, PRO207, .A-ai Ubátá .. z.???????? - - PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362., PR0356, PRO509 and PR0866 are included within the scope of the present invention. One type of covalent modification includes reacting white amino acid residues of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 with an organic derivatizing agent that is capable of react with the selected side chains or with the N- or C- terminal residues of PR0179, PR0207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. Derivatization with bifunctional agents is useful, for example, for crosslinking the polypeptides PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 in a support matrix insoluble in water or in a surface to utilize the purification method with anti PR0179, antiPRO207, antiPRO320, antiPR0219, antiPR0221, antiPR0224, antiPR0328, antiPR? 301, antiPR0526, antiPR0362, antiPR0356, antiPRO509 or antiPR0866, and vice versa. Commonly used crosslinking agents include, e. g. , 1,1-bis- (diazoacetyl) -2-phenylethane, glutaraldehyde, N-hydroxysuccinimide esters, for example esters with 4-azidosalicylic acid, homobifunctional imidoesters, including disuccinimidyl esters such as 3, 3'-dithiobis- - - (succinimidylpropionate), bifunctional aleimides such as bis-N-maleimido-1,8-octane and agents such as methyl 3- [(p-azidophenyl) -dithio] -propioimidate. Other modifications include the desaturation of glutaminyl and asparaginyl residues to obtain the corresponding glutamyl and aspartyl residues, respectively, the hydroxylation of proline and lysine, the phosphorylation of hydroxyl groups of seryl or threonyl residues, the methylation of the a-amino groups of the chains laterals of the plant, arginine and histidine [T. E. Creighton, Proteins: Structure and Molecular Properti, W. H. Freema & Co. , San Francisco, pp. 79-86 (1983)], the acetylation of the N-terminal amine and the amidation of any C-terminal carboxyl group. Another type of covalent modification of the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 included in the scope of the present invention, comprises the alteration of the native glycosylation pattern of the polypeptide. The term "alteration of the native glycosylation pattern" as used herein means eliminating one or more carbohydrate moieties found in the native sequence PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 (either by removing the underlying glycosylation site, or, by eliminating glycosylation by chemical and / or enzymatic means) and / or by adding one or more glycosylation sites that are not present in the native polypeptide sequence PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. In addition, the phrase includes qualitative changes in the glycosylation of the native proteins, including a change in the nature and various carbohydrate moieties present. The addition of glycosylation sites to the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 can be carried out by altering the amino acid sequence. The alteration may be performed, for example, by the addition or substitution of one or more serine or threonine residues of the native PR0179 sequence., PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 (for glycosylation sites linked to O). The amino acid sequence PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 can optionally be altered by changes at the DNA level, particularly by mutation of the DNA encoding the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 on bases , *: * < *, -aJ.l.JtltiH. - - preselected, in such a way that codons are generated that will be translated into the amino acids. Another mechanism for increasing the number of carbohydrate moieties in the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0301, PR0526, PR0362, PR0356, PRO509 or PR0866, is by chemical or enzymatic coupling of glycosides to the polypeptide. Such methods are described in the art, for example in International Publication WO 87/05330 published on September 11, 1987 and in Aplin and Wriston, CRC Cri t. Rev. Bochem. , pp. 259-306 (1981). The removal of the carbohydrate moieties present in the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PR0509 or PR0866 can be carried out chemically or enzymatically, or by mutational substitution of codons which code for amino acid residues that serve as targets for glycosylation. Chemical deglycosylation techniques are known and described, for example, in Hakimuddin et al. , Arch. Biochem. Biophys. , 259: 52 (1987) and in Edge et al. , Anal. Biochem. , 118: 131 (1981). Enzymatic cleavage of carbohydrate moieties in the polypeptides can be carried out using a variety of endoglycosidases and - exoglycosidases, in the manner described by Thotakura et al. , Meth. Enzymol. , 138: 350 (1987). Another type of covalent modification of the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 comprises ligating the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 to one of a variety of non-protein polypeptides, eg, polyethylene glycol (PEG), polypropylene glycol or polyoxyalkylenes, in the manner described in U.S. Patent Nos. 4,640,835; 4,496,689; 4,301,144; 4,670,417; 4,791,192 OR 4,179,337. The polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 of the present invention can also be modified in a manner to form a chemical molecule comprising the polypeptide PR0179, PRO207 , PR0320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 merged. with another heterologous polypeptide or heterologous amino acid sequence. In one embodiment, such a chimeric molecule comprises a fusion of the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 with a tag polypeptide that provides an epitope which can be link .. * ** í *** *** * * * * * - - selectively an antibody directed against the brand. The epitope of the tag is generally placed at the amino-terminal or carboxyl-terminal end of the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0301, PR0526, PR0362, PR0356, PRO509 or PR0866. The presence of such forms with labeled epitopes of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PR0509 or PR0866, can be detected using an antibody against the tag polypeptide. Likewise, providing the epitope with tag makes it possible for the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 to be easily purified by affinity purification, using an antibody against the brand or another type of affinity matrix that joins the brand epitope. Various brand polypeptides and their respective antibodies are known in the art. Some examples include polyhistidine (poly-His) or polyhistin-glycine (poly-His-Gly) labels; the FL-tag polypeptide HA and its antibody 12CA5 [Field et al. , Mol. Cell. Biol. , 8: 2159-2165 (1988)]; the c-myc tag and the 8F9, 3C7, 6E10, G4, B7 and 9E10 antibodies directed against it [Evan et al. , Molecular and Cellular Biology, 5: 3610-3616 (1985)]; and glycoprotein D (gD) of Herpes Simplex virus and its corresponding antibody [Paborsky et al. , Protein Engineering, 3 (6): 547-553 (1990)]. Other brand polypeptides include the Flag peptide [Hopp et al. , BioTechnology, 6: 1204-1210 (1988)]; the epitope KT3 peptide [Maartin et al. , Science, 255: 192-194 (1992)]; an epitopic peptide a-tubulin [Skinner et al. , J. Biol. Chem., 26 (5: 15163-15166 (1991)], and the protein-tag peptide of gene 10 of T7 [Lutz-Freyermuth et al., Proc. Na tl. Acad. Sci. Usa, 87: 6393-6397 (1990).] In an alternative embodiment, the chimeric molecule may comprise a fusion of the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 with an immunoglobulin or a region particular of an immunoglobulm For a bivalent form of the chimeric molecule (also referred to as "immunoadhesin"), such a fusion could with the Fc region of an IgG molecule.Ig fusions preferably include the substitution of a soluble form (transmembrane domain). deleted or inactivated) of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 instead of at least one variable region within an Ig molecule. preferred, the fusion immunoglobulin it includes the hinge regions, CH2 and CH3, or the hinge regions CH1, CH2 and CH3 of an IgG1 molecule. For the - - production of fusion immunoglobulins, see also US Patent No. US5,428,130 issued June 27, 1995. D. Preparation of PRQ179, PRO207, PRO320, PRQ219, PRQ221, PRQ224, PRQ328, PRO301, PRQ526, PRQ362, PRQ356, PRO509 and PRQ866. The description presented below, mainly refers to the production of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 by culturing cells transformed or transfected with a vector containing nucleic acid of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. Of course, it is contemplated that alternative methods, known in the art, may be employed to prepare the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. For example, the polypeptide sequence PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or portions thereof can be produced by direct synthesis of the polypeptide using solid phase techniques. [see, for example, Stewart et al. , Solid-Phase Peptide Synthesis, W. H. Freeman Co., San Francisco, CA (1969); Merrifield, J. Am. Chem. Soc., 85: 2149-2154 (1963)]. Can be done ? • ..-? * ¿?.?. ***. - *, **%. *** - - a protein synthesis in vi tro using manual techniques or automation. The automated synthesis can be carried out, for example, by using an Applied Biosystems Peptide Synthesizer (Foster City, CA) following the manufacturer's instructions. Various portions of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 polypeptides can be chemically synthesized separately and can be combined using chemical or enzymatic methods to produce PR0179 polypeptide , PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 full-length. 1. Isolation of DNA encoding PRQ179 Polypeptide, PRO207, PRO320, PRQ219, PRQ221, PRQ22, PRQ328, PRO301, PR0526, PRQ362, PRQ356, PRO509 or PRQ866. DNA encoding PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 can be obtained from a cDNA library prepared from tissues thought to possess PR0179 mRNA. , PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 and express it at a detectable level. In accordance with this, DNA of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 can be conveniently obtained from a ** ~ 4 w. - - cDNA library prepared from a human tissue, as described in the Examples. The gene encoding PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 can also be obtained from a genomic library or by known synthetic methods (eg, automated synthesis of nucleic acids). Libraries can be selected with probes (such as antibodies directed against PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or oligonucleotides of at least 20 to 80 bases) designed for identify the gene of interest or the protein encoded by it. The selection of a 7? DNc or genomic library with the selected probe can be carried out using standard procedures, as described in Sambrook et al. , Molecular Cloning: A Laboratory Manual (New York: Cold Spring Harbor Laboratory Press, 1989). An alternative means to isolate the gene encoding PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 polypeptide is the PCR methodology [Sambrook et al. , supra; Dieffenbanch et al. , PCR Primer: A Labora tory Manual (Cold Spring Harbor Laboratory Press, 1995)]. . *, **** * t? m, t - - - The Examples presented below describe the techniques for selecting a cDNA library. The sequences of oligonucleotides selected as probes must be of sufficient length and be unambiguous so that false-positive results are minimized. The oligonucleotide is preferably labeled such that it can be detected by hybridization to the DNA of a library being investigated. Marking methods are known in the art and include the use of radiolabels, such as 32 P-labeled ATP, biotinylation or enzyme labeling. Hybridization conditions, including moderate rigor and high stringency (moderately strict and highly stringent conditions), are provided in Sambrook et al. , supra. The sequences identified in such library selection methods can be compared and alienated with other known deposited and publicly available sequences, such as GenBank or other private sequence databases. The identity of the sequence (at the amino acid or nucleotide level) within defined regions of the molecule or through the full length sequence can be determined using methods known in the art, such as those described herein. ** kt * U * i **? íl * t * .t ** á iítd * Í *** í *** "* Í * Í ™ Íjfc- ** **** ******. * - **, 'I **. 1. *. ***. * * * *, ********, * ^ ********, * * ^ *. ** ****** ** 1. * *., Aaa, Jj S.aJÍ..Í., Í .i - - The protein coding sequence having the nucleic acid can be obtained by selecting selected .DNAc or genomic libraries, using the deduced amino acid sequence described herein for the first time and, if necessary, using primer extension methods. conventional, as described in Sambrook et al. , supra, to detect mRNA processing precursors and intermediates that may not have been reverse transcribed into cDNA. 2. Selection and Transformation of Host Cells. Host cells are transfected or transformed with the expression or cloning vectors described herein for the production of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 and are cultured in conventional nutritive media, modified as appropriate, to induce promoters, to select, transformants or to amplify the genes encoding the desired sequences. The culture conditions, such as media, temperature, pH and the like, can be selected by those skilled in the art without undue experimentation. In general, the fundamentals, protocols and practical techniques to maximize the LiJü * M ** * *? * M * ¡* *? L *.

- - Cell culture productivity, can be found in Mammalian Cell Biotechnology: a Practical Approach, M: Butler, ed. (IRL Press, 1991) and Sambrook et al. , supra. Methods for the transfection of eukaryotic cells and the transformation of prokaryotic cells are known to those skilled in the art, for example, CaCl2, CaP04, mediated by liposome and electroporation. Depending on the host cell used, the transformation is carried out using the appropriate standard techniques for such cells. The treatment with calcium using calcium chloride, as described Sambrook et al. , supra, or electroporation, are generally used for prokaryotes. Infection with Agrobacterium tumefaciens is used for the transformation of certain plant cells, as described in Shaw et al. , Gene, 23: 315 (1983) and in International Publication WO 89/05859 published June 29, 1989. For mammalian cells without cell walls, the precipitation method can be used-with Graham's calcium phosphate and van der Eb, Virology, 52: 456-457 (1978). General aspects of transfections in mammalian host cells are described in US Pat. No. 4,399,216. Transformations in yeast are typically carried out with the method of Van Solingen et al. , J. Bact. , 130: 946 (1977) and Hsiao et al. , Proc. Natl. Acad.

- - Sci. (USA), 76: 3829 (1979). However, other methods can be used to introduce DNA into cells, such as nuclear microinjection, electroporation, fusion of bacterial protoplasts with intact cells or polycations, e.g., polybrene, polyornithine. For more information about the various mammalian cell transformation techniques, see Keown et al. , Methods in Enzymol ogy, 185: 521-531 (1990) and Mansour et al. , Nature, 336: 348-352 (1988). Suitable host cells for cloning or expressing the .DNA in the vectors herein include prokaryotic, yeast or higher eukaryotic cells. Suitable prokaryotic cells include, but are not limited to eubacteria, such as Gram-negative or Gram-positive microorganisms, enterobacteriaceae such as E. coli. Several strains of E. coli are available to the public, such as E. coli strain K12 MM294 (ATCC 31,446); E. coli X1776 (ATCC 31,537); strain E. coli W3110 (ATCC 27.325) and K5 772 (ATCC 5.3.635). Other suitable prokaryotic host cells include enterobacteriaceae such as Escherichia, e. g. , E. coli, Enterobacter, Erwinia, Klebsiella, Proteus, Salmonella, e. g. , Salmonella typhimuri um, Serratia, e. g. , Serratia marcescens and Shigella, as well as bacilli such as B. subtilis and B. licheniformis (e.g., B. licheniformis 41P described in 2 - . 2 - DD document 266,710 published April 12, 1989), Pseudomonas such as P. aeruginosa and Streptomyces. These examples are illustrative and not limiting. Strain W3110 is a particularly preferred host or a particularly preferred progenitor host, because it is a common host strain for the fermentation of recombinant DNA products. Preferably, the host cell secretes minimal amounts of proteolytic enzymes. For example, strain W3110 can be modified to effect a genetic mutation in the genes encoding proteins endogenous to the host, wherein examples of such hosts include E. coli W3110 strain 1A2, which has the complete tonA genotype; E. coli W3110 strain 9E4, which has the complete genotype tonA ptr3; E. coli W3110 strain 27C7 (ATCC 55,244), which has the complete genotype tonA ptr3 phoA E15 (argF-lac) 1 69 degP ompT kan '; E. coli W3110 strain 37D6, which has the complete genotype tonA ptr3 phoA E15 (argF-lac) 1 69 degP ompT rbs 7 il vG kan '; E. coli W3110 strain 40b4, which is strain 37D6 with a deletion mutation of the degP gene not resistant to kanamycin; and an E. coli strain having a mutant periplasmic protease described in U.S. Patent No. 4,946,783 issued August 7, 1990. Alternatively, cloning methods are suitable, e. g. , PCR or other nucleic acid polymerase reactions.

^^^^^^ Sg ^^^^^ á & ^^^ * - - In addition to prokaryotes, eukaryotic microbes such as filamentous fungi or yeasts are suitable hosts for cloning or expressing vectors encoding PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. Saccharomyces cerevisiae is a commonly used lower eukaryotic host microorganism. Others include Schizosaccharomyces pombe (Beach and Nurse, Nature, 290: 140

[1981]; European Patent EP 139,383 published May 2, 1985); Kl uyveromyces hosts (U.S. Patent No. 4,943,529; Fleer et al., Bio / Technology, 9: 968-975 (1991)) such as, eg, K. lactis (MW98-8C, CBS4574; Louvencourt et al., J. Bacteriol ., 737

[1983]), K. fragilis (ATCC 12,424), K bulgaricus (ATCC 16,045), K. wickeramii (ATCC 24,178), K. wal tii (ATCC 56,500), K. drosophilarum (ATCC 36,906, Van den Berg et al., Bio / Technology, 8: 135 (1990)), K. thermotolerans and K. marxianus; yarrowia (European Patent EP 402,226); Pichia pastoris (European Patent EP 183,070; Sreekrishna et al., J. Basic Microbiol., 28: 265-278

[1988]); Candida; Trichoderma reesia (European Patent EP 244,234); Neurospora crassa (Case et al., Proc. Natl. Acad. Sci. USA, 76: 5259-5263

[1979]); Schwanniomyces such as Western Schwanniomyces (European Patent EP 394,538 published October 31, 1990) and filamentous fungi such as, e.g., ? t -'--- * * - * i * _t * .it: U ** t ** ^ * * i. *. , * i, ^ i..r **** ...

- - Neurospora, Penicillium, Tolypocladi um (Publication International WO 91/00357 published January 10, 1991) and Aspergillus such as A. nidulans (Balance et al., Biochem. Biophys., Res. Commun., 112: 284-289

[1983]; Tilburn et al., Gene, 26: 205-221

[1983], Yelton et al., Proc. Natl. Acad. Sci. USA, 81: 1470-1474

[1984]) and A niger (Kelly and Hynes, EMBO J., 4: 475-479

[1985]). Methylotropic yeasts are suitable herein and include, but are not limited to, yeasts capable of growing in methanol, which are selected from the genera consisting of Hansenula, Candida, Kloeckera, Pichia, Saccharomyces, Torulopsis and Rhodotorula. A list of specific species that are examples of this class of yeasts, can be found in C. Anthony, The Biochemistry of Methylotrophs, 269 (1982). Suitable host cells for the expression of glycosylated PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0328, PR0301, PR0526, PR0362, PR0366, PR0356, PRO509 or PR0866 PR0236 polypeptides are derived from multicellular organisms. Examples of invertebrate cells include insect cells such as Drosophila S2 and Spodoptera Sf9, as well as plant cells. Examples of useful mammalian host cells include the Chinese hamster ovary (CHO) and COS cell lines. More specific examples include the monkey kidney cell line aaLua ».

- - CV1 transformed with SV40 (COS-7 ATCC CRL 1651); the human embryonic kidney cell line (293 cells or 293 cells subcloned to grow in suspension culture, Graham et al., J. Gen. Virol., 36: 59 (1977)); Chinese hamster ovary cells / -DHFR (CHO, Urlaub and Chasin, Proc. Natl. Acad. Sci. USA, 77: 4216 (1989)); murine sertoli cells (tm4, Mather, Biol. Reprod., 23: 243-251 (1980)); human lung cells (W138, ATCC CCL 75); human liver cells (Hep G2, HB 8065); and murine mammary tumor cells (MMT 060562, ATCC CCL51). The selection of the appropriate host cell is considered within the scope of those skilled in the art. 3. Selection and Use of a Replicable Vector. The nucleic acid (eg, .DNAc or genomic DNA) encoding the PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0366, PRO509 or PR0866 polypeptide can be inserted into a replicable vector for cloning (DNA amplification) or for expression. There are several vectors available to the public. The vector can, for example, be in the form of a plasmid, cosmid, viral particle or phage. The appropriate nucleic acid sequence can be inserted into the vector by a variety of methods. In general, the DNA is inserted into an appropriate restriction endonuclease site (s) using the known techniques.

- - The vector components generally include, but are not limited to, one or more signal sequences, an origin of replication, one or more marker genes, an enhancer element, a promoter and a transcription termination sequence. The construction of suitable vectors containing one or more of these components employs standard ligation techniques that are known to those skilled in the art. The polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 can be produced recombinantly not only directly, but also in the form of a fusion polypeptide with a polypeptide heterologous, which may be a signal sequence or other polypeptide having a specific yield site at the N-terminus of the mature protein or polypeptide. In general, the signal sequence can be a component of the vector, or it can be part of the DNA encoding PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PR0509 or PR0866 which are inserted in the vector. The signal sequence may be a prokaryotic signal sequence that is selected from the group consisting of alkaline phosphatase, penicillinase, lpp or thermostable endotoxin II. For secretion in yeast, the signal sequence can be, e.g., the - Leader sequence of yeast invertase, the alpha leader factor, (including Saccharomyces and Kluyveromyces factor a, the latter described in US Pat. No. 5,010,182) or a leader sequence of acid phosphatase, the leader glucoamylase of C. albi cans ( European Patent EP 362,179 published April 4, 1990) or the signal described in International Publication WO 90/13646 published November 15, 1990. In expression in mammalian cells, mammalian signal sequences can be used to direct the secretion of the protein, such as signal sequences from secreted polypeptides of the same species or a related species, as well as viral secretory leaders. Both the expression and the cloning vectors contain a nucleic acid sequence that makes it possible for the vector to replicate in one or more selected host cells. Such sequences are known for a variety of bacteria, yeasts and viruses. The origin of replication of plasmid pBR322 is suitable for most Gram-negative bacteria, the origin of plasmid 2μ is suitable for yeast and various viral origins (SV40, polyoma, adenovirus, VSV or BPV) are useful for cell cloning vectors of a mammal The expression and cloning vectors will typically contain a selection gene, also called a selectable marker. Typical selection genes encode proteins that (a) confer resistance to antibiotics or other toxins, eg, ampicillin, neomycin, methotrexate or tetracycline, (b) complement auxotrophic deficiencies, or (c) provide critical nutrients that are not available in complex media, eg, the gene encoding the enzyme D-alanine racemase of the genus Bacilus. An example of selectable markers suitable for mammalian cells are those that make it possible to identify competent cells to incorporate the nucleic acid encoding PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356 , PRO509 or PR0866, such as DHFR or thymidine kinase. An appropriate host cell when wild-type DHFR is employed is the CHO cell line deficient in DHFR activity, prepared and propagated in the manner described by Urlaub et al. , Proc. Natl. Acad. Sci. USA, 77: 4216 (1980). A suitable selection gene for use in yeast is the trpl gene present in yeast plasmid YRp7 [Stinchcomb et al. , Na ture, 282: 39 (1979); Kingsman et al. , Gene, 7: 141 (1979); Tschemper et al. , Gene, 10: 151 (1980)]. The trpl gene provides a selectable marker for a mutant strain of yeast lacking the ability to grow in the presence of tryptophan, for example strains ATCC 44076 or PEP4-1 [Jones, Genetics, 85:12 (1977)]. Expression and cloning vectors typically contain a promoter operably linked to the nucleic acid sequence encoding PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866, to direct the synthesis of mRNA. Promoters recognized by a variety of potential host cells are known. Suitable promoters for use with prokaryotic host cells include the β-lactamase and lactose promoter systems [Chang et al. , Na ture, 275: 615 (1978); Goeddel et al. , Na ture, 281: 544 (1979)], alkaline phosphatase, a tryptophan (trp) promoter system [Goeddel, Nucleic Acids Res. , 8: 4057 (1980); European Patent EP 36,776] and hybrid promoters such as the tac promoter [de Boer et al. , Proc. Natl. Acad. Sci. USA, 80: 21-25 (1983)]. Promoters for use in bacterial systems will also contain a Shine-Dalgarno (S, D.) Sequence operably linked with the DNA encoding PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362. , PR0356, PRO509 or PR0866. Examples of suitable promoter sequences for use with yeast hosts include promoters for the enzyme 3-phosphoglycerate kinase [Hitzeman - - et al. , J. Biol. Chem., 255: 2013 (1980)] or other glycolytic enzymes [Hess et al. , J. Adv. Enzyme Reg., 7: 149 (1968); Holland, Biochemisty, 17: 4900 (1978)], such as enolase, glyceraldehyde-3-phosphate dehydrogenase, hexokinase, pyruvate decarboxylase, phosphofructokinase, glucose-6-phosphate isomerase, 3-phosphoglycerate mutase, pyruvate kinase, triosephosphate isomerase, phosphoglucose isomerase and glucokinase. Other yeast promoters, which are inducible promoters that have the additional advantage of transcription controlled by culture conditions, are the promoter regions for the enzymes alcohol dehydrogenase 2, isocitochrome C, acid phosphatase, degradative enzymes associated with nitrogen metabolism, metallothionein, glyceraldehyde-3-phosphate dehydrogenase and enzymes responsible for the use of maltose and galactose. Suitable vectors and promoters for use in yeast expression are further described in European Patent EP 73,657. The transcription of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 of vectors in mammalian host cells is controlled, for example, by promoters obtained from virus genomes such such as the polyoma virus, the avian pustular eruption virus (Patent - - British UK 2,211,504 published July 5, 1989), adenovirus 8tal as Adenovirus 2), bovine papilloma virus, avian sarcoma virus, cytomegalovirus, a retrovirus, hepatitis B virus and simian virus 40 (SV40), promoters heterologous mammals, eg, the actin promoter or an immunoglobulin promoter, and heat shock promoters, as long as such promoters are compatible with the host cell systems. The transcription of a DNA encoding the polypeptides PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 by higher eukaryotes, can be increased by inserting an enhancer sequence into the vector. Intensifiers are cis-acting elements of DNA, usually about 10 to 300 bp, that act on a promoter to increase their transcription. Many sequences of enhancers are known from mammalian genes (globin, elastase, albumin, α-fetoprotein and insulin). However, a virus eukaryotic cell enhancer will typically be used. Some examples include the SV40 enhancer on the origin of replication side (bp 100 to 270), the cytomegalovirus early promoter enhancer, the polyoma enhancer on the origin side of replication and enhancers of adenovirus. The intensifier can be spliced into the vector in a position 5 'or 3' with respect to the coding sequence of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866, but preferably it is located in a site towards 5 'of the promoter. Expression vectors used in eukaryotic host cells (yeast, fungi, insect, plant, animal, human or nucleated cells of other multicellular organisms) will also contain the sequences necessary to complete the transcription and stabilize the mRNA. Such sequences are commonly available 5 'and occasionally 3', untranslated regions of viral or eukaryotic DNA or cDNA. These regions contain the nucleotide segments transcribed as polyadenylated fragments in the untranslated portion of the mRNA encoding the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. Still other suitable methods, vectors and host cells to adapt to the synthesis of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 in recombinant vertebrate cell cultures are described in Gething et *********. .. ***. * ... ******, ...., ... ***, * .. «..,.". ,, ,,. ^ ¡¿¿, 4 - - al. , Nature, 293: 620-625 (1981); Mantei et al. , Nature, 281: 40-46 (1979); European Patent EP 117,060 and European Patent EP 117,058. 4. Detection of Gene Amplification / Expression. The amplification and / or expression of genes can be measured in a sample directly, for example, by the conventional methods of Southern blotting, Northern blotting to quantify the transcription of the mRNA [Thomas, Proc. Natl. Acad. Sci. USA, 77: 5201-5205 (1980)], by spot immunoblotting (DNA analysis) or by in-situ hybridization, using an appropriately labeled probe, based on the sequences provided herein. Alternatively, antibodies can be used that can recognize specific pairs, including DNA pairs, RNA pairs and hybrid DNA-RNA pairs or DNA-protein pairs. The antibodies, in turn, can be labeled and the assay can be carried out when the pair is bound to a surface, such that when the pair is formed on the surface the presence of the antibody bound to the duple can be detected. Gene expression, alternatively, can be measured by immunological methods, such as staining ^. S n ÍJJ l h & - - immunohistochemistry of cells or sections of tissues and the evaluation of cell cultures or body fluids to directly quantify the expression of the gene product. Antibodies useful for immunohistochemical staining and / or testing of fluid samples can be monoclonal or polyclonal and can be prepared in any mammal. Conveniently, antibodies against a PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0362, PR0356, PRO509 or PR0866 native sequence or against a synthetic peptide can be prepared based on the DNA sequences provided in present, or against an exogenous sequence fused to DNA of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 and which codes for a specific antibody epitope. 5. Purification of the Polypeptide. The polypeptide forms PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 are. they can recover from the culture medium or lysates of the host cells. If it is bound to a membrane, it can be released from it by using a suitable detergent solution (e.g., Triton-X 100), or by enzymatic disruption. The cells used in the expression of the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, ? ** í? *? ** í- h *. *. í * * _m * á ** ****? **. *, *** * _ *. *. »" ** ** ** *,. . "* _. , * _ **** ** -? -. ** **** TO. . * H * í ***? * JL? PR0356, PRO509 or PR0866 can be broken by various physical or chemical means, such as freeze-thaw cycles, sonication, mechanical rupture or cell-using agents. One could wish to purify the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 from recombinant cell proteins or polypeptides. The following procedures are examples of suitable purification procedures: by fractionation in an ion exchange column; precipitation with ethanol; high performance liquid chromatography (HPLC) reverse phase; chromatography on silica gel or on a cation exchange resin, such as DE.AE; chromatofocusing; EGPA- DSS; precipitation with ammonium sulfate; gel filtration using, for example, Sephadex G-75; Protein A-sepharose columns to remove contaminants such as IgG; and columns with metal chelators to bind to epitope-labeled forms of the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. Various methods of protein purification can be employed and such methods are known in the art and are described, for example, in Deutscher, Methods in Enzymology, 182 (1990); Scopes, Proteins Purification: Principles and Practice, Springer- - - Verlag, New York (1982). The selected purification steps will depend, for example, on the nature of the production process used and the particular PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 produced. E. Antibodies Some drug candidates for use in the compositions and methods of the present invention are antibodies and antibody fragments that mimic the 10 biological activity of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. 1. Polyclonal antibodies The methods for preparing antibodies 15 polyclonal are known to the technicians in the field. Polyclonal antibodies can be induced in a mammal, for example by one or more injections of an immunizing agent and, if desired, an adjuvant. Typically, the immunizing agent and / or adjuvant will be 20 injected into the mammal by multiple subcutaneous or intraperitoneal injections. The immunizing agent includes the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or a fusion protein thereof. It can be useful 25 conjugate the immunizing agent with a protein that is known - which is immunogenic in the mammal that is being immunized. Examples of such immunogenic proteins include, but are not limited to, limpet hemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsin inhibitor. Examples of adjuvants that may be employed include Freund's complete adjuvant and MPL-TDM adjuvant (monophosphoryl lipid A, synthetic trehalose dicorinomycolate). The immunization protocol can be selected by the person skilled in the art without undue experimentation. 2. Monoclonal antibodies. The antibodies, alternatively, may be monoclonal antibodies. Monoclonal antibodies can be prepared using hybridoma methods, such as those described by Kohler and Milstein, Nature, 256: 495 (1975). In a hybridoma method, a mouse, hamster or any other appropriate host animal, is typically immunized with an immunizing agent to induce lymphocytes to produce or be capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, lymphocytes can be immunized in vi tro. The immunizing agent typically includes the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or - a fusion protein thereof. Generally, peripheral blood lymphocytes ("LSP") are used if cells of human origin are desired, or spleen or lymph node cells are used, if non-human mammalian sources are desired. Then, the lymphocytes are fused with an immortalized cell line using a suitable fusion agent, such as polyethylene glycol, to form a hybridoma cell [Goding, Monoclonal Antibodies: Principles and Practice, Academic Press, (1986) pp 59-103] .

The lines of immortalized cells are normally transformed into mammalian cells, particularly rodent myeloma cells, or of bovine and human origin. Normally rat or murine myeloma cell lines are used. The hybridoma cells can be cultured in a suitable culture medium which, preferably, contains one or more substances that inhibit the growth or survival of unfused, immortalized cells. For example, if the progeny cells lack the hypoxanthine enzyme guanine phosphoribosyltransferase (HGPRT or HPRT), the culture medium of the hybridomas will typically include hypoxanthine, aminopterin and thymidine ("HAT medium"), substances that prevent the growth of HGPRT deficient cells. The preferred immortalized cell lines are those that are efficiently fused, that support i-? iaHMlMlliiir? -tTiií i - **. ** ^ * t ***** t **** .. i. ** ~ t * * ***. ** *** - * * "*. * k *? * i * ií ***? **** ¡* Í *? * t * Ms?, * s ** í ** -,?. * *! **** & ** ??, t J?. * - - a high level of stable expression of the antibody by the selected antibody producing cells and which are sensitive to a culture medium such as the HAT medium. The most preferred immortalized cell lines are those of murine myeloma, which can be obtained, for example, from the Salk Institute Cell Distribution Center, San Diego, California, and from the American Type Culture Collection, Manassas, Virginia. lines of human myeloma cells and murine-human heteromyeloma, for the production of human monoclonal antibodies [Kozbor, J. Immunol., 133: 3001 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and ications, Marcel Dekker, Inc., New York, (1987) pp. 51-63.] The medium in which the hybridoma cells are grown, subsequently, can be tested for the presence of direct monoclonal antibodies. against PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. Preferably, the binding specificity of the monoclonal antibodies produced by the hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as a radioimmunoassay (RIA) or an enzyme linked immunosorbent assay (ELISA). Such techniques and tests are known. The binding affinity of the monoclonal antibody, for example, can be determined - by the Scatchard analysis of Munson and Pollard, Anal. Biochem. , 107: 220 (1980). After the desired hybridoma cells are identified, the clones can be subcloned by limiting the dilution and growth procedures by standard techniques [Goding, supra]. Suitable culture media for this purpose include, for example, Eagle's Medium Modified by Dulbecco and RPMI-1640 Medium. Alternatively, the hybridoma cells can be grown in vivo as ascites in a mammal. The monoclonal antibodies secreted by the subclones can be isolated or purified from the culture medium or ascites fluid, by conventional immunoglobulin purification methods, such as for example protein A-sepharose, hydroxylapatite chromatography, gel electrophoresis , dialysis or affinity chromatography. Monoclonal antibodies can also be prepared by recombinant DNA methods, such as those described in U.S. Patent No. 4,816,567. The 7DNA encoding the monoclonal antibodies of the present invention can be easily isolated and sequenced using conventional methods (e.g., using oligonucleotide probes that are capable of . *** J. ****** *. ..i **. ****. * £ ** », * * i -, - - specifically bind to genes that code for the heavy and light chains of murine antibodies. The hybridoma cells of the present invention serve as a preferred source of such DNA. Once isolated, the DNA can be placed in expression vectors, which are subsequently transfected into host cells, such as simian COS cells, Chinese hamster ovary cells (CHO) or myeloma cells that do not otherwise produce immunoglobulins. , to obtain the synthesis of the monoclonal antibodies in the recombinant host cells. The DNA can also be modified, for example, by replacing the coding sequence of the constant domains of the heavy and light chains instead of the homologous murine sequences [U.S. Patent No. 4,816,567; Morrison et al. , supra] or by the covalent attachment of all or a part of the coding sequence of a non-immunoglobulin polypeptide, to the immunoglobulin coding sequence. Such a non-immunoglobulin polypeptide can be substituted for the constant domains of an antibody of the present invention or can be substituted for the variable domains of an antigen combining site of an antibody of the present invention, to create a chimeric bivalent antibody. The antibodies can be antibodies - - monovalent. Methods for preparing monovalent antibodies are known in the art. For example, one method includes the recombinant expression of the modified light chain and heavy chain of an immunoglobulin. The heavy chain is generally truncated at any point in the Fc region, to avoid cross-linking with heavy chains. Alternatively, the relevant cysteine residues are replaced by other amino acid residues or are deleted, to prevent cross-linking. In vi tro methods are also suitable for preparing monovalent antibodies. The digestion of antibodies to produce fragments thereof, particularly Fab fragments, can be carried out using known routine techniques. 3. Human and Humanized Antibodies The antibodies of the present invention can further comprise humanized or human antibodies. The humanized forms of antibodies, non-human (eg, murine), are chimeric immunoglobulins, chains or immunoglobulin fragments thereof (such as Fv, Fab, Fab ', F (ab') 2 fragments or other antigen-binding subsequences of antibodies) that contain minimal sequences derived from non-human immunoglobulins. Humanized antibodies include - - human immunoglobulins (receptor antibody) in which the residues of a complementarity determining region (RDC) of the receptor are replaced by residues of an RDC of a non-human species (donor antibody) such as a murine, rat or rabbit that has the desired specificity, affinity and capacity. In some cases, the residues of the Fv framework of the human immunoglobulin are replaced by the corresponding non-human residues. The humanized antibodies may also comprise residues that are not found in the recipient antibody or in the imported RDC or in the frame sequence. In general, the humanized antibody will substantially comprise all of at least one, and typically two, variable domains in which all or substantially all of the RDC regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a consensual human immunoglobulin sequence. The humanized antibody optimally will also comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin [Jones et al. , Nature, 321: 522-525 (1986); Riechmann et al. , Nature 332: 323-329 (1988) and Presta, Curr. Op. Struct. Biol. 2: 593-596 (1992)]. Methods to humanize non-human antibodies - - are known in the art. Generally a humanized antibody has one or more amino acid residues that have been introduced from a non-human source. These non-human amino acid residues are often referred to as "imported" residues, which are typically taken from an "imported" variable domain. Humanization can be carried out essentially following the method of Winter et al. [Jones et al. Nature, 321: 522-525 (1986); Riechmann et al. , Na ture, 332: 323-327 (1988); Verhoeyen et al. , Science, 239: 1534-1536 (1988)], substituting rodent RDC or RDC sequences for the corresponding sequences of a human antibody. Accordingly, such "humanized" antibodies are chimeric antibodies (U.S. Patent No. 4,816,567), wherein substantially less than an intact human variable domain has been replaced by the corresponding sequence from a non-human species. In practice, humanized antibodies are typically human antibodies in which some RDC residues and possibly some FR residues are replaced by residues from analogous sites of rodent antibodies. Human antibodies can also be produced using various known techniques, including - - the phage display libraries [Hoogenboom and Winter, J. Mol. Biol., 227: 381 (1991); Marks et al., J. Mol. Biol. 222: 581 (1991)]. The techniques of Colé et al., And Boerner et al., Are also available for the preparation of human monoclonal antibodies (Colé et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p.77 (1985) and Boerner et al. al., J. Immunol., 147 (1): 86-95 (1991).] Similarly, human antibodies can be prepared by introducing loci of human immunoglobulins into transgenic animals, eg mice, in which the endogenous immunoglobulin genes They have been partially or completely inactivated.After a challenge, human antibody production is observed, which closely resembles that seen in humans in all aspects, including gene rearrangement, assembly and antibody repertoire This approach is described, for example, in U.S. Patent Nos. 5,545,807, 5,545,806, 5,569,825, 5,625,126, 5,633,425, and 5,661,016 and in the following scientific publications: Marks et al., Bio / Technology, 10: 119-183 (1992). ); Lonberg et al., Nature, 368: 856-859 (1994); Morrison, Nature, 368: 812-13 (1994); Fishwild et al., Nature Biotechnology 14: 845-51 (1996); Neuberger, Nature Biotechnology, 14: 826 (1996); Lonberg and * AA ** t ***** Jtíi-.il. .... ****** ». * > ** .., - *. * • ** __ * * £ *! ** to * ** ^ * j **** ***** ^ ** * - &**; my? ff-? ..- * ¡¡¡*****. * .... ^ .rfftf ^ ifflUm ii p? T iliij - - Huszar, Intern. Rev. Immunol. 13: 65-93 (1995). 4. Bispecific Antibodies Bispecific antibodies are monoclonal antibodies, preferably human or humanized, that have binding specificities for at least two different antigens. In the present case, one of the binding specificities is by the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 and the other is by any other antigen and, preferably, by a cell surface protein or a receptor or a receptor subunit. Methods for preparing bispecific antibodies are known in the art. Traditionally, the recombinant production of bispecific antibodies is based on the coexpression of two heavy chain / immunoglobulin light chain pairs, where the two heavy chains have different specificities [Milstein and Cuello, Nature, 305: 531-539 (1983)] . Due to the random arrangement of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of ten different antibody molecules, of which only one has the correct bispecific structure. The purification of the correct molecule is normally carried out by chromatography of **** * ... * * .. - "- * - * - affinity Similar procedures are described in International Publication WO 93/08829, published May 13, 1993 and in Traunecker et al., EMBO J., 10: 3655-3659 (1991) Variable domains of antibody having the desired binding specificities (antibody-antigen combination sites) can be fused to immunoglobulin constant domain sequences. Immunoglobulin heavy chain constant domain comprising at least a portion of the hinge region, the CH2 region and the CH3 region It is preferred that the first heavy chain constant region (CH1) contains the necessary site for the binding of The light chain in at least one of the fusions The DNAs encoding the immunoglobulin heavy chain fusions and, if desired, the immunoglobulin light chains, are inserted into expression vectors separately and are cotransfected in a proper host tourism. For more details on the generation of bispecific antibodies, see for example, Suresh et al. , Methods in Enzymology, 121: 210 (1986). In accordance with another approach described in International Publication WO 96/27011, the interface between a pair of antibody molecules can be engineered to maximize the percentage of - - heterodimers that are recovered from the culture of recombinant cells. The preferred interface comprises at least a portion of the CH3 region of an antibody constant domain. In this method, one or more side chains of small amino acids from the interface of the first antibody molecule are replaced by larger side chains (e.g., tyrosine or tryptophan). Compensatory "cavities" of identical or similar size to the large side chains at the interface of the second antibody molecule are created by replacing the side chains of large amino acid other small (e.g., alanine or threonine). This provides a mechanism for increasing the yield of the heterodimer with respect to other undesired end products, such as homodimers. Bispecific antibodies can be prepared in the form of full-length antibodies or as antibody fragments (e.g., bispecific antibodies F (ab ') 2). The techniques for generating bispecific antibodies from fragments, of antibodies, have been described in the scientific literature. For example, bispecific antibodies can be prepared by chemical ligation. Brennan et al. , Science, 229: 81 (1985) describe a method in which intact antibodies are proteolytically cleaved to generate F (ab ') 2 fragments. These fragments are reduced in JbJ. fc'_j * ¿^ £ * \ * d *. * g * - * ¿¿. - - presence of a complex agent of sodium arsenite dithiol to stabilize vicinal dithioles and prevent the intermolecular formation of disulphide bridges. The generated Fab 'fragments are subsequently transformed into thionitrobenzoate derivatives (TNB). One of the Fab'-TNB derivatives is reconverted into Fab '-thiol by a reduction with mercaptoethylamine and mixed with an equimolar amount of the other Fab'-TNB derivative, to form the bispecific antibody. The bispecific antibodies produced can be used as agents for the selective immobilization of enzymes. Fab 'fragments can be recovered directly from E. coli and chemically coupled to form bispecific antibodies. Shalaby et al. , J. Exp. Med., 1 75: 211-225 (1992) describe the production of a fully humanised bispecific antibody molecule (F (ab ') 2. Each Fab' fragment was secreted separately in E. coli and subjected to directed chemical coupling in vi tro, to .formar the bispecific antibody. the bispecific antibody thus formed was able to bind to cells overexpressing the ErbB2 receptor and normal human T cells, also was able trigger the lytic activity human cytotoxic lymphocytes against human mammary tumor target cells. ? i *? ..*,?to*.? In addition, various techniques for preparing and isolating bispecific antibody fragments directly from recombinant cell cultures have also been described. For example, bispecific antibodies have been produced using leucine zippers, Kostelny et al. , J. Immunol. , 148 (5): 1457-1553 (1992). The leucine zipper peptides of the Fos and Jun proteins were ligated to the Fab 'portions of two different antibodies, by gene fusion. The antibody homodimers were reduced in the hinge region to form monomers and then reoxidized to form antibody heterodimers. This method can also be used for the production of antibody homodimers. The "diabody" technology described by Hollinger et al. , Proc. Nat '1 Acad. Sci. USES. Na tl. Acad. Sci. USA, 90: 6444-6448 (1993) has provided an alternative mechanism for the preparation of bispecific antibody fragments. The fragments comprise a variable domain of heavy chain (VH) connected to a light chain variable domain (VL) by a linker that is too short to allow pairing between the two domains in the same chain. Accordingly, the VH and VL domains of one fragment are forced to pair with complementary VH and V domains of another fragment, thereby forming two antigen binding sites. Another strategy has also been reported I ** *** ****** * Ai - - to prepare bispecific antibody fragments by the use of single chain Fv dimers (sFv). See Gruber et al. , J. Immunol. 152: 5368 (1994). Antibodies with more than two valences are also contemplated. For example, trispecific antibodies can be prepared, Tutt et al. , J. Immunol. , 147: 60 (1991). Exemplary bispecific antibodies can be attached to two different epitopes in a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 of the present invention. Alternatively, an anti-PR0179-, anti-PRO207-, anti-PRO320-, anti-PR0219-, anti-PR0221-, anti-PR0224-, anti-PR0328-, anti-PR? 301-, anti-PR0526- antibody , anti-PR0362-, anti-PR0356-, anti-PRO509- or anti-PR0866- can be combined with an antibody arm that binds to a trigger molecule in a leukocyte, such as a T-cell receptor molecule (eg, CD2, CD3, CD28 or B7), or Fc receptors for IgG (Fc? R), such as Fc? RI (CD64), Fc? RII (CD32) and Fc? RIII (CD16) to focus cellular defense mechanisms towards the cell expressing the PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 polypeptide. Bispecific antibodies can also be used to localize cytotoxic agents in cells expressing a polypeptide PR0179, PRO207, PRO320, PR0219, Ui A > «* • - &** -" ** '»» £. ** £ - - PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 particular. These antibodies have a binding arm to PR0179-, PRO207-, PRO320-, PR0219-, PR0221-, PR0224-, PR0328-, PRO301-, PR0526-, PR0362-, PR0356-, PRO509- or PR0866- and an arm that it binds to a cytotoxic agent or a radionuclide chelator, such as EOTUBE, DPTA, DOTA or TETA. Another bispecific antibody of interest binds to the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 and also binds to tissue factor (TF). 5. Heteroconjugate Antibodies Heteroconjugate antibodies are also within the scope of the present invention. Heteroconjugate antibodies are composed of two antibodies covalently linked. Such antibodies have been proposed, for example, to direct the cells of the immune system against undesirable cells [US Patent No. 4,67,6,980], and for the treatment of HIV infection (WO 91/00360, WO 92 / 200373; EP 03089] It is contemplated that antibodies can be prepared in vi tro by the use of methods known in synthetic protein chemistry, including those involving cross-linking agents, for example, immunotoxins can be constructed using a *** £ ** ***? * F, M * i .. .-. 'frf - - disulfide exchange reaction or forming a thioether bond. Examples of suitable reagents for this purpose include iminothiolate and methyl-4-mercaptobutyrimidate and those described, for example, in U.S. Patent No. 4,676,980. 6. Manipulation by Engineering of the Effector Function It may be desirable to modify the antibody of the present invention with respect to effector function, to increase, e.g. the effectiveness of the antibody in the treatment of cancer. For example, cysteine residues can be introduced into the Fc region, thus allowing the formation of interchain disulfide bridges in that region. The homodimeric antibody generated in this way may have an improved internalization capacity and / or increased complement-mediated cell death and increased antibody-dependent cellular cytotoxicity (CCDA). See Carón et al. , J. Exp. Med. 176: 1191-1195 (1992) and Shopes, J. Immunol. , 148: 2918-2922 (1992). Homodimeric antibodies with greater antitumor activity can also be prepared using heterobifunctional crosslinkers, in the manner described in Wolff et al. , Cancer Research, 53: 2560-2565 (1993). Alternatively, an antibody having dual Fc regions can be engineered and thus its lysis capacity caused by the .. f - ** - * - *: ¿... tiAr, - * '. í & L - - complement and its capacity of CCDA. See Stevenson et al. , Anti-Cancer Drug Design, 3: 219-230 (1989). 7. Immunoconjugates The present invention also relates to immunoconjugates comprising an antibody conjugated with a cytotoxic agent, such as a chemotherapeutic agent, a toxin (eg an enzymatically active toxin of bacterial, fungal, plant or animal origin, or fragments of the same) or a radioactive isotope (ie, a 10 radioconjugate). Chemotherapeutic agents useful in the generation of such immunoconjugates have already been described. Enzymatically active toxins and fragments thereof can be used including the diphtheria chain 15 A, active non-inhibitory fragments of diphtheria toxin, the endotoxin A chain (from Pseudomonas aeruginosa), the ricin A chain, the abrin A chain, the modecina A chain, alpha-sarcin, proteins of Aleuri tes fordii, diantine proteins, proteins of 20 Phytolaca americana (PAPI, PAPII and PAP-S), inhibitor of Momordica charantia, curcinia, crotina, inhibitor of Sapaonaria officinalis, gelonin, mitogeline, restrictocin, fenomycin, enomycin and trichothecenes. A variety of radionuclides are available for production 25 of radioconjugated antibodies. Some examples include «? £ ** • *; 212Bi, 131I, 131 ln, 90Y and 186Re. Antibody conjugates and cytotoxic agents are prepared using a variety of bifunctional protein coupling agents, such as N-succinimidyl 3- (2-pyridyldithiol) propionate (SPDP), iminothiolane (IT), bifunctional derivatives of imidoesters (such as dimethyl adipimidate-HCl), active esters (such as disuccinimidyl suberate), aldehydes (such as glutaraldehyde), bis-azido compounds (such as bis (p-azidobenzoyl) hexanediamine), bis-diazonium derivatives (such as bis- (p-diazonium benzoyl) -ethylenediamine), isocyanates (such as 2,6-tolienium diisocyanate) and bis-active fluorine compounds (such as 1,5-difluoro-2,4-dinitrobenzene). For example, a ricin immunotoxin can be prepared in the manner described in Vitetta et al. , Science, 238: 1098 (1987). The 1-isothiocyanatobenzyl-3-methyldiethylene triaminopentaacetic acid (MX-DTPA) labeled with carbon 14 is an exemplary chelating agent for the conjugation of the radionucleotide with the antibody, see International Publication WO 94/11026. In another embodiment, the antibody can be conjugated to a "receptor" (such as streptavidin) for use in the preparation to a tumor target, wherein the antibody-receptor conjugate is administered to the patient, followed by removal of unbound conjugate from the I. A i iiAsi a. ** H α * - H α * -, α a ** - circulation using a purifying agent and then the administration of a "ligand" (e.g., avidin) which is conjugated to a cytotoxic agent (e.g., a radionucleotide). 8. Immunoliposomes The antibodies described herein may also be formulated as immunoliposomes. Liposomes containing the antibody are prepared by methods known in the art, such as those described in Epstein et al. , Proc. Natl. Acad. Sci. USES. 82: 3688 (1985); Hwang et al. , Proc. Natl. Acad. Sci. USA 77: 4030 (1980) and US Patents Nos. 4,485,045 and 4,544,545. Liposomes with a better circulation time are described in US Pat. No. 5,013,556. Particularly useful liposomes can be generated by the reverse phase evaporation method with a lipid composition comprising phosphatidylcholine, cholesterol and phosphatidylethanolamine derived with PEG (PEG-PE). The liposomes are extruded ugh filters of defined pore size, to obtain liposomes of the desired diameter. The Fab 'fragments of the antibodies of the present invention can be conjugated to the liposomes in the manner described in Martin et al. , J. Biol. Chem., 257: 286-288 (1982) ugh a disulfide exchange reaction. Optionally in the liposome *********************************************************************************************** See Gabizon et al. , J. Na ti onal Cancer Inst. 81 (19): 1484 (1989). F. Identification of Proteins Able to Inhibit the Growth or Proliferation of Neoplastic Cells The proteins described in the present application were tested on a panel of 60 tumor cell lines currently used in the selection and detection of 10 drugs in vi tro, oriented to the investigation of diseases of the National Cancer Institute (NCI by its abbreviations in English) of the United States. The purpose of this selection is to identify molecules that have cytotoxic and / or cytostatic activity against different 15 types of tumors. The NCI selects more than 10,000 new molecules per year (Monks et al., J. Na tl. Cancer Inst. 83: 151-166 (19919; Boyd, Cancer, Princ. Pract. Oncol. Update, 3 (10) -. 1-12 (

[1989]). The tumor cell lines used in this study, - are described in Monks 20 et al. , supra. The cell lines whose growth has been significantly inhibited by the proteins of the present application are specified in the examples. The results have shown that the proteins tested have cytostatic activity and in some cases 25 and cytotoxic activity concentrations, in a variety of - - cancer cell lines and, therefore, are useful candidates for tumor therapy. Other cell-based assays and animal models for tumors (eg, cancers) can also be used to verify the results of NCI selection and to further understand the relationship between the protein identified herein and the development and pathogenesis of cell growth. neoplastic For example, primary cultures derived from tumors in transgenic animals (which are described below) may be used in the cell-based assays herein, although stable cell lines are preferred. Techniques for deriving continuous cell lines from transgenic animals are known (see e.g., Samll et al., Mol.Cell. Biol., 5: 642-648

[1985]). G. Animal Models A variety of known animal models can be employed to further understand the function of the molecules identified herein in the development and pathogenesis of tumors and to test the efficacy of candidate therapeutic agents, including antibodies, and other agonists of the native polypeptides, including small molecule agonists. The in vivo nature of such models makes them particularly predictive of responses in human patients. The animal models of Á? Il. Ií &iÁ.i lÁi ?, ***** 1 * 1 * 1 **. * ^ *. _ **? e * K * í **. ¿o * ** **, * *. * *. • * * .t **** i *****? , Ji ******** *** *** *, * *****. ** A * * Í., L i - tumors and cancers (e.g., breast cancer, colon cancer, prostate cancer, lung cancer, etc.) include both non-recombinant animals and recombinant (transgenic) animals. Models in non-recombinant animals 5 include, for example, models in rodents, e.g. murine models. Such models can be generated by introducing tumor cells into syngeneic mice, using standard techniques, e.g. subcutaneous injection, injection into the tail vein, implantation in the spleen, implantation 10 intraperitoneal, implantation under the renal capsule or orthopne implantation, e.g. colon cancer cells implanted in colon tissue (see e.g., PCT Publication WO 97/33551, published September 18, 1997). Probably the animal species used with more The frequency in cancer studies is immunodeficient mice and, in particular, nude mice. The observation that the nude mouse with hypo / aplasia could successfully act as a host for xenografts of human tumors, has led to its development. Wide use for this 20 purpose. The autosomal recessive gene has been introduced in a very large number of different congenic strains of nude mice, including for example, strains ASW, A / He, AKR, BALB / c, B10. POLYGLYCIN LIGATOR, C17, C3H, C57BL , C57, CBA, DBA, DDD, I / st, NC, NFR, NFS, NFS / N, NZB, 25 NZC, NZW, P, RUI and SJL. In addition, a wide variety of - - other animals with inherited immunological defects other than nude mice, have been bred and have been used as recipients of tumor xenografts. For more details see e.g. The Nude Mouse in Oncol ogy Research, E. Boven and B. Winograd, eds., CRC Press, Inc., 1991. Cells introduced into such animals can be derived from known tumors / cancer cell lines, such as any from the above-listed tumor cell lines and, for example, the B104-1-1 cell line (line of stable NIH-3T3 cells transfected with the neu proto-oncogene), NIH-3T3 cells transfected with ras; Caco-2 (ATCC HTB-37); a moderately well-differentiated grade II human colon adenocarcinoma cell line, HT-29 (ATCC HTB-38) or tumors and cancers. Tumor or cancer cell samples may be obtained from patients undergoing surgery, using standard conditions including freezing and storage in liquid nitrogen (Karmali et al., Br. J. Cancer, 48: 689-696

[1983]. ]). It is possible to introduce tumor cells in animals, such as nude mice, by a variety of procedures. The subcutaneous space (s.c.) of the mice is very suitable for the implantation of tumors. Tumors can be transplanted s.c. in the form of blocks - - solids, in the form of needle biopsies or in the form of cell suspensions. For solid block or needle implantation, fragments of tumor tissue of adequate size are introduced into the s.c. Cell suspensions are prepared from the primary tumors or from stable tumor cell lines and injected subcutaneously. The tumor cells can also be injected as subdermal implants. In this location, the inoculum is deposited between the lower part of the dermal connective tissue and the subcutaneous tissue, Boven and Winograd (1991), supra. Animal models of breast cancer can be generated, for example, by implanting rat neuroblastoma cells (of which the neu oncogene was micially isolated) or NIH-3T3 cells transformed with neu, in nude mice, essentially in the manner described by Drebin et al. al , Proc. Na tl. Acad. Sci. USES. 83: 9129-9133 (1986). Similarly, animal models of colon cancer can be generated by making a passage of colon cancer cells in animals, e.g. nude mice, which causes the appearance of tumors in these animals. An orthotopic transplantation model of human colon cancer in nude mice has been described, for example, by Wang et al. , Cancer Research, 54: 4726-4728 (1994) and by Too et al. , Cancer Research, 55: 681-684 (1995). This model is based on - the so-called "METAMOUSE" sold by AntiCancer, Inc., (San Diego, California). Tumors that arise in animals can be removed and cultured in vi tro. The cells of in vi tro cultures, then, can be passed through animals. Such tumors may serve as targets for further testing or for drug selection. Alternatively, the tumors resulting from the passage can be isolated and the RNA from the cells before passage and from the cells isolated after one or more rounds of passage can be analyzed to investigate the differential expression of the genes of interest. Such passing techniques can be performed with any known tumor or cancer cell lines. For example, Meth A, CMS4, CMS5, CMS21 and WEHI-164 cells are chemically induced fibrosarcomas in female BALB / c mice (DeLeo et al., J. Exp. Med. 146: 120

[1977]), which provide a highly controllable model system for studying the antitumor activity of several agents (Paladino et al., J. Immunol., 138: 4023-4032

[1987]). Briefly, tumor cells are propagated in vi tro in cell culture. 7 Before injecting the animals, the cell lines are washed and suspended in buffer solution, at a cell density of approximately 10 x 10 5 to 10 x 10 7 cells / mL. Afterwards, the animals are infected subcutaneously with 10 to 100 - - μL of the cell suspension, allowing one to three weeks for the tumor to appear. In addition, Lewis lung carcinoma (3LL) in mice, which is one of the most highly studied experimental tumors, can be used as a model to investigate tumors. The efficacy in this tumor model has been correlated with beneficial effects in the treatment of human patients diagnosed with small cell lung carcinoma (SCLC). This tumor can be oduced normal mice by injecting tumor fragments from an affected mouse or cells mained in culture (Zupi et al., Br. J. Cancer, 41, suppl 4: 309

[1980]), and the evidence indicates that tumors can be started from the injection of even a single cell and that a very high proportion of infected tumor cells survive. For more information about this tumor model, see Zacharski, Haemostasis, 16: 300-320

[1986]). One way to evaluate the effectiveness of a test compound in an animal model, implanted tumor, is to measure the size of the tumor before and after treatment. Traditionally, the size of implanted tumors is measured with a calibrator in two or three dimensions. Measurement limited to two dimensions does not accurately reflect tumor size; therefore, it usually becomes the corresponding volume using a ****** - - mathematical formula. However, the measurement of tumor size is very inaccurate. The therapeutic effects of a candidate drug can best be described in the form of growth-induced delay and specific growth retardation. Another important variable in the description of tumor growth is the time of duplication of tumor volume. Computer programs are also available to calculate and describe tumor growth, such as the program reported by Rygaard and Spang-Thomsen, Proc. 6ch Int. Workshop on Immune-Def icient Animáis, Wu and Sheng eds. Base, 1989, 301. However, it is observed that necrosis and inflammatory responses after treatment can actually result in an increase in tumor size, at least initially. Therefore, these changes need to be carefully monitored by a combination of a morphometric method with flow cytometric analysis. Models of recombinant (transgenic) animals can be engineered by introducing the decoding portion of the genes identified herein into the genome of the animals of interest, using standard techniques for the production of transgenic animals. Animals that can serve as targets for transgenic manipulation include, without - - limitations, mice, rats, rabbits, guinea pigs, sheep, goats, pigs and non-human primates, e.g. papiones, chimpanzees and monkeys. Known techniques for introducing a transgene into such animals include pronucleic microinjection (Hoppe and Wanger, U.S. Patent No. 4,873,191); gene transfer mediated by retroviruses in germ lines (e.g., Van der Putten et al., Proc. Na t'l Acad. Sci. USA. 82: 6148-615 [1985 [); white genes in embryonic undifferentiated stem cells (Thompson et al., Cell, 56: 313-321

[1989]); embryo electroporation (lo, Mol, Cell, Biol., 3: 1803-1814

[1983]); sperm-mediated gene transfer (Lavitrano et al., Cell, 57: 717-73

[1989]). For a review, see, for example, U.S. Patent No. 4,736,866. For the purposes of the present invention, the transgenic animals include those that are carriers of the transgene only in part of their cells ("mosaic animals"). The transgene can be integrated as a single transgene, or in concatamers, e.g. tandems head with head or head with tail. The selective introduction of a transgene into a particular cell type is also possible following, for example, the Lasko et al. , Proc. Na t 'l Acad. Sci. USA, 89: 6232-636 (1992). The expression of the transgene in animals ******** kM * A * L * á ** ñ **? *** Ll * ^ ** t ***** - .. * .... ,. *.! - **, * * & -., * - * * z * * * ** ** ^^^ _ 1 * s * m ********* t **** * ^ *********** *****, .. **** *******? * ák * A * ii - transgenic can be monitored by standard techniques. For example, Southern blot analysis or PCR amplification can be used to verify the integration of the transgene. The level of mRNA expression can be analyzed by employing techniques such as in-situ hybridization, Northern blot, RCP or immunocytochemistry. The animals are further examined for signs of tumor or cancer development. The effectiveness of the antibodies to specifically bind to the polypeptides identified herein and to other drug candidates can also be tested in the treatment of spontaneous animal tumors. A suitable target for such studies is feline oral squamous cell carcinoma (SCC). Feline oral CCE is a highly invasive malignant tumor that is the most common oral cancer in cats, accounting for more than 60% of the oral tumors reported in this species. Rarely metastasizes to distant sites, although this low incidence of metastasis is merely reflection of the short survival times of cats suffering from this tumor. These tumors are not usually susceptible to surgery, mainly to the anatomy of the feline oral cavity. At present, there is no treatment * '*, l. *? *, ¿. * "I ,. .J * .. * > ? ** a ^ *. -. ., f - - effective for this tumor. Before entering the study, each cat undergoes a complete clinical examination, biopsy and a computed tomography (CT) scan. Cats diagnosed with oral squamous cell sublingual tumors were excluded from the study. The tongue can be paralyzed as a result of tumors and even if the treatment kills the tumor, the animals may not be able to feed. Each cat was treated repeatedly for a prolonged period of time. Photographs of the tumors were taken daily during the treatment period and at each subsequent verification. After the treatment, each cat was subjected to another CT scan. CT scans and chest x-rays were evaluated every 8 weeks after treatment. The data were evaluated with respect to differences in survival, response and toxicity, compared to a control group. The positive response may require evidence of tumor regression, preferably with an improvement in quality of life and / or an increase in longevity. In addition, other spontaneous animal tumors such as fibrosarcoma, adenocarcinoma, lymphoma, crondroma, leiomyosarcoma in dogs, cats and baboons can also be tested. Of these, mammary adenocarcinoma in dogs and cats is a preferred model, since its appearance and behavior are very similar to those seen in humans.

A J t? A táí - 1 ** - »- - • ^ a", ** ¿** ** Jl * t **. * ****** *? ******* t *** Human. However, the use of this model is limited by the rare presence of this type of tumors in animals. H. Candidate Drug Screening Assays Candidate drug screening assays are designed to identify compounds that competitively bind or complex with the receptor or receptors of the polypeptides identified herein or otherwise signaling through such receivers. These screening assays will include high throughput screening assays of chemical libraries, making them particularly suitable for identifying candidate small molecule drugs. The contemplated small molecules include synthetic organic or inorganic compounds, including peptides, preferably soluble peptides, fusions of (poly) peptide-immunoglobulin and, in particular, antibodies including, without limitation, polyclonal and monoclonal antibodies and fragments of antibodies, antibodies of a single chain, antiidiotypic antibodies and chimeric or humanized versions of such antibodies or fragments, as well as human antibodies and antibody fragments. These assays can be performed in a variety of formats, including protein-protein binding assays, biochemical selection assays, immunoassays and cell-based assays, which are well characterized in the i ^? á ^? j ?? - Miß *. ******* ^.! **,. ** ^ * ^ ***. *. »* aM *. . * **. ^ M * ^? * ~ ^ ** ***. *, ***. * ¿. **. *, **, ^. *** ** ,. Jí **. * **. L * - 24 - technique. In binding assays, the interaction is the binding and the complex formed can be isolated or detected in the reaction mixture. In a particular embodiment, a receptor of a polypeptide encoded by the gene identified herein or the candidate drug, is immobilized on a solid phase, e.g. in a microplate, by means of covalent or non-covalent bonds. The non-covalent binding is generally carried out by coating the solid surface with a solution of the polypeptide and drying. Alternatively, an immobilized antibody, e.g. a monoclonal antibody specific for the polypeptide to be immobilized, to anchor it on a solid surface. The assay is performed by adding the non-immobilized component, which may be labeled with a detectable label, to the immobilized component, e.g. the coated surface containing the anchored component. When the reaction concludes, the components that did not react are -removed, e.g. by a wash, and the complexes anchored in the solid surface are detected. When the non-immobilized component originally carries a detectable label, detection of the immobilized label on the surface indicates that the complexation occurred. When the originally non-immobilized component does not carry a brand, * A * 1 - * Í * ** ?? tÁ .- * - - ____ -, the complex can be detected, for example, by using a labeled antibody directed specifically against the immobilized complex. If the candidate compound interacts but does not bind to a particular receptor, its interaction with that polypeptide can be assayed by known methods to detect protein-protein interactions. Such assays include traditional approaches, such as cross-linking, coinmunoprecipitation and copurification through gradients or chromatographic columns. In addition, protein-protein interactions can be monitored using a yeast-based genetic system described by Fields et al. [Fields and Song, Nature (London), 340: 245-246 (1989); Chien et al. , Proc. Nat 'l Acad. Sci. USA, 88: 9578-9582 (1991) as described by Chevray and Nathans [Proc. Nat 'l Acad. Sci. USA, 88: 5789-5793 (1991)]. Many transcriptional activators, such as yeast GAL4, consist of two physically discrete modular domains, one of which acts as the DNA binding domain, while the other functions as the transcription activation domain. The yeast expression system described in the following publications (generally referred to as the "two-hybrid system") takes advantage of this property and employs two hybrid proteins, one in which the white protein is fused to the **** * * al? * Í * L DNA binding of GAL4, and another in which candidate activator proteins are fused to the activation domain. The expression of the GALl-JacZ reporter gene under the control of a promoter activated by GAL4, depends on the reconstruction of the G.AL4 activity by a protein-protein interaction. Colonies containing interacting polypeptides are detected with a chromogenic substrate for β-galactosidase. A complete package (MATCHMAKER ™) is commercially available to identify protein-protein interactions between two specific proteins, using the two-hybrid technique, and can be purchased from Clontech. This system can also be extended to the mapping of protein domains involved in specific protein interactions, as well as point (or individual) amino acid residues that are crucial for these interactions. I. Pharmaceutical Compositions The polypeptides of the present invention, agonist antibodies that bind -specifically to the proteins identified herein, as well as other molecules identified by the screening assays described herein, can be administered for the treatment of tumors, including cancers. , in the form of pharmaceutical compositions. When antibody fragments are used, the *** * * í - ** i * - *****. *** .. smaller inhibitory fragment that binds specifically the binding domain of the target protein, is preferred. For example, based on the variable region sequences of an antibody, peptide molecules that retain the ability to bind to the target protein sequence can be designed. Such peptides can be chemically synthesized and / or can be produced by recombinant DNA technology (see e.g., Marasco et al., Proc. Nat'l Acad. Sci. USA, 90: 7889-7893

[1993]). The formulation herein may also contain more than one active compound, as necessary for the particular indication being treated, preferably with complementary activities that do not adversely affect one another. Alternatively, or in addition, the composition may comprise an agent that improves its function, for example, a cytotoxic agent, a cytokine, chemotherapeutic agent or growth inhibitory agent. Such molecules, suitably, are presented in combination, in amounts that are effective for the intended purpose. Therapeutic formulations of the polypeptides identified herein or agonists thereof, are prepared to be stored by mixing the active ingredient having the desired degree of purity, with optional pharmaceutically acceptable carriers, or* .*? *** ******. & mi. * * excipients or stabilizers (-Remington's Pharmaceutical Sciences, 16th edition, Osol, A. ed.

[1980]), in the form of lyophilized formulations or aqueous solutions. Acceptable vehicles, excipients or stabilizers are not toxic to the patient at the doses and concentrations employed and include regulatory solutions such as phosphates, citrates and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzylamino chloride, hexamethonium chloride, benzalkonium chloride, benzethonium chloride, phenol, butyl or benzyl alcohol, alkyl parabens such as methyl paraben or porpilparaben, catechol, resorcinol, cyclohexanol, 3-pentanol and m-cresol); low molecular weight polypeptides (less than about 10 residues); proteins such as serum albumin, gelatin or immunoglobulins, hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine or lysine; monosaccharides, disaccharides and other carbohydrates including glucose, mannose or dextrins; chelating agents such as EDTA, sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counterions such as sodium; metal complexes (e.g. Zn-protein complexes); and / or nonionic surfactants such as TWENN ™, PLUORNICS ™ or polyethylene glycol (PEG).

The formulation herein may also contain more than one active compound, as necessary, for the particular indication being treated, preferably those with complementary activities that do not adversely affect one another. Alternatively or in addition, the composition may comprise a cytotoxic agent, a cytokine or a growth inhibitory agent. Such molecules are present, suitably, in combination in amounts that are effective for the intended purpose. The active ingredients can also be entrapped in microcapsules prepared, for example, by coacervation or interfacial polymerization techniques, for example microcapsules of hydroxymethylcellulose or gelatin and poly (methylmethacrylate) microcapsules, respectively, in colloidal drug delivery systems (for example). examples are liposomes, albumin microspheres, microemulsions, nanoparticles and nanocapsules) or in macroemulsions. Such techniques are described in Remington's Pharmaceutical Sciences, 16tn edition, Osol, A. ed. (1980). The formulations to be used for in vivo administration must be sterile. This is easily achieved by filtration through sterile membranes, before or after lyophilization and reconstitution. The therapeutic compositions herein are generally placed in a container having a sterile access port, for example, an intravenous solution bag or a bottle having a stopper that can be pierced by a hypodermic injection needle. Sustained release preparations can be prepared. Suitable examples of sustained release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody, wherein these matrices are in the form of shaped articles, e.g. in the form of film or microcapsules. Examples of sustained release matrices include polyesters, hydrogels (e.g., poly (2-hydroxyethylmethacrylate) or poly (vinylalcohol)), polylactides (U.S. Patent No. 3,773,919), L-glutamic acid copolymers, and? -ethyl -L-glutamate, non-degradable ethylene vinyl acetate, degradable lactic acid-glycolic acid copolymers such as LUPRON-DEPOT ™ (injectable microspheres composed of a copolymer of lactic acid-glycolic acid and leuprolide acetate) and poly-D- acid ( -) -3-hydroxybutyric. While polymers such as ethylene vinyl acetate and lactic acid-glycolic acid are capable of releasing molecules for more than 100 days, certain hydrogels release proteins for periods of time. of shorter time. When the encapsulated antibodies remain in the body for a long time, they can be denatured or added as a consequence of exposure to humidity at 37 ° C, which results in a loss of biological activity and possible changes in immunogenicity. You can devise rational strategies for stabilization, depending on the mechanism involved. For example, if it is discovered that the aggregation mechanism is the formation of intermolecular SS bonds through thio-disulfide exchange, the stabilization can be carried out by modifying the sulfhydryl residues, lyophilizing in acid solutions, controlling the moisture content, using appropriate additives and developing specific polymer matrix compositions. J. Methods of Treatment It is contemplated that the polypeptides of the present invention and their agonists, including antibodies, peptides and small molecule agonists, can be used for the treatment of various tumors, e.g. cancers Some exemplary conditions or disorders that can be treated include benign or malignant tumors (e.g., kidney, liver, kidney, bladder, mammary, gastric, ovarian, colorectal, prostate, pancreatic, pulmonary, vulvar, thyroid, carcinomas tumors. hepatic sarcomas; glioblastomas and various tumors of the head and neck); leukemias and malignant lymphoid diseases; other disorders such as astrocytes, hypothalamic and other glandular disorders, macrophage, epithelial, stromal and blastocoelic disorders; and inflammatory, angiogenic and immunological disorders. The antitumor agents of the present invention (including the polypeptides described herein and agonists that mimic their activity, eg, antibodies, peptides and small organic molecules), are administered to a mammal, preferably a human, in accordance with the methods known, such as intravenous administration in the form of a bolus or continuous infusion over a period of time or by intramuscular, intraperitoneal, intracerebroespinal, intraocular, intraarterial, intralesional, subcutaneous, intraarticular, intrasynovial, intrathecal, oral, topical or inhalation injection. Other therapeutic regimens may be combined with the administration of the anticancer agents of the present invention. For example, the patient can be treated with such anticancer agents but can also receive radiation therapy. Alternatively or in addition, a chemotherapeutic agent may be administered to the patient. The preparation and dose schedules for such chemotherapeutic agents can be used for ta¿IA Í? r * ** Á »Í '. * .. *, 3 * I ** [, **. . according to the manufacturer's instructions or can be determined empirically by the person skilled in the art. Preparation and dosing programs for such chemotherapies are also described in Chemotherapy Service, ed., M.C. Perry, Williams & Wilins, Baltimore, MD (1992). The chemotherapeutic agent may precede or may follow the administration of the antitumor agent of the present invention, or may be administered concurrently therewith. The anti-cancer agents of the present invention can be combined with an antiestrogenic compound, such as tamoxifen, or an anti-progesterone compound, such as onapristone (see European Patent EP 616812), in known doses for such molecules. It may also be desirable to administer antibodies against tumor-associated antigens, such as antibodies that bind to ErbB2, EGFR, ErbB3, ErbB4 or vascular endothelial factor (VEGF). Alternatively or in addition, two or more antibodies that bind to the same or two different antigens associated with the cancer can be co-administered to-1 patient. Sometimes it may also be beneficial to administer one or more cytokines to the patient. In a preferred embodiment, the anticancer agents herein are co-administered with a growth inhibitory agent. For example, the agent * * l * j á A ** lil * ** i, * ** íi ***** í í, **. * **. • *,! *** & **, * ** .A. ., «., ** **. **. **, * my *** t *** í .. * **? ****** *** f *** ji **** *** ******** .. .Í ..? TO .

Growth inhibitor can be administered first, followed by administration of the anti-cancer agent of the present invention. However, simultaneous administration or administration of the anticancer agent of the present invention is also contemplated. Suitable doses for the growth inhibitory agent are those currently used and may be decreased due to the combined action (synergy) of the growth inhibitory agent and the antibody herein. For the prevention or treatment of diseases, the appropriate dose of the antitumor agent herein will depend on the type of disease being treated, as defined above, of the severity and course of the disease, regardless of whether the agent is administered. For preventive purposes or for therapeutic purposes, the dose will also depend on the previous treatment, the patient's clinical history and the response to the agent and the discretion of the attending physician. The agent is suitably administered to the patient only once or in a series of treatments. Experiments in animals provide reliable guidelines for the determination of effective doses for human therapy. The interspecies escalation of the effective doses can be carried out following the principles established by Mordenti, J. and Cappell, W. "The use of interspecies scaling in toxicokinetics "in Toxicokinetics and New Drug Development, Yacobi et al., eds., Pergamon Press, New York 1989, pp. 42-96 For example, depending on the type and severity of the disease, a dose of about 1 μg / kg at 15 mg / kg (eg 0.1 to 20 mg / kg) of an antitumor agent, is an initial candidate dose to be administered to the patient, either, for example, in one or more separate administrations, or in form of a continuous infusion A typical daily dose could be in the range of about 1 μg / kg to 100 mg / kg or more, depending on the factors mentioned above For repeated administrations in several days or more, depending on the condition, The treatment is sustained until a desired suppression of the symptoms of the disease occurs, however, other dosage regimens may be useful.The progress of this therapy is easily monitored by conventional techniques and trials. Particular management plans are provided in the scientific literature; see, for example, U.S. Patent Nos. 4,657,760; 5,206,344 or 5,225,212. It is anticipated that different formulations will be effective for different treatment compounds and different diseases, where administration directed towards a organ or tissue, for example, may need a different distribution to that of another organ or tissue. K. Articles of Manufacture In another embodiment of the present invention, there is provided a manufacturing article containing materials useful for the diagnosis or treatment of the disorders described above. The article of manufacture comprises a container and a label. Suitable containers include, for example, bottles, flasks, syringes and test tubes. The containers can be manufactured with a variety of materials, such as glass or plastic. The container retains a composition that is effective in diagnosing or treating a disorder and can have a sterile access port (e.g., the container can be an intravenous solution bag or can be a bottle having a cap that can be pierced by a hypodermic needle). The active agent in the composition is an antitumor agent of the present invention. The label on, or associated with, the container indicates that the composition is used for the diagnosis or treatment of the chosen disease. The article of manufacture may further comprise a second container comprising a pharmaceutically acceptable regulatory solution., such as phosphate buffer salt solution, Ringer's solution and dextrose solution. It may also include other desirable materials from a commercial and user's point of view, including other regulatory solutions, diluents, filters, needles, syringes and package inserts with instructions for use. The following examples are offered for illustrative purposes only and are not intended to limit the scope of the present invention, in any way. All patents and references of scientific literature cited in the present disclosure are hereby incorporated by reference in their entirety. EXAMPLES Commercially available reagents were used in the examples, in accordance with the manufacturer's instructions, unless stated otherwise. The source of the cells identified in the following examples and throughout the description is with the ATCC access numbers of the American Type Culture Collection, Manassas, VA. EXAMPLE 1 Selection of Extracellular Domain Homology to Identify New Polypeptides and cDNA Encoding for Same Extracellular domain (DEC) sequences (including secretion signal sequences, if any) of approximately 950 known secreted proteins in the Swiss-Prot public database were used to investigate EST databases. The EST databases included public databases, (e.g. Dayhoff, GenBank) and private databases (e.g. LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA). The search was performed using the BLAST computer program or BLAST-2 (Altschul et al., Methods in Enzymology, 266: 460-480 (1996) as a comparison of the DECs of the protein sequences to 6 translation frames of the EST sequences Those comparisons that had a BLAST score of 70 (or in some cases 90) or more, which do not code for known proteins, were pooled and assembled into consensual DNA sequences with the "phrap" program (Phil Green, University of Washington, Seattle, Washington.) Using this selection of extracellular domain homology, consensual .DNA sequences were assembled relative to other EST sequences identified using the phrap program, and consensual DNA sequences obtained often (but not always). they were extended using repeated cycles of BLAST or BLAST-2 and phrap, to extend the consensual sequence as much as possible, using the sources of EST sequences previously described. Based on the consensual sequences obtained in the manner described above, oligonucleotides were synthesized and used to identify, by PCR, a cDNA library containing the sequence of interest and were also used as probes to isolate a clone from the coding sequence of full length of a PRO polypeptide. The forward and reverse PCR primers generally range from 20 to 30 nucleotides and are often designed to obtain a PCR product of approximately 100 to 1000 bp in length. Probe sequences typically are 40 to 55 bp in length. In some cases, additional oligonucleotides were synthesized when the consensual sequence was greater than about 1-1.5 kbp. In order to select several libraries for a full-length clone, DNA from the libraries was selected by PCR amplification in the manner described by Ausubel et al. , Current Protocols in Molecular Biology, with the pair of PCR primers. A positive library was then used to isolate clones that encoded the gene of interest, using the oligonucleotide probe and one of the pair of primers. The cDNA libraries used to isolate the cDNA clones were constructed by standard methods, employing commercially available reagents such as those from Invitrogen, San Diego, CA. The cDNA was primed with oligo-dT containing a NotI site, ligated at a blunt end with Sali adapters, subjected to a cut with the NotI enzyme, given an appropriate size by gel electrophoresis and cloned in a defined orientation in a suitable cloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D not containing the Sfil site, see Holmes et al., Science, 253: 1278-1280 (1991) at the unique sites Xhol and Notl. EXAMPLE 2 Isolation of cDNA Clones Coding for Human PR0179 A cDNA clone (DNA16451-1078) encoding a human PR0179 polypeptide using a selection in yeast was identified in a human fetal liver library that preferentially represents the 5 'ends. of the primary cDNA clones The primers used for the identification of DNA16451-1078 are the following: 0LI114: 5'-CCACGTTGGCTTGAAATTGA-3 '(SEQ ID NO: 3) 0LI115: 5'-CCTTTAGAATTGATCAAGACAATTCATGATTTGATTCTCTATCTCC AGAG-3 '(SEQ ID NO: 4) OLI116: 5'-TCGTCTAACATAGCAAATC-3 '(SEQ ID NO: 5) The clone DNA16451-1078 contains a single open reading frame with an apparent translation start site at the positions of nucleotides 37 to 39 and an apparent stop codon at the nucleotide positions of 1417-1419 (Figure 1; SEQ ID NO: 1). The predicted polypeptide precursor is 460 amino acids in length. The full length PR0179 protein is shown in Figure 2 (SEQ ID NO: 2). The analysis of the full-length sequence of PR0179 shown in Figure 2 (SEQ ID NO: 2) evidences the presence of important polypeptide domains as shown in Figure 2, where the given locations for these important polypeptide domains are approximately , as described above. Analysis of the full-length PR0179 sequence (Figure 2, SEQ ID NO: 2) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 16; N-glycosylation sites at about amino acid 23 to about amino acid 27, from about amino acid 115 to about amino acid 119, from about amino acid 296 to about amino acid 300 and about amino acid 357 to about amino acid 361; phosphorylation sites 1-Hr? MM? i -ttl-tn -fi '~ VWt ~ - ía- ~ frfÍH with cAMP-dependent protein kinase and cGMP from about amino acid 100 to about amino acid 104 and about amino acid 204 to about amino acid 208; a phosphorylation site with torosine kinase from about amino acid 342 to about amino acid 351; N-myristylation sites from about amino acid 279 to about amino acid 285, from about amino acid 352 to about amino acid 358 and from about amino acid 367 to about amino acid 373; and leucine zipper patterns of about amino acid 120 to about amino acid 142 and about amino acid 127 to about amino acid 149. The clone of DNA16451-1078 was deposited in the ATCC on September 18, 1997 and assigned the ATCC deposit number 209281. The full-length protein PR0179 shown in Figure 2 has an estimated molecular weight of approximately 53.637. daltons and an isoelectric point (pl) of about 6.61. An analysis of the Dayhoff database (version 35.45 SwissProt 35) of the full-length sequence shown in Figure 2 (SEQ ID NO: 2), evidenced the presence of a fibrinogen-like domain that exhibits a high degree of homology of sequence with the known human ligands of the TIE-2 receptor (h-TIE-2L1 and h-TIE-2L2). The abbreviation "TIE" is an acronym meaning "homology domains of Ig and EGF containing tyrosine kinase" and this term was coined to designate a new family of tyrosine kinase receptors. In accord with this, PR0179 has been identified as a new member of the TIE ligand family. EXAMPLE 3 Isolation of cDNA Clones Coding for Human PRO207 A DNA database (EST) of expressed sequence tags (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, CA) was investigated and an EST was identified that showed homology with the Human Apo-2 ligand. A cDNA library of human fetal kidney was then investigated. The mRNA isolated from the human fetal kidney tissue (Clontech) was used to prepare the cDNA library. This RNA was used to generate a cDNA library primed with oligo-dT in the pRK5D vector, using reagents and protocols from Life Technologies, Gaithersburg, MD (Super Script Plasmid System). In this procedure, the double-stranded cDNA was given a size greater than 1000 bp and the ligated Sall / Notl cDNA was cloned into a vector that was subjected to a disruption with XhoI / NotI. PRK5D is a cloning vector that has a transcription start site sp6, followed by a Sfil restriction enzyme site preceding the cloning sites of .DNAc ol / Notl. The library was screened by hybridization with a synthetic oligonucleotide probe: 5 '-CCAGCCCTCTGCGCTACAACCGCCAGATCGGGGAGTTTATAGTCACCCGG-3' (SEQ ID NO: 8) based on EST. A clone of .ADNc was sequenced in its entirety. A nucleotide sequence of full length DNA 30879-1152 is shown in Figure 3 (SEQ ID NO: 6). The DNA30879-1152 clone contains a single open reading frame with an apparent translation start site at the nucleotide positions 58 through 60 (Figure 3, SEQ ID NO: 6) and an apparent stop codon at the positions of nucleotides from 805 to 807. The predicted polypeptide precursor is 249 amino acids in length. The analysis of the full length PRO207 sequence shown in Figure 4 (SEQ ID NO: 7) evidences the presence of important polypeptide domains as shown in Figure 4, where the given locations for these important polypeptide domains are approximately described above. Analysis of the full length PRO207 sequence (Figure 4, SEQ ID NO: 7) evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 40; sites ** & N-glycosylation at about amino acid 139 to about amino acid 143; N-myristylation sites from about amino acid 27 to about amino acid 33, from about amino acid 29 to about amino acid 35, from about amino acid 36 to about amino acid 42, from about amino acid 35 to about amino acid 51, from approximately amino acid 118 to about amino acid 124, from about amino acid 121 to about amino acid 127, from about amino acid 125 to about amino acid 131 and from about amino acid 128 to about amino acid 134; amidation sites from about amino acid 10 to about amino acid 14 and from about amino acid 97 to about amino acid 101; a prokaryotic membrane lipoprotein binding site of about amino acid 24 to about amino acid 35. The DNA clone 30879-1152 was deposited with the ATCC on October 10, 1997 and assigned the ATCC deposit number 209358. The protein Full length PRO207 shown in Figure 4, has an estimated molecular weight of about 27,216 daltons and a pl of about 9.61. Based on an alignment analysis of BLAST and FastA sequence (using the ALIGN-2 computer program) of the full length PRO207 sequence shown in Figure 4 (SEQ ID NO: 7), the PRO207 polypeptide shows an amino acid sequence identity with several family members of TNF cytokines and particularly with the human lymphotoxin-beta (23.4%) and with the human CD40 ligand (19.8%). EXAMPLE 4 Isolation of cDNA Clones Coding for Human PRO320 A consensual DNA sequence was assembled relative to other EST sequences using the phrap program as described in Example 1 above. This consensual sequence is designated as DNA28739. Based on the consensual sequence DNA28739, oligonucleotides were synthesized: 1) to identify, by PCR, a cDNA library containing the sequence of interest and 2) to be used as probes for the isolation of a clone from the coding sequence, of length complete for the PRO320 polypeptide. A pair of PCR primers (forward and reverse) was synthesized: forward PCR primer:, 5'-CCTCAGTGGCCACATGCTCATG-3 '(SEQ ID NO: 11) reverse PCR primer: 5'-GGCTGCACGTATGGCTATCCATAG-3 '(SEQ ID NO: 12) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensual DNA28739 sequence, wherein said probe had the following nucleotide sequence: hybridization probe: '-GATAAACTGTCAGTACAGCTGTGAAGACACAGAAGAAGGGCCACAGTGCC-3' (SEQ ID NO: 13) In order to select several libraries for a source of a full-length clone, DNA from the libraries was investigated by PCR amplification, with the pair of PCR primers previously identified. A positive library was then used to isolate clones encoding the PRO320 gene using the oligonucleotide probe and one of the PCR primers. The RNA for the construction of the cDNA libraries was isolated from human fetal lung tissue (LIB025). DNA sequencing of the clones isolated in the manner described above, produced a full-length DNA sequence for DNA32284-1307 [Figure 5, SEQ ID NO: 9]; and the derived protein sequence for PRO320. The complete coding sequence of DNA32284-1307 is included in Figure 5 (SEQ ID NO: 9). The clone DNA32284-1307 contains a single open reading frame with ? "** -» t .., .., (. Ait.n ttm ri.. And *., ***, - ft. * ... *. *, ** .. .. *, * *, ... &"... .., rf, ...," ^,,? t * .iA. an apparent translation start site at the nucleotide positions of 135 to 137 and an apparent stop codon at the nucleotide positions of 1149 to 1151. The predicted polypeptide precursor is 338 amino acids in length. Analysis of the full length PRO320 sequence shown in Figure 6 (SEQ ID NO: 10) evidences the presence of a variety of important polypeptide domains, wherein the locations given for these important polypeptide domains are approximately those described above. Analysis of the full-length PRO320 polypeptide shown in Figure 6 demonstrates the presence of the following: a signal peptide from about amino acid 1 to about amino acid 21; an amidation site of about amino acid 330 to about amino acid 334; hydroxylation sites of aspartic acid and asparagine from about amino acid 109 to about amino acid 121, from about amino acid 191 to about amino acid 203 and from about amino acid 236 to about amino acid 248; a cysteine pattern of EGF-like domain from about amino acid 80 to about amino acid 91; calcium-binding EGF-like domains of about amino acid 103 to about amino acid 125, about Í? **you*? Í »?, í ** & ., - * m, *. "^ * ..,, * .o, s * * iiiA ,. *, **, ^ * ^ ***., * ^ .. M "to ^. " ^^ ^ r ^ amino acid 230 to approximately amino acid 252 and from approximately amino acid 185 to approximately amino acid 207. Clone DNA32284-1307 was deposited with the ATCC on March 11, 1998 and assigned the deposit number ATCC 209670 The full-length PRO320 protein shown in Figure 6 has an estimated molecular weight of about 37,143 daltons and a pl of about 8.92. EXAMPLE 5 Isolation of cDNA Clones Encoding for Human PR0219 A consensual DNA sequence was assembled relative to other EST sequences using the phrap program as described in Example 1 above. This consensual sequence was designated herein as DNA28729. Based on the consensual sequence DNA28729, oligonucleotides were synthesized: 1) to identify, by PCR, an .ADNc library containing the sequence of interest and 2) to be used as probes for the isolation of a clone of the length coding sequence complete for PR0219. A pair of PCR primers (forward and reverse) was synthesized: forward PCR primer: 5'-GTGACCCTGGTTGTGAATACTCC-3 '(SEQ ID NO: 16) **TO" " ". ^ Reverse PCR primer: 5? CAGCCATGGTCTATAGCTTGG-3 '(SEQ ID NO: 17) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensual DNA28729 sequence, wherein said probe had the following nucleotide sequence : Hybridization probe: 5 '-GCCTGTCAGTGTCCTGAGGGACACGTGCTCCGCAGCGATGGGAAG-3' (SEQ ID NO: 18) In order to select several libraries in search of a source of a full-length clone, .ADN of the libraries was investigated by PCR amplification, with the pair of PCR primers previously identified.

A positive library was then used to isolate clones encoding the PR0219 gene using the oligonucleotide probe and one of the PCR primers. The RNA for the construction of the cDNA libraries was isolated from human fetal kidney tissue. The DNA sequencing of. clones isolated in the manner previously described, produced a sequence of Full-length DNA for DNA32290-1164 [Figure 7, SEQ ID NO: 14]; and the derived protein sequence for PR0219. The complete coding sequence of DNA32290-1164 is included in Figure 7 (SEQ ID NO: 14). The clone DNA32290-1164 contains a single open reading frame with an apparent translation start site at the nucleotide positions of 204 to 206 and an apparent stop codon at the nucleotide positions of 2949 to 2951. The predicted polypeptide precursor has 1005 amino acids in length. The analysis of the full length sequence PR0219 shown in Figure 8 (SEQ ID NO: 15) evidences the presence of a variety of important polypeptide domains, wherein the locations given for these important polypeptide domains are approximately those described above. Analysis of the full length PR0219 polypeptide shown in Figure 8 demonstrates the presence of the following: a signal peptide from about amino acid 1 to about amino acid 23; a N-glycosylation site of about amino acid 221 to about amino acid 225; cAMP-dependent protein kinase and cGMP phosphorylation sites from about 115 amino acid to about amino acid 119, from about amino acid 606 to about amino acid 610 and from about amino acid 892 to about amino acid 896; N-myristylation sites of about amino acid 133 to about amino acid 139, from about amino acid 258 to about amino acid 264, of approximately amino acid 299 to about amino acid 305, from about amino acid 340 to about amino acid 346, from about amino acid 453 to about amino acid 459, from about amino acid 494 to about amino acid 500, from about amino acid 639 to about amino acid 645, from about amino acid 690 to about amino acid 694, from about amino acid 752 to about amino acid 758 and from about amino acid 792 to about amino acid 798; amidation sites from about amino acid 314 to about amino acid 318, from about amino acid 560 to about amino acid 564 and from about amino acid 601 to about amino acid 605; and hydroxylation sites of aspartic acid and asparagine from about amino acid 253 to about amino acid 265, from about amino acid 294 to about amino acid 306, from about amino acid 335 to about amino acid 347, from about amino acid 376 to about amino acid 388, from about amino acid 417 to about amino acid 429, from about amino acid 458 to about amino acid 470, from about amino acid 540 to about amino acid 552 and from about amino acid 581 to about amino acid 593. The clone DNA32290-1164 was deposited with the ATCC on October 17, 1997 and assigned the ATCC deposit number 209384. The full length protein PR0219 shown in Figure 8 has an estimated molecular weight of approximately 102,233 daltons and a pl of approximately 6.02. An analysis of the full-length sequence PR0219 shown in Figure 8 (SEQ ID NO: 15) suggests that portions of it possess significant homology with murine and human matrilin-2 precursor polypeptides. EXAMPLE 6 Isolation of cDNA Clones Coding for Human PR0221 A consensual DNA sequence was assembled relative to other EST sequences, using the phrap program as described in Example 1 above. This consensus sequence is designated herein as DNA28756. Based on the consensual sequence DNA28756, oligonucleotides were synthesized: 1) to identify, by PCR, a cDNA library containing the sequence of interest and 2) to be used as probes for the isolation of a clone from the full-length coding sequence for PR0221.

A pair of PCR primers (forward and reverse) was synthesized: forward PCR primer: 5'-CCATGTGTCTCCTCCTACAAAG-3 '(SEQ ID NO: 21) reverse PCR primer: 5'-GGGAATAGATGTGATCTGATTGG-3' ( SEQ ID NO: 22) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensual DNA28756 sequence, wherein said probe had the following nucleotide sequence: hybridization probe: 5 '-CACCTGTAGCAATGCAAATCTCAAGGAAATACCTAGAGATCTTCCTCCTG-3' (SEQ ID NO: 23) In order to select several libraries in search of a source of a full-length clone, DNA from the libraries was investigated by PCR amplification, with the pair of PCR primers identified above. A positive library was then used to isolate clones encoding the PR0221 gene, using the oligonucleotide probe and one of the PCR primers. He RNA for the construction of cDNA libraries was isolated from human fetal lung tissue. DNA sequencing of the clones isolated in the manner described above, produced a full-length DNA sequence for DNA33089-1132 [Figure 9, * i.AÁ -? ** á? á ** ^ A i, "., * .., - ^ .." ^ _. ... .. . , ^, ^. ^ ..... _ "_ ..., ._....,» ¿,., T t ^, ^^^ SEQ ID NO: 19]; and the derived protein sequence for PR0221. The complete coding sequence of DNA33089-1132 is included in Figure 9 (SEQ ID NO: 19). The clone DNA33089-1132 contains a single open reading frame with an apparent translation start site at nucleotide positions 179 through 181 and an apparent stop codon at the nucleotide positions from 956 to 958. The predicted polypeptide precursor has 259 amino acids in length. The analysis of the full length sequence PR0221 shown in Figure 10 (SEQ ID NO: 20) evidences the presence of a variety of important polypeptide domains, where the locations given for these important polypeptide domains are approximately those described above. Analysis of the full-length PR0221 polypeptide shown in Figure 10 demonstrates the presence of the following: a signal peptide from about amino acid 1 to about amino acid 33; a transmembrane domain of about amino acid 204, at about amino acid 219, N-glycosylation sites at about amino acid 47 to about amino acid 51 and about amino acid 94 to about amino acid 98; a cGMP-dependent protein kinase phosphorylation site of about j **. * i, ** .1 Á ..1 * **** t ** i.,. . * amino acid 199 to about amino acid 203; and N-myristylation sites from about amino acid 37 to about amino acid 43, from about amino acid 45 to about amino acid 51 and from about 5 amino acid 110 to about amino acid 116. The clone of DNA33089-1132 was deposited in the ATCC on September 16, 1997 and assigned the ATCC deposit number 209262. The full-length PR0221 protein shown in Figure 10 has a weight 10 estimated molecular weight of approximately 29,275 daltons and a pl of approximately 6.92. An analysis of the full-length sequence PR0221 shown in Figure 10 (SEQ ID NO: 20), shows that it has homology with members of the superfamily of 15 proteins with leucine-rich repeats, including the SLIT protein. EXAMPLE 7 Isolation of cDNA Clones Coding for Human PR0224 A consensual DNA sequence was assembled relative to other EST sequences using the phrap program as described in Example 1 above. This consensual sequence was designated herein as DNA30845. Based on the consensual sequence DNA30845, 25 synthesized oligonucleotides: 1) to identify, by -rflHMilHiNTr v L ***********! *. ^. * t * **** t **. ***? * M *,?, .. l.? t.

PCR, an .ADNc library containing the sequence of interest and 2) to be used as probes for the isolation of a clone of the full-length coding sequence for PR0224. A pair of PCR primers (forward and reverse) was synthesized: forward PCR primer: 5'-AAGTTCCAGTGCCGCACCAGTGGC-3 '(SEQ ID NO: 26) reverse PCR primer: 5'-TTGGTTCCACAGCCGAGCTCGTCG-3' ( SEQ ID NO: 27) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensual DNA30845 sequence, wherein said probe had the following nucleotide sequence: hybridization probe: 5'-GAGGAGGAGTGCAGGATTGAGCCATGTACCCAGAAAGGGCAATGCCCACC-3 '(SEQ ID NO: 28) In order to select several libraries for a source of a full-length clone, the .ADN of the libraries was investigated by PCR amplification, with the above-identified pair of PCR primers. A positive library was then used to isolate clones encoding the PR0224 gene using the oligonucleotide probe and one of the PCR primers. The RNA for the construction of the cDNA libraries was isolated "Í% P .láaÜ iíla. of human fetal liver tissue. DNA sequencing of the clones isolated in the manner described above produced a sequence of Full-length DNA of the clone DNA-33221-1133 [Figure 11, SEQ ID NO: 24]; and the derived protein sequence for PR0224. The complete coding sequence of DNA33221- 1133 is included in Figure 11 (SEQ ID NO: 24). The clone DNA33221-1133 contains a single open reading frame with an apparent translation start site at the nucleotide positions 33 to 35 and an apparent stop codon at the nucleotide positions from 879 to 881. The predicted polypeptide precursor has 282 amino acids in length. The analysis of the full-length sequence PR0224 shown in Figure 12 (SEQ ID NO: 25) evidences the presence of a variety of important polypeptide domains, wherein the locations given for these important polypeptide domains are approximately those described above. Analysis of the full-length PR0224 polypeptide shown in Figure 12 demonstrates the presence of the following: a signal peptide from about amino acid 1 to about amino acid 30; a transmembrane domain of about amino acid 231 to about amino acid 248; N-glycosylation sites of ? *** k ** k í- * * n * á * í *** t * __. approximately amino acid 126 to about amino acid 130, from about amino acid 195 to about amino acid 199 and about amino acid 213 to about amino acid 217; N-myristylation sites from about amino acid 3 to about amino acid 9, from about amino acid 10 to about amino acid 16, from about amino acid 26 to about amino acid 32, from about amino acid 30 to about amino acid 36, from approximately amino acid 112 to about amino acid 118, from about amino acid 166 to about amino acid 172, from about amino acid 212 to about amino acid 218, from about amino acid 224, to about amino acid 230, from about amino acid 230 to approximately amino acid 236 and from about amino acid 263 to about amino acid 269, a lipid binding site of prokaryotic membrane lipoprotein of about amino acid 44, of about amino acid 55 and a leucine zipper pattern of about amino acid 17 to approximately amino acid 39. The clone DNA33221-1133 was deposited with the ATCC on September 16, 1997 and assigned the ATCC deposit number 209263. The protein PR0224 in length complete shown in Figure 12 has an estimated molecular weight of approximately 28, 991 daltons and a pl of about 4.62. An analysis of the full-length sequence PR0224 shown in Figure 12 (SEQ ID NO: 25) suggests that it has homology with very low density lipoprotein receptors, the apolipoprotein E receptor and the chicken oocyst P95 receptor. Based on an analysis of sequence alignment by BLAST and FastA of the full-length sequence, PR0224 polypeptide has an amino acid sequence identity with portions of these proteins, in the range of 28 to 45% and a global identity with these proteins in the range of 33 to 39%. EXAMPLE 8 Isolation of cDNA Clones Encoding for Human PR0328 A consensual DNA sequence was assembled relative to other EST sequences using the phrap program as described in Example 1 above. This consensual sequence was designated herein as DNA35615. Based on the consensual sequence DNA35615, oligonucleotides were synthesized: 1) to identify, by PCR, a cDNA library containing the sequence of interest and 2) to be used as probes for the -afc isolation of a clone from the full-length coding sequence for PR0328. A pair of PCR primers (forward and reverse) was synthesized: forward PCR primer: 5'-TCCTGCAGTTTCCTGATGC-3 '(SEQ ID NO: 31) reverse PCR primer: 5'-CTCATATTGCACACCAGTAATTCG-3' ( SEQ ID NO: 32) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensual DNA35615 sequence, wherein said probe had the following nucleotide sequence: hybridization probe: 5'-ATGAGGAGAAACGTTTGATGGTGGAGCTGCACAACCTCTACCGGG-3 '(SEQ ID NO: 33) In order to select several libraries for a source of a full-length clone, DNA from the libraries was investigated by PCR amplification, with the pair of PCR primers identified above. A positive library was then used to isolate clones encoding the PR0328 gene using the oligonucleotide probe and one of the PCR primers. The RNA for the construction of the cDNA libraries was isolated from human fetal kidney tissue. DNA sequencing of the clones isolated in the manner described above, produced a full-length DNA sequence for DNA40587-1231 [Figure 13, SEQ ID NO: 29]; and the derived protein sequence for PR0328. The complete coding sequence of DNA40587- 1231 is included in Figure 13 (SEQ ID NO: 29). The clone DNA40587-1231 contains a single open reading frame with an apparent translation start site at nucleotide positions from 15 to 17 and an apparent stop codon at nucleotide positions from 1404 to 1406. The predicted polypeptide precursor has 463 amino acids in length. The analysis of the full length sequence PR0328 shown in Figure 14 (SEQ ID NO: 30) evidences the presence of a variety of important polypeptide domains, wherein the locations given for these important polypeptide domains are approximately those described above. Analysis of the full-length PR0328 polypeptide shown in Figure 14, evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 22; N-glycosylation sites from about amino acid 114 to about amino acid 118, from about amino acid 403 to about amino acid 407 and about amino acid 409 to about i? A ** i **. * **************? ******? ... * * ^ *** _ **** *** *, **. amino acid 413; an inoglycan glucose binding site of about amino acid 439 to about amino acid 443; N-myristylation sites of about amino acid 123 to about amino acid 129, from about amino acid 143 to about amino acid 149, from about amino acid 152 to about amino acid 158, from about amino acid 169 to about amino acid 175, approximately amino acid 180 to about amino acid 186, from about amino acid 231 to about amino acid 237 and about amino acid 250 to about amino acid 256; amidation sites of about amino acid 82 to about amino acid 88 and about amino acid 172 to about amino acid 176; a ligand-hem identification site proximal to peroxidase from about amino acid 287 to about amino acid 298; an extracellular protein identification domain 1 SCP / Tpx-1 / Ag5 / PR-1 / Sc7 from about amino acid 127 to about amino acid 138; and an extracellular protein identification domain 2 SCP / Tpx-l / Ag5 / PR-1 / Sc7 from about amino acid 160 to about amino acid 172. The clone DNA40587-1231 was deposited with the ATCC on November 7, 1997 and it was assigned the deposit number ATCC 209438. The full-length protein PR0328 shown in Figure 14 has an estimated molecular weight of approximately 49., 471 daltons and a pl of approximately 5.36. An analysis of the full-length sequence PR0328 shown in Figure 14 (SEQ ID NO: 30), suggests that portions of it possess significant homology to the human glioblastoma protein and to the secretory protein rich in cysteine, indicating this PR0328 can be a new glioblastoma protein or a new secretory protein rich in cysteine. EXAMPLE 9 Isolation of cDNA Clones Coding for Human PRO301 A consensual DNA sequence was assembled relative to other EST sequences, using the phrap program as described in Example 1 above. This consensual sequence was designated-herein as DNA35936. Based on the consensual sequence DNA35936, oligonucleotides were synthesized: 1) to identify, by PCR, a cDNA library containing the sequence of interest and 2) to be used as probes for the isolation of a clone from the full-length coding sequence for PRO301. , *** i *** **.

The oligonucleotides used in the above procedure were the following: forward PCR primer 1: 5'-TCGCGGAGCTGTGTTCTGTTTCCC-3 '(SEQ ID NO: 36) forward PCR primer 2: 5'-ACACCTGGTTCAAAGATGGG-3' (SEQ ID NO: 37) PCR forward primer 3: 5'-TTGCCTTACTCAGGTGCTAC-3 '(SEQ ID NO: 38) Reverse PCR primer 1: 5'-TAGGAAGAGTTGCTGAAGGCACGG-3' (SEQ ID NO: 39) PCR primer of Reverse 2: 5'-ACTCAGCAGTGGTAGGAAAG-3 '(SEQ ID NO: 40) 1: 5' Hybridization probe -TGATCGCGATGGGGACAAAGGCGCAAGCTCGAGAGGAAACTGTTGTGCCT-3 '(SEQ ID NO: 41) In order to select several libraries in search of a source of a full-length clone, DNA from the libraries was investigated by PCR amplification, with the pair of PCR primers identified above. A positive library was then used to isolate clones encoding the PRO301 gene using the oligonucleotide probe and one of the PCR primers. The RNA for the construction of the cDNA libraries was isolated from human fetal kidney tissue. DNA sequencing of clones isolated from the manner described above, produced a full-length DNA sequence for DNA40628-1216 [Figure 15, SEQ ID NO: 34]; and the derived protein sequence for PR0301. The complete coding sequence of DNA40628-1216 is included in Figure 15 (SEQ ID NO: 34). Clone DNA40628-1216 contains a single open reading frame with an apparent translation start site at nucleotide positions 52 through 54 and an apparent stop codon at nucleotide positions from 949 to 951. The predicted polypeptide precursor has 299 amino acids in length. The analysis of the full length PRO301 sequence shown in Figure 16 (SEQ ID NO: 35) evidences the presence of a variety of important polypeptide domains, wherein the locations given for these important polypeptide domains are approximately those described above. Analysis of the full-length PRO301 polypeptide shown in Figure 16 demonstrates the presence "of the following: a signal peptide from about amino acid 1 to about amino acid 27; a transmembrane domain from about amino acid 235 to about amino acid 256 an N-glycosylation site of about amino acid 185 to about amino acid 189, and a phosphorylation site with ** H * .A. * Á **? * ~, T ** d * A * .í *. * ************ »! *. ! * *. ******** .... í **,., .. * &? ***? M¡Éá * í? **. j,] t .il, .. im t ,, .... ^ ... .h,.,. *. ^ * * £. ** .. * t ... - 2 - Protein kinase dependent on cAMP and cGMP of about amino acid 270 to about amino acid 274; and N-myristylation sites from about amino acid 105 to about amino acid 111, from about amino acid 116 to about amino acid 122, from about amino acid 158 to about amino acid 164, from about amino acid 219 to about amino acid 225, from about amino acid 237 to about amino acid 243 and from about amino acid 256 to about amino acid 262. The clone DNA40628-1216 was deposited with the ATCC on November 7, 1997 and assigned the ATCC deposit number 209432. PRO301 full-length protein shown in Figure 16 has an estimated molecular weight of about 32,583 daltons and a pl of about 8.29. Based on a sequence alignment using BLAST and FastA of the full length PRO301 sequence shown in Figure 16 (SEQ ID NO: 35), the PRO301 polypeptide shows an amino acid sequence identity with the antigen precursor A33 (30% ) and the coxsackie and adenovirus receptor protein (29%).

EXAMPLE 10 Isolation of cDNA Clones Coding for Human PR0526 A consensual DNA sequence was assembled relative to other EST sequences using the phrap program as described in Example 1 above. An initial consensual sequence designated herein as DNA39626 was identified. init. In addition, the initial consensual DNA sequence was extended using repeated BLAST and phrap sites to extend the initial consensual sequence as much as possible, using the sources of EST sequences described above. The assembled consensual sequence is designated herein as >; consen01 > . Based on the consensual sequence < consens01 > , oligonucleotides were synthesized: 1) to identify, by PCR, a cDNA library containing the sequence of interest and 2) to be used as probes for the isolation of a clone of the full-length coding sequence for PR0526. A pair of PCR primers (forward and reverse) was synthesized: forward PCR primer: 5'-TGGCTGCCCTGCAGTACCTCTACC-3 '(SEQ ID NO: 44) reverse PCR primer: 5'-CCCTGCAGGTCATTGGCAGCTAGG-3' ( SEQ ID NO: 45) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the consensual sequence < consens01 > , wherein said probe had the following nucleotide sequence: hybridization probe: 5 '-AGGCACTGCCTGATGACACCTTCCGCGACCTGGGCAACCTCACAC-3' (SEQ ID NO: 46) In order to select several libraries in search of a source of a full-length clone, investigated library DNA by PCR ification, with the above-identified pair of PCR primers. A positive library was then used to isolate clones encoding the PR0526 gene, using the oligonucleotide probe and one of the PCR primers. RNA for the construction of cDNA libraries was isolated from human fetal liver tissue (LIB228). DNA sequencing of the clones isolated in the manner described above, produced a full-length DNA sequence for DNA44184-1319 [Figure 17, SEQ ID NO: 42]; and the protein sequence derived for PR0526. The complete coding sequence of DNA44184-1319 is included in Figure 17 (SEQ ID NO: 42). Clone DNA44184-1319 contains a single open reading frame with an apparent translation start site in the positions lA * A **. *. * i **? ** A ^ I * r. *! ***** **. *** "* * M a ^» *, $. » ,. to . . to. **** . _, *, -. * *** ***. * .._ **** > . . *, "Fc__" "^^ j ^ J *. nucleotides from 514 to 516 and an apparent stop codon at nucleotide positions from 1933 to 1935. The predicted polypeptide precursor is 473 amino acids in length. The analysis of the full length sequence PR0526 shown in Figure 18 (SEQ ID NO: 43), evidences the presence of a variety of important polypeptide domains, wherein the locations given for these important polypeptide domains are approximately those described above. Analysis of the full length PR0526 polypeptide shown in Figure 18, demonstrates the presence of the following: a signal peptide from about amino acid 1 to about amino acid 26; a leucine zipper pattern of about amino acid 135 to about amino acid 157; a glycosaminoglycan binding site of about amino acid 436 to about amino acid 440; N-glycosylation sites from about amino acid 82 to about amino acid 86, from about amino acid 179 to about amino acid 183, from about amino acid 237 to about amino acid 241, from about amino acid 372 to about amino acid 376 and from about amino acid 423 to about amino acid 427; and a von Willebrand Factor (VWF) type C domain of approximately amino acid 411 to about amino acid 427. Clone DNA44184-1319 was deposited with the ATCC on March 26, 1998 and assigned the ATCC deposit number 209704. The full-length PR0526 protein shown in Figure 18 has a estimated molecular weight of approximately 50,708 daltons and a pl of approximately 9.28. An analysis of the full length sequence PR0526 shown in Figure 18 (SEQ ID NO: 43), suggests that portions of it possess significant homology with proteins rich in leucine repeats including ALS, SLIT, carboxypeptidase and platelet glycoprotein V, indicating in this way PR0526 polypeptide is a new protein that is involved in protein-protein interactions. EXAMPLE 11 Isolation of cDNA Clones Encoding for Human PR0362 A consensual DNA sequence was assembled relative to other EST sequences, using the phrap program as described in Example 1 above. This consensual sequence was designated here as DNA42257. Based on the consensual sequence DNA42257, oligonucleotides were synthesized: 1) to identify, by PCR, a cDNA library containing the sequence of i * í *. **** A, --- *: - ".- * - ** ...... ** - -ff "* ~ f - - interest and 2) to be used as a probe for the isolation of a clone of the full-length coding sequence for PR0362. A pair of PCR primers (forward and reverse) was synthesized: primer CPR forward 1: 5 '-TATCCCTCCAATTGAGCACCCTGG-3' (SEQ ID NO: 49) PCR forward primer 2 5 '-GTCGGAAGACATCCCAACAAG-3' (SEQ ID NO: 50) Reverse PCR primer 1: 5 '- CTTCACAATGTCGCTGTGCTGCTC-3 '(SEQ ID NO: 51) Reverse PCR primer 2: 5' -AGCCAAATCCAGCAGCTGGCTTAC-3 '(SEQ ID NO: 52) Additionally, a synthetic oligonucleotide hybridization probe was constructed from the DNA sequence42257 consensual, wherein said probe had the following nucleotide sequence: hybridization probe: 5'-TGGATGACCGGAGCCACTACACGTGTGAAGTCACCTGGCAGACTCCTGAT-3 '(SEQ ID NO: 53) In order to select several libraries in search of a source of a full-length clone, DNA from libraries was investigated by amplifies CPR, with the pair of PCR primers previously identified. Then a positive library was used to isolate clones encoding the PR0362 gene using the oligonucleotide probe and one of the PCR primers. RNA for the construction of cDNA libraries was isolated from human fetal brain tissue (LIB153). DNA sequencing of the clones isolated in the manner described above, produced a full-length DNA sequence for DNA45416-1251 [Figure 19, SEQ ID NO: 47]; and the derived protein sequence for PR0362. The complete coding sequence of DNA45416-1251 is included in Figure 19 (SEQ ID NO: 47). The clone DNA45416-1251 contains a single open reading frame with an apparent translation start site at the nucleotide positions of 119 to 121 and an apparent stop codon at the nucleotide positions from 1082 to 1084. The predicted polypeptide precursor has 321 amino acids in length. The analysis of the full-length sequence PR0362 shown in Figure 20 (SEQ ID NO: 48), evidences the presence of a variety of important polypeptide domains, wherein the locations given for these important polypeptide domains are approximately those described above. Analysis of the full-length PR0362 polypeptide shown in Figure 20, evidences the presence of the following: a signal peptide of about - - amino acid 1 to about amino acid 19; a transmembrane domain of about amino acid 281 to about amino acid 300; a glycosaminoglycan binding site of about amino acid 149 to about amino acid 153; a phosphorylation site with cAMP-dependent protein kinase and cGMP from about amino acid 308 to about amino acid 312; and N-myristylation sites from about amino acid 2 to about amino acid 8, from about amino acid 148 to about amino acid 154, from about amino acid 158 to about amino acid 164, from about amino acid 207 to about amino acid 213 and from about amino acid 215 to about amino acid 221. The clone DNA45416-1251 was deposited with the ATCC on February 5, 1998 and assigned the ATCC deposit number 209620. The full-length PR0362 protein shown in Figure 20 has an estimated molecular weight of approximately 35,544 daltons and a pl of approximately 8.51. An analysis of the full-length sequence PR0362 shown in Figure 20 (SEQ ID NO: 48) suggests that it possesses a significant similarity to the A33 antigen protein and the HCAR protein. More specifically, an analysis of the Dayhoff database (version 35.45 SwissProt 35) showed a significant homology between the amino acid sequence of PR0362 and the following Dayhoff sequences: AB002341_1, HSU55258_1, HSC7NRCAM_1, R? TU81037_1, A33_HUMAN, P_W14158, NMNCAMR1_1, HSTITINN2_1, S71824_l and HSU63041_1. EXAMPLE 12 Isolation of cDNA Clones Coding for Human PR0356 A database of -DNA (EST) of expressed sequence tags (LIFSEQ®,, Incyte) was investigated.

Pharmaceuticals, Palo Alto, CA) and an EST was identified (# 2939340) that had homology with PR0179 polypeptide [identified in EXAMPLE 2 above and designated as DNA16451-1078 (Figure 1; SEQ ID NO: 1)]. To clone PR0356, a human fetal lung library prepared from mRNA purchased from Clontech, Inc. was used.

(Palo Alto, CA), catalog # 6528-1, following the manufacturer's instructions. DNA libraries used to isolate cDNA clones encoding human PR0356 were constructed by standard methods using commercially available reagents such as those from Invitrogen, San Diego, CA. The cDNA was primed with oligo-dT containing a NotI site, ligated with a blunt end to Sali hemicinase adapters, subjected to breaking with Notl i * i. ? * .í *********** ***. .., .-! *. * > * Í ^^ H *** ***** i *. S ****!. *. * .. *. ^. . -. -!., * * * * * * * **. J ** * **** e * t * ^. **% £ *! * & _M ** k2 ?? was given an appropriate size by gel electrophoresis and cloned in a defined orientation in a suitable cloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D not containing the Sfil site, see Holmes et al., Science, 253: 1278-1280 (1991) at the unique Xhol and Notl sites, then oligonucleotide probes were synthesized based on the EST sequence described above: 1) to identify, by PCR, a cDNA library containing the sequence of interest and ) to be used as a probe for the isolation of a clone from the full-length coding sequence for PR0356. The forward and reverse PCR primers generally range from 20 to 30 nucleotides and are often designed to produce a PCR product of approximately 100 to 1000 bp in length. The sequences of the probes are typically 40 to 55 bp in length. In order to select several libraries for a full-length clone, the DNA of the libraries was selected by PCR amplification, according to the method of Ausubel et al. , Current Protocols in Molecular Biology, supra, with the pair of PCR primers. A positive library was then used to isolate clones encoding the gene of interest, using the oligonucleotide probe and one of the primer pairs. ,. ^ .j. The oligonucleotide sequences used were the following: 5'-TTCAGCACCAAGGACAAGGACAATGACAACT-3 (SEQ ID NO: 56) 5'-TGTGCACACTTGTCCAAGCAGTTGTCATTGTC-3 '(SEQ ID NO: 57) 5'-GTAGTACACTCCATTGAGGTTGG-3' (SEQ ID NO: 58) The cDNA clone was identified and sequenced in its entirety. The complete nucleotide sequence of clone DNA47470-1130-P1 is shown in Figure 21 (SEQ ID NO: 54). The clone DNA47470-1130-P1 contains a single open reading frame with an apparent translation start site at nucleotide positions 215 to 217 and a stop codon at the nucleotide positions of 1253 through 1255 (Figure 21; ID NO: 54). The predicted polypeptide precursor is 346 amino acids in length and has a calculated molecular weight of about 40,018 daltons and an estimated pl of about 8.19. The full length PR0356 protein is shown in Figure 22 (SEQ ID NO: 55). Analysis of the full-length sequence of PR0356 shown in Figure 22 (SEQ ID NO: 55), demonstrates the presence of important polypeptide domains as shown in Figure 22, where the locations given for these important polypeptide domains are approximately as described above. The analysis of the PR0356 sequence of * Á **. T .A. * Á.ÁMrf. ». ***** full length (Figure 22, SEQ ID NO: 55), evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 26; N-glycosylation sites at about amino acid 58 to about amino acid 62, from about amino acid 253 to about amino acid 257 and about amino acid 267 to about amino acid 271; a glycosaminoglycan binding site of about amino acid 167 to about amino acid 171; a phosphorylation site with c7AMP-dependent protein kinase and cGMP from about amino acid 176 to about amino acid 180; N-myristylation sites from about amino acid 168 to about amino acid 174, from about amino acid 196 to about amino acid 202, from about amino acid 241 to about amino acid 247, from about amino acid 252 to about amino acid 258, from approximately - amino acid 256 to about amino acid 262 and about amino acid 327 to about amino acid 333; and a cell-binding sequence from about amino acid 199 to about amino acid 202. The clone of DNA47470-1130-P1 was deposited with the ATCC on October 28, 1997 and assigned the number ATCC Deposit 209422. It should be understood that the deposited clone is the actual correct sequence, rather than the representations provided herein. An analysis of the Dayhoff database (version 35.45 SwissProt 35), using the ALIGN-2 sequence alignment analysis of the full-length sequence shown in Figure 22 (SEQ ID NO: 55), shows the sequence identity of amino acids between the amino acid sequence of PR0356 and the proteins TIE-2L1 (32%) and TIE-2L2 (34%). The abbreviation "TIE" is an acronym (in English) which means "homology domains of Ig and EGF containing tyrosine kinase" and this term was coined to designate a new family of tyrosine kinase receptors. EXAMPLE 13 Isolation of cDNA Clones Coding for Human PRO509 To isolate a cDNA from clone DNA50148-1068, a bacteriophage library of human retinal cDNA (commercially available in Clontech) was selected by hybridization, with a synthetic oligonucleotide probe based on an EST sequence (GenBank, locus AA021617), which showed some degree of homology with members of the TNFR family. The oligonucleotide probe used in the selection was 60 bp in length. Five were identified positive clones (containing cDNA inserts of 1.8 to 1.9 kb) in the cDNA library and positive clones were confirmed to be specific, by PCR, using the above hybridization probe as a primer for PCR. Single phage plaques containing each of the five positive clones were isolated by limiting dilution and the DNA was purified using the Wizard Lambda Prep .ADN purification kit (commercially available from Promega). The .ADNc inserts from three of the five bacteriophage clones were cut from the vector arms by digestion with the £ coRI enzyme, gel purified and subcloned into pRK5 and both strands were sequenced. The three clones contained an identical open reading frame (with the exception of an intron found in one of the clones). The complete nucleotide sequence of clone DNA50148-1068 is shown in Figure 23 (SEQ ID NO: 59). The cDNA contained an open reading frame with a translation start site assigned to the ATG codon at nucleotide positions 82 to 84. The ends of the open reading frame and the TGA stop codon were found at nucleotide positions 931 to 933. The predicted amino acid sequence of the full-length PRO509 polypeptide contains 283 ?,? eá *** í * ^ * «.afea ,,» s ** M ** M? * ^? , * * n¡ * t A ** ± - ^ .. *., ...... "? ^ * .. *. * ***** **, **, * _, * _ & ** .. - 30 - amino acids. The full-length PRO509 protein is shown in Figure 24 (SEQ ID NO: 60) and has an estimated molecular weight of approximately 34,420 daltons and a pl of approximately 7.34. The analysis of the full length sequence of PRO509 shown in Figure 24 (SEQ ID NO: 60), evidences the presence of important polypeptide domains as shown in Figure 24, where the locations given for these important polypeptide domains are approximately as described above. Analysis of the full-length PRO509 sequence (Figure 24, SEQ ID NO: 60), evidences the presence of the following: a signal peptide from about amino acid 1 to about amino acid 36; a transmembrane domain of about amino acid 205 to about amino acid 221; N-glycosylation sites of about amino acid 110 to about amino acid 114 and about amino acid 173- to about amino acid 177; N-myristylation sites from about amino acid 81 to about amino acid 87, from about amino acid 89 to about amino acid 95, from about amino acid 104 to about amino acid 110, from about amino acid 120 to about amino acid 126, from about amino acid 153 to about amino acid 159, from about amino acid 193 to about amino acid 199, from about amino acid 195 to about amino acid 201 and from about amino acid 220 to about amino acid 226; and a cell-binding sequence from about amino acid 231 to about amino acid 234. An alignment (using the ALIGN® computer program) of a cytoplasmic region of 58 amino acids in length of the PRO509 polypeptide, with other known members of the family of human TNF receptors, showed similarity of sequence and in particular with CD40 (12 identities) and with the LT-beta receptor (11 identities). EXAMPLE 14 Isolation of cDNA Clones Coding for Human PRO866 A consensual DNA sequence was assembled relative to other EST sequences, using the phrap program as described in Example 1 above. This consensual sequence was designated herein as DNA44708. Based on the consensus sequence DNA44708, oligonucleotides were synthesized: 1) to identify, by PCR, a cDNA library containing the sequence of interest and 2) to be used as a probe for the isolation of a clone of the full-length coding sequence for PR0866. CPR primers (forward and reverse) were synthesized: forward PCR primer 1: 5'-CAGCACTGCCAGGGGAAGAGGG-3 '(SEQ ID NO: 63) forward PCR primer 2: 5'-CAGGACTCGCTACGTCCG-3' ( SEQ ID NO: 64) PCR forward primer 3: 5'-CAGCCCCTTCTCCTCCTTTCTCC-3 '(SEQ ID NO: 65) Reverse PCR primer 1: 5'-GCAGTTATCAGGGACGCACTCAGCC-3' (SEQ ID NO: 66) primer Reverse PCR 2: 5'-CCAGCGAGAGGCAGATAG-3 '(SEQ ID NO: 67) Reverse PCR primer 3: 5'-CGGTCACCGTGTCCTGCGGGATG-3' (SEQ ID NO: 68) In addition, an oligonucleotide hybridization probe was constructed Synthetic from the consensual DNA44708 sequence, wherein said probe had the following nucleotide sequence: hybridization probe: 5 * -CAGCCCCTTCTCCTCCTTTCTCCCTGTCCTATCTGCCTCTC-3 '(SEQ ID NO: 69) In order to select several libraries in átk? ** ** ********* ,. - - - "fclH a, ***** *. *. * *., * &*, *. ***. * ^ * j * n ® ** l. _ *.? nf *. * ^ *? *****! ********* *** i ^?, 1 you are looking for a source of a full-length clone, 7DNA libraries were investigated by PCR amplification, with the previously identified pair of PCR primers, then a positive library was used to isolate clones encoding the PR0866 gene using the oligonucleotide probe and one of the PCR primers The .RNA for the construction of the cDNA libraries was Human fetal kidney tissue isolate (LIB228) The DNA sequencing of clones isolated in the manner described above produced a full-length DNA sequence for DNA53971-1359 [Figure 25, SEQ ID NO: 61]; the derived protein sequence for PR0866. The complete coding sequence of DNA53971-1359 is included in Figure 25 (SEQ ID NO: 61) The clone DNA53971-1359 contains a single open reading frame with an apparent site of initiation. io of translation at nucleotide positions from 275 to 277 and an apparent stop codon at nucleotide positions from 1268 to 1270. The predicted polypeptide precursor is 331 amino acids in length. The analysis of the full length sequence PR0866 shown in Figure 26 (SEQ ID NO: 62), demonstrates the presence of a variety of important polypeptide domains, where the locations given for these important polypeptide domains are approximately those described above. Analysis of the full-length PR0866 polypeptide shown in Figure 26 demonstrates the presence of the following: a signal peptide from about amino acid 1 to about amino acid 26; a glycosaminoglycan binding site of about amino acid 131 to about amino acid 135; a phosphorylation site with cAMP-dependent protein kinase and cGMP from about amino acid 144 to about amino acid 148; and N-myristylation sites from about amino acid 26 to about amino acid 32, from about amino acid 74 to about amino acid 80, from about amino acid 132 to about amino acid 138, from about amino acid 134 to about amino acid 140, from about amino acid 190 to about amino acid 196, from about amino acid 287 to about amino acid 293 and from about amino acid 290 to about amino acid 296. Clone DNA53971-1359 was deposited with the ATCC on April 7, 1998 and it was assigned the ATCC deposit number 209750. The full-length PR0866 protein shown in Figure 26 has an estimated molecular weight of about 35,844 daltons and a pl of about 5.45.

? .Zi £ - "B - ^. ***. * -i ß An analysis of the full length sequence PR0866 shown in Figure 26 (SEQ ID NO: 62), suggests that it has a significant similarity with the family of mindina / spondine proteins, indicating in this way that the PR0866 polypeptide can be a new homolog of mindina.More specifically, an analysis of the Dayhoff database (version 35.45 SwissProt 35) evidenced a significant homology between the amino acid sequence of PR0866 and the following Dayhoff sequences: AB006085_1, AB006084_1, AB006086_1, AF017267_1, CWU42213_1, AC004160_1, CPMICRP_1, S49108, A48569 and 146687. EXAMPLE 15 Hybridization ± ns ± tu In situ hybridization is a powerful and versatile technique for detection and localization of sequences of nucleic acids in cell or tissue preparations can be useful, for example, to identify gene expression sites, to analyze the tissue distribution of the transcript, to identify Icar and locate viral infections, to track changes in the synthesis of specific .RNA and as an aid in chromosome mapping. Hybridization in itself was done following an optimized version of Lu and Gillett's protocol, Ceil Vision, 1: 169-176 (1994), employing riboprobes generated by PCR labeled with 33P. Briefly, tissues were cut J ta ii. ? n & amp; i < t. A * **** 'fixed in formalin and soaked with paraffin, deparaffinized, deproteinized in proteinase K (20 g / mL) for 15 minutes at 37 ° C and further processed for in situ hybridization, in the manner described by Lu and Gillett, supra. An antisense riboprobe labeled with (- "P) UTP was generated from a PCR product and hybridized at 55 ° C overnight The sections were immersed in a Kodak NTB2 ™ nuclear tracking emulsion and exposed for 4 weeks Synthesis of the 33P-riboprobe We dried in vacuo and at a speed of 6.0 μL (125 mCi) of 33P-UTP (Amersham BF 1002, SA <2000 Ci / mmol) To each tube containing the drying "P-UTP, the following ingredients were added: 2.0 μL of 5x transcription regulatory solution 1.0 μL of DTT (100 mM) 2.0 μL of NTP mixture (2.5 mM: 10 μL of each of the following: 10 mM GTP, CTP and ATP + 10 μL of H20) 1.0 μL of UTP (50 μM) 1.0 μL of RNAs without 1.0 μL of DNA template (1 μg) 1.0 μL of H20 1.0 μL of RNA polymerase (for products RCP T3 = AS, T7 = S, normally) tubes were incubated at 37 ° C for 1 hour. HE added a total of 1.0 μL of RQ1 DNAse, followed by an incubation at 37 ° C for 15 minutes. A total of 90 μL of TE (10 mM Tris, pH 7.6 / 1 mM AEDT, pH 8.0) was added and the mixture was pipetted onto an DE81 paper. The remaining solution was loaded into a MICROCON-50 ™ ultrafiltration unit and rotated using program 10 (6 minutes). The filtration unit was emptied into a second tube and put into rotation using program 2 (3 minutes). After the final recovery, a total of 100 μL of TE was added and then 1 μL of the final product was pipetted onto an DE81 paper and subjected to the count in 6 mL of BIOFLUOR II ™. The probe was run on a TBE / urea gel. A total of 1-3 μL of the probe or 5 μL of RNA Mrk III was added to 3 μL of the charge buffer. After heating in a heating block at 95 ° C for 3 minutes, the gel was immediately placed on ice. The gel wells were flooded and the mixture was charged and run at 180-250 volts for 45 minutes. The gel was wrapped in plastic (brand SARÁN ™) and exposed to an XAR film with an intensification screen, in a freezer at -70 ° C for a period from 1 hour to overnight. 3jP-hybridization A. Pretreatment of frozen sections i * *** ** j t ***,, ^? *? Slices were taken from the freezer, placed on aluminum trays and thawed at room temperature for five minutes. The trays were placed in an incubator at 55 ° C for 5 minutes to reduce condensation. The slices were fixed for 10 minutes in paraformaldehyde in 4% on ice, in a hood for emissions and washed in 0.5 x SSC for 5 minutes, at room temperature (25 mL 20 x SSC + 975 mL of SQ H20). After deproteinization at 0.5 μg / mL of proteinase K for 10 minutes at 37 ° C (12.5 μL of 10 mg / mL of stock solution in 250 mL of RNAse buffer without RNAse, preheated), the sections were washed with 0.5 x SSC for 10 minutes at room temperature. Sections were dehydrated in 70%, 95% and 100% ethanol for 2 minutes in each. B. Pretreatment of thin sections The sections were deparaffinized, placed in SEQ ID NO: h29 and rinsed twice by 2 x SSC at room temperature for 5 minutes each time. The sections were deproteinized in 20 μg / ml of proteinase K (500 μL of 10 mg / mL in 250 mL of RNSA regulatory solution without RNAse, 37 ° C, 15 minutes) for human embryonic tissue, or 8 x proteinase K ( 100 μL in 250 mL of RNAse buffer, 37 ° C, 30 minutes) for the tissues in formalin. After a rinse was performed Utt ** t * 1 1 *. * flÁ, ^. *. . __ .I. , **, **. ^ *. _. . **. *. ** *. to .*. *, * * *, 0.5 x SSC and dehydration, in the manner described above. C. Pre-curing The sections were placed in a box 5 plastic lined with filter paper saturated with Box buffer solution (4 x SSC, 50% formamide). The tissue was covered with 50 μL of hybridization buffer (3.75 g of dextran sulfate + 6 mL of SQ H20), vortexed and heated in a microwave oven for 10 2 minutes with the lid loose. After cooling on ice, 18.75 mL of formamide, 3.75 mL of 20 x SSC and 9 mL of SQ H20 were added, and the tissue vortexed and incubated at 42 ° C for 1-4 hours. D. Hybridization 15 A probe with 1.0 x 106 cpm and 1.0 μL of tRNA (50 mg / mL, stock) per section was heated at 95 ° C for 3 minutes. The sections were chilled on ice and 48 μL of hybridization buffer was added per section. After shaking in a vortex, 50 were added 20 μL of 33P mixture to 50 μL of prehybridization solution in the sections. The sections were incubated overnight at 55 ° C. E. The washes were washed for 2 x 10 minutes with 25 2 x SSC, EDTA at room temperature (400 mL of 20 x SSC + aaa Ü * **? i * ** *. m 7 *. ***************, *****. *. ***, < *. *. **. ***. i? t 17 mL of EDTA 0.25 M, Vf = 4 L), followed by a treatment with RNAse A at 37 ° C for 30 minutes (500 μL of 10 mg / mL in 250 L of RNAse regulatory solution = 20 μg / mL) . Sections (or slices or slices) were washed 2 x 10 minutes with 2 x SSC,. EDTA at room temperature. The strict conditions of the washes were the following: 2 hours at 55 ° C, 0.1 x SSC, .AEDT (20 mL of 20 x SSC + 16 mL of .AEDT, Vf = 4 L). F. Oligonucleotides The in-situ analysis was performed on 5 of the .ADN sequences described herein. The oligonucleotides used for these analyzes were the following: (1) DNA30879-1152 (PRO207) pl: 5 '-GGA TTC TAA TAC GAC TCA CTA TAG GGC TCC TGC GCC TTT CCT GAA CC-3' (SEQ ID NO: 70) p2: 5 '-CTA TGA AAT TAA CCC TCA CTA AAG GGA CAC TCC TTG CCC ACA GAG-3' (SEQ ID NO: 71) (2) DNA33089-1132 (PRQ221) pl: 5 '-GGA TTC TAA TAC GAC TCA CTA TAG GGC TGT GCT TTT ATT CTG CCA GTA-3 '(SEQ ID NO: 72) p2: 5 '-CTA TGA -AAT TAA CCC TCA CTA AAG GGA GGG TAC AAT TAA GGG GTG GAT-3 '(SEQ ID NO: 73) (3) DNA33221-1133 (PRQ224) Pl: 5' -GGA TTC TAA TAC GAC TCA CTA TAG GGC GCA GCG ATG GCA GCG ATG AGG-3 '(SEQ ID NO: 74) p2: 5' -CTA TGA AAT TAA CCC TCA CTA AAG GGA CAG ACG GGG CAG CAG GGA GTG-3 '(SEQ ID NO: 75) (4) DNA40628-1216 (PRQ301) Pl: 5' -GGA TTC TAA TAC GAC TCA CTA TAG GGC GAG TCC TTC GGC GGC TGT T-3 '(SEQ ID NO: 76) p2: 5' -CTA TGA AAT TAA CCC TCA CTA AAG GGA CGG GTG CTT TTG GGA TTC GTA-3 '(SEQ ID NO: 77) (5) DNA45416-1251 (PRQ362) pl: 5' -GGA TTC TAA TAC GAC TCA CTA TAG GGC CTC CAA GCC CAC AGT GAC AA-30 (SEQ ID NO: 78 ) p2: 5 '-CTA TGA AAT TAA CCC TCA CTA AAG GGA CCT CCA CAT TTC CTG CCA GTA-3 '(SEQ ID NO: 79) G. Resul tates An on-site analysis was carried out at 5 • i -.- j-alat hita, - »1 * 1 fcL .., previous DNA sequences described herein. The results of these analyzes are as follows: (1) DNA30879-1152 (PRO207) (Apo2L homolog) Low level expression was observed in a chondrosarcoma and in another soft tissue sarcoma. All other tissues were negative. The human fetal tissues examined (E12-E16 weeks) included: placenta, umbilical cord, liver, kidney, suprarenal glands, thyroid, lungs, heart, large vessels, esophagus, stomach, small intestine, spleen, thymus, pancreas, brain, eye , spinal cord, body wall, pelvis and lower limb. The adult tissues examined included: kidney (normal and late stage), adrenal gland, myocardium, spleen, lymph node, pancreas, lung, skin, eye (including the retina), bladder and liver (normal, cirrhotic and with acute insufficiency) . Non-human primate tissues examined included: chimp tissues: salivary gland, stomach, thyroid, parathyroid, tongue, thymus, ovary and lymph node. Rhesus monkey tissues: cerebral cortex, hippocampus, cerebellum, penis. (2) DNA33089-1132 (PR0221) (1 TM receptor) ? J ".. jAA *. . .to, .. * " * ** . 1 ..., ** * * & *** **. **, **** ** * ,,. . TO * *-., .

Specific expression was observed in white matter and fetal brain gray matter, as well as in neurons of the spinal cord. The probe appears to cross-react with rats. Low level expression was observed in cerebellar neurons in adult rhesus monkey brain. All other tissues were negative. The fetal tissues examined (E12-E16 weeks) included: placenta, umbilical cord, liver, kidney, adrenal gland, thyroid, lung, heart, large vessels, esophagus, stomach, small intestine, spleen, thymus, pancreas, brain, eye, spinal cord, body wall, pelvis and lower limb. Adult tissues examined included: liver, kidney, adrenal gland, myocardium, aorta, spleen, lymph node, pancreas, lung, skin, cerebral cortex (rm), hippocampus (rm), cerebellum (rm), penis, eye, bladder , stomach, gastric carcinoma, colon, colonic carcinoma and chondrosarcoma; Liver damaged by acetaminophen and liver Gon cirrhosis was also included. (3) DNA33221-1133 (PR0224) (LDLR-1 TM homolog) The expression observed was limited to vascular endothelium of fetal spleen, adult spleen, fetal liver, adult thyroid and adult lymph node (chimpanzee). An additional site of expression was observed in spinal ganglia in development. All other tissues were negative. The human fetal tissues examined (E12-E16 weeks) included: placenta, umbilical cord, liver, kidney, adrenal gland, thyroid, lung, heart, large vessels, esophagus, stomach, small intestine, spleen, thymus, pancreas, brain, eye , spinal cord, body wall, pelvis and lower limb. Adult tissues examined included: kidney (normal and end-stage), adrenal gland, myocardium, aorta, spleen, lymph node, pancreas, lung, skin, eye (including retina), bladder and liver (normal, cirrhotic and with acute failure). The non-human tissues examined included: Chimpanzee tissues: salivary gland, stomach, thyroid, parathyroid, skin, thymus, ovary, lymph node. Rhesus monkey tissues: cerebral cortex, hippocampus, cerebellum, penis. (4) DNA40628-1216 (PRO301) (homologue CD22 (JAM hlog, A33 Ag hlog) Expression in inflamed human tissues (psoriasis, IBD, inflamed kidney, inflamed lung, hepatis, normal amygdala, and multiple adult blocks and of chimpanzee): ** *. , & i *? * * M uí. * .dsÁ? g »*. .

The expression was predominantly evaluated in human tissue inflamed with some tissues of normal humans and non-human primates. Expression was observed throughout the evaluated epithelial structure, including the mucosal epithelium of the colon, bronchial large airway epithelium, oral mucosa (tongue), mucosa of the tonsillar crypts, placental mucosa, prostatic mucosa, mucosa of the glandular stomach, epithelial cells of the corpuscles of Hassall thymic, hepatocytes, biliary epithelium and placental epithelium. The only evidence of expression outside of an epithelial structure was very low, and it was an inconsistent expression in the germinal centers of the follicles in an amygdala with reactive hip'erplasia. In tissues of non-human primates, the following was observed: Chimpanzee tissues: a weak diffuse expression was observed in the epidermis of the epithelium of the tongue; in the thymus a weak specific expression was observed in the Hassall corpuscles of the thymic epithelium; In the stomach a moderate diffuse expression was observed in the epithelium of the glandular mucosa. In human tissues: in the liver (including multiple blocks: chronic cholangitis, lobular hyperplasia, acetaminophen toxicity): there was a diffuse low to moderate expression in hepatocytes and biliary epithelium. ********** to *****. **) Expression was more prominent in perilobular / periportal hepatocytes. It was more prominent in the biliary epithelium in secretions of the liver with chronic sclerosing cholangitis. The expression was not present in all the present samples; this could reflect the quality of the sample rather than the variability of the expression. In psoriasis: a weak expression was observed in the epidermis. In lung with chronic interstitial pneumonia or chronic bronchitis: a low diffuse expression was observed in the mucosal epithelium of the large airways; We also observed a weak diffuse expression in alveolar epithelium. There was no expression in the epithelium of the submucosal glands of the bronchi / bronchioles. In placenta: there was moderate diffuse expression in placental epithelium. In the prostate: there was a low diffuse expression in prostatic epithelium. In the gallbladder: there was a moderate diffuse expression in the mucosal epithelium. In amygdala with reactive hyperplasia: a high diffuse expression was observed in the epithelium of the tonsillar mucosa and in the crypts; the signal was higher in the mucosal cells lining the tonsillar crypts.

There was an inconsistent weak diffuse expression in the germinal centers of the cortical follicles (areas of B lymphocytes); however, in no other tissue evaluated with lymphoid structures or lymphocytic inflammation, no expression was observed in B lymphocytes. In the colon with inflammatory bowel disease and polyps / adenomatous changes: a low expression was observed in the mucosal epithelium, the expression was higher at the tips of the hairs. In the specimen with 10 polyps there was no evidence of a greater expression of the dysplastic epithelium of the polyp compared to the adjacent mucosa. There was no obvious expression in reactive mucosal lymphoid tissue, which was present in many of the other cuts. 15 (5) DNA45416-1251 (PR0362) (homologous Ig domain) Expression in inflamed human tissues (psoriasis, IBD, inflamed kidney, inflamed lung, hepatitis and normal amygdala, multiple adult blocks and chimpanzees): 20 The expression of this new Protein was evaluated in a variety of tissues from human and non-human primates and was found to be highly restricted. The expression was present only in alveolar macrophages in the lung and in Kupffer cells of the hepatic sinusoids. The The expression in these cells increased significantly when these different cell populations were activated. Although these two subpopulations of tissue macrophages are located in different organs, they have similar biological functions. Both types of these phagocytes act as biological filters to remove material from the bloodstream or airways, including pathogens, senile cells and proteins, and are capable of secreting a wide variety of important proinflammatory cytokines. In inflamed lung (seven patient samples), expression was prominent in populations of reactive alveolar macrophage cells defined as large, pale, often vacuolated cells, present alone or in aggregates within the alveoli and was weak or negative in macrophages normal non-reactive (scattered cells alone of normal size). Expression in alveolar macrophages increased during inflammation when these cells grew in number and size (activated). Despite the presence of histiocytes in areas of intestinal inflammation and peribronchial lymphoid hyperplasia in these tissues, the expression was restricted to alveolar macrophages. Many of the inflamed lungs also suffered from some degree of suppurative inflammation; the expression was not present in neutrophil granulocytes.

In the liver, there was strong expression in reactive / activated Kupffer cells in livers suffering from acute centrilobular necrosis (acetaminophen toxicity) or expression was marked in periportal inflammation. However, there was weak expression or there was no expression in Kupffer cells of normal liver or liver that suffered only mild inflammation or mild to moderate lobular hyperplasia / hypertrophy. Thus, as in the lung, there was an increase in expression in activated / active cells. There was no expression of this molecule in the histiocytes / macrophages present in the inflamed gut, in hyperplastic / reactive tonsils or in normal lymph nodes. The lack of expression in these tissues, of which all contain a histiocytic inflammation or populations of resident macrophages, strongly supports expression restricted to populations of unique macrophages defined as alveolar macrophages and hepatic Kupffer cells. The human tissues evaluated that did not have a detectable expression included: inflammatory bowel disease (seven samples from patients with moderate to severe disease), tonsils with reactive hyperplasia, peripheral lymph nodes, psoriatic skin (two samples from patients with mild to moderate disease ), a ***. *, * * diL * heart and peripheral nerves. Chimpanzee tissues evaluated that did not present a detectable expression included:, stomach and thymus. EXAMPLE 16 Use of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0301, PR0526, PR0362, PR0356, PRO509 or PR0866 as Hybridization Probe The following method describes the use of a coding nucleotide sequence for PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 as hybridization probe. DNA comprising the full-length or mature coding sequence of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0301, PR0526, PR0362, PR0356, PRO509 or PR0866 (as shown in Figures 1, 3) was employed. , 5, 7, 9, 11, 13, 15, 17, 19, 21, 23 and 25, respectively, SEQ ID NOS: 1, 6, 9, 14, 19, 24, 29, 34, 42, 47, 54 , 59 and 61, respectively) or a fragment thereof, as a probe for the selection of homologous DNAs (such as those encoding for naturally occurring variants of the PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328 polypeptides. , PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866) in human tissue cDNA libraries or human tissue genomic libraries. l ** A ***** ** ^ **? A *? * m * m **? i? * ***, a ^^ a ^ .. ^. J ^ ... ^^ a ^ .a.¿M? ¡, Jn ******. ^ .. *. ** ****. ^. *, .. ^? .. H * LA Hybridization and washing of filters that contained any of the DNA libraries, was performed under the following highly stringent conditions. Hybridization of the radiolabelled probe derived from the gene coding for a PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0366, PR0356, PRO509 or PR0866 polypeptide with the filters was performed in a formamide solution 50%, 5x SSC, 0.1% SDS, 0.1% sodium pyrophosphate, 50 mM sodium phosphate, pH 6.8, 2x Denhardt's solution and 10% dextran sulfate, at 42 ° C for 20 hours. The filters were washed in an aqueous solution of 0.1 x SSC and 0.1% SDS at 42 ° C. Then, the DNAs having a desired sequence identity with the DNA encoding the full-length native sequence can be identified using standard known techniques. EXAMPLE 17 Expression of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PRQ362, PR0356, PRO509 or PRO866 in E. coli This example illustrates the preparation of a non-glycosylated form of PR0179, PRO207, PRO320 polypeptide , PR0219, PR0221, PR0224, PR0328, PR0301, PR0526, PR0362, PR0356, PRO509 or PR0866 by recombinant expression in E. coli.

The DNA coding sequence of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 is initially amplified using selected PCR primers. The primers must contain restriction enzyme sites corresponding to the restriction enzyme sites of the selected expression vector. A variety of expression vectors can be employed. An example of a suitable vector is pBR322 (derived from E. coli, see Bolivar et al., Gene, 2: 95 (1977), which contains genes for resistance to ampicillin and tetracycline.) The vector is digested With restriction enzymes and dephosphorylates, the sequences amplified by PCR are subsequently ligated to the vector.The vector will preferably include sequences encoding an antibiotic resistance gene, a trp promoter, a poly-His leader sequence (including the first six STII codons, the poly-His sequence and the enterokinase cleavage site), the coding region of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866, the lambda transcription terminator and an argU gene, then the ligation mixture is used to transform a selected E. coli strain, using the methods described in Sambrook et al., supra.

Transformants are identified by their ability to grow on plates of LB medium and antibiotic resistant colonies are selected. Plasmid 7DNA can be isolated and confirmed by restriction analysis and .DNA sequencing. The selected clones can be grown overnight in a liquid culture medium, such as LB broth supplemented with antibiotics. the culture of a night, subsequently, can be used to inoculate a culture on a larger scale. Then, the cells are grown to a desired optical density, during which time the expression promoter is activated. After culturing the cells for several more hours, they are harvested by centrifugation. The cell pellet obtained by centrifugation can be solubilized using several agents known in the art and the PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 solubilized protein are subsequently solubilized. It can be purified using a metal chelating column under conditions that allow a strong binding of the protein. The polypeptide PR0179, PRO207, PR0320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 can be expressed in E. coli in a poly-His labeled form, employing the following procedure. i * i ?? A _? A? * * h? .,. *,., **, * ^., *. , * * * * ***** ** __ **. _ .. ** *. * .. * * * "Je ^ t t,.

- - The DNA encoding PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 is initially amplified using selected PCR primers. The primers will contain restriction enzyme sites corresponding to the restriction enzyme sites of the selected expression vector and other useful sequences that provide efficient and reliable translation initiation, rapid purification on a metal chelation column and proteolytic removal with enterokinase. The PCR-amplified and poly-His-labeled sequences are ligated into an expression vector, which is used to transform an E. coli host cell based on strain 52 (W3110 fuhA (tonA) Ion galE rpoHts (htpRts) clpP (lacll) The transformants are first grown in LB medium containing 50 mg / mL carbenicillin, at 30 ° C with agitation until a D06oo of 3-5 is reached, then the cultures are diluted 50 to 100 times in middle CRAP (prepared by mixing 3.57 g of (NH4) 2S04, 0.71 g of sodium citrate • 2H20, 1.07 g of KCl, 5.36 g of Difco yeast extract, 5.36 g of Sheffield hycse SF in 500 mL of water, as well as MPOS 110 mM , pH 7.3, glucose at 0.55% (w / v) and 7 mM MgSO4) and is grown for about 20-30 hours at 30 ° C with shaking. Samples are taken to verify expression by SDS-PAGE analysis and the remaining culture is centrifuged to form cell pellets. The cell pellets are frozen until their purification and refolding. The paste of E. coli from 0.5 to 1 L of 5 fermentations (6-10 g of pellet) is resuspended in 10 volumes (w / v) of guanidine 7M, Tris 20 mM, regulatory solution pH 8. Sodium sulfite is added solid and tetrathionate sodium to a final concentration of 0.1M and 0.02M, respectively, and the solution is stirred for 10 a night at 4 ° C. This step results in the denaturation of the protein with all the cysteine residues blocked by sulfitolization. The solution is centrifuged at 40,000 rpm in a Beckman ultracentrifuge for 30 minutes. The supernatant is diluted with 3-5 15 volumes of column buffer solution with metal chelator (6M guanidine, 20 M Tris, pH 7.4) and filtered through 0.22 micron filters to clarify. The clarified or rinsed extract is loaded onto a column with 5 mL of Qiagen Ni ~ -NTA equilibrated with the solution 20 column regulator with metal chelator. The column is washed with additional buffer solution containing 50 mM imidazole (Calbiochem, Utrol grade), pH 7.4. The protein is eluted with buffer solution containing 250 mM imidazole. The fractions that contain the protein The desired mixture is mixed and the mixture is stored at 4 ° C. HE ¡¡ Í? ÁÁ *? * K *? % to". ***** - * ****,.,, r [f (. ******. ** *.. ***, .., * .. *. *. estimate the protein concentration by its absorbance at 280 nm, using the extinction coefficient calculated based on the amino acid sequence. The proteins are refolded by diluting the sample slowly in freshly prepared refolding buffer, consisting of: 20 mM Tris, pH 8.6, 0.3 M NaCl, 2.5 M urea, 5 mM cysteine, 20 mM glycine and 1 mM EDTA. . The refolding volumes are selected so that the final concentration of the protein is between 50 and 100 μg / mL. The refolding solution is gently stirred at 4 ° C for 12-36 hours. The refolding reaction is stopped by the addition of trifluoroacetic acid (ATF) to a final concentration of 0.4% (pH of about 3). Before further purification of the protein, the solution is filtered through a 0.22 micron filter and acetonitrile is added to a final concentration of 2 to 10%. The refolded protein is subjected to chromatography on a Proso Rl / H reverse phase column, using a 0.1% mobile ATF regulatory solution., eluting with a gradient of acetonitrile from 10 to 80%. Aliquots of fractions with an A28o absorbance are analyzed in SDS-polyacrylamide gels and the fractions containing the homogeneous refolded protein are mixed. Generally, the appropriately refolded species of most proteins elutes at the lowest concentrations of acetonitrile, since those species are the most compact with their hydrophobic interiors protected from interaction with the reverse phase resin. Aggregate species usually elute at higher acetonitrile concentrations. In addition, to resolve the misfolded forms of the proteins and separate them from the desired shape, the reverse phase step also removes the endotoxin from the samples. The fractions containing the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 desired folding are mixed and the acetonitrile is removed using a gentle stream of nitrogen directed at the solution.

The proteins are formulated in 20 mM Hepes, pH 6.8, with 0.14 M sodium chloride and 4% mannitol, by dialysis or by gel filtration using G25 Superfine resins (Pharmacia) balances with the regulatory solution of the formulation and is filtered under sterile conditions. The PRO207, PR0224 and PRO301 polypeptides were successfully expressed in E. coli, in a poly-His-labeled form, by the above procedure. EXAMPLE 18 Expression of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PRO866 in Mammalian Cells ^ Att-i - 33 - This example illustrates the preparation of a potentially glycosylated form of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866, by recombinant expression in 5 mammalian cells. The vector pRK5 (see European Patent EP 307,247, published March 15, 1989), is used as the expression vector. Optionally, the 7? DN of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, 10 PR0526, PR0362, PR0356, PR0509 or PR0866 is ligated into pRK5 with the selected restriction enzymes, to allow insertion of the 7DNA of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356 , PRO509 or PR0866 using the linking methods 15 described by Sambrook et al. , supra. The resulting vector is designated pRK5-PR0179, pRK5-PR? 207, pRK5-PRO320, pRK5-PR0219, pRK5-PR0221, pRK5-PR0224, pRK5-PR0328, pRK5-PR? 301, pRK5-PR0526, pRK5-PR0362, pRK5 -PR0356, pRK5-PR? 509 or pRK5-PR0866, respectively. In one embodiment, the selected host cells can be 293 cells. Human 293 cells (ATCC CCL 1573) are grown to confluence in tissue culture plates, in a medium such as DMEM supplemented with fetal bovine serum and Optionally, nutritious components are added and / or antibiotics Approximately 10 μg of PRK5-PR0179 DNA, pRK5-PRO207, pRK5-PRO320, pRK5-PR0219, pRK5-PR0221, pRK5-PR0224, pRK5-PR0328, pRK5-PR? 301, pRK5-PR0526, pRK5-PR0362, are mixed. pRK5-PR0356, pRK5-PRO509 or pRK5-PR0866 with approximately 1 μg of .ADN coding for the VA RNA gene [Thimmappaya et al. , Cell, 31: 543 (1982)] and dissolved in 500 μl of 1 mM Tris-HCl, 1 M EDT, 0.227 M CaCl 2. 500 μl of 50 mM HEPES are added dropwise to this mixture (pH 7.351, 280 mM NaCl, 1.5 mM NaP04 and a precipitate is allowed to form for 10 to 25 ° C. The precipitate is suspended and added to the 293 cells and allowed to settle for about 4 hours at 37 ° C. culture is aspirated and 2 ml of 20% glycerol in PBS are added over a period of 30 seconds, then the 293 cells are washed with serum-free culture medium, fresh culture medium is added and the cells are incubated for approximately 5 days.Approximately 24 hours after transfections, the culture medium is removed and replaced by culture medium (alone) or by culture medium containing 200 μCi / ml of 35S-cysteine and 200 μCi / ml of 35S- Methionine After incubation for 12 hours, the conditioned medium is collected, concentrated on a rotary filter and loaded in a l of SDS at 15%. The processed gel can be dried and exposed to a film for a selected period to reveal the presence of the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. Cultures containing transfected cells can be subjected to further incubation (in medium without serum) and the medium is tested by selected bioassays. In an alternative technique, the .ADN of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 can be introduced into 293 cells transiently, using the dextran sulfate method described by Somparyrac et al. , Proc. Matl. Acad. Sci. , 12: 1515 (1981). The 293 cells are grown to maximum density in a shake flask and 700 μg of 7DNA are added from pRK5-PR0179, pRK5-PRO207, pRK5-PRO320, pRK5-PR0219, pRK5-PR0221, pRK5-PR0224, pRK5-PR0328, pRK5-PRO301, pRK5-PR0526, pRK5-PR0362, pRK5-PR0356, pRK5-PRO509 or pRK5-PR0866. The cells are first concentrated in the flask by centrifugation and 1-advanced with PBS. The .DNA precipitated with dextran is incubated in the cell pellet for four hours. Cells are treated with 20% glycerol for 90 seconds, washed with tissue culture medium and reintroduced into a shake flask containing tissue culture medium, 5 μg / ml bovine insulin and 0.1 μg / ml bovine transferrin. After about four days, the conditioned medium is centrifuged and filtered to remove the cells and debris. The sample containing the PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0366, PRO509 or PR0866 polypeptide, expressed subsequently, can be concentrated and purified by any selected method, such as dialysis and / or column chromatography. In another embodiment, PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0301, PR0526, PR0362, PR0356, PRO509 or PR0866 can be expressed in CHO cells. 7DNA can be transferred from pRK5-PR0179, pRK5-PRO207, pRK5-PRO320, pRK5-PR0219, pRK5-PR0221, pRK5-PR0224, pRK5-PR0328, pRK5-PRO301, pRK5-PR0526, pRK5-PR0362, pRK5-PR0356, pRK5 - PRO509 or pRK5-PR0866 in CHO cells using the known reagents such as CaP04 or DE7AE-dextran. As described above, the cell cultures can be incubated and the medium is replaced by culture medium (alone) or by culture medium containing a radioactive label such as S-methionine. After determining the presence of a PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866, the culture medium is replaced by culture medium without serum. Preferably, the cultures are incubated for about 6 days and then the conditioned medium is harvested. The medium containing the PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0301, PR0526, PR0362, PR0356, PRO509 or PR0866 expressed, subsequently, can be concentrated and purified by any selected method. It is also possible to express PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 marked with epitope in CHO host cells. PR0179, PR0207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 can be subcloned out of vector pRK5. The subcloned insert can be subjected to a PCR to be fused, within the framework, with a selected epitope tag, such as a poly-His tag, into a baculovirus expression vector. PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0301, PR0526, PR0362, PR0356, PRO509 or PR0866 labeled with poly-His can be subcloned into an SV40-driven vector containing a selection marker such as DHFR for selection of stable clones. Finally, the CHO cells are transfected (in the manner previously described) with the vector directed by SV40. A marking can be done, in the manner described above, to verify the ai*? na *? * ** n * l * A ** á *** *** - * ?? ** - í. * -? - *, ***. ******. ** * * **. ***** * expression. The culture medium containing PR-labeled PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PR0509 or PR0866 can be concentrated and purified by any selected method, for example by affinity chromatography with Ni 2 + -kelate. PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 can also be expressed in CHO and / or COS 10 cells by a transient expression method, or in CHO cells by some other stable expression procedure. Stable expression in CHO cells is carried out using the following procedure. The proteins are expressed as an IgG construct (immunoadhesin) in which the coding sequences for the soluble forms (eg, extracellular domains) of the respective proteins are fused with a constant region of IgG1 containing the hinge domains, CH1 and CH2 and / or in the form of a sequence labeled with poly-His. After a PCR amplification, the respective DNAs are subcloned into a CHO expression vector using standard techniques, such as those described by Ausubel et al. , Current Protocols of Molecular Biology, 25 Unit 3.16, John Wiley and Sons (1997). They are built JÍMWMBli ^ ii ^ d.iLÉtlAt ^ iafcjMto ^ - *** * *. *. * ****** ** * i ** ****,, - ** *****. *** ***** ..... ^^ **. a. ^ j ^, CHO expression vectors having restriction sites compatible at 5 'and 3' with the DNA of interest, to allow convenient transport of the cDNAs. The vector used in the expression in CHO cells is described in Lucas et al. , Nucí. Acids Res. , 24: 9 1774-1779 (1996) and utilizes the SV40 early promoter / enhancer to direct the expression of 7? D? C of interest and dihydrofolate reductase (DHFR). The expression of DHRF allows the selection of cells that stably maintain the plasmid after transfection. Twelve micrograms of AD? The desired plasmid is introduced into approximately 10 million CHO cells, using commercially available transfection reagents Superfect® (Quiagen), Dosper® or Fugene® (Boehringer Mannheim). The cells are grown in the manner described in Lucas et al., Supra. About 3 x 10 cells are frozen in an ampule for further culture and production in the manner described below. The ampules that contain the AD? plasmidic are thawed by placing them in a water bath and mixed in a vortex. The contents are pipetted into a centrifuge tube containing 10 ml of culture medium and centrifuged at 1000 rpm for 5 minutes. The supernatant is aspirated and the cells are resuspended in 10 ml of medium selective (filter PS20 0.2 μm with 5% fetal bovine serum diafiltered in a 0.2 μm filter). Aliquots are then made with the cells in a 100 ml flask containing 90 ml of selective medium. After 1 or 2 5 days, the cells are transferred to a 250 ml flask with 150 ml of selective culture medium and incubated at 37 ° C. After another 2 or 3 days, 250, 500 and 2000 ml flasks are seeded with 3 x 10 5 cells / ml. The cell culture media are exchanged for fresh medium by centrifugation and resuspension in the production medium. Although any suitable culture medium can be employed for CHO cells, a production medium described in US Pat. No. 5,122,469 issued June 16, 1992 can be used. A 3 1 15 production flask is inoculated at 1.2 x 10 cells / ml. On day 0, the cell number and pH are determined. On day 1, the flask is sampled and a bubbling with filtered air is started. On day 2, the flask is sampled, the temperature is changed to 33 ° C and 30 ml glucose of 20 500 g / 1 and 0.6 ml of 10% antifoam are taken (eg, 35% polydimethylsiloxane emulsion, Dow Corning 365 Medical Grade Emulsion). During production, the pH is adjusted as necessary to maintain it at approximately 7.2. After 10 days or until viability drops below of 70%, the cell culture is harvested by centrifugation and filtered through a 0.22 μm filter. The filtrate is stored at 4 ° C or placed immediately in columns for purification. 5 For constructs labeled with poly-His, the proteins are purified using a Ni 2 + -NTA column (Qiagen). Before purification, imidazole is added to the conditioned medium to a concentration of 5 mM. The conditioned medium is pumped into a 6 ml column of 10 Ni2 + -NTA equilibrated with 20 mM HEPES, pH 7.4, buffer solution containing 0.3 M NaCl and 5 mM imidazole, at a flow rate of 4-5 ml / min, at 4 ° C. After loading, the column is washed with additional equilibration buffer solution and the protein is eluted with solution 15 equilibration buffer containing 0.25 M imidazole. The highly purified protein is subsequently desalinated in a buffer storage solution containing 10 mM HEPES, 0.14 M NaCl and 4% mannitol, pH 6.8, in a 25 ml column of G25 Superfine (Pharmacia) and 20 stored at -80 ° C. The immunoadhesin constructs (containing Fc) are purified from the conditioned medium in the following manner. The conditioned medium is pumped into a 5 ml Protein A column (Pharmacia) which has been : * t W «tl. fetfBHrMÉilaffl l'l * Í * J * Í é. I * M ** H *** lt ** *** l *** *. *. ** ***** - _., _. .. ^ a ... * ^ *****. «**** _. *. * Balanced with sodium phosphate buffer, 20 mM, pH 6.8. After loading, the column is extensively washed with equilibration buffer before eluting with 100 mM citric acid, pH 3.5. The eluted protein 5 is immediately neutralized by collecting 1 ml fractions in tubes containing 275 μl of 1 M Tris buffer, pH 9. The highly purified protein is subsequently desalted in a storage buffer, in the manner described above for the proteins marked with poly-His. The homogeneity in polyacrylamide gels is evaluated with SDS and an N-terminal amino acid sequencing is performed by the Edman degradation method. The polypeptides PR0179, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0356, PRO509 and PR0866 were stably expressed in CHO cells by the method described above. In addition, PR0224, PR0328, PRO301 and PR0356 polypeptides were expressed in CHO cells by the transient expression method. EXAMPLE 19 Expression of PRQ179, PRO207, PRO320, PRQ219, PRQ221, PRQ224, PRQ328, PRO301, PRQ526, PRQ362, PRQ356, PRO509 or PRQ866 in Yeast The following method describes the recombinant expression of PR0179, PRO207, PRO320, , * + taBa, ... ^ a. ,. .., a ^ ** ***. **** .. * * ^ ** t *** * **. ***** - ** ^ **.,.

PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 in yeasts. First, yeast expression vectors are constructed for the intracellular production or secretion of the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 from the 7ADH2 / GAPDH promoter. Inserted .ADN encoding PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0301, PR0526, PR0362, PR0356, PRO509 or PR0866 and the promoter into suitable restriction enzyme sites in the selected plasmid, to direct the intracellular expression of the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. For secretion, 7DNA encoding PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 can be cloned into the selected plasmid, together with 7DNA encoding the ADH2 promoter / GAPDH, a native signal peptide of PR0179, RRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or other mammalian signal peptide, or, for example, a factor- yeast alpha or signal sequence / invertase secretory leader, and linker sequences (if necessary) for the expression of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0366, PRO509 or PR0866. Yeast cells, such as yeast strain AB110, can be transformed with the expression plasmids described above and cultured in selected fermentation media. Supernatants of transformed yeasts can be analyzed by precipitation with 10% trichloroacetic acid and separation by SDS-PAGE, followed by a staining of the gels with Coomassie Blue. The PR0179, PRO207, PRO320, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0362, PR0356, PRO509 or PR0866 recombinant PR0866 polypeptide can be isolated and purified by removing the yeast cells from the fermentation medium and centrifuging, and then concentrating the medium using selected cartridge filters. The concentrate containing the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. it can be purified using selected column chromatography resin. EXAMPLE 20 Expression of PRQ179, PRO207, PRO320, PRQ219, PRQ221, PRQ224, PRQ328, PRO301, PRQ526, PRQ362, PRQ356, PRO509 or PRQ866 in Insect Cells Infected by Baculovirus. The following method describes the expression *******! . -. * * & * ti. *, ****, *,. **. * *. * ** &. * - * **. recombinant in insect cells infected by Baculovirus. The coding sequence of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 is fused upstream of an epitope tag contained within a baculovirus expression vector. Such epitope tags include poly-His tags and immunoglobulin tags (such as Fc regions of IgG). A variety of plasmids can be employed, including plasmids derived from commercial sources such as pVL1393 (Novagen). Briefly, the coding sequence of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or the desired portion of the decorating sequence of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 (such as the coding sequence of the extracellular domain of a transmembrane protein or the coding sequence of the mature protein, if the protein is extracellular), is amplified by PCR with primers complementary to the 5 'and 3' regions. The 5 'primer can be incorporated into flanking restriction enzyme sites (selected). Then, the product is digested with those selected restriction enzymes and subcloned into the expression vector.

The recombinant baculovirus is generated by cotransfection of the aforementioned plasmid and BaculoGold ™ .DNA viral (Phar igen) in Spodoptera frugiperda ("Sf9") cells (ATCC CRL 1711), using lipofectin 5 (commercially available from GIBCO- BRL). After 4 to 5 days of incubation at 28 ° C, the released viruses are harvested and used for further amplifications. The viral infection and the expression of the protein are carried out in the manner described by O'Reilley et al. , Baculovirus 10 expression vectors: A Laboratory Manual, Oxford: Oxford University Press (1994). The PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 marked with poly-His which is expressed, can be Purify, for example, by affinity chromatography with Ni 2 + -kelate, as follows. Extracts of the Sf9 recombinant cells infected with the virus are prepared in the manner described by Rupert et al. , Nature, 362: 175-179 (1993). Briefly, the "Sf9 cells are washed, resuspended in a sonication buffer solution (25 ml HEPES, pH 7.9, 12.5 mM MgCl2, 0.1 mM EDTA, 10% glycerol, 0.1% NP-40, 0.4 M KCl) and are sonicated twice for 20 seconds on ice.The sonicates are clarified by centrifugation and the supernatant is diluted 50 times in charge buffer solution (50 mM phosphate, 300 mM NaCl, 10% glycerol, pH 7.8) and filtered through a 0.45 mm .2+ filter. An agarose column with Ni-NTA (commercially available in Qiagen) is prepared, with a bed volume of 5 ml, washed with 25 ml of water and equilibrated with 25 ml of charge buffer. The filtered cell extract is loaded onto the column at a rate of 0.5 ml per minute. The column is washed to an absorbance A280 of baseline with charge buffer, at which point the collection of fractions begins. Next, the column is washed with a secondary washing buffer (50 mM phosphate, 300 mM NaCl, 10% glycerol, pH 6.0), which elutes nonspecifically bound proteins. After reaching the baseline absorbance A28o again, the column is developed with an imidazole gradient from 0 to 500 mM in the secondary wash buffer. 1 ml fractions are collected and analyzed by SDS-PAGE and stained with silver stain, or subjected to a Western blot with Ni 2 + -NTA conjugated with alkaline phosphatase (Qiagen). The fractions containing PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PRO866 labeled with Hisium eluted, respectively, are mixed and dialyzed against the charge buffer. Alternatively, the purification of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 labeled with IgG (or labeled with Fc), can be performed by chromatographic techniques, including chromatography in column with protein A or with protein G. After amplification by PCR, the respective coding sequences are subcloned into a baculovirus expression vector (pb.PH.IgG for the fusions with IgG and pb.PH.His.c for the proteins labeled with poly-His) and the vector, together with Baculogold® baculovirus DNA (Pharmigen) are co-transfected into 10 cells of Spodoptera frugiperda ("Sf9") (ATCC CRL 1711), using Lipofectin (Gibco BRL). Vectors pb.PH.IgG and pb.PH.His are modifications of commercially available baculovirus expression vectors pVL1393 (Pharmigen), with modified polylinker regions to include the His or Fc tag sequences. Cells are grown in Hink's TNM-FH medium supplemented with 10% fetal bovine serum (FBS) (Hyclone). The cells are incubated for 5 days at 28 ° C. The supernatant is harvested and subsequently used for the first viral amplification by infecting Sf9 cells in Hink TNM-FH medium supplemented with 10% FBS, at an approximate multiplicity of infection (MDI). *? **, * t l i.t flAja- aj a.i aal a. 10. The cells are incubated for 3 days at 28 ° C. The supernatant is harvested and the expression of the constructs in the baculovirus expression vector is determined by a binding of 1 ml of supernatant with 25 ml of Ni2 + -NTA beads (Qiagen) for the histidine-tagged proteins or with protein A beads Sepharose CL-4B (Pharmacia) for proteins labeled with IgG, followed by an analysis with SDS-PAGE comparing with a known concentration of a protein standard, using Coomassie Blue staining. The first supernatant of viral amplification is used to infect a culture in shake flasks (500 ml) of Sf9 cells grown in ESF-921 medium (Expression Systems LLC), to MDI approximate 0.1. The cells are incubated for 3 days at 28 ° C. The supernatant is harvested and filtered. The batch-binding operation and the DSPA-DSS analysis are repeated, as necessary, until the expression of the culture is confirmed. The conditioned medium "of the transfected cells (from 0.5 to 3 1) is harvested by centrifugation to remove the cells and filtered through 0.22 micron filters.For the poly-His tagged constructs, the protein construct is purified using a Ni 2+ -NTA column (Qiagen) Prior to purification, imidazole is added to the conditioned medium to a concentration of 5 mM The conditioned medium is pumped into a 6 ml Ni 2+ -NTA column equilibrated with 20 mM HEPES, pH 7.4, buffer solution containing 0.3 M NaCl and 5 mM imidazole, at a flow rate of 4-5 ml / min, at 4 ° C. After loading, the column is loaded with additional equilibration buffer and the protein is loaded. elute with equilibration solution containing 0.25 mM imidazole The highly purified protein is subsequently desalted in a storage buffer solution containing 10 mM HEPES, 0.14 M NaCl and 4% mannitol, pH 6.8, in a 25 ml G2 column 5 Superfine (Pharmacia) and stored at -80 ° C. The immunoadhesin constructs (containing Fc) of the proteins are purified from the conditioned medium in the following manner. The conditioned medium is pumped into a 5 ml Protein A column (Pharmacia) equilibrated with 20 mM Na phosphate buffer, pH 6.8. After loading, "the column is extensively washed with equilibration buffer before eluting with 100 mM citric acid, pH 3.5 The eluted protein is immediately neutralized by collecting 1 ml fractions in tubes containing 275 ml of 1 M Tris buffer , pH 9. The highly purified protein, subsequently, is desalted in solution jti - *** - *. .. Jti M «Mrta» É ^^^^ > ÉttgA..t .. ^, ^ ak, rt .. ^. ^^. ^^. , ... *.,., _ * * _ * ... + storage regulatory AU in the manner previously described for poly-His tagged proteins. The homogeneity of the proteins is verified by polyacrylamide gel electrophoresis (PEG) with SDS and an N-terminal amino acid sequencing is performed by the Edman degradation method. The PRO301, PR0362, PR0356, PRO509 and PR0866 polypeptides were expressed in Sf9 insect cells infected with baculovirus. Alternatively, a modified baculovirus method incorporating high-5 cells can be employed. In this procedure, DNA encoding the desired sequence is amplified by suitable systems, such as Pfu (Stratagene) or fused upstream (away from 5 ') from the contained epitope tag, with a baculovirus expression vector. Such epitope tags include poly-His tags and immunoglobulin tags (such as Fc regions of IgG). A variety of plasmids can be used. including plasmids derived from commercial sources such as pIEl-1 (Novagen). The vectors pIEl-1 and pIEl-2 are designed for the constitutive expression of recombinant proteins of the baculovirus iel promoter, in stably transformed insect cells (1). The plasmids differ only in the orientation of the multiple sites of JtlaAri * * - »-« .- j a, af.afca.ía ti. , .Aki cloning and contain all the promoter sequences that are known to be important for the expression of iel-mediated genes in uninfected insect cells, as well as the hr5 enhancer element. The pIEl-1 and pIEl-2 vectors include the translation start site and can be used to produce fusion proteins. Briefly, the desired sequence or the desired sequence portion (such as the coding sequence of the extracellular domain of a transmembrane protein) is amplified by PCR with primers complementary to the 5 'and 3' regions. The 5 'primer can incorporate flanking restriction enzyme sites (selected). The product is subsequently digested with those selected restriction enzymes and subcloned into the expression vector. For example, pIEl-1 derivatives can include the Fc region of human IgG (pb.PH.IgG) or can include a tag of 8 histidines (pb.PH.His) downstream (away from 3 ') of the desired sequence. Preferably, the construction of the vector is subjected to a sequencing for confirmation. High-5 cells are grown to 50% confluence under 27 ° C conditions, without C02, without pen / strep. For each 150 mm plate, 30 μg of the pIE-based vector containing the sequence is mixed with 1 ml of Ex-Cell medium (Medium: Ex-Cell 401 + 1/100 L-Glu JRH **. * ^ ** * t? ***********. * ^ *** ^ *** ^! »^. * ^ *. i **: A? A ~ t t. > i Biosciences # 14401-78P (note: this medium is sensitive to light)) and in a separate tube, 100 μl of CellFectin (CellFECTIN (Gibco BRL # 10362-010) (mixed in vortex)) is mixed with 1 ml of Ex-Cell medium. The two solutions are combined and left and allowed to incubate at room temperature for 15 minutes. 8 ml of the Ex-Cell medium is added to the 2 ml of DNA-CellFECTIN mixture and this mixture is applied on high-5 cells that were washed once with Ex-Cell medium. The plate is then incubated in the dark for 1 hour at room temperature. Then, the DNA-CellFECTIN mixture is aspirated and the cells are washed once with Ex-Cell medium to remove excess CellFECTIN, 30 ml of fresh Ex-Cell medium are added and the cells are incubated for 3 days at 28 °. C. The supernatant is harvested and the expression of the sequence in the baculovirus expression vector is determined by batching 1 ml of the supernatant to 25 ml of Ni 2 + -NTA beads (Qiagen) for the histidine-tagged proteins, or , in Protein A sepharose CL-4B (Pharmacia) accounts for proteins marked with IgG, which is followed by an analysis by SDS-EGPA? comparing with a known concentration of a protein standard, staining with Coomassie Blue. The conditioned medium of the transfected cells (from 0.5 to 3 1) is harvested by centrifugation to remove the cells and filter through 0.22 micron filters. For the poly-His tagged constructs, the protein comprising the sequence is purified using a Ni-NTA column (Qiagen). Before the purification, imidazole is added to the conditioned medium to a concentration of 5 mM. The conditioned medium is pumped into a 6 ml column of Ni2 + -NTA equilibrated with 20 mM HEPES, pH 7.4, buffer solution containing 0.3 M NaCl and 5 mM imidazole, at a flow rate of 4-5 ml / min, at 10 48 ° C. After loading, the column is washed with additional equilibration buffer solution and the protein is eluted with equilibration buffer containing 0.25 M imidazole. The highly purified protein is subsequently desalinated in a buffer solution. 15 storage containing 10 mM HEPES, 0.14 M NaCl, 4% mannitol, pH 6.8, in a 25 ml G25 Superfine column (Pharmacia) and stored at -80 ° C. The immunoadhesin constructs (containing Fc) of the proteins, are purified "from the conditioned medium 20 as follows. The conditioned medium is pumped into a 5 ml Protein A column (Pharmacia) equilibrated with 20 mM Na phosphate buffer, pH 6.8. After loading, the column is extensively washed with equilibration buffer before eluting with acid *****? i **. ** í; t j.i, ¿ait¿.,. * *. ~ *, ¿ . * Í **. * S »& .Í **? ^. citric 100 mM, pH 3.5. The eluted protein is immediately neutralized by collecting 1 ml fractions in tubes containing 275 μl of 1 M Tris buffer, pH 9. The highly purified protein is subsequently desalinated in a storage buffer in the manner previously described for the proteins. marked with poly-His. The homogeneity is evaluated by polyacrylamide gel electrophoresis with SDS and an N-terminal amino acid sequencing is performed by the Edman degradation method and by other analytical procedures, as desired or necessary. The polypeptides PR0179, PR0221, PR0224, PR0328, PRO301, PR0356, PR0362 and PR0356 were expressed using the above baculovirus procedure, using high-5 cells. EXAMPLE 21 Preparation of Antibodies that bind to PRQ179, PRO207, PRO320, PRQ219, PRQ221, PRQ22, PRQ328, PRO301, PRQ526, PRQ362, PRQ356, PRO509 or PRQ866. This Example illustrates the preparation of monoclonal antibodies that can bind specifically to PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. The techniques for producing monoclonal antibodies are known and are described, for example, in AiAa Goding, supra. Immunogens that may be used include PR0179, PRO207, PRO320, PR0219, PR0221, PR0225, PR0328, PR0328, PR0301, PR0526, PR0362, PR0362, PR0356, PRO509 or PR0866 purified fusion proteins containing PR0179, PRO207, PRO320, PR0219, PR0221 polypeptide, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 and PR0179, PRO207, PRO320, PR0219, PR0221, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 recombinant PR0276 or PR0866 polypeptides cell phone. The selection of the immunogen can be carried out by a person skilled in the art without undue experimentation. Mice, such as Balb / c mice, are immunized with immunogens PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 emulsified in complete Freund's adjuvant and injected via subcutaneous or intraperitoneal in an amount of 1 to 100 micrograms. Alternatively, the immunogen is emulsified in MPL-TDM adjuvant (Ribi Immunochemical Research, Hamilton, MT) and injected into the plantar pad of the hind legs of the animals. Mice subsequently immunized are boosted 10 to 12 days later, with additional immunogen emulsified in the selected adjuvant. Then, for several weeks, the mice can be reinforced with additional immunization injections. Serum samples of the mice can be obtained periodically by retro-orbital puncture to perform tests in ELISA assays to detect the anti-PR0179, anti-PRO207, anti-PR? 320, anti-PR0219, anti-PR0221, anti-PR0224 antibodies. , anti-PR0328, anti-PRO301, anti-PR0526, anti-PR0362, anti-PR0356, anti-PR? 509 or anti-PR0866. After an adequate antibody titer has been detected, the animals "positive" for the 10 antibodies can be injected with a final intravenous injection of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. Three to four days later, the mice are sacrificed and the spleen cells are 15 harvest. Spleen cells are fused (using 35% polyethylene glycol) with a selected murine myeloma cell line, such as P3X63AgU.l cells, available from the ATCC with the number CRL 1597. The fusions generate hybridoma cells, which Subsequently, they can be cultured in 96-well tissue culture plates containing HAT medium (hypoxanthine, aminopterin and thymidine), to inhibit the proliferation of unfused cells, myeloma hybrids and spleen cell hybrids.

Hybridoma cells will be selected by ELISA for their reactivity against PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PR0509 or PR0866. The determination of the "positive" hybridoma cells that secrete the desired monoclonal antibodies against PR0179, PR0207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866, is within the knowledge of the technicians in the matter. Hybridoma positive cells can be injected intraperitoneally in syngeneic Balb / c mice to produce ascites containing the monoclonal antibodies anti-PR0179, anti-PRO207, anti-PRO320, anti-PR0219, anti-PR0221, anti-PR0224 , anti-PR0328, 15 anti-PRO301, anti-PR0526, anti-PR0362, anti-PR0356, anti-PRO509 or anti-PR0866. Alternatively, the hybridoma cells can be grown in tissue culture bottles or cylindrical bottles. The purification of the monoclonal antibodies produced in the ascites can be 20 carried out by precipitation with ammonium sulfate, followed by gel exclusion chromatography. Alternatively, affinity chromatography can be used based on the binding of the antibody with protein A or protein G. *? - a? iil? -.?, * - *., * íí¡l í * i .i .. ,,,.; EXAMPLE 22 Purification of PRQ179, PRO207, PRO320 polypeptides, PR0219, PRQ221, PR0224, PRQ328, PRO301, PRQ526, PRQ362, PRQ356, PRO509 or PRQ866 Using Specific Antibodies. The polypeptides PR0179, PRO207, PRO320, PR0219, Native or recombinant PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 can be purified by a variety of standard techniques in the field of protein purification. For example, the pro-PR0179 polypeptide, pro-PR0207, pro-PRO320, pro-PR0219, pro-PR0221, pro-PR0224, pro-PR0328, pro-PRO301, pro-PR0526, pro-PR0362, pro-PR0356, pro -PR? 509 or pro-PR? 866, mature PR0179 polypeptide, mature PRO207, mature PRO320, mature PR0219, mature PR0221, mature PR0224, mature PR0328, mature PRO301, mature PR0526, mature PR0362, mature PR0356, mature PR0509 or PR0866 mature, or the pre-PR0179 polypeptide, pre-PR0207, pre-PRO320, pre-PR0219, pre-PR0221, pre-PR0224, pre-PR0328, pre-PRO301, pre-PR0526, pre-PR0362, pre-PR0356, pre -PR? 509 or pre-PR0866, is purified by immunoaffinity chromatography using specific antibodies against the pro-PR0179 polypeptide, pro-PRO207, pro-PRO320, pro-PR0219, pro-PR0221, pro-PR0224, pro-PR0328, pro -PRO301, pro-PR0526, pro-PR0362, pro-PR0356, pro-PR0509 or pro-PR0866, of interest. In general, an immunoaffinity column is constructed by the covalent coupling of the ltl? .__? A, J- -tH- *. - * to. . **** "... __, ^, * '. •.-.-- a' - *" - - - - - • - * 1 .--, fa * .. "A * * * SS ** * t **?. ** ^ anti-PR0179 antibodies, anti-PRO207, anti-PRO320, anti-PR0219, anti-PR0221, anti-PR0224, anti-PR0328, anti-PRO301, anti-PR0526, anti-PR0362, anti-PR0356, anti-PRO509 or anti-PR0866, in an activated chromatographic resin Polyclonal immunoglobulins are prepared from immune sera either by precipitation with ammonium sulfate, or by purification on a column with Protein A immobilized (Pharmacia LKB Biotechnology, Piscataway, NJ) Similarly, monoclonal antibodies are prepared from murine ascites fluid by precipitation with ammonium sulfate or by chromatography on a column with immobilized Protein A. Partially purified immunoglobulin is covalently bound to a chromatographic resin, such as SEPHAROSE activated with CnBr (Pharmacia LKB Biotechnology). The antibody is attached to the resin, the resin is blocked and the resin is washed in accordance with the manufacturer's instructions. Such an immunoaffinity column is used for the purification of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0301, PR0526, PR0362, PR0362, PR0356, PR0509 or PR0866 polypeptides, preparing a fraction from cells containing PR0179 polypeptide, PRO207 , PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 in soluble form.

«T, t_« A? i 1 i *! *. ^ * _ ** j *. * .l * ii "-AÍ, to '****. *****. ** ^. ******** - * .- *, ****. *** *, * *** * í * J¡, This preparation is derived by solubilization of whole cells or of a subcellular fraction obtained by differential centrifugation by the addition of detergent or by other methods known in the art .. Alternatively, the PR0179, PRO207, PRO320, PR0219, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0366, PR0356, PRO509 or PR0866 PR0866 soluble polypeptide containing a signal sequence, can be secreted in a useful amount in the medium in which they were grown The PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0362, PR0356, PR0509, PR0509 or PR0866 soluble PR0866 polypeptide is prepared on an immunoaffinity column and the column is washed under conditions that allow the preferential absorbance of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0 polypeptides 866 (e.g., regulatory solutions of high ionic strength in the presence of a detergent). Then, the column is eluted under conditions that break the binding-of the antibody / PR0179, antibody / PRO207, antibody / PR3203, antibody / PR2.19, antibody / PR0221, antibody / PR0224, antibody / PR0328, antibody / PRO301, antibody / PR0526 antibody / PR0362 antibody / PR0356 antibody / PR? 509 or antibody / PR0866 (eg, a low pH buffer such as approximately pH 1-3, or a high concentration of a chaotrope, such as urea or thiocyanate ions) and the polypeptide PR0179, PRO207, PR0320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 are collected. EXAMPLE 23 Drug Selection The present invention is particularly useful for selecting compounds using the PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0366, PRO509 or PR0866 polypeptides or a binding fragment thereof. , in any of a variety of drug selection techniques. The polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or the fragment used in such tests, can be free in solution, can be fixed to a solid support, can originate on a cell surface or can be located intracellularly. A method of drug selection utilizes eukaryotic or prokaryotic host cells that were stably transformed with recombinant nucleic acids expressing PR0179 polypeptide, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or a fragment thereof. The drugs are selected against such transformed cells in competitive binding assays. Such cells, either in viable form or in fixed form, can be used to perform the standard binding assays. One can measure, for example, the formation of complexes between a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or a fragment thereof, and the agent that is Its testing. Alternatively, the decrease in complex formation between the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 and its target cell or its target receptors can be examined in where said decrease is caused by the agent being tested. Thus, the present invention provides methods for screening drugs or any other agent that can affect a disease or disorder associated with PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. These methods comprise contacting the agent with a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or a fragment thereof, and evaluating (i) the presence of a complex between the agent and the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or fragment thereof, or (ii) the presence of a complex between the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or fragment thereof and the cell, by methods known in the art. In such competitive binding assays, the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0301, PR0526, PR0362, PR0356, PRO509 or PR0866 or fragment thereof, is typically labeled. After a suitable incubation, the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or fragment thereof which is free, is separated from that which is present in the form bound, and the amount of uncomplexed polypeptide is a measure of the ability of the particular agent to bind PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PR0509 or PR0866 polypeptide or to interfere with the formation of the polypeptide complex PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 / cell. Another technique for drug selection provides a high throughput screening for compounds that have the proper binding affinity for a polypeptide, and is described in greater detail in International Publication WO 84/03564, published September 13, 1984. Briefly , a large number of different small peptide test compounds are synthesized on a solid substrate, such as plastic pins or some other surface. As it is applied to a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 the test peptide reacts with the polypeptide PR0179, PRO207, PRO320, PR0219, PR0221 , PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 and washed. The PR0179, PRO207, PR0320, PR0219, PR0221, PR0224, PR0328, PR0301, PR0301, PR0526, PR0362, PR0366, PR0356, PRO509 or PR0866 polypeptide are bound by methods known in the art. PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0362, PR0356, PRO509 or PR0866 purified PR0866 polypeptide can also be directly coated on plates for use in the aforementioned drug selection techniques. In addition, non-neutralizing antibodies can be used to capture the peptide and immobilize it on a solid support. The present invention also contemplates the use of competitive drug selection assays, in which neutralizing antibodies capable of binding to polypeptide PR0179, PR0207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866, compete specifically with a test compound for binding to PR0179 polypeptide, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or fragments thereof. Thus, the antibodies can be used to detect the presence of any peptide that shares one or more antigenic domains with a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. EXAMPLE 24 Fundamentals of Drug Design The goal of the drug design rationale is to produce structural analogues of a biologically active polypeptide of interest (ie, a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PR0301, PR0526, PR0362 , PR0356, PRO509 or PR0866) or small molecules with which it interacts, eg, agonists, antagonists or inhibitors. Any of these examples can be used to produce drugs that are more active or more stable forms of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 polypeptides or that increase or interfere with the function of the PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0362, PR0356, PRO509 or PR0866 polypeptide in vivo (cf, Hodgson, Bio / Technology, 9: 19-21 (1991)) . In one approach, the three-dimensional structure of the polypeptide complex PR0179, PRO207, PRO320, PR0219, ? rf l-la é * é *? i * ¿- ** ¡a e *. * & * _. ^ -i _ ^ _ ^ a? »M8i ??? a? IMMiM? I ?? i ?? iateA), aj. , a., -, .JiAB ^ aifc ... ** ** ** ^ ** v *** .. * *****,. aA¡ < LLl PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866-inhibitor is determined by X-ray crystallography, by computer modeling or, more typically, by a combination of these two procedures. Both the form and changes of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 polypeptides should be checked to elucidate the structure and to determine the active site (s) of the molecule. Less frequently, useful information can be obtained regarding the structure of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0366, PRO509 or PR0866 by modeling based on protein structure. homologous In both cases, relevant structural information is used to design molecules similar to PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 analog polypeptides or to identify efficient inhibitors. Useful examples of the basis of drug designs may include molecules having an unproven activity or stability, as shown in Braxton and Wells, Biochemistry, 31: 1196-1801 (1992) or which act as inhibitors, agonists or antagonists of the native peptides, as shown in Athauda et al. , J. Biochem. , 113: 742-746 (1993).

? AA. *? T * í ** tt * and ** ^ * í ***** ,, * "., .. ,, * * ^ _ ** ** ***, * .., * ***. **** * ..., *** & * «* **», * *** * .. *, ,,, 4 ,, ". ^ .a.at.at.ait ..

It is also possible to isolate an antibody with specific target, it is selected by a functional assay in the manner described above and then its crystal structure is resolved. This approach, in principle, produces a pharmacor (drug core) on which the drug design can be based. It is possible to skip the crystallography of the protein by generating anti-idiotypic antibodies against a functional, pharmacologically active antibody. As a mirror image, the anti-idiotypic antibody binding site is expected to be analogous to the original receptor. The anti-idiotypic antibody, then, can be used to identify and isolate peptides from chemically or biologically produced peptide libraries. The isolated peptides, then, would act like the pharmacore. By virtue of the present invention, sufficient quantities of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0366, PR0356, PRO509 or PR0866 polypeptide can be prepared to perform such analytical studies, such as crystallography In addition, knowledge of the amino acid sequence of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0366, PR0356, PRO509 or PR0866 polypeptides provided herein will provide guidelines for those who use modeling techniquesIM v. on computer, in place or in addition to X-ray crystallography. EXAMPLE 25 In Vitro Antitumoral Assay The antiproliferative activity of PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0232, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 and PR0866 was determined in the disease-oriented anti-cancer drug discovery assay of the National Cancer Institute (NCI), using a sulforhodamine B (SRB) dye binding assay essentially in the manner described by Skehan et al., J. Natl. Cancer Inst. , 82: 1107-1112 (1990). The 60 tumor cell lines used in this study ("the NCI panel"), as well as the conditions for their maintenance and in vitro culture, have been described by Monks et al., J. Natl. Cancer Inst. , 83: 757-766 (1991). The purpose of this selection is to initially evaluate the cytotoxic and / or cytostatic activity of the test compounds against different types of tumors Monks et al. , supra; Boyd, Cancer: Princ. Pract Oncol. Update, 3 (10): 1-12

[1989]). Cells from approximately 60 human tumor cell lines were harvested with trypsin / AEDT (Gibco), washed once, resuspended in IMEM medium and their viability was determined. The suspensions Cells were added by pipetting (100 μl volume) to 96-well microplates separately. The cell density of the 6-day incubation was lower than that of the 2-day incubation to prevent excess growth. The inoculations were left in a preincubation period for 24 hours at 37 ° C for stabilization. Dilutions were added at twice the test concentration sought at time 0, in a 100 μl aliquot to the wells of the microplates (dilution 1: 2). The test compounds were evaluated at dilutions of five logarithmic media (from 1000 to 100,000). Incubations were carried out for two days and six days in an atmosphere with 5% C02 and 100% humidity. After incubation, the culture medium was removed and the cells were fixed in 0.1 ml of 10% trichloroacetic acid at 40 ° C. The plates were rinsed five times with deionized water, dried, stained for 30 minutes with 0.1 ml of 0.4% sulforhodamine B dye (Sigma) dissolved in 1% acetic acid, rinsed four times with 1% acetic acid to Remove the unbound dye, dry and stain for five minutes with 0.1 ml of 10 mM Tris-base [tris- (hydroxymethyl) -aminomethane], pH 10.5. The absorbance (OD) of sulforrodamine B at 492 nm using a computer with a 96 well reader interface. A test sample was considered positive if it showed an effect of 40% inhibition of growth at one or more concentrations. The results are shown in the following Table 4, where the abbreviations of the cell type are the following: CPNCP = non-small cell lung carcinoma; CNS = central nervous system.

Table 4 Compound Type of Tumor Cell Designation PR0179 Leukemia CCRF-CEM PR0179 Breast HS 578T PR0179 CPNCP SR PR0179 Breast NCI / 7ADR-RES PR0179 Leukemia HL-60 (TB); SR PR0179 CPNCP HOP-62; NCI-H460 breast PR0179 MDA-N PR0179 CPNCP NCI-H522 PR0179 colon COLO 205; HCC-2998 PR0179 of SNC SF-295 breast PR0179 MDA-MB-435 PR0179 of prostate PC-3 PR0179 leukemia MOLT-4 L? - í JÍ, < * ?? 1 »t.? * ^. ** or? MJfa «t ^^ JL ^ PR0179 melanoma SK-MEL-5; SK-MEL-2 breast PR0179 MDA-MD-435; T-47D PR0179 melanoma MALME-3M PR0179 CPNCP NCI-H322 PR0179 colon HCT-15 PR0179 ovarian OVCAR-3 PR0179 CPNCP NCI-H226 PR0179 renal RXF-393 Renal PRO207 CAKI-1; RXF-393 PRO207 leukemia MOLT-4; SR PRO207 CPNCP NCI-H322M; NCI-H522 PRO207 CPNCP HOP-62 PRO207 colon COLO 205 PRO207 melanoma LOX PRO207 ovarian IGROVI PRO207 renal ACHN PRO207 prostate PC-3 breast PRO207 MDA-MB-231 / ATCC PRO320 leukemia CCRF-CEM; RPMI-8226 PRO320 CPNCP HOP62; NCI H322M PRO320 colon HCT-116 PRO320 renal SN12C PRO320 breast MDA-N PRO320 ovarian OVCAR-3 PRO320 melanoma MALME-3M PR0219 leukemia SR PR0219 CPNCP NCI-H5222 breast PR0219 MCF7 PR0219 leukemia K-562; RPMI-8226 PR0219 CPNCP H0P-62; NCI-H322M PR0219 CPNCP NCI-H460 PR0219 from colon HT29; KM12; HCT-116 PR0219 of SNC SF-539; Prostate U251 PR0219 Prostate DU-145 PR0219 breast MDA-N PR0219 ovarian IGROVI PR0219 CPNCP NCI-H226 PR0219 leukemia MOLT-4 PR0219 CPNCP A549 / ATCC; EKVX; NCI-H23 PR0219 from colon HCC-2998 PR0219 from SNC SF-295; SNB-19 PR0219 melanoma SK-MEL-2; SK-MEL-5 PR0219 melanoma UACC-257; UACC-62 PR0219 ovarian OCAR-4; SK-OV-3 PR0219 renal 786-0; ACHN; CAKI-1; SN12C PR0219 renal TK-10; UO-31 breast PR0219 NCI / ADR-RES; BT-549; T-47D Breast PR0219 MDA-MB-435 PR0221 leukemia CCRF-CEM PR0221 leukemia M0LT-4 PR0221 CPNCP HOP-62 breast PR0221 MDA-N PR0221 leukemia RPMI-8226; SR PR0221 CPNCP NCI-H460 PR0221 colon HCC-2998 PR0221 ovarian IGROVI PR0221 renal TK-10 PR0221 breast MCF7 PR0221 leukemia K-562 breast PR0221 MDA-MB-435 PR0224 ovarian 0VCAR-4 PR0224 renal RXF 393 prostate PR0224 DU-145 PR0224 CPNCP HOP-62; NCI-H322M PR0224 melanoma LÓX LIP OVI PR0224 ovarian OVCAR-8 PR0224 leukemia SR PR0224 CPNCP NCI-H460 PR0224 of SNC SF-295 PR0224 leukemia RPMI-8226 &JS. S. * Í .-. Í *. **. ** - * - *. l ^ ggjj ^ S ^^^^^ k ^^^^ l ^^^^^^^^^^ of breast BT-549 PR0224 leukemia CCRF-CEM; LH-60 (TB) PR0224 of colon HCT-116 PR0224 of breast MDA-MB-435 PR0224 leukemia HL-60 (TB) PR0224 of colon HCC-2998 PR0224 of prostate PC-3 PR0224 of SNC U251 PR0224 of colon HCT-15 PR0224 of SNC SF-539 PR0224 renal ACHN PR0328 leukemia RPMI-8226 PR0328 CPNCP A549 / ATCC; EKVX; HOP-62 PR0328 CPNCP NCI-H23; NCI-H322M PR0328 of colon HCT-15; KM12 PR0328 of SNC SF-295; SF-539; SNB-19; U251 PR0328 melanoma M14; UACC-257; UCAA-62 PR0328 renal 786-0; ACHN PR0328 breast MCF7 PR0328 leukemia SR PR0328 colon NCI-H23 PR0328 melanoma SK-MEL-5 PR0328 prostate DU-145 PR0328 melanoma LOX IMVI 'a A-aá.t? f 4 ** t A *. ** *. á, ± * - - PR0328 Breast MDA-MB-435 PR0328 Ovarian OVCAR-3 Breast PR0328 T-47D PRO301 CPNCP NCI-H322M PRO301 leukemia MOLT-4; SR PRO301 CPNCP A549 / ATCC; EKVX PRO301 CPNCP NCI-H23; NCI-460; NCI-H226 Colon PRO301 COLO 205; HCC-2998 PRO301 colon HCT-15; KM12; HT29; PRO301 colon HCT-116 PRO301 of SNC SF-268; SF-295; SNB-19 PRO301 melanoma MALME-3M; SK-MEL-2 PRO.301 melanoma SK-MEL-5; UACC-257 PRO301 melanoma UACC-62 PRO301 ovarian IGROVI; OVCAR-4 PRO301 ovarian OVCAR-5 PRO301 ovarian OVCAR-8; SKOOV-3 PRO301 renal ACHN; CAKI-1; TK-10; UO-31 Prostate PRO301 PC-3; DU-145 breast PRO301 NCI / ADR-RES; HS 578T Breast PRO301 MDA-MB-435; MDA-N; T-47D PRO301 melanoma M14 PRO301 leukemia CCRF-CEM-HL-60 (TB); K-562 PRO301 leukemia RPMI-8226 í¿í * ^ * Á '? i¿ ?. i ^ PRO301 melanoma LOX IMVI PRO301 renal 786-0; SN12C breast PRO301 MCF7; MDA-MB-231 / ATCC PRO301 breast BT-549 PRO301 CPNCP HOP-62 PRO301 of SNC SF-539 PRO301 ovarian OVCAR-3 PR0526 CPNCP HOP-62; NCI-H322M PR0526 of colon HCT-116 PR0526 melanoma LOX IMVI; SK-MEL-2 PR0526 ovarian OVCAR-3 prostate PR0526 PC-3 PR0526 CPNCP NCI-H226 PR0526 of SNC SF-539 PR0526 renal CAKI-1; RXF 393 PR0362 CPNCP NCI-H322M PR0362 of colon HCT-116 PR0362 of SNC SF-295 PR0362 melanoma LOX IMVI PR0362 leukemia MOLT-4; RPMI-8226; SR PR0362 colon COLO 205 PR0362 breast HS 578T; MDA-N prostate PR0362 PC-3 *. **. 4. t¡¡ **** * .i, í. ? J t, - 3 - PR0362 leukemia HL-60 (TB); K-562 PR0362 CPNCP EKVX; NCI-H23 PR0362 from colon HCC-2998 PR0362 from SNC U251 PR0362 melanoma UACC-257; UACC-62 PR0362 ovarian OVCAR-8 breast PR0362 T-47D PR0362 CPNCP NCI-H522 renal PR0362 RXF 393; UO-31 breast PR0362 MDA-MB-435 PR0362 CPNCP HOP-62; NCI-H522 PR0362 of colon KM12 PR0362 melanoma MALME-3M; SK-MEL-2 PR0362 melanoma SK-MEL-28; SK-MEL-5 PR0362 ovarian OVCAR-3; OVCAR-4 PR0362 breast MCF7 PR0356 CCRF-CEM leukemia; M0LT-4; SR PR0356 CPNCP NCI -H23; NCI-H322M PR0356 CPNCP NCI-H460 PR0356 CPNCP A549 / ATCC PR0356 colon HCT-116; HCT-15; H29; KM12 PR0356 of SNC SF-268; SF-295; SF-539 PR0356 of SNC SNB-19 PR0356 melanoma LOX IMVI; SK-MEL-5 i i LA. • A.? * Á *. t * i, Í * ¡PR0356 melanoma UACC-257 PR0356 melanoma UACC-62 PR0356 ovarian OVCAR-8; OVCAR-5 PR0356 renal SN12C prostate PR0356 DU-145 PR0356 leukemia K-562 PR0356 leukemia HL-60 (TB) Breast PR0356 MDA-N PR0356 CPNCP EKVX; HOP-92 PR0356 of colon COLO 205; SW-620 PR0356 of SNC SNB-75; U251 PR0356 melanoma M14 PR0356 ovarian IGROVI; OVCAR-4 PR0356 Renal RXF 393 Breast PR0356 BT-549 PR0356 CPNCP NCI-H226 Breast PR0356 MDA-MB-435 PR0356 CPNCP HOP-62 PR0356 Renal UO-31 PR0356 Leukemia RPMI-8226 PRO509 leukemia K-562; MOLT-4 PRO509 CPNCP HOP-92 PRO509 of colon SW-620 PRO509 of SNC U251 , ** .J * & í * * *. ,,. fcfc, .. ** * »** > * &amp * * ** & I. & í PRO509 melanoma SK-MEL-28 PRO509 renal A498 PRO509 breast MDA-MB-435 PRO509 leukemia RPMI-8226 PRO509 melanoma SK-MEL-2 PRO509 ovarian OVCAR-3 PRO509 renal CAKI-1 PR0866 leukemia HL-60 (TB); M0LT-4; SR PR0866 CPNCP HOP-62 PR0866 CPNCP HOR-92 PR0866 colon KM12 PR0866 SNC SF-295 PR0866 ovarian IGROVI PR0866 breast MDA-MB-435 PR0866 melanoma LOX IMVI Deposit of Materials The following materials were deposited in the North American Type Culture Collection, 10801 University Blvd., Manassas, VA 20110-2209, USA (ATCC): Material No. of Deposit ATCC Date of Deposit DNA16451-1078 209281 September 18, 1997 DNA30879-1152 209358 October 10, 1997 DNA32284-1307 209670 March 11, 1998 DNA32290-1164 209384 October 17, 1997 DNA33089-1132 209262 September 16, 1997 DNA33221-1133 209263 September 16, 1997 DNA40587-1231 209438 November 7, 1997 DNA40628-1216 209432 November 7, 1997 DNA44184-1319 209704 March 26, 1998 DNA45416-1251 209620 February 5, 1998 NDA47470-1131-P1 209422 October 28, 1997 DNA53971-1359 209750 April 7, 1998 These deposits were made under the provisions of the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedures and their Regulations (Budapest Treaty). This ensures the maintenance of a viable crop of the deposit for 30 years starting from the date of deposit. The deposits will be made available in the ATCC under the terms of the Budapest Treaty and will be subject to an agreement between Genentech, Inc. and the ATCC, which ensures the permanent and unrestricted availability of the progeny of the crop deposited to the public upon its issuance. pertinent US Patent or upon making public any application for a US or foreign patent, whichever comes first, and * lJk * á? *** ,: í * i *. **** 4 * - 1 - ensures the availability of progeny for whom the United States Patent and Trademark Commission determines that they are entitled to it, in accordance with USC § 122 and the Regulations of the Commission with respect to this (including 37 CFR §1.14 with particular reference to 886 OG 638). The assignee of the present application has agreed that if a crop of the materials on deposit dies or is lost or destroyed when cultivated under suitable conditions, the materials will be quickly replaced by the same upon receipt of a notification. The availability of the deposited material is not considered as a license for the practice of the present invention in contrariety to the rights granted under the authority of any government, in accordance with its patent laws. The present written description is considered as sufficient for a person skilled in the art to practice the present invention. The present invention is not limited to the scope of the deposited constructions, since the deposited modalities are intended to illustrate certain aspects of the invention and any construction that is functionally equivalent is within the scope of the present invention. The deposit of the material hereof does not constitute a ******** - **, ********** *? ? *? t Jhd. - - admission that the present written description contained is inadequate to make possible the practice of any aspect of the invention, including the best mode thereof, nor is it considered as limiting the scope of the claims to the specific illustrations they represent. In fact, those skilled in the art will be able to devise several modifications of the invention in addition to those shown and described herein, without departing from the scope of the appended claims. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims

CLAIMS The invention having been described as an antecedent, the content of the following claims is claimed as property: 1. A composition useful for inhibiting the growth of neoplastic cells, characterized in that it comprises an effective amount of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PR0509 or PR0866 or an agonist thereof, mixed with a pharmaceutically acceptable carrier. The composition according to claim 1, characterized in that it comprises a growth inhibitory amount of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or an agonist of the same. 3. A composition according to claim 1, characterized in that it comprises a cytotoxic amount of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or an agonist thereof. . 4. The composition according to claim 1, characterized in that it also comprises i i?,? j? ** 3iá & í *, -other growth inhibitory agent, cytotoxic agent or chemotherapeutic agent. 5. A composition useful for the treatment of a tumor in a mammal, characterized in that it comprises a therapeutically effective amount of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or an agonist thereof. 6. The composition according to claim 5, characterized in that the tumor is a cancer. The composition according to claim 6, characterized in that the cancer is selected from the group consisting of breast cancer, ovarian cancer, renal cancer, colorectal cancer, uterine cancer, prostate cancer, lung cancer, bladder cancer, cancer of the central nervous system, melanoma and leukemia. 8. The use of a PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 polypeptide or an agonist thereof for the manufacture of a medicament for inhibiting the growth of a cell tumor. 9. The use according to claim 8, characterized in that the agonist is an anti-PR0179 antibody, anti-PRO207, anti-PRO320, anti-PR0219, anti-PR0221, ** ******** «* • * • - * • - £ **** .. *, *****. anti-PR0224, anti-PR0328, anti-PRO301, anti-PR0526, anti-PR0362, anti-PR0356, anti-PRO509 or anti-PR0866 agonist. 10. The use according to claim 8, characterized in that the agonist is a small molecule that mimics the biological activity of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. 11. The use according to claim 8, characterized in that the exposure step occurs in vi tro. 12. The use according to claim 8, characterized in that the exposure step occurs in vivo. 13. A manufacturing article, characterized in that it comprises: (a) a container; Y (b) a composition comprising an active agent contained in the container; wherein the active agent of the composition is a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866 or an agonist thereof. 14. The article of manufacture according to claim 13, characterized in that it further comprises a label fixed to the container or a packaging insert included in the container, which refers to the use of the composition to inhibit the growth of neoplastic cells. 15. The article according to claim 13, characterized in that the agonist is an anti-PR0179 antibody, anti-PRO207, anti-PRO320, anti-PR0219, anti-PR0221, anti-PR0224, anti-PR0328, anti-PRO301, anti-PR0526, anti-PR0362, anti-PR0356, anti-PRO509 or anti-PR0866 agonist. 16. The article of manufacture according to claim 13, characterized in that the agonist is a small molecule that mimics the biological activity of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866. 17. The article of manufacture according to claim 13, characterized in that the active agent is present in an amount that is effective for the treatment of a tumor in a mammal. 18. The article of manufacture according to claim 13, characterized in that the composition additionally comprises another growth inhibitory agent, cytotoxic agent or chemotherapeutic agent. 19. An isolated nucleic acid molecule, characterized in that it has at least 80% nucleic acid sequence identity with a nucleotide sequence encoding an amino acid sequence that is selected from the group consisting of the amino acid sequence shown in Figure 2 (SEQ ID No. 2), in Figure 4 (SEQ ID No. 7), in Figure 6 (SEQ ID No. 10), in Figure 8 (SEQ ID No. 15), in Figure 10 (SEQ ID No. 20), in Figure 12 (SEQ ID No. 25), in Figure 14 (SEQ ID No. 30), in Figure 16 (SEQ ID No. 35), in Figure 18 (SEQ ID No 43), in Figure 20 (SEQ ID No. 48), in Figure 22 (SEQ ID No. 55), in Figure 24 (SEQ ID No. 60), and in Figure 26 (SEQ ID No. 62). 20. An isolated nucleic acid, characterized in that it has at least 80% nucleic acid sequence identity with a nucleotide sequence that is selected from the group consisting of the nucleotide sequence shown in Figure 1 (SEQ ID No. 1) ), in Figure 3 (SEQ ID No. 6), in Fiqura 5 (SEQ ID No. 9), in Figure 7 (SEQ ID No. 14), in Figure 9 (SEQ ID No. 19), in Figure 11 (SEQ ID No. 24), in Figure 13 (SEQ ID No. 29), in Figure 15 (SEQ ID No. 34), in Figure 17 (SEQ ID No. 42), in the Figure 19 (SEQ ID No. 47), in Figure 21 (SEQ ID No. 54), in Figure 23 (SEQ ID No. 59), and in Figure 25 (SEQ ID No. 61). JL 21. An isolated nucleic acid, characterized in that it has at least 80% nucleic acid sequence identity with a nucleotide sequence that is selected from the group consisting of the full-length coding sequence of the nucleotide sequence shown in the Figure 1 (SEQ ID No. 1), in Figure 3 (SEQ ID No. 6), in Figure 5 (SEQ ID No. 9), in Figure 7 (SEQ ID No. 14), in Figure 9 ( SEQ ID No. 19), in Figure 11 (SEQ ID No. 24), in Figure 13 (SEQ ID No. 29), in Figure 15 (SEQ ID No. 34), in Figure 17 (SEQ ID No. 42), in Figure 19 (SEQ ID No. 47), in Figure 21 (SEQ ID No. 54), in Figure 23 (SEQ ID No. 59), and in Figure 25 (SEQ ID No 61). 22. An isolated nucleic acid, characterized in that it has at least 80% nucleic acid sequence identity with the full-length coding sequence of 7DNA deposited with the ATCC with accession number, 209281, 209358, 209670, 209384, 209262, 209263, 209438, 209432, 209704, 209620, 209422 or 209750. 23. A vector characterized in that it comprises the nucleic acid according to any of claims 19 to 22. 24. The vector according to claim 23, characterized in that it is ligated operable to control sequences that are recognized I ¡ÁAMLÁ? * I -ÉaÉa ka ¿.jJ > fckMa * *. by a host cell transformed with said vector. 25. A host cell characterized in that it comprises the vector according to claim 23. 26. The host cell according to claim 25, characterized in that it is a CHO cell. 27. The host cell according to claim 25, characterized in that it is an E. coli cell. 28. The host cell according to claim 25, characterized in that it is a yeast cell. 29. The host cell according to claim 25, characterized in that it is an insect cell infected by baculovirus. 30. A process for the production of a polypeptide PR0179, PRO207, PRO320, PR0219, PR0221, PR0224, PR0328, PRO301, PR0526, PR0362, PR0356, PRO509 or PR0866, characterized in that it comprises the steps of culturing the host cell in accordance with Claim 25 under conditions suitable for the expression of the polypeptide and recover the polypeptide from the cell culture. 31. An isolated polypeptide, characterized in that it has at least 80% amino acid sequence identity with an amino acid sequence that is *? í¡ **** LÁ * í. **** - ¡¡¡*.:,. I_ - * i *: i..i, .í fc. select from the group consisting of the amino acid sequence shown in Figure 2 (? EQ ID No. 2), in Figure 4 (SEQ ID No. 7), in Figure 6 (SEQ ID No. 10), in Figure 8 (SEQ ID No. 15), in Figure 10 (SEQ ID No. 20), in Figure 12 (SEQ ID No. 25), in Figure 14 (SEQ ID No. 30), in Figure 16 (SEQ ID No. 35), in Figure 18 (SEQ ID No. 43), in Figure 20 (SEQ ID No. 48), in Figure 22 (SEQ ID No. 55), in Figure 24 (SEQ ID No. 60), and in Figure 26 (SEQ ID No. 62). 32. An isolated polypeptide, characterized in that it qualifies at least 80% positives when compared to an amino acid sequence that is selected from the group consisting of the amino acid sequence shown in Figure 2 (SEQ ID No. 2), Figure 4 (SEQ ID No. 7), in Figure 6 (SEQ ID No. 10), in Figure 8 (SEQ ID No. 15), in Figure 10 (SEQ ID No. 20), in Figure 12 (SEQ ID No. 25), in Figure 14 (SEQ ID No. 30), in Figure 16 (SEQ ID No. 35), in Figure 18 (SEQ ID No. 43), in Figure 20 (SEQ. ID No. 48), in Figure 22 (SEQ ID No. 55), in Figure 24 (SEQ ID No. 60), and in Figure 26 (SEQ ID No. 62). 33. An isolated polypeptide, characterized in that it has at least 80% amino acid sequence identity with an amino acid sequence encoded by the full length coding sequence of the DNA - - deposited with the ATCC with the access number, 209281, 209358, 209670, 209384, 209262, 209263, 209438, 209432, 209704, 209620, 209422 or 209750. 34. A chimeric molecule characterized in that it comprises a polypeptide in accordance with any of claims 31 to 33, fused to a heterologous amino acid sequence. 35. The chimeric molecule according to claim 34, characterized in that the heterologous amino acid sequence is an epitope tag sequence. 36. The chimeric molecule according to claim 34, characterized in that the heterologous amino acid sequence is an Fc region of an immunoglobulin. 37. An antibody characterized by specifically binding to a polypeptide according to any of claims 31 to 33. 38. The antibody according to claim 37, characterized in that it is a monoclonal antibody, a humanized antibody or a single chain antibody. . 39. An isolated nucleic acid, characterized in that it has at least 80% nucleic acid sequence identity with: (a) a nucleotide sequence encoding the polypeptide shown in Figure 2 (SEQ ID No. 2), Figure 4 (SEQ ID No. 7), in Figure 6 (SEQ ID No. 10), in Figure 8 (SEQ ID No. 15), in Figure 10 (SEQ ID No. 20), in Figure 12 (SEQ ID No. 25), in Figure 5 14 (SEQ ID No. 30), in Figure 16 (SEQ ID No. 35), in Figure 18 (SEQ ID No. 43), in Figure 20 ( SEQ ID No. 48), in Figure 22 (SEQ ID No. 55), in Figure 24 (SEQ ID No. 60), or in Figure 26 (SEQ ID No. 62), which lacks its own peptide. associated signal; 10 (b) a nucleotide sequence encoding an extracellular domain of the polypeptide shown in Figure 2 (SEQ ID No. 2), in Figure 4 (SEQ ID No. 7), in Figure 6 (SEQ ID No. 10), in Figure 8 (SEQ ID No. 15), in Figure 10 (SEQ ID No. 20), in Figure 12 (SEQ. 15 ID No. 25), in Figure 14 (SEQ ID No. 30), in Figure 16 (SEQ ID No. 35), in Figure 18 (SEQ ID No. 43), in Figure 20 (SEQ ID No. 48), in Figure 22 (SEQ ID No. 55), in Figure 24 (SEQ ID No. 60), or in Figure 26 (SEQ ID No. 62), which has its associated signal peptide; (C) a nucleotide sequence encoding an extracellular domain of the polypeptide shown in Figure 2 (SEQ ID No. 2), in Figure 4 (SEQ ID No. 7), in Figure 6 (SEQ ID No. 10), in Figure 8 (SEQ ID No. 15), in Figure 10 (SEQ ID No. 20), in Figure 12 (SEQ. 25 ID No. 25), in Figure 14 (SEQ ID No. 30), in Figure - 16 (SEQ ID No. 35), in Figure 18 (SEQ ID No. 43), in Figure 20 (SEQ ID No. 48), in Figure 22 (SEQ ID No. 55), in Figure 24 ( SEQ ID No. 60), or in Figure 26 (SEQ ID No. 62), which lacks its associated signal peptide. 40. An isolated polypeptide characterized in that it has at least 80% sequence identity with: (a) the polypeptide shown in Figure 2 (SEQ ID No. 2), in Figure 4 (SEQ ID No. 7), in Figure 6 (SEQ ID No. 10), in Figure 8 (SEQ ID No. 15), in Figure 10 (SEQ ID No. 20), in Figure 12 (SEQ ID No. 25), in Figure 14 (SEQ ID No. 30), in Figure 16 (SEQ ID No. 35), in Figure 18 (SEQ ID No. 43), in Figure 20 (SEQ ID No. 48), in Figure 22 (SEQ ID No. 55), in the Figure 24 (SEQ ID No. 60), or in Figure 26 (SEQ ID No. 62), which lacks its associated signal peptide; (b) an extracellular domain of the polypeptide shown in Figure 2 (SEQ ID No. 2), in Figure 4 (SEQ. ID No. 7), in Figure 6 (SEQ ID No. 10), in Figure 8 (SEQ ID No. 15), in Figure 10 (SEQ ID No. 20), in Figure 12 (SEQ ID No. 25), in Figure 14 (SEQ ID No. 30), in Figure 16 (SEQ. ID No. 35), in Figure 18 (SEQ ID No. 43), in Figure 20 (SEQ ID No. 48), in Figure 22 (SEQ ID No. 55), in Figure 24 (SEQ ID No. 60), in the Figure 26 (SEQ ID No. 62), in Figure 28 (SEQ ID No. 76), in Figure 30 (SEQ ID No. 78), in Figure 32 (SEQ ID) * j «al.m3. * - > » i.it. - 9 - No. 83), or in Figure 34 (SEQ ID No. 91), which has its associated signal peptide; (c) an extracellular domain of the polypeptide shown in Figure 2 (SEQ ID No. 2), in Figure 4 (SEQ 5 ID No. 7), in Figure 6 (SEQ ID No. 10), in Figure 8 (SEQ ID No. 15), in Figure 10 (SEQ ID No. 20), in Figure 12 (SEQ ID No. 25), in Figure 14 (SEQ ID No. 30), in Figure 16 (SEQ. ID No. 35), in Figure 18 (SEQ ID No. 43), in Figure 20 (SEQ ID No. 48), in Figure 22 10 (SEQ ID No. 55), in Figure 24 (SEQ ID No. 60), in Figure 26 (SEQ ID No. 62), in Figure 28 (SEQ ID No. 76), in Figure 30 (SEQ ID No. 78), in Figure 32 (SEQ ID No. 83), or in Figure 34 (SEQ ID No. 91), which lacks its associated signal peptide.