CN1461310A - 结合人白介素-18的抗体及制备和使用方法 - Google Patents
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Abstract
Description
24IL-18: YFGK-LESKLS-VIRNLNDQVLFIDQGNRPLFE--DMT-DSDCRD--NAPIL-1β: AP-VRS-LNCTLRDSQQKSLVMS-G--P-YELKALHLQGQ--D--MEQIL-1RA: SSKMQA-FR--IWDVNQKTFYLR-N--N--QLVAGYLQGP--NVNLEE80IL-18: RTIFIISMY-KDSQPRG-MAVTISVKCEKISTLSC----ENK-IISFKEMIL-1β:QVVFSMS-FVQGEESNDKIPVALGLK-EKNLYLSCVLK-DDKPTLQLESVIL-1RA:KI--DV---VP-IEPH---ALFLGIH-GGKMCLSCV-KSGDETRLQLEAV123IL-18: NPPDNI-KDTKSDIIF-FQRSVPGHDNKMQFESSSYEGYFLACE-KERDLIL-1β:DPKNYP-KK-KMEKRFVFNK-I-EINNKLEFESAQFPNWYISTS-QAENMIL-1RA:NITDLSENR-KQDKRFAFIR-S-DSGPTTSFESAACPGWFLCTAMEADQ-170IL-18: FKLILKKED-ELGDRSIM-FTVQNED (SEQ ID NO:4)IL-1β:-PVFL--GG-TKGGQDITDFTMQFVSS (SEQ ID NO:5)IL-1RA:-PVSL--TNMPDEGVMVTKFYFQED (SEQ ID NO:6) |
分子 | IL-18 | IL-1β | IL-1RA | IL-1Rec | IL-18Rec |
IL-18 | - | 20.0 | 21.8 | - | - |
IL-1b | 53.5 | - | 27.5 | - | - |
IL-1RA | 50.6 | 54.4 | - | - | - |
IL-1Rec | - | - | - | - | 26.1 |
IL-18Rec | - | - | - | 50.5 | - |
IL-1β | IL-1RA | IL-1Rec | IL-18(模型) | IL-18Rec(模型) | |
包装质量 | -1.6 | -2.3 | -3.6 | -5.5 | -5.7 |
RamachandranPlot | -2.0 | -1.3 | -2.9 | -3.3 | -2.3 |
旋转异构体当量浓度 | -1.6 | -0.8 | -1.5 | -0.6 | -0.6 |
主链构象 | -1.7 | +0.5 | -1.6 | -5.6 | -2.7 |
22IL-18 Rec:CTSRPHITVVEGEPFYLKHCSCSLAHEIETTTKSWYKSSGSQEHVELNPRIL-1 Rec:CKEREEKIILVSSANEIDVRPCPLNPNEHKGTITWYKDD-SKTPVSTEQA72IL-18 Rec:SSSRIALHDCVLEFWPVELNDTGSYFFQMKNYTQKWKLNVIRRNKHS---IL-1 Rec:S--RIHQHKEKLWFVPAKVEDSGHYYCVVRNSSYCLRIKISAKFVENEPN119IL-18 Rec:-CFTERQVTSKIVEVKKFFQITCENSYYQTLVNST----SLYKNCKKLLLIL-1 Rec:LCYNAQAIFKQKLPVAGDGGLVCPYMEFFKNENNELPKLQWYKDCKPLLL163IL-18 Rec:EN-----NKNPTIKKNAEFEDQGYYSCVHFLHHNGKLFNITKTFNITIVEIL-1 Rec:DNIHFSGVKDRLIVMNVAKKHRGNYTCHASYTYLGKQYPITRVIEFITLE209IL-18 Rec:DRSNIVPVLLGPKLNHVAVELGKNVRLNCSALLNEEDVIYWMF-GEE-NGIL-1 Rec:ENKPTRPVIVSPANETMEVDLGSQIQLICNVTGQLSDIAYWKWNGSVIDE257IL-18 Rec:SDPNIHEE-KEMRIMTPEGKWHASKVLRIENIGESNLNVLYNCTVASTGGIL-1 Rec:DDPVLGEDYYSVENPANKRRSTLITVLRISEIESRFYKHPFTCFAKNTHG306IL-18 Rec:TDTKSFILVRKAD(SEQ ID NO:7)IL-1 Rec:IDAAYIQLIYPVT(SEQ ID NO:8) |
肽序列 | SEQ ID NO: |
PLFEDMTDSDCRDNA | (SEQ ID NO:1) |
CPLFEDMTDSDCRDNA | (SEQ ID NO:2) |
PLFEDMTDSDCR | (SEQ ID NO:3) |
YFGKLESKLSVIRN | (SEQ ID NO:31) |
ESKLSVIRNLNDQV | (SEQ ID NO:32) |
VIRNLNDQVLFIDQ(LT28结合表位) | (SEQ ID NO:33) |
NDQVLFIDQGNRPL | (SEQ ID NO:34) |
FIDQGNRPLFFDMT | (SEQ ID NO:35) |
NRPLFEDMTDSDCR(2E1结合表位) | (SEQ ID NO:36) |
EDMTDSDCRDNAPR | (SEQ ID NO:37) |
SDCRDNAPRTIFII | (SEQ ID NO:38) |
NAPRTIFIISMYKD | (SEQ ID NO:39) |
IFIISMYKDSQPRG | (SEQ ID NO:40) |
MYKDSQPRGMAVTI | (SEQ ID NO:41) |
QPRGMAVTISVKCE | (SEQ ID NO:42) |
AVTISVKCEKISTL | (SEQ ID NO:43) |
VKCEKISTLSCENK | (SEQ ID NO:44) |
ISTLSCENKIISFK | (SEQ ID NO:45) |
CENKIISFKEMNPP | (SEQ ID NO:46) |
ISFKEMNPPDNIKD | (SEQ ID NO:47) |
MNPPDNIKDTKSDI | (SEQ ID NO:48) |
NIKDTKSDIIFFQR | (SEQ ID NO:49) |
KSDIIFFQRSVPGH | (SEQ ID NO:50) |
FFQRSVPGHDNKMQ | (SEQ ID NO:51) |
VPGHDNKMQFESSS | (SEQ ID NO:52) |
NKMQFESSSYEGYF | (SEQ ID NO:53) |
ESSSYEGYFLACEK | (SEQ ID NO:54) |
EGYFLACEKERDLF | (SEQ ID NO:55) |
ACEKERDLFKLILK | (SEQ ID NO:56) |
RDLFKLILKKEDEL | (SEQ ID NO:57) |
LILKKEDELGDRSI | (SEQ ID NO:58) |
EDELGDRSIMFTVQ | (SEQ ID NO:59) |
DRSIMFTVQNED | (SEQ ID NO:60) |
YFGKLESKLSVIRNLNDQVLFIDQGNRPLFEDMTDSDCRDNAPRTIFIISMYKDSQPRGMAVTISVKCEKISTLSCENKIISFKEMNPPDNIKDTKSDIIFFQRSVPGHDNKMQFESSSYEGYFLACEKERDLFKLILKKEDELGDRSIMFTVQNED | (SEQ ID NO:61)粗体表示LT28表位和2E1表位 |
2E1重链(SEQ ID NO:18) |
CDR1(SEQ ID NO:9)QVQLVQSGAEVKKPGASMKVSCKTSGYTF TGYYIHWVRQAHGQGFEWICDR2(SEQ ID NO:10) CDR3(SEQ ID NO:11)GRLNPTTGDANFAEKFQGRVALTRDTSISTAYLQLDSLKSDDTAVYYCAG KEGAWGQGTLVTVSS |
2E1轻链(SEQ ID NO:19) |
CDR1(SEQ ID NO:12) CDR2(SEQ ID NO:13)SSELTQDPAVSVALGQTVRITC QGCSLRHFYPNWYQQKPGQAPVLVIY GENNRPPSCDR3(SEQ ID NO:14)GIPDRFSGSGSGNTGSLTITGAQAEDEADYYC GSRDSSGIHVVFGGGTKVTVLG |
重链突变 | |
CDR/Kabat位置 | 被取代的残基 |
GDR1 | |
H30 | A,R,N,D,C,G,H,I,F,P,S,or V |
H31 | A,C,H,S,T,or Y |
H32 | R,N,C,H,P,S,or T |
H33 | N,D,C,Q,H,L,M,F,S,or V |
H35 | N,D,L,or F |
CDR2 | |
H52 | T |
H52a | R,Q,L S,T,or W |
H53 | A,R,N,L,P,S,or Y |
H54 | A,R,N,D,Q,L,K,M,P,S,or Y |
H56 | A,R,N,C,G,H,I,L,or F |
H58 | A,R,Q,E,H,I,L,K,M,F,S,T,Y,P,S,T,W,Y,or V |
CDR3 | |
H95 | A,R,E,Q,S,Y,V,H,P,W,or C |
H96 | A,R,Q,S,Y,V,H,P,W,or C |
H97 | A,R,E,Q,S,Y,V,H,P,W,or C |
H98 | R,E,Q,S,Y,V,H,P,W,or C |
轻链突变 | |
CDR/Kabat位置 | 被取代的残基 |
CDR1 |
L30 | N,D,C,G,I,L,S,W,or Y |
L31 | R,N,D,C,G,H,I,L,P,S,T,or Y |
L32 | R,N,D,E,G,I,L,P,S,T,or V |
L34 | A,R,N,D,E,R,I,L,K,M,F,P,S,T,Y,or V |
CDR2 | |
L50 | A,N,I,L,F,P,S,W,Y,or V |
L52 | A,R,D,E,H,I,L,M,F,P,S,T,or V |
L53 | A,R,C,I,L,K,M,P,S,or T |
L55 | A,R,N,D,C,G,H,I,L,S,T,or Y |
CDR3 | |
L89 | A,R,E,Q,S,Y,V,H,P,W,or C |
L90 | A,R,E,Q,Y,V,H,P,W,or C |
L91 | R,E,Q,S,Y,V,H,P,W,or C |
L92 | A,R,E,Q,S,Y,V,H,P,W,or C |
L93 | A,R,E,Q,Y,V,H,P,W,or C |
L94 | A,R,E,Q,Y,V,H,P,W,or C |
L95 | A,R,E,Q,S,Y,V,H,P,W,or C |
L95a | A,R,E,Q,S,Y,V,H,P,W,or C |
L95b | A,R,E,Q,S,Y,V,P,W,or C |
L96 | A,R,E,Q,S,Y,H,P,W,or C |
L97 | A,R,E,Q,S,Y,H,P,W,or C |
LT28重链(SEQ ID NO:28) |
CDR1(SEQ ID NO:20)CDR2(SEQ ID NO:21)LVQPGGSLRLSCAASGFTFS SYAMSWVRQAPGKGLEWVS AISGSGGSTYYADSVKGCDR3(SGQ ID NO:22)RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DDDDYDFDYWGRGTMVTVSS |
LT28轻链(SEQ ID NO:29) |
CDR1(SEQ ID NO:23) CDR2(SEQ ID NO:24)QSVLTQPPSASGTPGQRVTISC SGSSSNIGINAVNWYQQLPGTAPKLLIY GNDQRPSCDR3(SEQ ID NO:25)GVPDRFSGSKSGTSASLAISGLQSEDEADYYC AAWDDSLSGPVFGGGTKLTVLG |
重链突变 | |
CDR/Kabat位置 | 被取代的残基 |
CDR1 | |
H31 | A,R,E,Q,S,Y,V,H,P,W,or C |
H32 | A,R,E,Q,S,Y,V,H,P,W,or C |
H33 | A,R,E,Q,S,Y,V,H,P,W,or C |
H35 | A,R,E,Q,S,Y,V,H,P,W,or C |
CDR2 | |
R50 | A,R,E,Q,S,Y,V,H,P,W,or C |
H51 | A,R,E,Q,S,Y,V,H,P,W,or C |
H52 | A,R,E,Q,S,Y,V,H,P,W,or C |
H52a | A,R,E,Q,S,Y,V,H,P,W,or C |
H53 | A,R,E,Q,S,Y,V,H,P,W,or C |
H54 | A,R,E,Q,S,Y,V,H,P,W,or C |
H56 | A,R,E,Q,S,Y,V,H,P,W,or C |
H58 | A,R,E,Q,S,Y,V,H,P,W,C |
CDR3 | |
H95 | A,R,E, Q,S,Y,V,H,P,W,or C |
H96 | A,R,E,Q,S,Y,V,H,P,W,or C |
H97 | A,R,E,Q,S,Y,V,H,P,W,or C |
H98 | A,R,E,Q,S,Y,V,H,P,W,or C |
H99 | A,R,E,Q,S,Y,V,H,P,W,or C |
H100 | A,R,E,Q,S,Y,V,H,P,W,or C |
H100a | A,R,E,Q,S,Y,V,H,P,W,or C |
H101 | A,R,E,Q,S,Y,V,H,P,W,or C |
H102 | A,R,E,Q,S,Y,V,H,P,W,or C |
轻链突变 | |
CDR/位置 | 被取代的残基 |
CDR1 | |
L30 | A,R,E,Q,S,Y,V,H,P,W,C |
L31 | A,R,E,Q,S,Y,V,H,P,W,C |
L32 | R,E,Q,S,Y,V,H,P,W,C,G |
L34 | A,R,E,Q,S,Y,V,H,P,W,C |
CDR2 | |
L50 | A,R,E,Q,S,Y,V,H,P,C |
L52 | A,R,E,S,Y,V,H,P,W,C |
L53 | A,R,E,S,Y,V,H,P,W,C,N |
L55 | A,E,Q,S,Y,V,H,P,W,C |
CDR3 | |
L89 | A,R,E,Q,S,Y,V,H,P,W,C |
L90 | A,R,E,Q,S,Y,V,H,P,W,C |
L91 | A,R,E,Q,S,Y,V,H,P,W,C |
L92 | A,R,E,Q,S,Y,V,H,P,W,C |
L93 | A,R,E,Q,S,Y,V,H,P,W,C |
L94 | A,R,E,Q,S,Y,V,H,P,W,C |
L95 | A,R,E,Q,S,Y,V,H,P,W,C |
L95a | A,R,E,Q,S,Y,V,H,P,W,C |
L95b | A,R,E,Q,S,Y,V,H,P,W,C |
L96 | A,R,E,Q,S,Y,V,H,P,W,C |
L97 | A,R,E,Q,S,Y,V,H,P,W,C |
抗体克隆 | 缔合速率(M-1s-1) | 解离速率(s-1) | Kd(M) | IC50值* |
2E1亲代抗体和突变体 | ||||
2E1(亲代)ScFV | 2.6E+3 | 6.42E-03 | 1.5E-07 | 3.3E-8M |
2E1(亲代)IgG | 9.0E-10M | |||
L34S | 1.69E-04 | 1.5E-8M | ||
H53R | 2.34E-03 | 2.5E-8M | ||
H53Y | - | 1.5E-8M | ||
H58Q | - | 1.6E-8M | ||
L34S+H53R(2E1RS) | 2.7E+03 | 6.82E-05 | 2.3E-08 | 3.0E-09M |
L34S+H58Q | - | 1.5E-8M | ||
L34S+H53Y | 5.28E-05 | 6.7E-9M | ||
H53R+H58Q | - | 1.2E-8M | ||
H53Y+H58Q | - | 1.2E-8M | ||
L34S+H53R+H58Q | 6.18E-05 | 2.8E-9M | ||
L34S+H53Y+H58Q | - | 8.0E-9M | ||
L90C | 4x | |||
L93C | 2-4x | |||
L94P、Q或R | 2-4x | |||
L95R,Y | 3-8x | |||
L95bE,W | 2-4x | |||
LT28亲代抗体和突变体 | ||||
LT28(亲代) | 1.3E+04 | 4.8E-04 | 3.9E-08 | 9.0E-8M |
H54Q | 2-3x | |||
H58W | 2-3x | |||
1 | ||||
125-2H | 1.7E+05 | 1.1E-04 | 6.2E-10 | 2.E-10M |
318-M | 1.2E+04 | 1.1E-04 | 9.6E-09 | 4.0E-9M |
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CN103339147A (zh) * | 2010-12-20 | 2013-10-02 | 米迪缪尼有限公司 | 抗il-18抗体和其用途 |
US11673950B2 (en) | 2016-03-10 | 2023-06-13 | Viela Bio, Inc. | ILT7 binding molecules and methods of using the same |
CN113056481A (zh) * | 2018-06-13 | 2021-06-29 | 新加坡保健服务私人有限公司 | Il-11抗体 |
CN113156134A (zh) * | 2020-11-26 | 2021-07-23 | 江苏荃信生物医药有限公司 | 用于检测人白介素23的elisa试剂盒及检测方法 |
CN113156134B (zh) * | 2020-11-26 | 2024-01-23 | 江苏荃信生物医药股份有限公司 | 用于检测人白介素23的elisa试剂盒及检测方法 |
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