Novel Anti-l1CAM antibody

Abstract

Provided are a fully humanized monoclonal antibody which binds to a human L1CAM with a high specificity, an antigen-binding fragment thereof, a bispecific antibody thereof, etc. The antibody can be used in the diagnosis and treatment of cancers.

Description

Example 4: The binding of anti-LlCAM human-mouse chimeric antibodies to endogenously expressed human LI CAM on HeLa cells This example utilizes HeLa cells and LI CAM-knockout HeLa cells (purchased from Abeam) to determine the binding of mouse anti-LlCAM monoclonal antibodies to endogenously expressed human LI CAM on the cell surface. LI CAM-knockout HeLa cells are referred to as HeLa KO cells in this invention. HeLa cells are cultured in DMEM complete medium (purchased from Coming) containing 10% FBS (purchased from Gibco) and lOOU / mL penicillin mixture (Thermofisher, 15140122). When the cell coverage in the culture container reaches 8090%, TrypLE (purchased from Thermofisher) is used to digest the HeLa and HeLa KO cells from the culture container, and they are seeded in a 96-well plate (purchased from AXYGEN) at a density of 4x106 cells / ml, with 100,000 cells (25 pL DMEM complete medium) per well. Then, the human-mouse chimeric antibodies are serially diluted in DMEM complete medium, with 25 pL of the diluted chimeric antibody solution added to each well, gently mixed, and incubated at 4°C for 1 hour. Then, 150pL of PBS buffer containing 2% FBS (purchased from Corning) is added to each well, centrifuged at 1400 rpm for 4 minutes, the supernatant is removed, and the wells are washed once more. Then, 50pL of Alexa Flour 647-labeled goat anti-human fluorescent secondary antibody (purchased from Jacksonimmuno) diluted 1:800 is added to each well, and the 96-well plate is incubated at 4°C for 0.5 hours. The cells are washed twice with PBS solution containing 2% FBS, then resuspended in 120pL of PBS, and the cell surface fluorescence signal is detected using a flow cytometer (BD FACSCelesta), obtaining the median fluorescence intensity (MFI). A dose-response curve is generated, and the half-maximal effective concentration (EC50) is calculated using non-linear regression with GraphPad software. HeLa cells endogenously express high levels of LI CAM, and the expression level of LI CAM in HeLa KO cells is significantly reduced relative to wild-type HeLa due to the knockout of the LI CAM gene, allowing the binding ability of antibodies to LI CAM on the surface of HeLa cells to be determined by flow cytometry, and the specificity of the antibodies is assessed by detecting the fluorescence signal on the surface of HeLa KO cells. Table 2. The binding of anti-L1CAM humanmouse chimeric antibodies to HeLa cells and HeLa cells HelaCell Hela KO Cell chimeric antibodies NO. EC50(nM) Maxium MFI EC50(nM) Maxium MFI ch25F8H8 0.8331 29253 1.557 372 ch26A12Cl 0.7392 44705 0.319 1165 ch46FlD5 0.8452 43085 0.4688 1739 ch49E10Hl 0.9783 42858 0.3136 2640 chlO3E9B3 1.113 45397 N / A N / A Note: N / A represents data not available Example 5: Production of humanized antibodies against L1CAM Mouse anti-LlCAM monoclonal antibodies 46F1D5, 49E10H1, and 103E9B3 are selected as clones for humanization. The antibody sequences are aligned with human germline sequences to determine the best fit model. Based on homology with the original mouse antibody sequences, the most matching human germline sequences are selected as templates for humanization. The CDRs from the mouse antibody sequences are grafted onto the template along with residues that preserve the upper and central core structures of the antibody. Optimized mutations are introduced into the framework region to produce variants of the humanized heavy chain variable region and the humanized light chain variable region, which are mixed and matched to provide multiple humanized antibody clones. They are recombinantly expressed in mammalian cells and purified for further analytical testing. Example 6: Determination of humanized L1CAM antibody binding on the surface of HeLa cells The experimental principle is as follows: HeLa cells express high levels of LI CAM protein on their surface. After incubating humanized LI CAM antibodies with the cells, the binding ability of the antibodies to LI CAM on the surface of HeLa cells can be determined by flow cytometry. The experimental method is descripted as following: Humanized LI CAM antibodies (Human IgGl-Kappa) are diluted in complete medium in a four-fold serial dilution, with seven concentration gradient points. HeLa cells are cultured in DMEM complete medium (Corning, 10-013-CVR) containing 10% FBS (Gibco, 10099-141) and lOOU / mL penicillin mixture (Thermofisher, 15140122). When the cell coverage in the culture container reaches 8090%, TrypLE (Thermofisher, 12604-013) is used to digest the HeLa cells from the culture container, and they are seeded in a 96-well plate (AXYGEN, P-96-450V-C) at a density of 2.2 X 106 cells / ml, with 100,000 cells (45pL complete medium) per well. Then, 5pL of the antibody dilution is added to each well, gently mixed, and the 96-well plate is incubated at 4°C for 1 hour. Then, 150pL of PBS solution containing 2% FBS (Coming, 21-040-CVC) is added to each well, centrifuged at 1400 rpm for 4 minutes, the supernatant is removed, and the wells are washed once more. Then, 50pL of Alexa Flour 647-labeled goat anti-human fluorescent secondary antibody (Jacksonimmuno, 109-605-088) diluted 1:800 is added to each well, and the 96-well plate is incubated at 4°C for 0.5 hours. The cells are washed twice with PBS solution containing 2% FBS, then resuspended in 120pL of PBS, and the cell surface fluorescence signal is detected using a flow cytometer (BD FACS Celesta), obtaining the median fluorescence intensity (MFI). A dose-response curve is generated, and the half-maximal effective concentration (EC50) is calculated using non-linear regression with GraphPad software. Table 3 Binding affinity to Hela cell of Humanized 26A12C1 antibody Humanized antibody NO. EC50(nM) hz26A12ClHlLl N / A hz26A12ClHlL2 N / A hz26A12ClHlL3 N / A hz26A12ClH2Ll 24.69 hz26A12ClH2L2 7.819 hz26A12ClH2L3 0.8529 hz26A12ClH3Ll 2.988 hz26A12ClH3L2 2.333 hz26A12ClH3L3 0.838 hz26A12ClH4Ll 0.646 hz26A12ClH4L2 0.5621 hz26A12ClH4L3 0.7378 Table 4 Binding affinity to Hela cell of Humanized 49E10H1 antibody Humanized antibody NO. EC50(nM) hz49E10HlH4L5 2.15 hz49E10HlH4L6 0.8533 hz49E10HlH4L7 0.6764 hz49E10HlH5L5 0.6326 hz49E10HlH5L6 0.4042 hz49E10HlH5L7 0.3767 hz49E10HlH6L5 24.33 hz49E10HlH6L6 1.03 hz49E10HlH6L7 0.9962 hz49E10HlH7L5 10.39 hz49E10HlH7L6 1.051 hz49E10HlH7L7 0.8516 hz49E10HlH8L5 9.274 hz49E10HlH8L6 1.06 hz49E10HlH8L7 0.8204 Table 5 Binding affinity to Hela cell of Humanized 103E9B3 antibody Humanized antibody NO. EC50(nM) chlO3E9B3 1.21 hzlO3E9B3H5L4 6.845 hzlO3E9B3H5L5 1.682 hzlO3E9B3H5L6 1.926 hzlO3E9B3H6L4 6.595 hzlO3E9B3H6L5 1.483 hzlO3E9B3H6L6 2.184 hzlO3E9B3H7L4 5.323 hzlO3E9B3H7L5 2.133 hzlO3E9B3H7L6 2.034 hzlO3E9B3H8L4 5.795 hzlO3E9B3H8L5 1.54 hzlO3E9B3H8L6 1.997 hzlO3E9B3H9L4 5.564 hzlO3E9B3H9L5 1.964 hzlO3E9B3H9L6 2.065 In the present invention, the humanized antibody number is indicated as "hz + hybridoma clone number + heavy chain number + light chain number", for example, the humanized antibody "hz46FlD5HlL2" represents a humanized antibody derived from the mouse anti-LlCAM monoclonal antibody 46F1D5, and the variable region heavy chain is VH1 (i.e., SEQ ID NO: 60), and the variable region light chain is VL2 (i.e., SEQ ID NO: 65). In the present invention, the human-mouse chimeric antibody number is indicated as "ch+ hybridoma clone number", for example, the human-mouse chimeric antibody "ch46FlD5" represents the human-mouse chimeric antibody derived from the mouse anti-LlCAM monoclonal antibody 46F1D5, and the variable region heavy chain is the heavy chain variable region of the mouse monoclonal antibody 46F1D5, the variable region light chain is the light chain variable region of the mouse monoclonal antibody 46F1D5, and the constant region is the human IgGl constant region. Antibody Sequence information: Table 6 Mouse monoclonal antibody complementary determinant amino acid sequence Antibody NO. Amino acid Sequence SEQ ID NO. 25F8H8 HCDR HCDR1 TYWMH 1 HCDR2 YINPSTGYTDYNQKFKD 2 HCDR3 RQLGLPLFDY 3 LCDR LCDR1 KASQDVGTAVA 4 LCDR2 WASTRHT 5 LCDR3 QQYSNYPLT 6 26A12C 1 HCDR HCDR1 GYTFTNYW 7 HCDR2 INPSTYYS 8 HCDR3 ARRQFGLPLFDY 9 LCDR LCDR1 QDVGTA 10 LCDR2 WAS 11 LCDR3 QQYSNYPLT 12 46F1D5 HCDR HCDR1 GYTFTRYW 13 HCDR2 INPSTGYT 14 HCDR3 ARRHLGLPLFDY 15 LCDR LCDR1 QDVGTA 16 LCDR2 WAS 17 LCDR3 QQYSNYPLT 18 49E10H 1 HCDR HCDR1 GYSITSDYA 19 HCDR2 ITYSGTT 20 HCDR3 TLDHYGNYAYFDY 21 LCDR LCDR1 SSVSF 22 LCDR2 ASS 23 LCDR3 QQWSSNPST 24 49’E10H 1 HCDR HCDR1 GGSISSDYA 25 HCDR2 ITYSGTT 26 HCDR3 ARDHYGNYAYFDY 27 LCDR LCDR1 SSVSF 28 LCDR2 ASS 29 LCDR3 QQWSSNPST 30 49”E10 Hl HCDR HCDR1 GGSISSDYA 31 HCDR2 ITYSGTT 32 HCDR3 TLDHYGNYAYFDY 33 LCDR LCDR1 SSVSF 34 LCDR2 ASS 35 LCDR3 QQWSSNPST 36 103E9B3 HCDR HCDR1 GYTFTSYT 37 HCDR2 INPNYGGT 38 HCDR3 AREGATGTWYFDV 39 LCDR LCDR1 SSVSF 40 LCDR2 LTS 41 LCDR3 QQWRSNPPT 42 Table 7 Mouse monoclonal antibody amino acid sequence Antibody Amino acid sequence SEQ ID NO. 25F8H8 Variable full length of heavy chain (VH) QVQLQQSGAELAKPGASVKMSCQASGYTF TTYWMHWVKQRPGQGLEWIGYINPSTGYT DYNQKFKDKATLTADKSSSTAYMQLSSLTS EDSAVYYCARRQLGLPLFDYWGQGTTLTV SS 43 Variable full length of light chain (VL) DIVMTQSHKFLSTSVGDRVSITCKASQDVG TAVAWYQHKPGQSPKLLIFWASTRHTGVPD RFTGSGSGTDFTLTISNVQSEDLADYFCQQY SNYPLTFGAGPKLELK 44 26A12C Variable MERHWIFLFLFSATAGVHSQVQLQQSGAEL 45 1 full length of heavy chain (VH) AKPGASVKMSCKASGYTFTNYWMQWVKQ RPGQGLEWIGYINPSTYYSDYNQKFKDKAT LTADKSSSTAFMQLSSLTSEDSAVYYCARRQ FGLPLFDYWGQGTTLTLSS Variable full length of light chain (VL) METHSQVFVYMLLWLSGVEGDIVMTQSHK FMSTSVGDRVSITCKASQDVGTAVAWYQQK PGQSPKLLIYWASTRHTGVPDRFTGSGSGT DFTLTISNVQSEDLTDYFCQQYSNYPLTFGA GTELELK 46 46F1D5 Variable full length of heavy chain (VH) MERHWIFLFLFSVTAGVYSQVQVQQSGAEL AKPGASMKMSCKASGYTFTRYWMQWVK QRPGQGLEWIGYINPSTGYTDYNQNFKDK ATLTADKSSSTAYMQLSSLTSEDSAVYYCAR RHLGLPLFDYWGQGTTLTVSS 47 Variable full length of light chain (VL) METHSQVFVYMLLWLSGVEGDIVMTQSHK FMSTSLGDRVSITCKASQDVGTAVAWYQQK PGQSPKLLIYWASTRHTGVPDRFTGSGSGT DFTLTISNVQSEDLAEYFCQQYSNYPLTFGA GTKLDLK 48 49E10H 1 Variable full length of heavy chain (VH) MRVLILLWLFTAFPGILSDVQLQESGPGLVK PSQSLSLTCTVTGYSITSDYAWNWIRQFPGN RLEWMGYITYSGTTTYNPSLKSRISITRDTS KNQFFLQLNSVTTADTATYYCTLDHYGNYA YFDYWGQGTTLTVSS 49 Variable full length of light chain (VL) MDFQVQIFSFLLISASVIMSRGQIVLSQSPAI LSASPGEKVTMTCRASSSVSFMHWYQQKP RSSPKPWIYASSNLVSGVPTRFSGSGSGTSY SLTISRVEAEDAATYYCQQWSSNPSTFGAGT KLELK 50 103E9B3 Variable full length of heavy chain MGWSWIFLFLLSGTAGVLSEVQLQQSGPEL LKPGASVKISCKASGYTFTSYTMHWVKQS HGKSLEWIGDINPNYGGTSYNEKFKDKATL TVDKSSSTAYMELRSLTSEDSAVYYCAREG 51 (VH) ATGTWYFDVWGTGTTVTVSS Variable full length of light chain (VL) MDFQVQIFSFLLMSASVIMSRGQIVLTQSPA LMSASPGEKVTMTCSASSSVSFMFWYQQK PRSSPKPWIYLTSNLASGVPARFSGSGSGTS YSLTISSMEAEDAATYYCQQWRSNPPTFGA GTKLELK 52 Table 8 Humanized monoclonal antibody variable region amino acid sequence Antibody NO. SEQ ID NO: Amino acid sequence hz26A12ClHl LI VH 53 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTNYWISWVRQAPGQGLEWMGGINPSTY YSNYAQKFQGRVTITADESTSTAYMELSSL RSEDTAVYYCARRQFGLPLFDYWGQGTT VTVSS VL 57 DIQMTQSPSSLSASVGDRVTITCRASQDV GTALAWYQQKPGKVPKLLIYWASTLQSG VPSRFSGSGSGTDFTLTISSLQPEDVATYY CQQYSNYPLTFGGGTKVEIK hz26A12ClHl L2 VH 53 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTNYWISWVRQAPGQGLEWMGGINPSTY YSNYAQKFQGRVTITADESTSTAYMELSSL RSEDTAVYYCARRQFGLPLFDYWGQGTT VTVSS VL 58 DIQMTQSPSSLSASVGDRVTITCRASQDV GTAVAWYQQKPGKVPKLLIYWASTLHSG VPSRFSGSGSGTDFTLTISSLQPEDVATYY CQQYSNYPLTFGGGTKVEIK hz26A12ClHl L3 VH 53 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTNYWISWVRQAPGQGLEWMGGINPSTY YSNYAQKFQGRVTITADESTSTAYMELSSL RSEDTAVYYCARRQFGLPLFDYWGQGTT VTVSS VL 59 DIQMTQSPSSLSASVGDRVTITCRASQDV GTAVAWYQQKPGKVPKLLIYWASTLHSG VPSRFSGSGSGTDFTLTISSLQPEDVATYFC QQYSNYPLTFGGGTKVEIK hz26A12ClH2 LI VH 54 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTNYWIQWVRQAPGQGLEWMGYINPST YYSDYAQKFQGRVTITADESTSTAYMELS SLRSEDTAVYYCARRQFGLPLFDYWGQG TTVTVSS VL 57 DIQMTQSPSSLSASVGDRVTITCRASQDV GTALAWYQQKPGKVPKLLIYWASTLQSG VPSRFSGSGSGTDFTLTISSLQPEDVATYY CQQYSNYPLTFGGGTKVEIK hz26A12ClH2 L2 VH 54 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTNYWIQWVRQAPGQGLEWMGYINPST YYSDYAQKFQGRVTITADESTSTAYMELS SLRSEDTAVYYCARRQFGLPLFDYWGQG TTVTVSS VL 58 DIQMTQSPSSLSASVGDRVTITCRASQDV GTAVAWYQQKPGKVPKLLIYWASTLHSG VPSRFSGSGSGTDFTLTISSLQPEDVATYY CQQYSNYPLTFGGGTKVEIK hz26A12ClH2 L3 VH 54 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTNYWIQWVRQAPGQGLEWMGYINPST YYSDYAQKFQGRVTITADESTSTAYMELS SLRSEDTAVYYCARRQFGLPLFDYWGQG TTVTVSS VL 59 DIQMTQSPSSLSASVGDRVTITCRASQDV GTAVAWYQQKPGKVPKLLIYWASTLHSG VPSRFSGSGSGTDFTLTISSLQPEDVATYFC QQYSNYPLTFGGGTKVEIK hz26A12C!H3 VH 55 QVQLVQSGAEVKKPGSSVKVSCKASGYT LI FTNYWIQWVRQAPGQGLEWIGYINPSTY YSDYAQKFQGRVTLTADESTSTAYMELSS LRSEDTAVYYCARRQFGLPLFDYWGQGT TVTVSS VL 57 DIQMTQSPSSLSASVGDRVTITCRASQDV GTALAWYQQKPGKVPKLLIYWASTLQSG VPSRFSGSGSGTDFTLTISSLQPEDVATYY CQQYSNYPLTFGGGTKVEIK hz26A12ClH3 L2 VH 55 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTNYWIQWVRQAPGQGLEWIGYINPSTY YSDYAQKFQGRVTLTADESTSTAYMELSS LRSEDTAVYYCARRQFGLPLFDYWGQGT TVTVSS VL 58 DIQMTQSPSSLSASVGDRVTITCRASQDV GTAVAWYQQKPGKVPKLLIYWASTLHSG VPSRFSGSGSGTDFTLTISSLQPEDVATYY CQQYSNYPLTFGGGTKVEIK hz26A12ClH3 L3 VH 55 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTNYWIQWVRQAPGQGLEWIGYINPSTY YSDYAQKFQGRVTLTADESTSTAYMELSS LRSEDTAVYYCARRQFGLPLFDYWGQGT TVTVSS VL 59 DIQMTQSPSSLSASVGDRVTITCRASQDV GTAVAWYQQKPGKVPKLLIYWASTLHSG VPSRFSGSGSGTDFTLTISSLQPEDVATYFC QQYSNYPLTFGGGTKVEIK hz26A12ClH4 LI VH 56 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTNYWIQWVRQAPGQGLEWIGYINPSTY YSDYNQKFQGRVTLTADKSTSTAYMELSS LRSEDTAVYYCARRQFGLPLFDYWGQGT TVTVSS VL 57 DIQMTQSPSSLSASVGDRVTITCRASQDV GTALAWYQQKPGKVPKLLIYWASTLQSG VPSRFSGSGSGTDFTLTISSLQPEDVATYY CQQYSNYPLTFGGGTKVEIK hz26A12ClH4 L2 VH 56 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTNYWIQWVRQAPGQGLEWIGYINPSTY YSDYNQKFQGRVTLTADKSTSTAYMELSS LRSEDTAVYYCARRQFGLPLFDYWGQGT TVTVSS VL 58 DIQMTQSPSSLSASVGDRVTITCRASQDV GTAVAWYQQKPGKVPKLLIYWASTLHSG VPSRFSGSGSGTDFTLTISSLQPEDVATYY CQQYSNYPLTFGGGTKVEIK hz26A12ClH4 L3 VH 56 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTNYWIQWVRQAPGQGLEWIGYINPSTY YSDYNQKFQGRVTLTADKSTSTAYMELSS LRSEDTAVYYCARRQFGLPLFDYWGQGT TVTVSS VL 59 DIQMTQSPSSLSASVGDRVTITCRASQDV GTAVAWYQQKPGKVPKLLIYWASTLHSG VPSRFSGSGSGTDFTLTISSLQPEDVATYFC QQYSNYPLTFGGGTKVEIK hz46FlD5HlL 1 VH 60 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTRYWISWVRQAPGQGLEWMGGINPSTG YTNYAQKFQGRVTITADESTSTAYMELSS LRSEDTAVYYCARRHLGLPLFDYWGQGT TVTVSS VL 64 DIQMTQSPSSVSASVGDRVTITCRASQDV GTALAWYQQKPGKAPKLLIYWASSLQSG VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYSNYPLTFGGGTKVEIK hz46FlD5HlL 2 VH 60 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTRYWISWVRQAPGQGLEWMGGINPSTG YTNYAQKFQGRVTITADESTSTAYMELSS LRSEDTAVYYCARRHLGLPLFDYWGQGT TVTVSS VL 65 DIQMTQSPSSVSASVGDRVTITCRASQDV GTALAWYQQKPGKAPKLLIYWASSLHSG VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYSNYPLTFGGGTKVEIK hz46FlD5HlL 3 VH 60 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTRYWISWVRQAPGQGLEWMGGINPSTG YTNYAQKFQGRVTITADESTSTAYMELSS LRSEDTAVYYCARRHLGLPLFDYWGQGT TVTVSS VL 66 DIQMTQSPSSVSASVGDRVTITCRASQDV GTAVAWYQQKPGKAPKLLIYWASSLHSG VPSRFSGSGSGTDFTLTISSLQPEDFATYFC QQYSNYPLTFGGGTKVEIK hz46FlD5H2L 1 VH 61 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTRYWIQWVRQAPGQGLEWMGYINPSTG YTNYAQKFQGRVTITADESTSTAYMELSS LRSEDTAVYYCARRHLGLPLFDYWGQGT TVTVSS VL 64 DIQMTQSPSSVSASVGDRVTITCRASQDV GTALAWYQQKPGKAPKLLIYWASSLQSG VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYSNYPLTFGGGTKVEIK hz46FlD5 H2L2 VH 61 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTRYWIQWVRQAPGQGLEWMGYINPSTG YTNYAQKFQGRVTITADESTSTAYMELSS LRSEDTAVYYCARRHLGLPLFDYWGQGT TVTVSS VL 65 DIQMTQSPSSVSASVGDRVTITCRASQDV GTALAWYQQKPGKAPKLLIYWASSLHSG VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYSNYPLTFGGGTKVEIK hz46F!D5 VH 61 QVQLVQSGAEVKKPGSSVKVSCKASGYT H2L3 FTRYWIQWVRQAPGQGLEWMGYINPSTG YTNYAQKFQGRVTITADESTSTAYMELSS LRSEDTAVYYCARRHLGLPLFDYWGQGT TVTVSS VL 66 DIQMTQSPSSVSASVGDRVTITCRASQDV GTAVAWYQQKPGKAPKLLIYWASSLHSG VPSRFSGSGSGTDFTLTISSLQPEDFATYFC QQYSNYPLTFGGGTKVEIK hz46FlD5H3L 1 VH 62 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTRYWIQWVRQAPGQGLEWMGYINPSTG YTDYNQKFQGRVTITADESTSTAYMELSS LRSEDTAVYYCARRHLGLPLFDYWGQGT TVTVSS VL 64 DIQMTQSPSSVSASVGDRVTITCRASQDV GTALAWYQQKPGKAPKLLIYWASSLQSG VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYSNYPLTFGGGTKVEIK hz46FlD5 H3L2 VH 62 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTRYWIQWVRQAPGQGLEWMGYINPSTG YTDYNQKFQGRVTITADESTSTAYMELSS LRSEDTAVYYCARRHLGLPLFDYWGQGT TVTVSS VL 65 DIQMTQSPSSVSASVGDRVTITCRASQDV GTALAWYQQKPGKAPKLLIYWASSLHSG VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYSNYPLTFGGGTKVEIK hz46FlD5 H3L3 VH 62 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTRYWIQWVRQAPGQGLEWMGYINPSTG YTDYNQKFQGRVTITADESTSTAYMELSS LRSEDTAVYYCARRHLGLPLFDYWGQGT TVTVSS VL 66 DIQMTQSPSSVSASVGDRVTITCRASQDV GTAVAWYQQKPGKAPKLLIYWASSLHSG VPSRFSGSGSGTDFTLTISSLQPEDFATYFC QQYSNYPLTFGGGTKVEIK hz46FlD5H4L 1 VH 63 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTRYWIQWVRQAPGQGLEWMGYINPSTG YTDYNQKFQGRVTITADKSTSTAYMELSS LRSEDTAVYYCARRHLGLPLFDYWGQGT TVTVSS VL 64 DIQMTQSPSSVSASVGDRVTITCRASQDV GTALAWYQQKPGKAPKLLIYWASSLQSG VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYSNYPLTFGGGTKVEIK hz46FlD5 H4L2 VH 63 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTRYWIQWVRQAPGQGLEWMGYINPSTG YTDYNQKFQGRVTITADKSTSTAYMELSS LRSEDTAVYYCARRHLGLPLFDYWGQGT TVTVSS VL 65 DIQMTQSPSSVSASVGDRVTITCRASQDV GTALAWYQQKPGKAPKLLIYWASSLHSG VPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYSNYPLTFGGGTKVEIK hz46FlD5 H4L3 VH 63 QVQLVQSGAEVKKPGSSVKVSCKASGYT FTRYWIQWVRQAPGQGLEWMGYINPSTG YTDYNQKFQGRVTITADKSTSTAYMELSS LRSEDTAVYYCARRHLGLPLFDYWGQGT TVTVSS VL 66 DIQMTQSPSSVSASVGDRVTITCRASQDV GTAVAWYQQKPGKAPKLLIYWASSLHSG VPSRFSGSGSGTDFTLTISSLQPEDFATYFC QQYSNYPLTFGGGTKVEIK hz49E10HlHl LI VH 67 QVQLQESGPGLVKPSQTLSLTCTVSGYSIT SDYAWSWIRQPPGKGLEWIGYITYSGTTY YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 75 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLNWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlHl L2 VH 67 QVQLQESGPGLVKPSQTLSLTCTVSGYSIT SDYAWSWIRQPPGKGLEWIGYITYSGTTY YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 76 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLHWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlHl L3 VH 67 QVQLQESGPGLVKPSQTLSLTCTVSGYSIT SDYAWSWIRQPPGKGLEWIGYITYSGTTY YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 77 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlHl L4 VH 67 QVQLQESGPGLVKPSQTLSLTCTVSGYSIT SDYAWSWIRQPPGKGLEWIGYITYSGTTY YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 78 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10H!Hl VH 67 QVQLQESGPGLVKPSQTLSLTCTVSGYSIT L5 SDYAWSWIRQPPGKGLEWIGYITYSGTTY YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 79 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKLLIYASSNLVSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlHl L6 VH 67 QVQLQESGPGLVKPSQTLSLTCTVSGYSIT SDYAWSWIRQPPGKGLEWIGYITYSGTTY YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 80 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPWIYASSNLVSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQ QWSSNPSTFGGGTKVEIK hz49E10HlHl L7 VH 67 QVQLQESGPGLVKPSQTLSLTCTVSGYSIT SDYAWSWIRQPPGKGLEWIGYITYSGTTY YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 81 QIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPWIYASSNLVSGVP SRFSGSGSGTDYTLTISSLQPEDFATYYCQ QWSSNPSTFGGGTKVEIK hz49E10HlH2 LI VH 68 DVQLQESGPGLVKPSQTLSLTCTVSGYSIT SDYAWNWIRQPPGKGLEWIGYITYSGTTY YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 75 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLNWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH2 L2 VH 68 DVQLQESGPGLVKPSQTLSLTCTVSGYSIT SDYAWNWIRQPPGKGLEWIGYITYSGTTY YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 76 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLHWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH2 L3 VH 68 DVQLQESGPGLVKPSQTLSLTCTVSGYSIT SDYAWNWIRQPPGKGLEWIGYITYSGTTY YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 77 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH2 L4 VH 68 DVQLQESGPGLVKPSQTLSLTCTVSGYSIT SDYAWNWIRQPPGKGLEWIGYITYSGTTY YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 78 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH2 L5 VH 68 DVQLQESGPGLVKPSQTLSLTCTVSGYSIT SDYAWNWIRQPPGKGLEWIGYITYSGTTY YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 79 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKLLIYASSNLVSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH2 L6 VH 68 DVQLQESGPGLVKPSQTLSLTCTVSGYSIT SDYAWNWIRQPPGKGLEWIGYITYSGTTY YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 80 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPWIYASSNLVSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQ QWSSNPSTFGGGTKVEIK hz49E10HlH2 L7 VH 68 DVQLQESGPGLVKPSQTLSLTCTVSGYSIT SDYAWNWIRQPPGKGLEWIGYITYSGTTY YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 81 QIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPWIYASSNLVSGVP SRFSGSGSGTDYTLTISSLQPEDFATYYCQ QWSSNPSTFGGGTKVEIK hz49E10HlH3 LI VH 69 DVQLQESGPGLVKPSQTLSLTCTVSGYSIT SDYAWNWIRQPPGKGLEWMGYITYSGTT YYNPSLKSRVTISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 75 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLNWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH3 VH 69 DVQLQESGPGLVKPSQTLSLTCTVSGYSIT L2 SDYAWNWIRQPPGKGLEWMGYITYSGTT YYNPSLKSRVTISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 76 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLHWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH3 L3 VH 69 DVQLQESGPGLVKPSQTLSLTCTVSGYSIT SDYAWNWIRQPPGKGLEWMGYITYSGTT YYNPSLKSRVTISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 77 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH3 L4 VH 69 DVQLQESGPGLVKPSQTLSLTCTVSGYSIT SDYAWNWIRQPPGKGLEWMGYITYSGTT YYNPSLKSRVTISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 78 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH3 L5 VH 69 DVQLQESGPGLVKPSQTLSLTCTVSGYSIT SDYAWNWIRQPPGKGLEWMGYITYSGTT YYNPSLKSRVTISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 79 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKLLIYASSNLVSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH3 L6 VH 69 DVQLQESGPGLVKPSQTLSLTCTVSGYSIT SDYAWNWIRQPPGKGLEWMGYITYSGTT YYNPSLKSRVTISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 80 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPWIYASSNLVSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQ QWSSNPSTFGGGTKVEIK hz49E10HlH3 L7 VH 69 DVQLQESGPGLVKPSQTLSLTCTVSGYSIT SDYAWNWIRQPPGKGLEWMGYITYSGTT YYNPSLKSRVTISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 81 QIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPWIYASSNLVSGVP SRFSGSGSGTDYTLTISSLQPEDFATYYCQ QWSSNPSTFGGGTKVEIK hz49E10HlH4 LI VH 70 QVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWIGYITYSGTTT YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCARDHYGNYAYFDYWGQGTTV TVSS VL 75 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLNWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH4 L2 VH 70 QVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWIGYITYSGTTT YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCARDHYGNYAYFDYWGQGTTV TVSS VL 76 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLHWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH4 L3 VH 70 QVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWIGYITYSGTTT YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCARDHYGNYAYFDYWGQGTTV TVSS VL 77 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH4 L4 VH 70 QVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWIGYITYSGTTT YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCARDHYGNYAYFDYWGQGTTV TVSS VL 78 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH4 L5 VH 70 QVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWIGYITYSGTTT YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCARDHYGNYAYFDYWGQGTTV TVSS VL 79 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKLLIYASSNLVSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH4 VH 70 QVQLQESGPGLVKPSQTLSLTCTVSGGSIS L6 SDYAWNWIRQPPGKGLEWIGYITYSGTTT YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCARDHYGNYAYFDYWGQGTTV TVSS VL 80 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPWIYASSNLVSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQ QWSSNPSTFGGGTKVEIK hz49E10HlH4 L7 VH 70 QVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWIGYITYSGTTT YNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCARDHYGNYAYFDYWGQGTTV TVSS VL 81 QIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPWIYASSNLVSGVP SRFSGSGSGTDYTLTISSLQPEDFATYYCQ QWSSNPSTFGGGTKVEIK hz49E10HlH5 LI VH 71 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCARDHYGNYAYFDYWGQGTT VTVSS VL 75 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLNWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH5 L2 VH 71 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCARDHYGNYAYFDYWGQGTT VTVSS VL 76 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLHWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH5 L3 VH 71 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCARDHYGNYAYFDYWGQGTT VTVSS VL 77 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH5 L4 VH 71 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCARDHYGNYAYFDYWGQGTT VTVSS VL 78 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH5 L5 VH 71 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCARDHYGNYAYFDYWGQGTT VTVSS VL 79 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKLLIYASSNLVSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH5 L6 VH 71 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCARDHYGNYAYFDYWGQGTT VTVSS VL 80 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPWIYASSNLVSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQ QWSSNPSTFGGGTKVEIK hz49E10HlH5 L7 VH 71 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCARDHYGNYAYFDYWGQGTT VTVSS VL 81 QIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPWIYASSNLVSGVP SRFSGSGSGTDYTLTISSLQPEDFATYYCQ QWSSNPSTFGGGTKVEIK hz49E10HlH6 LI VH 72 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWIGYITYSGTTT YNPSLKSRVTISRDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 75 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLNWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH6 L2 VH 72 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWIGYITYSGTTT YNPSLKSRVTISRDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 76 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLHWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH6 VH 72 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS L3 SDYAWNWIRQPPGKGLEWIGYITYSGTTT YNPSLKSRVTISRDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 77 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH6 L4 VH 72 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWIGYITYSGTTT YNPSLKSRVTISRDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 78 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH6 L5 VH 72 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWIGYITYSGTTT YNPSLKSRVTISRDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 79 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKLLIYASSNLVSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH6 L6 VH 72 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWIGYITYSGTTT YNPSLKSRVTISRDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 80 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPWIYASSNLVSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQ QWSSNPSTFGGGTKVEIK hz49E10HlH6 L7 VH 72 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWIGYITYSGTTT YNPSLKSRVTISRDTSKNQFSLKLSSVTAA DTAVYYCTLDHYGNYAYFDYWGQGTTV TVSS VL 81 QIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPWIYASSNLVSGVP SRFSGSGSGTDYTLTISSLQPEDFATYYCQ QWSSNPSTFGGGTKVEIK hz49E10HlH7 LI VH 73 QVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 75 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLNWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH7 L2 VH 73 QVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 76 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLHWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH7 L3 VH 73 QVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 77 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH7 L4 VH 73 QVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 78 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH7 L5 VH 73 QVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 79 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKLLIYASSNLVSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH7 L6 VH 73 QVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGKGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 80 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPWIYASSNLVSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQ QWSSNPSTFGGGTKVEIK hz49E10HlH7 VH 73 QVQLQESGPGLVKPSQTLSLTCTVSGGSIS L7 SDYAWNWIRQPPGKGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 81 QIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPWIYASSNLVSGVP SRFSGSGSGTDYTLTISSLQPEDFATYYCQ QWSSNPSTFGGGTKVEIK hz49E10HlH8 LI VH 74 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGNGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 75 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLNWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH8 L2 VH 74 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGNGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 76 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLHWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH8 L3 VH 74 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGNGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 77 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKLLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH8 L4 VH 74 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGNGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 78 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPLIYASSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH8 L5 VH 74 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGNGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 79 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKLLIYASSNLVSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WSSNPSTFGGGTKVEIK hz49E10HlH8 L6 VH 74 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGNGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 80 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPWIYASSNLVSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQ QWSSNPSTFGGGTKVEIK hz49E10HlH8 L7 VH 74 DVQLQESGPGLVKPSQTLSLTCTVSGGSIS SDYAWNWIRQPPGNGLEWMGYITYSGTT TYNPSLKSRITISRDTSKNQFSLKLSSVTA ADTAVYYCTLDHYGNYAYFDYWGQGTT VTVSS VL 81 QIQMTQSPSSLSASVGDRVTITCRASSSVS FMHWYQQKPGKAPKPWIYASSNLVSGVP SRFSGSGSGTDYTLTISSLQPEDFATYYCQ QWSSNPSTFGGGTKVEIK hzlO3E9B3Hl LI VH 82 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGIINPNYG GTSYAQKFQGRVTMTRDTSTSTVYMELS SLRSEDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 91 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLNWYQQKPGKAPKLLIYLTSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3Hl L2 VH 82 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGIINPNYG GTSYAQKFQGRVTMTRDTSTSTVYMELS SLRSEDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 92 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLFWYQQKPGKAPKLLIYLTSSLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3Hl L3 VH 82 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGIINPNYG GTSYAQKFQGRVTMTRDTSTSTVYMELS SLRSEDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 93 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMFWYQQKPGKAPKPLIYLTSSLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hz!03E9B3Hl VH 82 EVQLVQSGAEVKKPGASVKVSCKASGYT L4 FTSYTMHWVRQAPGQGLEWMGIINPNYG GTSYAQKFQGRVTMTRDTSTSTVYMELS SLRSEDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 94 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKLLIYLTSNLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3Hl L5 VH 82 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGIINPNYG GTSYAQKFQGRVTMTRDTSTSTVYMELS SLRSEDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 95 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKPLIYLTSNLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3Hl L6 VH 82 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGIINPNYG GTSYAQKFQGRVTMTRDTSTSTVYMELS SLRSEDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 96 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKPWIYLTSNLASGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQ QWRSNPPTFGGGTKVEIK hzlO3E9B3H2 LI VH 83 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYAQKFQGRVTMTRDTSTSTVYMEL SSLRSEDTAVYYCAREGATGTWYFDVWG QGTTVTVSS VL 91 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLNWYQQKPGKAPKLLIYLTSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H2 L2 VH 83 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYAQKFQGRVTMTRDTSTSTVYMEL SSLRSEDTAVYYCAREGATGTWYFDVWG QGTTVTVSS VL 92 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLFWYQQKPGKAPKLLIYLTSSLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H2 L3 VH 83 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYAQKFQGRVTMTRDTSTSTVYMEL SSLRSEDTAVYYCAREGATGTWYFDVWG QGTTVTVSS VL 93 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMFWYQQKPGKAPKPLIYLTSSLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H2 L4 VH 83 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYAQKFQGRVTMTRDTSTSTVYMEL SSLRSEDTAVYYCAREGATGTWYFDVWG QGTTVTVSS VL 94 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKLLIYLTSNLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H2 L5 VH 83 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYAQKFQGRVTMTRDTSTSTVYMEL SSLRSEDTAVYYCAREGATGTWYFDVWG QGTTVTVSS VL 95 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKPLIYLTSNLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H2 L6 VH 83 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYAQKFQGRVTMTRDTSTSTVYMEL SSLRSEDTAVYYCAREGATGTWYFDVWG QGTTVTVSS VL 96 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKPWIYLTSNLASGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQ QWRSNPPTFGGGTKVEIK hzlO3E9B3H3 LI VH 84 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYAQKFQGRVTLTVDTSTSTVYMELS SLRSEDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 91 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLNWYQQKPGKAPKLLIYLTSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H3 L2 VH 84 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYAQKFQGRVTLTVDTSTSTVYMELS SLRSEDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 92 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLFWYQQKPGKAPKLLIYLTSSLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hz!03E9B3H3 VH 84 EVQLVQSGAEVKKPGASVKVSCKASGYT L3 FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYAQKFQGRVTLTVDTSTSTVYMELS SLRSEDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 93 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMFWYQQKPGKAPKPLIYLTSSLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H3 L4 VH 84 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYAQKFQGRVTLTVDTSTSTVYMELS SLRSEDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 94 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKLLIYLTSNLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H3 L5 VH 84 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYAQKFQGRVTLTVDTSTSTVYMELS SLRSEDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 95 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKPLIYLTSNLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H3 L6 VH 84 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYAQKFQGRVTLTVDTSTSTVYMELS SLRSEDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 96 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKPWIYLTSNLASGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQ QWRSNPPTFGGGTKVEIK hzlO3E9B3H4 LI VH 85 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYNQKFQGRVTLTVDTSTSTVYMELS SLRSEDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 91 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLNWYQQKPGKAPKLLIYLTSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H4 L2 VH 85 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYNQKFQGRVTLTVDTSTSTVYMELS SLRSEDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 92 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLFWYQQKPGKAPKLLIYLTSSLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H4 L3 VH 85 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYNQKFQGRVTLTVDTSTSTVYMELS SLRSEDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 93 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMFWYQQKPGKAPKPLIYLTSSLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H4 L4 VH 85 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYNQKFQGRVTLTVDTSTSTVYMELS SLRSEDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 94 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKLLIYLTSNLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H4 L5 VH 85 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYNQKFQGRVTLTVDTSTSTVYMELS SLRSEDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 95 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKPLIYLTSNLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H4 L6 VH 85 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYNQKFQGRVTLTVDTSTSTVYMELS SLRSEDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 96 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKPWIYLTSNLASGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQ QWRSNPPTFGGGTKVEIK hzlO3E9B3H5 LI VH 86 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYNEKFKDRVTMTTDTSTSTAYMEL RSLRSDDTAVYYCAREGATGTWYFDVWG QGTTVTVSS VL 91 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLNWYQQKPGKAPKLLIYLTSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hz!03E9B3H5 VH 86 EVQLVQSGAEVKKPGASVKVSCKASGYT L2 FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYNEKFKDRVTMTTDTSTSTAYMEL RSLRSDDTAVYYCAREGATGTWYFDVWG QGTTVTVSS VL 92 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLFWYQQKPGKAPKLLIYLTSSLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H5 L3 VH 86 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYNEKFKDRVTMTTDTSTSTAYMEL RSLRSDDTAVYYCAREGATGTWYFDVWG QGTTVTVSS VL 93 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMFWYQQKPGKAPKPLIYLTSSLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H5 L4 VH 86 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYNEKFKDRVTMTTDTSTSTAYMEL RSLRSDDTAVYYCAREGATGTWYFDVWG QGTTVTVSS VL 94 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKLLIYLTSNLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H5 L5 VH 86 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYNEKFKDRVTMTTDTSTSTAYMEL RSLRSDDTAVYYCAREGATGTWYFDVWG QGTTVTVSS VL 95 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKPLIYLTSNLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H5 L6 VH 86 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYNEKFKDRVTMTTDTSTSTAYMEL RSLRSDDTAVYYCAREGATGTWYFDVWG QGTTVTVSS VL 96 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKPWIYLTSNLASGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQ QWRSNPPTFGGGTKVEIK hzlO3E9B3H6 LI VH 87 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYNEKFKDRATMTTDTSTSTAYMEL RSLRSDDTAVYYCAREGATGTWYFDVWG QGTTVTVSS VL 91 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLNWYQQKPGKAPKLLIYLTSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H6 L2 VH 87 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYNEKFKDRATMTTDTSTSTAYMEL RSLRSDDTAVYYCAREGATGTWYFDVWG QGTTVTVSS VL 92 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLFWYQQKPGKAPKLLIYLTSSLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H6 L3 VH 87 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYNEKFKDRATMTTDTSTSTAYMEL RSLRSDDTAVYYCAREGATGTWYFDVWG QGTTVTVSS VL 93 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMFWYQQKPGKAPKPLIYLTSSLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H6 L4 VH 87 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYNEKFKDRATMTTDTSTSTAYMEL RSLRSDDTAVYYCAREGATGTWYFDVWG QGTTVTVSS VL 94 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKLLIYLTSNLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H6 L5 VH 87 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYNEKFKDRATMTTDTSTSTAYMEL RSLRSDDTAVYYCAREGATGTWYFDVWG QGTTVTVSS VL 95 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKPLIYLTSNLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H6 L6 VH 87 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWMGDINPNY GGTSYNEKFKDRATMTTDTSTSTAYMEL RSLRSDDTAVYYCAREGATGTWYFDVWG QGTTVTVSS VL 96 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKPWIYLTSNLASGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQ QWRSNPPTFGGGTKVEIK hz!03E9B3H7 VH 88 EVQLVQSGAEVKKPGASVKVSCKASGYT LI FTSYTMHWVRQAPGQGLEWIGDINPNYG GTSYNEKFKDRATLTTDTSTSTAYMELRS LRSDDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 91 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLNWYQQKPGKAPKLLIYLTSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H7 L2 VH 88 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWIGDINPNYG GTSYNEKFKDRATLTTDTSTSTAYMELRS LRSDDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 92 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLFWYQQKPGKAPKLLIYLTSSLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H7 L3 VH 88 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWIGDINPNYG GTSYNEKFKDRATLTTDTSTSTAYMELRS LRSDDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 93 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMFWYQQKPGKAPKPLIYLTSSLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H7 L4 VH 88 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWIGDINPNYG GTSYNEKFKDRATLTTDTSTSTAYMELRS LRSDDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 94 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKLLIYLTSNLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H7 L5 VH 88 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWIGDINPNYG GTSYNEKFKDRATLTTDTSTSTAYMELRS LRSDDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 95 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKPLIYLTSNLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H7 L6 VH 88 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWIGDINPNYG GTSYNEKFKDRATLTTDTSTSTAYMELRS LRSDDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 96 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKPWIYLTSNLASGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQ QWRSNPPTFGGGTKVEIK hzlO3E9B3H8 LI VH 89 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWIGDINPNYG GTSYNEKFKDRATLTTDTSTSTAYMELRS LRSDDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 91 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLNWYQQKPGKAPKLLIYLTSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H8 L2 VH 89 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWIGDINPNYG GTSYNEKFKDRATLTVDTSTSTAYMELRS LRSDDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 92 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLFWYQQKPGKAPKLLIYLTSSLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H8 L3 VH 89 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWIGDINPNYG GTSYNEKFKDRATLTVDTSTSTAYMELRS LRSDDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 93 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMFWYQQKPGKAPKPLIYLTSSLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H8 L4 VH 89 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWIGDINPNYG GTSYNEKFKDRATLTVDTSTSTAYMELRS LRSDDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 94 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKLLIYLTSNLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H8 L5 VH 89 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWIGDINPNYG GTSYNEKFKDRATLTVDTSTSTAYMELRS LRSDDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 95 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKPLIYLTSNLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hz!03E9B3H8 VH 89 EVQLVQSGAEVKKPGASVKVSCKASGYT L6 FTSYTMHWVRQAPGQGLEWIGDINPNYG GTSYNEKFKDRATLTVDTSTSTAYMELRS LRSDDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 96 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKPWIYLTSNLASGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQ QWRSNPPTFGGGTKVEIK hzlO3E9B3H9 LI VH 90 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWIGDINPNYG GTSYNEKFKDRATLTVDKSTSTAYMELRS LRSDDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 91 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLNWYQQKPGKAPKLLIYLTSSLQSGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H9 L2 VH 90 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWIGDINPNYG GTSYNEKFKDRATLTVDKSTSTAYMELRS LRSDDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 92 DIQMTQSPSSLSASVGDRVTITCRASSSVS FLFWYQQKPGKAPKLLIYLTSSLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H9 L3 VH 90 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWIGDINPNYG GTSYNEKFKDRATLTVDKSTSTAYMELRS LRSDDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 93 DIQMTQSPSSLSASVGDRVTITCRASSSVS FMFWYQQKPGKAPKPLIYLTSSLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H9 L4 VH 90 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWIGDINPNYG GTSYNEKFKDRATLTVDKSTSTAYMELRS LRSDDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 94 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKLLIYLTSNLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H9 L5 VH 90 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWIGDINPNYG GTSYNEKFKDRATLTVDKSTSTAYMELRS LRSDDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 95 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKPLIYLTSNLASGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQQ WRSNPPTFGGGTKVEIK hzlO3E9B3H9 L6 VH 90 EVQLVQSGAEVKKPGASVKVSCKASGYT FTSYTMHWVRQAPGQGLEWIGDINPNYG GTSYNEKFKDRATLTVDKSTSTAYMELRS LRSDDTAVYYCAREGATGTWYFDVWGQ GTTVTVSS VL 96 DIQMTQSPSSLSASVGDRVTITCSASSSVS FMFWYQQKPGKAPKPWIYLTSNLASGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQ QWRSNPPTFGGGTKVEIK

Claims

1. An antibody or antigen binding fragment thereof specifically binding to LI CAM comprising a light chain variable region comprising light chain complementarity determining regions LCDR1, LCDR2 and LCDR3 and / or a heavy chain variable region comprising heavy chain complementarity determining regions HCDR1, HCDR2 and HCDR3, wherein the antibody or antigen binding fragment thereof can specifically bind to the Igl or FN-4 domain of LI-CAM and does not have the same or equivalent combination of CDRs as antibody Ll-9. 3 or UJ127.

2. The antibody or antigen binding fragment according to claim 1, wherein the heavy chain variable region that comprises HCDR1, HCDR2 and HCDR3 comprising at least 80%, 90% or 100% identity to the HCDR1, HCDR2 and HCDR3 of the heavy chain variable region sequences selected from the group comprising SEQ ID NOs: 43, 45, 47, 49 and 51, and the light chain variable region that comprises LCDR1, LCDR2 and LCDR3 comprising at least 80% identity to the LCDR1, LCDR2 and LCDR3 of the light chain variable region sequences selected from the group comprising SEQ ID NOs: 44, 46, 48, 50 and 52.

3. The antibody or antigen binding fragment according to claim 1 or 2, comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region and the light chain variable region comprise a combination of CDRs selected from the group comprising of:(1) HCDR1, HCDR2 and HCDR3 comprising at least 80% identity to HCDR1, HCDR2 and HCDR3 of the heavy chain variable region sequence of SEQ ID NO: 43, LCDR1, LCDR2 and LCDR3 comprising at least 80% identity to LCDR1, LCDR2 and LCDR3 of the light chain variable region sequence of SEQ ID NO: 44;(2) HCDR1, HCDR2 and HCDR3 comprising at least 80% identity to HCDR1, HCDR2 and HCDR3 of the heavy chain variable region sequence of SEQ ID NO: 45, LCDR1, LCDR2 and LCDR3 comprising at least 80% identity to LCDR1, LCDR2 and LCDR3 of the light chain variable region sequence of SEQ ID NO: 46;(3) HCDR1, HCDR2 and HCDR3 comprising at least 80% identity to HCDR1, HCDR2 and HCDR3 of the heavy chain variable region sequence of SEQ ID NO: 47, LCDR1, LCDR2 and LCDR3 comprising at least 80% identity to LCDR1, LCDR2 and LCDR3 of the light chain variable region sequence of SEQ ID NO: 48;(4) HCDR1, HCDR2 and HCDR3 comprising at least 80% identity to HCDR1, HCDR2 and HCDR3 of the heavy chain variable region sequence of SEQ ID NO: 49,LCDR1, LCDR2 and LCDR3 comprising at least 80% identity to LCDR1, LCDR2 and LCDR3 of the light chain variable region sequence of SEQ ID NO: 50; And(5) HCDR1, HCDR2 and HCDR3 comprising at least 80% identity to HCDR1, HCDR2 and HCDR3 of the heavy chain variable region sequence of SEQ ID NO: 51, LCDR1, LCDR2 and LCDR3 comprising at least 80% identity to LCDR1, LCDR2 and LCDR3 of the light chain variable region sequence of SEQ ID NO: 52.

4. The antibody or antigen-binding fragment according to any one of claims 1 to 3, wherein:(1) the HCDR1 comprises at least 80% identity to a sequence selected from SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 13, SEQ ID NO: 19, SEQ ID NO: 25, SEQ ID NO: 31, SEQ ID NO: 37;(2) the HCDR2 comprises at least 80% identity to a sequence selected from SEQ ID NO: 2, SEQ ID NO: 8, SEQ ID NO: 14, SEQ ID NO: 20, SEQ ID NO: 26, SEQ ID NO: 32, SEQ ID NO: 38;(3) the HCDR3 comprises at least 80% identity to a sequence selected from SEQ ID NO: 3, SEQ ID NO: 9, SEQ ID NO: 15, SEQ ID NO: 21, SEQ ID NO: 27, SEQ ID NO: 33, SEQ ID NO: 39;(4) the LCDR1 comprises at least 80% identity to a sequence selected from SEQ ID NO: 4, SEQ ID NO: 10, SEQ ID NO: 16, SEQ ID NO: 22, SEQ ID NO: 28, SEQ ID NO: 34, SEQ ID NO: 40;(5) the LCDR2 comprises at least 80% identity to a sequence selected from SEQ ID NO: 5, SEQ ID NO: 11, SEQ ID NO: 17, SEQ ID NO: 23, SEQ ID NO: 29, SEQ ID NO: 35, SEQ ID NO: 41;(6) the LCDR3 comprises at least 80% identity to a sequence selected from SEQ ID NO: 6, SEQ ID NO: 12, SEQ ID NO: 18, SEQ ID NO: 24, SEQ ID NO: 30, SEQ ID NO: 36, SEQ ID NO: 42.

5. The antibody or antigen-binding fragment according to any one of claims 1 to 4, wherein:(1) the HCDRl comprises the amino acid sequence set forth in SEQ ID NO: 1;(2) the HCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 2;(3) the HCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 3;(4) the LCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 4;(5) the LCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 5;(6) the LCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 6.

6. The antibody or antigen-binding fragment according to any one of claims 1 to 4, wherein:(1) the HCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 7;(2) the HCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 8;(3) the HCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 9;(4) the LCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 10;(5) the LCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 11;(6) the LCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 12.

7. The antibody or antigen-binding fragment according to any one of claims 1 to 4, wherein:(1) the HCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 13;(2) the HCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 14;(3) the HCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 15;(4) the LCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 16;(5) the LCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 17;(6) the LCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 18.

8. The antibody or antigen-binding fragment according to any one of claims 1 to 4, wherein:(1) the HCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 19;(2) the HCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 20;(3) the HCDR3 comprises an amino acid sequence as set forth in SEQ ID NO: 21;(4) the LCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 22;(5) the LCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 23;(6) the LCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 24.

9. The antibody or antigen-binding fragment according to any one of claims 1 to 4, wherein:(1) the HCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 25;(2) the HCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 26;(3) the HCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 27;(4) the LCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 28;(5) the LCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 29;(6) the LCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 30.

10. The antibody or antigen-binding fragment according to any one of claims 1 to 4, wherein:(1) the HCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 31;(2) the HCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 32;(3) the HCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 33;(4) the LCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 34;(5) the LCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 35;(6) the LCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 36.

11. The antibody or antigen-binding fragment according to any one of claims 1 to 4, wherein:(1) the HCDRl comprises the amino acid sequence set forth in SEQ ID NO: 37;(2) the HCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 38;(3) the HCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 39;(4) the LCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 40;(5) the LCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 41;(6) the LCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 42.

12. The antibody or antigen-binding fragment of any one of claims 1 to 11, wherein the heavy chain variable region comprises an amino acid sequence comprising at least 90%, at least 95%, or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 43 or to SEQ ID NO: 43.

13. The antibody or antigen-binding fragment of any one of claims 1 to 11, wherein the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 44 or an amino acid sequence comprising at least 90%, at least 95%, or 100% sequence identity to SEQ ID NO: 44.

14. The antibody or antigen-binding fragment of any one of claims 1 to 11, wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 45 or an amino acid sequence comprising at least 90%, at least 95% or more sequence identity to SEQ ID NO: 45.

15. The antibody or antigen-binding fragment of any one of claims 1 to 11, wherein the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 46 or an amino acid sequence comprising at least 90%, at least 95% or more sequence identity to SEQ ID NO: 46.

16. The antibody or antigen-binding fragment of any one of claims 1 to 11, wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQID NO: 47 or an amino acid sequence comprising at least 90%, at least 95% or more sequence identity to SEQ ID NO: 47.

17. The antibody or antigen-binding fragment of any one of claims 1 to 11, wherein the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 48 or an amino acid sequence comprising at least 90%, at least 95% or more sequence identity to SEQ ID NO: 48.

18. The antibody or antigen-binding fragment of any one of claims 1 to 9, wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 49 or an amino acid sequence comprising at least 90%, at least 95% or more sequence identity to SEQ ID NO: 49.

19. The antibody or antigen-binding fragment according to any one of claims 1 to 11, wherein the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 50 or an amino acid sequence comprising at least 90%, at least 95% or more sequence identity to SEQ ID NO: 50.

20. The antibody or antigen-binding fragment according to any one of claims 1 to 11, wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 51 or an amino acid sequence comprising at least 90%, at least 95% or more sequence identity to SEQ ID NO: 51.

21. The antibody or antigen-binding fragment according to any one of claims 1 to 11, wherein the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 52 or an amino acid sequence comprising at least 90%, at least 95% or more sequence identity to SEQ ID NO: 52.

22. The antibody or antigen-binding fragment according to any one of claims 1-21, wherein the antibody is a humanized antibody.

23. The antibody or antigen-binding fragment according to claim 22, comprising a heavy chain variable region and / or a light chain variable region, wherein the heavy chain variable region comprises one of the amino acid sequences set forth in SEQ ID NO: 53 or SEQ ID NO: 54 or SEQ ID NO: 55 or SEQ ID NO: 56, and the light chain variable region comprises one of the amino acid sequences set forth in SEQ ID NO: 57 or SEQ ID NO: 58 or SEQ ID NO: 59.

24. The antibody or antigen-binding fragment according to claim 23, which comprises a heavy chain variable region and / or a light chain variable region, wherein:2) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 53, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 58; or3) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 53, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 59; or4) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 54, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 57; or5) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 54, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 58; or6) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 54, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 59; or7) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 55, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 57; or8) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 55, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 58; or9) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 55, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 59; or10) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 56, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 57; or11) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 56, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 58; or25. The antibody or antigen-binding fragment according to claim 23, wherein the heavy chain variable region comprises one of the amino acid sequences set forth in SEQ ID NO: 60 or SEQ ID NO: 61 or SEQ ID NO: 62 or SEQ ID NO: 63, and the light chain variable region comprises one of the amino acid sequences set forth in SEQ ID NO: 64 or SEQ ID NO: 65 or SEQ ID NO: 66.

26. The antibody or antigen binding fragment according to claim 25, comprising a heavy chain variable region and / or a light chain variable region, wherein,1) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 60, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 64; or2) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 60, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 65; or3) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 60, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 66; or4) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 61, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 64; or5) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 61, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 65; or6) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 61, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 66; or7) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 62, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 64; or8) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 62, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 65; or10) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 63, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 64; or11) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 63, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 65; or12) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 63, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 66.

27. The antibody or antigen-binding fragment according to claim 22, wherein the heavy chain variable region comprises one of the amino acid sequences set forth in SEQ ID NO: 67 or SEQ ID NO: 68 or SEQ ID NO: 69 or SEQ ID NO: 70 or SEQ ID NO: 71 or SEQ ID NO: 72 or SEQ ID NO: 73 or SEQ ID NO: 74 and the light chain variable region comprises one of the amino acid sequences set forth in SEQ ID NO: 75 or SEQ ID NO: 76 or SEQ ID NO: 77 or SEQ ID NO: 78 or SEQ ID NO: 79 or SEQ ID NO: 80 or SEQ ID NO: 81.

28. The antibody or antigen binding fragment according to claim 27, comprising a heavy chain variable region and / or a light chain variable region, wherein,1) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 67, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 75; Or2) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 67, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 76; Or3) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 67, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 77; Or4) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 67, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 78; Or6) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 67, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 80; Or7) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 67, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 81; Or8) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 68 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 75; Or9) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 68, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 76; Or10) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 68, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 77; Or11) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 68, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 78; Or12) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 68, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 79; Or13) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 68, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 80; Or14) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 68, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 81; Or15) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 69, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 75; Or17) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 69, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 77; Or18) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 69, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 78; Or19) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 69, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 79; Or20) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 69, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 80; Or21) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 69, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 81; Or22) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 70, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 75; Or23) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 70, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 76; Or24) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 70, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 77; Or25) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 70, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 78; Or26) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 70, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 79; Or28) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 70, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 81; Or29) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 71, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 75; Or30) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 71, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 76; Or31) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 71, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 77; Or32) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 71, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 78; Or33) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 71, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 79; Or34) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 71, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 80; Or35) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 71, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 81; Or36) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 72, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 75; Or37) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 72, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 76; Or39) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 72, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 78; Or40) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 72, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 79; Or41) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 72, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 80; Or42) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 72, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 81; Or43) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 73, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 75; Or44) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 73, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 76; Or45) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 73, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 77; Or46) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 73, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 78; Or47) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 73, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 79; Or48) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 73, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 80; Or50) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 74, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 75; Or51) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 74, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 76; Or52) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 74, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 77; Or53) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 74, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 78; Or54) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 74, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 79; Or55) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 74, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 80; Or56) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 74, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 81.

29. The antibody or antigen-binding fragment according to claim 22, wherein the heavy chain variable region comprises one of the amino acid sequences set forth in SEQ ID NO: 82 or SEQ ID NO: 83 or SEQ ID NO: 84 or SEQ ID NO: 85 or SEQ ID NO: 86 or SEQ ID NO: 87 or SEQ ID NO: 88 or SEQ ID NO: 89 or SEQ ID NO: 90, and the light chain variable region comprises one of the amino acid sequences set forth in SEQ ID NO: 91 or SEQ ID NO: 92 or SEQ ID NO: 93 or SEQ ID NO: 94 or SEQ ID NO: 95 or SEQ ID NO: 96.

30. The antibody or antigen-binding fragment according to claim 29, which comprises a heavy chain variable region and / or a light chain variable region, wherein,2) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 82, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 92; Or3) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 82, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 93; Or4) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 82, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 94; Or5) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 82, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 95; Or6) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 82, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 96; Or7) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 83, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 91; Or8) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 83, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 92; Or9) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 83, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 93; Or10) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 83, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 94; Or11) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 83, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 95; Or13) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 84, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 91; Or14) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 84, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 92; Or15) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 84, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 93; Or16) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 84, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 94; Or17) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 84, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 95; Or18) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 84, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 96; Or19) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 85, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 91; Or20) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 85, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 92; Or21) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 85, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 93; Or22) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 85, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 94; Or24) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 85, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 96; Or25) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 86, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 91; Or26) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 86, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 92; Or27) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 86, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 93; Or28) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 86, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 94; Or29) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 86, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 95; Or30) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 86, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 96; Or31) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 87, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 91; Or32) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 87, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 92; Or33) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 87, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 93; Or35) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 87, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 95; Or36) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 87, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 96; Or37) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 88, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 91; Or38) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 88, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 92; Or39) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 88, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 93; Or40) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 88, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 94; Or41) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 88, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 95; Or42) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 88, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 96; Or43) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 89, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 91; Or44) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 89, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 92; Or46) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 89, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 94; Or47) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 89, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 95; Or48) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 89, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 96; Or49) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 90, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 91; Or50) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 90, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 92; Or51) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 90, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 93; Or52) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 90, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 94; Or53) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 90, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 95; Or54) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 90, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 96.

31. The antibody or antigen-binding fragment according to any one of claims 1-30, further comprising an Fc region, optionally that of a human immunoglobulin (Ig), or optionally that of a human IgG, whereas the Fc region is derived from human IgGl, IgG2, IgG3, IgG4, IgAl, IgA2 or IgM.

32. The antibody or antigen-binding fragment according to any one of claims 1-31, wherein the antigen-binding fragment is a scFv, scFv-Fc, Fv, Fab, Fab ’, F (ab)2 or F (ab ')233. The antibody or antigen-binding fragment according to any one of claims 1-32 which is a monoclonal antibody, a bispecific antibody, a multi-specific antibody, a recombinant antibody, a chimeric antibody, a divalent antibody, an anti-idiotypic antibody, or a fusion protein.

34. An antibody-drug conjugate comprising the antibody or antigen-binding fragment according to any one of claims 1-33, and an additional effector molecule conjugate 35. A nucleic acid molecule encoding the antibody or antigen-binding fragment of any one of claims 1-33.

36. The nucleic acid molecule according to claim 39, operably linked to a promoter.

37. A recombinant expression vector comprising the nucleic acid molecule of claim 39 or 40.

38. A plasmid comprising the nucleic acid molecule of claim 39 or 40.

39. A host cell comprising the nucleic acid molecule of claim 39 or 40, the recombinant expression vector of claim 41 or the plasmid of claim 42.

40. A method for detecting the expression of LI CAM in a biological sample comprising the steps of contacting said biological sample with the antibody or antigen-binding fragment thereof of any one of claims 1-33 and detecting the presence or absence of an immune complex, wherein the presence of an immune complex indicates the presence of LI CAM in the biological sample41. A pharmaceutical composition comprising, as an active substance, the antibody or the antigen-binding fragment thereof of any one of claims 1 to 33, the antibody-drug conjugate of any one of claims 34 to 38, and a pharmaceutically acceptable carrier42. A kit comprising the antibody or antigen-binding fragment thereof according to any one of claims 1 to 33, the antibody-drug conjugate according to claim 34 and / or the pharmaceutical composition according to claim 4543. A method of treating cancer comprising administering to a subject in need thereof the antibody or antigen-binding fragment thereof of any one of claims 1-33, the antibody-drug conjugate of claim 34, or the pharmaceutical composition of claim 45 44. The method according to claim 47, further comprising detecting the presence of LI-CAM in a cancer sample prior to administration of the medicament.

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