RU2801535C1 - Anti-lilrb1 antibody and its use - Google Patents

Abstract

FIELD: pharmaceuticals.

SUBSTANCE: invention relates to an anti-LILRB1 antibody having increased specificity for LILRB1. The invention also relates to a pharmaceutical composition containing an anti-LILRB1 antibody or antigen-binding fragment thereof for the treatment or prevention of cancer characterized by MHC class I overexpression, a nucleic acid molecule encoding an anti-LILRB1 antibody or an antigen-binding fragment thereof, a recombinant expression vector, a recombinant cell producing an anti-LILRB1 antibody or antigen-binding fragment thereof, and a method for producing an anti-LILRB1 antibody or antigen-binding fragment thereof.

EFFECT: obtaining anti-lilrb1 antibody and its use.

9 cl, 12 dwg, 28 tbl, 11 ex

Description

The field of technology to which the invention belongs

Cross-reference to related applications

This application claims the benefits of KR 10-2019-0173414 filed on December 23, 2019 and KR 10-2020-0061907 filed on May 22, 2020, which are filed with the Korean Intellectual Property Office, the full disclosure of which is hereby incorporated by reference.

The present invention relates to an anti-LILRB1 antibody and uses thereof. More specifically, an anti-LILRB1 antibody or antigen-binding fragment thereof and its use in the treatment of cancer are provided.

Prerequisites for the creation of the invention

Leukocyte immunoglobulin-like receptor B subfamily member 1 (LILRB1; also known as ILT2, CD85j, or LIR-1) is an inhibitory receptor that is expressed on cells such as B cells, T cells, NK cells, dendritic cells, macrophages, and other immune cells. LILRB1 is involved in the signal transduction mechanism of inhibition of immune cell activity by binding to classical and non-classical MHC class I.

Meanwhile, there have been reports that various cancer cells overexpress MHC class I, such as HLA-G, to evade immune surveillance. It is assumed that blocking the binding of LILRB1 to MHC class I allows the restoration of the inhibited activity of immune cells, thereby exhibiting anticancer effects.

Therefore, it is necessary to develop a new agent that binds to LILRB1 and blocks the binding of LILRB1 to MHC class I and/or the interaction between LILRB1 and MHC class I.

Disclosure

Technical task

The present invention provides antibodies that bind to LILRB1, act on LILRB1 expressing immune cells, regulate immune cell activity and exhibit anti-cancer effects as well as their use in cancer treatment.

An embodiment provides an anti-LILRB1 antibody that binds to LILRB1, or an antigen-binding fragment thereof. An anti-LILRB1 antibody, or antigen-binding fragment thereof, may have the activity to block the binding of LILRB1 to MHC class I and/or block the interaction between LILRB1 and MHC class I. In addition In addition, an anti-LILRB1 antibody, or antigen-binding fragment thereof, may have activity to inhibit immune evasion of cancer cells. Moreover, an anti-LILRB1 antibody, or an antigen-binding fragment thereof, may have an anti-cancer effect. The anticancer effect can be directed against cancer cells expressing or overexpressing MHC class I on their cell surface.

Another embodiment provides a pharmaceutical composition for the treatment and/or prevention of cancer, the composition comprising an anti-LILRB1 antibody or an antigen-binding fragment thereof as an active ingredient.

Another embodiment provides a pharmaceutical composition for inhibiting the binding of LILRB1 to MHC class I and/or blocking the interaction between LILRB1 and MHC class I, wherein the composition comprises an anti-LILRB1 antibody or an antigen-binding fragment thereof as an active ingredient.

Yet another embodiment provides a pharmaceutical composition for inhibiting immune surveillance evasion of cancer cells, the composition comprising an anti-LILRB1 antibody or an antigen-binding fragment thereof as an active ingredient.

Technical solution

An embodiment provides an anti-LILRB1 antibody that binds to LILRB1, or an antigen-binding fragment thereof. An anti-LILRB1 antibody, or antigen-binding fragment thereof, may have the activity to block the binding of LILRB1 to MHC class I and/or block the interaction between LILRB1 and MHC class I. In addition In addition, an anti-LILRB1 antibody, or antigen-binding fragment thereof, may have activity to inhibit immune evasion of cancer cells. In addition, an anti-LILRB1 antibody, or an antigen-binding fragment thereof, may have an anti-cancer effect.

An anti-LILRB1 antibody, or antigen-binding fragment thereof, may include the following complementarity-determining regions (CDRs):

(1) based on CDR definition according to Kabat numbering (Kabat, E.A., Wu, T.T., Perry, H., Gottesman, K. and Foeller, C. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition. NIH Publication No. 91-3242; http://www.abysis.org/),

CDR-L1 containing the amino acid sequence of SEQ ID NO: 1, 7, 13, 19, 25, 31, 37, 43, 49, 55, 61, 67, 73, 79, 85, 91, 97, 103, 109 or 115 ,

CDR-L2 containing the amino acid sequence of SEQ ID NO: 2, 8, 14, 20, 26, 32, 38, 44, 50, 56, 62, 68, 74, 80, 86, 92, 98, 104, 110, or 116 ,

CDR-L3 containing the amino acid sequence of SEQ ID NO:3, 9, 15, 21, 27, 33, 39, 45, 51, 57, 63, 69, 75, 81, 87, 93, 99, 105, 111, or 117 ,

CDR-H1 containing the amino acid sequence of SEQ ID NO: 4, 10, 16, 22, 28, 34, 40, 46, 52, 58, 64, 70, 76, 82, 88, 94, 100, 106, 112, or 118 ,

CDR-H2 containing the amino acid sequence of SEQ ID NO: 5, 11, 17, 23, 29, 35, 41, 47, 53, 59, 65, 71, 77, 83, 89, 95, 101, 107, 113 or 119 , And

CDR-H3 containing the amino acid sequence of SEQ ID NO:6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, 102, 108, 114, or 120 ; or

(2) based on the definition of the CDR according to the IMGT numbering (http://www.imgt.org/),

CDR-L1 containing the amino acid sequence of SEQ ID NO:121, 126, 131, 136, 141, 146, 151, 156, 161, 166, 171, 176, 181, 186, 191, 196, 201, 206, 211, or 216 ,

CDR-L2 containing the amino acid sequence of SEQ ID NO:122, 127, 132, 137, 142, 147, 152, 157, 162, 167, 172, 177, 182, 187, 192, 197, 202, 207, 212, or 217 ,

CDR-L3 containing the amino acid sequence of SEQ ID NO:3, 9, 15, 21, 27, 33, 39, 45, 51, 57, 63, 69, 75, 81, 87, 93, 99, 105, 111, or 117 ,

CDR-H1 containing the amino acid sequence of SEQ ID NO:123, 128, 133, 138, 143, 148, 153, 158, 163, 168, 173, 178, 183, 188, 193, 198, 203, 208, 213, or 218 ,

CDR-H2 containing the amino acid sequence of SEQ ID NO:124, 129, 134, 139, 144, 149, 154, 159, 164, 169, 174, 179, 184, 189, 194, 199, 204, 209, 214, or 219 , And

CDR-H3 containing the amino acid sequence SEQ ID NO:125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, or 220 .

In a particular embodiment, combinations of the 6 CDRs (CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2, and CDR-H3) that may be contained in an anti-LILRB1 antibody or antigen-binding fragment thereof provided herein disclosure are illustrated in Table 1:

Table 1 CDR Amino acid sequence (N→C) (Kabat) SEQID NO Amino acid sequence (N→C) (IMGT) SEQID NO E3/E3.1 CDR-L1 QGDSLRNFYAS 1 SLRNFY 121 CDR-L2 GKNNRPS 2 GKN 122 CDR-L3 NSRDSSGSHLTGV 3 NSRDSSGSHLTGV 3 CDR-H1 SYAMS 4 GFTFSSYA 123 CDR-H2 AISGSGGSTYYADSVKG 5 ISGSGGST 124 CDR-H3 DTYYYGSGRSNAFDI 6 ARDTYYYGSGRSNAFDI 125 B3 CDR-L1 QASQDISNYLN 7 QDISNY 126 CDR-L2 DASNLET 8 DAS 127 CDR-L3 QQYDNLP 9 QQYDNLP 9 CDR-H1 DYAMH 10 GFTFDDYA 128 CDR-H2 GISWNSGSIGYADSVKG eleven ISWNSGSI 129 CDR-H3 VGDSSGWSDAFDI 12 ARVGDSSGWSDAFDI 130 A10 CDR-L1 RASQSVSSNLA 13 QSVSSN 131 CDR-L2 GASTRAT 14 GAS 132 CDR-L3 QQYGSPRMYT 15 QQYGSPRMYT 15 CDR-H1 SYAIS 16 GGTFSSYA 133 CDR-H2 GIIPIFGTANYAQKFQG 17 IIPIFGTA 134 CDR-H3 GGLGELDNWFDP 18 ARGGLGELDNWFDP 135 G1 CDR-L1 SGYKLGDRYVS 19 KLGDRY 136 CDR-L2 KDSQRPS 20 KDS 137 CDR-L3 QAWDSGTGV 21 QAWDSGTGV 21 CDR-H1 SYGIS 22 GGTFSSYG 138 CDR-H2 WISAYNGNTNYAQELQG 23 ISAYNGNT 139 CDR-H3 VGVAGKLDY 24 ARVGVAGKLDY 140 G9 CDR-L1 TGSSSDVGGYNYVS 25 SSDVGGYNY 141 CDR-L2 DVSNRPS 26 DVS 142 CDR-L3 SSYTGSSTLDVL 27 SSYTGSSTLDVL 27 CDR-H1 SYWIG 28 GYSFTSYW 143 CDR-H2 IIYPGDSDTRYSPSFQG 29 IYPGDSDT 144 CDR-H3 QYYDGGYYMDV thirty ASQYYDGGYYMDV 145 H2 CDR-L1 QGDSLRNYYAS 31 SLRNYY 146 CDR-L2 GNNKRPS 32 GNN 147 CDR-L3 NSLDSTYNHPI 33 NSLDSTYNHPI 33 CDR-H1 SYDIH 34 GYTFTSYD 148 CDR-H2 WISAYNGNTNYAQKLQG 35 ISAYNGNT 149 CDR-H3 DGGDAFDI 36 ARDGGDAFDI 150 H11 CDR-L1 QGDSLRSYYAS 37 SLRSYY 151 CDR-L2 GRNRPS 38 GRN 152 CDR-L3 KSRDSSGNHYV 39 KSRDSSGNHYV 39 CDR-H1 SYYMH 40 GYTFTSYY 153 CDR-H2 IINPSGGSTSYAQKFQG 41 INPSGGST 154 CDR-H3 DAGSSSDY 42 ARDAGSSSDY 155 F12 CDR-L1 AGTSSDIGDYDYVS 43 SSDIGDYDY 156 CDR-L2 DVSRRPS 44 DVS 157 CDR-L3 ASYTSSSVVV 45 ASYTSSSVVV 45 CDR-H1 SYWIG 46 GYSFTSYW 158 CDR-H2 IIYPGDSDTRYSPSFQG 47 IYPGDSDT 159 CDR-H3 QYYDGGYYMDV 48 ASQYYDGGYYMDV 160 B9 CDR-L1 RASQSISRYLN 49 QSISRY 161 CDR-L2 GASSLQS 50 GAS 162 CDR-L3 QQAYGFPLT 51 QQAYGFPLT 51 CDR-H1 SYAIS 52 GGTFSSYA 163 CDR-H2 GIIPIFGTANYAQKFQG 53 IIPIFGTA 164 CDR-H3 GEIAVAQNWDYYGMDV 54 ARGEIAVAQNWDYYGMDV 165 G11 CDR-L1 TGTSSDVGGYNYVS 55 SSDVGGYNY 166 CDR-L2 DVSKRPS 56 DVS 167 CDR-L3 SSYSSSSTLVV 57 SSYSSSSTLVV 57 CDR-H1 SYWIG 58 GYSFTSYW 168 CDR-H2 IIYPGDSDTRYSPSFQG 59 IYPGDSDT 169 CDR-H3 QYYDGGYYMDV 60 ASQYYDGGYYMDV 170 G6 CDR-L1 QGDSLRRYYAT 61 SLRRY 171 CDR-L2 GQNYRPS 62 GQN 172 CDR-L3 NSRDSSGNHVV 63 NSRDSSGNHVV 63 CDR-H1 SYYMH 64 GYTFTSYY 173 CDR-H2 GIIPIFGTANYAQKFQG 65 IIPIFGTA 174 CDR-H3 GWGYSSSFDY 66 ARGWGYSSSFDY 175 F11 CDR-L1 SGSSSNIGTNTVN 67 SSNIGTNT 176 CDR-L2 SNDQRPS 68 SND 177 CDR-L3 ETWDDSLKGPV 69 ETWDDSLKGPV 69 CDR-H1 SYAMS 70 GFTFSSYA 178 CDR-H2 TISGSGDSTYYADSVKG 71 ISGSGDST 179 CDR-H3 EWELGDAFDI 72 AREWELGDAFDI 180 D3 CDR-L1 RASQSISSYLN 73 QSISSY 181 CDR-L2 AASSLQS 74 AAS 182 CDR-L3 QQSYSTRWT 75 QQSYSTRWT 75 CDR-H1 SYAMS 76 GSTFSSYA 183 CDR-H2 AISGSGGSTYYADSVKG 77 ISGSGGST 184 CDR-H3 DRGSYGYYYGMDV 78 AKDRGSYGYYYGMDV 185 B12 CDR-L1 RASQSISSYLN 79 QSISSY 186 CDR-L2 AASSLQS 80 AAS 187 CDR-L3 QQSYSTLRT 81 QQSYSTLRT 81 CDR-H1 GYYMH 82 GYTFTGYY 188 CDR-H2 WINPNSGGTNYAQKFQG 83 INPNSGGT 189 CDR-H3 AGASIVGATALDY 84 TRAGASIVGATALDY 190 E4 CDR-L1 TRSSGSIASNYVQ 85 SGSIASNY 191 CDR-L2 EDNQRPS 86 EDN 192 CDR-L3 QSYDTGNRNYV 87 QSYDTGNRNYV 87 CDR-H1 SYTIS 88 GGTFSSYT 193 CDR-H2 RIIPILGIANYAQKFQG 89 IIPILGIA 194 CDR-H3 GPSLNYAGYFDN 90 VRGPSLNYAGYFDN 195 E12 CDR-L1 QGDSLRSYYAS 91 SLRSYY 196 CDR-L2 GKEKRPS 92 GKE 197 CDR-L3 NSRGSTTDYMV 93 NSRGSTTDYMV 93 CDR-H1 SYAMH 94 GFTFSSYA 198 CDR-H2 VISYDGSNKKYYADSVKG 95 ISYDGSNK 199 CDR-H3 ERGSGMDV 96 ARERGSGMDV 200 D1 CDR-L1 KASQDIDDDMN 97 QDIDDDD 201 CDR-L2 EASTLVP 98 EAS 202 CDR-L3 LQHDKFPYT 99 LQHDKFPYT 99 CDR-H1 SYGIS 100 GYTFTSYG 203 CDR-H2 WINPNSGGTNYAQKFQG 101 INPNSGGT 204 CDR-H3 RGVDEGDY 102 ASRGVDEGDY 205 E6 CDR-L1 TGSSGNIASNYVQ 103 SGNIASNY 206 CDR-L2 RDDQRPS 104 RDD 207 CDR-L3 QSYDSSSWV 105 QSYDSSSWV 105 CDR-H1 TYDIT 106 GYTFTTYD 208 CDR-H2 WMNPNSGNSRSAQKFQG 107 MNPNSGNS 209 CDR-H3 GDYSGVVLTATALDY 108 ATGDYSGVVLTATALDY 210 E9 CDR-L1 SGSSSNIGNNYVY 109 SSNIGNNY 211 CDR-L2 RNNQRPS 110 RNN 212 CDR-L3 AAWDDSLSGWV 111 AAWDDSLSGWV 111 CDR-H1 SYGMH 112 GFTFSSYG 213 CDR-H2 NIKQDGSEKYYVDSVKG 113 IKQDGSEK 214 CDR-H3 EDRIAAAGMRELDY 114 AREDRIAAAGMRELDY 215 A11 CDR-L1 RSSQSLLHSNGYNYLD 115 QSLLHSNGYNY 216 CDR-L2 LGSNRAS 116 LGS 217 CDR-L3 MQGTHWPPYT 117 MQGTHWPPYT 117 CDR-H1 SYAMT 118 GFSFTSYA 218 CDR-H2 GISSDGTTTTYADSVRG 119 ISSDGTTT 219 CDR-H3 DQLLGWDALNV 120 ARDQLLGWDALNV 220

In one embodiment, an anti-LILRB1 antibody, or antigen-binding fragment thereof, may include:

a light chain variable region comprising CDR-L1, CDR-L2 and CDR-L3, and

a heavy chain variable region comprising CDR-H1, CDR-H2 and CDR-H3, wherein the CDRs are as described above.

More specifically, an anti-LILRB1 antibody, or antigen-binding fragment thereof, may include:

a light chain variable region comprising the amino acid sequence of SEQ ID NOs: 221, 223, 225, 227, 229, 231, 233, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259 or 345, and

a heavy chain variable region comprising the amino acid sequence of SEQ ID NOs: 222, 224, 226, 228, 230, 232, 234, 236, 238, 240, 242, 244, 246, 248, 250, 252, 254, 256, 258, or 260.

In a specific embodiment, combinations of a light chain variable region and a heavy chain variable region that may be contained in an anti-LILRB1 antibody or antigen-binding fragment thereof provided in this disclosure are illustrated in Table 2:

table 2 variable region Amino acid sequence (N→C) SEQID NO E3 light chain variable region SYELTQDPAVSVALGQTVRITCQGDSLRNFYASWYQQKSGQAPVLVMYGKNNRPSGIPDRFSGSTSGNTASLTITGAQAEDEADYYCNSRDSSGSHLTGVFGGGTKVTVLGQPAAA 221 heavy chain variable region QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMISLRAEDTAVYYCARDTYYYGSGRSNAFDIWGQGTLVTVSS 222 B3 light chain variable region DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPFGGGTKVDIKRTAAA 223 heavy chain variable region EVQLLESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVGDSSGWSDAFDIWGQG™VTVSS 224 A10 light chain variable region DIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYGSPRMYTFGQGTKVDIKRTAAA 225 heavy chain variable region QMQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADKSISTAYMELSSLRSEDTAVYYCARGGLGELDNWFDPWGQGTLVTVSS 226 G1 light chain variable region SYELTQPPSLSVSPGQTASITCSGYKLGDRYVSWYQQKTGQSPVVVIYKDSQRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSGTGTGVFGGGTKLTVLGQPAAA 227 heavy chain variable region EVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQELQGRV™TTDTSTSTAYMELRSLRSDDTAVYYCARVGVAGKLDYWGQGTLVTVSS 228 G9 light chain variable region QSALTQPASVSGSPGQSITISCTGSSSDVGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGVSDRFSGSKSGNMASLTISGLQAEDEADYYCSSYTGSSTLDVLFGGGTKLTVLGQPAAA 233 heavy chain variable region QVQLVQPGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCASQYYDGGYYMDVWGQGTLVTVSS 234 H2 light chain variable region SYELTQDPAVSVALGQTVRITCQGDSLRNYYASWYQQKPGQAPILVISGNNKRPSGIPDRFSGSSSGDTASLTISGAQAEDEADYYCNSLDSTYNHPIFGGGTKVTVLGQPAAA 235 heavy chain variable region QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIHWVRQATGQGLEWMGWISAYNGNTNYAQKLQGRV™TTDTSTSTAYMELRSLRSDDTAVYYCARDGGDAFDIWGQGTLVTVSS 236 H11 light chain variable region SYELTQDPAASVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVVVIYGRNNRPSGIPDRFSGSSSGDTASLTITGAQAEDEADYYCKSRDSSGNHYVFGTGTKLTVLGQPAAA 231 heavy chain variable region QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRV™TRDTSTSTVYMELSSLRSEDTAVYYCARDAGSSSDYWGRGTLVTVSS 232 F12 light chain variable region QSVLTQPASVSGSPGQSITISCAGTSSDIGDYDYVSWYQQHPGKTPKLMIYDVSRRPSGVPDRFSGSKSGNTASLTISGLQTEDEADYYCASYTSSSVVVFGGGTKLTVLGQPAAA 237 heavy chain variable region QVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCASQYYDGGYYMDVWGQGTLVTVSS 238 B9 light chain variable region DIQMTQSPSSLSASVGDRVTITCRASQSISRYLNWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYHCQQAYGFPLTLGGGTKVEIKRTAAA 229 heavy chain variable region QVQLVESGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGEIAVAQNWDYYGMDVWGQGTLVTVSS 230 G11 light chain variable region QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSKRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYCSSYSSSSTLVVFGGGTKLTVLGQPAAA 239 heavy chain variable region QVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCASQYYDGGYYMDVWGQGTLVTVSS 240 G6 light chain variable region SYELTQDPAVSVALGQTVTITCQGDSLRRYYATWYQQKPGQAPVLVIYGQNYRPSGIPDRFSGSNSGTTASLTITGAQAEDEADYYCNSRDSSGNHVVFGGGTKLTVLGQPAAA 241 heavy chain variable region EVQLVESGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGWGYSSSFDYWGQGTTVTVSS 242 F11 light chain variable region QSVLTQPPSTSGTPGQTFSIFCSGSSSNIGTNTVNWYQQLPGTAPKLLIYSNDQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCETWDDSLKGPVFGGGTKVTVLGQPAAA 243 heavy chain variable region EVQLVESGGGLVQPGGSLKLSCAASGFTFSSYAMSWVRRAPGKGLEWVSTISGSGDSTYYADSVKGRFTISRDNSKNTLYLQMNNLRAEDTAVYYCAREWELGDAFDIWGRGTLVTVSS 244 D3 light chain variable region DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTRWTFGQGTKVEIKRTAAA 245 heavy chain variable region EVQLLESGGGVVQPGRSLRLSCAASGTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDRGSYGYYGMDVWGQG™VTVSS 246 B12 light chain variable region DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTLRTFGQGTKVEIKRTAAA 247 heavy chain variable region QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCTRAGASIVGATALDYWGQGTLVTVSS 248 E4 light chain variable region NFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSSPTTVIYEDNQRPSGVPDRFSGSIDSSSSNSASLTISGLKTEDEADYYCQSYDTGNRNYVFGTGTQLTVLGQPAAA 249 heavy chain variable region QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYTISWVRQAPGQGLEWMGRIIPILGIANYAQKFQGRV™TRDMSTDTAYMELSSLTYDDTAVYFCVRGPSLNYAGYFDNWGQGTLVTVSS 250 E12 light chain variable region SYELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKSGQAPVLVIYGKEKRPSGIPDRFSGSSSGNTASLTITGARAEDEADYYCNSRGSTTDYMVFGGGTQLTVLGQPAAA 251 heavy chain variable region QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARERGSGMDVWGQGTLVTVSS 252 D1 light chain variable region ETTLTQSPAFMSATPGDKVNISCKASQDIDDDMNWYQQKPGEAAISIIQEASTLVPGIPPRFSGSGYGTDFTLTINNIESEDAAYYFCLQHDKFPYTFGQGTKLEIKRTAAA 253 heavy chain variable region EVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRV™TRDTSISTAYMELSRLRSDDTAVYYCASRGVDEGDYWGQG™VTVSS 254 E6 light chain variable region NFMLTQPHSVSESPGKTVTLSCTGSSGNIASNYVQWYQHRPGSAPTTVIYRDDQRPSGVPDRFSGSIDSSSSNSASLTISGLRPEDEADYYCQSYDSSSWVFGGGTKLTVLGQPAAA 255 heavy chain variable region QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYDITWVRQAPGQGLEWMGWMNPNSGNSRSAQKFQGRVSMTSDSSISTAYMELSSLRSEDTAVYYCATGDYSGVVLTATALDYWGQGTLVTVSS 256 E9 light chain variable region QSELTQLPSASETPGQRVTISCSGSSSNIGNNYVYWYQQLPGTAPKLLIYRNNQRPSGVPDRFSSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSGWVFGGGTKLTVLGQPAAA 257 heavy chain variable region QVQLVESGGGLVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVANIKQDGSEKYYVDSVKGRFTISRDNAKNTLYLQMNSLRAEDTAVYYCAREDRIAAAGMRELDYWGQGTLVTVSS 258 A11 light chain variable region DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGTHWPPYTFGQGTKVEIKRTAAA 259 heavy chain variable region EVQLLESGGGLEQPGGFLRLSCAASGFSFTSYAMTWVRQAPGKGLEWVSGISSDGTTTTYADSVRGRFTISRDNAKNTVYLQMNSLRDEDTAVYYCARDQLLGWDALNVWGQG™VTVSS 260 E3.1 light chain variable region SYELTQDPAVSVALGQTVRITCQGDSLRNFYASWYQQKSGQAPVLVMYGKNNRPSGIPDRFSGSTSGNTASLTITGAQAEDEADYYCNSRDSSGSHLTGVFGGGTKVTVL 345 heavy chain variable region QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMISLRAEDTAVYYCARDTYYYGSGRSNAFDIWGQGTLVTVSS 222

In the present disclosure, the expression "antibody or antigen-binding fragment (e.g., CDR, variable region, or heavy chain/light chain) comprises, consists of, or is represented by a specific amino acid sequence" may refer to an antigen-binding fragment that consists essentially of (1) a specific amino acid sequence or (2) an amino acid sequence, where a minor mutation (eg, substitution, deletion, and/or addition of amino acid residue(s) not affecting antibody activity) has been introduced into the amino acid sequence of (1).

An anti-LILRB1 antibody or antigen-binding fragment provided herein may have a binding affinity (K _D ) for LILRB1 (e.g., human LILRB1) of 10 mM or less, 5 mM or less, 1 mM or less, 0.5 mM, or less, 0.2 mM or 0.15 mM or less, for example 0.001 nM - 10 mM, 0.005 nM - 10 mM, 0.01 nM - 10 mM, 0.05 nM - 10 mM, 0.1 nM - 10 mM , 0.5 nM - 10 mM, 1 nM - 10 mM, 0.001 nM - 5 mM, 0.005 nM - 5 mM, 0.01 nM - 5 mM, 0.05 nM - 5 mM, 0.1 nM - 5 mM , 0.5 nM - 5 mM, 1 nM - 5 mM, 0.001 nM - 1 mM, 0.005 nM - 1 mM, 0.01 nM - 1 mM, 0.05 nM - 1 mM, 0.1 nM - 1 mM , 0.5 nM - 1 mM, 1 nM - 1 mM, 0.001 nM - 0.5 mM, 0.005 nM - 0.5 mM, 0.01 nM - 0.5 mM, 0.05 nM - 0.5 mM , 0.1 nM - 0.5 mM, 0.5 nM - 0.5 mM, 1 nM - 0.5 mM, 0.001 nM - 0.2 mM, 0.005 nM - 0.2 mM, 0.01 nM - 0.2 mM, 0.05 nM - 0.2 mM, 0.1 nM - 0.2 mM, 0.5 nM - 0.2 mM, 1 nM - 0.2 mM, 0.001 nM - 0.15 mM , 0.005 nM - 0.15 mM, 0.01 nM - 0.15 mM, 0.05 nM - 0.15 mM, 0.1 nM - 0.15 mM, 0.5 nM - 0.15 mM or 1 nM - 0.15 mM, as measured by the surface plasmon resonance (SPR) method.

Another embodiment provides a pharmaceutical composition containing an anti-LILRB1 antibody, or an antigen-binding fragment thereof, as an active ingredient. For example, the pharmaceutical composition may be a pharmaceutical composition for the treatment and/or prevention of cancer. The pharmaceutical composition may have activity to inhibit the binding of LILRB1 to MHC class I and/or the interaction between LILRB1 and MHC class I. The cancer may be cancer associated with an interaction between LILRB1 and MHC class I. In one embodiment, the pharmaceutical composition may have activity for inhibition of evasion of the immune surveillance of the cancer cell. The cancer cell may be a cell that expresses or overexpresses MHC class I on the cell surface.

Another embodiment provides a composition for blocking LILRB1 binding to MHC class I and/or interaction between LILRB1 and MHC class I, wherein the composition comprises an anti-LILRB1 antibody or antigen-binding fragment thereof as an active ingredient.

Another embodiment provides a composition for inhibiting immune evasion of a cancer cell, the composition comprising an anti-LILRB1 antibody or an antigen-binding fragment thereof as an active ingredient.

Another embodiment provides a method for treating and/or preventing cancer, comprising administering (orally or parenterally) a pharmaceutically effective amount of an anti-LILRB1 antibody or antigen-binding fragment thereof to a subject (e.g., a mammal, including a human) in need of cancer treatment and/or prevention.

Another embodiment provides a method for blocking the binding of LILRB1 to MHC class I and/or a method for blocking an interaction between LILRB1 and MHC class I, comprising administering (orally or parenterally) a pharmaceutically effective amount of an anti-LILRB1 antibody or antigen-binding fragment thereof to a subject (e.g., a mammal, including human) in need of inhibition of LILRB1 binding to MHC class I and/or interaction between LILRB1 and MHC class I.

Another embodiment provides a method for inhibiting cancer cell immune surveillance evasion, comprising administering (orally or parenterally) a pharmaceutically effective amount of an anti-LILRB1 antibody or antigen-binding fragment thereof to a subject (e.g., a mammal, including a human) in need of inhibiting cancer cell immune surveillance evasion. .

The methods provided in the present disclosure may further include the step of identifying a subject in need of cancer treatment and/or prevention, inhibition of LILRB1 binding to MHC class I and/or interaction between LILRB1 and MHC class I, and/or inhibition of evasion of cancer immune surveillance. cells, before the injection stage.

Another embodiment provides a nucleic acid molecule (polynucleotide) encoding at least one polypeptide selected from the group consisting of CDRs (CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2, CDR-H3, combinations of CDR-L1, CDR-L2 and CDR-L3 or combinations of CDR-H1, CDR-H2 and CDR-H3), a light chain variable region including CDR-L1, CDR-L2 and CDR-L3, a heavy chain variable region, including CDR-H1, CDR-H2 and CDR-H3; a light chain comprising the light chain variable region; and a heavy chain comprising the heavy chain variable region of the anti-LILRB1 antibody described above.

Another embodiment provides a recombinant vector comprising a nucleic acid molecule. In one embodiment, the recombinant vector may include a nucleic acid molecule encoding a light chain variable region or a light chain and a nucleic acid molecule encoding a heavy chain variable region or heavy chain, respectively (e.g., in two separate vectors) or all together (e.g., in one vector). A recombinant vector can be used as an expression vector.

Another embodiment provides a recombinant cell containing a nucleic acid molecule or a recombinant vector.

Another embodiment provides a method for producing an anti-LILRB1 antibody, or antigen-binding fragment thereof, comprising expressing the nucleic acid molecule in a cell. The step of expressing the nucleic acid molecule may include culturing the recombinant cell.

As described herein, an antigen-binding fragment of an anti-LILRB1 antibody may refer to a fragment derived from an anti-LILRB1 antibody and retaining the binding affinity of the antibody for antigen (LILRB1). In one embodiment, the antigen-binding fragment may be a polypeptide comprising the 6 CDRs of an anti-LILRB1 antibody as described above and, for example, may be scFv, scFv-Fc, scFv-Ck (kappa constant region), scFv-Cλ (constant lambda region), (scFv) ₂ , Fab, Fab' or a F(ab') ₂ , but not limited to. In one embodiment, the antigen binding fragment may be an scFv, a fusion polypeptide (scFv-Fc), wherein the scFv is fused to the Fc region of an immunoglobulin (e.g., IgA, IgD, IgE, IgG (IgG1, IgG2, IgG3, IgG4), IgM, etc. .e) or a fusion polypeptide (scFv-Ck or scFv-Cλ) wherein the scFv is fused to a light chain constant region (eg, kappa or lambda).

An anti-LILRB1 antibody, or antigen-binding fragment thereof, may have regulatory activity, such as antagonistic or agonistic activity, for the LILRB1 protein. In addition, an anti-LILRB1 antibody or antigen-binding fragment thereof may have the activity of blocking the binding of LILRB1 to MHC class I and/or interaction between LILRB1 and MHC class I. cancer cell surveillance. Moreover, an anti-LILRB1 antibody, or an antigen-binding fragment thereof, may have an anti-cancer effect.

The LILRB1 protein, which is the antigen of the anti-LILRB1 antibody or antigen-binding fragment thereof provided in the present disclosure, can be obtained from a mammal. For example, LILRB1 as an antigen may be human LILRB1 (e.g. GenBank accession numbers AAH15731.1 (SEQ ID NO:348), NP_001265328.2, NP_001265327.2, NP_001075108.2, NP_001075107.2, NP_001075106.2, NP _006660 .4, NM_001081637.2, NM_001081638.3, NM_001081639.3, NM_001278398.2, NM_001278399.2 etc.), but not limited to this.

Class I MHC may be one of the classes of major histocompatibility complex (MHC) molecules. In one embodiment, the class I MHC may be a human class I MHC, and may be at least one selected from the group consisting of HLA (human leukocyte antigen)-A, HLA-B, HLA-C, HLA-E, HLA -F and HLA-G, but not limited to.

As described herein, the term "antibody" may refer to a protein that specifically binds to a specific antigen, and may be a protein produced by stimulation of an antigen in the immune system, or a protein obtained by chemical synthesis or obtained recombinantly, without particular limitation. The antibody may be non-naturally occurring, eg recombinantly or synthetically. The antibody may be an animal antibody (eg, a mouse antibody, etc.), a chimeric antibody, a humanized antibody, or a human antibody. The antibody may be a monoclonal or polyclonal antibody.

In an anti-LILRB1 antibody or antigen-binding fragment provided herein, the portion, excluding portions of the heavy chain CDR and light chain CDR or heavy and light chain variable regions as defined above, may be derived from any immunoglobulin subtype (e.g., IgA , IgD, IgE, IgG (IgG1, IgG2, IgG3, IgG4), IgM, etc.), and, for example, derived from the frame parts, and/or light chain constant region, and/or heavy chain constant region. In one embodiment, the anti-LILRB1 antibody provided in the present disclosure may be a human IgG antibody, such as, but not limited to, IgG1, IgG2, IgG3, or IgG4.

An intact antibody (eg, IgG type) has a structure with two full length light chains and two full length heavy chains, in which each light chain is linked to the corresponding heavy chain via a disulfide bond. The constant region of an antibody is divided into a heavy chain constant region and a light chain constant region. The heavy chain constant region is of type gamma (γ), mu (μ), alpha (α), delta (δ) or epsilon (ε) and has gamma1 (γ1), gamma2 (γ2), gamma3 (γ3), gamma4 ( γ4), alpha1 (α1) or alpha2 (α2) as its subclass. The light chain constant region is either of the kappa (κ) or lambda (λ) type.

In the context of the present application, the term “heavy chain” may encompass full-length heavy chains and fragments thereof, and a full-length heavy chain may include a VH variable region containing amino acid sequences sufficient to provide antigen specificity, three constant regions CH1, CH2 and CH3 and a hinge. The term “light chain” may encompass full length light chains and fragments thereof, wherein a full length light chain may include a VL variable region containing amino acid sequences sufficient to provide antigen specificity and a CL constant region.

The term “complementarity determining region (CDR)” may refer to the portion that confers antigen-binding specificity to the variable region of an antibody, and may refer to an amino acid sequence found in the hypervariable region of an immunoglobulin heavy chain or light chain. The heavy and light chains may respectively include three CDRs (CDRH1, CDRH2 and CDRH3; and CDRL1, CDRL2 and CDRL3). The CDR may provide contact residues that play an important role in the binding of an antibody to its antigen or antigen epitope. In the context of the present application, the terms "specifically binding" and "specifically recognizing" may have the same general meaning known to those skilled in the art and indicate that the antibody and antigen specifically interact with each other, resulting in an immunological reaction.

In the present disclosure, unless otherwise indicated, the term "antibody" may encompass not only an intact antibody, but also an antigen-binding fragment of an antibody having antigen-binding ability.

The term “antigen-binding fragment” as used herein may refer to any type of polypeptide that includes a moiety (e.g. 6 CDRs as described herein) capable of binding to an antigen and, for example, may be an scFv, (scFv ) ₂ , scFv-Fc, Fab, Fab′ or F(ab′) ₂ , but not limited to this. In addition, as described above, the antigen binding fragment may be an scFv, a fusion polypeptide, wherein the scFv is fused to an immunoglobulin Fc region (e.g., IgA, IgD, IgE, IgG (IgG1, IgG2, IgG3, IgG4), IgM, etc. ) or a constant region (like kappa or lambda).

Among the antigen-binding fragments, the Fab includes the light chain and heavy chain variable regions, the light chain constant region, and the first CH1 heavy chain constant region.

Fab' differs from Fab in that Fab' includes a hinge region having at least one cysteine residue at the C-terminus of CH1.

F(ab') ₂ antibody is formed by disulfide bonding of cysteine residues in the Fab' hinge region.

Fv is the minimum antibody fragment consisting of only the heavy chain variable region and the light chain variable region. Recombinant methods for obtaining an Fv fragment are widely known in the art.

The double chain Fv includes a heavy chain variable region and a light chain variable region that are non-covalently linked to each other. A single chain Fv typically includes a heavy chain variable region and a light chain variable region that are covalently linked to each other via a peptide linker or directly linked at the C-terminus to form a dimeric structure similar to a double-chain Fv.

Antigen-binding fragments can be generated using a protease (eg, a Fab can be generated by restrictive digestion of the whole antibody with papain and an F(ab') ₂ fragment can be generated by digestion with pepsin) or can be generated using a genetic recombination technique.

The term "hinge region" may refer to the region between the CH1 and CH2 domains in the heavy chain of an antibody, the function of which is to provide flexibility to the antigen-binding site in the antibody.

The anti-LILRB1 antibody may be a monoclonal or polyclonal antibody, and is, for example, a monoclonal antibody. The monoclonal antibody can be obtained using a method widely known in the art, for example, using the phage display method. Alternatively, the anti-LILRB1 antibody can be constructed as a mouse monoclonal antibody in a conventional manner.

At the same time, individual monoclonal antibodies can be screened using a typical ELISA (enzyme immunoassay) format based on the binding potential with respect to LILRB1. Inhibitory activity can be tested using a functional assay, such as a competitive ELISA to test for molecular interactions of binding structures, or a functional assay, such as a cellular assay. Then, with respect to representatives of monoclonal antibodies selected on the basis of their strong inhibitory activity, their affinities (Kd values) for LILRB1 can be tested.

The pharmaceutical composition may further include a pharmaceutically acceptable carrier in addition to the active ingredient (anti-LILRB1 antibody or antigen-binding fragment thereof). The pharmaceutically acceptable carrier may be any of those commonly used to prepare antibody compositions. For example, the pharmaceutically acceptable carrier may be one or more selected from the group consisting of lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum arabic, calcium phosphate, alginates, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water. , syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, and the like, but are not limited to. The pharmaceutical composition may further include one or more substances selected from the group consisting of a diluent, excipient, lubricant, wetting agent, sweetener, flavor enhancer, emulsifier, suspending agent, preservative, and the like, which can usually be used to obtain a pharmaceutical compositions.

The pharmaceutical composition or the antibody or antigen-binding fragment thereof can be administered orally or parenterally in a pharmaceutically effective amount. Parenteral administration may be intravenous injection, subcutaneous injection, muscle injection, intraperitoneal injection, endothelial administration, intranasal administration, intrapulmonary administration, rectal administration, or topical administration to the lesion. Since proteins or peptides are degraded upon oral administration, the active ingredient in oral compositions may be coated or formulated to prevent degradation in the stomach. In addition, the antibody or compositions can be administered using an optional device that allows the active ingredient to be delivered to target cells (eg, cancer cells).

The anti-LILRB1 antibody, or antigen-binding fragment thereof, may be included in a pharmaceutical composition or may be administered to a subject in a pharmaceutically effective amount. In the context of the present application, the term "pharmaceutically effective amount" may refer to the amount of the active ingredient (antibody or fragment thereof), in which the active ingredient can exhibit the desired effect (for example, anticancer effect). A pharmaceutically effective amount can be determined in various ways depending on various factors such as age, body weight, sex, pathological conditions, diet, rate of excretion and/or allergic reaction of the subject, types of drug, time of administration, interval between administrations, route of administration. , method of administration, etc. For example, an anti-LILRB1 antibody or an antigen-binding fragment thereof can be administered in an amount of 0.005 μg/kg - 1000 mg/kg, 0.005 μg/kg - 500 mg/kg, 0.005 μg/kg - 250 mg/ kg, 0.005 mcg/kg - 100 mg/kg, 0.005 mcg/kg - 75 mg/kg, 0.005 mcg/kg - 50 mg/kg, 0.01 mcg/kg - 1000 mg/kg, 0.01 mcg/kg - 500 mg/kg, 0.01 mcg/kg - 250 mg/kg, 0.01 mcg/kg - 100 mg/kg, 0.01 mcg/kg - 75 mg/kg, 0.01 mcg/kg - 50 mg/kg, 0.05 mcg/kg - 1000 mg/kg, 0.05 mcg/kg - 500 mg/kg, 0.05 mcg/kg - 250 mg/kg, 0.05 mcg/kg - 100 mg/kg kg, 0.05 mcg/kg - 75 mg/kg or 0.05 mcg/kg - 50 mg/kg per day, but not limited to this. The daily dose may be formulated into a single dosage form as a single dosage form, or formulated into dosage forms suitably divided, or may be formulated to be contained in a multi-dose container.

Pharmaceutical compositions may be formulated as an oily or aqueous solution, suspension, syrup, emulsifying solution, extract, powder, granule, tablet or capsule, and may further include a dispersing or stabilizing agent to formulate the composition.

The subject for which the antibody, pharmaceutical composition, or method of this disclosure is applied may be selected from mammals, including mammals including primates such as humans and monkeys, rodents such as rats and mice, and the like.

The cancer can be solid cancer or cancer of the blood. The cancer may be, but is not limited to, one or more selected from the group consisting of lung cancer (e.g., squamous cell lung cancer, small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma), peritoneal carcinoma, skin cancer, squamous cell carcinoma, melanoma of the skin or eyeball, rectal cancer, cancer of the area near the anus, cancer of the esophagus, tumor of the small intestine, endocrine cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, cancer of the urethra, leukemia (for example, chronic or acute leukemia), lymphocytic lymphoma, hepatoma, gastric cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatocellular adenoma, breast cancer, bowel cancer, colon cancer, endometrial carcinoma, or uterine carcinoma , salivary gland tumors, renal cell carcinoma, kidney cancer, prostate cancer, vulvar cancer, thyroid cancer, head and neck cancer, brain cancer, biliary tract cancer, gallbladder cancer, bone osteosarcoma, etc. Cancer can be primary cancer or metastatic cancer. The cancer may be a cancer characterized by expression or overexpression of MHC class I on the surface of the cancer cell, and, for example, may be colon adenocarcinoma, small cell lung carcinoma, breast cancer, pancreatic cancer, malignant melanoma, bone osteosarcoma, renal cell carcinoma. carcinoma or cancer of the stomach. Overexpression of MHC class I may refer to overexpression over normal cells or cancer cells that are unresponsive or resistant to immunotherapy, such as T cell mediated immunotherapy (eg, cytotoxic T cells).

In the context of this application, the term “cancer treatment” may refer to all anti-cancer activities that prevent, alleviate or improve the symptoms of cancer or partially or completely remove cancer, such as cancer cell death, inhibition of cancer cell proliferation, inhibition of cancer metastasis, and the like. .

An anti-LILRB1 antibody or antigen-binding fragment thereof as provided herein may be co-administered with another drug, e.g., at least one selected from the group consisting of commonly used immunotherapy agents, anticancer agents, cytotoxic agents, etc. n. Accordingly, an embodiment provides a pharmaceutical composition for combined administration for the treatment and/or prevention of cancer, comprising (1) an anti-LILRB1 antibody, or an antigen-binding fragment thereof, and (2) at least one of an agent selected from the group consisting of agents for immunotherapy, anti-cancer agents, cytotoxic agents, and the like. Another embodiment provides a method for treating and/or preventing cancer, comprising administering (1) an anti-LILRB1 antibody or antigen-binding fragment thereof, and (2) at least one of the agents selected from the group consisting of immunotherapy agents, anticancer agents, cytotoxic agents, and the like, to a subject in need of cancer treatment and/or prevention. Immunotherapy agents, anti-cancer agents, cytotoxic agents may include any drugs which are commonly used in the treatment of cancer and/or which have cytotoxic activity and, for example, they may be at least one selected from the group consisting of proteins, such as antibodies, nucleic acid molecules such as siRNAs, and/or small molecule chemicals such as, but not limited to, paclitaxel, docetaxel, and the like.

Another embodiment provides a polypeptide molecule comprising a heavy chain complementarity determining region (CDR-H1, CDR-H2, CDR-H3, or a combination thereof), a light chain complementarity determining region (CDR-L1, CDR-L2, CDR-L3, or a combination thereof). ), their combination; or a heavy chain variable region, a light chain variable region, or a combination thereof, of an anti-LILRB1 antibody as described above. The polypeptide molecule can be used in the production of an antibody as an antibody precursor, or it can be incorporated into a protein scaffold having an antibody-like structure (eg, a peptide body), a bispecific antibody, or a multispecific antibody as a component thereof. In another embodiment, the polypeptide molecule can be used as a target (antigen) recognition domain or secreted antibody in a targeted therapy cell therapy such as CAR-T. In another embodiment, the polypeptide molecule can be used to construct anti-LILRB1 antibody secreting cells as a cell therapy.

Another embodiment provides a nucleic acid molecule encoding a complementarity determining region of a heavy chain (CDR-H1, CDR-H2, CDR-H3, or a combination thereof), a heavy chain variable region, or the heavy chain of an anti-LILRB1 antibody.

Another embodiment provides a nucleic acid molecule encoding a complementarity determining light chain region (CDR-L1, CDR-L2, CDR-L3, or a combination thereof), a light chain variable region, or a light chain of an anti-LILRB1 antibody.

Another embodiment provides a recombinant vector comprising a nucleic acid molecule encoding the heavy chain variable region or heavy chain of an anti-LILRB1 antibody and the light chain variable region or light chain of an anti-LILRB1 antibody, respectively, in two separate vectors or together in one vector.

Another embodiment provides a recombinant cell containing a nucleic acid molecule or a recombinant vector.

The term “vector” refers to means for expressing a target gene in a host cell, such as a plasmid vector, a cosmid vector, and a viral vector such as a bacteriophage vector, a lentiviral vector, an adenovirus vector, a retroviral vector, and an adeno-associated viral vector. The recombinant vector can be constructed from a plasmid (e.g., pSC101, pGV1106, pACYC177, ColE1, pKT230, pME290, pBR322, pUC8/9, pUC6, pBD9, pHC79, pIJ61, pLAFR1, pHV14, pGEX series, pET series, pUC19, etc.). etc.), phage (eg, λgt4λB, λ-Charon, λδz1, M13, etc.) or viral vector (eg, SV40, etc.), which are commonly used in the art, or by manipulation.

In a recombinant vector, the nucleic acid molecule may be operably linked to a promoter. The term “operably linked” refers to a functional relationship between a nucleotide sequence of interest and an expression control sequence (eg, a promoter sequence). By being "operably linked", a regulatory element can control transcription and/or translation of a polynucleotide of interest.

The recombinant vector may be constructed, typically as a cloning or expression vector. For recombinant expression vectors, a vector commonly available in the art for expressing a foreign protein in plant, animal, or microbial cells can be used. Various methods well known in the art can be used to construct recombinant vectors.

For use in hosts, such as prokaryotic or eukaryotic cells, the recombinant vector can be designed accordingly. For example, when a vector is designed as an expression vector for use in a prokaryotic host, the vector typically includes a strong promoter for transcription (e.g., pLλ promoter, CMV promoter, trp promoter, lac promoter, tac promoter, T7 promoter, etc.), a binding site ribosomes for translation initiation and transcription/translation termination sequences. On the other hand, an expression vector for use in a eukaryotic host includes an origin of replication operable in a eukaryotic cell such as an f1 origin, an SV40 origin of replication, a pMB1 origin of replication, an adeno origin of replication, an AAV origin of replication, and an origin of replication BBV replication, but not limited to. In addition, the expression vector typically includes a promoter derived from mammalian cell genomes (e.g., metallothionein promoter) or from mammalian viruses (e.g., adenovirus late promoter, vaccinia 7.5K promoter, SV40 promoter, cytomegalovirus promoter, HSV tk promoter, etc.) , and a polyadenylation sequence as a transcription termination sequence.

A recombinant cell can be obtained by introducing a recombinant vector into a suitable host cell. Provided that this allows consistent cloning and expression of the recombinant vector in a stable manner, any host cell known in the art can be used in the present invention. Examples of a prokaryotic host cell available for the present invention may be selected from E. coli, e.g. E. coli JM109, E. coli BL21, E. coli RR1, E. coli LE392, E. coli B, E. coli X 1776 , E. coli W3110, Bacillus spp., such as Bacillus subtilis and Bacillus thuringiensis, and strains of enterobacteria, such as Salmonella typhimurium , Serratia marcescens , and various Pseudomonas species. Eukaryotic host cells that can be used for transformation can be selected from, but not limited to, Saccharomyces cerevisiae , insect cells, and animal cells such as Sp2/0, CHO (Chinese Hamster Ovary) K1, CHO DG44, CHO S , CHO DXB11, CHO GS-KO, PER.C6, W138, BHK, COS-7, 293, HepG2, Huh7, 3T3, RIN, MDCK, etc.

The nucleic acid molecule, or a recombinant vector carrying it, can be introduced (transfected) into a host cell using a method well known in the relevant art. For example, this transfection can be performed using CaCl ₂ or the electroporation method when the host cell is prokaryotic. For eukaryotic host cells, genetic introduction can be achieved using, but not limited to, microinjection, calcium phosphate precipitation, electroporation, liposome-mediated transfection, or particle bombardment.

To select a transformed host cell, one can take advantage of the phenotype associated with the selectable marker, according to methods well known in the art. For example, when the selectable marker is a gene conferring resistance to a particular antibiotic, host cells can be grown in the presence of the antibiotic in media to select the transformant of interest.

Another embodiment provides a method for producing an anti-LILRB1 antibody, or antigen-binding fragment thereof, comprising expressing the nucleic acid molecule or recombinant vector in a host cell. The expression step can be carried out by culturing the recombinant cell comprising the nucleic acid molecule (eg, in a recombinant vector) under conditions that allow expression of the nucleic acid molecule. The method may further include isolating and/or purifying the antibody or fragment thereof from the cell culture after the expression or culture step.

Useful effects

The anti-LILRB1 antibody or antigen-binding fragment thereof provided in the present disclosure can have a strong anti-cancer effect by inhibiting the immune surveillance evasion mechanism of cancer cells, allowing the immune cells to exert their anti-cancer effect.

Description of drawings

1 is an electrophoresis showing the results of SDS-PAGE gel analysis of anti-LILRB1 antibodies purified in the example.

2 is a sensorgram showing the results of an SPR (surface plasmon resonance) analysis for anti-LILRB1 antibody B3 according to the example.

3 is a sensogram showing the results of the SPR analysis for the anti-LILRB1 antibody E3 according to the example.

4a is a graph showing the binding capacity of anti-LILRB1 antibody A10 according to the natural human killer cell example, KHYG-1; 4b is a graph showing the binding capacity of the anti-LILRB1 antibody E3 according to the natural human killer cell example, KHYG-1; and FIG. 4c is a graph showing the binding ability of a human IgG4 antibody as an isotype control to a natural human killer cell, KHYG-1.

5 is a graph showing the level of binding of recombinant LILRB1-Fc proteins to an HLA-G overexpressing cell surface measured by the iQue screening device when treated with anti-LILRB1 antibodies according to the example and human IgG4 antibody as an isotype control, respectively.

6 is a graph showing the in vivo anti-tumor effects of anti-LILRB1 antibodies E3 and B3 according to the example.

7a-7d are flow cytometry diagrams of anti-LILRB1 antibody E3.1 binding according to the example of cells expressing various members of the human LILR family.

8a-8d are flow cytometry diagrams of the binding of anti-LILRB1 antibody H11, as exemplified, to cells expressing various members of the human LILR family.

9 is a graph showing the level of release of granzyme B in a natural human killer cell, KHYG-1, when treated with anti-LILRB1 antibody E3.1 or H11 according to the example, compared to a cell treated with a control antibody (human IgG4 isotype).

10 is a graph showing the level of perforin release in a natural human killer cell, KHYG-1, when treated with anti-LILRB1 antibody E3.1 or H11 according to the example, compared to a cell treated with a control antibody (human IgG4 isotype).

11 is a graph showing the results of a luciferase reporter assay to evaluate the ability of anti-LILRB1 antibodies E3.1 or H11 according to the example to block the LILRB1 signaling pathway.

12 is a graph showing the in vivo anti-cancer effects of anti-LILRB1 antibodies E3.1 and H11 according to the example.

Method for carrying out the invention

Hereinafter, the present invention will be described in detail by way of examples.

The following examples are only intended to illustrate the invention and are not intended to limit the invention.

Example 1: Obtaining human antibodies against LILRB1

1.1. Selection of human antibodies against LILRB1 using phage display

To select antibodies that specifically recognize human LILRB1, phage display screening was performed using a library consisting of human scFv antibodies. Human LILRB1-His (cat. no. 8989-T2) and human LILRB1-Fc (cat. no. 2017-T2) (RnD systems) were used as antigen, respectively. For use, each antigen was conjugated to biotin using the EZ-Link Sulfo-NHS-Biotin kit (ThermoFisher Scientific).

Phage display screening was performed using all 4 types of LILRB1 antigens (LILRB1-His, LILRB1-Fc, LILRB1-His-Biotin and LILRB1-Fc-Biotin) through solid phase and solution screening. Additional screens were performed by gradually reducing the concentration of the antigen used, competitive elution with control antibodies against LILRB1, negative selection for Fc using LILRB1-Fc as antigen, etc. Selected products were confirmed for their antigen binding using polyclonal phage ELISA.

1.2. Screening and analysis of monoclonal soluble scFv

The scFv-encoding genes whose antigen binding was confirmed in Example 1.1 were amplified by PCR to obtain expression vectors. For each selection, a certain number of transformants were transferred to a 96-well culture plate for screening. ScFv antibodies were expressed using Autoinduction medium (Studier, F.W. (2005) Protein Expression and Purification 41, 207-34) and then analyzed for their antigen binding using the DELFIA immunoassay (PerkinElmer). In addition, a certain amount of each scFv antibody was allowed to be captured on the surface, followed by DELFIA on the antigen to determine a rating score based on antigen-antibody binding affinity.

1.3. Converting screened scFvs to IgG antibodies

Of the clones whose antigen binding was confirmed in Example 1.2, a total of 376 clones were selected, and the DNA sequences of the genes encoding the selected scFvs were analyzed by total DNA sequencing to remove duplicate clones. In addition, a total of 93 clones were selected based on the antigen-antibody binding affinity score determined in Example 1.2. The genes encoding the heavy chain variable region (VH) and the light chain variable region (VL), respectively, were amplified by PCR from each of the genes encoding the selected scFvs and inserted into an expression vector (pTRIOZ-hIgG4, InvivoGen; alternatively, one can use any of the vectors comprising the CMV promoter or the CMV/CHO beta-actin fusion promoter (KR10-1038126B1) and the genes encoding the heavy chain constant region and the human IgG4 kappa or lambda light chain constant region), wherein the expression vector was designed to encode human IgG4 antibody (IgG4 Fc: SEQ ID NO:341, kappa constant region: SEQ ID NO:342, lambda constant region: SEQ ID NO:343). The DNA sequence of the expression vector was confirmed by sequencing.

1.4. Obtaining Selected Antibodies

The vectors constructed in Example 1.3 were purified using the Plasmid Plus Maxi kit (Qiagen). Purified vectors were used to express antibodies in ExpiCHO-S™ cells or Expi293™ cells.

Specifically, the vectors constructed in Example 1.3 were transfected into ExpiCHO-S™ cells (Gibco) (1.5×10 ⁸ cells/25 ml culture volume) by adding 80 μl of ExpiFectamine™ CHO reagent (Thermo Fisher). One day after transfection, 150 μl ExpiCHO™ Enhancer (Thermo Fisher) and 4 ml ExpiCHO™ Feed (Thermo Fisher) were added to the culture. On day 5, 4 ml of ExpiCHO™ Feed was added to the culture. Transfected cells were cultured under conditions at 32°C and 5% CO ₂ for a total of 7-11 days.

In addition, the vectors constructed in Example 1.3 were transfected into Expi293F™ cells (Gibco) (3×10 ⁸ cells/100 ml culture volume) by adding 320 μl of ExpiFectamine™ 293 reagent (Gibco) according to the manufacturer's protocol. One day after transfection, ExpiFectamine™ 293 Enhancer 1 (Thermo Fisher), ExpiFectamine™ Enhancer 2 (Thermo Fisher) and glucose were added at 0.6 ml per 100 ml culture volume, 6 ml per 100 ml culture volume and 3.6 g per liter, respectively. Transfected cells were cultured under conditions at 36.5°C and 5% CO ₂ for a total of 5 days. The cultured cells of the two types, respectively, were centrifuged at 4000 rpm at 4° C. for 20 minutes and then filtered using a 0.22 μm bottle-top filter system (Corning). The culture supernatant was collected and purified using AKTA Pure L (GE Healthcare). The culture supernatant was loaded into AKTA Pure L equipped with a 1 ml Hitrap MabSelectSure column (GE healthcare) at a flow rate of 1 ml/min and the column was washed with 20 column volumes (CV) of 1X PBS. An elution buffer (0.1 M sodium citrate buffer, pH 3.4) was then loaded onto the column to elute the protein of interest. The eluate was concentrated using an Amicon Ultra Filter Device (MWCO 10K, Merck), centrifuged and buffer exchanged with 1X PBS buffer.

Purified antibody samples were diluted with 1X PBS to a final concentration of about 1 mg/mL. Ten (10) µl of reconstituted loading buffer (3X) or non-reducing loading buffer (3X) and 20 µl of purified antibody sample were mixed and left in a heating bath at 95°C for 2 minutes, and then removed from the bath and cooled. The sample was injected into an SDS-PAGE gradient gel (4-20% or 4-12%) on an electrophoresis device at 10 μg per well and developed on the gel. To analyze the molecular weight of the sample, two-color Precision Plus Protein™ (BIO-RAD) standards were injected into another separate well. The gel was stained with Coomassie staining solution and decolorized to obtain images of the gel.

Of the 93 antibodies, gel electrophoresis images for antibodies A10, B3, E3, G1, G9, and H2 are representatively shown in FIG. As shown in Fig. 1, the production of antibodies having a disulfide bond was confirmed.

1.5. Binding affinity analysis of selected antibodies

The binding affinity of the 93 antibodies selected in Example 1.3 to the antigen, LILRB1, was measured using a Biacore T200 (GE healthcare). An anti-human IgG (Fc) antibody (GE healthcare, catalog # BR-1008-39, final concentration 25 μg/ml) was passed at a flow rate of 5 μl/min for 360 seconds to immobilize at 5000-7000 RU on a CM5 sensor chip S Series (GE healthcare, p/n BR-1005-30) using the Amine Coupling Kit (GE healthcare, p/n BR-1000-508). The antigen, human LILRB1 protein (LILRB1-His, RnD systems cat# 8989-T2), was injected at 4~9 different concentrations from 3.13 nM to 1600 nM at a flow rate of 30 µl/min to determine k _a and k _d values , as shown in Table 3, and the K _D value was calculated.

Of the 93 antibodies, 20 _antibodies showing excellent binding affinity (K _D values) were selected and are shown in Table 3. an E3 antibody showing a LILRB1 binding affinity (K _D ) of about 101.2 nM is shown in Figures 2 and 3, respectively (Figure 2: SPR sensorgram for B3, Figure 3: SPR sensorgram for E3):

Table 3 Antigen binding affinity (K _D ) of anti-LILRB1 antibodies to human LILRB1 clone name k _a (× 10 ⁵ ) (1/ms) k _d (× 10 ^-4 ) (1/sec) K _D (nM) A10 0.504 76.5 152 A11 0.001801 9.814 5448 B3 0.149 14.87 99.8 B9 0.09324 6.16 66.1 B12 1.84 14.42 7.84 D1 1.165 57.44 49.33 D3 0.0311 5.58 180 E3 0.3460 35.00 101.2 E4 0.1065 7.73 72.55 E6 0.2679 16.27 60.73 E9 0.105 10.48 99.86 E12 2.331 102.6 44.01 F11 2.72 6.15 2.26 F12 2.811 9.731 3.462 G1 4.33 14.19 3.28 G6 2.58 152.4 59.06 G9 1.43 4.36 3.05 G11 0.454 20.53 45.23 H2 5.865 95 16.20 H11 2.962 22.57 7.621

1.6. Sequence Analysis of Selected Antibodies

In the 20 antibodies that were assayed for antigen binding affinity in Example 1.5, the amino acid sequences of the CDRs defined according to Kabat numbering, light chain variable region, heavy chain variable region, light chain and heavy chain, and the nucleic acid sequence encoding the light chain variable region and the heavy chain variable region were analyzed using common amino acid sequencing and DNA sequencing methods and are presented in Tables 4-23:

Table 4 E3 antibody clone Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 QGDSLRNFYAS 1 CDR-L2 GKNNRPS 2 CDR-L3 NSRDSSGSHLTGV 3 CDR-H1 SYAMS 4 CDR-H2 AISGSGGSTYYADSVKG 5 CDR-H3 DTYYYGSGRSNAFDI 6 light chain variable region SYELTQDPAVSVALGQTVRITCQGDSLRNFYASWYQQKSGQAPVLVMYGKNNRPSGIPDRFSGSTSGNTASLTITGAQAEDEADYYCNSRDSSGSHLTGVFGGGTKVTVLGQPAAA 221 light chain variable region gene TCCTATGAGCTGACTCAGGACCCTGCTGTGTCTGTGGCCTTGGGACAGACAGTCAGGATCACATGCCAGGGAGACAGCCTCAGAAACTTTTATGCAAGCTGGTACCAGCAGAAGTCAGGACAGGCCCCAGTTCTTGTCATGTATGGTAAAAACAACCGGCCCTCAGGGATCCCAGACCGATTCTCTGGCTCCACCTCAGGAAACACAAGCTTCCTTGACCATCACTGGG GCTCAGGCGGAAGATGAGGCTGACTATTACTGTAACTCCCGGGACAGCAGTGGTAGCCATTTGACGGGCGTATTCGGCGGAGGGACCAAGGTCACCGTCCTAGGTCAGCCCGCGGCCGCA 261 heavy chain variable region QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMISLRAEDTAVYYCARDTYYYGSGRSNAFDIWGQGTLVTVSS 222 heavy chain variable region gene CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGTCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCC AGAGACAATTCCAAGAATACGCTGTATCTGCAAATGATTAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATACGTATTACTATGGTTCGGGGAGAAGTAATGCTTTTGATATATGGGGCCAGGGAACCCTGGTCACCGTCTCGAGT 262 light chain (lambda) SYELTQDPAVSVALGQTVRITCQGDSLRNFYASWYQQKSGQAPVLVMYGKNNRPSGIPDRFSGSTSGNTASLTITGAQAEDEADYYCNSRDSSGSHLTGVFGGGTKVTVLGQPAAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVT HEGSTVEKTVAPTECS 301 heavy chain QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMISLRAEDTAVYYCARDTYYYGSGRSNAFDIWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTK TYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 302

Table 5 B3 antibody clone Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 QASQDISNYLN 7 CDR-L2 DASNLET 8 CDR-L3 QQYDNLP 9 CDR-H1 DYAMH 10 CDR-H2 GISWNSGSIGYADSVKG eleven CDR-H3 VGDSSGWSDAFDI 12 light chain variable region DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPFGGGTKVDIKRTAAA 223 light chain variable region gene GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAAGTCACCATCACTTGCCAGGCGAGTCAGGACATTAGCAACTATTTGAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTACGATGCATCCAATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTG CAGCCTGAAGATATTGCAACATATTACTGTCAACAGTATGATAATCTCCCTTTCGGCGGAGGGACCAAAGTGGATATCAAACGTACCGCGGCCGCA 263 heavy chain variable region EVQLLESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVGDSSGWSDAFDIWGQG™VTVSS 224 heavy chain variable region gene GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGCAGGTCCCTGAGACTCTCCTGTGTCAGCCTCTGGATTCACCTTTGATGATTATGCCATGCACTGGGTCCGGCAAGCTCCAGGGAAGGGCCTGGAGTGGGTCTCAGGTATTAGTTGGAATAGTGGTAGCATAGGCTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGAC AATTCCAAGAACACGCTGTATCTTCAAATGAACAGTCTGAGAGCCGAGGACACGGCCGTGTATTACTGTGCGAGAGTTGGGGATAGCAGTGGCTGGTCCGATGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCGAGT 264 light chain (kappa) DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPFGGGTKVDIKRTAAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK HKLYACEVTHQGLSSPVTKSFNRGEC 303 heavy chain EVQLLESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVGDSSGWSDAFDIWGQG™VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTY TCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 304

Table 6 A10 antibody clone Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 RASQSVSSNLA 13 CDR-L2 GASTRAT 14 CDR-L3 QQYGSPRMYT 15 CDR-H1 SYAIS 16 CDR-H2 GIIPIFGTANYAQKFQG 17 CDR-H3 GGLGELDNWFDP 18 light chain variable region DIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYGSPRMYTFGQGTKVDIKRTAAA 225 light chain variable region gene GATATTGTGATGACACAAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCACCAGGGCCACCGGTATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCAC CATCAGCAGCCCTGCAGTCTGAAGATTTTGCAGTTTATTACTGTCAGCAGTATGGTAGCTCACCTCGGATGTACACTTTTGGCCAGGGGACCAAAGTGGATATCAAACGTACCGCGGCCGCA 265 heavy chain variable region QMQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADKSISTAYMELSSLRSEDTAVYYCARGGLGELDNWFDPWGQGTLVTVSS 226 heavy chain variable region gene CAAATGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCTTCTGGAGGCACCTTCAGCAGCTATGCTATCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGTGGGATCATCCCTATCTTTGGTACAGCAAACTACGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGA CAAATCCATCAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAGGCGGCCTCGGGGAGTTGGACAACTGGTTCGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGT 266 light chain (kappa) DIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYGSSPRMYTFGQGTKVDIKRTAAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKLYACE VTHQGLSSPVTKSFNRGEC 305 heavy chain . TYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 306

Table 7 G1 antibody clone Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 SGYKLGDRYVS 19 CDR-L2 KDSQRPS 20 CDR-L3 QAWDSGTGV 21 CDR-H1 SYGIS 22 CDR-H2 WISAYNGNTNYAQELQG 23 CDR-H3 VGVAGKLDY 24 light chain variable region SYELTQPPSLSVSPGQTASITCSGYKLGDRYVSWYQQKTGQSPVVVIYKDSQRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSGTGTGVFGGGTKLTVLGQPAAA 227 light chain variable region gene TCCTATGAGCTGACTCAGCCACCCTCACTGTCCGTGTCCCCAGGACAGACAGCCAGCATCACCCTGCTCAGGATATAAACTGGGAGATAGATATGTTTCCTGGTATCAGCAGAAGACAGGCCAGTCCCCTGTGGTGGTCATCTATAAAGATAGCCAGCGGCCCTCAGGGTCCCTGAACGATTCTCTGGCTCCAACTCTGGAACACAGCCACTCTGACCATCAGCGG GACCCAGGCTATGGATGAGGCTGACTATTACTGTCAGGCGTGGGACAGCGGCACTGGGGTATTCGGCGGAGGACCAAGCTGACCGTCCTAGGTCAGCCCGCGGCCGCA 267 heavy chain variable region EVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQELQGRV™TTDTSTSTAYMELRSLRSDDTAVYYCARVGVAGKLDYWGQGTLVTVSS 228 heavy chain variable region gene GAAGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCTTCTGGAGGCACCTTCAGCAGCTATGGTATCAGCTGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGCTTACAATGGTAACACAAACTATGCACAGGAGCTCCAGGGCAGAGTCACCATGACCACAGAC ACATCCACGAGCACAGCCCTATATGGAGCTGAGGAGCCTGAGATCTGACGACACGGCCGTGTATTACTGTGCGAGAGTAGGGGTGGCTGGTAAACTTGACTACTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT 268 light chain (lambda) SYELTQPPSLSVSPGQTASITCSGYKLGDRYVSWYQQKTGQSPVVVIYKDSQRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSGTGTGVFGGGTKLTVLGQPAAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKEDSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQ VTHEGSTVEKTVAPTECS 307 heavy chain EVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQELQGRV™TTDTSTSTAYMELRSLRSDDTAVYYCARVGVAGKLDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTC NVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 308

Table 8 G9 antibody clone Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 TGSSSDVGGYNYVS 25 CDR-L2 DVSNRPS 26 CDR-L3 SSYTGSSTLDVL 27 CDR-H1 SYWIG 28 CDR-H2 IIYPGDSDTRYSPSFQG 29 CDR-H3 QYYDGGYYMDV thirty light chain variable region QSALTQPASVSGSPGQSITISCTGSSSDVGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGVSDRFSGSKSGNMASLTISGLQAEDEADYYCSSYTGSSTLDVLFGGGTKLTVLGQPAAA 233 light chain variable region gene CAGTCTGCGCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAAGCAGCAGTGACGTTGGTGGTTATAACTATGTCTCCTGGTACCAGCAACACCCAGGCAAAGCCCCCAAACTCATGATTATGATGTCAGTAATCGGCCCTCAGGGGTTTCTGATCGCTTCTCTGGCTCCAAGTCTGGCAACATGGCTCCCTGACCAT CTCTGGGCCTCCAGGCTGAGGACGAGGCTGATTATTACTGCAGCTCATATACAGGAAGCAGCACTCTCGACGTGCTATTCGGCGGAGGACCAAGCTGACCGTCCTAGGTCAGCCCGCGGCCGCA 269 heavy chain variable region QVQLVQPGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCASQYYDGGYYMDVWGQGTLVTVSS 234 heavy chain variable region gene CAGGTGCAGCTGGTGCAAGCCTGGAGCAGGTGAAAAAGCCGGGGAGTCTCTGAAGATCTCCTGTAAGGGTTCTGGATACAGCTTTACCAGCTACTGGATCGGCTGGGTGCGCCAGATGCCCGGGAAGGGCCTGGAGTGGATGGGGATCATCTATCCTGGTGACTCTGATACCAGATACAGCCCGTCCTTCCAAGGCCAGGTCACCATCTCAGCCGA CAAGTCCATCAGCACCGCCTACCTGCAGTGGAGCAGCCTGAAGGCCTCGGACACCGCCATGTATTACTGTGCGAGTCAATATTACGATGGGGGTTACTACATGGACGTCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGT 270 light chain (lambda) QSALTQPASVSGSPGQSITISCTGSSSDVGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGVSDRFSGSKSGNMASLTISGLQAEDEADYYCSSYTGSSTLDVLFGGGTKLTVLGQPAAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQ VTHEGSTVEKTVAPTECS 309 heavy chain QVQLVQPGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCASQYYDGGYYMDVWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 310

Table 9 H2 antibody clone Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 QGDSLRNYYAS 31 CDR-L2 GNNKRPS 32 CDR-L3 NSLDSTYNHPI 33 CDR-H1 SYDIH 34 CDR-H2 WISAYNGNTNYAQKLQG 35 CDR-H3 DGGDAFDI 36 light chain variable region SYELTQDPAVSVALGQTVRITCQGDSLRNYYASWYQQKPGQAPILVISGNNKRPSGIPDRFSGSSSGDTASLTISGAQAEDEADYYCNSLDSTYNHPIFGGGTKVTVLGQPAAA 235 light chain variable region gene TCCTATGAGCTGACTCAGGACCCTGCTGTGTCGGTGGCCTTGGGACAGACAGTCAGGATCACATGCCAAGGAGACAGCCTCAGAAACTATTATGCAAGCTGGTACCAGCAGAAGCCAGGACAGGCCCCTATTCTTGTCATCTCTGGTAACAACAAACGGCCCTCGGGGATCCCAGACCGATTCTCTGGCTCCAGCTCAGGAGACACAAGCTTCCTTGACCATCTCTGG GGCTCAGGCGGAAGATGAGGCTGACTATTACTGTAACTCCCTAGACAGCACTTATAACCATCCGATATTCGGCGGAGGGACCAAGGTCACCGTCCTAGGTCAGCCCGCGGCCGCA 271 heavy chain variable region QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIHWVRQATGQGLEWMGWISAYNGNTNYAQKLQGRV™TTDTSTSTAYMELRSLRSDDTAVYYCARDGGDAFDIWGQGTLVTVSS 236 heavy chain variable region gene CAGGTCCAGCTTGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGATACACCTTCACCAGTTATGATATCCACTGGGTGCGACAGGCCACTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGCTTACAATGGTAACACAAACTATGCACAGAAGCTCCAGGGCAGAGTCACCATGACCACAGACA CATCCACGAGCACAGCCTACATGGAGCTGAGGAGCCTGAGATCTGACGACACGGCCGTGTATTACTGTGCGAGAGATGGGGGTGATGCTTTTGATATCTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT 272 light chain (lambda) SYELTQDPAVSVALGQTVRITCQGDSLRNYYASWYQQKPGQAPILVISGNNKRPSGIPDRFSGSSSGDTASLTISGAQAEDEADYYCNSLDSTYNHPIFGGGTKVTVLGQPAAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTV EKTVAPTECS 311 heavy chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDIHWVRQATGQGLEWMGWISAYNGNTNYAQKLQGRV™TTDTSTSTAYMELRSLRSDDTAVYYCARDGGDAFDIWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTY TCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 312

Table 10 H11 antibody clone Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 QGDSLRSYYAS 37 CDR-L2 GRNRPS 38 CDR-L3 KSRDSSGNHYV 39 CDR-H1 SYYMH 40 CDR-H2 IINPSGGSTSYAQKFQG 41 CDR-H3 DAGSSSDY 42 light chain variable region SYELTQDPAASVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVVVIYGRNNRPSGIPDRFSGSSSGDTASLTITGAQAEDEADYYCKSRDSSGNHYVFGTGTKLTVLGQPAAA 231 light chain variable region gene TCCTATGAGCTGACTCAGGACCCTGCTGCGTCTGTGGCCTTGGGACAGACAGTCAGGATCACATGCCAAGGAGACAGCCTCAGAAGCTATTATGCAAGCTGGTACCAGCAGAAGCCAGGACAGGCCCCTGTAGTTGTCATCTATGGTAGAAACAACCGGCCCTCAGGGATCCCAGACCGATTCTCTGGCTCCAGCTCAGGAGACACAAGCTTCCTTGACCATCACTGGG GCTCAGGCGGAAGATGAGGCTGACTATTACTGTAAGTCCCGGGACAGCAGTGGTAACCATTATGTCTTCGGAACTGGGACCAAGCTGACCGTCCTAGGTCAGCCCGCGGCCGCA 273 heavy chain variable region QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRV™TRDTSTSTVYMELSSLRSEDTAVYYCARDAGSSSDYWGRGTLVTVSS 232 heavy chain variable region gene CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGCAAGGCATCTGGATACACCTTCACCAGCTACTATATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAATAATCAACCCTAGTGGTGGTAGCACAAGCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAGGGACACG TCCACGAGCACAGTCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAGATGCCGGCAGCTCGTCCGATTACTGGGGCCGTGGCACCCTGGTCACCGTCTCGAGT 274 light chain (lambda) SYELTQDPAASVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVVVIYGRNNRPSGIPDRFSGSSSGDTASLTITGAQAEDEADYYCKSRDSSGNHYVFGTGTKLTVLGQPAAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGS TVEKTVAPTECS 313 heavy chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRV™TRDTSTSTVYMELSSLRSEDTAVYYCARDAGSSSDYWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTY TCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 314

Table 11 F12 antibody clone Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 AGTSSDIGDYDYVS 43 CDR-L2 DVSRRPS 44 CDR-L3 ASYTSSSVVV 45 CDR-H1 SYWIG 46 CDR-H2 IIYPGDSDTRYSPSFQG 47 CDR-H3 QYYDGGYYMDV 48 light chain variable region QSVLTQPASVSGSPGQSITISCAGTSSDIGDYDYVSWYQQHPGKTPKLMIYDVSRRPSGVPDRFSGSKSGNTASLTISGLQTEDEADYYCASYTSSSVVVFGGGTKLTVLGQPAAA 237 light chain variable region gene CAGTCTGTGCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCGCTGGAACCAGCAGTGACATTGGTGATTATGACTATGTCTCCTGGTACCAACAGCACCCAGGCAAGACTCCCAAACTCATGATTATGATGTCAGTAGGCGGCCCTCAGGGGTCCCTGATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCAT CTCTGGGCCTCCAGACTGAGGACGAGGCTGATTATTACTGCGCCTCATATACAAGCAGCAGCGTCGTGGTCTTCGGCGGAGGGACCAAGCTGACCGTCCTAGGTCAGCCCGCGGCCGCA 275 heavy chain variable region QVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCASQYYDGGYYMDVWGQGTLVTVSS 238 heavy chain variable region gene CAGGTGCAGCTGGTGCAGTCTGGAGCAGAGGTGAAAAAGCCCGGGGAGTCTCTGAAGATCTCCTGTAAGGGTTCTGGATACAGCTTTACCAGCTACTGGATCGGCTGGGTGCGCCAGATGCCCGGGAAAGGCCTGGAGTGGATGGGGATCATCTATCCTGGTGACTCTGATACCAGATACAGCCCGTCCTTCCAAGGCCAGGTCACCATCTCAGCCGACA AGTCCATCAGCACCGCCTACCTGCAGTGGAGCAGCCTGAAGGCCTCGGACACCGCCATGTATTACTGTGCGAGTCAATATTACGATGGGGGTTACTACATGGACGTCTGGGGCCAGGGCACCCTGGTCACCGTCTCGAGT 276 light chain (lambda) QSVLTQPASVSGSPGQSITISCAGTSSDIGDYDYVSWYQQHPGKTPKLMIYDVSRRPSGVPDRFSGSKSGNTASLTISGLQTEDEADYYCASYTSSSVVVFGGGTKLTVLGQPAAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSC QVTHEGSTVEKTVAPTECS 315 heavy chain QVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCASQYYDGGYYMDVWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 316

Table 12 B9 antibody clone Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 RASQSISRYLN 49 CDR-L2 GASSLQS 50 CDR-L3 QQAYGFPLT 51 CDR-H1 SYAIS 52 CDR-H2 GIIPIFGTANYAQKFQG 53 CDR-H3 GEIAVAQNWDYYGMDV 54 light chain variable region DIQMTQSPSSLSASVGDRVTITCRASQSISRYLNWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYHCQQAYGFPLTLGGGTKVEIKRTAAA 229 light chain variable region gene GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAAGTCACCATCACTTGCCGGCAAGTCAGAGCATTAGCAGGTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCCAAGCTCCTGATCTATGGTGCATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAG TCTGCAGCCTGAAGATTTCGCAACTTACCATTGTCAACAGGCTTACGGTTTCCCCCTCACTCTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACCGCGGCCGCA 277 heavy chain variable region QVQLVESGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGEIAVAQNWDYYGMDVWGQGTLVTVSS 230 heavy chain variable region gene CAGGTGCAGCTGGTGGAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCTTCTGGAGGCACCTTCAGCAGCTATGCTATCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAGGATCATCCCTATCTTTGGTACAGCAAACTACGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGA CGAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAGGGGAAATAGCAGTGGCTCAAAACTGGGACTACTACGGTATGGACGTCTGGGGCCAGGGCACCCTGGTCACCGTCTCGAGT 278 light chain (kappa) DIQMTQSPSSLSASVGDRVTITCRASQSISRYLNWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYHCQQAYGFPLTLGGGTKVEIKRTAAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK LYACEVTHQGLSSPVTKSFNRGEC 317 heavy chain QVQLVESGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGEIAVAQNWDYYGMDVWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 318

Table 13 G11 antibody clone Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 TGTSSDVGGYNYVS 55 CDR-L2 DVSKRPS 56 CDR-L3 SSYSSSSTLVV 57 CDR-H1 SYWIG 58 CDR-H2 IIYPGDSDTRYSPSFQG 59 CDR-H3 QYYDGGYYMDV 60 light chain variable region QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSKRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYCSSYSSSSTLVVFGGGTKLTVLGQPAAA 239 light chain variable region gene CAGTCTGCGCTGACTCAGCCTCGCTCAGTGTCCGGGTCTCCTGGACAGTCAGTCACCATCTCCTGCACTGGAACCAGCAGTGTGATGTTGGTGGTTATAACTATGTCTCCTGGTACCAACAGCACCCAGGCAAAGCCCCCAAACTCATGATTATGATGTCAGTAAGCGGCCCTCAGGGGTCCCTGATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACAAT CTCTGGGCCTCCAGGCTGAGGACGAGGCTGATTATTACTGCAGCTCATATTCAAGCAGCAGCACTCTCGTGGTTTTCGGCGGAGGACCAAGCTGACCGTCCTAGGTCAGCCCGCGGCCGCA 279 heavy chain variable region QVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCASQYYDGGYYMDVWGQGTLVTVSS 240 heavy chain variable region gene CAGGTCCAGCTGGTACAGTCTGGAGCAGAGGTGAAAAAGCCGGGGAGTCTCTGAAGATCTCCTGTAAGGGTTCTGGATACAGCTTTACCAGCTACTGGATCGGCTGGGTGCGCCAGATGCCCGGGAAAGGCCTGGAGTGGATGGGGATCATCTATCCTGGTGACTCTGATACCAGATACAGCCCGTCCTTCCAAGGCCAGGTCACCATCTCAGCCGA CAAGTCCATCAGCACCGCCTACCTGCAGTGGAGCAGCCTGAAGGCCTCGGACACCGCCATGTATTACTGTGCGAGTCAATATTACGATGGGGGTTACTACATGGACGTCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGT 280 light chain (lambda) QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSKRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYCSSYSSSSTLVVFGGGTKLTVLGQPAAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSC QVTHEGSTVEKTVAPTECS 319 heavy chain QVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCASQYYDGGYYMDVWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 320

Table 14 G6 antibody clone Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 QGDSLRRYYAT 61 CDR-L2 GQNYRPS 62 CDR-L3 NSRDSSGNHVV 63 CDR-H1 SYYMH 64 CDR-H2 GIIPIFGTANYAQKFQG 65 CDR-H3 GWGYSSSFDY 66 light chain variable region SYELTQDPAVSVALGQTVTITCQGDSLRRYYATWYQQKPGQAPVLVIYGQNYRPSGIPDRFSGSNSGTTASLTITGAQAEDEADYYCNSRDSSGNHVVFGGGTKLTVLGQPAAA 241 light chain variable region gene TCCTATGAGCTGACTCAGGACCCTGCTGTGTCTGTGGCCTTGGGACAGACAGTCACGATCACCATGCCAAGGAGACAGCCTCAGAAGGTATTATGCAACCTGGTACCAGCAGAAGCCAGGACAGGCCCCTGTCCTTGTCATCTATGGTCAAAACTACCGGCCCTCGGGGATCCCAGACCGATTCTCTGGCTCCAACTCAGGAACCACAAGCTTCCTTGACCATCACTGGG GCTCAGGCGGAAGATGAGGCTGACTATTACTGTAACTCCCGGGACAGCAGTGGTAACCATGTGGTATTCGGCGGAGGGACCAAGCTGACCGTCCTAGGTCAGCCCGCGGCCGCA 281 heavy chain variable region EVQLVESGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGWGYSSSFDYWGQGTTVTVSS 242 heavy chain variable region gene GAGGTGCAGCTGGTGGAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGCAAGGCATCTGGATACACCTTCACCAGCTACTATATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAGGATCATCCCTATCTTTGGTACAGCAAACTACGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGAC GAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTACTACTGTGCGAGAGGGTGGGGGTATAGCAGCTCGTTTGACTACTGGGGGCAAGGGACCACGGTCACCGTCTCGAGT 282 light chain (lambda) SYELTQDPAVSVALGQTVTITCQGDSLRRYYATWYQQKPGQAPVLVIYGQNYRPSGIPDRFSGSNSGTTASLTITGAQAEDEADYYCNSRDSSGNHVVFGGGTKLTVLGQPAAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVT HEGSTVEKTVAPTECS 321 heavy chain EVQLVESGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGWGYSSSFDYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTY TCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 322

Table 15 F11 antibody clone Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 SGSSSNIGTNTVN 67 CDR-L2 SNDQRPS 68 CDR-L3 ETWDDSLKGPV 69 CDR-H1 SYAMS 70 CDR-H2 TISGSGDSTYYADSVKG 71 CDR-H3 EWELGDAFDI 72 light chain variable region QSVLTQPPSTSGTPGQTFSIFCSGSSSNIGTNTVNWYQQLPGTAPKLLIYSNDQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCETWDDSLKGPVFGGGTKVTVLGQPAAA 243 light chain variable region gene CAGTCTGTGCTGACTCAGCCACCCTCAACGTCTGGGACCCCCGGGCAGACGTTCTCCATTTTTTGTTCTGGAAGCAGTTCGAACATCGGAACTAATACTGTTAATTGGTACCAGCAGCTCCCAGGAACGGCCCCCAAACTCCTCATCTATAGTAATGATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTG GGCTCCAGTCTGAGGATGAGGCTGATTATTACTGTGAAACATGGGATGACAGCCTGAAAGGCCCGGTGTTCGGCGGGGGGACCAAGGTCACCGTCCTAGGTCAGCCCGCGGCCGCA 283 heavy chain variable region EVQLVESGGGLVQPGGSLKLSCAASGFTFSSYAMSWVRRAPGKGLEWVSTISGSGDSTYYADSVKGRFTISRDNSKNTLYLQMNNLRAEDTAVYYCAREWELGDAFDIWGRGTLVTVSS 244 heavy chain variable region gene GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAAACTCTCCTGTGCAGCGTCTGGATTCACCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCGGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAACTATTAGTGGTAGTGGTGATAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCC AGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAACCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAGAGAATGGGAACTAGGCGATGCTTTTGATATCTGGGGCCGTGGCACCCTGGTCACCGTCTCGAGT 284 light chain (lambda) QSVLTQPPSTSGTPGQTFSIFCSGSSSNIGTNTVNWYQQLPGTAPKLLIYSNDQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCETWDDSLKGPVFGGGTKVTVLGQPAAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQ VTHEGSTVEKTVAPTECS 323 heavy chain EVQLVESGGGLVQPGGSLKLSCAASGFTFSSYAMSWVRRAPGKGLEWVSTISGSGDSTYYADSVKGRFTISRDNSKNTLYLQMNNLRAEDTAVYYCAREWELGDAFDIWGRGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCN VDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK TTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 324

Table 16 Clone D3 antibody Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 RASQSISSYLN 73 CDR-L2 AASSLQS 74 CDR-L3 QQSYSTRWT 75 CDR-H1 SYAMS 76 CDR-H2 AISGSGGSTYYADSVKG 77 CDR-H3 DRGSYGYYYGMDV 78 light chain variable region DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTRWTFGQGTKVEIKRTAAA 245 light chain variable region gene GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAAGTCACCATCACTTGCCGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCGGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAACGTACCGCGGCCGCA 285 heavy chain variable region EVQLLESGGGVVQPGRSLRLSCAASGTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDRGSYGYYGMDVWGQG™VTVSS 246 heavy chain variable region gene GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGTCAGCCTCTGGATCCACCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAG AGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAAAGACAGGCAGCTATGGTTACTACTACGGTATGGACGTCTGGGGCCAAGGGACAATGGTCACCGTCTCGAGT 286 light chain (kappa) DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTRWTFGQGTKVEIKRTAAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGS TVEKTVAPTECS 325 heavy chain EVQLLESGGGVVQPGRSLRLSCAASGTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDRGSYGYYGMDVWGQG™VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS SLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWES NGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 326

Table 17 B12 antibody clone Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 RASQSISSYLN 79 CDR-L2 AASSLQS 80 CDR-L3 QQSYSTLRT 81 CDR-H1 GYYMH 82 CDR-H2 WINPNSGGTNYAQKFQG 83 CDR-H3 AGASIVGATALDY 84 light chain variable region DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTLRTFGQGTKVEIKRTAAA 247 light chain variable region gene GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAAGTCACCATCACTTGCCGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTC TGCAACCTGAAGATTTTGCAACTTACTACTGTCAACAGAGTTACAGTACCCTCCGGACGTTCGGCCAAGGGACCAAGGTGGAGATCAAACGTACCGCGGCCGCA 287 heavy chain variable region QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCTRAGASIVGATALDYWGQGTLVTVSS 248 heavy chain variable region gene CAGGTCCAGCTGGTACAGTCTGGGGCTGAGGTGAAGAAGCCTGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGATACACCTTCACCGGCTACTATATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAACCCTAACAGTGGTGGCACAAACTACGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGAC GAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTACGAGAGCCGGTGCTTCTATAGTGGGAGCTACCGCGCTTGACTACTGGGCCAGGGAACCCTGGTCACCGTCTCGAGT 288 light chain (kappa) DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTLRTFGQGTKVEIKRTAAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKH KLYACEVTHQGLSSPVTKSFNRGEC 327 heavy chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCTRAGASIVGATALDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL GTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 328

Table 18 E4 antibody clone Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 TRSSGSIASNYVQ 85 CDR-L2 EDNQRPS 86 CDR-L3 QSYDTGNRNYV 87 CDR-H1 SYTIS 88 CDR-H2 RIIPILGIANYAQKFQG 89 CDR-H3 GPSLNYAGYFDN 90 light chain variable region NFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSSPTTVIYEDNQRPSGVPDRFSGSIDSSSSNSASLTISGLKTEDEADYYCQSYDTGNRNYVFGTGTQLTVLGQPAAA 249 light chain variable region gene AATTTTATGCTGACTCAGCCCCACTCTGTGTCGGAGTCTCCGGGAAAGACGGTAACCATCTCCTGCACCCGCAGCAGTGGCAGCATTGCCAGCAACTATGTGCAGTGGTACCAGCAGCGCCCGGGCAGTTCCCCCACCACTGTGATCTATGAGGATAACCAAAGACCCTCTGGGGTCCCTGATCGGTTCTCTGGCTCCATCGACAGCTCCTCCAACTCTGCCTCCCTCAC CATCTCTGGACTGAAGACTGAGGACGAGGCTGACTACTACTGTCAGTCTTATGATACCGGCAATCGGAATTATGTCTTCGGAACTGGACCCAGCTCACCGTCCTAGGTCAGCCCGCGGCCGCA 289 heavy chain variable region QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYTISWVRQAPGQGLEWMGRIIPILGIANYAQKFQGRV™TRDMSTDTAYMELSSLTYDDTAVYFCVRGPSLNYAGYFDNWGQGTLVTVSS 250 heavy chain variable region gene CAGGTGCAGCTGGTGCAATCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCTTCTGGAGGCACCTTCAGCAGCTATACTATCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAAGGATCATCCCTATCCTTGGTATAGCAAACTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAGGGACAT GTCCACAGACACAGCCTACATGGAGTTGAGCAGCCTGACATATGATGACACGGCCGTATATTTTTGTGTGTGAGAGGCCTAGTCTTAATTATGCCGGCTATTTTGACAACTGGGCCAGGGCACCCTGGTCACCGTCTCGAGT 290 light chain (lambda) NFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSSPTTVIYEDNQRPSGVPDRFSGSIDSSNSASLTISGLKTEDEADYYCQSYDTGNRNYVFGTGTQLTVLGQPAAAPSVTLFPPSSEEIQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVT HEGSTVEKTVAPTECS 329 heavy chain QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYTISWVRQAPGQGLEWMGRIIPILGIANYAQKFQGRV™TRDMSTDTAYMELSSLTYDDTAVYFCVRGPSLNYAGYFDNWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTK TYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 330

Table 19 E12 antibody clone Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 QGDSLRSYYAS 91 CDR-L2 GKEKRPS 92 CDR-L3 NSRGSTTDYMV 93 CDR-H1 SYAMH 94 CDR-H2 VISYDGSNKKYYADSVKG 95 CDR-H3 ERGSGMDV 96 light chain variable region SYELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKSGQAPVLVIYGKEKRPSGIPDRFSGSSSGNTASLTITGARAEDEADYYCNSRGSTTDYMVFGGGTQLTVLGQPAAA 251 light chain variable region gene TCCTATGAGCTGACTCAGGACCCTGCTGTGTCTGTGGCCTTGGGACAGACAGTCAGGATCACATGCCAAGGAGACAGCCTCAGAAGCTATTATGCAAGCTGGTACCAGCAGAAGTCAGGACAGGCCCCTGTACTTGTCATCTATGGTAAAGAAAAGCGCCCCTCAGGGATCCCAGACCGATTCTCTGGCTCCAGCTCAGGAAACACAGCTTCCTTGACCATCACTGGGGC TCGGGCGGAAGATGAGGCTGACTATTACTGTAACTCCCGGGGCAGCACTACTGACTATATGGTGTTCGGCGGGGGACCCAGCTCACCGTCCTAGGTCAGCCCGCGGCCGCA 291 heavy chain variable region QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARERGSGMDVWGQGTLVTVSS 252 heavy chain variable region gene CAGGTGCAGCTGGTGGAGTCCGGGGGAGGCTTAGTTCAGCCTGGGGGTCCCTGAGACTCTCCTGTGTCAGCCTCTGGATTACACCTTCAGTAGCTATGCTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAGCAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAA TTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGAACGGGGAAGTGGTATGGACGTCTGGGGCCAAGGAACCCTGGTCACCGTCTCGAGT 292 light chain (lambda) SYELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKSGQAPVLVIYGKEKRPSGIPDRFSGSSSGNTASLTITGARAEDEADYYCNSRGSTTDYMVFGGGTQLTVLGQPAAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVT HEGSTVEKTVAPTECS 331 heavy chain QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARERGSGMDVWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCN VDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK TTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 332

Table 20 Clone D1 antibody Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 KASQDIDDDMN 97 CDR-L2 EASTLVP 98 CDR-L3 LQHDKFPYT 99 CDR-H1 SYGIS 100 CDR-H2 WINPNSGGTNYAQKFQG 101 CDR-H3 RGVDEGDY 102 light chain variable region ETTLTQSPAFMSATPGDKVNISCKASQDIDDDMNWYQQKPGEAAISIIQEASTLVPGIPPRFSGSGYGTDFTLTINNIESEDAAYYFCLQHDKFPYTFGQGTKLEIKRTAAA 253 light chain variable region gene GAAACGACACTCAGCAGTCTCAGCATTCATGTCAGCGACTCCAGGAGACAAAGTCAACATCTCCTGCAAAGCCAGCCAAGACATTGATGATGATATGAACTGGTACCAACAGAAACCAGGAGAAGCTGCTATTTCCATTATTCAAGAAGCTAGTACTCTCGTTCCTGGAATCCCACCTCGATTCAGTGTGGCAGCGGGTATGGAACAGATTTTACCCTCACAATTAATAACATAGAATCT GAGGATGCTGCATATTACTTCTGTCTACAACATGATAAGTTCCCGTACACTTTTGGCCAGGGGACCAAGCTGGAGATCAAACGTACCGCGGCCGCA 293 heavy chain variable region EVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRV™TRDTSISTAYMELSRLRSDDTAVYYCASRGVDEGDYWGQG™VTVSS 254 heavy chain variable region gene GAAGTGCAGCTGGTGCAGTCTGGAGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGTTACACCTTTACCAGCTATGGTATCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAACCCTAACAGTGGTGGCACAAACTATGCACAGAAGTTTCAGGGCAGGGTCACCATGACCAGGGA CACGTCCATCAGCACAGCCTACATGGAGCTGAGCAGGCTGAGATCTGACGACACGGCCGTGTATTACTGTGCGAGTCGGGGGGTTGATGAGGGGGACTACTGGGGCCAAGGGACAATGGTCACCGTCTCGAGT 294 light chain (kappa) ETTLTQSPAFMSATPGDKVNISCKASQDIDDDMNWYQQKPGEAAISIIQEASTLVPGIPPRFSGSGYGTDFTLTINNIESEDAAYYFCLQHDKFPYTFGQGTKLEIKRTAAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKLY ACEVTHQGLSSPVTKSFNRGEC 333 heavy chain EVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRV™TRDTSISTAYMELSRLRSDDTAVYYCASRGVDEGDYWGQG™VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTK TYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 334

Table 21 E6 antibody clone Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 TGSSGNIASNYVQ 103 CDR-L2 RDDQRPS 104 CDR-L3 QSYDSSSWV 105 CDR-H1 TYDIT 106 CDR-H2 WMNPNSGNSRSAQKFQG 107 CDR-H3 GDYSGVVLTATALDY 108 light chain variable region NFMLTQPHSVSESPGKTVTLSCTGSSGNIASNYVQWYQHRPGSAPTTVIYRDDQRPSGVPDRFSGSIDSSSSNSASLTISGLRPEDEADYYCQSYDSSSWVFGGGTKLTVLGQPAAA 255 light chain variable region gene AATTTTATGCTGACTCAGCCCCACTCTGTGTCGGAGTCTCCGGGGAAGACGGTTACCCTCTCCTGCACCGGCAGCAGCGGCAACATTGCCAGTAACTATGTGCAGTGGTACCAGCACCGCCCGGGCAGTGCCCCCACCACTGTGATCTACCGGGATGACCAAAGACCCTCTGGAGTCCCTGATCGCTTCTCTGGCTCCATCGACAGTTCATCCAACTCTGCCTCCCTCAC GATCTCTGGACTGAGGCCTGAGGACGAGGCTGACTATTACTGTCAGTCTTATGATAGCAGCTCTTGGGTGTTCGGCGGAGGACCAAGCTGACCGTCCTAGGTCAGCCCGCGGCCGCA 295 heavy chain variable region QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYDITWVRQAPGQGLEWMGWMNPNSGNSRSAQKFQGRVSMTSDSSISTAYMELSSLRSEDTAVYYCATGDYSGVVLTATALDYWGQGTLVTVSS 256 heavy chain variable region gene CAGGTCCAGCTTGTGCAGTCTGGAGCAGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGATACACCTTCACCACTTATGATATCACCTGGGTGCGACAGGCCCCTGGACAAGGCCTTGAGTGGATGGGATGGATGAACCCGAACAGTGGTAACTCACGCTCTGCACAGAAGTTCCAGGGCAGAGTCAGCATGACCAGTGACTCCTCCATAA GCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCAACAGGAGACTACTCGGGTGTGGTACTAACTGCAACAGCACTTGACTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGT 296 light chain (lambda) NFMLTQPHSVSESPGKTVTLSCTGSSGNIASNYVQWYQHRPGSAPTTVIYRDDQRPSGVPDRFSGSIDSSSSNSASLTISGLRPEDEADYYCQSYDSSSWVFGGGTKLTVLGQPAAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGS TVEKTVAPTECS 335 heavy chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYDITWVRQAPGQGLEWMGWMNPNSGNSRSAQKFQGRVSMTSDSSISTAYMELSSLRSEDTAVYYCATGDYSGVVLTATALDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG TKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 336

Table 22 E9 antibody clone Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 SGSSSNIGNNYVY 109 CDR-L2 RNNQRPS 110 CDR-L3 AAWDDSLSGWV 111 CDR-H1 SYGMH 112 CDR-H2 NIKQDGSEKYYVDSVKG 113 CDR-H3 EDRIAAAGMRELDY 114 light chain variable region QSELTQLPSASETPGQRVTISCSGSSSNIGNNYVYWYQQLPGTAPKLLIYRNNQRPSGVPDRFSSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSGWVFGGGTKLTVLGQPAAA 257 light chain variable region gene CAGTCTGAGCTGACTCAGCTACCCTCAGCGTCTGAGACCCCCGGGCAGAGGGTCACCATCTCTTGTTCTGGAAGCAGCTCCAACATCGGAAATAATTATGTATACTGGTACCAGCAACTCCCCGGAACGGCCCCCAAACTCCTCATCTATAGGAATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTG GGCTCCGGTCCGAGGATGAGGCTGATTATTACTGTGCAGCATGGGATGACAGCCTGAGTGGTTGGTGTTCGGCGGAGGACCAAGCTGACCGTCCTAGGTCAGCCCGCGGCCGCA 297 heavy chain variable region QVQLVESGGGLVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVANIKQDGSEKYYVDSVKGRFTISRDNAKNTLYLQMNSLRAEDTAVYYCAREDRIAAAGMRELDYWGQGTLVTVSS 258 heavy chain variable region gene CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCTGGATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAAGCAAGATGGAAGTGAGAAATACTATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGAC AACGCCAAGAACACGCTGTATCTCCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGAGGACCGTATAGCAGCAGCTGGGATGCGGGAGTTGGACTACTGGGCCAGGGCACCCTGGTCACCGTCTCGAGT 298 light chain (lambda) QSELTQLPSASETPGQRVTISCSGSSSNIGNNYVYWYQQLPGTAPKLLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSGWVFGGGTKLTVLGQPAAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGS TVEKTVAPTECS 337 heavy chain QVQLVESGGGLVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVANIKQDGSEKYYVDSVKGRFTISRDNAKNTLYLQMNSLRAEDTAVYYCAREDRIAAAGMRELDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG TKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 338

Table 23 A11 antibody clone Amino acid sequence (N→C) / Nucleic acid sequence (5'→3') SEQID NO CDR-L1 RSSQSLLHSNGYNYLD 115 CDR-L2 LGSNRAS 116 CDR-L3 MQGTHWPPYT 117 CDR-H1 SYAMT 118 CDR-H2 GISSDGTTTTYADSVRG 119 CDR-H3 DQLLGWDALNV 120 light chain variable region DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGTHWPPYTFGQGTKVEIKRTAAA 259 light chain variable region gene GATATTGTGATGACCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTGCAGGTCTAGTCAGAGCCTCCTGCATAGTAATGGATACAACTATTTGGATTGGTACCTGCAGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTATTTGGGTTTCTAACCGGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAG ATTTTACACTGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAAGGTACACACTGGCCTCCGTACACCTTTGGCCAGGGGACCAAGGTGGAGATCAAACGTACCGCGGCCGCA 299 heavy chain variable region EVQLLESGGGLEQPGGFLRLSCAASGFSFTSYAMTWVRQAPGKGLEWVSGISSDGTTTTYADSVRGRFTISRDNAKNTVYLQMNSLRDEDTAVYYCARDQLLGWDALNVWGQG™VTVSS 260 heavy chain variable region gene GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGAACAGCCTGGGGGTTCCTGAGACTCTCCTGTGTCAGCCTCTGGATTCTCCTTTACCAGCTACGCCATGACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGGTATTAGTAGTGATGGGACCACTACAACCTACGCGGACTCCGTGAGGGGCCGGTTCACCATCTCCAG AGACAACGCCAAGAACACGGTGTATCTCCAAATGAACAGTCTGAGAGACGAGGACACGGCTGTGTATTTGTGCAAGAGATCAATTGTTGGGCTGGGATGCTCTGAATGTCTGGGGCCAAGGGACAATGGTCACCGTCTCGAGT 300 light chain (kappa) DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGTHWPPYTFGQGTKVEIKRTAAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKAD YEKHKLYACEVTHQGLSSPVTKSFNRGEC 339 heavy chain EVQLLESGGGLEQPGGFLRLSCAASGFSFTSYAMTWVRQAPGKGLEWVSGISSDGTTTTYADSVRGRFTISRDNAKNTVYLQMNSLRDEDTAVYYCARDQLLGWDALNVWGQG™VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTK TYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 340

Example 2: Analysis of the biological activity of selected antibodies in vitro

2.1. Natural killer cell (NK cell) surface binding assay

In order to check whether the 93 antibodies selected in Example 1.4 bind LILRB1 expressed on the surface of immune cells, a natural killer cell (NK cell) surface binding assay was performed. Human NK cells, KHYG-1 cells (JCRB), were cultured in RPMI 1640 medium (Gibco) supplemented with 10% (w/v) FBS (Gibco) and 100 U/ml interleukin-2 (Novartis). KHYG-1 cells were added to a 96-well U-bottom tissue culture plate (BD Falcon) at 5×10 ⁴ cells/well. Each of the selected antibodies was added to the well to a final concentration of 50 μg/ml per well and incubated at 4°C for 1 hour.

In order to see the level of LILRB1-specific binding of selected antibodies, a human IgG4 isotype control antibody (Biolegend) was treated in the same manner. After washing with FACS buffer, cells were treated with an antibody to human Fc-biotin (life technologies) and incubated at 4°C for 1 hour. After washing with FACS buffer, cells were treated with streptavidin PE (BD Pharmigen) and incubated at 4° C. for 30 minutes. After washing with FACS buffer, cells were resuspended and analyzed using an iQue screening device (Sartorius).

From the results obtained, the results for antibodies A10, E3, E4, F12, G1, G9, G11, H2, and H11 were representatively compared with those for the human IgG4 isotype (control), which are shown in Table 24. Flow cytometry plots for A10, E3, and isotype Human IgG4 (control) are shown in Figures 4a (A10), 4b (E3) and 4c (IgG4 isotype), respectively:

Table 24 Average fluorescence intensity % population 2 Human IgG4 as an isotype control 142917.2 2.95 A10 222660.2 28.68 E3 268702.2 40.22 E4 272295.5 43.25 F12 262012.7 38.02 G1 321051.7 56.23 G9 263079.3 41.32 G11 262771.9 40.11 H2 238570.9 29.00 H11 244818.2 32.59

As shown in Table 24 and FIGS. 4a-4c, the antibodies tested show a higher level of binding to human NK cells (surface) compared to the human IgG4 isotype control antibody.

2.2. Assay of Inhibition of LILRB1 Binding to HLA-G by Selected Antibodies

In order to test whether the antibodies selected in Example 1.5 have an inhibitory effect on the binding of LILRB1 to its ligand, HLA-G, the degree of blocking by the selected antibodies was analyzed.

For this purpose, JEG-3 cells (ATCC cat# HTB-36) were used, which showed a high level of HLA-G expression. JEG-3 cells were cultured in MEM medium (Gibco) supplemented with 10% (v/v) FBS (Gibco) and 1% (v/v) penicillin-streptomycin (Gibco). JEG-3 cells were added to a 96-well U-bottom tissue culture plate (BD Falcon) at 5×10 ⁴ cells/well. The well plate was washed with 1X PBS buffer. Each of the antibodies selected in Example 1.5 (A10, E3, F12, G1, G9, H2 and H11) and LILRB1-Fc (RnD systems) were mixed in FACS buffer (1X PBS+1% BSA+1 mM EDTA) to final concentrations of 10 µg/ml and 5 µg/ml, respectively. Cells were treated with 100 μl of the mixture solution per well and incubated on ice for 2 hours. An anti-LILRB1 antibody (clone HP-F1, Abcam) was treated in the same manner as a positive control and an anti-lysozyme IgG4 antibody (clone D1.3) as a negative control. After washing twice with FACS buffer, cells were treated with PE-anti-huIgG-Fc antibody (Biolegend, 10 μg/ml) and incubated on ice for one hour. After washing twice with FACS buffer, the cells were resuspended in 100 μl of the same buffer and analyzed using the iQue screening device (Sartorius).

The results obtained are shown in Fig.5. As shown in Figure 5, all A10, E3, F12, G1, G9, H2 and H11 antibodies tested were effective in inhibiting the binding of LILRB1-Fc to the HLA-G overexpressing cell line.

2.3. Cancer cell lysis analysis by NK cells

In order to test whether the selected antibodies increase the rate of lysis of cancer cells by NK cells, the rate of death of HLA-G-overexpressing HEK293 cells by KHYG-1 NK cells was analyzed. KHYG-1 (JCRB) cells were added to a 96-well tissue culture plate (BD Falcon) at 2 x 10⁴ cells/well (4×10⁴ cells/ml, total volume 50 µl). Cells were treated with each antibody (Table 25) to a final concentration of 20 μg/ml per well and left at 37°C for one hour.

As a negative control, a human IgG4 isotype control antibody (Biolegend) was treated in the same manner.

HLA-G-overexpressing HEK293 cells (which were obtained by transducing HEK293 cells (American Typo Culture Collection) with a lentivirus engineered to express HLA-G) were stained with IncuCyte CytoLight Rapid Red reagent (Sartorius) according to the manufacturer's protocol. An hour later, HLA-G-overexpressing HEK293 cells were added to the plate in the amount of 1×10⁴ cells/well (2×10⁴ cells/ml, total volume 50 µl). The plate was placed in an IncuCyte S3 (Sartorius) equipped with an incubator at 37°C and 5% CO₂, And images were obtained within 72 hours. Red region confluence was measured, indicating the density of live HLA-G-overexpressing HEK293 cells, and cell viability was calculated. The resulting cell viability scores are shown in Table 25 (where cell viability is shown as relative to control antibody (cell viability in IgG4 isotype-treated well=1)):

Table 25 Antibody Relative cell viability (IgG4 isotype=1) Human IgG4 as an isotype control 1.00 A10 0.70 B9 0.81 D3 0.83 E1 0.82 E3 0.64 F12 0.81 G1 0.64 G6 0.78 G9 0.77 G11 0.82 H2 0.78 H11 0.60

As shown in Table 25, all antibodies tested, including A10, B9, D3, E1, E3, F12, G1, G6, G9, G11, H2, and H11, increase cell death of HLA-G-overexpressing HEK293 cells induced by KHYG-1 compared to a human IgG4 isotype control antibody.

Example 3: Analysis of the biological activity of selected antibodies in vivo

Of the antibodies selected in Example 1.5, two antibodies (E3 and B3) were tested for their anti-cancer efficacy in vivo . To this end, it was tested whether the introduction of these two antibodies reduces the size of the tumor, where the specified tumor was obtained by inoculating mice with human colorectal carcinoma cells (Bioware Brite Cell Line HCT116 Red-Fluc (PerkinElmer) colorectal carcinoma cells) and macrophages derived from THP-1 . As a negative control, human colon cancer xenograft mice, prepared as above, were treated with a human IgG1 isotype control antibody (BioXcell, cat#BP0297). The processes are described in detail below:

Obtaining macrophages derived from THP-1

The THP-1 derived macrophages used above were generated by THP-1 cell differentiation (ATCC) using 150 nM phorbol 12-myristate-13-acetate (PMA, Sigma), 20 ng/ml interferon gamma (Peprotech) and 10 pg /ml lipopolysaccharide (LPS, Sigma).

Measurement of anti-cancer efficacy in a mouse model

5-week-old female CIEA NOG mice [NOG immunodeficient mouse] (Central Institute for Experimental Animals, Japan) were subcutaneously injected with a mixture of 3×10 ⁶ HCT116 Red-Fluc colorectal carcinoma cells, 3×10 ⁶ macrophage cells derived from THP-1, and each of the two antibodies tested (antibody E3 or B3; 20 μg per mouse). From the 4th day after tumor transplantation, the antibody was administered to the mouse model at a dose of 5 mg/kg by intraperitoneal injection 2 times a week. The size (mm ³ ) of the transplanted tumor was then measured, as shown in FIG. As shown in Figure 6, all antibodies tested, especially the E3 antibody, exhibited a statistically significant tumor growth inhibiting effect in mouse models transplanted with HCT116 colon cancer cells and THP-1 derived macrophages.

Example 4 Preparation of Anti-LILRB1 Antibody (E3.1)

The nucleic acid sequence encoding the full length heavy chain (SEQ ID NO:302) of the E3 antibody, which was confirmed to have a particularly significant effect in Example 3, was amplified by PCR. The nucleic acid sequence encoding the variable light chain (VL) region Ser1 to Leu110 (SEQ ID NO:221) of antibody E3 was amplified by PCR and ligated with the nucleic acid sequence encoding the lambda constant region (Lambda CL.1, SEQ ID NO:344) for amplifying a nucleic acid sequence encoding a lambda light chain by PCR. The amplified sequences were inserted into an expression vector (pTRIOZ-hIgG4, InvivoGen; alternatively, any of the vectors comprising the CMV promoter or the CMV/CHO beta-actin fusion promoter (KR10-1038126B1) and genes encoding the human IgG4 heavy chain constant region and lambda light chain region), where an expression vector has been designed to encode a human IgG4 antibody. The DNA sequence of the expression vector was confirmed by sequencing.

An antibody (E3.1) was generated using the constructed expression vector according to Example 1.4, and the antibody sequence was analyzed according to Example 1.6 and shown in Table 26:

Table 26 E3.1 antibody clone amino acid sequence (N→C) / nucleic acid sequence (5'→3') SEQID NO CDR-L1 QGDSLRNFYAS 1 CDR-L2 GKNNRPS 2 CDR-L3 NSRDSSGSHLTGV 3 CDR-H1 SYAMS 4 CDR-H2 AISGSGGSTYYADSVKG 5 CDR-H3 DTYYYGSGRSNAFDI 6 light chain variable region SYELTQDPAVSVALGQTVRITCQGDSLRNFYASWYQQKSGQAPVLVMYGKNNRPSGIPDRFSGSTSGNTASLTITGAQAEDEADYYCNSRDSSGSHLTGVFGGGTKVTVL 345 light chain variable region gene TCCTATGAGCTGACTCAGGACCCTGCTGTGTCTGTGGCCTTGGGACAGACAGTCAGGATCACATGCCAGGGAGACAGCCTCAGAAACTTTTATGCAAGCTGGTACCAGCAGAAGTCAGGACAGGCCCCAGTTCTTGTCATGTATGGTAAAAACAACCGGCCCTCAGGGATCCCAGACCGATTCTCTGGCTCCACCTCAGGAAACACAAGCTTCCTTGACCATCACTGGG GCTCAGGCGGAAGATGAGGCTGACTATTACTGTAACTCCCGGGACAGCAGTGGTAGCCATTTGACGGGCGTATTCGGCGGAGGACCAAGGTCACCGTCCTA 346 heavy chain variable region QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMISLRAEDTAVYYCARDTYYYGSGRSNAFDIWGQGTLVTVSS 222 heavy chain variable region gene CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGTCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCC AGAGACAATTCCAAGAATACGCTGTATCTGCAAATGATTAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATACGTATTACTATGGTTCGGGGAGAAGTAATGCTTTTGATATATGGGGCCAGGGAACCCTGGTCACCGTCTCGAGT 262 light chain (lambda) SYELTQDPAVSVALGQTVRITCQGDSLRNFYASWYQQKSGQAPVLVMYGKNNRPSGIPDRFSGSTSGNTASLTITGAQAEDEADYYCNSRDSSGSHLTGVFGGGTKVTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQ VTHEGSTVEKTVAPTECS 347 heavy chain QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMISLRAEDTAVYYCARDTYYYGSGRSNAFDIWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTK TYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 302

Example 5 Generation of Cell Lines Overexpressing Human LILR

Nucleic acid sequences encoding full-length human LILR family proteins (Table 27) were amplified by PCR, and each of the amplified sequences was inserted into an expression vector (pTRIOZ-hIgG4, InvivoGen; alternatively, any of the vectors comprising the CMV promoter or the beta-fusion promoter can be used. CMV/CHO actin (KR10-1038126B1), and genes encoding the human IgG4 heavy chain constant region and the lambda light chain constant region). The DNA sequence of the expression vector was confirmed by sequencing. The constructed vector was transfected into CHO cells to obtain 11 stable cell lines overexpressing each LILR protein on their surface.

Table 27 Protein Access No. in GenBank amino acid sequence (N→C) SEQID NO Antibody LILRB1 AAH15731 MTPILTVLICLGLSLGPRTHVQAGHLPKPTLWAEPGSVITQGSPVTLRCQGGQETQEYRLYREKKTAPWITRIPQELVKKGQFPIPSITWEHAGRYRCYYGSDTAGRSESSDPLELVVTGAYIKPTLSAQPSPVVNSGGNVTLQCDSQVAFDGFILCKEGEDEHPQCLNSQPHARGSSRAIFSVGPVSPSRRWWYRCYAYDS NSPYEWSLPSDLLELLVLGVSKKPSLSVQPGPIVAPEETLTLQCGSDAGYNRFVLYKDGERDFLQLAGAQPQAGLSQANFTLGPVSRSYGGQYRCYGAHNLSSEWSAPSDPLDILIAGQFYDRVSLSVQPGPTVASGENVTLLCQSQGWMQTFLLTKEGAADDPWRLRSTYQSQKYQAEFPMGPVTSAHAGTYRCY GSQSSKPYLLTHPSDPLELVVSGPSGGPSSPTTGPTSTSGPEDQPLTPTGSDPQSGLGRHLGVVIGILVAVILLLLLLLLFLILRHRRQGKHWTSTQRKADFQHPAGAVGPEPTDRGLQWRSSPAADAQEENLYAAVKHTQPEDGVEMDTRSPHDEDPQAVTYAEVKHSRPRREMASPPSPLSGEFLDTKDRQAEEDR QMDTEAAASEAPQDVTYAQLHSLTLRRKATEPPPSQEGPSPAVPSIYATLAIH 348 Antibody to human LILRB1 (ab185796, Abcam) LILRB2 AAH36827 MTPIVTVLICLGLSLSLSLSLSLSTHVQPTLWAEPDSVITLSPVTLSCQEAQEYRYARARYRIRPSASSAWITRIRPELVKFIPSITGRWSRARWSDPLVMTGAYPKPTLSAQPSPV VTSGGRVTLQCesQVAFGGFILCKKEGEPHPHRAIFSVGPVSPNRWSHRCYGYGYDLNSPSDLLLVPSKPSLSVPVAPGPGPGPGSVSVSDVSDRFVSDRFVLLEKEKEGER Dlrqlpgrqpqglsqanftlgpvsrsygqygaygaygaygaygaynlssapsapsaplitgqigtpfisvasgpgenvtlcswrqswrqflltkagaadaplrlrsihepkyefpvtsahag TyrcygslnsdpyllshpseplelvvssssssssssspppepgpagpedptgsdpqsdpqsglgllllllllllllllllllllrrqhwtstqrkpagpagpagpagwaptdrglqwqwqwqwqwqwqwqwqWQWQWIs SPAADAQEENLAAVKDTQPEDTRAASEASEAPQDVTYAQLHSLTLRKATPSQEPAPAPAPAPSIYATLAIH 349 Anti-human LILRB2/CD85d/ILT4 antibody (MAB2078, R&D Systems) LILRB3 XP_006726377 MTPALTALLCLGLSLGPRTRVQAGPFPKPTLWAEPGSVISWGSPVTIWCQGSLEAQEYRLDKEGSPEPLDRNNPLEPKNKARFSIPSMTEHHAGRYRCHYYSSAGWSEPSDPLELVMTGFYNKPTLSALPSPVVASGGNMTLRCGSQKGYHHFVLMKEGEHQLPRTLDSQQLHSGGFQALFPVGPVNPSHRWRFTCYYYYMNT PQVWSHPSDPLEILPSGVSRKPSLLTLQGPVLAPGQSLTLQCGSDVGYDRFVLYKEGERDFLQRPGQQPQAGLSQANFTLGPVSPSHGQYRCYGAHNLSSEWSAPSDPLNILMAGQIYDTVSLSAQPGPTVASGENVTLLCQSWWQFDTFLLTKEGAAHPPLRLRSMYGAHKYQAEFPMSPVTSAHAGTYRCYGSYSS NPHLLSFPSEPLELMVSGHSGGSSLPTGPPSTPGLGRYLEVLIGVSVAFVLLFLLLFLLLRRQRHSKHRTSDQRKTDFQRPAGAAETEPKDRGLLRRSSPAADVQEENLYAAVKDTQSEDRVELDSQSPHDEDPQAVTYAPVKHSSPRREMASPPSSLSGEFLDTKDRQVEEDRQMDTEAAASEASQDVTYAQLHSLTLR RKATEPPPSQEGEPPAEPSIYATLAIH 350 Anti-human LILRB3/CD85a/ILT5 antibody (MAB1806, R&D Systems) LILRB4 NP_001265355 MIPTFTALLCLGLSLGPRTHMQAGPLPKPTLWAEPGSVISWGNSVTIWCQGTLEAREYRLDKEESPAPWDRQNPLEPKNKARFSIPSMTEDYAGRYRCYYRSPVGWSQPSDPLELVMTGAYSKPTLSALPSPLVTSGKSVTLLCQSRSPMDTFLLIKERAAHPLLHLRSEHGAQHQAEFPMSPVTSVHGTYGRCFSSHGFSHYLL SHPSDPLELIVSGSLEGPRPSPTRSVSTAAGPEDQPLMPTGSVPHSGLRRHWEVLIGVLVVSILLLSLLLFLLLQHWRQGKHRTLAQRQADFQRPPGAAEPEPKDGGLQRRSSPAADVQGENFCAAVKNTQPEDGVEMDTRQSPHDEDPQAVTYAKVKHSRPRREMASPPSPLSGEFLDTKDRQAEEDRQMDTEAAASEAPQ DVTYARLHSFTLRQKATEPPPSQEGASPAEPSVYATLAIH 351 Antibody to human LILRB4/CD85k/ILT3 (MAB24251, R&D Systems) LILRB5 NP_006831 MTLTLSVLICLGLSVGPRTCVQAGTLPKPTLWAEPASVIARGKPVTLWCQGPLETEEYRLDKEGLPWARKRQNPLEPGAKAKFHIPSTVYDSAGRYRCYYETPAGWSEPSDPLELVATGFYAEPTLLALPSPVVASGGNVTLQCDTLDGLLTFVLVEEEQKLPRTLYSQKLPKGPSQALFPVGPVTPSCRWRFRCYYYY RKNPQVWSNPSDLLEILVPGVSRKPSLLIPQGSVVARGGSLTLQCRSDVGYDIFVLYKEGEHDLVQGSGQQPQAGLSQANFTLGPVSRSHGQYRCYGAHNLSPRWSAPSDPLDILIAGLIPDIPALSVQPGPKVASGENVTLLCQSWHQIDTFFLTKEGAAHPPLCLKSKYQSYRHQAEFSMSPVTSAQGGTYRC YSAIRSYPYLLSSPSYPQELVVSGPSGDPSLSPTGSTPTPGPEDQPLTPTGLDPQSGLGRHLGVVTGVSVAFVLLLFLLLFLLLRHRHQSKHRTSAHFYRPAGAAGPEPKDQGLQKRASPVADIQEEILNAAVKDTQPKDGVEMDARAAASEAPQDVTYAQLHSLTLRREATEPPPSQEREPPAEPSIYAPLAIH 352 Anti-human LILRB5/CD85c/LIR-8 (MAB3065, R&D Systems) LILRA1 NP_006854 MTPIVTVLICLRLSLGPRTHVQAGTLPKPTLWAEPGSVITQGSPVTLWCQGILETQEYRLYREKKTAPWITRIPQEIVKKGQFPIPSITWEHTGRYRCFYGSHTAGWSEPSDPLELVVTGAYIKPTLSALPSPVVTSGGNVTLHCVSQVAFGSFILCKEGEDEHPQCLNSQPRTHGWSRAIFSVGPVSPSRRWSYRCYAYDSNSPH VWSLPSDLLELLVLGVSKKPSLSVQPGPIVAPGESLTLQCVSDVSYDRFVLYKEGERDFLQLPGPQPQAGLSQANFTLGPVSRSYGQYRCSGAYNLSSEWSAPSDPLDILIAGQFRGRPFISVHPGPTVASGENVTLLCQSWGPFHTFLLTKAGAADAPLRLRSIHEYPKYQAEFPMSPVTSAHSGTYRCYGSLSSNPYLLSHPS DSLELMVSGAAETLSPPQNKSDSKAGAANTLSPSQNKTASHPQDYTVENLIRMGIAGLVLVVLGILLFEAQHSQRSL 353 Antibody to human LILRA1/LILRB1 (MAB30851, R&D Systems) LILRA2 AAH17412 MTPILTVLICLGLSLGPRTHVQAGHLPKPTLWAEPGSVIIQGSPVTLRCQGSLQAEEYHLYRENKSASWVRRIQEPGKNGQFPIPSITWEHAGRYHCQYYSHNHSSEYSDPLELVVTGAYSKPTLSALPSPVVTLGGNVTLQCVSQVAFDGFILCKEGEDEHPQRLNSHSHARGWSWAIFSVGPVSPSRRWSYRCYAYDSNSPY VWSLPSDLLELLVPGVSKKPSLSVQPGPMVAPGESLTLQCVSDVGYDRFVLYKEGERDFLQRPGWQPQAGLSQANFTLGPVSPSHGQYRCYSAHNLSSEWSAPSDPLDILITGQFYDRPSLSVQPVPTVAPGKNVTLLCQSRGQFHTFLLTKEGAGHPPLHLRSEHQAQQNQAEFRMGPVTSAHVGTYRCY SSLSSNPYLLSLPSDPLELVVSASLGQHPQDYTVENLIRMGVAGLVLVVLGILLFEAQHSQRSLQDAAGR 354 Antibody to human LILRA2/CD85h/ILT1 (MAB6364, R&D Systems) LILRA3 AAH28208 MTSILTVLICLGLSLDPRTHVQAGPLPKPTLWAEPGSVITQGSPVTLRCQGSLETQEYHLYREKKTALWITRIPQELVKKGQFPILSITWEHAGRYCCIYGSHTVGLSESSDPLELVVTGAYSKPTLSALPSPVVTSGGNVTIQCDSQVAFDGFILCKEGEDEHPQCLNSHSHARGSSRAIFSVGPVSPSRRWSYRCYGYDSRA PYVWSLPSDLLGLLVPGVSKKPSLSVQPGPVVAPGEKLTFQCGSDAGYDRFVLYKEWGRDFLQRPGRQPQAGLSQANFTLGPVSRSYGQYTCSGAYNLSSEWSAPSDPLDILITGQIRARPFLSVRPGPTVASGENVTLLCQSQGGMHTFLLTKEGAADSPLRLKSKRQSHKYQAEFPMSPVTSAHAGTYRCYGSLSSNPYLL THPSDPLELVVSGAAEETLSPPQNKSDSKAGE 355 Anti-human LILRA3/CD85e antibody (PA5-47349, Invitrogen) LILRA4 NP_036408 MTLILTSLLFFGLSLGPRTRVQAENLPKPILWAEPGPVITWHNPVTIWCQGTLEAQGYRLDKEGNSMSRHILKTLESENKVKLSIPSMMWEHAGRYHCYYQSPAGWSEPSDPLELVVTAYSRPTLSALPSPVVTSGVNVTLRCASRLGLGRFTLIEEGDHRLSWTLNSHQHNHGKFQALFPMGPLTFSNRGTFRCYGYENNTP YVWSEPSDPLQLLVSGVSRKPSLLTLQGPVVTPGENLTLQCGSDVGYIRYTLYKEGADGLPQRPGRQPQAGLSQANFTLSPVSRSYGQYRCYGAHNVSSEWSAPSDPLDILIAGQISDRPSLSVQPGPTVTSGEKVTLLCQSWDPMFTFLLTKEGAAHPPLRLRSMYGAHKYQAEFPMSPVTSAHAGTYRCYGSRSSNPYLL SHPSEPLELVVSGATETLNPAQKKSDSKTAPHLQDYTVENLIRMGVAGLVLLFLGILLFEAQHSQRSPPRCSQEANSRKDNAPFRVVEPWEQI 356 Antibody to CD85g (ILT7) (16-5179-82, Invitrogen) LILRA5 NP_067073 MAPWSHPSAQLQPVGGDAVSPALMVLLCLGLSLGPRTHVQAGNLSKATLWAEPGSVISRGNSVTIRCQGTLEAQEYRLVKEGSPEPWDTQNPLEPKNKARFSIPSMTEHHAGRYRCYYYSPAGWSEPSDPLELVVTGFYNKPTLSALPSPVVTSGENVTLQCGSRLRFDRFILTEEGDHKLSWTLDSQLTPSGQFQALFPVGP VTPSHRWMLRCYGSRRHILQVWSEPSDLLEIPVSGAADNLSPSQNKSDSGTASHLQDYAVENLIRMGMAGLILVVLGILIFQDWHSQRSPQAAAGR 357 Anti-human LILRA5/CD85f antibody (MAB6754, R&D Systems) LILRA6 NP_001347096 MTPALTALLCLGLSLGPRTRVQAGPFPKPTLWAEPGSVISWGSPVTIWCQGSLEAQEYQLDKEGSPEPLDRNNPLEPKNKARFSIPSMTQHHAGRYRCHYYSSAGWSEPSDPLELVMTGFYNKPTLSALPSPVVASGGNMTLRCGSQKGYHHFVLMKEGEHQLPRTLDSQQLHSGGFQALFPVGPVTPSHRWRFTCYYYYTNTPRV WSHPSDPLEILPSGVSRKPSLLTLQGPVLAPGQSLTLQCGSDVGYDRFVLYKEGERDFLQRPGQQPQAGLSQANFTLGPVSPSHGQYRCYGAHNLSSEWSAPSDPLNILMAGQIYDTVSLSAQPGPTVASGENVTLLCQSRGYFDTFLLTKEGAAHPPLRLRSMYGAHKYQAEFPMSPVTSAHAGTYRCYGSYSSNPHLLS FPSEPLELMVSGHSGGSSLPPTGPPSTPASHAKDYTVENLIRMGMAGLVLVFLGILLFEAQHSQRNPQDAAGR 358 Anti-human LILRA6/CD85b antibody (MAB8656, R&D Systems)

Example 6: Definition of EC ₅₀ to bind selected antibodies to LILRB1-overexpressing cell surface

In order to determine the EC ₅₀ values of the antibodies obtained in Examples 1 and 4 for binding to cell lines overexpressing human LILRB1, a cell surface binding assay was performed. Measured EC ₅₀ values of antibodies E3.1 and H11, representing the obtained antibodies. The CHO cells obtained in Example 5, which overexpress LILRB1 on the surface, were added to a 96-well U-bottom tissue culture plate (BD Falcon) at 1×10 ⁵ cells/well. Received three-fold serial dilutions of antibodies E3.1 and H11, starting with final concentrations of 600 μg/ml and 27 μg/ml, respectively. Cells were treated with each of the diluted antibodies and incubated at 4°C for 60 minutes. After washing with FACS buffer, cells were treated with anti-human Fc-biotin antibody (Invitrogen) and incubated at 4°C for 30 minutes. for 30 minutes. After washing with FACS buffer, the cells were resuspended and analyzed using the iQue screening device (Sartorius). EC ₅₀ values were calculated using the GraphPad Prism software non-linear regression formula and the results are shown in Table 28:

Table 28 E3.1 H11 EC ₅₀ (nM) 7.154 0.376

Example 7 Evaluation of Cross-Reactivity of Selected Antibodies with Cell Lines Overexpressing Human LILR Family Proteins

To confirm whether the selected antibodies bind to human LILR family proteins other than LILRB1, a cell surface binding assay was performed. CHO cells (prepared in Example 5) surface-expressing each of the various LILR family proteins were added to a 96-well U-bottom tissue culture plate (BD Falcon) at 1×10 ⁵ cells/well. Cells in each well were treated with the selected antibody at a final concentration of 20 μg/mL and incubated at 4°C for 60 minutes. After washing with FACS buffer, cells were treated with streptavidin (BD Pharmigen) fluorescently labeled with PE or FITC and incubated at 4° C. for 30 minutes. After washing with FACS buffer, cells were resuspended and analyzed using an iQue screening device (Sartorius). Cells treated with each LILR protein-specific antibody (Table 27) were used as a positive control, and cells treated with a human IgG4 isotype control antibody (Biolegend) were used as a negative control.

The results obtained for the E3.1 antibody are shown in Figs. 7a-7d (E3.1: red; LILR-specific antibody: blue; Isotype (hIgG4) control: gray) and the results obtained for the H11 antibody are shown in Fig. .8a-8d (H11: red; LILR-specific antibody: blue; Isotype (hIgG4) control: gray). As shown in Figs. 7a-7d and Figs. 8a-8d, antibodies E3.1 and H11 do not bind at all or hardly bind to LILRs other than LILRB1. These results show that the antibodies provided in the examples have the ability to specifically bind to LILRB1.

Example 8 Measurement of Granzyme B and Perforin Release by ELISPOT

In order to confirm whether antibodies E3.1 and H11 increase the level of cytotoxicity of NK cells, carried out the analysis of enzyme-linked immunosorbent stains (ELISPOT). The level of cytotoxicity was determined by the release of cytotoxic granules, granzyme B and perforin, in NK cells.

5×10 ³ LILRB1-expressing KHYG-1 (JCRB) cell lines and 5×10 ³ HLA-G overexpressing K562 cells (obtained by transducing K562 cells (American Type Culture Collection) with a lentivirus engineered to express HLA-G) were co-cultured in a 96-well U-bottom tissue culture plate. Each antibody (E3.1, H11 or human IgG4 isotype control antibody) was added at a final concentration of 50 μg/ml to each well and left to incubate at 37°C for 30 minutes. Co-cultured cells were transferred to 96-well plates (Immunospot , Cat. HGZBPFN-2M) (PVDF membrane) for ELISPOT, which were coated with anti-perforin antibody and anti-granzyme B, respectively, and further incubated at 37° C. for 8 hours. The PVDF membranes were washed with a wash solution (0.05% tween 20 in PBS), then treated with anti-granzyme B-HRP and anti-perforin-biotin antibodies. Detection was then carried out according to the manufacturer's protocol. The PVDF membranes were dried at room temperature for 24 hours and the spots for granzyme B and perforin were counted using an ELISPOT analyzer (Immunospot).

The results are shown in Fig. 9 (granzyme b; Gzmb) and Fig. 10 (perforin; Prf), respectively (y-axis indicates total number of spots). As shown in Fig. 9 and Fig. 10, the release levels of both granzyme B and perforin were significantly increased in the E3.1 or H11 antibody treated group compared to the human IgG4 isotype control antibody treated group. An unpaired T-test was used and all experiments were performed three times under the same conditions for the reliability of the experiment, and the results are presented as means.

Example 9: preparation of chimeric antibody GHI/75

In order to see if the antibodies shown in the examples showed higher efficacy compared to pre-existing antibodies, a chimeric GHI/75 antibody was prepared that included the variable region of the GHI/75 antibody (Biolegend, cat# 333721), which is a murine antibody to human LILRB1, and a human antibody constant region.

More specifically, the amino acid sequence of the GHI/75 antibody was analyzed by peptide mapping and a vector was obtained in which the nucleic acid sequence corresponding to the variable region (VH and VL domain) of the human IgG4 antibody was replaced with the nucleic acid sequence corresponding to the variable region (VH and VL domain) mouse antibody GHI/75. In the vector, the human IgG4 upper hinge region was replaced with a nucleic acid sequence corresponding to the human IgG1 upper hinge amino acid sequence (EPKSCDKTHT; SEQ ID NO:359). The vector was expressed as described in Example 1.4 and the resulting antibody was purified and used as a reference antibody in the examples below.

Example 10: Measurement of the Inhibitory Effect of Selected Antibodies on LILRB1 Signaling Using the Luciferase Assay Under the Control of the IL-2 Promoter

In order to confirm whether the antibodies obtained in Examples 1 and 4 inhibit signaling by LILRB1, a luciferase reporter assay was performed. Of the antibodies obtained in Examples 1 and 4, analysis was performed representative of antibodies E3.1 and H11, and the chimeric antibody GHI/75 obtained in Example 9 was used for comparison. Jurkat cells expressing LILRB1 and interleukin 2 (IL-2) were used. the luciferase promoter (obtained by inserting the IL-2 luciferase promoter vector (Promega) into a Jurkat cell line (American Type Culture Collection) followed by transduction with a lentivirus engineered to express LILRB1), and K562 cells overexpressing HLA-G. 96-well plates were coated with anti-CD3 antibody (Biolegend) by incubation with the antibody overnight at 4°C. The next day, Jurkat cells expressing LILRB1 and IL-2 luciferase promoter were added to 96-well U-bottomed plates at 1×10 ⁵ cells/well and the plates were treated with each antibody (E3.1, H11, chimeric GHI/ 75 or human IgG4 isotype (control)) to a final concentration of 20 μg/ml and incubated at 37°C for one hour. HLA-G overexpressing K562 cells (1×10 ⁵ cells/well) were added to the plates and incubated at 37°C for 30 minutes. The resulting suspension was transferred to a plate coated with anti-CD3 antibody and anti-CD28 antibody (Biolegend ) to a final concentration of 10 µg/mL. The tablet was incubated at 37°C for 6 hours. Steady-Glo® solution (Promega) was added to each well and luminescence intensity was recorded using a luminometer (Envision, PerkinElmer).

The results are shown in Fig.11. As shown in Figure 11, the E3.1 and H11 antibodies of the examples showed significantly higher LILRB1 signaling inhibitory activity compared to the human IgG4 isotype control antibody and the GHI/75 chimeric control antibody.

Example 11 Analysis of Anticancer Effect of Selected Antibodies in a Mouse Model

To analyze the anti-cancer effects of selected antibodies, according to Example 3, a mixture of 3×10 ⁶ HCT116 Red-Fluc colorectal carcinoma cells, 3×10 ⁶ THP-1 derived macrophage cells, and antibody (20 μg/mouse) were injected subcutaneously with 5 - week-old female CIEA NOG mice (NOG immunodeficient mice; Central Institute for Experimental Animals, Japan). The antibody used was an E3.1 or H11 antibody, and the human IgG4 isotype was used as a control antibody for comparison. From the 4th day after inoculation of the tumor cells of the mouse model, the antibody was administered at a dose of 5 mg/kg by intra-abdominal injection twice a week, and the tumor volume was measured, as shown in FIG. As shown in Fig. 12, the E3.1 and H11 antibodies exhibited a significant tumor growth inhibiting effect in mice transplanted with HCT116 colon cancer cells and THP-1 derived macrophages compared to the control antibody.

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SEQUENCE LIST

<110> LG CHEM, LTD.

<120> ANTI-LILRB1 ANTIBODY AND ITS USE

<130>OPP20204082KR

<150> 10-2019-0173414

<151> 2019-12-23

<150> 10-2020-0061907

<151> 2020-05-22

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Gln Gly Asp Ser Leu Arg Asn Phe Tyr Ala Ser

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Gly Lys Asn Asn Arg Pro Ser

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Asn Ser Arg Asp Ser Ser Gly Ser His Leu Thr Gly Val

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<211> 5

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<223> CDR-H1 from E3 or E3.1 (Kabat)

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Ser Tyr Ala Met Ser

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<212> Protein

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<223> CDR-H2 from E3 or E3.1 (Kabat)

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Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys

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Asp Thr Tyr Tyr Tyr Gly Ser Gly Arg Ser Asn Ala Phe Asp Ile

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<212> Protein

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<223> CDR-L1 of B3 (Kabat)

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Gln Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn

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<210> 8

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<223> CDR-L2 of B3 (Kabat)

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Asp Ala Ser Asn Leu Glu Thr

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<211> 7

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<223> CDR-L3 of B3 (Kabat)

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Gln Gln Tyr Asp Asn Leu Pro

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<211> 5

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<223> CDR-H1 of B3 (Kabat)

<400> 10

Asp Tyr Ala Met His

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<210> 11

<211> 17

<212> Protein

<213> Artificial sequence

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<223> CDR-H2 of B3 (Kabat)

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Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val Lys

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<210> 12

<211> 13

<212> Protein

<213> Artificial sequence

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<223> CDR-H3 of B3 (Kabat)

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Val Gly Asp Ser Ser Gly Trp Ser Asp Ala Phe Asp Ile

1 5 10

<210> 13

<211> 11

<212> Protein

<213> Artificial sequence

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<223> CDR-L1 from A10 (Kabat)

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Arg Ala Ser Gln Ser Val Ser Ser Asn Leu Ala

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<210> 14

<211> 7

<212> Protein

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<223> CDR-L2 from A10 (Kabat)

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Gly Ala Ser Thr Arg Ala Thr

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<211> 11

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<223> CDR-L3 from A10 (Kabat)

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Gln Gln Tyr Gly Ser Ser Pro Arg Met Tyr Thr

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<210> 16

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<223> CDR-H1 from A10 (Kabat)

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Ser Tyr Ala Ile Ser

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<210> 17

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<212> Protein

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<223> CDR-H2 from A10 (Kabat)

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Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln

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<211> 12

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<223> CDR-H3 from A10 (Kabat)

<400> 18

Gly Gly Leu Gly Glu Leu Asp Asn Trp Phe Asp Pro

1 5 10

<210> 19

<211> 11

<212> Protein

<213> Artificial sequence

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<223> CDR-L1 of G1 (Kabat)

<400> 19

Ser Gly Tyr Lys Leu Gly Asp Arg Tyr Val Ser

1 5 10

<210> 20

<211> 7

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from G1 (Kabat)

<400> 20

Lys Asp Ser Gln Arg Pro Ser

15

<210> 21

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L3 from G1 (Kabat)

<400> 21

Gln Ala Trp Asp Ser Gly Thr Gly Val

15

<210> 22

<211> 5

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 of G1 (Kabat)

<400> 22

Ser Tyr Gly Ile Ser

15

<210> 23

<211> 17

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from G1 (Kabat)

<400> 23

Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Glu Leu Gln

1 5 10 15

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<210> 24

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from G1 (Kabat)

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Val Gly Val Ala Gly Lys Leu Asp Tyr

15

<210> 25

<211> 14

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 of G9 (Kabat)

<400> 25

Thr Gly Ser Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val Ser

1 5 10

<210> 26

<211> 7

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from G9 (Kabat)

<400> 26

Asp Val Ser Asn Arg Pro Ser

15

<210> 27

<211> 12

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L3 from G9 (Kabat)

<400> 27

Ser Ser Tyr Thr Gly Ser Ser Thr Leu Asp Val Leu

1 5 10

<210> 28

<211> 5

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 of G9 (Kabat)

<400> 28

Ser Tyr Trp Ile Gly

15

<210> 29

<211> 17

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from G9 (Kabat)

<400> 29

Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe Gln

1 5 10 15

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<210> 30

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from G9 (Kabat)

<400> 30

Gln Tyr Tyr Asp Gly Gly Tyr Tyr Met Asp Val

1 5 10

<210> 31

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from H2 (Kabat)

<400> 31

Gln Gly Asp Ser Leu Arg Asn Tyr Tyr Ala Ser

1 5 10

<210> 32

<211> 7

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from H2 (Kabat)

<400> 32

Gly Asn Asn Lys Arg Pro Ser

15

<210> 33

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L3 from H2 (Kabat)

<400> 33

Asn Ser Leu Asp Ser Thr Tyr Asn His Pro Ile

1 5 10

<210> 34

<211> 5

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from H2 (Kabat)

<400> 34

Ser Tyr Asp Ile His

15

<210> 35

<211> 17

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from H2 (Kabat)

<400> 35

Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Lys Leu Gln

1 5 10 15

gly

<210> 36

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from H2 (Kabat)

<400> 36

Asp Gly Gly Asp Ala Phe Asp Ile

15

<210> 37

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from H11 (Kabat)

<400> 37

Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala Ser

1 5 10

<210> 38

<211> 7

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from H11 (Kabat)

<400> 38

Gly Arg Asn Asn Arg Pro Ser

15

<210> 39

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L3 from H11 (Kabat)

<400> 39

Lys Ser Arg Asp Ser Ser Gly Asn His Tyr Val

1 5 10

<210> 40

<211> 5

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 of H11 (Kabat)

<400> 40

Ser Tyr Tyr Met His

15

<210> 41

<211> 17

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 of H11 (Kabat)

<400> 41

Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 42

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 of H11 (Kabat)

<400> 42

Asp Ala Gly Ser Ser Ser Asp Tyr

15

<210> 43

<211> 14

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from F12 (Kabat)

<400> 43

Ala Gly Thr Ser Ser Asp Ile Gly Asp Tyr Asp Tyr Val Ser

1 5 10

<210> 44

<211> 7

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from F12 (Kabat)

<400> 44

Asp Val Ser Arg Arg Pro Ser

15

<210> 45

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L3 from F12 (Kabat)

<400> 45

Ala Ser Tyr Thr Ser Ser Ser Val Val Val

1 5 10

<210> 46

<211> 5

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from F12 (Kabat)

<400> 46

Ser Tyr Trp Ile Gly

15

<210> 47

<211> 17

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from F12 (Kabat)

<400> 47

Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe Gln

1 5 10 15

gly

<210> 48

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from F12 (Kabat)

<400> 48

Gln Tyr Tyr Asp Gly Gly Tyr Tyr Met Asp Val

1 5 10

<210> 49

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 of B9 (Kabat)

<400> 49

Arg Ala Ser Gln Ser Ile Ser Arg Tyr Leu Asn

1 5 10

<210> 50

<211> 7

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 of B9 (Kabat)

<400> 50

Gly Ala Ser Ser Leu Gln Ser

15

<210> 51

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L3 of B9 (Kabat)

<400> 51

Gln Gln Ala Tyr Gly Phe Pro Leu Thr

15

<210> 52

<211> 5

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 of B9 (Kabat)

<400> 52

Ser Tyr Ala Ile Ser

15

<210> 53

<211> 17

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 of B9 (Kabat)

<400> 53

Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 54

<211> 16

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 of B9 (Kabat)

<400> 54

Gly Glu Ile Ala Val Ala Gln Asn Trp Asp Tyr Tyr Gly Met Asp Val

1 5 10 15

<210> 55

<211> 14

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 of G11 (Kabat)

<400> 55

Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val Ser

1 5 10

<210> 56

<211> 7

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from G11 (Kabat)

<400> 56

Asp Val Ser Lys Arg Pro Ser

15

<210> 57

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L3 from G11 (Kabat)

<400> 57

Ser Ser Tyr Ser Ser Ser Ser Thr Leu Val Val

1 5 10

<210> 58

<211> 5

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 of G11 (Kabat)

<400> 58

Ser Tyr Trp Ile Gly

15

<210> 59

<211> 17

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from G11 (Kabat)

<400> 59

Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe Gln

1 5 10 15

gly

<210> 60

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from G11 (Kabat)

<400> 60

Gln Tyr Tyr Asp Gly Gly Tyr Tyr Met Asp Val

1 5 10

<210> 61

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 of G6 (Kabat)

<400> 61

Gln Gly Asp Ser Leu Arg Arg Tyr Tyr Ala Thr

1 5 10

<210> 62

<211> 7

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from G6 (Kabat)

<400> 62

Gly Gln Asn Tyr Arg Pro Ser

15

<210> 63

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L3 from G6 (Kabat)

<400> 63

Asn Ser Arg Asp Ser Ser Gly Asn His Val Val

1 5 10

<210> 64

<211> 5

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from G6 (Kabat)

<400> 64

Ser Tyr Tyr Met His

15

<210> 65

<211> 17

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from G6 (Kabat)

<400> 65

Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 66

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from G6 (Kabat)

<400> 66

Gly Trp Gly Tyr Ser Ser Ser Phe Asp Tyr

1 5 10

<210> 67

<211> 13

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from F11 (Kabat)

<400> 67

Ser Gly Ser Ser Ser Asn Ile Gly Thr Asn Thr Val Asn

1 5 10

<210> 68

<211> 7

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from F11 (Kabat)

<400> 68

Ser Asn Asp Gln Arg Pro Ser

15

<210> 69

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L3 from F11 (Kabat)

<400> 69

Glu Thr Trp Asp Asp Ser Leu Lys Gly Pro Val

1 5 10

<210> 70

<211> 5

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from F11 (Kabat)

<400> 70

Ser Tyr Ala Met Ser

15

<210> 71

<211> 17

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from F11 (Kabat)

<400> 71

Thr Ile Ser Gly Ser Gly Asp Ser Thr Tyr Tyr Ala Asp Ser Val Lys

1 5 10 15

gly

<210> 72

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from F11 (Kabat)

<400> 72

Glu Trp Glu Leu Gly Asp Ala Phe Asp Ile

1 5 10

<210> 73

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from D3 (Kabat)

<400> 73

Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn

1 5 10

<210> 74

<211> 7

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from D3 (Kabat)

<400> 74

Ala Ala Ser Ser Leu Gln Ser

15

<210> 75

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L3 from D3 (Kabat)

<400> 75

Gln Gln Ser Tyr Ser Thr Arg Trp Thr

15

<210> 76

<211> 5

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from D3 (Kabat)

<400> 76

Ser Tyr Ala Met Ser

15

<210> 77

<211> 17

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from D3 (Kabat)

<400> 77

Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys

1 5 10 15

gly

<210> 78

<211> 13

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from D3 (Kabat)

<400> 78

Asp Arg Gly Ser Tyr Gly Tyr Tyr Tyr Gly Met Asp Val

1 5 10

<210> 79

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 of B12 (Kabat)

<400> 79

Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn

1 5 10

<210> 80

<211> 7

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 of B12 (Kabat)

<400> 80

Ala Ala Ser Ser Leu Gln Ser

15

<210> 81

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L3 of B12 (Kabat)

<400> 81

Gln Gln Ser Tyr Ser Thr Leu Arg Thr

15

<210> 82

<211> 5

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 of B12 (Kabat)

<400> 82

Gly Tyr Tyr Met His

15

<210> 83

<211> 17

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 of B12 (Kabat)

<400> 83

Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 84

<211> 13

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 of B12 (Kabat)

<400> 84

Ala Gly Ala Ser Ile Val Gly Ala Thr Ala Leu Asp Tyr

1 5 10

<210> 85

<211> 13

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from E4 (Kabat)

<400> 85

Thr Arg Ser Ser Gly Ser Ile Ala Ser Asn Tyr Val Gln

1 5 10

<210> 86

<211> 7

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from E4 (Kabat)

<400> 86

Glu Asp Asn Gln Arg Pro Ser

15

<210> 87

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L3 from E4 (Kabat)

<400> 87

Gln Ser Tyr Asp Thr Gly Asn Arg Asn Tyr Val

1 5 10

<210> 88

<211> 5

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from E4 (Kabat)

<400> 88

Ser Tyr Thr Ile Ser

15

<210> 89

<211> 17

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from E4 (Kabat)

<400> 89

Arg Ile Ile Pro Ile Leu Gly Ile Ala Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 90

<211> 12

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from E4 (Kabat)

<400> 90

Gly Pro Ser Leu Asn Tyr Ala Gly Tyr Phe Asp Asn

1 5 10

<210> 91

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from E12 (Kabat)

<400> 91

Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala Ser

1 5 10

<210> 92

<211> 7

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from E12 (Kabat)

<400> 92

Gly Lys Glu Lys Arg Pro Ser

15

<210> 93

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L3 from E12 (Kabat)

<400> 93

Asn Ser Arg Gly Ser Thr Thr Asp Tyr Met Val

1 5 10

<210> 94

<211> 5

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from E12 (Kabat)

<400> 94

Ser Tyr Ala Met His

15

<210> 95

<211> 17

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from E12 (Kabat)

<400> 95

Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val Lys

1 5 10 15

gly

<210> 96

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from E12 (Kabat)

<400> 96

Glu Arg Gly Ser Gly Met Asp Val

15

<210> 97

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 of D1 (Kabat)

<400> 97

Lys Ala Ser Gln Asp Ile Asp Asp Asp Met Asn

1 5 10

<210> 98

<211> 7

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from D1 (Kabat)

<400> 98

Glu Ala Ser Thr Leu Val Pro

15

<210> 99

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L3 from D1 (Kabat)

<400> 99

Leu Gln His Asp Lys Phe Pro Tyr Thr

15

<210> 100

<211> 5

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from D1 (Kabat)

<400> 100

Ser Tyr Gly Ile Ser

15

<210> 101

<211> 17

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from D1 (Kabat)

<400> 101

Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 102

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from D1 (Kabat)

<400> 102

Arg Gly Val Asp Glu Gly Asp Tyr

15

<210> 103

<211> 13

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from E6 (Kabat)

<400> 103

Thr Gly Ser Ser Gly Asn Ile Ala Ser Asn Tyr Val Gln

1 5 10

<210> 104

<211> 7

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from E6 (Kabat)

<400> 104

Arg Asp Asp Gln Arg Pro Ser

15

<210> 105

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L3 from E6 (Kabat)

<400> 105

Gln Ser Tyr Asp Ser Ser Ser Trp Val

15

<210> 106

<211> 5

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from E6 (Kabat)

<400> 106

Thr Tyr Asp Ile Thr

15

<210> 107

<211> 17

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from E6 (Kabat)

<400> 107

Trp Met Asn Pro Asn Ser Gly Asn Ser Arg Ser Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 108

<211> 15

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from E6 (Kabat)

<400> 108

Gly Asp Tyr Ser Gly Val Val Leu Thr Ala Thr Ala Leu Asp Tyr

1 5 10 15

<210> 109

<211> 13

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from E9 (Kabat)

<400> 109

Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn Tyr Val Tyr

1 5 10

<210> 110

<211> 7

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from E9 (Kabat)

<400> 110

Arg Asn Asn Gln Arg Pro Ser

15

<210> 111

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L3 from E9 (Kabat)

<400> 111

Ala Ala Trp Asp Asp Ser Leu Ser Gly Trp Val

1 5 10

<210> 112

<211> 5

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from E9 (Kabat)

<400> 112

Ser Tyr Gly Met His

15

<210> 113

<211> 17

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from E9 (Kabat)

<400> 113

Asn Ile Lys Gln Asp Gly Ser Glu Lys Tyr Tyr Val Asp Ser Val Lys

1 5 10 15

gly

<210> 114

<211> 14

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from E9 (Kabat)

<400> 114

Glu Asp Arg Ile Ala Ala Ala Gly Met Arg Glu Leu Asp Tyr

1 5 10

<210> 115

<211> 16

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 of A11 (Kabat)

<400> 115

Arg Ser Ser Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu Asp

1 5 10 15

<210> 116

<211> 7

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from A11 (Kabat)

<400> 116

Leu Gly Ser Asn Arg Ala Ser

15

<210> 117

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L3 from A11 (Kabat)

<400> 117

Met Gln Gly Thr His Trp Pro Pro Tyr Thr

1 5 10

<210> 118

<211> 5

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from A11 (Kabat)

<400> 118

Ser Tyr Ala Met Thr

15

<210> 119

<211> 17

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from A11 (Kabat)

<400> 119

Gly Ile Ser Ser Asp Gly Thr Thr Thr Thr Tyr Ala Asp Ser Val Arg

1 5 10 15

gly

<210> 120

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from A11 (Kabat)

<400> 120

Asp Gln Leu Leu Gly Trp Asp Ala Leu Asn Val

1 5 10

<210> 121

<211> 6

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from E3 or E3.1 (IGMT)

<400> 121

Ser Leu Arg Asn Phe Tyr

15

<210> 122

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from E3 or E3.1 (IGMT)

<400> 122

Gly Lys Asn

1

<210> 123

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from E3 or E3.1 (IGMT)

<400> 123

Gly Phe Thr Phe Ser Ser Tyr Ala

15

<210> 124

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from E3 or E3.1 (IGMT)

<400> 124

Ile Ser Gly Ser Gly Gly Ser Thr

15

<210> 125

<211> 17

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from E3 or E3.1 (IGMT)

<400> 125

Ala Arg Asp Thr Tyr Tyr Tyr Gly Ser Gly Arg Ser Asn Ala Phe Asp

1 5 10 15

ile

<210> 126

<211> 6

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from B3 (IGMT)

<400> 126

Gln Asp Ile Ser Asn Tyr

15

<210> 127

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from B3 (IGMT)

<400> 127

Asp Ala Ser

1

<210> 128

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from B3 (IGMT)

<400> 128

Gly Phe Thr Phe Asp Asp Tyr Ala

15

<210> 129

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from B3 (IGMT)

<400> 129

Ile Ser Trp Asn Ser Gly Ser Ile

15

<210> 130

<211> 15

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from B3 (IGMT)

<400> 130

Ala Arg Val Gly Asp Ser Ser Gly Trp Ser Asp Ala Phe Asp Ile

1 5 10 15

<210> 131

<211> 6

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from A10 (IGMT)

<400> 131

Gln Ser Val Ser Ser Asn

15

<210> 132

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from A10 (IGMT)

<400> 132

Gly Ala Ser

1

<210> 133

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from A10 (IGMT)

<400> 133

Gly Gly Thr Phe Ser Ser Tyr Ala

15

<210> 134

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from A10 (IGMT)

<400> 134

Ile Ile Pro Ile Phe Gly Thr Ala

15

<210> 135

<211> 14

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from A10 (IGMT)

<400> 135

Ala Arg Gly Gly Leu Gly Glu Leu Asp Asn Trp Phe Asp Pro

1 5 10

<210> 136

<211> 6

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from G1 (IGMT)

<400> 136

Lys Leu Gly Asp Arg Tyr

15

<210> 137

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from G1 (IGMT)

<400> 137

Lys Asp Ser

1

<210> 138

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from G1 (IGMT)

<400> 138

Gly Gly Thr Phe Ser Ser Tyr Gly

15

<210> 139

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from G1 (IGMT)

<400> 139

Ile Ser Ala Tyr Asn Gly Asn Thr

15

<210> 140

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from G1 (IGMT)

<400> 140

Ala Arg Val Gly Val Ala Gly Lys Leu Asp Tyr

1 5 10

<210> 141

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 of G9 (IGMT)

<400> 141

Ser Ser Asp Val Gly Gly Tyr Asn Tyr

15

<210> 142

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from G9 (IGMT)

<400> 142

Asp Val Ser

1

<210> 143

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from G9 (IGMT)

<400> 143

Gly Tyr Ser Phe Thr Ser Tyr Trp

15

<210> 144

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from G9 (IGMT)

<400> 144

Ile Tyr Pro Gly Asp Ser Asp Thr

15

<210> 145

<211> 13

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from G9 (IGMT)

<400> 145

Ala Ser Gln Tyr Tyr Asp Gly Gly Tyr Tyr Met Asp Val

1 5 10

<210> 146

<211> 6

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from H2 (IGMT)

<400> 146

Ser Leu Arg Asn Tyr Tyr

15

<210> 147

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from H2 (IGMT)

<400> 147

Gly Asn Asn

1

<210> 148

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from H2 (IGMT)

<400> 148

Gly Tyr Thr Phe Thr Ser Tyr Asp

15

<210> 149

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from H2 (IGMT)

<400> 149

Ile Ser Ala Tyr Asn Gly Asn Thr

15

<210> 150

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from H2 (IGMT)

<400> 150

Ala Arg Asp Gly Gly Asp Ala Phe Asp Ile

1 5 10

<210> 151

<211> 6

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from H11 (IGMT)

<400> 151

Ser Leu Arg Ser Tyr Tyr

15

<210> 152

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from H11 (IGMT)

<400> 152

Gly Arg Asn

1

<210> 153

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from H11 (IGMT)

<400> 153

Gly Tyr Thr Phe Thr Ser Tyr Tyr

15

<210> 154

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from H11 (IGMT)

<400> 154

Ile Asn Pro Ser Gly Gly Ser Thr

15

<210> 155

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from H11 (IGMT)

<400> 155

Ala Arg Asp Ala Gly Ser Ser Ser Asp Tyr

1 5 10

<210> 156

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from F12 (IGMT)

<400> 156

Ser Ser Asp Ile Gly Asp Tyr Asp Tyr

15

<210> 157

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from F12 (IGMT)

<400> 157

Asp Val Ser

1

<210> 158

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from F12 (IGMT)

<400> 158

Gly Tyr Ser Phe Thr Ser Tyr Trp

15

<210> 159

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from F12 (IGMT)

<400> 159

Ile Tyr Pro Gly Asp Ser Asp Thr

15

<210> 160

<211> 13

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from F12 (IGMT)

<400> 160

Ala Ser Gln Tyr Tyr Asp Gly Gly Tyr Tyr Met Asp Val

1 5 10

<210> 161

<211> 6

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from B9 (IGMT)

<400> 161

Gln Ser Ile Ser Arg Tyr

15

<210> 162

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from B9 (IGMT)

<400> 162

Gly Ala Ser

1

<210> 163

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from B9 (IGMT)

<400> 163

Gly Gly Thr Phe Ser Ser Tyr Ala

15

<210> 164

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from B9 (IGMT)

<400> 164

Ile Ile Pro Ile Phe Gly Thr Ala

15

<210> 165

<211> 18

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from B9 (IGMT)

<400> 165

Ala Arg Gly Glu Ile Ala Val Ala Gln Asn Trp Asp Tyr Tyr Gly Met

1 5 10 15

Asp Val

<210> 166

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 of G11 (IGMT)

<400> 166

Ser Ser Asp Val Gly Gly Tyr Asn Tyr

15

<210> 167

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from G11 (IGMT)

<400> 167

Asp Val Ser

1

<210> 168

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from G11 (IGMT)

<400> 168

Gly Tyr Ser Phe Thr Ser Tyr Trp

15

<210> 169

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from G11 (IGMT)

<400> 169

Ile Tyr Pro Gly Asp Ser Asp Thr

15

<210> 170

<211> 13

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from G11 (IGMT)

<400> 170

Ala Ser Gln Tyr Tyr Asp Gly Gly Tyr Tyr Met Asp Val

1 5 10

<210> 171

<211> 6

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from G6 (IGMT)

<400> 171

Ser Leu Arg Arg Tyr Tyr

15

<210> 172

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from G6 (IGMT)

<400> 172

Gly Gln Asn

1

<210> 173

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from G6 (IGMT)

<400> 173

Gly Tyr Thr Phe Thr Ser Tyr Tyr

15

<210> 174

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from G6 (IGMT)

<400> 174

Ile Ile Pro Ile Phe Gly Thr Ala

15

<210> 175

<211> 12

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from G6 (IGMT)

<400> 175

Ala Arg Gly Trp Gly Tyr Ser Ser Ser Phe Asp Tyr

1 5 10

<210> 176

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from F11 (IGMT)

<400> 176

Ser Ser Asn Ile Gly Thr Asn Thr

15

<210> 177

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from F11 (IGMT)

<400> 177

Ser Asn Asp

1

<210> 178

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from F11 (IGMT)

<400> 178

Gly Phe Thr Phe Ser Ser Tyr Ala

15

<210> 179

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from F11 (IGMT)

<400> 179

Ile Ser Gly Ser Gly Asp Ser Thr

15

<210> 180

<211> 12

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from F11 (IGMT)

<400> 180

Ala Arg Glu Trp Glu Leu Gly Asp Ala Phe Asp Ile

1 5 10

<210> 181

<211> 6

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from D3 (IGMT)

<400> 181

Gln Ser Ile Ser Ser Tyr

15

<210> 182

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from D3 (IGMT)

<400> 182

Ala Ala Ser

1

<210> 183

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from D3 (IGMT)

<400> 183

Gly Ser Thr Phe Ser Ser Tyr Ala

15

<210> 184

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from D3 (IGMT)

<400> 184

Ile Ser Gly Ser Gly Gly Ser Thr

15

<210> 185

<211> 15

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from D3 (IGMT)

<400> 185

Ala Lys Asp Arg Gly Ser Tyr Gly Tyr Tyr Tyr Gly Met Asp Val

1 5 10 15

<210> 186

<211> 6

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 of B12 (IGMT)

<400> 186

Gln Ser Ile Ser Ser Tyr

15

<210> 187

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from B12 (IGMT)

<400> 187

Ala Ala Ser

1

<210> 188

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from B12 (IGMT)

<400> 188

Gly Tyr Thr Phe Thr Gly Tyr Tyr

15

<210> 189

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from B12 (IGMT)

<400> 189

Ile Asn Pro Asn Ser Gly Gly Thr

15

<210> 190

<211> 15

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from B12 (IGMT)

<400> 190

Thr Arg Ala Gly Ala Ser Ile Val Gly Ala Thr Ala Leu Asp Tyr

1 5 10 15

<210> 191

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from E4 (IGMT)

<400> 191

Ser Gly Ser Ile Ala Ser Asn Tyr

15

<210> 192

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from E4 (IGMT)

<400> 192

Glu Asp Asn

1

<210> 193

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from E4 (IGMT)

<400> 193

Gly Gly Thr Phe Ser Ser Tyr Thr

15

<210> 194

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from E4 (IGMT)

<400> 194

Ile Ile Pro Ile Leu Gly Ile Ala

15

<210> 195

<211> 14

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from E4 (IGMT)

<400> 195

Val Arg Gly Pro Ser Leu Asn Tyr Ala Gly Tyr Phe Asp Asn

1 5 10

<210> 196

<211> 6

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from E12 (IGMT)

<400> 196

Ser Leu Arg Ser Tyr Tyr

15

<210> 197

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from E12 (IGMT)

<400> 197

Gly Lys Glu

1

<210> 198

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from E12 (IGMT)

<400> 198

Gly Phe Thr Phe Ser Ser Tyr Ala

15

<210> 199

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from E12 (IGMT)

<400> 199

Ile Ser Tyr Asp Gly Ser Asn Lys

15

<210> 200

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from E12 (IGMT)

<400> 200

Ala Arg Glu Arg Gly Ser Gly Met Asp Val

1 5 10

<210> 201

<211> 6

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from D1 (IGMT)

<400> 201

Gln Asp Ile Asp Asp Asp

15

<210> 202

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from D1 (IGMT)

<400> 202

Glu Ala Ser

1

<210> 203

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from D1 (IGMT)

<400> 203

Gly Tyr Thr Phe Thr Ser Tyr Gly

15

<210> 204

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from D1 (IGMT)

<400> 204

Ile Asn Pro Asn Ser Gly Gly Thr

15

<210> 205

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from D1 (IGMT)

<400> 205

Ala Ser Arg Gly Val Asp Glu Gly Asp Tyr

1 5 10

<210> 206

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from E6 (IGMT)

<400> 206

Ser Gly Asn Ile Ala Ser Asn Tyr

15

<210> 207

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from E6 (IGMT)

<400> 207

Arg Asp Asp

1

<210> 208

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from E6 (IGMT)

<400> 208

Gly Tyr Thr Phe Thr Thr Tyr Asp

15

<210> 209

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from E6 (IGMT)

<400> 209

Met Asn Pro Asn Ser Gly Asn Ser

15

<210> 210

<211> 17

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from E6 (IGMT)

<400> 210

Ala Thr Gly Asp Tyr Ser Gly Val Val Leu Thr Ala Thr Ala Leu Asp

1 5 10 15

Tyr

<210> 211

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from E9 (IGMT)

<400> 211

Ser Ser Asn Ile Gly Asn Asn Tyr

15

<210> 212

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from E9 (IGMT)

<400> 212

Arg Asn Asn

1

<210> 213

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from E9 (IGMT)

<400> 213

Gly Phe Thr Phe Ser Ser Tyr Gly

15

<210> 214

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from E9 (IGMT)

<400> 214

Ile Lys Gln Asp Gly Ser Glu Lys

15

<210> 215

<211> 16

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from E9 (IGMT)

<400> 215

Ala Arg Glu Asp Arg Ile Ala Ala Ala Gly Met Arg Glu Leu Asp Tyr

1 5 10 15

<210> 216

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L1 from A11 (IGMT)

<400> 216

Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr

1 5 10

<210> 217

<211> 3

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-L2 from A11 (IGMT)

<400> 217

Leu Gly Ser

1

<210> 218

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H1 from A11 (IGMT)

<400> 218

Gly Phe Ser Phe Thr Ser Tyr Ala

15

<210> 219

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H2 from A11 (IGMT)

<400> 219

Ile Ser Ser Asp Gly Thr Thr Thr

15

<210> 220

<211> 13

<212> Protein

<213> Artificial sequence

<220>

<223> CDR-H3 from A11 (IGMT)

<400> 220

Ala Arg Asp Gln Leu Leu Gly Trp Asp Ala Leu Asn Val

1 5 10

<210> 221

<211> 116

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (E3)

<400> 221

Ser Tyr Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln

1 5 10 15

Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Asn Phe Tyr Ala

20 25 30

Ser Trp Tyr Gln Gln Lys Ser Gly Gln Ala Pro Val Leu Val Met Tyr

35 40 45

Gly Lys Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

Thr Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Ser His

85 90 95

Leu Thr Gly Val Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly Gln

100 105 110

Pro Ala Ala Ala

115

<210> 222

<211> 124

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (E3 or E3.1)

<400> 222

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Ile Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Thr Tyr Tyr Tyr Gly Ser Gly Arg Ser Asn Ala Phe Asp

100 105 110

Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 223

<211> 110

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (B3)

<400> 223

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Asn Leu Pro Phe

85 90 95

Gly Gly Gly Thr Lys Val Asp Ile Lys Arg Thr Ala Ala Ala

100 105 110

<210> 224

<211> 122

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (B3)

<400> 224

Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Val Gly Asp Ser Ser Gly Trp Ser Asp Ala Phe Asp Ile Trp

100 105 110

Gly Gln Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 225

<211> 114

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (A10)

<400> 225

Asp Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Asn

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Arg

85 90 95

Met Tyr Thr Phe Gly Gln Gly Thr Lys Val Asp Ile Lys Arg Thr Ala

100 105 110

Ala Ala

<210> 226

<211> 121

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (A10)

<400> 226

Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Gly Leu Gly Glu Leu Asp Asn Trp Phe Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 227

<211> 112

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (G1)

<400> 227

Ser Tyr Glu Leu Thr Gln Pro Ser Leu Ser Val Ser Pro Gly Gln

1 5 10 15

Thr Ala Ser Ile Thr Cys Ser Gly Tyr Lys Leu Gly Asp Arg Tyr Val

20 25 30

Ser Trp Tyr Gln Gln Lys Thr Gly Gln Ser Pro Val Val Val Ile Tyr

35 40 45

Lys Asp Ser Gln Arg Pro Ser Gly Val Pro Glu Arg Phe Ser Gly Ser

50 55 60

Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala Met

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Gln Ala Trp Asp Ser Gly Thr Gly Val

85 90 95

Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Ala Ala Ala

100 105 110

<210> 228

<211> 118

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (G1)

<400> 228

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Glu Leu

50 55 60

Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Val Gly Val Ala Gly Lys Leu Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser

115

<210> 229

<211> 112

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (B9)

<400> 229

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Arg Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Gly Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr His Cys Gln Gln Ala Tyr Gly Phe Pro Leu

85 90 95

Thr Leu Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Ala Ala Ala

100 105 110

<210> 230

<211> 125

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (B9)

<400> 230

Gln Val Gln Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Glu Ile Ala Val Ala Gln Asn Trp Asp Tyr Tyr Gly Met

100 105 110

Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 231

<211> 114

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (H11)

<400> 231

Ser Tyr Glu Leu Thr Gln Asp Pro Ala Ala Ser Val Ala Leu Gly Gln

1 5 10 15

Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala

20 25 30

Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Val Val Ile Tyr

35 40 45

Gly Arg Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

Ser Ser Gly Asp Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Lys Ser Arg Asp Ser Ser Gly Asn His

85 90 95

Tyr Val Phe Gly Thr Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Ala

100 105 110

Ala Ala

<210> 232

<211> 117

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (H11)

<400> 232

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Ile Ile Asn Pro Ser Gly Ser Thr Ser Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Ala Gly Ser Ser Ser Asp Tyr Trp Gly Arg Gly Thr Leu

100 105 110

Val Thr Val Ser Ser

115

<210> 233

<211> 118

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (G9)

<400> 233

Gln Ser Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln

1 5 10 15

Ser Ile Thr Ile Ser Cys Thr Gly Ser Ser Ser Asp Val Gly Gly Tyr

20 25 30

Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu

35 40 45

Met Ile Tyr Asp Val Ser Asn Arg Pro Ser Gly Val Ser Asp Arg Phe

50 55 60

Ser Gly Ser Lys Ser Gly Asn Met Ala Ser Leu Thr Ile Ser Gly Leu

65 70 75 80

Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Thr Gly Ser

85 90 95

Ser Thr Leu Asp Val Leu Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105 110

Gly Gln Pro Ala Ala Ala

115

<210> 234

<211> 120

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (G9)

<400> 234

Gln Val Gln Leu Val Gln Pro Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Ser Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Ser Gln Tyr Tyr Asp Gly Gly Tyr Tyr Met Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 235

<211> 114

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (H2)

<400> 235

Ser Tyr Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln

1 5 10 15

Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Asn Tyr Tyr Ala

20 25 30

Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Ile Leu Val Ile Ser

35 40 45

Gly Asn Asn Lys Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

Ser Ser Gly Asp Thr Ala Ser Leu Thr Ile Ser Gly Ala Gln Ala Glu

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Leu Asp Ser Thr Tyr Asn His

85 90 95

Pro Ile Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly Gln Pro Ala

100 105 110

Ala Ala

<210> 236

<211> 117

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (H2)

<400> 236

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Asp Ile His Trp Val Arg Gln Ala Thr Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Lys Leu

50 55 60

Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Gly Gly Asp Ala Phe Asp Ile Trp Gly Gln Gly Thr Leu

100 105 110

Val Thr Val Ser Ser

115

<210> 237

<211> 116

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (F12)

<400> 237

Gln Ser Val Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln

1 5 10 15

Ser Ile Thr Ile Ser Cys Ala Gly Thr Ser Ser Asp Ile Gly Asp Tyr

20 25 30

Asp Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Thr Pro Lys Leu

35 40 45

Met Ile Tyr Asp Val Ser Arg Arg Pro Ser Gly Val Pro Asp Arg Phe

50 55 60

Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu

65 70 75 80

Gln Thr Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ser Tyr Thr Ser Ser

85 90 95

Ser Val Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln

100 105 110

Pro Ala Ala Ala

115

<210> 238

<211> 120

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (F12)

<400> 238

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Ser Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Ser Gln Tyr Tyr Asp Gly Gly Tyr Tyr Met Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 239

<211> 117

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (G11)

<400> 239

Gln Ser Ala Leu Thr Gln Pro Arg Ser Val Ser Gly Ser Pro Gly Gln

1 5 10 15

Ser Val Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr

20 25 30

Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu

35 40 45

Met Ile Tyr Asp Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe

50 55 60

Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu

65 70 75 80

Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ser Ser Ser

85 90 95

Ser Thr Leu Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly

100 105 110

Gln Pro Ala Ala Ala

115

<210> 240

<211> 120

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (G11)

<400> 240

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Ser Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Ser Gln Tyr Tyr Asp Gly Gly Tyr Tyr Met Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 241

<211> 114

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (G6)

<400> 241

Ser Tyr Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln

1 5 10 15

Thr Val Thr Ile Thr Cys Gln Gly Asp Ser Leu Arg Arg Tyr Tyr Ala

20 25 30

Thr Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr

35 40 45

Gly Gln Asn Tyr Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

Asn Ser Gly Thr Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Asn His

85 90 95

Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Ala

100 105 110

Ala Ala

<210> 242

<211> 119

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (G6)

<400> 242

Glu Val Gln Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Trp Gly Tyr Ser Ser Ser Phe Asp Tyr Trp Gly Gln Gly

100 105 110

Thr Thr Val Thr Val Ser Ser

115

<210> 243

<211> 116

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (F11)

<400> 243

Gln Ser Val Leu Thr Gln Pro Pro Ser Thr Ser Gly Thr Pro Gly Gln

1 5 10 15

Thr Phe Ser Ile Phe Cys Ser Gly Ser Ser Ser Asn Ile Gly Thr Asn

20 25 30

Thr Val Asn Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Ser Asn Asp Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Gln

65 70 75 80

Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Glu Thr Trp Asp Asp Ser Leu

85 90 95

Lys Gly Pro Val Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly Gln

100 105 110

Pro Ala Ala Ala

115

<210> 244

<211> 119

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (F11)

<400> 244

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Ser Gly Ser Gly Asp Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Asn Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Trp Glu Leu Gly Asp Ala Phe Asp Ile Trp Gly Arg Gly

100 105 110

Thr Leu Val Thr Val Ser Ser

115

<210> 245

<211> 112

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (D3)

<400> 245

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Arg Trp

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Ala Ala Ala

100 105 110

<210> 246

<211> 122

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (D3)

<400> 246

Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Ser Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Asp Arg Gly Ser Tyr Gly Tyr Tyr Tyr Gly Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 247

<211> 112

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (B12)

<400> 247

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Leu Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Ala Ala Ala

100 105 110

<210> 248

<211> 122

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (B12)

<400> 248

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Thr Arg Ala Gly Ala Ser Ile Val Gly Ala Thr Ala Leu Asp Tyr Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 249

<211> 118

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (E4)

<400> 249

Asn Phe Met Leu Thr Gln Pro His Ser Val Ser Glu Ser Pro Gly Lys

1 5 10 15

Thr Val Thr Ile Ser Cys Thr Arg Ser Ser Gly Ser Ile Ala Ser Asn

20 25 30

Tyr Val Gln Trp Tyr Gln Gln Arg Pro Gly Ser Ser Pro Thr Thr Val

35 40 45

Ile Tyr Glu Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Ile Asp Ser Ser Ser Asn Ser Ala Ser Leu Thr Ile Ser Gly

65 70 75 80

Leu Lys Thr Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Tyr Asp Thr

85 90 95

Gly Asn Arg Asn Tyr Val Phe Gly Thr Gly Thr Gln Leu Thr Val Leu

100 105 110

Gly Gln Pro Ala Ala Ala

115

<210> 250

<211> 121

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (E4)

<400> 250

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Thr Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Ile Pro Ile Leu Gly Ile Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Met Ser Thr Asp Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Thr Tyr Asp Asp Thr Ala Val Tyr Phe Cys

85 90 95

Val Arg Gly Pro Ser Leu Asn Tyr Ala Gly Tyr Phe Asp Asn Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 251

<211> 114

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (E12)

<400> 251

Ser Tyr Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln

1 5 10 15

Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala

20 25 30

Ser Trp Tyr Gln Gln Lys Ser Gly Gln Ala Pro Val Leu Val Ile Tyr

35 40 45

Gly Lys Glu Lys Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Arg Ala Glu

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Gly Ser Thr Thr Asp Tyr

85 90 95

Met Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Gly Gln Pro Ala

100 105 110

Ala Ala

<210> 252

<211> 117

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (E12)

<400> 252

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Glu Trp Val

35 40 45

Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Arg Gly Ser Gly Met Asp Val Trp Gly Gln Gly Thr Leu

100 105 110

Val Thr Val Ser Ser

115

<210> 253

<211> 112

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (D1)

<400> 253

Glu Thr Thr Leu Thr Gln Ser Pro Ala Phe Met Ser Ala Thr Pro Gly

1 5 10 15

Asp Lys Val Asn Ile Ser Cys Lys Ala Ser Gln Asp Ile Asp Asp Asp

20 25 30

Met Asn Trp Tyr Gln Gln Lys Pro Gly Glu Ala Ala Ile Ser Ile Ile

35 40 45

Gln Glu Ala Ser Thr Leu Val Pro Gly Ile Pro Pro Arg Phe Ser Gly

50 55 60

Ser Gly Tyr Gly Thr Asp Phe Thr Leu Thr Ile Asn Asn Ile Glu Ser

65 70 75 80

Glu Asp Ala Ala Tyr Tyr Phe Cys Leu Gln His Asp Lys Phe Pro Tyr

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Ala Ala Ala

100 105 110

<210> 254

<211> 117

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (D1)

<400> 254

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Ser Arg Gly Val Asp Glu Gly Asp Tyr Trp Gly Gln Gly Thr Met

100 105 110

Val Thr Val Ser Ser

115

<210> 255

<211> 116

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (E6)

<400> 255

Asn Phe Met Leu Thr Gln Pro His Ser Val Ser Glu Ser Pro Gly Lys

1 5 10 15

Thr Val Thr Leu Ser Cys Thr Gly Ser Ser Gly Asn Ile Ala Ser Asn

20 25 30

Tyr Val Gln Trp Tyr Gln His Arg Pro Gly Ser Ala Pro Thr Thr Val

35 40 45

Ile Tyr Arg Asp Asp Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Ile Asp Ser Ser Ser Asn Ser Ala Ser Leu Thr Ile Ser Gly

65 70 75 80

Leu Arg Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Tyr Asp Ser

85 90 95

Ser Ser Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln

100 105 110

Pro Ala Ala Ala

115

<210> 256

<211> 124

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (E6)

<400> 256

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Thr Tyr

20 25 30

Asp Ile Thr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Trp Met Asn Pro Asn Ser Gly Asn Ser Arg Ser Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Ser Met Thr Ser Asp Ser Ser Ile Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Thr Gly Asp Tyr Ser Gly Val Val Leu Thr Ala Thr Ala Leu Asp

100 105 110

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 257

<211> 116

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (E9)

<400> 257

Gln Ser Glu Leu Thr Gln Leu Pro Ser Ala Ser Glu Thr Pro Gly Gln

1 5 10 15

Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn

20 25 30

Tyr Val Tyr Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asn Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg

65 70 75 80

Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ala Trp Asp Asp Ser Leu

85 90 95

Ser Gly Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln

100 105 110

Pro Ala Ala Ala

115

<210> 258

<211> 123

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (E9)

<400> 258

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ala Asn Ile Lys Gln Asp Gly Ser Glu Lys Tyr Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Asp Arg Ile Ala Ala Ala Gly Met Arg Glu Leu Asp Tyr

100 105 110

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 259

<211> 118

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (A11)

<400> 259

Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser

20 25 30

Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly

85 90 95

Thr His Trp Pro Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Thr Ala Ala Ala

115

<210> 260

<211> 120

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain variable region (A11)

<400> 260

Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Glu Gln Pro Gly Gly

1 5 10 15

Phe Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Thr Ser Tyr

20 25 30

Ala Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Ser Asp Gly Thr Thr Thr Thr Tyr Ala Asp Ser Val

50 55 60

Arg Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Asp Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Gln Leu Leu Gly Trp Asp Ala Leu Asn Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 261

<211> 348

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (E3)

<400> 261

tcctatgagc tgactcagga ccctgctgtg tctgtggcct tgggacagac agtcaggatc 60

acatgccagg gagacagcct cagaaacttt tatgcaagct ggtaccagca gaagtcagga 120

caggccccag ttcttgtcat gtatggtaaa aacaaccggc cctcagggat cccagaccga 180

ttctctggct ccacctcagg aaacacagct tccttgacca tcactggggc tcaggcggaa 240

gatgaggctg actattactg taactcccgg gacagcagtg gtagccattt gacgggcgta 300

ttcggcggag ggaccaaggt caccgtccta ggtcagcccg cggccgca 348

<210> 262

<211> 372

<212> DNA

<213> Artificial sequence

<220>

<223> Gene encoding heavy chain variable region (E3 or E3.1)

<400> 262

caggtgcagc tggtggagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttagc agctatgcca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagct attagtggta gtggtggtag cacatactac 180

gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa tacgctgtat 240

ctgcaaatga ttagcctgag agctgaggac acggctgtgt attactgtgc gagagatacg 300

tattactatg gttcggggag aagtaatgct tttgatatat ggggccaggg aaccctggtc 360

accgtctcga gt 372

<210> 263

<211> 330

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (B3)

<400> 263

gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc aggcgagtca ggacattagc aactatttga attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctacgat gcatccaatt tggaaacagg ggtcccatca 180

aggttcagtg gaagtggatc tgggacagat tttactttca ccatcagcag cctgcagcct 240

gaagatattg caacatatta ctgtcaacag tatgataatc tccctttcgg cggagggacc 300

aaagtggata tcaaacgtac cgcggccgca 330

<210> 264

<211> 366

<212> DNA

<213> Artificial sequence

<220>

<223> Gene encoding heavy chain variable region (B3)

<400> 264

gaggtgcagc tgttggagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120

ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag cataggctac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240

cttcaaatga acagtctgag agccgaggac acggccgtgt attactgtgc gagagttggg 300

gatagcagtg gctggtccga tgcttttgat atctggggcc aagggacaat ggtcaccgtc 360

tcgagt 366

<210> 265

<211> 342

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (A10)

<400> 265

gatattgtga tgacacagtc tccagccacc ctgtctgtgt ctccagggga aagagccacc 60

ctctcctgca gggccagtca gagtgttagc agcaacttag cctggtacca gcagaaacct 120

ggccaggctc ccaggctcct catctatggt gcatccacca gggccaccgg tatcccagcc 180

aggttcagtg gcagtgggtc tgggacagag ttcactctca ccatcagcag cctgcagtct 240

gaagattttg cagtttatta ctgtcagcag tatggtagct cacctcggat gtacactttt 300

ggccagggga ccaaagtgga tatcaaacgt accgcggccg ca 342

<210> 266

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Heavy chain variable region gene (A10)

<400> 266

caaatgcagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60

tcctgcaagg cttctggagg caccttcagc agctatgcta tcagctgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggtggg atcatcccta tctttggtac agcaaactac 180

gcacagaagt tccagggcag agtcacgatt accgcggaca aatccatcag cacagcctac 240

atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gagaggcggc 300

ctcggggagt tggacaactg gttcgacccc tggggccagg gaaccctggt caccgtctcg 360

agt 363

<210> 267

<211> 336

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (G1)

<400> 267

tcctatgagc tgactcagcc accctcactg tccgtgtccc caggacagac agccagcatc 60

acctgctcag gatataaact gggagataga tatgtttcct ggtatcagca gaagacaggc 120

cagtcccctg tggtggtcat ctataaagat agccagcggc cctcaggggt ccctgaacga 180

ttctctggct ccaactctgg gaacacagcc actctgacca tcagcgggac ccaggctatg 240

gatgaggctg actattactg tcaggcgtgg gacagcggca ctggggtatt cggcggaggg 300

accaagctga ccgtcctagg tcagcccgcg gccgca 336

<210> 268

<211> 354

<212> DNA

<213> Artificial sequence

<220>

<223> Gene encoding heavy chain variable region (G1)

<400> 268

gaagtgcagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60

tcctgcaagg cttctggagg caccttcagc agctatggta tcagctgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcagcgctt acaatggtaa cacaaactat 180

gcacaggagc tccaggggcag agtcaccatg accacagaca catccacgag cacagcctat 240

atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagtaggg 300

gtggctggta aacttgacta ctggggccaa ggaaccctgg tcaccgtctc gagt 354

<210> 269

<211> 354

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (G9)

<400> 269

cagtctgcgc tgactcagcc tgcctccgtg tctgggtctc ctggacagtc gatcaccatc 60

tcctgcactg gaagcagcag tgacgttggt ggttataact atgtctcctg gtaccagcaa 120

cacccaggca aagcccccaa actcatgatt tatgatgtca gtaatcggcc ctcaggggtt 180

tctgatcgct tctctggctc caagtctggc aacatggcct ccctgaccat ctctgggctc 240

caggctgagg acgaggctga ttattactgc agctcatata caggaagcag cactctcgac 300

gtgctattcg gcggagggac caagctgacc gtcctaggtc agcccgcggc cgca 354

<210> 270

<211> 360

<212> DNA

<213> Artificial sequence

<220>

<223> Gene encoding heavy chain variable region (G9)

<400> 270

caggtgcagc tggtgcagcc tggagcagag gtgaaaaagc cgggggagtc tctgaagatc 60

tcctgtaagg gttctggata cagctttacc agctactgga tcggctgggt gcgccagatg 120

cccgggaagg gcctggagtg gatggggatc atctatcctg gtgactctga taccagatac 180

agcccgtcct tccaaggcca ggtcaccatc tcagccgaca agtccatcag caccgcctac 240

ctgcagtgga gcagcctgaa ggcctcggac accgccatgt attactgtgc gagtcaatat 300

tacgatgggg gttactacat ggacgtctgg ggccagggaa ccctggtcac cgtctcgagt 360

360

<210> 271

<211> 342

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (H2)

<400> 271

tcctatgagc tgactcagga ccctgctgtg tcggtggcct tgggacagac agtcaggatc 60

acatgccaag gagacagcct cagaaactat tatgcaagct ggtaccagca gaagccagga 120

caggccccta ttcttgtcat ctctggtaac aacaaacggc cctcggggat cccagaccga 180

ttctctggct ccagctcagg agacacagct tccttgacca tctctggggc tcaggcggaa 240

gatgaggctg actattactg taactcccta gacagcactt ataaccatcc gatattcggc 300

ggagggacca aggtcaccgt cctaggtcag cccgcggccg ca 342

<210> 272

<211> 351

<212> DNA

<213> Artificial sequence

<220>

<223> Gene encoding heavy chain variable region (H2)

<400> 272

caggtccagc ttgtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60

tcctgcaagg cttctggata caccttcacc agttatgata tccactgggt gcgacaggcc 120

actggacaag ggcttgagtg gatgggatgg atcagcgctt acaatggtaa cacaaactat 180

gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240

atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagagatggg 300

ggtgatgctt ttgatatctg gggccaagga accctggtca ccgtctcgag t 351

<210> 273

<211> 342

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (H11)

<400> 273

tcctatgagc tgactcagga ccctgctgcg tctgtggcct tgggacagac agtcaggatc 60

acatgccaag gagacagcct cagaagctat tatgcaagct ggtaccagca gaagccagga 120

caggcccctg tagttgtcat ctatggtaga aacaaccggc cctcagggat cccagaccga 180

ttctctggct ccagctcagg agacacagct tccttgacca tcactggggc tcaggcggaa 240

gatgaggctg actattactg taagtcccgg gacagcagtg gtaaccatta tgtcttcgga 300

actgggacca agctgaccgt cctaggtcag cccgcggccg ca 342

<210> 274

<211> 351

<212> DNA

<213> Artificial sequence

<220>

<223> Heavy chain variable region gene (H11)

<400> 274

caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtt 60

tcctgcaagg catctggata caccttcacc agctactata tgcactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggaata atcaacccta gtggtggtag cacaagctac 180

240

atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gagagatgcc 300

ggcagctcgt ccgattactg gggccgtggc accctggtca ccgtctcgag t 351

<210> 275

<211> 348

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (F12)

<400> 275

cagtctgtgc tgactcagcc tgcctccgtg tctgggtctc ctggacagtc gatcaccatc 60

tcctgcgctg gaaccagcag tgacattggt gattatgact atgtctcctg gtaccaacag 120

cacccaggca agactcccaa actcatgatt tatgatgtca gtaggcggcc ctcaggggtc 180

cctgatcgct tctctggctc caagtctggc aacacggcct ccctgaccat ctctgggctc 240

cagactgagg acgaggctga ttattactgc gcctcatata caagcagcag cgtcgtggtc 300

ttcggcggag ggaccaagct gaccgtccta ggtcagcccg cggccgca 348

<210> 276

<211> 360

<212> DNA

<213> Artificial sequence

<220>

<223> Heavy chain variable region gene (F12)

<400> 276

caggtgcagc tggtgcagtc tggagcagag gtgaaaaagc ccggggagtc tctgaagatc 60

tcctgtaagg gttctggata cagctttacc agctactgga tcggctgggt gcgccagatg 120

cccgggaaag gcctggagtg gatggggatc atctatcctg gtgactctga taccagatac 180

agcccgtcct tccaaggcca ggtcaccatc tcagccgaca agtccatcag caccgcctac 240

ctgcagtgga gcagcctgaa ggcctcggac accgccatgt attactgtgc gagtcaatat 300

tacgatgggg gttactacat ggacgtctgg ggccagggca ccctggtcac cgtctcgagt 360

360

<210> 277

<211> 336

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (B9)

<400> 277

gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc aggtatttaa attggtatca gcagaaacca 120

gggaaagccc ccaagctcct gatctatggt gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcagcct 240

gaagatttcg caacttacca ttgtcaacag gcttacggtt tccccctcac tctcggcgga 300

gggaccaagg tggagatcaa acgtaccgcg gccgca 336

<210> 278

<211> 375

<212> DNA

<213> Artificial sequence

<220>

<223> Gene encoding heavy chain variable region (B9)

<400> 278

caggtgcagc tggtggagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60

tcctgcaagg cttctggagg caccttcagc agctatgcta tcagctgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggaggg atcatcccta tctttggtac agcaaactac 180

240

atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gagaggggaa 300

atagcagtgg ctcaaaactg ggactactac ggtatggacg tctggggcca gggcaccctg 360

gtcaccgtct cgagt 375

<210> 279

<211> 351

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (G11)

<400> 279

cagtctgcgc tgactcagcc tcgctcagtg tccgggtctc ctggacagtc agtcaccatc 60

tcctgcactg gaaccagcag tgatgttggt ggttataact atgtctcctg gtaccaacag 120

cacccaggca aagcccccaa actcatgatt tatgatgtca gtaagcggcc ctcaggggtc 180

cctgatcgct tctctggctc caagtctggc aacacggcct ccctgacaat ctctgggctc 240

caggctgagg acgaggctga ttattactgc agctcatatt caagcagcag cactctcgtg 300

gttttcggcg gagggaccaa gctgaccgtc ctaggtcagc ccgcggccgc a 351

<210> 280

<211> 360

<212> DNA

<213> Artificial sequence

<220>

<223> Heavy chain variable region gene (G11)

<400> 280

caggtccagc tggtacagtc tggagcagag gtgaaaaagc cgggggagtc tctgaagatc 60

tcctgtaagg gttctggata cagctttacc agctactgga tcggctgggt gcgccagatg 120

cccgggaaag gcctggagtg gatggggatc atctatcctg gtgactctga taccagatac 180

agcccgtcct tccaaggcca ggtcaccatc tcagccgaca agtccatcag caccgcctac 240

ctgcagtgga gcagcctgaa ggcctcggac accgccatgt attactgtgc gagtcaatat 300

tacgatgggg gttactacat ggacgtctgg ggccagggaa ccctggtcac cgtctcgagt 360

360

<210> 281

<211> 342

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (G6)

<400> 281

tcctatgagc tgactcagga ccctgctgtg tctgtggcct tgggacagac agtcacgatc 60

acatgccaag gagacagcct cagaaggtat tatgcaacct ggtaccagca gaagccagga 120

caggcccctg tccttgtcat ctatggtcaa aactaccggc cctcggggat cccagaccga 180

ttctctggct ccaactcagg aaccacagct tccttgacca tcactggggc tcaggcggaa 240

gatgaggctg actattactg taactcccgg gacagcagtg gtaaccatgt ggtattcggc 300

ggagggacca agctgaccgt cctaggtcag cccgcggccg ca 342

<210> 282

<211> 357

<212> DNA

<213> Artificial sequence

<220>

<223> Gene encoding heavy chain variable region (G6)

<400> 282

gaggtgcagc tggtggagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtt 60

tcctgcaagg catctggata caccttcacc agctactata tgcactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggaggg atcatcccta tctttggtac agcaaactac 180

240

atggagctga gcagcctgag atctgaggac acggccgtgt actactgtgc gagagggtgg 300

gggtatagca gctcgtttga ctactggggg caagggacca cggtcaccgt ctcgagt 357

<210> 283

<211> 348

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (F11)

<400> 283

cagtctgtgc tgactcagcc accctcaacg tctgggaccc cggggcagac gttctccatt 60

120

cgggaacgg cccccaaact cctcatctat agtaatgatc agcggccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccag 240

tctgaggatg aggctgatta ttactgtgaa acatgggatg acagcctgaa aggcccggtg 300

ttcggcgggg ggaccaaggt caccgtccta ggtcagcccg cggccgca 348

<210> 284

<211> 357

<212> DNA

<213> Artificial sequence

<220>

<223> Heavy chain variable region gene (F11)

<400> 284

gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgaaactc 60

tcctgtgcag cgtctggatt cacctttagc agctatgcca tgagctgggt ccgccgggct 120

ccagggaagg ggctggagtg ggtctcaact attagtggta gtggtgatag cacatactac 180

gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa cacgctgtat 240

ctgcaaatga acaacctgag agccgaggac acggccgtat attactgtgc gagagaatgg 300

gaactaggcg atgcttttga tatctggggc cgtggcaccc tggtcaccgt ctcgagt 357

<210> 285

<211> 336

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (D3)

<400> 285

gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttacagta cccggtggac gttcggccaa 300

gggaccaagg tggaaatcaa acgtaccgcg gccgca 336

<210> 286

<211> 366

<212> DNA

<213> Artificial sequence

<220>

<223> Gene encoding heavy chain variable region (D3)

<400> 286

gaggtgcagc tgttggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60

tcctgtgcag cctctggatc cacctttagc agctatgcca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagct attagtggta gtggtggtag cacatactac 180

gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa cacgctgtat 240

ctgcaaatga acagcctgag agccgaggac acggccgtat attactgtgc gaaagacaga 300

ggcagctatg gttactacta cggtatggac gtctggggcc aagggacaat ggtcaccgtc 360

tcgagt 366

<210> 287

<211> 336

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (B12)

<400> 287

gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttacagta ccctccggac gttcggccaa 300

gggaccaagg tggagatcaa acgtaccgcg gccgca 336

<210> 288

<211> 366

<212> DNA

<213> Artificial sequence

<220>

<223> Gene encoding heavy chain variable region (B12)

<400> 288

caggtccagc tggtacagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60

tcctgcaagg cttctggata caccttcacc ggctactata tgcactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgg cacaaactac 180

240

atggagctga gcagcctgag atctgaggac acggccgtgt attactgtac gagagccggt 300

gcttctatag tgggagctac cgcgcttgac tactggggcc agggaaccct ggtcaccgtc 360

tcgagt 366

<210> 289

<211> 354

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (E4)

<400> 289

aattttatgc tgactcagcc ccactctgtg tcggagtctc cgggaaagac ggtaaccatc 60

tcctgcaccc gcagcagtgg cagcattgcc agcaactatg tgcagtggta ccagcagcgc 120

ccgggcagtt cccccaccac tgtgatctat gaggataacc aaagaccctc tggggtccct 180

gatcggttct ctggctccat cgacagctcc tccaactctg cctccctcac catctctgga 240

ctgaagactg aggacgaggc tgactactac tgtcagtctt atgataccgg caatcggaat 300

tatgtcttcg gaactgggac ccagctcacc gtcctaggtc agcccgcggc cgca 354

<210> 290

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Gene encoding heavy chain variable region (E4)

<400> 290

caggtgcagc tggtgcaatc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60

tcctgcaagg cttctggagg caccttcagc agctatacta tcagctgggt gcgacaggcc 120

ccttggacaag ggcttgagtg gatgggaagg atcatcccta tccttggtat agcaaactac 180

gcacagaagt tccaggggcag agtcaccatg accagggaca tgtccacaga cacagcctac 240

atggagttga gcagcctgac atatgatgac acggccgtat atttttgtgt gagaggccct 300

agtcttaatt atgccggcta ttttgacaac tggggccagg gcaccctggt caccgtctcg 360

agt 363

<210> 291

<211> 342

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (E12)

<400> 291

tcctatgagc tgactcagga ccctgctgtg tctgtggcct tgggacagac agtcaggatc 60

acatgccaag gagacagcct cagaagctat tatgcaagct ggtaccagca gaagtcagga 120

caggcccctg tacttgtcat ctatggtaaa gaaaagcgcc cctcagggat cccagaccga 180

ttctctggct ccagctcagg aaacacagct tccttgacca tcactggggc tcgggcggaa 240

gatgaggctg actattactg taactcccgg ggcagcacta ctgactatat ggtgttcggc 300

ggggggaccc agctcaccgt cctaggtcag cccgcggccg ca 342

<210> 292

<211> 351

<212> DNA

<213> Artificial sequence

<220>

<223> Gene encoding heavy chain variable region (E12)

<400> 292

caggtgcagc tggtggagtc cgggggaggc ttagttcagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggatt caccttcagt agctatgcta tgcactgggt ccgccaggct 120

ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagcaa taaatactac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240

ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagagaacgg 300

ggaagtggta tggacgtctg gggccaagga accctggtca ccgtctcgag t 351

<210> 293

<211> 336

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (D1)

<400> 293

gaaacgacac tcacgcagtc tccagcattc atgtcagcga ctccaggaga caaagtcaac 60

atctcctgca aagccagcca agacattgat gatgatatga actggtacca acagaaacca 120

ggagaagctg ctatttccat tattcaagaa gctagtactc tcgttcctgg aatcccacct 180

cgattcagtg gcagcgggta tggaacagat tttaccctca caattaataa catagaatct 240

gaggatgctg catattactt ctgtctacaa catgataagt tcccgtacac ttttggccag 300

gggaccaagc tggagatcaa acgtaccgcg gccgca 336

<210> 294

<211> 351

<212> DNA

<213> Artificial sequence

<220>

<223> Gene encoding heavy chain variable region (D1)

<400> 294

gaagtgcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60

tcctgcaagg cttctggtta cacctttacc agctatggta tcagctgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgg cacaaactat 180

gcacagaagt ttcaggggcag ggtcaccatg accagggaca cgtccatcag cacagcctac 240

atggagctga gcaggctgag atctgacgac acggccgtgt attactgtgc gagtcggggg 300

gttgatgagg gggactactg gggccaaggg acaatggtca ccgtctcgag t 351

<210> 295

<211> 348

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (E6)

<400> 295

aattttatgc tgactcagcc ccactctgtg tcggagtctc cggggaagac ggttaccctc 60

tcctgcaccg gcagcagcgg caacattgcc agtaactatg tgcagtggta ccagcaccgc 120

ccgggcagtg cccccaccac tgtgatctac cgggatgacc aaagaccctc tggagtccct 180

gatcgcttct ctggctccat cgacagttca tccaactctg cctccctcac gatctctgga 240

ctgaggcctg aggacgaggc tgactattac tgtcagtctt atgatagcag ctcttgggtg 300

ttcggcggag ggaccaagct gaccgtccta ggtcagcccg cggccgca 348

<210> 296

<211> 372

<212> DNA

<213> Artificial sequence

<220>

<223> Gene encoding heavy chain variable region (E6)

<400> 296

caggtccagc ttgtgcagtc tggagcagag gtgaagaagc ctggggcctc agtgaaggtc 60

tcctgcaagg cttctggata caccttcacc acttatgata tcacctgggt gcgacaggcc 120

cctggacaag gccttgagtg gatgggatgg atgaacccga acagtggtaa ctcacgctct 180

gcacagaagt tccagggcag agtcagcatg accagtgact cctccataag cacagcctac 240

atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc aacaggagac 300

tactcgggtg tggtactaac tgcaacagca cttgactact ggggcgggg aaccctggtc 360

accgtctcga gt 372

<210> 297

<211> 348

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (E9)

<400> 297

cagtctgagc tgactcagct accctcagcg tctgagaccc ccgggcagag ggtcaccatc 60

tcttgttctg gaagcagctc caacatcgga aataattatg tatactggta ccagcaactc 120

ccgggaacgg cccccaaact cctcatctat aggaataatc agcggccctc aggggtccct 180

gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tgggctccgg 240

tccgaggatg aggctgatta ttactgtgca gcatgggatg acagcctgag tggttgggtg 300

ttcggcggag ggaccaagct gaccgtccta ggtcagcccg cggccgca 348

<210> 298

<211> 369

<212> DNA

<213> Artificial sequence

<220>

<223> Gene encoding heavy chain variable region (E9)

<400> 298

caggtgcagc tggtggagtc tgggggaggc ttggtacagc ctgggaggtc cctgagactc 60

tcctgtgcag cgtctggatt caccttcagt agctatggca tgcactgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtggccaac ataaagcaag atggaagtga gaaatactat 180

gtggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa cacgctgtat 240

ctccaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagagaggac 300

cgtatagcag cagctgggat gcgggagttg gactactggg gccagggcac cctggtcacc 360

gtctcgagt 369

<210> 299

<211> 354

<212> DNA

<213> Artificial sequence

<220>

<223> Light chain variable region gene (A11)

<400> 299

gatattgtga tgacccagtc tccactctcc ctgcccgtca cccctggaga gccggcctcc 60

atctcctgca ggtctagtca gagcctcctg catagtaatg gatacaacta tttggattgg 120

tacctgcaga agccaggggca gtctccacag ctcctgatct atttgggttc taaccgggcc 180

tccggggtcc ctgacaggtt cagtggcagt ggatcaggca cagattttac actgaaaatc 240

agcagagtgg aggctgagga tgttggggtt tattactgca tgcaaggtac acactggcct 300

ccgtacacct ttggccaggg gaccaaggtg gagatcaaac gtaccgcggc cgca 354

<210> 300

<211> 360

<212> DNA

<213> Artificial sequence

<220>

<223> Gene encoding heavy chain variable region (A11)

<400> 300

gaggtgcagc tgttggagtc tgggggaggc ttggaacagc ctggggggtt cctgagactc 60

tcctgtgcag cctctggatt ctcctttacc agctacgcca tgacctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcaggt attagtagtg atgggaccac tacaacctac 180

gcggactccg tgaggggccg gttcaccatc tccagagaca acgccaagaa cacggtgtat 240

ctccaaatga acagtctgag agacgaggac acggctgtgt attattgtgc aagagatcaa 300

ttgttgggct gggatgctct gaatgtctgg ggccaaggga caatggtcac cgtctcgagt 360

360

<210> 301

<211> 216

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (E3)

<400> 301

Ser Tyr Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln

1 5 10 15

Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Asn Phe Tyr Ala

20 25 30

Ser Trp Tyr Gln Gln Lys Ser Gly Gln Ala Pro Val Leu Val Met Tyr

35 40 45

Gly Lys Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

Thr Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Ser His

85 90 95

Leu Thr Gly Val Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly Gln

100 105 110

Pro Ala Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu

115 120 125

Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr

130 135 140

Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys

145 150 155 160

Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr

165 170 175

Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His

180 185 190

Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys

195 200 205

Thr Val Ala Pro Thr Glu Cys Ser

210 215

<210> 302

<211> 451

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain (E3 or E3.1)

<400> 302

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Ile Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Thr Tyr Tyr Tyr Gly Ser Gly Arg Ser Asn Ala Phe Asp

100 105 110

Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys

115 120 125

Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu

130 135 140

Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro

145 150 155 160

Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr

165 170 175

Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val

180 185 190

Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn

195 200 205

Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser

210 215 220

Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly

225 230 235 240

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met

245 250 255

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln

260 265 270

Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val

275 280 285

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr

290 295 300

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

305 310 315 320

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile

325 330 335

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val

340 345 350

Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser

355 360 365

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu

370 375 380

Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro

385 390 395 400

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val

405 410 415

Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met

420 425 430

His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser

435 440 445

Leu Gly Lys

450

<210> 303

<211> 212

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (B3)

<400> 303

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Asn Leu Pro Phe

85 90 95

Gly Gly Gly Thr Lys Val Asp Ile Lys Arg Thr Ala Ala Ala Pro Ser

100 105 110

Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala

115 120 125

Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val

130 135 140

Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser

145 150 155 160

Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr

165 170 175

Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu Tyr Ala Cys

180 185 190

Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn

195 200 205

Arg Gly Glu Cys

210

<210> 304

<211> 449

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain (B3)

<400> 304

Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Val Gly Asp Ser Ser Gly Trp Ser Asp Ala Phe Asp Ile Trp

100 105 110

Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

115 120 125

Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr

130 135 140

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

145 150 155 160

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

165 170 175

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

180 185 190

Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp

195 200 205

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr

210 215 220

Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro

225 230 235 240

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

245 250 255

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp

260 265 270

Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

275 280 285

Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val

290 295 300

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

305 310 315 320

Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys

325 330 335

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr

340 345 350

Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr

355 360 365

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu

370 375 380

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu

385 390 395 400

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys

405 410 415

Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu

420 425 430

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

Lys

<210> 305

<211> 216

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (A10)

<400> 305

Asp Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Asn

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Arg

85 90 95

Met Tyr Thr Phe Gly Gln Gly Thr Lys Val Asp Ile Lys Arg Thr Ala

100 105 110

Ala Ala Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys

115 120 125

Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg

130 135 140

Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn

145 150 155 160

Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser

165 170 175

Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys

180 185 190

Leu Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr

195 200 205

Lys Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 306

<211> 448

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain (A10)

<400> 306

Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Gly Leu Gly Glu Leu Asp Asn Trp Phe Asp Pro Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 307

<211> 212

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (G1)

<400> 307

Ser Tyr Glu Leu Thr Gln Pro Ser Leu Ser Val Ser Pro Gly Gln

1 5 10 15

Thr Ala Ser Ile Thr Cys Ser Gly Tyr Lys Leu Gly Asp Arg Tyr Val

20 25 30

Ser Trp Tyr Gln Gln Lys Thr Gly Gln Ser Pro Val Val Val Ile Tyr

35 40 45

Lys Asp Ser Gln Arg Pro Ser Gly Val Pro Glu Arg Phe Ser Gly Ser

50 55 60

Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala Met

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Gln Ala Trp Asp Ser Gly Thr Gly Val

85 90 95

Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Ala Ala Ala

100 105 110

Pro Ser Val Thr Leu Phe Pro Ser Ser Glu Glu Glu Leu Gln Ala Asn

115 120 125

Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val

130 135 140

Thr Val Ala Trp Lys Glu Asp Ser Ser Pro Val Lys Ala Gly Val Glu

145 150 155 160

Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser

165 170 175

Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg Ser Tyr Ser

180 185 190

Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro

195 200 205

Thr Glu Cys Ser

210

<210> 308

<211> 445

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain (G1)

<400> 308

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Glu Leu

50 55 60

Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Val Gly Val Ala Gly Lys Leu Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro

115 120 125

Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly

130 135 140

Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn

145 150 155 160

Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln

165 170 175

Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser

180 185 190

Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser

195 200 205

Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys

210 215 220

Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu

225 230 235 240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250 255

Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln

405 410 415

Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 309

<211> 218

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (G9)

<400> 309

Gln Ser Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln

1 5 10 15

Ser Ile Thr Ile Ser Cys Thr Gly Ser Ser Ser Asp Val Gly Gly Tyr

20 25 30

Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu

35 40 45

Met Ile Tyr Asp Val Ser Asn Arg Pro Ser Gly Val Ser Asp Arg Phe

50 55 60

Ser Gly Ser Lys Ser Gly Asn Met Ala Ser Leu Thr Ile Ser Gly Leu

65 70 75 80

Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Thr Gly Ser

85 90 95

Ser Thr Leu Asp Val Leu Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105 110

Gly Gln Pro Ala Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser

115 120 125

Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp

130 135 140

Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro

145 150 155 160

Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn

165 170 175

Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys

180 185 190

Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val

195 200 205

Glu Lys Thr Val Ala Pro Thr Glu Cys Ser

210 215

<210> 310

<211> 447

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy Chain (G9)

<400> 310

Gln Val Gln Leu Val Gln Pro Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Ser Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Ser Gln Tyr Tyr Asp Gly Gly Tyr Tyr Met Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

210 215 220

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

225 230 235 240

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

245 250 255

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

260 265 270

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

275 280 285

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

290 295 300

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

305 310 315 320

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

325 330 335

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

340 345 350

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

355 360 365

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

370 375 380

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

385 390 395 400

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

405 410 415

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

420 425 430

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 311

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (H2)

<400> 311

Ser Tyr Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln

1 5 10 15

Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Asn Tyr Tyr Ala

20 25 30

Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Ile Leu Val Ile Ser

35 40 45

Gly Asn Asn Lys Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

Ser Ser Gly Asp Thr Ala Ser Leu Thr Ile Ser Gly Ala Gln Ala Glu

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Leu Asp Ser Thr Tyr Asn His

85 90 95

Pro Ile Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly Gln Pro Ala

100 105 110

Ala Ala Pro Ser Val Thr Leu Phe Pro Ser Ser Glu Glu Leu Gln

115 120 125

Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly

130 135 140

Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly

145 150 155 160

Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala

165 170 175

Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg Ser

180 185 190

Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val

195 200 205

Ala Pro Thr Glu Cys Ser

210

<210> 312

<211> 444

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain (H2)

<400> 312

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Asp Ile His Trp Val Arg Gln Ala Thr Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Lys Leu

50 55 60

Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Gly Gly Asp Ala Phe Asp Ile Trp Gly Gln Gly Thr Leu

100 105 110

Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu

115 120 125

Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys

130 135 140

Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser

145 150 155 160

Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser

165 170 175

Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser

180 185 190

Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn

195 200 205

Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro

210 215 220

Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe

225 230 235 240

Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val

245 250 255

Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe

260 265 270

Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro

275 280 285

Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr

290 295 300

Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val

305 310 315 320

Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala

325 330 335

Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln

340 345 350

Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly

355 360 365

Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro

370 375 380

Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser

385 390 395 400

Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu

405 410 415

Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His

420 425 430

Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440

<210> 313

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (H11)

<400> 313

Ser Tyr Glu Leu Thr Gln Asp Pro Ala Ala Ser Val Ala Leu Gly Gln

1 5 10 15

Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala

20 25 30

Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Val Val Ile Tyr

35 40 45

Gly Arg Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

Ser Ser Gly Asp Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Lys Ser Arg Asp Ser Ser Gly Asn His

85 90 95

Tyr Val Phe Gly Thr Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Ala

100 105 110

Ala Ala Pro Ser Val Thr Leu Phe Pro Ser Ser Glu Glu Leu Gln

115 120 125

Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly

130 135 140

Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly

145 150 155 160

Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala

165 170 175

Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg Ser

180 185 190

Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val

195 200 205

Ala Pro Thr Glu Cys Ser

210

<210> 314

<211> 444

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy Chain (H11)

<400> 314

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Ile Ile Asn Pro Ser Gly Ser Thr Ser Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Ala Gly Ser Ser Ser Asp Tyr Trp Gly Arg Gly Thr Leu

100 105 110

Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu

115 120 125

Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys

130 135 140

Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser

145 150 155 160

Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser

165 170 175

Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser

180 185 190

Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn

195 200 205

Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro

210 215 220

Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe

225 230 235 240

Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val

245 250 255

Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe

260 265 270

Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro

275 280 285

Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr

290 295 300

Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val

305 310 315 320

Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala

325 330 335

Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln

340 345 350

Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly

355 360 365

Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro

370 375 380

Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser

385 390 395 400

Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu

405 410 415

Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His

420 425 430

Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440

<210> 315

<211> 216

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (F12)

<400> 315

Gln Ser Val Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln

1 5 10 15

Ser Ile Thr Ile Ser Cys Ala Gly Thr Ser Ser Asp Ile Gly Asp Tyr

20 25 30

Asp Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Thr Pro Lys Leu

35 40 45

Met Ile Tyr Asp Val Ser Arg Arg Pro Ser Gly Val Pro Asp Arg Phe

50 55 60

Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu

65 70 75 80

Gln Thr Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ser Tyr Thr Ser Ser

85 90 95

Ser Val Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln

100 105 110

Pro Ala Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu

115 120 125

Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr

130 135 140

Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys

145 150 155 160

Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr

165 170 175

Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His

180 185 190

Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys

195 200 205

Thr Val Ala Pro Thr Glu Cys Ser

210 215

<210> 316

<211> 447

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain (F12)

<400> 316

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Ser Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Ser Gln Tyr Tyr Asp Gly Gly Tyr Tyr Met Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

210 215 220

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

225 230 235 240

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

245 250 255

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

260 265 270

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

275 280 285

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

290 295 300

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

305 310 315 320

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

325 330 335

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

340 345 350

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

355 360 365

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

370 375 380

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

385 390 395 400

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

405 410 415

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

420 425 430

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 317

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (B9)

<400> 317

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Arg Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Gly Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr His Cys Gln Gln Ala Tyr Gly Phe Pro Leu

85 90 95

Thr Leu Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Ala Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 318

<211> 452

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy Chain (B9)

<400> 318

Gln Val Gln Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Glu Ile Ala Val Ala Gln Asn Trp Asp Tyr Tyr Gly Met

100 105 110

Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr

115 120 125

Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser

130 135 140

Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu

145 150 155 160

Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His

165 170 175

Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser

180 185 190

Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys

195 200 205

Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu

210 215 220

Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu

225 230 235 240

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

245 250 255

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

260 265 270

Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu

275 280 285

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr

290 295 300

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

305 310 315 320

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser

325 330 335

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

340 345 350

Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val

355 360 365

Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val

370 375 380

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

385 390 395 400

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr

405 410 415

Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val

420 425 430

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

435 440 445

Ser Leu Gly Lys

450

<210> 319

<211> 217

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (G11)

<400> 319

Gln Ser Ala Leu Thr Gln Pro Arg Ser Val Ser Gly Ser Pro Gly Gln

1 5 10 15

Ser Val Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr

20 25 30

Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu

35 40 45

Met Ile Tyr Asp Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe

50 55 60

Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu

65 70 75 80

Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ser Ser Ser

85 90 95

Ser Thr Leu Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly

100 105 110

Gln Pro Ala Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu

115 120 125

Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe

130 135 140

Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val

145 150 155 160

Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys

165 170 175

Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser

180 185 190

His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu

195 200 205

Lys Thr Val Ala Pro Thr Glu Cys Ser

210 215

<210> 320

<211> 447

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain (G11)

<400> 320

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Ser Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Ser Gln Tyr Tyr Asp Gly Gly Tyr Tyr Met Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

210 215 220

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

225 230 235 240

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

245 250 255

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

260 265 270

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

275 280 285

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

290 295 300

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

305 310 315 320

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

325 330 335

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

340 345 350

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

355 360 365

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

370 375 380

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

385 390 395 400

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

405 410 415

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

420 425 430

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 321

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (G6)

<400> 321

Ser Tyr Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln

1 5 10 15

Thr Val Thr Ile Thr Cys Gln Gly Asp Ser Leu Arg Arg Tyr Tyr Ala

20 25 30

Thr Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr

35 40 45

Gly Gln Asn Tyr Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

Asn Ser Gly Thr Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Asn His

85 90 95

Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Ala

100 105 110

Ala Ala Pro Ser Val Thr Leu Phe Pro Ser Ser Glu Glu Leu Gln

115 120 125

Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly

130 135 140

Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly

145 150 155 160

Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala

165 170 175

Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg Ser

180 185 190

Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val

195 200 205

Ala Pro Thr Glu Cys Ser

210

<210> 322

<211> 446

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy Chain (G6)

<400> 322

Glu Val Gln Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Trp Gly Tyr Ser Ser Ser Phe Asp Tyr Trp Gly Gln Gly

100 105 110

Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe

115 120 125

Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro

210 215 220

Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe

225 230 235 240

Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro

245 250 255

Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val

260 265 270

Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr

275 280 285

Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val

290 295 300

Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys

305 310 315 320

Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser

325 330 335

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

340 345 350

Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val

355 360 365

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

370 375 380

Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp

385 390 395 400

Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp

405 410 415

Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

420 425 430

Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 323

<211> 216

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (F11)

<400> 323

Gln Ser Val Leu Thr Gln Pro Pro Ser Thr Ser Gly Thr Pro Gly Gln

1 5 10 15

Thr Phe Ser Ile Phe Cys Ser Gly Ser Ser Ser Asn Ile Gly Thr Asn

20 25 30

Thr Val Asn Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Ser Asn Asp Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Gln

65 70 75 80

Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Glu Thr Trp Asp Asp Ser Leu

85 90 95

Lys Gly Pro Val Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly Gln

100 105 110

Pro Ala Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu

115 120 125

Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr

130 135 140

Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys

145 150 155 160

Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr

165 170 175

Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His

180 185 190

Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys

195 200 205

Thr Val Ala Pro Thr Glu Cys Ser

210 215

<210> 324

<211> 446

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain (F11)

<400> 324

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Ser Gly Ser Gly Asp Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Asn Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Trp Glu Leu Gly Asp Ala Phe Asp Ile Trp Gly Arg Gly

100 105 110

Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe

115 120 125

Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro

210 215 220

Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe

225 230 235 240

Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro

245 250 255

Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val

260 265 270

Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr

275 280 285

Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val

290 295 300

Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys

305 310 315 320

Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser

325 330 335

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

340 345 350

Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val

355 360 365

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

370 375 380

Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp

385 390 395 400

Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp

405 410 415

Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

420 425 430

Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 325

<211> 212

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (D3)

<400> 325

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Arg Trp

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Ala Ala Ala

100 105 110

Pro Ser Val Thr Leu Phe Pro Ser Ser Glu Glu Glu Leu Gln Ala Asn

115 120 125

Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val

130 135 140

Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu

145 150 155 160

Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser

165 170 175

Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg Ser Tyr Ser

180 185 190

Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro

195 200 205

Thr Glu Cys Ser

210

<210> 326

<211> 449

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy Chain (D3)

<400> 326

Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Ser Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Asp Arg Gly Ser Tyr Gly Tyr Tyr Tyr Gly Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

115 120 125

Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr

130 135 140

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

145 150 155 160

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

165 170 175

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

180 185 190

Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp

195 200 205

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr

210 215 220

Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro

225 230 235 240

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

245 250 255

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp

260 265 270

Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

275 280 285

Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val

290 295 300

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

305 310 315 320

Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys

325 330 335

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr

340 345 350

Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr

355 360 365

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu

370 375 380

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu

385 390 395 400

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys

405 410 415

Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu

420 425 430

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

Lys

<210> 327

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (B12)

<400> 327

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Leu Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Ala Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 328

<211> 449

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain (B12)

<400> 328

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Thr Arg Ala Gly Ala Ser Ile Val Gly Ala Thr Ala Leu Asp Tyr Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

115 120 125

Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr

130 135 140

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

145 150 155 160

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

165 170 175

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

180 185 190

Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp

195 200 205

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr

210 215 220

Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro

225 230 235 240

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

245 250 255

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp

260 265 270

Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

275 280 285

Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val

290 295 300

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

305 310 315 320

Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys

325 330 335

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr

340 345 350

Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr

355 360 365

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu

370 375 380

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu

385 390 395 400

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys

405 410 415

Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu

420 425 430

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

435 440 445

Lys

<210> 329

<211> 218

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (E4)

<400> 329

Asn Phe Met Leu Thr Gln Pro His Ser Val Ser Glu Ser Pro Gly Lys

1 5 10 15

Thr Val Thr Ile Ser Cys Thr Arg Ser Ser Gly Ser Ile Ala Ser Asn

20 25 30

Tyr Val Gln Trp Tyr Gln Gln Arg Pro Gly Ser Ser Pro Thr Thr Val

35 40 45

Ile Tyr Glu Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Ile Asp Ser Ser Ser Asn Ser Ala Ser Leu Thr Ile Ser Gly

65 70 75 80

Leu Lys Thr Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Tyr Asp Thr

85 90 95

Gly Asn Arg Asn Tyr Val Phe Gly Thr Gly Thr Gln Leu Thr Val Leu

100 105 110

Gly Gln Pro Ala Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser

115 120 125

Glu Glu Ile Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp

130 135 140

Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro

145 150 155 160

Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn

165 170 175

Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys

180 185 190

Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val

195 200 205

Glu Lys Thr Val Ala Pro Thr Glu Cys Ser

210 215

<210> 330

<211> 448

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain (E4)

<400> 330

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Thr Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Ile Pro Ile Leu Gly Ile Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Met Ser Thr Asp Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Thr Tyr Asp Asp Thr Ala Val Tyr Phe Cys

85 90 95

Val Arg Gly Pro Ser Leu Asn Tyr Ala Gly Tyr Phe Asp Asn Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

225 230 235 240

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

260 265 270

Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

275 280 285

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

290 295 300

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

305 310 315 320

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

325 330 335

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

340 345 350

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

355 360 365

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

370 375 380

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

385 390 395 400

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

405 410 415

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

420 425 430

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 331

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (E12)

<400> 331

Ser Tyr Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln

1 5 10 15

Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala

20 25 30

Ser Trp Tyr Gln Gln Lys Ser Gly Gln Ala Pro Val Leu Val Ile Tyr

35 40 45

Gly Lys Glu Lys Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Arg Ala Glu

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Gly Ser Thr Thr Asp Tyr

85 90 95

Met Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Gly Gln Pro Ala

100 105 110

Ala Ala Pro Ser Val Thr Leu Phe Pro Ser Ser Glu Glu Leu Gln

115 120 125

Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly

130 135 140

Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly

145 150 155 160

Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala

165 170 175

Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg Ser

180 185 190

Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val

195 200 205

Ala Pro Thr Glu Cys Ser

210

<210> 332

<211> 444

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain (E12)

<400> 332

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Glu Trp Val

35 40 45

Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Arg Gly Ser Gly Met Asp Val Trp Gly Gln Gly Thr Leu

100 105 110

Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu

115 120 125

Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys

130 135 140

Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser

145 150 155 160

Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser

165 170 175

Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser

180 185 190

Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn

195 200 205

Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro

210 215 220

Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe

225 230 235 240

Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val

245 250 255

Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe

260 265 270

Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro

275 280 285

Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr

290 295 300

Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val

305 310 315 320

Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala

325 330 335

Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln

340 345 350

Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly

355 360 365

Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro

370 375 380

Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser

385 390 395 400

Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu

405 410 415

Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His

420 425 430

Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440

<210> 333

<211> 214

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (D1)

<400> 333

Glu Thr Thr Leu Thr Gln Ser Pro Ala Phe Met Ser Ala Thr Pro Gly

1 5 10 15

Asp Lys Val Asn Ile Ser Cys Lys Ala Ser Gln Asp Ile Asp Asp Asp

20 25 30

Met Asn Trp Tyr Gln Gln Lys Pro Gly Glu Ala Ala Ile Ser Ile Ile

35 40 45

Gln Glu Ala Ser Thr Leu Val Pro Gly Ile Pro Pro Arg Phe Ser Gly

50 55 60

Ser Gly Tyr Gly Thr Asp Phe Thr Leu Thr Ile Asn Asn Ile Glu Ser

65 70 75 80

Glu Asp Ala Ala Tyr Tyr Phe Cys Leu Gln His Asp Lys Phe Pro Tyr

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Ala Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 334

<211> 444

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain (D1)

<400> 334

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Ser Arg Gly Val Asp Glu Gly Asp Tyr Trp Gly Gln Gly Thr Met

100 105 110

Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu

115 120 125

Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys

130 135 140

Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser

145 150 155 160

Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser

165 170 175

Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser

180 185 190

Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn

195 200 205

Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro

210 215 220

Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe

225 230 235 240

Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val

245 250 255

Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe

260 265 270

Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro

275 280 285

Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr

290 295 300

Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val

305 310 315 320

Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala

325 330 335

Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln

340 345 350

Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly

355 360 365

Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro

370 375 380

Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser

385 390 395 400

Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu

405 410 415

Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His

420 425 430

Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440

<210> 335

<211> 216

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (E6)

<400> 335

Asn Phe Met Leu Thr Gln Pro His Ser Val Ser Glu Ser Pro Gly Lys

1 5 10 15

Thr Val Thr Leu Ser Cys Thr Gly Ser Ser Gly Asn Ile Ala Ser Asn

20 25 30

Tyr Val Gln Trp Tyr Gln His Arg Pro Gly Ser Ala Pro Thr Thr Val

35 40 45

Ile Tyr Arg Asp Asp Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Ile Asp Ser Ser Ser Asn Ser Ala Ser Leu Thr Ile Ser Gly

65 70 75 80

Leu Arg Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Tyr Asp Ser

85 90 95

Ser Ser Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln

100 105 110

Pro Ala Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu

115 120 125

Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr

130 135 140

Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys

145 150 155 160

Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr

165 170 175

Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His

180 185 190

Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys

195 200 205

Thr Val Ala Pro Thr Glu Cys Ser

210 215

<210> 336

<211> 451

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain (E6)

<400> 336

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Thr Tyr

20 25 30

Asp Ile Thr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Trp Met Asn Pro Asn Ser Gly Asn Ser Arg Ser Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Ser Met Thr Ser Asp Ser Ser Ile Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Thr Gly Asp Tyr Ser Gly Val Val Leu Thr Ala Thr Ala Leu Asp

100 105 110

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys

115 120 125

Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu

130 135 140

Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro

145 150 155 160

Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr

165 170 175

Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val

180 185 190

Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn

195 200 205

Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser

210 215 220

Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly

225 230 235 240

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met

245 250 255

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln

260 265 270

Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val

275 280 285

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr

290 295 300

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

305 310 315 320

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile

325 330 335

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val

340 345 350

Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser

355 360 365

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu

370 375 380

Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro

385 390 395 400

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val

405 410 415

Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met

420 425 430

His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser

435 440 445

Leu Gly Lys

450

<210> 337

<211> 216

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (E9)

<400> 337

Gln Ser Glu Leu Thr Gln Leu Pro Ser Ala Ser Glu Thr Pro Gly Gln

1 5 10 15

Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn

20 25 30

Tyr Val Tyr Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu

35 40 45

Ile Tyr Arg Asn Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg

65 70 75 80

Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ala Trp Asp Asp Ser Leu

85 90 95

Ser Gly Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln

100 105 110

Pro Ala Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu

115 120 125

Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr

130 135 140

Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys

145 150 155 160

Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr

165 170 175

Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His

180 185 190

Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys

195 200 205

Thr Val Ala Pro Thr Glu Cys Ser

210 215

<210> 338

<211> 450

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain (E9)

<400> 338

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ala Asn Ile Lys Gln Asp Gly Ser Glu Lys Tyr Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Asp Arg Ile Ala Ala Ala Gly Met Arg Glu Leu Asp Tyr

100 105 110

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly

115 120 125

Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser

130 135 140

Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val

145 150 155 160

Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe

165 170 175

Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val

180 185 190

Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val

195 200 205

Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys

210 215 220

Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly

225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

245 250 255

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu

260 265 270

Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His

275 280 285

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg

290 295 300

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu

325 330 335

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

340 345 350

Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu

355 360 365

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

370 375 380

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

385 390 395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp

405 410 415

Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His

420 425 430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu

435 440 445

Gly Lys

450

<210> 339

<211> 220

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (A11)

<400> 339

Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser

20 25 30

Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly

85 90 95

Thr His Trp Pro Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Thr Ala Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp

115 120 125

Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn

130 135 140

Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu

145 150 155 160

Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp

165 170 175

Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr

180 185 190

Glu Lys His Lys Leu Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser

195 200 205

Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215 220

<210> 340

<211> 447

<212> Protein

<213> Artificial sequence

<220>

<223> Heavy chain (A11)

<400> 340

Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Glu Gln Pro Gly Gly

1 5 10 15

Phe Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Thr Ser Tyr

20 25 30

Ala Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Ser Asp Gly Thr Thr Thr Thr Tyr Ala Asp Ser Val

50 55 60

Arg Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Asp Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Gln Leu Leu Gly Trp Asp Ala Leu Asn Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

210 215 220

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

225 230 235 240

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

245 250 255

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

260 265 270

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

275 280 285

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

290 295 300

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

305 310 315 320

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

325 330 335

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

340 345 350

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

355 360 365

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

370 375 380

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

385 390 395 400

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

405 410 415

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

420 425 430

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440 445

<210> 341

<211> 327

<212> Protein

<213> Artificial sequence

<220>

<223> IgG4 Fc

<400> 341

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg

1 5 10 15

Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr

20 25 30

Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser

35 40 45

Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser

50 55 60

Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr

65 70 75 80

Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys

85 90 95

Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro

100 105 110

Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys

115 120 125

Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val

130 135 140

Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp

145 150 155 160

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe

165 170 175

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp

180 185 190

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu

195 200 205

Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg

210 215 220

Glu Pro Gln Val Tyr Thr Leu Pro Ser Gln Glu Glu Met Thr Lys

225 230 235 240

Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp

245 250 255

Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys

260 265 270

Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

275 280 285

Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser

290 295 300

Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

305 310 315 320

Leu Ser Leu Ser Leu Gly Lys

325

<210> 342

<211> 102

<212> Protein

<213> Artificial sequence

<220>

<223> Kappa constant region

<400> 342

Pro Ser Val Phe Ile Phe Pro Ser Asp Glu Gln Leu Lys Ser Gly

1 5 10 15

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

20 25 30

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

35 40 45

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

50 55 60

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Leu Tyr

65 70 75 80

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

85 90 95

Phe Asn Arg Gly Glu Cys

100

<210> 343

<211> 100

<212> Protein

<213> Artificial sequence

<220>

<223> Lambda constant area

<400> 343

Pro Ser Val Thr Leu Phe Pro Ser Ser Glu Glu Glu Leu Gln Ala Asn

1 5 10 15

Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val

20 25 30

Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu

35 40 45

Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser

50 55 60

Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg Ser Tyr Ser

65 70 75 80

Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro

85 90 95

Thr Glu Cys Ser

100

<210> 344

<211> 106

<212> Protein

<213> Artificial sequence

<220>

<223> CL.1 constant region lambda

<400> 344

Gly Gln Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Pro Ser Ser

1 5 10 15

Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp

20 25 30

Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro

35 40 45

Val Lys Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn

50 55 60

Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys

65 70 75 80

Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val

85 90 95

Glu Lys Thr Val Ala Pro Thr Glu Cys Ser

100 105

<210> 345

<211> 110

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain variable region (E3.1)

<400> 345

Ser Tyr Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln

1 5 10 15

Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Asn Phe Tyr Ala

20 25 30

Ser Trp Tyr Gln Gln Lys Ser Gly Gln Ala Pro Val Leu Val Met Tyr

35 40 45

Gly Lys Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

Thr Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Ser His

85 90 95

Leu Thr Gly Val Phe Gly Gly Gly Thr Lys Val Thr Val Leu

100 105 110

<210> 346

<211> 330

<212> Protein

<213> Artificial sequence

<220>

<223> Gene encoding light chain variable region (E3.1)

<400> 346

Thr Cys Cys Thr Ala Thr Gly Ala Gly Cys Thr Gly Ala Cys Thr Cys

1 5 10 15

Ala Gly Gly Ala Cys Cys Cys Thr Gly Cys Thr Gly Thr Gly Thr Cys

20 25 30

Thr Gly Thr Gly Gly Cys Cys Thr Thr Gly Gly Gly Ala Cys Ala Gly

35 40 45

Ala Cys Ala Gly Thr Cys Ala Gly Gly Ala Thr Cys Ala Cys Ala Thr

50 55 60

Gly Cys Cys Ala Gly Gly Gly Ala Gly Ala Cys Ala Gly Cys Cys Thr

65 70 75 80

Cys Ala Gly Ala Ala Ala Cys Thr Thr Thr Thr Ala Thr Gly Cys Ala

85 90 95

Ala Gly Cys Thr Gly Gly Thr Ala Cys Cys Ala Gly Cys Ala Gly Ala

100 105 110

Ala Gly Thr Cys Ala Gly Gly Ala Cys Ala Gly Gly Cys Cys Cys Cys

115 120 125

Ala Gly Thr Thr Cys Thr Thr Gly Thr Cys Ala Thr Gly Thr Ala Thr

130 135 140

Gly Gly Thr Ala Ala Ala Ala Ala Cys Ala Ala Cys Cys Gly Gly Cys

145 150 155 160

Cys Cys Thr Cys Ala Gly Gly Gly Ala Thr Cys Cys Cys Ala Gly Ala

165 170 175

Cys Cys Gly Ala Thr Thr Cys Thr Cys Thr Gly Gly Cys Thr Cys Cys

180 185 190

Ala Cys Cys Thr Cys Ala Gly Gly Ala Ala Ala Cys Ala Cys Ala Gly

195 200 205

Cys Thr Thr Cys Cys Thr Thr Gly Ala Cys Cys Ala Thr Cys Ala Cys

210 215 220

Thr Gly Gly Gly Gly Cys Thr Cys Ala Gly Gly Cys Gly Gly Ala Ala

225 230 235 240

Gly Ala Thr Gly Ala Gly Gly Cys Thr Gly Ala Cys Thr Ala Thr Thr

245 250 255

Ala Cys Thr Gly Thr Ala Ala Cys Thr Cys Cys Cys Gly Gly Gly Ala

260 265 270

Cys Ala Gly Cys Ala Gly Thr Gly Gly Thr Ala Gly Cys Cys Ala Thr

275 280 285

Thr Thr Gly Ala Cys Gly Gly Gly Cys Gly Thr Ala Thr Thr Cys Gly

290 295 300

Gly Cys Gly Gly Ala Gly Gly Gly Ala Cys Cys Ala Ala Gly Gly Thr

305 310 315 320

Cys Ala Cys Cys Gly Thr Cys Cys Thr Ala

325 330

<210> 347

<211> 216

<212> Protein

<213> Artificial sequence

<220>

<223> Light chain (E3.1)

<400> 347

Ser Tyr Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln

1 5 10 15

Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Asn Phe Tyr Ala

20 25 30

Ser Trp Tyr Gln Gln Lys Ser Gly Gln Ala Pro Val Leu Val Met Tyr

35 40 45

Gly Lys Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

Thr Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Ser His

85 90 95

Leu Thr Gly Val Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly Gln

100 105 110

Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Pro Ser Ser Glu Glu

115 120 125

Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr

130 135 140

Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys

145 150 155 160

Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys Tyr

165 170 175

Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His

180 185 190

Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys

195 200 205

Thr Val Ala Pro Thr Glu Cys Ser

210 215

<210> 348

<211> 650

<212> Protein

<213> Artificial sequence

<220>

<223> LILRB1(AAH15731)

<400> 348

Met Thr Pro Ile Leu Thr Val Leu Ile Cys Leu Gly Leu Ser Leu Gly

1 5 10 15

Pro Arg Thr His Val Gln Ala Gly His Leu Pro Lys Pro Thr Leu Trp

20 25 30

Ala Glu Pro Gly Ser Val Ile Thr Gln Gly Ser Pro Val Thr Leu Arg

35 40 45

Cys Gln Gly Gly Gln Glu Thr Gln Glu Tyr Arg Leu Tyr Arg Glu Lys

50 55 60

Lys Thr Ala Pro Trp Ile Thr Arg Ile Pro Gln Glu Leu Val Lys Lys

65 70 75 80

Gly Gln Phe Pro Ile Pro Ser Ile Thr Trp Glu His Ala Gly Arg Tyr

85 90 95

Arg Cys Tyr Tyr Gly Ser Asp Thr Ala Gly Arg Ser Glu Ser Ser Asp

100 105 110

Pro Leu Glu Leu Val Val Thr Gly Ala Tyr Ile Lys Pro Thr Leu Ser

115 120 125

Ala Gln Pro Ser Pro Val Val Asn Ser Gly Gly Asn Val Thr Leu Gln

130 135 140

Cys Asp Ser Gln Val Ala Phe Asp Gly Phe Ile Leu Cys Lys Glu Gly

145 150 155 160

Glu Asp Glu His Pro Gln Cys Leu Asn Ser Gln Pro His Ala Arg Gly

165 170 175

Ser Ser Arg Ala Ile Phe Ser Val Gly Pro Val Ser Pro Ser Arg Arg

180 185 190

Trp Trp Tyr Arg Cys Tyr Ala Tyr Asp Ser Asn Ser Pro Tyr Glu Trp

195 200 205

Ser Leu Pro Ser Asp Leu Leu Glu Leu Leu Val Leu Gly Val Ser Lys

210 215 220

Lys Pro Ser Leu Ser Val Gln Pro Gly Pro Ile Val Ala Pro Glu Glu

225 230 235 240

Thr Leu Thr Leu Gln Cys Gly Ser Asp Ala Gly Tyr Asn Arg Phe Val

245 250 255

Leu Tyr Lys Asp Gly Glu Arg Asp Phe Leu Gln Leu Ala Gly Ala Gln

260 265 270

Pro Gln Ala Gly Leu Ser Gln Ala Asn Phe Thr Leu Gly Pro Val Ser

275 280 285

Arg Ser Tyr Gly Gly Gln Tyr Arg Cys Tyr Gly Ala His Asn Leu Ser

290 295 300

Ser Glu Trp Ser Ala Pro Ser Asp Pro Leu Asp Ile Leu Ile Ala Gly

305 310 315 320

Gln Phe Tyr Asp Arg Val Ser Leu Ser Val Gln Pro Gly Pro Thr Val

325 330 335

Ala Ser Gly Glu Asn Val Thr Leu Leu Cys Gln Ser Gln Gly Trp Met

340 345 350

Gln Thr Phe Leu Leu Thr Lys Glu Gly Ala Ala Asp Asp Pro Trp Arg

355 360 365

Leu Arg Ser Thr Tyr Gln Ser Gln Lys Tyr Gln Ala Glu Phe Pro Met

370 375 380

Gly Pro Val Thr Ser Ala His Ala Gly Thr Tyr Arg Cys Tyr Gly Ser

385 390 395 400

Gln Ser Ser Lys Pro Tyr Leu Leu Thr His Pro Ser Asp Pro Leu Glu

405 410 415

Leu Val Val Ser Gly Pro Ser Gly Gly Pro Ser Ser Pro Thr Thr Gly

420 425 430

Pro Thr Ser Thr Ser Gly Pro Glu Asp Gln Pro Leu Thr Pro Thr Gly

435 440 445

Ser Asp Pro Gln Ser Gly Leu Gly Arg His Leu Gly Val Val Ile Gly

450 455 460

Ile Leu Val Ala Val Ile Leu Leu Leu Leu Leu Leu Leu Leu Leu Phe

465 470 475 480

Leu Ile Leu Arg His Arg Arg Gln Gly Lys His Trp Thr Ser Thr Gln

485 490 495

Arg Lys Ala Asp Phe Gln His Pro Ala Gly Ala Val Gly Pro Glu Pro

500 505 510

Thr Asp Arg Gly Leu Gln Trp Arg Ser Ser Pro Ala Ala Asp Ala Gln

515 520 525

Glu Glu Asn Leu Tyr Ala Ala Val Lys His Thr Gln Pro Glu Asp Gly

530 535 540

Val Glu Met Asp Thr Arg Ser Pro His Asp Glu Asp Pro Gln Ala Val

545 550 555 560

Thr Tyr Ala Glu Val Lys His Ser Arg Pro Arg Arg Glu Met Ala Ser

565 570 575

Pro Pro Ser Pro Leu Ser Gly Glu Phe Leu Asp Thr Lys Asp Arg Gln

580 585 590

Ala Glu Glu Asp Arg Gln Met Asp Thr Glu Ala Ala Ala Ser Glu Ala

595 600 605

Pro Gln Asp Val Thr Tyr Ala Gln Leu His Ser Leu Thr Leu Arg Arg

610 615 620

Lys Ala Thr Glu Pro Pro Pro Ser Gln Glu Gly Pro Ser Pro Ala Val

625 630 635 640

Pro Ser Ile Tyr Ala Thr Leu Ala Ile His

645 650

<210> 349

<211> 598

<212> Protein

<213> Artificial sequence

<220>

<223> LILRB2(AAH36827)

<400> 349

Met Thr Pro Ile Val Thr Val Leu Ile Cys Leu Gly Leu Ser Leu Gly

1 5 10 15

Pro Arg Thr His Val Gln Thr Gly Thr Ile Pro Lys Pro Thr Leu Trp

20 25 30

Ala Glu Pro Asp Ser Val Ile Thr Gln Gly Ser Pro Val Thr Leu Ser

35 40 45

Cys Gln Gly Ser Leu Glu Ala Gln Glu Tyr Arg Leu Tyr Arg Glu Lys

50 55 60

Lys Ser Ala Ser Trp Ile Thr Arg Ile Arg Pro Glu Leu Val Lys Asn

65 70 75 80

Gly Gln Phe His Ile Pro Ser Ile Thr Trp Glu His Thr Gly Arg Tyr

85 90 95

Gly Cys Gln Tyr Tyr Ser Arg Ala Arg Trp Ser Glu Leu Ser Asp Pro

100 105 110

Leu Val Leu Val Met Thr Gly Ala Tyr Pro Lys Pro Thr Leu Ser Ala

115 120 125

Gln Pro Ser Pro Val Val Thr Ser Gly Gly Arg Val Thr Leu Gln Cys

130 135 140

Glu Ser Gln Val Ala Phe Gly Gly Phe Ile Leu Cys Lys Glu Gly Glu

145 150 155 160

Asp Glu His Pro Gln Cys Leu Asn Ser Gln Pro His Ala Arg Gly Ser

165 170 175

Ser Arg Ala Ile Phe Ser Val Gly Pro Val Ser Pro Asn Arg Arg Trp

180 185 190

Ser His Arg Cys Tyr Gly Tyr Asp Leu Asn Ser Pro Tyr Val Trp Ser

195 200 205

Ser Pro Ser Asp Leu Leu Glu Leu Leu Val Pro Gly Val Ser Lys Lys

210 215 220

Pro Ser Leu Ser Val Gln Pro Gly Pro Val Val Ala Pro Gly Glu Ser

225 230 235 240

Leu Thr Leu Gln Cys Val Ser Asp Val Gly Tyr Asp Arg Phe Val Leu

245 250 255

Tyr Lys Glu Gly Glu Arg Asp Leu Arg Gln Leu Pro Gly Arg Gln Pro

260 265 270

Gln Ala Gly Leu Ser Gln Ala Asn Phe Thr Leu Gly Pro Val Ser Arg

275 280 285

Ser Tyr Gly Gly Gln Tyr Arg Cys Tyr Gly Ala Tyr Asn Leu Ser Ser

290 295 300

Glu Trp Ser Ala Pro Ser Asp Pro Leu Asp Ile Leu Ile Thr Gly Gln

305 310 315 320

Ile His Gly Thr Pro Phe Ile Ser Val Gln Pro Gly Pro Thr Val Ala

325 330 335

Ser Gly Glu Asn Val Thr Leu Leu Cys Gln Ser Trp Arg Gln Phe His

340 345 350

Thr Phe Leu Leu Thr Lys Ala Gly Ala Ala Asp Ala Pro Leu Arg Leu

355 360 365

Arg Ser Ile His Glu Tyr Pro Lys Tyr Gln Ala Glu Phe Pro Met Ser

370 375 380

Pro Val Thr Ser Ala His Ala Gly Thr Tyr Arg Cys Tyr Gly Ser Leu

385 390 395 400

Asn Ser Asp Pro Tyr Leu Leu Ser His Pro Ser Glu Pro Leu Glu Leu

405 410 415

Val Val Ser Gly Pro Ser Met Gly Ser Ser Pro Pro Pro Thr Gly Pro

420 425 430

Ile Ser Thr Pro Ala Gly Pro Glu Asp Gln Pro Leu Thr Pro Thr Gly

435 440 445

Ser Asp Pro Gln Ser Gly Leu Gly Arg His Leu Gly Val Val Ile Gly

450 455 460

Ile Leu Val Ala Val Val Leu Leu Leu Leu Leu Leu Leu Leu Leu Phe

465 470 475 480

Leu Ile Leu Arg His Arg Arg Gln Gly Lys His Trp Thr Ser Thr Gln

485 490 495

Arg Lys Ala Asp Phe Gln His Pro Ala Gly Ala Val Gly Pro Glu Pro

500 505 510

Thr Asp Arg Gly Leu Gln Trp Arg Ser Ser Pro Ala Ala Asp Ala Gln

515 520 525

Glu Glu Asn Leu Tyr Ala Ala Val Lys Asp Thr Gln Pro Glu Asp Gly

530 535 540

Val Glu Met Asp Thr Arg Ala Ala Ala Ser Glu Ala Pro Gln Asp Val

545 550 555 560

Thr Tyr Ala Gln Leu His Ser Leu Thr Leu Arg Arg Lys Ala Thr Glu

565 570 575

Pro Pro Pro Ser Gln Glu Gly Glu Pro Pro Ala Glu Pro Ser Ile Tyr

580 585 590

Ala Thr Leu Ala Ile His

595

<210> 350

<211> 631

<212> Protein

<213> Artificial sequence

<220>

<223> LILRB3(XP_006726377)

<400> 350

Met Thr Pro Ala Leu Thr Ala Leu Leu Cys Leu Gly Leu Ser Leu Gly

1 5 10 15

Pro Arg Thr Arg Val Gln Ala Gly Pro Phe Pro Lys Pro Thr Leu Trp

20 25 30

Ala Glu Pro Gly Ser Val Ile Ser Trp Gly Ser Pro Val Thr Ile Trp

35 40 45

Cys Gln Gly Ser Leu Glu Ala Gln Glu Tyr Arg Leu Asp Lys Glu Gly

50 55 60

Ser Pro Glu Pro Leu Asp Arg Asn Asn Pro Leu Glu Pro Lys Asn Lys

65 70 75 80

Ala Arg Phe Ser Ile Pro Ser Met Thr Glu His His Ala Gly Arg Tyr

85 90 95

Arg Cys His Tyr Tyr Ser Ser Ala Gly Trp Ser Glu Pro Ser Asp Pro

100 105 110

Leu Glu Leu Val Met Thr Gly Phe Tyr Asn Lys Pro Thr Leu Ser Ala

115 120 125

Leu Pro Ser Pro Val Val Ala Ser Gly Gly Asn Met Thr Leu Arg Cys

130 135 140

Gly Ser Gln Lys Gly Tyr His His Phe Val Leu Met Lys Glu Gly Glu

145 150 155 160

His Gln Leu Pro Arg Thr Leu Asp Ser Gln Gln Leu His Ser Gly Gly

165 170 175

Phe Gln Ala Leu Phe Pro Val Gly Pro Val Asn Pro Ser His Arg Trp

180 185 190

Arg Phe Thr Cys Tyr Tyr Tyr Tyr Met Asn Thr Pro Gln Val Trp Ser

195 200 205

His Pro Ser Asp Pro Leu Glu Ile Leu Pro Ser Gly Val Ser Arg Lys

210 215 220

Pro Ser Leu Leu Thr Leu Gln Gly Pro Val Leu Ala Pro Gly Gln Ser

225 230 235 240

Leu Thr Leu Gln Cys Gly Ser Asp Val Gly Tyr Asp Arg Phe Val Leu

245 250 255

Tyr Lys Glu Gly Glu Arg Asp Phe Leu Gln Arg Pro Gly Gln Gln Pro

260 265 270

Gln Ala Gly Leu Ser Gln Ala Asn Phe Thr Leu Gly Pro Val Ser Pro

275 280 285

Ser His Gly Gly Gln Tyr Arg Cys Tyr Gly Ala His Asn Leu Ser Ser

290 295 300

Glu Trp Ser Ala Pro Ser Asp Pro Leu Asn Ile Leu Met Ala Gly Gln

305 310 315 320

Ile Tyr Asp Thr Val Ser Leu Ser Ala Gln Pro Gly Pro Thr Val Ala

325 330 335

Ser Gly Glu Asn Val Thr Leu Leu Cys Gln Ser Trp Trp Gln Phe Asp

340 345 350

Thr Phe Leu Leu Thr Lys Glu Gly Ala Ala His Pro Pro Leu Arg Leu

355 360 365

Arg Ser Met Tyr Gly Ala His Lys Tyr Gln Ala Glu Phe Pro Met Ser

370 375 380

Pro Val Thr Ser Ala His Ala Gly Thr Tyr Arg Cys Tyr Gly Ser Tyr

385 390 395 400

Ser Ser Asn Pro His Leu Leu Ser Phe Pro Ser Glu Pro Leu Glu Leu

405 410 415

Met Val Ser Gly His Ser Gly Gly Ser Ser Leu Pro Pro Thr Gly Pro

420 425 430

Pro Ser Thr Pro Gly Leu Gly Arg Tyr Leu Glu Val Leu Ile Gly Val

435 440 445

Ser Val Ala Phe Val Leu Leu Leu Phe Leu Leu Leu Phe Leu Leu Leu

450 455 460

Arg Arg Gln Arg His Ser Lys His Arg Thr Ser Asp Gln Arg Lys Thr

465 470 475 480

Asp Phe Gln Arg Pro Ala Gly Ala Ala Glu Thr Glu Pro Lys Asp Arg

485 490 495

Gly Leu Leu Arg Arg Ser Ser Pro Ala Ala Asp Val Gln Glu Glu Asn

500 505 510

Leu Tyr Ala Ala Val Lys Asp Thr Gln Ser Glu Asp Arg Val Glu Leu

515 520 525

Asp Ser Gln Ser Pro His Asp Glu Asp Pro Gln Ala Val Thr Tyr Ala

530 535 540

Pro Val Lys His Ser Ser Pro Arg Arg Glu Met Ala Ser Pro Pro Ser

545 550 555 560

Ser Leu Ser Gly Glu Phe Leu Asp Thr Lys Asp Arg Gln Val Glu Glu

565 570 575

Asp Arg Gln Met Asp Thr Glu Ala Ala Ala Ser Glu Ala Ser Gln Asp

580 585 590

Val Thr Tyr Ala Gln Leu His Ser Leu Thr Leu Arg Arg Lys Ala Thr

595 600 605

Glu Pro Pro Pro Ser Gln Glu Gly Glu Pro Pro Ala Glu Pro Ser Ile

610 615 620

Tyr Ala Thr Leu Ala Ile His

625 630

<210> 351

<211> 448

<212> Protein

<213> Artificial sequence

<220>

<223> LILRB4(NP_001265355)

<400> 351

Met Ile Pro Thr Phe Thr Ala Leu Leu Cys Leu Gly Leu Ser Leu Gly

1 5 10 15

Pro Arg Thr His Met Gln Ala Gly Pro Leu Pro Lys Pro Thr Leu Trp

20 25 30

Ala Glu Pro Gly Ser Val Ile Ser Trp Gly Asn Ser Val Thr Ile Trp

35 40 45

Cys Gln Gly Thr Leu Glu Ala Arg Glu Tyr Arg Leu Asp Lys Glu Glu

50 55 60

Ser Pro Ala Pro Trp Asp Arg Gln Asn Pro Leu Glu Pro Lys Asn Lys

65 70 75 80

Ala Arg Phe Ser Ile Pro Ser Met Thr Glu Asp Tyr Ala Gly Arg Tyr

85 90 95

Arg Cys Tyr Tyr Arg Ser Pro Val Gly Trp Ser Gln Pro Ser Asp Pro

100 105 110

Leu Glu Leu Val Met Thr Gly Ala Tyr Ser Lys Pro Thr Leu Ser Ala

115 120 125

Leu Pro Ser Pro Leu Val Thr Ser Gly Lys Ser Val Thr Leu Leu Cys

130 135 140

Gln Ser Arg Ser Pro Met Asp Thr Phe Leu Leu Ile Lys Glu Arg Ala

145 150 155 160

Ala His Pro Leu Leu His Leu Arg Ser Glu His Gly Ala Gln Gln His

165 170 175

Gln Ala Glu Phe Pro Met Ser Pro Val Thr Ser Val His Gly Gly Thr

180 185 190

Tyr Arg Cys Phe Ser Ser His Gly Phe Ser His Tyr Leu Leu Ser His

195 200 205

Pro Ser Asp Pro Leu Glu Leu Ile Val Ser Gly Ser Leu Glu Gly Pro

210 215 220

Arg Pro Ser Pro Thr Arg Ser Val Ser Thr Ala Ala Gly Pro Glu Asp

225 230 235 240

Gln Pro Leu Met Pro Thr Gly Ser Val Pro His Ser Gly Leu Arg Arg

245 250 255

His Trp Glu Val Leu Ile Gly Val Leu Val Val Ser Ile Leu Leu Leu

260 265 270

Ser Leu Leu Leu Phe Leu Leu Leu Gln His Trp Arg Gln Gly Lys His

275 280 285

Arg Thr Leu Ala Gln Arg Gln Ala Asp Phe Gln Arg Pro Pro Gly Ala

290 295 300

Ala Glu Pro Glu Pro Lys Asp Gly Gly Leu Gln Arg Arg Ser Ser Pro

305 310 315 320

Ala Ala Asp Val Gln Gly Glu Asn Phe Cys Ala Ala Val Lys Asn Thr

325 330 335

Gln Pro Glu Asp Gly Val Glu Met Asp Thr Arg Gln Ser Pro His Asp

340 345 350

Glu Asp Pro Gln Ala Val Thr Tyr Ala Lys Val Lys His Ser Arg Pro

355 360 365

Arg Arg Glu Met Ala Ser Pro Pro Ser Pro Leu Ser Gly Glu Phe Leu

370 375 380

Asp Thr Lys Asp Arg Gln Ala Glu Glu Asp Arg Gln Met Asp Thr Glu

385 390 395 400

Ala Ala Ala Ser Glu Ala Pro Gln Asp Val Thr Tyr Ala Arg Leu His

405 410 415

Ser Phe Thr Leu Arg Gln Lys Ala Thr Glu Pro Pro Pro Ser Gln Glu

420 425 430

Gly Ala Ser Pro Ala Glu Pro Ser Val Tyr Ala Thr Leu Ala Ile His

435 440 445

<210> 352

<211> 590

<212> Protein

<213> Artificial sequence

<220>

<223> LILRB5(NP_006831)

<400> 352

Met Thr Leu Thr Leu Ser Val Leu Ile Cys Leu Gly Leu Ser Val Gly

1 5 10 15

Pro Arg Thr Cys Val Gln Ala Gly Thr Leu Pro Lys Pro Thr Leu Trp

20 25 30

Ala Glu Pro Ala Ser Val Ile Ala Arg Gly Lys Pro Val Thr Leu Trp

35 40 45

Cys Gln Gly Pro Leu Glu Thr Glu Glu Tyr Arg Leu Asp Lys Glu Gly

50 55 60

Leu Pro Trp Ala Arg Lys Arg Gln Asn Pro Leu Glu Pro Gly Ala Lys

65 70 75 80

Ala Lys Phe His Ile Pro Ser Thr Val Tyr Asp Ser Ala Gly Arg Tyr

85 90 95

Arg Cys Tyr Tyr Glu Thr Pro Ala Gly Trp Ser Glu Pro Ser Asp Pro

100 105 110

Leu Glu Leu Val Ala Thr Gly Phe Tyr Ala Glu Pro Thr Leu Leu Ala

115 120 125

Leu Pro Ser Pro Val Val Ala Ser Gly Gly Asn Val Thr Leu Gln Cys

130 135 140

Asp Thr Leu Asp Gly Leu Leu Thr Phe Val Leu Val Glu Glu Glu Gln

145 150 155 160

Lys Leu Pro Arg Thr Leu Tyr Ser Gln Lys Leu Pro Lys Gly Pro Ser

165 170 175

Gln Ala Leu Phe Pro Val Gly Pro Val Thr Pro Ser Cys Arg Trp Arg

180 185 190

Phe Arg Cys Tyr Tyr Tyr Tyr Arg Lys Asn Pro Gln Val Trp Ser Asn

195 200 205

Pro Ser Asp Leu Leu Glu Ile Leu Val Pro Gly Val Ser Arg Lys Pro

210 215 220

Ser Leu Leu Ile Pro Gly Gly Ser Val Val Ala Arg Gly Gly Ser Leu

225 230 235 240

Thr Leu Gln Cys Arg Ser Asp Val Gly Tyr Asp Ile Phe Val Leu Tyr

245 250 255

Lys Glu Gly Glu His Asp Leu Val Gln Gly Ser Gly Gln Gln Pro Gln

260 265 270

Ala Gly Leu Ser Gln Ala Asn Phe Thr Leu Gly Pro Val Ser Arg Ser

275 280 285

His Gly Gly Gln Tyr Arg Cys Tyr Gly Ala His Asn Leu Ser Pro Arg

290 295 300

Trp Ser Ala Pro Ser Asp Pro Leu Asp Ile Leu Ile Ala Gly Leu Ile

305 310 315 320

Pro Asp Ile Pro Ala Leu Ser Val Gln Pro Gly Pro Lys Val Ala Ser

325 330 335

Gly Glu Asn Val Thr Leu Leu Cys Gln Ser Trp His Gln Ile Asp Thr

340 345 350

Phe Phe Leu Thr Lys Glu Gly Ala Ala His Pro Pro Leu Cys Leu Lys

355 360 365

Ser Lys Tyr Gln Ser Tyr Arg His Gln Ala Glu Phe Ser Met Ser Pro

370 375 380

Val Thr Ser Ala Gln Gly Gly Thr Tyr Arg Cys Tyr Ser Ala Ile Arg

385 390 395 400

Ser Tyr Pro Tyr Leu Leu Ser Ser Pro Ser Tyr Pro Gln Glu Leu Val

405 410 415

Val Ser Gly Pro Ser Gly Asp Pro Ser Leu Ser Pro Thr Gly Ser Thr

420 425 430

Pro Thr Pro Gly Pro Glu Asp Gln Pro Leu Thr Pro Thr Gly Leu Asp

435 440 445

Pro Gln Ser Gly Leu Gly Arg His Leu Gly Val Val Thr Gly Val Ser

450 455 460

Val Ala Phe Val Leu Leu Leu Phe Leu Leu Leu Phe Leu Leu Leu Arg

465 470 475 480

His Arg His Gln Ser Lys His Arg Thr Ser Ala His Phe Tyr Arg Pro

485 490 495

Ala Gly Ala Ala Gly Pro Glu Pro Lys Asp Gln Gly Leu Gln Lys Arg

500 505 510

Ala Ser Pro Val Ala Asp Ile Gln Glu Glu Ile Leu Asn Ala Ala Val

515 520 525

Lys Asp Thr Gln Pro Lys Asp Gly Val Glu Met Asp Ala Arg Ala Ala

530 535 540

Ala Ser Glu Ala Pro Gln Asp Val Thr Tyr Ala Gln Leu His Ser Leu

545 550 555 560

Thr Leu Arg Arg Glu Ala Thr Glu Pro Pro Pro Ser Gln Glu Arg Glu

565 570 575

Pro Pro Ala Glu Pro Ser Ile Tyr Ala Pro Leu Ala Ile His

580 585 590

<210> 353

<211> 489

<212> Protein

<213> Artificial sequence

<220>

<223> LILRA1(NP_006854)

<400> 353

Met Thr Pro Ile Val Thr Val Leu Ile Cys Leu Arg Leu Ser Leu Gly

1 5 10 15

Pro Arg Thr His Val Gln Ala Gly Thr Leu Pro Lys Pro Thr Leu Trp

20 25 30

Ala Glu Pro Gly Ser Val Ile Thr Gln Gly Ser Pro Val Thr Leu Trp

35 40 45

Cys Gln Gly Ile Leu Glu Thr Gln Glu Tyr Arg Leu Tyr Arg Glu Lys

50 55 60

Lys Thr Ala Pro Trp Ile Thr Arg Ile Pro Gln Glu Ile Val Lys Lys

65 70 75 80

Gly Gln Phe Pro Ile Pro Ser Ile Thr Trp Glu His Thr Gly Arg Tyr

85 90 95

Arg Cys Phe Tyr Gly Ser His Thr Ala Gly Trp Ser Glu Pro Ser Asp

100 105 110

Pro Leu Glu Leu Val Val Thr Gly Ala Tyr Ile Lys Pro Thr Leu Ser

115 120 125

Ala Leu Pro Ser Pro Val Val Thr Ser Gly Gly Asn Val Thr Leu His

130 135 140

Cys Val Ser Gln Val Ala Phe Gly Ser Phe Ile Leu Cys Lys Glu Gly

145 150 155 160

Glu Asp Glu His Pro Gln Cys Leu Asn Ser Gln Pro Arg Thr His Gly

165 170 175

Trp Ser Arg Ala Ile Phe Ser Val Gly Pro Val Ser Pro Ser Arg Arg

180 185 190

Trp Ser Tyr Arg Cys Tyr Ala Tyr Asp Ser Asn Ser Pro His Val Trp

195 200 205

Ser Leu Pro Ser Asp Leu Leu Glu Leu Leu Val Leu Gly Val Ser Lys

210 215 220

Lys Pro Ser Leu Ser Val Gln Pro Gly Pro Ile Val Ala Pro Gly Glu

225 230 235 240

Ser Leu Thr Leu Gln Cys Val Ser Asp Val Ser Tyr Asp Arg Phe Val

245 250 255

Leu Tyr Lys Glu Gly Glu Arg Asp Phe Leu Gln Leu Pro Gly Pro Gln

260 265 270

Pro Gln Ala Gly Leu Ser Gln Ala Asn Phe Thr Leu Gly Pro Val Ser

275 280 285

Arg Ser Tyr Gly Gly Gln Tyr Arg Cys Ser Gly Ala Tyr Asn Leu Ser

290 295 300

Ser Glu Trp Ser Ala Pro Ser Asp Pro Leu Asp Ile Leu Ile Ala Gly

305 310 315 320

Gln Phe Arg Gly Arg Pro Phe Ile Ser Val His Pro Gly Pro Thr Val

325 330 335

Ala Ser Gly Glu Asn Val Thr Leu Leu Cys Gln Ser Trp Gly Pro Phe

340 345 350

His Thr Phe Leu Leu Thr Lys Ala Gly Ala Ala Asp Ala Pro Leu Arg

355 360 365

Leu Arg Ser Ile His Glu Tyr Pro Lys Tyr Gln Ala Glu Phe Pro Met

370 375 380

Ser Pro Val Thr Ser Ala His Ser Gly Thr Tyr Arg Cys Tyr Gly Ser

385 390 395 400

Leu Ser Ser Asn Pro Tyr Leu Leu Ser His Pro Ser Asp Ser Leu Glu

405 410 415

Leu Met Val Ser Gly Ala Ala Glu Thr Leu Ser Pro Pro Gln Asn Lys

420 425 430

Ser Asp Ser Lys Ala Gly Ala Ala Asn Thr Leu Ser Pro Ser Gln Asn

435 440 445

Lys Thr Ala Ser His Pro Gln Asp Tyr Thr Val Glu Asn Leu Ile Arg

450 455 460

Met Gly Ile Ala Gly Leu Val Leu Val Val Leu Gly Ile Leu Leu Phe

465 470 475 480

Glu Ala Gln His Ser Gln Arg Ser Leu

485

<210> 354

<211> 466

<212> Protein

<213> Artificial sequence

<220>

<223> LILRA2(AAH17412)

<400> 354

Met Thr Pro Ile Leu Thr Val Leu Ile Cys Leu Gly Leu Ser Leu Gly

1 5 10 15

Pro Arg Thr His Val Gln Ala Gly His Leu Pro Lys Pro Thr Leu Trp

20 25 30

Ala Glu Pro Gly Ser Val Ile Ile Gln Gly Ser Pro Val Thr Leu Arg

35 40 45

Cys Gln Gly Ser Leu Gln Ala Glu Glu Tyr His Leu Tyr Arg Glu Asn

50 55 60

Lys Ser Ala Ser Trp Val Arg Arg Ile Gln Glu Pro Gly Lys Asn Gly

65 70 75 80

Gln Phe Pro Ile Pro Ser Ile Thr Trp Glu His Ala Gly Arg Tyr His

85 90 95

Cys Gln Tyr Tyr Ser His Asn His Ser Ser Glu Tyr Ser Asp Pro Leu

100 105 110

Glu Leu Val Val Thr Gly Ala Tyr Ser Lys Pro Thr Leu Ser Ala Leu

115 120 125

Pro Ser Pro Val Val Thr Leu Gly Gly Asn Val Thr Leu Gln Cys Val

130 135 140

Ser Gln Val Ala Phe Asp Gly Phe Ile Leu Cys Lys Glu Gly Glu Asp

145 150 155 160

Glu His Pro Gln Arg Leu Asn Ser His Ser His Ala Arg Gly Trp Ser

165 170 175

Trp Ala Ile Phe Ser Val Gly Pro Val Ser Pro Ser Arg Arg Trp Ser

180 185 190

Tyr Arg Cys Tyr Ala Tyr Asp Ser Asn Ser Pro Tyr Val Trp Ser Leu

195 200 205

Pro Ser Asp Leu Leu Glu Leu Leu Val Pro Gly Val Ser Lys Lys Pro

210 215 220

Ser Leu Ser Val Gln Pro Gly Pro Met Val Ala Pro Gly Glu Ser Leu

225 230 235 240

Thr Leu Gln Cys Val Ser Asp Val Gly Tyr Asp Arg Phe Val Leu Tyr

245 250 255

Lys Glu Gly Glu Arg Asp Phe Leu Gln Arg Pro Gly Trp Gln Pro Gln

260 265 270

Ala Gly Leu Ser Gln Ala Asn Phe Thr Leu Gly Pro Val Ser Pro Ser

275 280 285

His Gly Gly Gln Tyr Arg Cys Tyr Ser Ala His Asn Leu Ser Ser Glu

290 295 300

Trp Ser Ala Pro Ser Asp Pro Leu Asp Ile Leu Ile Thr Gly Gln Phe

305 310 315 320

Tyr Asp Arg Pro Ser Leu Ser Val Gln Pro Val Pro Thr Val Ala Pro

325 330 335

Gly Lys Asn Val Thr Leu Leu Cys Gln Ser Arg Gly Gln Phe His Thr

340 345 350

Phe Leu Leu Thr Lys Glu Gly Ala Gly His Pro Pro Leu His Leu Arg

355 360 365

Ser Glu His Gln Ala Gln Gln Asn Gln Ala Glu Phe Arg Met Gly Pro

370 375 380

Val Thr Ser Ala His Val Gly Thr Tyr Arg Cys Tyr Ser Ser Leu Ser

385 390 395 400

Ser Asn Pro Tyr Leu Leu Ser Leu Pro Ser Asp Pro Leu Glu Leu Val

405 410 415

Val Ser Ala Ser Leu Gly Gln His Pro Gln Asp Tyr Thr Val Glu Asn

420 425 430

Leu Ile Arg Met Gly Val Ala Gly Leu Val Leu Val Val Leu Gly Ile

435 440 445

Leu Leu Phe Glu Ala Gln His Ser Gln Arg Ser Leu Gln Asp Ala Ala

450 455 460

Gly Arg

465

<210> 355

<211> 439

<212> Protein

<213> Artificial sequence

<220>

<223> LILRA3(AAH28208)

<400> 355

Met Thr Ser Ile Leu Thr Val Leu Ile Cys Leu Gly Leu Ser Leu Asp

1 5 10 15

Pro Arg Thr His Val Gln Ala Gly Pro Leu Pro Lys Pro Thr Leu Trp

20 25 30

Ala Glu Pro Gly Ser Val Ile Thr Gln Gly Ser Pro Val Thr Leu Arg

35 40 45

Cys Gln Gly Ser Leu Glu Thr Gln Glu Tyr His Leu Tyr Arg Glu Lys

50 55 60

Lys Thr Ala Leu Trp Ile Thr Arg Ile Pro Gln Glu Leu Val Lys Lys

65 70 75 80

Gly Gln Phe Pro Ile Leu Ser Ile Thr Trp Glu His Ala Gly Arg Tyr

85 90 95

Cys Cys Ile Tyr Gly Ser His Thr Val Gly Leu Ser Glu Ser Ser Asp

100 105 110

Pro Leu Glu Leu Val Val Thr Gly Ala Tyr Ser Lys Pro Thr Leu Ser

115 120 125

Ala Leu Pro Ser Pro Val Val Thr Ser Gly Gly Asn Val Thr Ile Gln

130 135 140

Cys Asp Ser Gln Val Ala Phe Asp Gly Phe Ile Leu Cys Lys Glu Gly

145 150 155 160

Glu Asp Glu His Pro Gln Cys Leu Asn Ser His Ser His Ala Arg Gly

165 170 175

Ser Ser Arg Ala Ile Phe Ser Val Gly Pro Val Ser Pro Ser Arg Arg

180 185 190

Trp Ser Tyr Arg Cys Tyr Gly Tyr Asp Ser Arg Ala Pro Tyr Val Trp

195 200 205

Ser Leu Pro Ser Asp Leu Leu Gly Leu Leu Val Pro Gly Val Ser Lys

210 215 220

Lys Pro Ser Leu Ser Val Gln Pro Gly Pro Val Val Ala Pro Gly Glu

225 230 235 240

Lys Leu Thr Phe Gln Cys Gly Ser Asp Ala Gly Tyr Asp Arg Phe Val

245 250 255

Leu Tyr Lys Glu Trp Gly Arg Asp Phe Leu Gln Arg Pro Gly Arg Gln

260 265 270

Pro Gln Ala Gly Leu Ser Gln Ala Asn Phe Thr Leu Gly Pro Val Ser

275 280 285

Arg Ser Tyr Gly Gly Gln Tyr Thr Cys Ser Gly Ala Tyr Asn Leu Ser

290 295 300

Ser Glu Trp Ser Ala Pro Ser Asp Pro Leu Asp Ile Leu Ile Thr Gly

305 310 315 320

Gln Ile Arg Ala Arg Pro Phe Leu Ser Val Arg Pro Gly Pro Thr Val

325 330 335

Ala Ser Gly Glu Asn Val Thr Leu Leu Cys Gln Ser Gln Gly Gly Met

340 345 350

His Thr Phe Leu Leu Thr Lys Glu Gly Ala Ala Asp Ser Pro Leu Arg

355 360 365

Leu Lys Ser Lys Arg Gln Ser His Lys Tyr Gln Ala Glu Phe Pro Met

370 375 380

Ser Pro Val Thr Ser Ala His Ala Gly Thr Tyr Arg Cys Tyr Gly Ser

385 390 395 400

Leu Ser Ser Asn Pro Tyr Leu Leu Thr His Pro Ser Asp Pro Leu Glu

405 410 415

Leu Val Val Ser Gly Ala Ala Glu Thr Leu Ser Pro Pro Gln Asn Lys

420 425 430

Ser Asp Ser Lys Ala Gly Glu

435

<210> 356

<211> 499

<212> Protein

<213> Artificial sequence

<220>

<223> LILRA4(NP_036408)

<400> 356

Met Thr Leu Ile Leu Thr Ser Leu Leu Phe Phe Gly Leu Ser Leu Gly

1 5 10 15

Pro Arg Thr Arg Val Gln Ala Glu Asn Leu Pro Lys Pro Ile Leu Trp

20 25 30

Ala Glu Pro Gly Pro Val Ile Thr Trp His Asn Pro Val Thr Ile Trp

35 40 45

Cys Gln Gly Thr Leu Glu Ala Gln Gly Tyr Arg Leu Asp Lys Glu Gly

50 55 60

Asn Ser Met Ser Arg His Ile Leu Lys Thr Leu Glu Ser Glu Asn Lys

65 70 75 80

Val Lys Leu Ser Ile Pro Ser Met Met Trp Glu His Ala Gly Arg Tyr

85 90 95

His Cys Tyr Tyr Gln Ser Pro Ala Gly Trp Ser Glu Pro Ser Asp Pro

100 105 110

Leu Glu Leu Val Val Thr Ala Tyr Ser Arg Pro Thr Leu Ser Ala Leu

115 120 125

Pro Ser Pro Val Val Thr Ser Gly Val Asn Val Thr Leu Arg Cys Ala

130 135 140

Ser Arg Leu Gly Leu Gly Arg Phe Thr Leu Ile Glu Glu Gly Asp His

145 150 155 160

Arg Leu Ser Trp Thr Leu Asn Ser His Gln His Asn His Gly Lys Phe

165 170 175

Gln Ala Leu Phe Pro Met Gly Pro Leu Thr Phe Ser Asn Arg Gly Thr

180 185 190

Phe Arg Cys Tyr Gly Tyr Glu Asn Asn Thr Pro Tyr Val Trp Ser Glu

195 200 205

Pro Ser Asp Pro Leu Gln Leu Leu Val Ser Gly Val Ser Arg Lys Pro

210 215 220

Ser Leu Leu Thr Leu Gln Gly Pro Val Val Thr Pro Gly Glu Asn Leu

225 230 235 240

Thr Leu Gln Cys Gly Ser Asp Val Gly Tyr Ile Arg Tyr Thr Leu Tyr

245 250 255

Lys Glu Gly Ala Asp Gly Leu Pro Gln Arg Pro Gly Arg Gln Pro Gln

260 265 270

Ala Gly Leu Ser Gln Ala Asn Phe Thr Leu Ser Pro Val Ser Arg Ser

275 280 285

Tyr Gly Gly Gln Tyr Arg Cys Tyr Gly Ala His Asn Val Ser Ser Glu

290 295 300

Trp Ser Ala Pro Ser Asp Pro Leu Asp Ile Leu Ile Ala Gly Gln Ile

305 310 315 320

Ser Asp Arg Pro Ser Leu Ser Val Gln Pro Gly Pro Thr Val Thr Ser

325 330 335

Gly Glu Lys Val Thr Leu Leu Cys Gln Ser Trp Asp Pro Met Phe Thr

340 345 350

Phe Leu Leu Thr Lys Glu Gly Ala Ala His Pro Pro Leu Arg Leu Arg

355 360 365

Ser Met Tyr Gly Ala His Lys Tyr Gln Ala Glu Phe Pro Met Ser Pro

370 375 380

Val Thr Ser Ala His Ala Gly Thr Tyr Arg Cys Tyr Gly Ser Arg Ser

385 390 395 400

Ser Asn Pro Tyr Leu Leu Ser His Pro Ser Glu Pro Leu Glu Leu Val

405 410 415

Val Ser Gly Ala Thr Glu Thr Leu Asn Pro Ala Gln Lys Lys Ser Asp

420 425 430

Ser Lys Thr Ala Pro His Leu Gln Asp Tyr Thr Val Glu Asn Leu Ile

435 440 445

Arg Met Gly Val Ala Gly Leu Val Leu Leu Phe Leu Gly Ile Leu Leu

450 455 460

Phe Glu Ala Gln His Ser Gln Arg Ser Pro Pro Arg Cys Ser Gln Glu

465 470 475 480

Ala Asn Ser Arg Lys Asp Asn Ala Pro Phe Arg Val Val Glu Pro Trp

485 490 495

Glu Gln Ile

<210> 357

<211> 299

<212> Protein

<213> Artificial sequence

<220>

<223> LILRA5(NP_067073)

<400> 357

Met Ala Pro Trp Ser His Pro Ser Ala Gln Leu Gln Pro Val Gly Gly

1 5 10 15

Asp Ala Val Ser Pro Ala Leu Met Val Leu Leu Cys Leu Gly Leu Ser

20 25 30

Leu Gly Pro Arg Thr His Val Gln Ala Gly Asn Leu Ser Lys Ala Thr

35 40 45

Leu Trp Ala Glu Pro Gly Ser Val Ile Ser Arg Gly Asn Ser Val Thr

50 55 60

Ile Arg Cys Gln Gly Thr Leu Glu Ala Gln Glu Tyr Arg Leu Val Lys

65 70 75 80

Glu Gly Ser Pro Glu Pro Trp Asp Thr Gln Asn Pro Leu Glu Pro Lys

85 90 95

Asn Lys Ala Arg Phe Ser Ile Pro Ser Met Thr Glu His His Ala Gly

100 105 110

Arg Tyr Arg Cys Tyr Tyr Tyr Ser Pro Ala Gly Trp Ser Glu Pro Ser

115 120 125

Asp Pro Leu Glu Leu Val Val Thr Gly Phe Tyr Asn Lys Pro Thr Leu

130 135 140

Ser Ala Leu Pro Ser Pro Val Val Thr Ser Gly Glu Asn Val Thr Leu

145 150 155 160

Gln Cys Gly Ser Arg Leu Arg Phe Asp Arg Phe Ile Leu Thr Glu Glu

165 170 175

Gly Asp His Lys Leu Ser Trp Thr Leu Asp Ser Gln Leu Thr Pro Ser

180 185 190

Gly Gln Phe Gln Ala Leu Phe Pro Val Gly Pro Val Thr Pro Ser His

195 200 205

Arg Trp Met Leu Arg Cys Tyr Gly Ser Arg Arg His Ile Leu Gln Val

210 215 220

Trp Ser Glu Pro Ser Asp Leu Leu Glu Ile Pro Val Ser Gly Ala Ala

225 230 235 240

Asp Asn Leu Ser Pro Ser Gln Asn Lys Ser Asp Ser Gly Thr Ala Ser

245 250 255

His Leu Gln Asp Tyr Ala Val Glu Asn Leu Ile Arg Met Gly Met Ala

260 265 270

Gly Leu Ile Leu Val Val Leu Gly Ile Leu Ile Phe Gln Asp Trp His

275 280 285

Ser Gln Arg Ser Pro Gln Ala Ala Ala Gly Arg

290 295

<210> 358

<211> 481

<212> Protein

<213> Artificial sequence

<220>

<223> LILRA6(NP_001347096)

<400> 358

Met Thr Pro Ala Leu Thr Ala Leu Leu Cys Leu Gly Leu Ser Leu Gly

1 5 10 15

Pro Arg Thr Arg Val Gln Ala Gly Pro Phe Pro Lys Pro Thr Leu Trp

20 25 30

Ala Glu Pro Gly Ser Val Ile Ser Trp Gly Ser Pro Val Thr Ile Trp

35 40 45

Cys Gln Gly Ser Leu Glu Ala Gln Glu Tyr Gln Leu Asp Lys Glu Gly

50 55 60

Ser Pro Glu Pro Leu Asp Arg Asn Asn Pro Leu Glu Pro Lys Asn Lys

65 70 75 80

Ala Arg Phe Ser Ile Pro Ser Met Thr Gln His His Ala Gly Arg Tyr

85 90 95

Arg Cys His Tyr Tyr Ser Ser Ala Gly Trp Ser Glu Pro Ser Asp Pro

100 105 110

Leu Glu Leu Val Met Thr Gly Phe Tyr Asn Lys Pro Thr Leu Ser Ala

115 120 125

Leu Pro Ser Pro Val Val Ala Ser Gly Gly Asn Met Thr Leu Arg Cys

130 135 140

Gly Ser Gln Lys Gly Tyr His His Phe Val Leu Met Lys Glu Gly Glu

145 150 155 160

His Gln Leu Pro Arg Thr Leu Asp Ser Gln Gln Leu His Ser Gly Gly

165 170 175

Phe Gln Ala Leu Phe Pro Val Gly Pro Val Thr Pro Ser His Arg Trp

180 185 190

Arg Phe Thr Cys Tyr Tyr Tyr Tyr Thr Asn Thr Pro Arg Val Trp Ser

195 200 205

His Pro Ser Asp Pro Leu Glu Ile Leu Pro Ser Gly Val Ser Arg Lys

210 215 220

Pro Ser Leu Leu Thr Leu Gln Gly Pro Val Leu Ala Pro Gly Gln Ser

225 230 235 240

Leu Thr Leu Gln Cys Gly Ser Asp Val Gly Tyr Asp Arg Phe Val Leu

245 250 255

Tyr Lys Glu Gly Glu Arg Asp Phe Leu Gln Arg Pro Gly Gln Gln Pro

260 265 270

Gln Ala Gly Leu Ser Gln Ala Asn Phe Thr Leu Gly Pro Val Ser Pro

275 280 285

Ser His Gly Gly Gln Tyr Arg Cys Tyr Gly Ala His Asn Leu Ser Ser

290 295 300

Glu Trp Ser Ala Pro Ser Asp Pro Leu Asn Ile Leu Met Ala Gly Gln

305 310 315 320

Ile Tyr Asp Thr Val Ser Leu Ser Ala Gln Pro Gly Pro Thr Val Ala

325 330 335

Ser Gly Glu Asn Val Thr Leu Leu Cys Gln Ser Arg Gly Tyr Phe Asp

340 345 350

Thr Phe Leu Leu Thr Lys Glu Gly Ala Ala His Pro Pro Leu Arg Leu

355 360 365

Arg Ser Met Tyr Gly Ala His Lys Tyr Gln Ala Glu Phe Pro Met Ser

370 375 380

Pro Val Thr Ser Ala His Ala Gly Thr Tyr Arg Cys Tyr Gly Ser Tyr

385 390 395 400

Ser Ser Asn Pro His Leu Leu Ser Phe Pro Ser Glu Pro Leu Glu Leu

405 410 415

Met Val Ser Gly His Ser Gly Gly Ser Ser Leu Pro Pro Thr Gly Pro

420 425 430

Pro Ser Thr Pro Ala Ser His Ala Lys Asp Tyr Thr Val Glu Asn Leu

435 440 445

Ile Arg Met Gly Met Ala Gly Leu Val Leu Val Phe Leu Gly Ile Leu

450 455 460

Leu Phe Glu Ala Gln His Ser Gln Arg Asn Pro Gln Asp Ala Ala Gly

465 470 475 480

Arg

<210> 359

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Human IgG1 upper hinge

<400> 359

Glu Pro Lys Ser Cys Asp Lys Thr His Thr

1 5 10

<---

Claims (171)

1. Anti-LILRB1 antibody or antigen-binding fragment containing the following complementarity-determining regions (CDRs): (1) CDR-L1 containing the amino acid sequence of SEQ ID NO: 1, CDR-L2 containing the amino acid sequence of SEQ ID NO: 2, CDR-L3 containing the amino acid sequence of SEQ ID NO: 3, CDR-H1 containing the amino acid sequence of SEQ ID NO: 4, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 5, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 6; (2) a CDR-L1 containing the amino acid sequence of SEQ ID NO: 7, CDR-L2 containing the amino acid sequence of SEQ ID NO: 8, CDR-L3 containing the amino acid sequence of SEQ ID NO: 9, CDR-H1 containing the amino acid sequence of SEQ ID NO: 10, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 11, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 12; (3) a CDR-L1 containing the amino acid sequence of SEQ ID NO: 13, CDR-L2 containing the amino acid sequence of SEQ ID NO: 14, CDR-L3 containing the amino acid sequence of SEQ ID NO: 15, CDR-H1 containing the amino acid sequence of SEQ ID NO: 16, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 17, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 18; (4) a CDR-L1 containing the amino acid sequence of SEQ ID NO: 19, CDR-L2 containing the amino acid sequence of SEQ ID NO: 20, CDR-L3 containing the amino acid sequence of SEQ ID NO: 21, CDR-H1 containing the amino acid sequence of SEQ ID NO: 22, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 23, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 24; (5) a CDR-L1 containing the amino acid sequence of SEQ ID NO: 25, CDR-L2 containing the amino acid sequence of SEQ ID NO: 26, CDR-L3 containing the amino acid sequence of SEQ ID NO: 27, CDR-H1 containing the amino acid sequence of SEQ ID NO: 28, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 29, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 30; (6) CDR-L1 containing the amino acid sequence of SEQ ID NO: 31, CDR-L2 containing the amino acid sequence of SEQ ID NO: 32, CDR-L3 containing the amino acid sequence of SEQ ID NO: 33, CDR-H1 containing the amino acid sequence of SEQ ID NO: 34, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 35, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 36; (7) CDR-L1 containing the amino acid sequence of SEQ ID NO: 37, CDR-L2 containing the amino acid sequence of SEQ ID NO: 38, CDR-L3 containing the amino acid sequence of SEQ ID NO: 39, CDR-H1 containing the amino acid sequence of SEQ ID NO: 40, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 41, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 42; (8) CDR-L1 containing the amino acid sequence of SEQ ID NO: 43, CDR-L2 containing the amino acid sequence of SEQ ID NO: 44, CDR-L3 containing the amino acid sequence of SEQ ID NO: 45, CDR-H1 containing the amino acid sequence of SEQ ID NO: 46, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 47, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 48; (9) CDR-L1 containing the amino acid sequence of SEQ ID NO: 49, CDR-L2 containing the amino acid sequence of SEQ ID NO: 50, CDR-L3 containing the amino acid sequence of SEQ ID NO: 51, CDR-H1 containing the amino acid sequence of SEQ ID NO: 52, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 53, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 54; (10) CDR-L1 containing the amino acid sequence of SEQ ID NO: 55, CDR-L2 containing the amino acid sequence of SEQ ID NO: 56, CDR-L3 containing the amino acid sequence of SEQ ID NO: 57, CDR-H1 containing the amino acid sequence of SEQ ID NO: 58, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 59, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 60; (11) CDR-L1 containing the amino acid sequence of SEQ ID NO: 61, CDR-L2 containing the amino acid sequence of SEQ ID NO: 62, CDR-L3 containing the amino acid sequence of SEQ ID NO: 63, CDR-H1 containing the amino acid sequence of SEQ ID NO: 64, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 65, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 66; (12) CDR-L1 containing the amino acid sequence of SEQ ID NO: 67, CDR-L2 containing the amino acid sequence of SEQ ID NO: 68, CDR-L3 containing the amino acid sequence of SEQ ID NO: 69, CDR-H1 containing the amino acid sequence of SEQ ID NO: 70, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 71, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 72; (13) CDR-L1 containing the amino acid sequence of SEQ ID NO: 73, CDR-L2 containing the amino acid sequence of SEQ ID NO: 74, CDR-L3 containing the amino acid sequence of SEQ ID NO: 75, CDR-H1 containing the amino acid sequence of SEQ ID NO: 76, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 77, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 78; (14) CDR-L1 containing the amino acid sequence of SEQ ID NO: 79, CDR-L2 containing the amino acid sequence of SEQ ID NO: 80, CDR-L3 containing the amino acid sequence of SEQ ID NO: 81, CDR-H1 containing the amino acid sequence of SEQ ID NO: 82, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 83, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 84; (15) CDR-L1 containing the amino acid sequence of SEQ ID NO: 85, CDR-L2 containing the amino acid sequence of SEQ ID NO: 86, CDR-L3 containing the amino acid sequence of SEQ ID NO: 87, CDR-H1 containing the amino acid sequence of SEQ ID NO: 88, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 89, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 90; (16) CDR-L1 containing the amino acid sequence of SEQ ID NO: 91, CDR-L2 containing the amino acid sequence of SEQ ID NO: 92, CDR-L3 containing the amino acid sequence of SEQ ID NO: 93, CDR-H1 containing the amino acid sequence of SEQ ID NO: 94, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 95, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 96; (17) CDR-L1 containing the amino acid sequence of SEQ ID NO: 97, CDR-L2 containing the amino acid sequence of SEQ ID NO: 98, CDR-L3 containing the amino acid sequence of SEQ ID NO: 99, CDR-H1 containing the amino acid sequence of SEQ ID NO: 100, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 101, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 102; (18) CDR-L1 containing the amino acid sequence of SEQ ID NO: 103, CDR-L2 containing the amino acid sequence of SEQ ID NO: 104, CDR-L3 containing the amino acid sequence of SEQ ID NO: 105, CDR-H1 containing the amino acid sequence of SEQ ID NO: 106, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 107, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 108; (19) CDR-L1 containing the amino acid sequence of SEQ ID NO: 109, CDR-L2 containing the amino acid sequence of SEQ ID NO: 110, CDR-L3 containing the amino acid sequence of SEQ ID NO: 111, CDR-H1 containing the amino acid sequence of SEQ ID NO: 112, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 113, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 114; or (20) CDR-L1 containing the amino acid sequence of SEQ ID NO: 115, CDR-L2 containing the amino acid sequence of SEQ ID NO: 116, CDR-L3 containing the amino acid sequence of SEQ ID NO: 117, CDR-H1 containing the amino acid sequence of SEQ ID NO: 118, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 119, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 120. 2. Anti-LILRB1 antibody or antigen-binding fragment according to claim 1, including: a light chain variable region comprising the amino acid sequence of SEQ ID NO:221, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 222, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 223, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 224, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 225, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 226, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 227, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 228, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 229, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 230, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 231, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 232, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 233, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 234, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 235, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 236, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 237, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 238, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 239, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 240, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 241, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 242, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 243, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 244, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 245, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 246, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 247, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 248, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 249, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 250, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 251, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 252, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 253, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 254, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 255, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 256, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 257, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 258, a light chain variable region comprising the amino acid sequence of SEQ ID NO: 259, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 260, or a light chain variable region comprising the amino acid sequence of SEQ ID NO: 345, and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 222. 3. An anti-LILRB1 antibody or antigen-binding fragment thereof according to claim 1, wherein the antibody is a human IgG1 or IgG4 antibody. 4. An anti-LILRB1 antibody or antigen-binding fragment thereof according to claim 1, wherein the antigen-binding fragment is scFv, (scFv) ₂ , Fab, Fab', F(ab') ₂ , a fusion polypeptide containing scFv fused to an immunoglobulin Fc, or a fusion polypeptide comprising an scFv fused to a light chain constant region. 5. Pharmaceutical composition for the treatment or prevention of cancer characterized by MHC class I overexpression, containing an anti-LILRB1 antibody or antigen-binding fragment thereof according to any one of claims 1 to 4 and a pharmaceutically acceptable carrier. 6. Nucleic acid molecule encoding an antibody or antigen-binding fragment according to any one of claims 1-4. 7. Recombinant expression vector containing the nucleic acid molecule according to claim 6. 8. A recombinant cell producing an antibody or an antigen-binding fragment thereof, wherein the cell contains a nucleic acid molecule according to claim 6 or a recombinant vector containing this nucleic acid molecule. 9. A method for producing an anti-LILRB1 antibody or antigen-binding fragment thereof, comprising culturing a recombinant cell according to claim 8.