Fc variants and preparation thereof

EP4634221A1Pending Publication Date: 2025-10-22ZYDUS LIFESCIENCES LTD
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Patent Information

Application Number
EP2023902930
Authority / Receiving Office
EP · EP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2022-12-22
Filing Date
2023-12-15
Publication Date
2025-10-22

AI Technical Summary

Technical Problem

Current monoclonal antibodies (mAbs) face challenges in achieving optimal stability and efficacy due to their inherent properties, such as susceptibility to proteolytic degradation and immunogenicity, which affect their therapeutic performance.

Method used

Development of Fc variants, specifically the H11A4.1, B14H11A4.1, W11A4.1, A3H11A4.0, A3H11A4.2, B14H11A4.0, A3H11A4.2, B14H11A4.2, A3H11A4.3, and B14H11A4.3, with engineered amino acid sequences that enhance stability and reduce immunogenicity by modifying the Fc region to improve biophysical properties and interaction with immune effector cells.

Benefits of technology

The engineered Fc variants demonstrate improved stability, reduced immunogenicity, and enhanced therapeutic efficacy by maintaining functional activity and prolonging serum half-life, thereby improving the overall performance of monoclonal antibodies.

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Abstract

The present invention relates to FcRn-antagonist or Fc variant(s) protein and preparation thereof. Said Fc variant(s) has altered binding affinity towards FcRn. In one aspect, the Fc variant(s) according to the present invention comprises L234A, L235A, T307N, V308P, L309Y, P329G, H433R, N434W amino acid substitutions. In another aspect, the Fc variant(s) according to the present invention comprises T307N, V3O8P, L309Y, H433R, N434W, M252Y, S254T, T256E amino acid substitutions. In one more aspect, the Fc variant(s) of the present invention comprises T307N, V308P, L309Y, H433R, N434W, M252Y, S254T, T256E, L234A, L235A, P329G amino acid substitutions. Fc variant(s) prepared according to the current invention can be used for making FcRn-antagonist composition or can be used for making an Fc variant(s) containing drug or molecule with altered effector function.
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Description

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[0023] SEQUENCE LISTING <110> ZYDUS LIFESCIENCES LIMITED <120> Fc variant and preparation thereof <130> ZLL-PCT0884 <160> 38 <170> PatentIn version 3.5 <210> 1 <211> 227 <212> PRT <213> Artificial Sequence <220> <223> Amino acid sequence of Fc variant(s) H11A4.1 <400> 1 Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 1 5 10 15 Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 20 25 30 Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 35 40 45 Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 50 55 60 His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 65 70 75 80 Arg Val Val Ser Val Leu Asn Pro Tyr His Gln Asp Trp Leu Asn Gly 85 90 95 Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile 100 105 110 Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 115 120 125 Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 130 135 140 Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 145 150 155 160 Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 165 170 175 Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 180 185 190 Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 195 200 205 His Glu Ala Leu Arg Trp His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 210 215 220 Pro Gly Lys 225 <210> 2 <211> 711 <212> DNA <213> Artificial Sequence <220> <223> Light Chain Nucleotide Sequence of A3 H11A4.1 (mAb) <400> 2 atgggctggt cctgcatcat tctgtttctg gtggctaccg ccaccggcgt gcactctcaa 60 tctgctttga ctcagcctgc ctccgtgtct ggctctcctg gccagtctat caccatctct 120 tgtaccggca cctctagcga cgtcggcggc tacaattacg tgtcctggta tcagcagcac 180 cccggcaagg ctcccaagct gatgatctac gatgtgtcca agcggccctc cggcgtgtcc 240 aacagattct ctggctctaa gtctggcaac accgccagcc tgacaatctc tggcctgcag 300 tctgaggacg aggccgacta ctactgcaac tccctgacct ccatctccac ctgggttttc 360 ggcggaggca caaagctgac agtgctgggc cagcctaagg ccaatcctac cgtgacactg 420 ttccctccat cctccgagga actgcaggct aacaaggcta ccctcgtgtg cctgatctcc 480 gatttttacc ctggcgctgt gaccgtggct tggaaggctg atggatctcc tgtgaaggcc 540 ggcgtggaaa ccaccaagcc tagcaagcag tccaacaaca aatacgccgc ctcctcctac 600 ctgtctctga cccctgaaca gtggaagtcc caccggtcct actcttgcca agtgacccat 660 gagggctcca ccgtggaaaa gacagtggcc cctaccgagt gctcttaatg a 711 <210> 3 <211> 235 <212> PRT <213> Artificial Sequence <220> <223> Light Chain Amino Acid Sequence of A3 H11A4.1 (mAb) <400> 3 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 10 15 Val His Ser Gln Ser Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser 20 25 30 Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val 35 40 45 Gly Gly Tyr Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala 50 55 60 Pro Lys Leu Met Ile Tyr Asp Val Ser Lys Arg Pro Ser Gly Val Ser 65 70 75 80 Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile 85 90 95 Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Leu 100 105 110 Thr Ser Ile Ser Thr Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val 115 120 125 Leu Gly Gln Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Pro Ser 130 135 140 Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser 145 150 155 160 Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser 165 170 175 Pro Val Lys Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn 180 185 190 Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp 195 200 205 Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr 210 215 220 Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 225 230 235 <210> 4 <211> 1413 <212> DNA <213> Artificial Sequence <220> <223> Heavy Chain Nucleotide Sequence of A3 H11A4.1 (mAb) <400> 4 atgggctggt cctgcatcat tctgtttctg gtggctaccg ccaccggcgt gcactctcag 60 gttcaattgg ttgaatctgg cggcggagtg gtgcagcctg gaagaagtct gagactgtct 120 tgtgccgcct ccggcttcac cttctccaac tacgctatgt actgggtccg acaggcccct 180 ggcaaaggac tggaatgggt cgccgtgatc tcctacgacg gctccaacaa gtactacgcc 240 gactccgtga agggcagatt caccatctct cgggacaact ccaagaacac cctgtacctg 300 cagatgaact ccctgagaac cgaggacacc gccgtgtact actgtgcctc tggctctgac 360 tacggcgact acctgctggt gtattgggga cagggaaccc tggtcaccgt gtcctctgct 420 tctacaaagg gcccctctgt gttcccactg gctcctagct ctaagtccac ctctggtgga 480 accgctgctc tgggctgtct ggtcaaggat tacttccctg agcctgtgac cgtgtcttgg 540 aactctggtg ctctgacctc tggcgtgcac acctttccag ctgtgctgca gtcctctggc 600 ctgtactctc tgtcctctgt cgtgaccgtg ccttctagct ctctgggcac ccagacctac 660 atctgcaacg tgaaccacaa gccttccaat accaaggtgg acaagaaggt ggaacccaag 720 tcctgcgaca agacccacac ctgtcctcca tgtcctgctc cagaagctgc tggcggaccc 780 tccgttttcc tgtttccacc taagcctaag gacaccctga tgatctctcg gacccctgaa 840 gtgacctgcg tggtggtgga tgtgtctcac gaggacccag aagtgaagtt taattggtac 900 gtggacggcg tggaagtgca caacgccaag accaagccta gagaggaaca gtacaactcc 960 acctacagag tggtgtccgt gctgaaccct taccaccagg attggctgaa cggcaaagag 1020 tacaagtgca aggtgtccaa caaggccctg ggcgctccca tcgaaaagac catctctaag 1080 gctaagggcc agcctcgcga gcctcaggtt tacacactgc ctccatctcg ggaagagatg 1140 accaagaacc aggtgtccct gacctgcctg gttaagggct tctacccttc cgatatcgcc 1200 gtggaatggg agtccaatgg ccagcctgag aacaactaca agacaacccc tcctgtgctg 1260 gactccgacg gctcattctt cctgtactcc aagctgacag tggacaagtc tcggtggcag 1320 cagggcaacg tgttctcttg tagtgtgatg cacgaggccc tgagatggca ctacacacag 1380 aagtccctgt ctctgagccc cggcaagtaa tga 1413 <210> 5 <211> 469 <212> PRT <213> Artificial Sequence <220> <223> Heavy Chain Amino Acid Sequence of A3 H11A4.1(mAb) <400> 5 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 10 15 Val His Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln 20 25 30 Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Asn Tyr Ala Met Tyr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala 65 70 75 80 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 85 90 95 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Thr Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Ser Gly Ser Asp Tyr Gly Asp Tyr Leu Leu Val Tyr 115 120 125 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly 130 135 140 Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 145 150 155 160 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 165 170 175 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 180 185 190 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 195 200 205 Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 210 215 220 Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys 225 230 235 240 Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala 245 250 255 Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 260 265 270 Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 275 280 285 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 290 295 300 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 305 310 315 320 Thr Tyr Arg Val Val Ser Val Leu Asn Pro Tyr His Gln Asp Trp Leu 325 330 335 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala 340 345 350 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 355 360 365 Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln 370 375 380 Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 385 390 395 400 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 405 410 415 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 420 425 430 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 435 440 445 Val Met His Glu Ala Leu Arg Trp His Tyr Thr Gln Lys Ser Leu Ser 450 455 460 Leu Ser Pro Gly Lys 465 <210> 6 <211> 705 <212> DNA <213> Artificial Sequence <220> <223> Light Chain Nucleotide Sequence of B14 H11A4.1(mAb) <400> 6 atgggctggt cctgcatcat tctgtttctg gtggctaccg ccaccggcgt gcactctgat 60 atccagatga cccagtctcc ttccagcctg tctgcctctg tgggcgacag agtgacaatc 120 acctgtcagg ccagccagga catcaccaac tacctgaact ggtatcagca gaagcccggc 180 aaggccccta agctgctgat ctacgccgcc tctaatctgg aaacaggcgt gccctccaga 240 ttctccggct ctggctctgg caccgacttc acctttacca tctctggcct gcagcctgag 300 gatatcgcca cctactactg ccagcagtac gacaacctgc ctctgacctt tggcggaggc 360 accaaggtgg aaatcaagag aaccgtggcc gctccttccg tgttcatctt cccaccatct 420 gacgagcagc tgaagtccgg cacagcttct gtcgtgtgcc tgctgaacaa cttctaccct 480 cgggaagcca aggtgcagtg gaaggtggac aatgccctgc agtccggcaa ctcccaagag 540 tctgtgaccg agcaggactc caaggactct acctacagcc tgtcctccac actgaccctg 600 tctaaggccg actacgagaa gcacaaggtg tacgcctgtg aagtgaccca ccagggactg 660 tctagccccg tgaccaagtc tttcaacaga ggcgagtgct aatga 705 <210> 7 <211> 233 <212> PRT <213> Artificial Sequence <220> <223> Light Chain Amino Acid Sequence of B14 H11A4.1(mAb) <400> 7 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 10 15 Val His Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala 20 25 30 Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile 35 40 45 Thr Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys 50 55 60 Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg 65 70 75 80 Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Gly 85 90 95 Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Asn 100 105 110 Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr 115 120 125 Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu 130 135 140 Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro 145 150 155 160 Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly 165 170 175 Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr 180 185 190 Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His 195 200 205 Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val 210 215 220 Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 <210> 8 <211> 1413 <212> DNA <213> Artificial Sequence <220> <223> Heavy Chain Nucleotide Sequence of B14 H11A4.1(mAb) <400> 8 atgggctggt cctgcatcat tctgtttctg gtggctaccg ccaccggcgt gcactctcag 60 gttcaattgg ttgagtctgg cggcggactt gtgaagcctg gtggatctct gagactgtct 120 tgtgccgcct ccggcttcac cttctccgac tactacatgt cctggatcag acaggcccct 180 ggcaaaggac tggaatgggt gtcctacatc acctactccg gctccaccat ctactacgcc 240 gactccgtga agggcagatt caccatctcc agagacaacg ccaagtccag cctgtacctg 300 cagatgaact ctctgagagc cgaggacacc gccgtgtact actgtgctag agacagaggc 360 accacaatgg tgcccttcga ttattggggc cagggcacac tggtcaccgt gtcctctgct 420 tctacaaagg gcccctctgt gttcccactg gctcctagct ctaagtccac ctctggtgga 480 accgctgctc tgggctgtct ggtcaaggat tacttccctg agcctgtgac cgtgtcttgg 540 aactctggtg ctctgacctc tggcgtgcac acctttccag ctgtgctgca gtcctctggc 600 ctgtactctc tgtcctctgt cgtgaccgtg ccttctagct ctctgggcac ccagacctac 660 atctgcaacg tgaaccacaa gccttccaat accaaggtgg acaagaaggt ggaacccaag 720 tcctgcgaca agacccacac ctgtcctcca tgtcctgctc cagaagctgc tggcggaccc 780 tccgttttcc tgtttccacc taagcctaag gacaccctga tgatctctcg gacccctgaa 840 gtgacctgcg tggtggtgga tgtgtctcac gaggacccag aagtgaagtt taattggtac 900 gtggacggcg tggaagtgca caacgccaag accaagccta gagaggaaca gtacaactcc 960 acctacagag tggtgtccgt gctgaaccct taccaccagg attggctgaa cggcaaagag 1020 tacaagtgca aggtgtccaa caaggccctg ggcgctccca tcgaaaagac catctctaag 1080 gctaagggcc agcctcgcga gcctcaggtt tacacactgc ctccatctcg ggaagagatg 1140 accaagaacc aggtgtccct gacctgcctg gttaagggct tctacccttc cgatatcgcc 1200 gtggaatggg agtccaatgg ccagcctgag aacaactaca agacaacccc tcctgtgctg 1260 gactccgacg gctcattctt cctgtactcc aagctgacag tggacaagtc tcggtggcag 1320 cagggcaacg tgttctcttg tagtgtgatg cacgaggccc tgagatggca ctacacacag 1380 aagtccctgt ctctgagccc cggcaagtaa tga 1413 <210> 9 <211> 469 <212> PRT <213> Artificial Sequence <220> <223> Heavy Chain Amino Acid Sequence of B14 H11A4.1(mAb) <400> 9 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 10 15 Val His Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys 20 25 30 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Asp Tyr Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ser Tyr Ile Thr Tyr Ser Gly Ser Thr Ile Tyr Tyr Ala 65 70 75 80 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser 85 90 95 Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Arg Asp Arg Gly Thr Thr Met Val Pro Phe Asp Tyr 115 120 125 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly 130 135 140 Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 145 150 155 160 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 165 170 175 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 180 185 190 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 195 200 205 Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 210 215 220 Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys 225 230 235 240 Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala 245 250 255 Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 260 265 270 Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 275 280 285 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 290 295 300 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 305 310 315 320 Thr Tyr Arg Val Val Ser Val Leu Asn Pro Tyr His Gln Asp Trp Leu 325 330 335 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala 340 345 350 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 355 360 365 Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln 370 375 380 Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 385 390 395 400 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 405 410 415 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 420 425 430 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 435 440 445 Val Met His Glu Ala Leu Arg Trp His Tyr Thr Gln Lys Ser Leu Ser 450 455 460 Leu Ser Pro Gly Lys 465 <210> 10 <211> 747 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide Sequence of H11A4.1 (Monomer) <400> 10 atgggctggt cttgcatcat tctgtttctg gtggctaccg ccaccggcgt gcactcctct 60 gacaagaccc acacctgtcc tccatgtcct gctccagaag ctgctggcgg accctccgtt 120 ttcctgtttc cacctaagcc taaggacacc ctgatgatct ctcggacccc tgaagtgacc 180 tgcgtggtgg tggatgtgtc tcacgaggac ccagaagtga agtttaattg gtacgtggac 240 ggcgtggaag tgcacaacgc caagaccaag cctagagagg aacagtacaa ctccacctac 300 agagtggtgt ccgtgctgaa cccttaccac caggattggc tgaacggcaa agagtacaag 360 tgcaaggtgt ccaacaaggc cctgggcgct cccatcgaaa agaccatctc taaggctaag 420 ggccagcctc gcgagcctca ggtttacaca ctgcctccat ctcgggaaga gatgaccaag 480 aaccaggtgt ccctgacctg cctggttaag ggcttctacc cttccgatat cgccgtggaa 540 tgggagtcca atggccagcc tgagaacaac tacaagacaa cccctcctgt gctggactcc 600 gacggctcat tcttcctgta ctccaagctg acagtggaca agtctcggtg gcagcagggc 660 aacgtgttct cttgtagtgt gatgcacgag gccctgagat ggcactacac acagaagtcc 720 ctgtctctga gccccggcaa gtaatga 747 <210> 11 <211> 247 <212> PRT <213> Artificial Sequence <220> <223> Amino Acid Sequence of H11A4.1 (Monomer) <400> 11 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 10 15 Val His Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 20 25 30 Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 35 40 45 Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 50 55 60 Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 65 70 75 80 Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 85 90 95 Asn Ser Thr Tyr Arg Val Val Ser Val Leu Asn Pro Tyr His Gln Asp 100 105 110 Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 115 120 125 Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 130 135 140 Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 145 150 155 160 Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 165 170 175 Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 180 185 190 Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 195 200 205 Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 210 215 220 Cys Ser Val Met His Glu Ala Leu Arg Trp His Tyr Thr Gln Lys Ser 225 230 235 240 Leu Ser Leu Ser Pro Gly Lys 245 <210> 12 <211> 1497 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide Sequence of W11A4.1 (Dimer) <400> 12 atgggctggt cctgcatcat tctgtttctg gtggctaccg ccaccggcgt gcactcctct 60 gataagacac acacctgtcc tccatgtcct gctccagaag ctgctggcgg accctctgtg 120 ttcctgtttc ctccaaagcc taaggacacc ctgatgatct ctcggacccc tgaagtgacc 180 tgcgtggtgg tggatgtgtc tcacgaggac ccagaagtga agttcaattg gtacgtggac 240 ggcgtggaag tgcacaacgc caagaccaag cctagagagg aacagtacaa ctccacctac 300 agagtggtgt ccgtgctgaa cccttaccac caggactggc tgaacggcaa agagtacaag 360 tgcaaggtgt ccaacaaggc cctgggcgct cccatcgaaa agaccatctc taaggctaag 420 ggccagcctc gcgagcctca ggtttacaca ctgcctccat ccagagatga gctgaccaag 480 aaccaggtgt ccctgacctg tctggtcaag ggcttctacc cttccgatat cgccgtggaa 540 tgggagtcca atggccagcc tgagaacaac tacaagacca cacctcctgt gctggactcc 600 gacggctcat tcttcctgta ctccaagctg accgtggaca agtccagatg gcagcagggc 660 aacgtgttct cctgctctgt gatgcacgag gccctgagat ggcactacac acagaagtcc 720 ctgtctctgt cccctggcaa aggcggaggt tctggcggtg gctctggtgg cggatctggc 780 ggaggatctt caggcggtgg ttctagctcc gacaagaccc acacaagccc accttctcca 840 gcacctgaag cagcaggcgg cccatcagtc tttctgttcc cacctaagcc aaaggataca 900 ctcatgatca gcagaacacc cgaagtgaca tgtgtcgtcg tggacgtgtc ccatgaagat 960 cccgaagtca agtttaattg gtatgtcgat ggcgtcgagg tccacaatgc taagacaaag 1020 ccacgggaag aacagtataa cagcacctac cgggtcgtgt ctgtcctgaa tccatatcat 1080 caggattggc tcaatgggaa agaatacaaa tgtaaagtct ctaacaaggc tctcggagcc 1140 ccaatcgaga aaaccatcag caaggccaag ggacagccca gagaacccca ggtgtacact 1200 ctgccaccta gcagggacga actcaccaag aatcaagtgt ctctcacatg cctcgtgaag 1260 gggttttacc ccagcgacat tgccgtcgag tgggagtcta acggacaacc cgaaaacaat 1320 tataagacaa ccccaccagt gctggatagc gacggctcat ttttcttgta tagcaagctc 1380 accgtcgata agagccggtg gcaacaggga aatgtgttca gctgcagcgt gatgcatgaa 1440 gctctgcggt ggcattatac ccagaaaagc ctgagcctgt ctccaggcaa gtaatga 1497 <210> 13 <211> 497 <212> PRT <213> Artificial Sequence <220> <223> Amino Acid Sequence of W11A4.1 (Dimer) <400> 13 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 10 15 Val His Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 20 25 30 Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 35 40 45 Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 50 55 60 Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 65 70 75 80 Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 85 90 95 Asn Ser Thr Tyr Arg Val Val Ser Val Leu Asn Pro Tyr His Gln Asp 100 105 110 Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 115 120 125 Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 130 135 140 Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 145 150 155 160 Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 165 170 175 Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 180 185 190 Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 195 200 205 Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 210 215 220 Cys Ser Val Met His Glu Ala Leu Arg Trp His Tyr Thr Gln Lys Ser 225 230 235 240 Leu Ser Leu Ser Pro Gly Lys Gly Gly Gly Ser Gly Gly Gly Ser Gly 245 250 255 Gly Gly Ser Gly Gly Gly Ser Ser Gly Gly Gly Ser Ser Ser Asp Lys 260 265 270 Thr His Thr Ser Pro Pro Ser Pro Ala Pro Glu Ala Ala Gly Gly Pro 275 280 285 Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 290 295 300 Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 305 310 315 320 Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 325 330 335 Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 340 345 350 Val Ser Val Leu Asn Pro Tyr His Gln Asp Trp Leu Asn Gly Lys Glu 355 360 365 Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys 370 375 380 Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 385 390 395 400 Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 405 410 415 Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 420 425 430 Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 435 440 445 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 450 455 460 Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 465 470 475 480 Ala Leu Arg Trp His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 485 490 495 Lys <210> 14 <211> 22 <212> PRT <213> Artificial Sequence <220> <223> Glycine-Serine linker <400> 14 Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser 1 5 10 15 Ser Gly Gly Gly Ser Ser 20 <210> 15 <211> 469 <212> PRT <213> Artificial Sequence <220> <223> Heavy Chain Amino Acid Sequence of A3H11A4.0 (mAb) <400> 15 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 10 15 Val His Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln 20 25 30 Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Asn Tyr Ala Met Tyr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala 65 70 75 80 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 85 90 95 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Thr Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Ser Gly Ser Asp Tyr Gly Asp Tyr Leu Leu Val Tyr 115 120 125 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly 130 135 140 Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 145 150 155 160 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 165 170 175 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 180 185 190 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 195 200 205 Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 210 215 220 Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys 225 230 235 240 Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 245 250 255 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 260 265 270 Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 275 280 285 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 290 295 300 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 305 310 315 320 Thr Tyr Arg Val Val Ser Val Leu Asn Pro Tyr His Gln Asp Trp Leu 325 330 335 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 340 345 350 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 355 360 365 Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 370 375 380 Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 385 390 395 400 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 405 410 415 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 420 425 430 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 435 440 445 Val Met His Glu Ala Leu Arg Trp His Tyr Thr Gln Lys Ser Leu Ser 450 455 460 Leu Ser Pro Gly Lys 465 <210> 16 <211> 235 <212> PRT <213> Artificial Sequence <220> <223> Light Chain Amino Acid Sequence of A3H11A4.0 (mAb) <400> 16 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 10 15 Val His Ser Gln Ser Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser 20 25 30 Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val 35 40 45 Gly Gly Tyr Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala 50 55 60 Pro Lys Leu Met Ile Tyr Asp Val Ser Lys Arg Pro Ser Gly Val Ser 65 70 75 80 Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile 85 90 95 Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Leu 100 105 110 Thr Ser Ile Ser Thr Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val 115 120 125 Leu Gly Gln Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Pro Ser 130 135 140 Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser 145 150 155 160 Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser 165 170 175 Pro Val Lys Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn 180 185 190 Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp 195 200 205 Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr 210 215 220 Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 225 230 235 <210> 17 <211> 469 <212> PRT <213> Artificial Sequence <220> <223> Heavy Chain Amino Acid Sequence of B14H11A4.0 (mAb) <400> 17 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 10 15 Val His Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys 20 25 30 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Asp Tyr Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ser Tyr Ile Thr Tyr Ser Gly Ser Thr Ile Tyr Tyr Ala 65 70 75 80 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser 85 90 95 Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Arg Asp Arg Gly Thr Thr Met Val Pro Phe Asp Tyr 115 120 125 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly 130 135 140 Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 145 150 155 160 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 165 170 175 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 180 185 190 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 195 200 205 Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 210 215 220 Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys 225 230 235 240 Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 245 250 255 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 260 265 270 Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 275 280 285 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 290 295 300 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 305 310 315 320 Thr Tyr Arg Val Val Ser Val Leu Asn Pro Tyr His Gln Asp Trp Leu 325 330 335 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 340 345 350 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 355 360 365 Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 370 375 380 Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 385 390 395 400 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 405 410 415 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 420 425 430 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 435 440 445 Val Met His Glu Ala Leu Arg Trp His Tyr Thr Gln Lys Ser Leu Ser 450 455 460 Leu Ser Pro Gly Lys 465 <210> 18 <211> 233 <212> PRT <213> Artificial Sequence <220> <223> Light Chain Amino Acid Sequence of B14H11A4.0 (mAb) <400> 18 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 10 15 Val His Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala 20 25 30 Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile 35 40 45 Thr Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys 50 55 60 Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg 65 70 75 80 Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Gly 85 90 95 Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Asn 100 105 110 Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr 115 120 125 Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu 130 135 140 Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro 145 150 155 160 Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly 165 170 175 Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr 180 185 190 Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His 195 200 205 Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val 210 215 220 Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 <210> 19 <211> 747 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide Sequence of H11A4.2 <400> 19 atgggctggt cttgcatcat tctgtttctg gtggctaccg ccaccggcgt gcactcctct 60 gataagacac acacctgtcc tccatgtcct gctccagaac tgctcggcgg accctctgtg 120 ttcctgtttc ctccaaagcc taaggacacc ctgtacatca cccgcgagcc tgaagtgacc 180 tgtgtggtgg tggatgtgtc ccacgaggac cccgaagtga agttcaattg gtacgtggac 240 ggcgtggaag tgcacaacgc caagaccaag cctagagagg aacagtacaa ctccacctac 300 agagtggtgt ccgtgctgaa cccttaccac caggattggc tgaacggcaa agagtacaag 360 tgcaaggtgt ccaacaaggc cctgcctgct cctatcgaaa agaccatctc caaggctaag 420 ggccagcctc gggaacctca ggtttacaca ctgcctccat ctcgggacga gctgaccaag 480 aatcaggtgt ccctgacctg cctggtcaag ggcttctacc cttccgatat cgccgtggaa 540 tgggagtcca atggccagcc tgagaacaac tacaagacca cacctcctgt gctggactcc 600 gacggctcat tcttcctgta ctccaagctg acagtggaca agtctcggtg gcagcagggc 660 aacgtgttct cctgttctgt gatgcacgag gccctgagat ggcactacac acagaagtcc 720 ctgtctctga gccccggcaa gtaatga 747 <210> 20 <211> 247 <212> PRT <213> Artificial Sequence <220> <223> Amino Acid Sequence of H11A4.2 <400> 20 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 10 15 Val His Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 20 25 30 Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 35 40 45 Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val 50 55 60 Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 65 70 75 80 Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 85 90 95 Asn Ser Thr Tyr Arg Val Val Ser Val Leu Asn Pro Tyr His Gln Asp 100 105 110 Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 115 120 125 Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 130 135 140 Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 145 150 155 160 Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 165 170 175 Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 180 185 190 Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 195 200 205 Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 210 215 220 Cys Ser Val Met His Glu Ala Leu Arg Trp His Tyr Thr Gln Lys Ser 225 230 235 240 Leu Ser Leu Ser Pro Gly Lys 245 <210> 21 <211> 711 <212> DNA <213> Artificial Sequence <220> <223> Light Chain Nucleotide Sequence of A3H11A4.2 <400> 21 atgggctggt cctgcatcat tctgtttctg gtggctaccg ccaccggcgt gcactctcaa 60 tctgctttga ctcagcctgc ctccgtgtct ggctctcctg gccagtctat caccatctct 120 tgtaccggca cctctagcga cgtcggcggc tacaattacg tgtcctggta tcagcagcac 180 cccggcaagg ctcccaagct gatgatctac gatgtgtcca agcggccctc cggcgtgtcc 240 aacagattct ctggctctaa gtctggcaac accgccagcc tgacaatctc tggcctgcag 300 tctgaggacg aggccgacta ctactgcaac tccctgacct ccatctccac ctgggttttc 360 ggcggaggca caaagctgac agtgctgggc cagcctaagg ccaatcctac cgtgacactg 420 ttccctccat cctccgagga actgcaggct aacaaggcta ccctcgtgtg cctgatctcc 480 gatttttacc ctggcgctgt gaccgtggct tggaaggctg atggatctcc tgtgaaggcc 540 ggcgtggaaa ccaccaagcc tagcaagcag tccaacaaca aatacgccgc ctcctcctac 600 ctgtctctga cccctgaaca gtggaagtcc caccggtcct actcttgcca agtgacccat 660 gagggctcca ccgtggaaaa gacagtggcc cctaccgagt gctcttaatg a 711 <210> 22 <211> 235 <212> PRT <213> Artificial Sequence <220> <223> Light Chain Amino Acid Sequence of A3H11A4.2 <400> 22 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 10 15 Val His Ser Gln Ser Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser 20 25 30 Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val 35 40 45 Gly Gly Tyr Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala 50 55 60 Pro Lys Leu Met Ile Tyr Asp Val Ser Lys Arg Pro Ser Gly Val Ser 65 70 75 80 Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile 85 90 95 Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Leu 100 105 110 Thr Ser Ile Ser Thr Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val 115 120 125 Leu Gly Gln Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Pro Ser 130 135 140 Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser 145 150 155 160 Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser 165 170 175 Pro Val Lys Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn 180 185 190 Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp 195 200 205 Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr 210 215 220 Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 225 230 235 <210> 23 <211> 1413 <212> DNA <213> Artificial Sequence <220> <223> Heavy Chain Nucleotide Sequence of A3H11A4.2 <400> 23 atgggctggt cctgcatcat tctgtttctg gtggctaccg ccaccggcgt gcactctcag 60 gttcaattgg ttgaatctgg cggcggagtg gtgcagcctg gaagaagtct gagactgtct 120 tgtgccgcct ccggcttcac cttctccaac tacgctatgt actgggtccg acaggcccct 180 ggcaaaggac tggaatgggt cgccgtgatc tcctacgacg gctccaacaa gtactacgcc 240 gactccgtga agggcagatt caccatctct cgggacaact ccaagaacac cctgtacctg 300 cagatgaact ccctgagaac cgaggacacc gccgtgtact actgtgcctc tggctctgac 360 tacggcgact acctgctggt gtattgggga cagggaaccc tggtcaccgt gtcctctgct 420 tctacaaagg gcccctctgt gttcccactg gctcctagct ctaagtccac ctctggtgga 480 accgctgctc tgggctgtct ggtcaaggat tacttccctg agcctgtgac cgtgtcttgg 540 aactctggtg ctctgacctc tggcgtgcac acctttccag ctgtgctgca gtcctctggc 600 ctgtactctc tgtcctctgt cgtgaccgtg ccttctagct ctctgggcac ccagacctac 660 atctgcaacg tgaaccacaa gccttccaat accaaggtgg acaagaaggt ggaacccaag 720 tcctgcgaca agacccacac ctgtcctcca tgtcctgctc cagaactgct cggcggaccc 780 tctgtgttcc tgtttcctcc aaagcctaag gacaccctgt acatcacccg cgagcctgaa 840 gtgacctgtg tggtggtgga tgtgtcccac gaggaccccg aagtgaagtt caattggtac 900 gtggacggcg tggaagtgca caacgccaag accaagccta gagaggaaca gtacaactcc 960 acctacagag tggtgtccgt gctgaaccct taccaccagg attggctgaa cggcaaagag 1020 tacaagtgca aggtgtccaa caaggccctg cctgctccta tcgaaaagac catctccaag 1080 gctaagggcc agcctcggga acctcaggtt tacacactgc ctccatctcg ggaagagctg 1140 accaagaatc aggtgtccct gacctgcctg gtcaagggct tctacccttc cgatatcgcc 1200 gtggaatggg agtccaatgg ccagcctgag aacaactaca agaccacacc tcctgtgctg 1260 gactccgacg gctcattctt cctgtactcc aagctgacag tggacaagtc tcggtggcag 1320 cagggcaacg tgttctcctg ttctgtgatg cacgaggccc tgagatggca ctacacacag 1380 aagtccctgt ctctgagccc cggcaagtaa tga 1413 <210> 24 <211> 469 <212> PRT <213> Artificial Sequence <220> <223> Heavy Chain Amino Acid Sequence of A3H11A4.2 <400> 24 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 10 15 Val His Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln 20 25 30 Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Asn Tyr Ala Met Tyr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala 65 70 75 80 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 85 90 95 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Thr Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Ser Gly Ser Asp Tyr Gly Asp Tyr Leu Leu Val Tyr 115 120 125 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly 130 135 140 Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 145 150 155 160 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 165 170 175 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 180 185 190 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 195 200 205 Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 210 215 220 Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys 225 230 235 240 Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 245 250 255 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 260 265 270 Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val 275 280 285 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 290 295 300 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 305 310 315 320 Thr Tyr Arg Val Val Ser Val Leu Asn Pro Tyr His Gln Asp Trp Leu 325 330 335 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 340 345 350 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 355 360 365 Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln 370 375 380 Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 385 390 395 400 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 405 410 415 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 420 425 430 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 435 440 445 Val Met His Glu Ala Leu Arg Trp His Tyr Thr Gln Lys Ser Leu Ser 450 455 460 Leu Ser Pro Gly Lys 465 <210> 25 <211> 705 <212> DNA <213> Artificial Sequence <220> <223> Light Chain Nucleotide Sequence of B14H11A4.2 <400> 25 atgggctggt cctgcatcat tctgtttctg gtggctaccg ccaccggcgt gcactctgat 60 atccagatga cccagtctcc ttccagcctg tctgcctctg tgggcgacag agtgacaatc 120 acctgtcagg ccagccagga catcaccaac tacctgaact ggtatcagca gaagcccggc 180 aaggccccta agctgctgat ctacgccgcc tctaatctgg aaacaggcgt gccctccaga 240 ttctccggct ctggctctgg caccgacttc acctttacca tctctggcct gcagcctgag 300 gatatcgcca cctactactg ccagcagtac gacaacctgc ctctgacctt tggcggaggc 360 accaaggtgg aaatcaagag aaccgtggcc gctccttccg tgttcatctt cccaccatct 420 gacgagcagc tgaagtccgg cacagcttct gtcgtgtgcc tgctgaacaa cttctaccct 480 cgggaagcca aggtgcagtg gaaggtggac aatgccctgc agtccggcaa ctcccaagag 540 tctgtgaccg agcaggactc caaggactct acctacagcc tgtcctccac actgaccctg 600 tctaaggccg actacgagaa gcacaaggtg tacgcctgtg aagtgaccca ccagggactg 660 tctagccccg tgaccaagtc tttcaacaga ggcgagtgct aatga 705 <210> 26 <211> 233 <212> PRT <213> Artificial Sequence <220> <223> Light Chain Amino acid Sequence of B14H11A4.2 <400> 26 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 10 15 Val His Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala 20 25 30 Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile 35 40 45 Thr Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys 50 55 60 Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg 65 70 75 80 Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Gly 85 90 95 Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Asn 100 105 110 Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr 115 120 125 Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu 130 135 140 Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro 145 150 155 160 Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly 165 170 175 Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr 180 185 190 Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His 195 200 205 Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val 210 215 220 Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 <210> 27 <211> 1413 <212> DNA <213> Artificial Sequence <220> <223> Heavy Chain Nucleotide Sequence of B14H11A4.2 <400> 27 atgggctggt cctgcatcat tctgtttctg gtggctaccg ccaccggcgt gcactctcag 60 gttcaattgg ttgagtctgg cggcggactt gtgaagcctg gtggatctct gagactgtct 120 tgtgccgcct ccggcttcac cttctccgac tactacatgt cctggatcag acaggcccct 180 ggcaaaggac tggaatgggt gtcctacatc acctactccg gctccaccat ctactacgcc 240 gactccgtga agggcagatt caccatctcc agagacaacg ccaagtccag cctgtacctg 300 cagatgaact ctctgagagc cgaggacacc gccgtgtact actgtgctag agacagaggc 360 accacaatgg tgcccttcga ttattggggc cagggcacac tggtcaccgt gtcctctgct 420 tctacaaagg gcccctctgt gttcccactg gctcctagct ctaagtccac ctctggtgga 480 accgctgctc tgggctgtct ggtcaaggat tacttccctg agcctgtgac cgtgtcttgg 540 aactctggtg ctctgacctc tggcgtgcac acctttccag ctgtgctgca gtcctctggc 600 ctgtactctc tgtcctctgt cgtgaccgtg ccttctagct ctctgggcac ccagacctac 660 atctgcaacg tgaaccacaa gccttccaat accaaggtgg acaagaaggt ggaacccaag 720 tcctgcgaca agacccacac ctgtcctcca tgtcctgctc cagaactgct cggcggaccc 780 tctgtgttcc tgtttcctcc aaagcctaag gacaccctgt acatcacccg cgagcctgaa 840 gtgacctgtg tggtggtgga tgtgtcccac gaggaccccg aagtgaagtt caattggtac 900 gtggacggcg tggaagtgca caacgccaag accaagccta gagaggaaca gtacaactcc 960 acctacagag tggtgtccgt gctgaaccct taccaccagg attggctgaa cggcaaagag 1020 tacaagtgca aggtgtccaa caaggccctg cctgctccta tcgaaaagac catctccaag 1080 gctaagggcc agcctcggga acctcaggtt tacacactgc ctccatctcg ggaagagctg 1140 accaagaatc aggtgtccct gacctgcctg gtcaagggct tctacccttc cgatatcgcc 1200 gtggaatggg agtccaatgg ccagcctgag aacaactaca agaccacacc tcctgtgctg 1260 gactccgacg gctcattctt cctgtactcc aagctgacag tggacaagtc tcggtggcag 1320 cagggcaacg tgttctcctg ttctgtgatg cacgaggccc tgagatggca ctacacacag 1380 aagtccctgt ctctgagccc cggcaagtaa tga 1413 <210> 28 <211> 469 <212> PRT <213> Artificial Sequence <220> <223> Heavy Chain Amino Acid Sequence of B14H11A4.2 <400> 28 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 10 15 Val His Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys 20 25 30 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Asp Tyr Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ser Tyr Ile Thr Tyr Ser Gly Ser Thr Ile Tyr Tyr Ala 65 70 75 80 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser 85 90 95 Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Arg Asp Arg Gly Thr Thr Met Val Pro Phe Asp Tyr 115 120 125 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly 130 135 140 Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 145 150 155 160 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 165 170 175 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 180 185 190 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 195 200 205 Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 210 215 220 Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys 225 230 235 240 Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 245 250 255 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 260 265 270 Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val 275 280 285 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 290 295 300 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 305 310 315 320 Thr Tyr Arg Val Val Ser Val Leu Asn Pro Tyr His Gln Asp Trp Leu 325 330 335 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 340 345 350 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 355 360 365 Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln 370 375 380 Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 385 390 395 400 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 405 410 415 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 420 425 430 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 435 440 445 Val Met His Glu Ala Leu Arg Trp His Tyr Thr Gln Lys Ser Leu Ser 450 455 460 Leu Ser Pro Gly Lys 465 <210> 29 <211> 711 <212> DNA <213> Artificial Sequence <220> <223> Light Chain Nucleotide Sequence of A3 H11A4.3 <400> 29 atgggctggt cctgcatcat tctgtttctg gtggctaccg ccaccggcgt gcactctcaa 60 tctgctttga ctcagcctgc ctccgtgtct ggctctcctg gccagtctat caccatctct 120 tgtaccggca cctctagcga cgtcggcggc tacaattacg tgtcctggta tcagcagcac 180 cccggcaagg ctcccaagct gatgatctac gatgtgtcca agcggccctc cggcgtgtcc 240 aacagattct ctggctctaa gtctggcaac accgccagcc tgacaatctc tggcctgcag 300 tctgaggacg aggccgacta ctactgcaac tccctgacct ccatctccac ctgggttttc 360 ggcggaggca caaagctgac agtgctgggc cagcctaagg ccaatcctac cgtgacactg 420 ttccctccat cctccgagga actgcaggct aacaaggcta ccctcgtgtg cctgatctcc 480 gatttttacc ctggcgctgt gaccgtggct tggaaggctg atggatctcc tgtgaaggcc 540 ggcgtggaaa ccaccaagcc tagcaagcag tccaacaaca aatacgccgc ctcctcctac 600 ctgtctctga cccctgaaca gtggaagtcc caccggtcct actcttgcca agtgacccat 660 gagggctcca ccgtggaaaa gacagtggcc cctaccgagt gctcttaatg a 711 <210> 30 <211> 235 <212> PRT <213> Artificial Sequence <220> <223> Light Chain Amino Acid Sequence of A3 H11A4.3 <400> 30 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 10 15 Val His Ser Gln Ser Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser 20 25 30 Pro Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val 35 40 45 Gly Gly Tyr Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala 50 55 60 Pro Lys Leu Met Ile Tyr Asp Val Ser Lys Arg Pro Ser Gly Val Ser 65 70 75 80 Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile 85 90 95 Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Leu 100 105 110 Thr Ser Ile Ser Thr Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val 115 120 125 Leu Gly Gln Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Pro Ser 130 135 140 Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser 145 150 155 160 Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser 165 170 175 Pro Val Lys Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn 180 185 190 Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp 195 200 205 Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr 210 215 220 Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 225 230 235 <210> 31 <211> 1413 <212> DNA <213> Artificial Sequence <220> <223> Heavy Chain Nucleotide Sequence of A3H11A4.3 <400> 31 atgggctggt cctgcatcat tctgtttctg gtggctaccg ccaccggcgt gcactctcag 60 gttcaattgg ttgaatctgg cggcggagtg gtgcagcctg gaagaagtct gagactgtct 120 tgtgccgcct ccggcttcac cttctccaac tacgctatgt actgggtccg acaggcccct 180 ggcaaaggac tggaatgggt cgccgtgatc tcctacgacg gctccaacaa gtactacgcc 240 gactccgtga agggcagatt caccatctct cgggacaact ccaagaacac cctgtacctg 300 cagatgaact ccctgagaac cgaggacacc gccgtgtact actgtgcctc tggctctgac 360 tacggcgact acctgctggt gtattgggga cagggaaccc tggtcaccgt gtcctctgct 420 tctaccaagg gaccctctgt gttcccactg gctcctagct ctaagtccac ctctggtgga 480 accgctgctc tgggctgtct ggtcaaggat tacttccctg agcctgtgac cgtgtcttgg 540 aactctggtg ctctgacctc tggcgtgcac acctttccag ctgtgctgca gtcctctggc 600 ctgtactctc tgtcctctgt cgtgaccgtg ccttctagct ctctgggcac ccagacctac 660 atctgcaacg tgaaccacaa gccttccaat accaaggtgg acaagaaggt ggaacccaag 720 tcctgcgaca agacccacac ctgtcctcca tgtcctgctc cagaagctgc tggcggtccc 780 tccgttttcc tgtttccacc taagcctaag gacaccctgt acatcactcg ggagcctgaa 840 gtgacctgcg tggtggtgga tgtgtctcac gaggacccag aagtgaagtt taattggtac 900 gtggacggcg tggaagtgca caacgccaag accaagccta gagaggaaca gtacaactcc 960 acctacagag tggtgtccgt gctgaaccct taccaccagg actggctgaa cggcaaagag 1020 tacaagtgca aggtgtccaa caaggccctg ggcgctccca tcgaaaagac catctctaag 1080 gctaagggcc agcctcgcga gcctcaggtt tacacactgc ctccatctcg ggaagagatg 1140 accaagaacc aggtgtccct gacctgcctg gttaagggct tctacccttc cgatatcgcc 1200 gtggaatggg agtccaatgg ccagcctgag aacaactaca agacaacccc tcctgtgctg 1260 gactccgacg gctcattctt cctgtactcc aagctgaccg tggacaagtc cagatggcag 1320 cagggcaacg tgttctcctg ctctgtgatg cacgaggccc tgagatggca ctacacacag 1380 aagtccctgt ctctgagccc cggcaagtga tga 1413 <210> 32 <211> 469 <212> PRT <213> Artificial Sequence <220> <223> Heavy Chain Amino Acid Sequence of A3H11A4.3 <400> 32 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 Val His Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln 20 25 30 Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Asn Tyr Ala Met Tyr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala 65 70 75 80 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 85 90 95 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Thr Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Ser Gly Ser Asp Tyr Gly Asp Tyr Leu Leu Val Tyr 115 120 125 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly 130 135 140 Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 145 150 155 160 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 165 170 175 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 180 185 190 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 195 200 205 Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 210 215 220 Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys 225 230 235 240 Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala 245 250 255 Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 260 265 270 Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val 275 280 285 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 290 295 300 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 305 310 315 320 Thr Tyr Arg Val Val Ser Val Leu Asn Pro Tyr His Gln Asp Trp Leu 325 330 335 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala 340 345 350 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 355 360 365 Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln 370 375 380 Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 385 390 395 400 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 405 410 415 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 420 425 430 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 435 440 445 Val Met His Glu Ala Leu Arg Trp His Tyr Thr Gln Lys Ser Leu Ser 450 455 460 Leu Ser Pro Gly Lys 465 <210> 33 <211> 705 <212> DNA <213> Artificial Sequence <220> <223> Light Chain Nucleotide Sequence of B14 H11A4.3 <400> 33 atgggctggt cctgcatcat tctgtttctg gtggctaccg ccaccggcgt gcactctgat 60 atccagatga cccagtctcc ttccagcctg tctgcctctg tgggcgacag agtgacaatc 120 acctgtcagg ccagccagga catcaccaac tacctgaact ggtatcagca gaagcccggc 180 aaggccccta agctgctgat ctacgccgcc tctaatctgg aaacaggcgt gccctccaga 240 ttctccggct ctggctctgg caccgacttc acctttacca tctctggcct gcagcctgag 300 gatatcgcca cctactactg ccagcagtac gacaacctgc ctctgacctt tggcggaggc 360 accaaggtgg aaatcaagag aaccgtggcc gctccttccg tgttcatctt cccaccatct 420 gacgagcagc tgaagtccgg cacagcttct gtcgtgtgcc tgctgaacaa cttctaccct 480 cgggaagcca aggtgcagtg gaaggtggac aatgccctgc agtccggcaa ctcccaagag 540 tctgtgaccg agcaggactc caaggactct acctacagcc tgtcctccac actgaccctg 600 tctaaggccg actacgagaa gcacaaggtg tacgcctgtg aagtgaccca ccagggactg 660 tctagccccg tgaccaagtc tttcaacaga ggcgagtgct aatga 705 <210> 34 <211> 233 <212> PRT <213> Artificial Sequence <220> <223> Light Chain Amino Acid Sequence of B14 H11A4.3 <400> 34 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 10 15 Val His Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala 20 25 30 Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile 35 40 45 Thr Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys 50 55 60 Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg 65 70 75 80 Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Gly 85 90 95 Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Asn 100 105 110 Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr 115 120 125 Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu 130 135 140 Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro 145 150 155 160 Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly 165 170 175 Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr 180 185 190 Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His 195 200 205 Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val 210 215 220 Thr Lys Ser Phe Asn Arg Gly Glu Cys 225 230 <210> 35 <211> 1413 <212> DNA <213> Artificial Sequence <220> <223> Heavy Chain Nucleotide Sequence of B14 H11A4.3 <400> 35 atgggctggt cctgcatcat tctgtttctg gtggctaccg ccaccggcgt gcactctcag 60 gttcaattgg ttgagtctgg cggcggactt gtgaagcctg gtggatctct gagactgtct 120 tgtgccgcct ccggcttcac cttctccgac tactacatgt cctggatcag acaggcccct 180 ggcaaaggac tggaatgggt gtcctacatc acctactccg gctccaccat ctactacgcc 240 gactccgtga agggcagatt caccatctcc agagacaacg ccaagtccag cctgtacctg 300 cagatgaact ctctgagagc cgaggacacc gccgtgtact actgtgctag agacagaggc 360 accacaatgg tgcccttcga ttattggggc cagggcacac tggtcaccgt gtcctctgct 420 tctaccaagg gaccctctgt gttccctctg gctccttcca gcaagtctac ctctggtgga 480 accgctgctc tgggctgcct ggtcaaggat tactttcctg agcctgtgac cgtgtcttgg 540 aactctggtg ctctgacctc tggcgtgcac acctttccag ctgtgctgca gtcctctggc 600 ctgtactctc tgtcctctgt cgtgaccgtg ccttctagct ctctgggcac ccagacctac 660 atctgcaacg tgaaccacaa gccttccaac accaaggtgg acaagaaggt ggaacccaag 720 tcctgcgaca agacccacac ctgtcctcca tgtcctgctc cagaagctgc tggcggtccc 780 tccgttttcc tgtttccacc taagcctaag gacaccctgt acatcactcg ggagcctgaa 840 gtgacctgcg tggtggtgga tgtgtctcac gaggacccag aagtgaagtt taattggtac 900 gtggacggcg tggaagtgca caatgccaag accaagccta gagaggaaca gtacaactcc 960 acctacagag tggtgtccgt gctgaaccct taccaccagg actggctgaa cggcaaagag 1020 tacaagtgca aggtgtccaa caaggccctg ggcgctccca tcgaaaagac catctctaag 1080 gctaagggcc agcctcgcga gcctcaggtt tacacactgc ctccatctcg ggaagagatg 1140 accaagaacc aggtgtccct gacctgcctc gtgaagggat tctacccttc cgatatcgcc 1200 gtggaatggg agtctaacgg ccagccagag aacaactaca agacaacccc tcctgtgctg 1260 gactccgacg gctcattctt cctgtactcc aagctgaccg tggacaagtc cagatggcag 1320 cagggcaacg tgttctcctg ctctgtgatg cacgaggccc tgagatggca ctacacacag 1380 aagtccctgt ctctgagccc cggcaagtga tga 1413 <210> 36 <211> 469 <212> PRT <213> Artificial Sequence <220> <223> Heavy Chain Amino Acid Sequence of B14 H11A4.3 <400> 36 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 10 15 Val His Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys 20 25 30 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 35 40 45 Ser Asp Tyr Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu 50 55 60 Glu Trp Val Ser Tyr Ile Thr Tyr Ser Gly Ser Thr Ile Tyr Tyr Ala 65 70 75 80 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser 85 90 95 Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 100 105 110 Tyr Tyr Cys Ala Arg Asp Arg Gly Thr Thr Met Val Pro Phe Asp Tyr 115 120 125 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly 130 135 140 Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 145 150 155 160 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 165 170 175 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 180 185 190 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 195 200 205 Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 210 215 220 Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys 225 230 235 240 Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala 245 250 255 Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 260 265 270 Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val 275 280 285 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 290 295 300 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 305 310 315 320 Thr Tyr Arg Val Val Ser Val Leu Asn Pro Tyr His Gln Asp Trp Leu 325 330 335 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala 340 345 350 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 355 360 365 Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln 370 375 380 Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 385 390 395 400 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 405 410 415 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 420 425 430 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 435 440 445 Val Met His Glu Ala Leu Arg Trp His Tyr Thr Gln Lys Ser Leu Ser 450 455 460 Leu Ser Pro Gly Lys 465 <210> 37 <211> 747 <212> DNA <213> Artificial Sequence <220> <223> Nucleotide Sequence of H11A4.3 <400> 37 atgggctggt cctgcatcat tctgtttctg gtggctaccg ccaccggcgt gcactcctct 60 gataagacac acacctgtcc tccatgtcct gctccagaag ctgctggcgg accctctgtg 120 ttcctgtttc ctccaaagcc taaggacacc ctgtacatca ctcgggagcc tgaagtgacc 180 tgcgtggtgg tggatgtgtc tcacgaggac ccagaagtga agttcaattg gtacgtggac 240 ggcgtggaag tgcacaacgc caagaccaag cctagagagg aacagtacaa ctccacctac 300 agagtggtgt ccgtgctgaa cccttaccac caggactggc tgaacggcaa agagtacaag 360 tgcaaggtgt ccaacaaggc cctgggcgct cccatcgaaa agaccatctc taaggctaag 420 ggccagcctc gcgagcctca ggtttacaca ctgcctccat ctcgggaaga gatgaccaag 480 aaccaggtgt ccctgacctg cctggtcaag ggcttctacc cttccgatat cgccgtggaa 540 tgggagtcca atggccagcc tgagaacaac tacaagacca cacctcctgt gctggactcc 600 gacggctcat tcttcctgta ctccaagctg accgtggaca agtccagatg gcagcagggc 660 aacgtgttct cctgctctgt gatgcacgag gccctgagat ggcactacac acagaagtcc 720 ctgtctctgt cccctggcaa gtgatga 747 <210> 38 <211> 247 <212> PRT <213> Artificial Sequence <220> <223> Amino Acid Sequence of H11A4.3 <400> 38 Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 1 5 10 15 Val His Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 20 25 30 Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 35 40 45 Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val 50 55 60 Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 65 70 75 80 Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 85 90 95 Asn Ser Thr Tyr Arg Val Val Ser Val Leu Asn Pro Tyr His Gln Asp 100 105 110 Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 115 120 125 Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 130 135 140 Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 145 150 155 160 Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 165 170 175 Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 180 185 190 Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 195 200 205 Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 210 215 220 Cys Ser Val Met His Glu Ala Leu Arg Trp His Tyr Thr Gln Lys Ser 225 230 235 240 Leu Ser Leu Ser Pro Gly Lys 245