(57)【要約】 本発明は、抗HLA − DRモノクローナル抗体を提供する。本
Contents
1. VO2003 033538 A1 2003 4 10 20 30 50 11 J P VO2003 033538 A12. 25 J WO2003 033538 A1 2003 4 24 HLHH nt H RE HHuHH ZARE ADR 1 A DR L929 human 126 poly RE HD3 IgG1 HD4 IgGl HD6 IgGl HD7 IgG3 HD8 IgG2 HD10 IgG2 aderito EE 000000 000000 000 10 20 30 50 26 WO2003 033538 Al 2003 4 24
3. 8 J P VO2003 033538 A1 2003 4 24 0 000 000 0 10 20 30 50 J P WO2003 033538 A1 2003 4 24 9 10 20 30 50
4. 10 20 30 50 19 J P VO2003 033538 A1 2003 4 24 0000 10 20 30 50 20 WO2003 033538 1 2003 4 24
5. 0 0 000 0 0 0 0 0 C none mnunnnn H n C C Pi ru REM PE C C C a C none C n nnnm n n ood HH 0 000 0 0 0 000 0 0 0 10 20 30 50 7 0 30 J P WO2003 033538 A1 2003 4 24 10000 BU lt HD4 gt 1 6 GTCGACCCAGCCCTGGGATTTTCAGGTGTTTTCAGGTGTTTTCATTTGGTGATCAGGACTGAACAGAGAGA ACTCACCATGGAGTTTGGGCTGAGCTGGCTTTTTCTTGTGGCTATTTTAAAAGGTGTCCAGTGTGAGGTGCA ACTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATT CACCTITAGCAGCTATGCCATGACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGGTAT TAGTGGTGGTGGTGATAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTC CAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAGAGA TCATGGTTCGGGGAGTTATTATCCCTACTGGTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTC AGCTAGC HD4 gt
6. C J P VO2003 033538 A1 2003 4 24 7 10 20 D 50
7. H x H H nn Hono 0 00000 und 0 H D C nn m O D 000 000 0 ie os Ein x 0 ii era area C 0 0 H H 10 20 30 50 21 J P VO2003 033538 A1 2003 4 24
8. 0 0 000 0 0 000 0 x Noe E aW x 5 5 n iens C 0 Y n G 0 D 10 20 30 50 27 JP VO2003 033538 1 2003 4 24 D C C 5 0 000 00000 lu eC 0 x non eas TE H ERO IRA 2 C D
9. 10 20 30 50 17 J P WO2003 033538 A1 2003 4 24 10 20 30 50 18 J P VO2003 033538 A1 2003 4 24
10. 10 20 30 50 33 J P VO2003 033538 A1 2003 4 24 HHHHHHHHHHHHHUHHHHHHHHHHHHHHHHHHHHHHHHILH 0000 500000 3 Du IgG1Ser HD8G1Ser L L L3 10 20 30 50 34 J P VO20
11. 10 20 30 37 SEQUENCE LISTING lt 1102 KIRIN BEER KABUSHIKI KAISHA lt 120 gt Anti HLA DR antibody 130 PH 1646 PCT lt 140 gt lt 141 gt 150 gt JP2001 317054 lt 151 gt 2001 10 15 lt 160 gt 147 170 PatentIn Ver 2 1 lt 210 gt 1 lt 211 gt 38 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence primer lt 400 gt 1 ccggaatlcc caccatggcc ataagiggag tccctgtg J P VO2003 033538 A1 2003 4 24 38 10 20 30 38 J P WO2003 033538 A1 2003 4 24 lt 210 gt 2 lt 211 gt 38 lt 212 gt DNA lt 213 gt Artificial Sequence 220 223 Description of Artificial Sequence primer 4002 2 aaageggecg cicattacag aggccecctg cgttctgc lt 210 gt 3 lt 211 gt 33 212 DNA lt 213 gt Artificial Sequence lt 220 4223 Description of Artificial Sequence primer lt 400 gt 3 ccggaattec tggtcctgtc ctgttctcca gca 210 gt 4 lt 211 gt 38 lt 212 gt DNA lt 213 gt Artificial Sequence 38 33 10 20 30 39 J P VO2003 033538 A1 2003 4 24 lt 220 gt 923 Description of Artificial Sequence primer lt 400 gt 4 aaagcggccg
12. 23 J P WO2003 033538 A1 2003 4 24 000 0 1000 B 1000 0 00000 0 000 B E _ EE K K E u k K 10 20 30 50 24 J P VO2003 033538 A1 2003 4 24 x 0 10 20 30 50
13. anti HLA DR antibody 1010 Proc Nat1 Acad Sci USA KOSTELNY 5 A et al Humanization and characterization of the Int J Cancer 2001 Aug Vol 93 No 4 556 565 NIMAN H L et al Generation of protein reactive antibodies by short peptides is an event of high frequency implications for the structural basis of immune recognition 1983 Vol 80 No 16 p 4949 4953 1 93 1 93 TAI FT X TL REET HERE HAT SILO ROR
14. Vga 0 0 L3 L3 J J J lt HD8 2 0 GTCGACTGGCTGACCAGGGCAGTCACCAGAGCTCCAGACAATGTCTGTCTCCTTCCTCATCTTCCTGCCCG T6CTGGGCCTCCCATGGGGTGTCCTGTCACAGGTTCAGCTGCAGCACTCAGGTCCAGGACTGGCTGAAGCCCT CGCAGACCCTCTCACTCACCTGTGCCATCTCCGGGGACAGTGTCTCTAGCAACAGTGCTTCTTGGAACTGGA TCAGGCAGTCCCCATCGAGGGGCCTTGAGTGGCTGGGAAGGACATACTACAGGTCCAAGTGGTATAATGATT ATGCAGTATCTGTGAAAAGTCGAATAGTCATCAACCCAGACACATCCAAGAACCAGTTCTCCCTGCAGCTGA ACTCTCTGACTCCCGAGGACACGGCTGTGTATTACTGTGCGAGAGAAAATTTCTATGGTTCGGAGACTTGTC ATAAGAAGTATTACTGCTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGCTAGC lt HD8 gt 2 1 MSYSFLIFLPVLGLPWGVLSQVQLQHSGPGLVKPSQTLSLTCAISGDSVSSNSASWNWIRQSPSRGLEWLGR TYYRSKWYNDYAYSVKSRIVINPDTSKNQFSLQLNSVTPEDTAVYYCARENFYGSETCHKKYYCYGMDVWGQ GITVTVSSAS lt HD8 gt 22 AGATCTGGGAGTCAGACCCACTCAGGACACAGCATGGACATGAGGGTCCCCGCTCAGCTCCTGGGGCTTCTG CTGCTCTGGCTCCCAGGTGCCAGATGTGCCATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTA GGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGGGCATTAGCAGTGCTTTAGCCTGGTATCAGCAGAAA CCAGGGAAAGCTCCTAAACTCCTGATCTATGATGCCTCCAGTTTGGAAAGTGGGGTCCCATCAAGGTTCAGC GGCAGTGGATCTGGGACAGATTTCACTCTCACCATCA
15. lU U U 000000 10 000 000 20 000 30 U U 40 000 50 3 J P WO2003 033538 A1 2003 4 24
16. Y 1 587 EA BARCEL 5 P U P r3 E MARS OIE A 150722210246 TERE 9281 I8 A J P m 1100 8915 35 03 3581 1101 WR 3448 PCT 1 SA 210 2 19984745 JP VO2003 033538 Al 2003 4 24 115 RHEES PCT IPO2 10665 C Y ULRICH R 6 et al Immune recognition of human major 1 93 histocompatibility antigens localization by a comprehensive sy
17. 10 20 30 50 J P WO2003 033538 A1 2003 4 24 28 10 20 30 50 C x 29 J P WO2003 033538 A1 2003 4 24
18. 10 20 30 50 4 J P VO2003 033538 A1 2003 4 24 000 000 ID dtu 10 20 30 50 J P VO2003 033538 A1 2003 4 24 5 10 20 0 0000
19. Nas HOES i Eee m dadg10D 1 0 ng head 4B HD4 5A Ra 9 HD8G1Ser HD8G2Ser HD8G1 hlgG 180000 t 160000 140000 120000 100000 80000 60000 40000 4 20000 00000 00000 EXE sores 4 VMW3ALTdSLAS MIA ASIA ASLASAHANDILK ANSEHSNDOLANI prend ADOLANZISHANI osuan Sutra AALS WATLO LA AMA TLO LUGO woziwooNo AlouwtoNon ouman 5 MOVARIDONTIM DIPINTA aopnamunaise ENTIS Se IS94A39SAS9A1 DALIOSASIATIN AS9SAS9 ATIN H DATINHMOTIDIH AHHDTdOIyPdAA WTdoySdAAIA 19OLSdMLNa DINSIARIA MAO ISAALANG AAA1ANaDAWNOA ALORS ANdOANSIDALIS3 S
20. VSH e 9 06 08 0L 09 05 Op o 02 0 I 5g at eg x 8 f ES 9 sa pegin ENG m 001 01 I 10 10 0 7 0 I 02 om 0tdH 09 08 PUH S 001 T B 0 3881416 1 1 0 0 19908 w 9ST98dH AN 224 E vex VSH 01QH 9 90H HH zb gp BAYS E ma J P VO2003 033538 A1 2003 4 24 110 9810 PORCH O 1950074 PORCH X9 6980H V 198dH 9814 980H T8STORCH gt V 1980H 20808 m s I 9 HOT 60 a e GV 208 202 de x a AGH H D814 10857980H V JeSTO8dH O X e ZII
21. 10 20 30 50 VO2003 033538 A1 2003 4 10 20 30 50 14 J P VO2003 033538 A1 2003 4 24 10 20 30 50 15 J P VO2003 033538 A
22. 10 20 30 50 22 J P VO2003 033538 A1 2003 4 24 10 20 30 50
23. D 30 C nonno 50 nnnnnn Eier and C J P VO2003 033538 A1 2003 4 24 6 10 C 20 30 50
24. MOO L3 LH 35 J P VO2003 033538 A1 2003 4 24 0 000 p ic ua B 0 00 10 20 30 50 36 JP WO2003 033538 A1 2003 4 24 Bp m gm 0000 B 0
25. lt 400 gt 62 Thr Glu Arg Val Arg Phe Leu Asp Arg Phe Asn l 5 10 lt 210 gt 63 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 63 Arg Val Arg Phe Leu Asp Arg Tyr Phe Tyr Asn Gin Glu 1 5 10 lt 210 gt 64 lt 2112 18 lt 212 gt PRT lt 213 gt Artificial Sequence 10 20 30 69 J P WO2003 033538 A1 2003 4 24 lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 64 Arg Phe Leu Asp Arg Tyr Phe Tyr Asn Gln Glu Glu Ser 1 10 lt 210 gt 65 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 65 Leu Asp Arg Tyr Phe Tyr Asn Gln Glu Glu Ser Val Arg l 5 10 lt 210 gt 66 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide 10 20 30 70 J P VO2003 033538 1 2003 4 24 400 66 Arg Tyr Phe Tyr Asn Gln Glu Glu Ser Val Arg Phe Asp 1 5 10 lt 210 gt 67 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 223 Description of Artificial Sequence peptide lt 400 gt 67 Phe Tyr Asn Gln Glu Glu Ser Val Arg Phe Asp Ser Asp 1 5 10 lt 210 gt 68 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence 2202 4223
26. 0 1 1 EUER Sp u ti HT SHE eT lt lt lt lt lt c lt lt lt lt lt lt lt lt ez c er ec er er ec n5 lt LL pZ lt se nz AS LLP Li LIS L2 LAS CL LL LLI LL LL CUI ac Sa Se Se c c gt z sz gt s z zz s ees won ASRLAR 65 05 61 62 63 64 65 66 67 68 69 70 71 72 73 H HH FERE ERRE 14 SALI iii pde t p sy lt lt lt lt se x clo cox IO zu mm
27. xit di E 113 Intemational application No PCT JP02 10665 INTERNATIONAL SEARCH REPORT A CLASSIFICATION OF SUBJECT MATTER Int Cl C07K16 28 C12N5 10 C12N15 13 C12N1 21 C12N1 19 C12P21 08 A61K39 395 According to International Patent Classification IPC to both national classification and IPC B FIELDS SEARCHED Minimum documentation searched classification system followed by classification symbols Int Cl C07K16 28 C12N5 10 C12N15 13 C12N1 21 C12N1 19 C12P21 08 A61K39 395 Documentation searched other than minimum documentation to the extent that such documents are inciuded in the fields searched Electronic data base consulted during the international search name of data base and where practicable search terms uscd REGISTRY STN CA STN MEDLINE STN WPI DIALOG BIOSIS DIALOG GenBank EMBL DDBJ GeneSeq SwissProt PIR GeneSeq C DOCUMENTS CONSIDERED TO BE RELEVANT Category Citation of document with indication where appropriate ot the relevant passages Relevant to claim No KOSTELNY S A et al Humanization and 1 93 characterization of the anti HLA DR antibody 1D10 Int J Cancer 2001 Aug Vol 93 No 4 pages 556 to 565 NIMAN H L et al Generation of protein reactive antibodies by short peptides is an event of high frequency implications for the structural basis of immune recognition Proc
28. E ES ESI E Jj J E3 EJ EJ L3 J J JJ L3 JJ Beale LEX E E E E EI 10 20 30 50 31 J P WO2003 033538 A1 2003 4 24 lO L3 Di 0 000 000 000 000 E E m 0O LE EJ 000 000 1 rrr n
29. 5 10 lt 210 gt 57 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 57 10 20 30 66 J P VO2003 033538 1 2003 4 24 Pro Lys Arg Glu Cys His Phe Asn Gly Thr Glu Arg l 5 10 lt 2102 58 lt 211 gt 13 212 PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 58 Arg Glu Cys His Phe Phe Asn Gly Thr Glu Arg Val Arg l 5 10 lt 210 gt 59 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 59 Cys His Phe Phe Asn Gly Thr Glu Arg Val Arg Phe Leu I 5 10 10 20 30 67 J P WO2003 033538 A1 2003 4 24 lt 210 gt 60 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 60 Phe Phe Asn Gly Thr Glu Arg Val Arg Phe Leu Asp Arg 1 5 10 lt 210 gt 61 lt 211 gt 13 lt 212 gt lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 61 Asn Gly Thr Glu Arg Val Arg Phe Leu Asp Arg Tyr Phe l 5 10 lt 210 gt 62 2112 13 10 20 30 68 J P VO2003 033538 A1 2003 4 24 lt 212 gt PRT 213 Artificial Sequence lt 220 gt 4223 Description of Artificial
30. lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 223 Description of Artificial Sequence peptide 400 74 Gly Glu Phe Arg Ala Val Thr Glu Leu Gly Arg Pro Asp 1 10 lt 210 gt 75 2112 13 212 PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide 10 20 30 74 J P VO2003 033538 A1 2003 4 24 lt 400 gt 75 Phe Arg Ala Val Thr Glu Leu Gly Arg Pro Asp Ala Glu l 5 10 lt 210 gt 76 lt 211 gt 13 2122 PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 76 Ala Val Thr Glu Leu Gly Arg Pro Asp Ala Glu Tyr Trp l 5 10 lt 210 gt 77 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 77 Thr Glu Leu Gly Arg Pro Asp Ala Glu Tyr Trp Asn Ser 10 20 30 75 J P WO2003 033538 A1 2003 4 24 l 9 10 lt 210 gt 78 lt 2112 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 78 Leu Gly Arg Pro Asp Ala Glu Tyr Trp Asn Ser Gin Lys 1 5 10 4210 19 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 79 Arg Pro Asp Ala Glu Tyr Trp Asn Ser Gln Lys Asp Hle I 5 10
31. 1 7 MEFGLSWLFLVAILKGVQCEVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMTWVRQAPGKGLEWYSGISG GGDSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDHGSGS YYPYWFDYWGQGTLVTVSSA HD4 gt 1 8 AGATCTGCTGCTCAGTTAGGACCCAGAGGGAACCATGGAAACCCCAGCGCAGCTTCTCTTCCTCCTGCTACT CTGGCTCCCAGATACCACCGGAGAACTTCTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGA AAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCCGCTACTTAGCCTGGTACCAGCAGAAACC TGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGG CAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACTG TCAGCAGTATGGTAGCTCACCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACG lt HD4 gt 1 9 METPAQLLFLLLLWLPDTTGELVLTQSPGTLSLSPGERATLSCRASQSVSSRYLAWYQQKPGQAPRLL 1 YGA SSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGGGTKVETKRT DI DI DI DI DI DI DI DI 0 0000 m 1 Ea E E EI
32. 10 20 30 76 J P 02003 033538 1 2003 4 24 lt 210 gt 80 2112 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 223 Description of Artificial Sequence peptide lt 400 gt 80 Asp Ala Glu Tyr Trp Asn Ser Gln Lys Asp Ile Leu Glu 5 10 lt 210 gt 81 42112 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 81 Glu Tyr Trp Asn Ser Gln Lys Asp Ile Leu Glu Gin Ala l 5 10 lt 210 gt 82 lt 211 gt 13 lt 212 gt PRT 10 20 30 77 J P WO2003 033538 A1 2003 4 24 lt 213 gt Artificial Sequence lt 220 gt 4223 Description ol Artificial Sequence peptide lt 400 gt 82 Trp Asn Ser Gln Lys Asp Leu Glu Gln Ala Arg Ala l 5 10 lt 210 gt 83 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 83 Ser GIn Lys Asp Ile Leu Glu Gln Ala Arg Ala Ala Val l 5 10 lt 210 gt 84 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 10 20 30 78 J P VO2003 033538 A1 2003 4 24 4223 Description of Artificial Sequence peptide 400 84 Lys Asp Leu Glu Gln Ala Arg Ala Ala Val Asp Thr l 5 10 42102 85 lt 211 gt 13 lt 212 gt lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 85
33. 215 Glu Val Val 120 Gln Tyr Lys Phe Tyr 200 Glu 107 5 105 Gln Pro Pro Ala Gin 185 Thr Trp 15 Trp Asn 90 Thr Arg Arg Leu Gln Gly Ser 155 Gly Met 170 Thr Leu Cys Gin Arg Ala Ser Cys Val His 140 Val Val Val Arg 220 VO2003 033538 Al 2003 4 24 Gln Lys Arg His 110 GIn Pro 125 His Asn L Glu Val Ser Thr Met Leu 190 205 Ser Glu 80 Ile 95 Tyr Lys Val Arg Trp 160 Gly Leu 175 Glu Thr Pro Ser Ser Ala 10 20 30 108 J WO2003 033538 A1 2003 4 24 Gln Ser Lys Met Leu Ser Gly Val Gly Gly Phe Val Leu Gly Leu Leu 225 230 235 240 Phe Leu Gly Ala Gly Leu Phe Phe Asn Gln Lys Gly His 245 250 255 10 Ser Gly Leu Gln Pro Thr Gly Phe Leu Ser 260 265 H H 20 H HHHHHHHHLuLHHHHHHHH 000 30 HHHHHH HHBHHHHH HE AEREI 000000 00800000 ood 00000 0 J P WO2003 033538 A1 2003 4 24 109
34. Description of Artificial Sequence peptide lt 400 gt 68 Asn Gln Glu Glu Ser Val Arg Phe Asp Ser Asp Val Gly l 5 10 10 20 30 71 J P WO2003 033538 A1 2003 4 24 lt 210 gt 69 lt 211 gt 13 lt 212 gt lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 69 Glu Glu Ser Val Arg Phe Asp Ser Asp Val Gly Glu Phe 1 5 10 lt 210 gt 70 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide 400 70 Ser Val Arg Phe Asp Ser Asp Val Gly Glu Phe Arg Ala 1 5 10 lt 210 gt 71 10 20 30 72 J P VO2003 033538 A1 2003 4 24 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 71 Arg Phe Asp Ser Asp Val Gly Glu Phe Arg Ala Val Thr 1 5 1 lt 210 gt 72 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 72 Asp Ser Asp Val Gly Glu Phe Arg Ala Val Thr Glu Leu 5 10 lt 210 gt 73 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence 10 20 30 73 J P VO2003 033538 A1 2003 4 24 lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 73 Asp Val Gly Glu Phe Arg Ala Val Thr Glu Leu Gly Arg b 10 lt 210 gt 74
35. His His Asn 5 10 lt 210 gt 103 lt 211 gt 13 lt 212 gt PRI lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 103 Pro Ser Lys Thr Gln Pro Leu Gln His His Asn Leu Leu l 5 10 lt 210 gt 104 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide 10 20 30 87 J P WO2003 033538 A1 2003 4 24 lt 400 gt 104 Lys Thr Gin Pro Leu Gln His His Asn Leu Leu Cys 1 5 10 lt 210 gt 105 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 105 Gln Pro Leu Gln His His Asn Leu Leu Val Cys Ser Val 1 5 10 lt 210 gt 106 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 106 Leu GIn His His Asn Leu Leu Val Cys Ser Val Ser Gly 10 20 30 88 J P VO2003 033538 A1 2003 4 24 l D 10 lt 210 gt 107 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide 400 gt 107 His His Asn Leu Leu Val Cys Ser Val Ser Gly Phe Tyr 1 5 10 lt 210 gt 108 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 223 Description of Artificial Sequence peptide lt 400
36. Ile Leu Glu Gln Ala Arg Ala Ala Val Asp Thr Tyr Cys l 5 10 lt 210 gt 86 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide 4002 86 10 20 30 79 J P VO2003 033538 A1 2003 4 24 Glu Gin Ala Arg Ala Ala Val Asp Thr Tyr Cys Arg His 10 lt 210 gt 87 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide 400 87 Ala Arg Ala Ala Val Asp Thr Tyr Cys Arg His Asn Tyr l 5 10 lt 210 gt 88 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 88 Ala Ala Val Asp Thr Tyr Cys Arg His Asn Tyr Gly Val l 5 10 10 20 30 80 J P WO2003 033538 1 2003 4 24 lt 210 gt 89 lt 211 gt 18 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 223 Description of Artificial Sequence peptide 400 89 Val Asp Thr Tyr Cys Arg His Asn Tyr Gly Val Val Glu 1 5 10 lt 210 gt 90 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 90 Thr Tyr Cys Arg His Asn Gly Val Val Glu Ser Phe l 5 10 210 gt 91 lt 211 gt 13 10 20 30 81 J P VO2003 033538 A1 2003 4 24 lt 212 gt PRT 4213 Artificial Sequence lt 220 gt lt 2
37. ctcatcagct caggaatcct gttggctg lt 210 gt 5 lt 211 gt 27 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence primer lt 400 gt 5 getccgggag atcatgaggg tgtcctt 4210 6 lt 211 gt 26 lt 212 gt DNA lt 213 gt Artificial Sequence 12202 4223 Description of Artificial Sequence primer 4002 6 38 27 10 20 30 40 J P VO2003 033538 A1 2003 4 24 gtgcacgccg ctggtcaggg cgcctg lt 210 gt 7 lt 211 gt 23 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence primer lt 400 gt 7 ggigccaggg ggaagaccga gg lt 210 gt 8 lt 211 gt 37 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence primer lt 400 gt 8 atatgtcgac ccagccctgg gattttcagg tettttc lt 210 gt 9 lt 211 gt 35 26 23 37 10 20 30 41 J P VO2003 033538 A1 2003 4 24 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence primer 400 9 10 atatgtcgac tggctgacca gggcagtcac cagag 35 lt 210 gt 10 lt 211 gt 31 lt 212 gt DNA 5 213 Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence primer lt 400 gt 10 30 gatgggccct tggtgctagc tgaggagacg g 31 lt 210 gt 11 lt 211 gt 26 lt 212 gt DNA lt 213 gt Artif
38. gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 114 Gly Ser Ile Glu Val Arg Trp Phe Leu Asn Gly Gln Glu l 5 10 lt 210 gt 115 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 115 10 20 30 92 J P VO2003 033538 1 2003 4 24 Glu Val Arg Trp Phe Leu Asn Gly Glu Glu Lys 5 10 lt 210 gt 116 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 116 Val Arg Trp Phe Leu Asn Gly Gin Glu Glu Lys Ala Gly 1 5 10 lt 210 gt 117 lt 211 gt 13 lt 212 gt lt 213 gt Artificial Sequence 220 lt 223 gt Description of Artificial Sequence peptide 400 117 Trp Phe Leu Asn Gly Gln Glu Glu Lys Ala Gly Met Val 5 10 10 20 30 93 J P WO2003 033538 A1 2003 4 24 lt 210 gt 118 lt 2112 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide 400 118 Leu Asn Gly Gln Glu Glu Lys Ala Gly Met Val Ser Thr 1 b 10 lt 210 gt 119 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 223 Description of Artificial Sequence peptide lt 400 gt 119 Gly Gln Glu Glu Lys Ala Gly Met Val Ser Thr Gly Leu I 5 10 lt 210 gt 120 lt 211 gt 1
39. 00 gt 125 Leu Ile Gln Asn Gly Asp Trp Thr Phe Gln Thr Leu Val 3 5 10 lt 210 gt 126 lt 211 gt 13 lt 212 gt lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 126 Gin Asn Gly Asp Trp Thr Phe Gin Thr Leu Val Met Leu 5 10 10 20 30 97 JP WO2003 033538 1 2003 4 24 lt 210 gt 127 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 127 Gly Asp Trp Thr Phe Gln Thr Leu Val Met Leu Glu Thr 1 5 10 lt 2102 128 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 128 Trp Thr Phe Gln Thr Leu Val Met Leu Glu Thr Val Pro l 5 10 lt 210 gt 129 10 20 30 98 J P WO2003 033538 A1 2003 4 24 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 129 Phe Gln Thr Leu Val Met Leu Glu Thr Val Pro Arg Ser 5 10 4210 130 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide 400 130 Thr Leu Val Met Leu Glu Thr Val Pro Arg Ser Gly Glu l 5 10 lt 210 gt 131 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence 10 20 30 99 J P WO2003 033538 A1
40. 02 St 8 2814 PORTH 498295 O org e PORCH VY eSg98H ZI80H Y I580H t peou 3rT 0 38 H Er xt VY lx 170 1070 10070 20 dE WEG Oe 111 J P VO2003 033538 A1 2003 4 24 00000 ss NAWALMMSLAS BAL 2a81AS H SADOSIASOA Fein AOOUM H3AG91AA39594 AOSLAA3954A DAANS9S98A137 PC Serino Kayra LauAODND abraoneraiss DBH91SAW9 23 pite Sanna Enel SA pere tt rst PENH NN NNN ROKOS Err oe ASA Erro poe pte Moon portet poner inerti oni onvevos PA NOON Marna Stopper POG sos poses TAY vases us EDIAN TAW0439505028 p VASZIONAFANOI 5 3AHHaAH 1 SN L
41. 03 033538 A1 2003 4 24 n RDO 0 00000 0 x 0g 0 1 1 g 1 u H H H H H H S hee SEPA dou e ME E INVE HE CEE 2 J E DL 0O
42. 1 2003 4 24 p NS B nn a HHH HHB zi ra 10 20 30 50 16 JP WO2003 033538 A1 2003 4 24 x D C
43. 1 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 137 Tyr Thr Cys Gln Val Glu His Pro Ser Val Thr Ser Pro 5 10 10 20 30 102 J P VO2003 033538 A1 2003 4 24 lt 210 gt 138 lt 2112 18 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 138 Cys Gln Val Glu His Pro Ser Val Thr Ser Pro Leu Thr l 5 10 lt 210 gt 139 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial lt 400 gt 139 Val Glu His Pro Ser Val Thr Ser Pro Leu Thr Val Glu I 5 10 210 140 lt 211 gt 13 lt 212 gt PRT 10 20 30 103 J P VO2003 033538 A1 2003 4 24 lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 140 His Pro Ser Val Thr Ser Pro Leu Thr Val Glu Trp Arg 1 5 10 lt 210 gt 141 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 141 Ser Val Thr Ser Pro Leu Thr Val Glu Trp Arg Ala Arg l 5 10 lt 210 gt 142 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 10 20 30 104 J P VO2003 033538 A1 2003 4 24 lt 223 gt Description of Artificial Sequence pept
44. 2003 4 24 C x 0 u C 0 H si s AE M E DN CEN T 10 20 30 50 12 WO2003 033538 1 2003 4 24 000 HA 000
45. 2003 4 24 lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 131 Val Met Leu Glu Thr Val Pro Arg Ser Gly Glu Val Tyr l 5 10 lt 210 gt 132 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence 220 lt 223 gt Description of Artificial Sequence peptide lt 400 gt 132 Leu Glu Thr Val Pro Arg Ser Gly Glu Val Tyr Thr Cys 1 5 10 lt 2102 133 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide 10 20 30 100 J P VO2003 033538 1 2003 4 24 lt 400 gt 133 Thr Val Pro Arg Ser Gly Glu Val Tyr Thr Cys GIn Val 5 10 210 134 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 134 Pro Arg Ser Gly Glu Val Tyr Thr Cys Gln Val Glu His 5 10 lt 210 gt 135 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 135 Ser Gly Glu Val Tyr Thr Cys Glo Val Glu His Pro Ser 10 20 30 101 J P VO2003 033538 A1 2003 4 24 l 9 10 lt 210 gt 136 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 136 Glu Val Tyr Thr Cys Gln Val Glu His Pro Ser Val Thr 5 10 lt 210 gt 137 lt 21
46. 23 gt Description of Artificial Sequence peptide lt 400 gt 91 Cys Arg His Asn Gly Val Val Glu Ser Phe Thr Val 10 lt 2102 92 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide 400 92 His Asn Tyr Gly Val Val Glu Ser Phe Thr Val GIn Arg l 5 10 lt 210 gt 93 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence 10 20 30 82 J P VO2003 033538 A1 2003 4 24 lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 93 Gly Val Val Glu Ser Phe Thr Val GIn Arg Arg Val l 5 10 lt 210 gt 94 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 223 Description of Artificial Sequence peptide 400 gt 94 Val Val Glu Ser Phe Thr Val Gln Arg Arg Val Gln Pro 5 10 210 95 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide 10 20 30 83 J P VO2003 033538 1 2003 4 24 400 95 Glu Ser Phe Thr Val Gln Arg Arg Val Gln Pro Lys Val 5 10 lt 210 gt 96 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 96 Phe Thr Val Gln Arg Arg Val Gln Pro Lys Val Thr Val l 5 10 lt 210 gt 97 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequenc
47. 3 10 20 30 94 J P WO2003 033538 A1 2003 4 24 lt 212 gt PRT 4213 Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 120 Glu Glu Lys Ala Gly Met Val Ser Thr Gly Leu Ile Gln l 5 10 lt 210 gt 121 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 223 Description of Artificial Sequence peptide lt 400 gt 121 Lys Ala Gly Met Val Ser Thr Gly Leu Ile Gin Asn Gly l 5 10 lt 210 gt 122 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence 10 20 30 95 J P WO2003 033538 A1 2003 4 24 lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 122 Gly Met Val Ser Thr Gly Leu Gln Asn Gly Asp Trp 5 10 210 gt 123 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 123 Val Ser Thr Gly Leu Ile Asn Gly Asp Trp Thr Phe 1 5 10 lt 210 gt 124 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide 10 20 30 96 J P WO2003 033538 A1 2003 4 24 lt 400 gt 124 Thr Gly Leu Ile Gin Asn Gly Asp Trp Thr Phe Gln Thr l 9 10 lt 210 gt 125 lt 211 gt 13 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 4
48. Asp Val 140 Leu Gly 30 Gly Ser Lys Asn Thr 110 Gly Trp Pro 15 Leu ASD Pro Trp Pro 95 Pro Ser Gly Trp Val Ser Ser 80 Asp Glu Glu Gln 10 20 30 49 J P VO2003 033538 A1 2003 4 24 Gly Thr Thr Val Thr Val Ser Ser Ala Ser 145 150 lt 210 gt 22 lt 211 gt 426 lt 212 gt DNA lt 213 gt Homo sapiens 400 22 agatctggga gtcagaccca ctcaggacac agcatggaca tgagggtcce cgclcagctc 60 ctggggcttc tgctgctctg gctcccaggt gccagatgtg ccatccagtt gacccagict 120 80 ccatcctccc tgtctgcatc tgtaggagac agagicacca tcacttgccg ggcaagtcag ggcattagca gtgctttagc ctggtatcag cagaaaccag ggaaagctcc taaactcctg 240 atctatgatg cciccagttt ggaaagtggg gtcccatcaa ggttcagcgg Cagtggatct 300 gggacagatt tcactctcac catcagcagc ctgcagcctg aagattttgc aacttattac 360 tgtcaacagt ttaatagttt cccgctcact cggcggag ggaccaaggt ggagatcaaa 420 cgtacg 426 210 23 lt 211 gt 132 lt 212 gt PRT 213 Homo sapiens 400 23 Met Asp Met Arg Val Pro Ala Leu Leu Gly Leu Leu Leu Leu l 5 10 15 Leu Leu Gin Ala 65 Pro Phe Lys Pro Gly Ala Arg 20 Ser Ala Ser Val 35 Gly Ile Ser Ser 50 Pro Lys Leu Leu Ser Arg Phe Ser 89 Ser Ser Leu Gln 100 Asn Ser Phe Pro 115 Arg Thr Val 130 lt 210 gt 24 2 1 gt 13 lt 212 gt PRT Cys G y Ala Ile 10 Gly Pro
49. DAL53AADA HOALHR3AABANO1 ALISSAADANHEO AN9ANHSOALQA Ed ANIONS NAT SS Avvavosnasps VEVOTIONOSNA yonwoxOSAwa porre MAINLY SETONALAMO TI NAAR ASL ESSEN ICM Aa1 MANIONA4H03 MOLON AMO 3 LONLIMODENAOM L ONSIHOFINIOM ORION proe Ete OAT REMI HD6 HD8 5C 160000 140000 120000 100000 80000 60000 40000 4 20000 350000 300000 250000 200000 150000 100000 50000 J P VO2003 033538 A1 2003 4 24 112 6 HD6 HD8 HD4
50. GCAGCCTGCAGCCTGAAGATTTTGCAACTTATTAC TGTCAACAGTTTAATAGTTTCCCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACG lt HD8 gt 2 3 MDMRVPAQLLGLLLLWLPGARCAIQLTQSPSSLSASVGDRYTI TCRASQGISSALAWYQQKPGKAPKLLIYD ASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSFPLTFGGGTKVETKRTV ua 0 0000000000000000000 00000000 0000000 8 A DE 10 20 30 50 24 32 J P 2003 033538 1 2003 4 at m 2 2 Cana RES SARAI E AA 2 DNA DNA No 7515 5 5 to 3 gat ggg cee tte gie cla gct gag gag acg
51. JP VO2003 033538 Al 2003 4 24 19 JP A1 11 W02003 033538 17 2 3 2005 2 3 43 15 4 24 2003 4 24 51 Int FI C12N 15 09 C12N 15 0 ZNAA AO1K 67 027 AO1K 67 027 A61K 39 395 AGIK 39 395 N A61P 35 00 A61P 35 00 A61P 35 02 A61P 35 02 A TREE A 116 2003 536276 P2003 536276 21 PCT JP2002 010665 22 14 10 15 2002 10 15 31 71 000253503 Rl eS RS tt 10 1 2001 317054 2001 317054 74 100091096 32 13 10 15 2001 10 15 33 JP 74 100118773 81 AP GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW EA AM AZ BY KG KZ MD RU TJ EP AT 74 100096183 BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LU MC RX NL PT SE SK TR OA BF BJ CG GA GN GQ GW 7 ML MR NE SN TD TG AE AG AL AM AT AU AZ BB BG 3 R BY BZ CA CH CN CO CR C
52. Leu 50 Ala Gln Leu Asp Arg 40 Leu Ala 29 Asp Ser Gly Glu Asp Thr Phe 120 25 Val Ala Ser Phe 105 Gly Thr Tyr Ser Gly 90 Ala Gly JP VO2003 033538 Al 2003 4 24 Thr Gln Ser Pro Ser Ser Ile Gln Ser 75 Thr Thr Gly Thr Gin 60 Leu Asp Tyr Thr Cys 45 Lys Glu Phe Tyr Lys 30 Arg Ala Ser Pro Ser Thr Cys 110 Val Gly Lys Glv Val Leu 95 80 Thr Gln Gln Glu 10 20 30 51 J P VO2003 033538 A1 2003 4 24 lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide 400 24 Trp Asn Ser 1 Lys Asp Phe Leu Glu Asp Arg Arg Ala 5 10 lt 210 gt 25 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence 220 223 Description of Artificial Sequence peptide 400 25 Asn Ser Gin Lys Asp Phe Leu Glu Arg Arg Arg Ala 1 5 10 lt 210 gt 26 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 10 20 30 52 J P WO2003 033538 A1 2003 4 24 223 Description of Artificial Sequence peptide lt 400 gt 26 Trp Asn Ser Gln Lys Asp Phe Leu Glu Asp Glu Arg Ala 5 10 4210 27 2112 13 lt 212 gt PRT 4213 Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide 400 27 Trp Asn Ser Gin Lys Asp Phe Leu Gl
53. Natl Acad Sci USA 1983 Vol 80 No 16 pages 4949 to 4953 ULRICH R G et al Immune recognition of human major histocompatibility antigens localization by a comprehensive synthetic strategy of the continuous antigenic sites in the first domain of HLA DR2 chain Eur J Immunol 1987 Vol 17 No 4 pages 497 to 502 Further documents are listed in the continuation of Box C See patent family later document published after the intemational filing date or document defining the general state of the art which is not priority date and not in conflict with the application but cited to considered to be of particular relevance understand the principle or theory underlying the invention earlier document but published on or after the international filing document of particular relevance the claimed invention cannot be date considered novel or cannot be considered to involve an inventive step when the document is taken alone document of particutar relevance the claimed invention cannot be Special categories of cited documents L document which may throw doubts on priority claim s or which is Cited to establish the publication date of another citation or other special reason as specified considered to involve an inventive stzp when the document is O document referring to an oral disclosure use exhibition or other combined with one or more other such documents such means combi
54. U CZ DE DK DM DZ EC EE ES GD GE GH GM HR HU ID IL IN IS JP KE KG KP 72 28 KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ N 3 MEZAR 0 NZ OM PH PL PT RO RU SD SE SG SI SK SL TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW 54 HLA DR 5 0000 0 00000000 000000000000000000000000000 00 0 000000000000000000000000000000000000000 0 000000000000000000000000000 00000000000 0 0000000000000000000 0000000000000000000 0 0 00000000000000000000000000000000000 00 00000000000000000 00000 2 J P VO2003 033538 A1 2003 4 24
55. aag ggecggitca aagaacacgc tglatctgca aatgaacagc clgagagccg tgtgcgagag atcatggttc ggggagttat tatecctact ggaaccctgg tcaccgtctc ctcagctagc lt 210 gt 17 lt 211 gt 143 lt 212 gt PRT lt 213 gt Homo sapiens lt 400 gt 17 Met Glu Phe Gly Leu Ser Trp Leu Phe Leu Val 5 10 Val Gin Cys Glu Val Gln Leu Leu Glu Ser Gly 20 25 Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala 35 40 Ser Ser Tyr Ala Met Thr Val Arg Ala 50 55 JP VO2003 033538 Al 2003 4 24 gatcaggact tttttcttgt ggctatttta gaggcttggt acagcctggg ttagcagcta tgccatgacc caggtattag tggtggtggt ccatctccag agacaaticc aggacacggc Cgtatattac ggtttgacta ctggggccag Aia Leu Lys 15 Gly Glv Leu Val Gln 30 Ser Gly Phe Thr Phe 45 Pro Gly Lys Gly Leu 60 10 20 30 45 J P VO2003 033538 A1 2003 4 24 Glu Trp Val Ser Gly Ser Gly Gly Gly Asp Ser Thr Tyr Tvr Ala 65 10 75 Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser 85 90 Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr 100 105 110 s Gly Ser Gly Ser Pro fet Tyr Tyr Cys Ala Arg Asp H 115 120 125 Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 130 135 140 lt 210 gt 18 211 gt 424 lt 212 gt DNA lt 213 gt Homo sapiens lt 400 gt 18 agatctgctg ctcagttagg acccagaggg aaccaiggaa CCtectgcta cagataccac cggagaactt gtgttgacgc caccctgtct ttgtctc
56. cag gggaaagagc tgcagggcca tagcagccgc tacttagcct ggtaccagca gaaaccigge ctatggigca tccagcaggg ccactggcat cccagacagg ttcagtggca gacagactic ggagcctgaa gattttgcag 80 Lys Asn 95 Ala Val Tyr Trp Ala agcttctctt 60 agtctccagg 120 gtcagagtgt 180 ggctcctcat 240 gtgggtctgg 300 tgtattactg 360 10 20 30 46 J P VO2003 033538 A1 2003 4 24 tcagcagtat ggtagctcac cgctcacttt cggcggaggg accaaggtgg agatcaaacg 420 424 lt 210 gt 19 lt 211 gt 130 lt 212 gt PRT lt 213 gt Homo sapiens 400 19 Met Glu Thr Pro Ala Gln Leu Leu Phe Leu Leu Leu Leu Trp Leu Pro 5 10 15 Asp Thr Thr Gly Glu Leu Val Leu Thr Gln Ser Pro Gly Thr Leu Ser 20 25 30 Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser 35 40 45 Val Ser Ser Arg Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala 50 55 60 Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro 65 70 75 80 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Phe Thr Leu Thr Ile 85 00 95 Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Cys Gln Gln Tyr 47 J P WO2003 033538 A1 2003 4 24 100 105 110 Gly Ser Ser Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Lys 115 120 125 Arg Thr 130 lt 210 gt 20 lt 211 gt 502 lt 212 gt DNA lt 213 gt Homo sapiens 400 20 gicgacigge tgaccagggc agtcaccaga gclccagaca atgtctgtct ccttcctcat 60
57. cttcctgccc gtgctgggcc tcccatgggg tgtcctgtca caggttcagc gcagcactc 120 aggtccagga ctggtgaagc cctcgcagac CCtctcactc acctgtgcca tctccgggga 180 cagtgtctct agcaacagtg cttcttggaa ctggatcagg cagtccccat Cgaggggcct 240 tgagtggctg ggaaggacat actacaggtc caagtggtat aatgattatg cagtatctgt 300 gaaaag cga atagtcatca acccagacac Cagttctccc tgcagctgaa 360 ctctgtgact cccgaggaca cggctgtgta ttactgtgcg agagaaaatt ctatggttc 420 ggagacttgt cataagaagt attacigcia cggtatggac gtctggggcc aagggaccac 480 ggtcaccgtc tcctcagcta gc 502 lt 210 gt 21 lt 211 gt 154 lt 212 gt PRT 10 20 30 lt 213 gt Homo sapiens 400 21 Met Ser l Gly Val Lys Pro Val Ser 50 Arg Gly 65 Asn Asp Thr Ser Asp Thr Thr Cys 130 Val Ser 35 Ser Leu Tyr Lys Ala His Ser Ser 20 Gin Asn Glu Ala Asn 100 Val Lys Phe Gln Thr Ser Trp Val 85 Gin Lys Leu Val Leu Ala Leu 10 Ser Phe Tyr Ser Ser 55 Gly Val Ser Cys 48 Phe Leu Leu 25 Leu Thr 40 Trp Asn Arg Thr Lys Ser Leu Gln 105 Pro Val 10 His Ser Cys Ala Trp Ile Tyr Tyr 15 Arg Ile 90 Leu Asn Ala Arg Glu Asn 120 Cys Gly Met JP VO2003 033538 Al 2003 4 24 Leu Gly Gly Pro 45 Arg 60 Arg Ser Val Ser Val Phe Tyr 125
58. e lt 220 gt 4223 Description of Artificial Sequence peptide 400 97 Val Gln Arg Arg Val Gln Pro Lys Val Thr Val Tyr Pro l 5 10 10 20 30 84 J 2003 033538 1 2003 4 24 lt 210 gt 98 lt 211 gt 13 lt 212 gt 4213 Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 98 Arg Arg Val Gln Pro Lys Val Thr Val Tyr Pro Ser Lys 1 5 10 lt 210 gt 99 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 99 Val GIn Pro Lys Val Thr Val Tyr Pro Ser Lys Thr GIn 1 5 10 lt 210 gt 100 10 20 30 85 JP WO2003 033538 1 2003 4 24 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 100 Pro Lys Val Thr Val Pro Ser Lys Thr Gin Pro Leu 5 10 lt 210 gt 101 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 101 Val Thr Val Tyr Pro Ser Lys Thr GIn Pro Leu Gln His l 5 10 lt 210 gt 102 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence 10 20 30 86 J P VO2003 033538 A1 2003 4 24 lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 102 Val Tyr Pro Ser Lys Thr Pro Leu
59. gt 108 Asn Leu Leu Val Cys Ser Val Ser Gly Phe Tyr Pro Gly 1 5 10 10 20 30 89 J P WD2003 033538 A1 2003 4 24 lt 210 gt 109 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 109 Leu Val Cys Ser Val Ser Gly Phe Tyr Pro Gly 1 5 10 lt 210 gt 110 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 110 Cys Ser Val Ser Gly Phe Tyr Pro Gly Ser Ile Glu Val l 5 10 4210 111 lt 211 gt 13 lt 212 gt PRT 10 20 30 90 J P WO2003 033538 A1 2003 4 24 lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt Ill Val Ser Gly Phe Tyr Pro Gly Ser Ile Glu Val Arg Trp l 5 10 lt 2102 112 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 112 Phe Pro Gly Ser Ile Glu Val Arg Trp Phe Leu 1 5 10 lt 210 gt 113 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 2202 10 20 30 91 J P VO2003 033538 A1 2003 4 24 lt 223 gt Description of Artificial Sequence peptide lt 400 gt 113 Tyr Pro Gly Ser Ile Glu Val Arg Trp Phe Leu Asn Gly 5 10 lt 2102 114 lt 211 gt 13 lt 212 gt PRT lt 213
60. ial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 45 Trp Ala Ser Gln Lys Asp Leu Leu Glu Gln Arg Arg Ala 1 5 10 lt 210 gt 46 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide 10 20 30 61 J P VO2003 033538 1 2003 4 24 lt 400 gt 46 Trp Asn Ala Gln Lys Asp Leu Leu Glu Gln Arg Arg Ala I 5 10 lt 210 gt 47 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 gt Description of Artificial Sequence peptide lt 400 gt 47 Trp Asn Ser Ala Lys Asp Leu Leu Glu Gln Arg Arg Ala 1 5 10 lt 2102 48 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide 400 48 Trp Asn Ser Gln Ala Asp Leu Leu Glu Gln Arg Arg Ala 10 20 30 62 J P WO2003 033538 A1 2003 4 24 l 9 10 lt 210 gt 49 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 49 Trp Asn Ser Gln Lys Ala Leu Leu Glu Gln Arg Arg Ala 5 10 210 50 lt 211 gt 13 212 PRT 213 Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 50 Trp Asn Ser Gin Lys Asp Leu Leu Ala Gln Arg Arg Ala l 5 10 10 20 30 63 J P WO2003 033538 1 2003 4 24 l
61. icial Sequence 40 lt 220 gt lt 223 gt Description of Artificial Sequence primer 42 J P VO2003 033538 A1 2003 4 24 lt 400 gt 11 gttgaagctc tttgtgacgg gcgagc lt 210 gt 12 lt 211 gt 26 212 DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence primer lt 400 gt 12 tggcgggaag atgaagacag atggtg lt 210 gt 13 lt 2112 38 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence primer lt 400 gt 13 atatagatct gclgclcagl taggacccag agggaacc 26 26 38 10 20 30 43 J P VO2003 033538 A1 2003 4 24 42102 14 lt 211 gt 37 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence primer lt 400 gt 14 atatagatci gggagtcaga cccactcagg acacagc lt 210 gt 15 lt 211 gt 32 212 DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence primer lt 400 gt 15 aagacagatg gtgcagccac cgtacgitig at lt 210 gt 16 lt 211 gt 510 lt 212 gt DNA lt 213 gt Homo sapiens 37 32 10 20 30 44 lt 400 gt 16 gicgacccag CCCtgggatt llcagglgtt ttcagglgll gaacagagag aactcaccat ggagtttggg ctgagctggc aaaggtgtcc agigtgaggi gcaactgttg gagtCtgggg gggiccctga gactctcctg gcagcctct ggattcacct 1gggtCCgCC aggclccagg gaaggggclg gagtgggtct gatagcacat actacgcaga ctccgtg
62. ide lt 400 gt 142 Thr Ser Pro Leu Thr Val Glu Trp Arg Ala Arg Ser Glu 5 10 lt 210 gt 143 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 143 Pro Leu Thr Val Glu Trp Arg Ala Arg Ser Glu Ser Ala l 5 10 lt 210 gt 144 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 223 Description of Artificial Sequence peptide lt 400 gt 144 10 20 30 105 J P VO2003 033538 A1 2003 4 24 Thr Val Glu Trp Arg Ala Arg Ser Glu Ser Ala Gln Ser l 9 10 lt 210 gt 145 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 145 Val Glu Trp Arg Ala Arg Ser Glu Ser Ala GIn 1 5 10 lt 210 gt 146 lt 211 gt 801 lt 212 gt DNA lt 213 gt Homo sapiens lt 400 gt 146 atggtgtgtc tgaagctcce tggaggctcc tgcatgacag gigctgagct CCCCaCtggC tttgtctggg gacacccgac aagagggagt gtcatttctt caatgggacg gagcggetec fataaccagg aggagtccgt gcecttcgac agcgacglgg gagctggggc ggcctgacgc tgagtactgg aacagccaga cgggccgcgg tggacaccta cigcagacac aactacgeggg Ser Lys cgctgacagt gacactgatg 60 cacgtttcct gtggcagcct 120 ggttcctgga cagatacttc 180 gggagttccg ggcggtgacg 240 aggacatcct ggagcaggcg 300 tgtggagag cttcacagtg 360 10 20 30 106 cagcggcgag ggtgactgia tatccttcaa cacaaccicc ggtctgc
63. nation being obvious to a person skilled in the art P document published prior to the international filing date but ater 8 document member of the same patent family than the priority date claimed Date of the actual completion of the international search 16 January 2003 16 01 03 Date of mailing of the international search report 28 January 2003 28 01 03 and mailing address of the ISA Authorized officer Japanese Patent Office Facsimile No Telephone No Form PCT ISA 210 second sheet July 1998 JP WO2003 033538 Al 2003 4 24 114 PCT JPO2 10665 A 1 PC Int CI CO7K 16 28 CI2N 5 10 CI2N 15 13 C12N 1 21 CI2N 1 19 C12P 21 08 39 395 B 1PC Int CO7K 16 28 C12N 5 10 C12N 15 13 CL2N 1 21 2 1 19 12 21 08 39 395 El REGISTRY STN STN MEDLINE STN WPI DIALOG BIOSIS DIALOG GenBank EMBL DDBJ GeneSeq SwissProt PIR GeneSeq BETS LBS ENS
64. nthetic strategy of the continuous antigenic sites in the first domain of HLA DR2 chain Eur J Immunol 1987 Vol 17 No 4 497 502 RAPCT ISA 210 2 1998 7 J P WO2003 033538 A1 2003 4 24 116 J P WO2003 033538 A1 2003 4 24 000000 51 Int a 37 02 37 02 H 37 06 3706 37 08 37 08 16 18 16 18 0000 vi HH 1 15 0000 1 19 1 19 121 1 21 5 10 0 21 02 21 02 2 08 21 08 5 00 5 00 IHHHHHHHHHHHHHHHHHHHH IHHHHHHHHHHHHHHHHHHHH IHHHHHHHHHHHHHHHHHHHH IHHHHHHHHHHHHHHHHHHHH IHHHHHHHHHHHHHHHHHHHH 000000000000
65. quence peptide 400 33 Trp Asn Ser Gln Lys Asp Ile Leu Glu Gin Ala Arg Ala 5 10 Q10 34 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 34 Trp Asn Ser Gln Lys Asp Leu Leu Glu Gln Arg Arg Ala 5 10 lt 210 gt 35 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence 10 20 30 56 J P WO2003 033538 A1 2003 4 24 lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 35 Trp Asn Ser Gln Lys Asp Leu Leu Glu Gln Ala Arg Ala b 0 lt 210 gt 36 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 36 Trp Asn Ser Gln Lys Asp Leu Leu Glu Gln Lys Arg Gly 5 10 210 37 lt 211 gt 13 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide 10 20 30 57 J P VO2003 033538 1 2003 4 24 400 37 Trp Asn Ser Gln Lys Asp Leu Leu Glu Asp Arg Arg Ala 5 10 lt 210 gt 38 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 38 Trp Asn Ser Gln Lys Asp Leu Leu Glu Arg Arg Arg Ala 5 10 lt 210 gt 39 2112 13 lt 212 gt PRT lt 213 gt Artificial Sequence 220 4223 Description of Artificial Sequence pep
66. t 210 gt 51 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence 220 223 Description of Artificial Sequence peptide lt 400 gt 51 Asn Ser Lys Asp Leu Leu Glu Gin Arg Ala Ala l 5 10 lt 210 gt 52 lt 211 gt 13 lt 212 gt lt 213 gt Artificial Sequence 220 4223 Description of Artificial Sequence peptide 400 52 Gly Asp Thr Arg Pro Arg Phe Leu Trp Gln Pro Lys Arg l 9 10 lt 210 gt 53 lt 211 gt 13 lt 212 gt PRT 10 20 30 64 J P VO2003 033538 A1 2003 4 24 lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 53 Thr Arg Pro Arg Phe Leu Trp Gin Pro Lys Arg Glu Cys 1 5 10 lt 210 gt 54 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 54 Pro Arg Phe Leu Trp Gln Pro Lys Arg Glu Cys His Phe 5 10 lt 210 gt 55 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 2202 10 20 30 65 J P VO2003 033538 A1 2003 4 24 4223 Description of Artificial Sequence peptide lt 400 gt 55 Phe Leu Trp Gln Pro Lys Arg Glu Cys His Phe Phe Asn 5 10 lt 210 56 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence 220 4223 Description of Artificial Sequence peptide lt 400 gt 56 Trp Gln Pro Lys Arg Glu Cys His Phe Phe Asn Gly Thr
67. tc tgtgagtggt ttctatccag ttcctgaacg gccaggaaga gaaggctggg atggtgtcca gactggacct tccagaccci ggtgatgctg gaaacagttc tggagcaccc aagcgtgaca tctgaatctg cacagagcaa gatgctgagt ggagtcgggg ttccttgggg ccgggctgtt catctacttc aggaatcaga ccaacaggat tectgagctg a lt 210 gt 147 lt 211 gt 266 lt 212 gt PRT lt 213 gt Homo sapiens lt 400 gt 147 Met Val Cys Leu Lys Leu Pro 5 Val Thr Leu Met Val Leu Ser 20 Arg Pro Arg Phe Leu Trp 35 Gly Thr Glu Arg Val Arg Phe 50 55 Ser Val Arg Phe Asp Ser Gly Gly Ser Cys 10 Ser Pro Leu Ala 25 Pro Lys Arg Glu 40 Leu Asp Arg Asp Val Gly Glu JP VO2003 033538 Al 2003 4 24 agacecagee cclgcagcac gcagcatlga agtcaggtgg caggcctgat ccagaatgga Clcgaagtgg agaggittac cagtggaatg gagagcacgg gct tgtgct gggcctgctc aaggacactc ggacttcag Met Thr Ala Leu fhr 15 Leu Ser Gly Asp Thr 30 Cys His Phe Phe Asn 45 Phe Tyr Asn Glu 60 Phe Arg Ala Val Thr 420 480 540 600 10 20 30 65 Leu Thr Val 145 Phe Val Val Leu Gly Arg Pro Glu Gln Val Val 115 Val Cys Leu Asn Gln Asn Ala 100 Glu Pro Val Gly Gly 180 Pro Arg Ser 195 Thr Ser 210 Pro 85 ATE Ser Ser Ser 165 Asp Leu 10 Asp Ala Ala Ala Phe Thr Lys Thr 135 Gly Phe 150 Glu Glu Trp Thr Glu Val Thr Val
68. tide 400 39 Trp Asn Ser Gin Lys Asp Leu Leu Glu Asp Glu Arg Ala l 5 10 10 20 30 58 J P VO2003 033538 1 2003 4 24 lt 210 gt 40 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 40 Trp Asn Ser Gin Lys Asp Ala Leu Glu Gln Arg Arg Ala 1 5 10 lt 210 gt 41 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 41 Trp Asn Ser Lys Asp Leu Leu Glu Ala Arg Arg Ala 5 10 lt 210 gt 42 10 20 30 59 J P WO2003 033538 1 2003 4 24 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 223 Description of Artificial Sequence peptide 400 42 Trp Asn Ser Gln Lys Asp Leu Leu Glu Gln Ala Arg Ala l 5 10 lt 210 gt 43 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 43 Asn Ser Gin Lys Asp Leu Leu Glu Gln Arg Arg Gly 1 5 10 lt 210 gt 44 lt 211 gt 13 42122 PRT lt 213 gt Artificial Sequence 10 20 30 60 J P WO2003 033538 A1 2003 4 24 lt 220 gt lt 223 gt Description of Artificial Sequence peptide lt 400 gt 44 Ala Asn Ser Gln Lys Asp Leu Leu Glu Gin Arg Arg Ala 5 10 lt 210 gt 45 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artific
69. u Gin Ala Arg Ala 5 10 lt 210 gt 28 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 223 Description of Artificial Sequence peptide lt 400 gt 28 10 20 30 53 J P VO2003 033538 A1 2003 4 24 Trp Asn Ser Gln Lys Asp Leu Glu Asp Glu Arg Ala 1 5 10 lt 210 gt 29 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide lt 400 gt 29 Trp Asn Ser Gln Lys Asp Leu Glu Gln Lys Arg Gly l 5 10 lt 210 gt 30 lt 211 gt 13 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 223 Description of Artificial Sequence peptide lt 400 gt 30 Trp Asn Ser Gln Lys Asp Ile Leu Glu Asp Arg Arg Ala 1 5 10 10 20 30 54 J P 02003 033538 1 2003 4 24 lt 210 gt 31 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence 4220 4223 Description Artificial Sequence peptide lt 400 gt 31 Trp Asn Ser Gln Lys Asp Ile Leu Glu Asp Arg Arg Gly l 5 10 lt 210 gt 32 lt 211 gt 13 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt 4223 Description of Artificial Sequence peptide 400 32 Trp Asn Ser Gln Lys Asp Ile Leu Glu Asp Lys Arg Ala l 5 10 lt 210 gt 33 lt 211 gt 18 10 20 30 55 J P VO2003 033538 A1 2003 4 24 lt 212 gt PRT lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Se
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