ME02862B - Protutijela protiv cgrp - Google Patents
Protutijela protiv cgrpInfo
- Publication number
- ME02862B ME02862B MEP-2017-280A MEP2017280A ME02862B ME 02862 B ME02862 B ME 02862B ME P2017280 A MEP2017280 A ME P2017280A ME 02862 B ME02862 B ME 02862B
- Authority
- ME
- Montenegro
- Prior art keywords
- ser
- val
- thr
- gly
- leu
- Prior art date
Links
- 108090000932 Calcitonin Gene-Related Peptide Proteins 0.000 title claims 9
- 102100025588 Calcitonin gene-related peptide 1 Human genes 0.000 title claims 9
- 125000003275 alpha amino acid group Chemical group 0.000 claims 8
- 239000000427 antigen Substances 0.000 claims 2
- 102000036639 antigens Human genes 0.000 claims 2
- 108091007433 antigens Proteins 0.000 claims 2
- 239000012634 fragment Substances 0.000 claims 2
- 208000019695 Migraine disease Diseases 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- BYYNJRSNDARRBX-YFKPBYRVSA-N Gly-Gln-Gly Chemical compound NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O BYYNJRSNDARRBX-YFKPBYRVSA-N 0.000 description 22
- YUJLIIRMIAGMCQ-CIUDSAMLSA-N Ser-Leu-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YUJLIIRMIAGMCQ-CIUDSAMLSA-N 0.000 description 21
- PDIDTSZKKFEDMB-UWVGGRQHSA-N Lys-Pro-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O PDIDTSZKKFEDMB-UWVGGRQHSA-N 0.000 description 19
- 108010073472 leucyl-prolyl-proline Proteins 0.000 description 17
- BMKNXTJLHFIAAH-CIUDSAMLSA-N Ser-Ser-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O BMKNXTJLHFIAAH-CIUDSAMLSA-N 0.000 description 16
- 241000880493 Leptailurus serval Species 0.000 description 15
- PRKWBYCXBBSLSK-GUBZILKMSA-N Pro-Ser-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O PRKWBYCXBBSLSK-GUBZILKMSA-N 0.000 description 15
- MNYNCKZAEIAONY-XGEHTFHBSA-N Thr-Val-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O MNYNCKZAEIAONY-XGEHTFHBSA-N 0.000 description 15
- 108010092854 aspartyllysine Proteins 0.000 description 15
- OYTPNWYZORARHL-XHNCKOQMSA-N Gln-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)N)N OYTPNWYZORARHL-XHNCKOQMSA-N 0.000 description 13
- ISJWBVIYRBAXEB-CIUDSAMLSA-N Arg-Ser-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(O)=O ISJWBVIYRBAXEB-CIUDSAMLSA-N 0.000 description 12
- NVTPVQLIZCOJFK-FOHZUACHSA-N Gly-Thr-Asp Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O NVTPVQLIZCOJFK-FOHZUACHSA-N 0.000 description 12
- PMGDADKJMCOXHX-UHFFFAOYSA-N L-Arginyl-L-glutamin-acetat Natural products NC(=N)NCCCC(N)C(=O)NC(CCC(N)=O)C(O)=O PMGDADKJMCOXHX-UHFFFAOYSA-N 0.000 description 12
- TYYLDKGBCJGJGW-UHFFFAOYSA-N L-tryptophan-L-tyrosine Natural products C=1NC2=CC=CC=C2C=1CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 TYYLDKGBCJGJGW-UHFFFAOYSA-N 0.000 description 12
- JFWDJFULOLKQFY-QWRGUYRKSA-N Ser-Gly-Phe Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JFWDJFULOLKQFY-QWRGUYRKSA-N 0.000 description 12
- UIGMAMGZOJVTDN-WHFBIAKZSA-N Ser-Gly-Ser Chemical compound OC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O UIGMAMGZOJVTDN-WHFBIAKZSA-N 0.000 description 12
- FQPDRTDDEZXCEC-SVSWQMSJSA-N Thr-Ile-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O FQPDRTDDEZXCEC-SVSWQMSJSA-N 0.000 description 12
- BIBYEFRASCNLAA-CDMKHQONSA-N Thr-Phe-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=CC=C1 BIBYEFRASCNLAA-CDMKHQONSA-N 0.000 description 12
- MBLJBGZWLHTJBH-SZMVWBNQSA-N Trp-Val-Arg Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)=CNC2=C1 MBLJBGZWLHTJBH-SZMVWBNQSA-N 0.000 description 12
- QUILOGWWLXMSAT-IHRRRGAJSA-N Tyr-Gln-Gln Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O QUILOGWWLXMSAT-IHRRRGAJSA-N 0.000 description 12
- 108010069020 alanyl-prolyl-glycine Proteins 0.000 description 12
- 108010008355 arginyl-glutamine Proteins 0.000 description 12
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 12
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 12
- 108010044292 tryptophyltyrosine Proteins 0.000 description 12
- OYJCVIGKMXUVKB-GARJFASQSA-N Ala-Leu-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N OYJCVIGKMXUVKB-GARJFASQSA-N 0.000 description 11
- CREYEAPXISDKSB-FQPOAREZSA-N Ala-Thr-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CREYEAPXISDKSB-FQPOAREZSA-N 0.000 description 11
- COXMUHNBYCVVRG-DCAQKATOSA-N Arg-Leu-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O COXMUHNBYCVVRG-DCAQKATOSA-N 0.000 description 11
- XYBJLTKSGFBLCS-QXEWZRGKSA-N Asp-Arg-Val Chemical compound NC(N)=NCCC[C@@H](C(=O)N[C@@H](C(C)C)C(O)=O)NC(=O)[C@@H](N)CC(O)=O XYBJLTKSGFBLCS-QXEWZRGKSA-N 0.000 description 11
- QNFRBNZGVVKBNJ-PEFMBERDSA-N Asp-Ile-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)O)N QNFRBNZGVVKBNJ-PEFMBERDSA-N 0.000 description 11
- MNQMTYSEKZHIDF-GCJQMDKQSA-N Asp-Thr-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O MNQMTYSEKZHIDF-GCJQMDKQSA-N 0.000 description 11
- BYLPQJAWXJWUCJ-YDHLFZDLSA-N Asp-Tyr-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O BYLPQJAWXJWUCJ-YDHLFZDLSA-N 0.000 description 11
- NSNUZSPSADIMJQ-WDSKDSINSA-N Gln-Gly-Asp Chemical compound NC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O NSNUZSPSADIMJQ-WDSKDSINSA-N 0.000 description 11
- YMUFWNJHVPQNQD-ZKWXMUAHSA-N Gly-Ala-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)CN YMUFWNJHVPQNQD-ZKWXMUAHSA-N 0.000 description 11
- GBYYQVBXFVDJPJ-WLTAIBSBSA-N Gly-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)CN)O GBYYQVBXFVDJPJ-WLTAIBSBSA-N 0.000 description 11
- USTCFDAQCLDPBD-XIRDDKMYSA-N Leu-Asn-Trp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N USTCFDAQCLDPBD-XIRDDKMYSA-N 0.000 description 11
- CQGSYZCULZMEDE-UHFFFAOYSA-N Leu-Gln-Pro Natural products CC(C)CC(N)C(=O)NC(CCC(N)=O)C(=O)N1CCCC1C(O)=O CQGSYZCULZMEDE-UHFFFAOYSA-N 0.000 description 11
- FEHQLKKBVJHSEC-SZMVWBNQSA-N Leu-Glu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC(C)C)C(O)=O)=CNC2=C1 FEHQLKKBVJHSEC-SZMVWBNQSA-N 0.000 description 11
- SJDQOYTYNGZZJX-SRVKXCTJSA-N Met-Glu-Leu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O SJDQOYTYNGZZJX-SRVKXCTJSA-N 0.000 description 11
- SPSSJSICDYYTQN-HJGDQZAQSA-N Met-Thr-Gln Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCC(N)=O SPSSJSICDYYTQN-HJGDQZAQSA-N 0.000 description 11
- UQFYNFTYDHUIMI-WHFBIAKZSA-N Ser-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CO UQFYNFTYDHUIMI-WHFBIAKZSA-N 0.000 description 11
- GJFYFGOEWLDQGW-GUBZILKMSA-N Ser-Leu-Gln Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CO)N GJFYFGOEWLDQGW-GUBZILKMSA-N 0.000 description 11
- AZWNCEBQZXELEZ-FXQIFTODSA-N Ser-Pro-Ser Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O AZWNCEBQZXELEZ-FXQIFTODSA-N 0.000 description 11
- LGIMRDKGABDMBN-DCAQKATOSA-N Ser-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CO)N LGIMRDKGABDMBN-DCAQKATOSA-N 0.000 description 11
- GXUWHVZYDAHFSV-FLBSBUHZSA-N Thr-Ile-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GXUWHVZYDAHFSV-FLBSBUHZSA-N 0.000 description 11
- VOCHZIJXPRBVSI-XIRDDKMYSA-N Trp-Met-Gln Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N VOCHZIJXPRBVSI-XIRDDKMYSA-N 0.000 description 11
- QOIKZODVIPOPDD-AVGNSLFASA-N Tyr-Cys-Gln Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(O)=O QOIKZODVIPOPDD-AVGNSLFASA-N 0.000 description 11
- KSGKJSFPWSMJHK-JNPHEJMOSA-N Tyr-Tyr-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KSGKJSFPWSMJHK-JNPHEJMOSA-N 0.000 description 11
- JQTYTBPCSOAZHI-FXQIFTODSA-N Val-Ser-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N JQTYTBPCSOAZHI-FXQIFTODSA-N 0.000 description 11
- 108010087924 alanylproline Proteins 0.000 description 11
- 108010090037 glycyl-alanyl-isoleucine Proteins 0.000 description 11
- 108010015792 glycyllysine Proteins 0.000 description 11
- 108010038320 lysylphenylalanine Proteins 0.000 description 11
- 108010003137 tyrosyltyrosine Proteins 0.000 description 11
- ARHJJAAWNWOACN-FXQIFTODSA-N Ala-Ser-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O ARHJJAAWNWOACN-FXQIFTODSA-N 0.000 description 10
- AOHKLEBWKMKITA-IHRRRGAJSA-N Arg-Phe-Ser Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N AOHKLEBWKMKITA-IHRRRGAJSA-N 0.000 description 10
- SZQCDCKIGWQAQN-FXQIFTODSA-N Cys-Arg-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O SZQCDCKIGWQAQN-FXQIFTODSA-N 0.000 description 10
- ZHHLTWUOWXHVQJ-YUMQZZPRSA-N His-Ser-Gly Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CO)C(=O)NCC(=O)O)N ZHHLTWUOWXHVQJ-YUMQZZPRSA-N 0.000 description 10
- MVJRBCJCRYGCKV-GVXVVHGQSA-N Leu-Val-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O MVJRBCJCRYGCKV-GVXVVHGQSA-N 0.000 description 10
- UWKNTTJNVSYXPC-CIUDSAMLSA-N Lys-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN UWKNTTJNVSYXPC-CIUDSAMLSA-N 0.000 description 10
- SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 10
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 10
- WPTYDQPGBMDUBI-QWRGUYRKSA-N Phe-Gly-Asn Chemical compound N[C@@H](Cc1ccccc1)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O WPTYDQPGBMDUBI-QWRGUYRKSA-N 0.000 description 10
- ZOHGLPQGEHSLPD-FXQIFTODSA-N Ser-Gln-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O ZOHGLPQGEHSLPD-FXQIFTODSA-N 0.000 description 10
- HVHJYXDXRIWELT-RYUDHWBXSA-N Tyr-Glu-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O HVHJYXDXRIWELT-RYUDHWBXSA-N 0.000 description 10
- SSYBNWFXCFNRFN-GUBZILKMSA-N Val-Pro-Ser Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O SSYBNWFXCFNRFN-GUBZILKMSA-N 0.000 description 10
- OWFGFHQMSBTKLX-UFYCRDLUSA-N Val-Tyr-Tyr Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O)N OWFGFHQMSBTKLX-UFYCRDLUSA-N 0.000 description 10
- 108010086434 alanyl-seryl-glycine Proteins 0.000 description 10
- 108010089804 glycyl-threonine Proteins 0.000 description 10
- 108010037850 glycylvaline Proteins 0.000 description 10
- 108010038745 tryptophylglycine Proteins 0.000 description 10
- ZFBBMCKQSNJZSN-AUTRQRHGSA-N Gln-Val-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZFBBMCKQSNJZSN-AUTRQRHGSA-N 0.000 description 9
- ZYRXTRTUCAVNBQ-GVXVVHGQSA-N Glu-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N ZYRXTRTUCAVNBQ-GVXVVHGQSA-N 0.000 description 9
- LKACSKJPTFSBHR-MNXVOIDGSA-N Ile-Gln-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N LKACSKJPTFSBHR-MNXVOIDGSA-N 0.000 description 9
- IXHKPDJKKCUKHS-GARJFASQSA-N Lys-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCCN)N IXHKPDJKKCUKHS-GARJFASQSA-N 0.000 description 9
- AIRZWUMAHCDDHR-KKUMJFAQSA-N Lys-Leu-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O AIRZWUMAHCDDHR-KKUMJFAQSA-N 0.000 description 9
- 108010050848 glycylleucine Proteins 0.000 description 9
- WGDNWOMKBUXFHR-BQBZGAKWSA-N Ala-Gly-Arg Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N WGDNWOMKBUXFHR-BQBZGAKWSA-N 0.000 description 8
- 108010065920 Insulin Lispro Proteins 0.000 description 8
- MPUMPERGHHJGRP-WEDXCCLWSA-N Thr-Gly-Lys Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)O)N)O MPUMPERGHHJGRP-WEDXCCLWSA-N 0.000 description 8
- BPGDJSUFQKWUBK-KJEVXHAQSA-N Thr-Val-Tyr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 BPGDJSUFQKWUBK-KJEVXHAQSA-N 0.000 description 8
- 108010068265 aspartyltyrosine Proteins 0.000 description 8
- 108010069117 seryl-lysyl-aspartic acid Proteins 0.000 description 8
- BPIMVBKDLSBKIJ-FCLVOEFKSA-N Phe-Thr-Phe Chemical compound C([C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 BPIMVBKDLSBKIJ-FCLVOEFKSA-N 0.000 description 7
- YOOAQCZYZHGUAZ-KATARQTJSA-N Thr-Leu-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YOOAQCZYZHGUAZ-KATARQTJSA-N 0.000 description 7
- 108010077435 glycyl-phenylalanyl-glycine Proteins 0.000 description 7
- 108010010147 glycylglutamine Proteins 0.000 description 7
- 108010051242 phenylalanylserine Proteins 0.000 description 7
- JXFLPKSDLDEOQK-JHEQGTHGSA-N Gln-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCC(N)=O JXFLPKSDLDEOQK-JHEQGTHGSA-N 0.000 description 6
- IESFZVCAVACGPH-PEFMBERDSA-N Glu-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CCC(O)=O IESFZVCAVACGPH-PEFMBERDSA-N 0.000 description 6
- JYGYNWYVKXENNE-OALUTQOASA-N Gly-Tyr-Trp Chemical compound [H]NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O JYGYNWYVKXENNE-OALUTQOASA-N 0.000 description 6
- ULVMNZOKDBHKKI-ACZMJKKPSA-N Ser-Gln-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O ULVMNZOKDBHKKI-ACZMJKKPSA-N 0.000 description 6
- WBINSDOPZHQPPM-AVGNSLFASA-N Ser-Glu-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)N)O WBINSDOPZHQPPM-AVGNSLFASA-N 0.000 description 6
- BDMWLJLPPUCLNV-XGEHTFHBSA-N Ser-Thr-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O BDMWLJLPPUCLNV-XGEHTFHBSA-N 0.000 description 6
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Classifications
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/26—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against hormones ; against hormone releasing or inhibiting factors
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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- C07K14/575—Hormones
- C07K14/57527—Calcitonin gene related peptide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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- A—HUMAN NECESSITIES
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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- C07K14/575—Hormones
- C07K14/57545—Neuropeptide Y
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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- C07K14/575—Hormones
- C07K14/57563—Vasoactive intestinal peptide [VIP]; Related peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
- C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
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- C07K2317/565—Complementarity determining region [CDR]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Landscapes
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Immunology (AREA)
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- Gastroenterology & Hepatology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
<br>SPISAK SLJEDOVA <br><ll o=""> Eli Lilly and Company <br><120> PROTUTIJELA PROTIV CGRP <br><130> X- 18827 <br><150> 61/353323 <br><151> 2010 - 06 - 10 <br><160> 43 <br><170> Patent In verzija 3 . 5 <br><210> l <br><2ll> 37 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> l <br>Ala Cys Asp Thr Ala Thr Cys Val Thr His Arg Leu Ala Gly Leu Leu <br>l 5 10 15 <br>Ser Arg Ser Gly Gly Val Val Lys Asn Asn Phe Val Pro Thr Asn Val <br>20 25 30 <br>Gly Ser Lys Al a Phe <br>35 <br><210> 2 <br><2ll> 37 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 2 <br>Ala Cys Asn Thr Ala Thr Cys Val Thr His Arg Leu Ala Gly Leu Leu <br>l 5 10 15 <br>Ser Arg Ser Gly Gly Met Val Lys Ser Asn Phe Val Pro Thr Asn Val <br>20 25 30 <br>Gly Ser Lys Ala Phe <br>35 <br>EP 2 579 894 B l ME 11 3448 <br><210> 3 <br><2ll> ll <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 3 <br>Arg Ala Ser Gln Asp Ile Asp Asn Tyr Leu Asn <br>l 5 10 <br><210> 4 <br><2ll> 7 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 4 <br>Tyr Thr Ser Glu Tyr His Ser <br>l 5 <br><210> 5 <br><2ll> 9 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sint etski konstrukt <br><400> 5 <br>Gln Gln Gly Asp Ala Leu Pro Pro Thr <br>l 5 <br><210> 6 <br><2ll> ll <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 6 <br>Arg Ala Ser Lys Asp Ile Ser Lys Tyr Leu Asn <br>l 5 10 <br><210> 7 <br><2ll> 7 <br><212> PRT <br><213> Umjetni slijed <br>2 <br>EP 2 579 894 Bl ME 113448 EP 2 579 894 B l <br><220> <br><223> Sintetski konstrukt <br><400> 7 <br>Tyr Thr Ser Gly Tyr His Ser <br>l 5 <br><210> 8 <br><2ll> ll <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 8 <br>Arg Ala Ser Arg Pro I l e Asp Lys Tyr Leu Asn <br>l 5 10 <br><210> 9 <br><2ll> ll <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 9 <br>Arg Ala Ser Gln Asp Il e Asp Lys Tyr Leu Asn <br>l 5 1 0 <br><210> lO <br><2ll> ll <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><220> <br><22 1> Miješana svojstva <br><222> ( 4) . . ( 4) <br><223> X aa na položaju 4 je Gl n , Arg ili Lys <br><220> <br><221> Miješana svojstva <br><222> (5) •• (5) <br><223> X aa na položaj u 5 je As p ili Pro <br><220> <br><221> Miješana svojstva <br><222> ( 7) . . (7) <br><223> X aa na položaju 7 je As p ili Ser <br>3 ME 113448 <br><220> <br><221> Miješana svojstva <br><222> (8) . . (8) <br><223> Xaa na položaju B je Asn ili Lys <br><400> 10 <br>Arg Ala Ser Xaa Xaa Ile Xaa Xaa Tyr Leu Asn <br>l 5 10 <br><210> ll <br><2ll> 7 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><220> <br><221> Miješana svojstva <br><222> (4) .. (4) <br><223> Xaa na položaju 4 je Gly ili Glu <br><4 OO> ll <br>Tyr Thr Ser Xaa Tyr His Ser <br>l 5 <br><210> 12 <br><2ll> lO <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 12 <br>Gly Tyr Thr Phe Gl y Asn Tyr Trp Met Gln <br>l 5 10 <br><210> 13 <br><2ll> 17 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 13 <br>Ala Ile Tyr Glu Gly Thr Gly Asp Thr Arg Tyr Ile Gln Lys Phe Ala <br>l 5 10 15 <br>Gly <br>4 <br>EP 2 579 894 B l ME 113448 <br><210> 14 <br><211> 10 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 14 <br>Leu Ser Asp Tyr Val Ser Gly Phe Ser Tyr <br>l 5 10 <br><210> 15 <br><211> 17 <br><212> PRT <br><213> Umjetni slij ed <br><220> <br><223> Sintetski konstrukt <br><400> 15 <br>Ala Ile Tyr Glu Gly Thr Gly Lys Thr Val Tyr Ile Gl n Lys Phe Ala <br>l 5 10 15 <br>Gly <br><210> 16 <br><211> 17 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 16 <br>Al a Ile Tyr Glu Gly Thr Gly Lys Thr Val Tyr Ile Gln Lys Phe Ala <br>l 5 10 15 <br>As p <br><210> 17 <br><211> 107 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 17 <br>5 <br>EP 2 579 894 B l ME 113448 EP 2 579 894 Bl <br>Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly <br>l 5 10 15 <br>Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Asp Asn Tyr <br>20 25 30 <br>Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile <br>35 40 45 <br>Tyr Tyr Thr Ser Glu Tyr His Ser Gly Val Pro Ser Arg Phe Ser Gly <br>50 55 60 <br>Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro <br>65 70 75 80 <br>Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ala Leu Pro Pro <br>85 90 95 <br>Thr Phe Gl y Gln Gl y Thr Lys Leu Glu Ile Lys <br>100 105 <br><210> 18 <br><211> 107 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 18 <br>Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly <br>l 5 10 15 <br>Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Asp Asn Tyr <br>20 25 30 <br>Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile <br>35 40 45 <br>Tyr Tyr Thr Ser Glu Tyr His Ser Gly Val Pro Ser Arg Phe Ser Gly <br>50 55 60 <br>Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro <br>65 70 75 80 <br>Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ala Leu Pro Pro <br>85 90 95 <br>6 ME 11 3448 EP 2 579 894 Bl <br>Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys <br>100 10 5 <br><210> 19 <br><211> 107 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 19 <br>Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly <br>l 5 10 15 <br>Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Lys Asp Ile Ser Lys Tyr <br>20 25 30 <br>Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile <br>35 40 45 <br>Tyr Tyr Thr Ser Gly Tyr His Ser Gly Val Pro Ser Arg Phe Ser Gly <br>50 55 60 <br>Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro <br>65 70 75 80 <br>Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ala Leu Pro Pro <br>85 90 95 <br>Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys <br>100 105 <br><210> 20 <br><211> 107 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 20 <br>Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly <br>l 5 10 15 <br>Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Arg Pro Ile Asp Lys Tyr <br>20 25 30 <br>7 ME 113448 <br>Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile <br>35 40 45 <br>Tyr Tyr Thr Ser Glu Tyr His Ser Gly Val Pro Ser Arg Phe Ser Gly <br>50 55 60 <br>Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro <br>65 70 75 80 <br>Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ala Leu Pro Pro <br>85 90 95 <br>Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys <br>100 105 <br><210> 21 <br><211> 107 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 21 <br>Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Al a Ser Val Gly <br>l 5 10 15 <br>Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Il e Asp Lys Tyr <br>20 25 30 <br>Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Al a Pro Lys Leu Leu Ile <br>35 40 45 <br>Tyr Tyr Thr Ser Gly Tyr His Ser Gly Val Pro Ser Arg Phe Ser Gl y <br>50 55 60 <br>Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro <br>65 70 75 80 <br>Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ala Leu Pro Pro <br>85 90 95 <br>Thr Phe Gly Gly Gly Thr Lys Va l Glu Ile Lys <br><210> 22 <br><211> 119 <br><212> PRT <br>100 105 <br>8 <br>EP 2 579 894 Bl ME 11 3448 <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 22 <br>Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala <br>l 5 10 15 <br>Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Gly Asn Tyr <br>20 25 30 <br>Trp Met Gln Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met <br>35 40 45 <br>Gly Ala Ile Tyr Gl u Gly Thr Gly Asp Thr Arg Tyr Ile Gln Lys Phe <br>50 55 60 <br>Ala Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr <br>65 70 75 80 <br>Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys <br>85 90 95 <br>Ala Arg Leu Ser Asp Tyr Val Ser Gly Phe Ser Tyr Trp Gly Gln Gly <br>100 105 110 <br>Thr Leu Val Thr Val Ser Ser <br>115 <br><210> 23 <br><211> 119 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 23 <br>Gln Val Gln Leu Val Gln Ser Gly Ala Gl u Val Lys Lys Pro Gly Ala <br>l 5 10 15 <br>Ser Val Lys Val Ser Cys Lys Al a Ser Gly Tyr Thr Phe Gly Asn Tyr <br>20 25 30 <br>Trp Met Gln Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met <br>35 40 45 <br>9 <br>EP 2 579 894 Bl ME 11 3448 <br>Gly Ala Ile Tyr Glu Gly Thr Gly Lys Thr Val Tyr Ile Gln Lys Phe <br>so ss 60 <br>Ala Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr <br>6S 70 7S 80 <br>Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys <br>8S 90 9S <br>Ala Arg Leu Ser Asp Tyr Val Ser Gly Phe Ser Tyr Trp Gly Gln Gly <br>100 lOS 110 <br>Thr Leu Val Thr Val Ser Ser <br>11S <br><210> 24 <br><211> 119 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 24 <br>Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser <br>l s 10 lS <br>Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Gly Asn Tyr <br>20 2S 30 <br>Trp Met Gln Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met <br>3S 40 4S <br>Gly Ala Ile Tyr Glu Gly Thr Gly Lys Thr Val Tyr Ile Gln Lys Phe <br>so ss 60 <br>Ala Asp Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr <br>6S 70 7S 80 <br>Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Va l Tyr Tyr Cys <br>8S 90 9S <br>Ala Arg Leu Ser Asp Tyr Val Ser Gly Phe Gly Tyr Trp Gly Gln Gly <br>100 lOS 110 <br>Thr Thr Val Thr Val Ser Ser <br>11S <br>JO <br>EP 2 579 894 B l ME 11 3448 <br><210> 25 <br><211> 119 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 25 <br>Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala <br>l 5 10 15 <br>Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Gly Asn Tyr <br>20 25 30 <br>Trp Met Gln Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met <br>35 40 45 <br>Gly Ala Ile Tyr Glu Gly Thr Gly Lys Thr Val Tyr Ile Gln Lys Phe <br>50 55 60 <br>Ala Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr <br>65 70 75 80 <br>Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys <br>85 90 95 <br>Ala Arg Leu Ser Asp Tyr Val Ser Gly Phe Gly Tyr Trp Gly Gln Gly <br>100 105 110 <br>Thr Leu Val Thr Val Ser Ser <br>115 <br><210> 26 <br><211> 119 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 26 <br>Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser <br>l 5 10 15 <br>Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Gly Asn Tyr <br>20 25 30 <br>l l <br>EP 2 579 894 Bl M E 113448 <br>Trp Met Gln Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met <br>35 40 45 <br>Gly Ala Ile Tyr Glu Gly Thr Gly Lys Thr Val Tyr Ile Gln Lys Phe <br>50 55 60 <br>Ala Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr <br>65 70 75 80 <br>Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys <br>85 90 95 <br>Ala Arg Leu Ser Asp Tyr Val Ser Gly Phe Gly Tyr Trp Gly Gln Gly <br>100 105 110 <br>Thr Thr Val Thr Val Ser Ser <br>115 <br><210> 27 <br><211> 214 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 27 <br>Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly <br>l 5 10 15 <br>Asp Arg Va l Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Asp Asn Tyr <br>20 25 30 <br>Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile <br>35 40 45 <br>Tyr Tyr Thr Ser Glu Tyr His Ser Gly Val Pro Ser Arg Phe Ser Gly <br>50 55 60 <br>Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro <br>65 70 75 80 <br>Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ala Leu Pro Pro <br>85 90 95 <br>Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala <br>100 105 110 <br>1 2 <br>EP 2 579 894 Bl ME 11 3448 <br>Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly <br>115 120 125 <br>Thr Ala Ser Val Va l Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala <br>130 135 140 <br>Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln <br>145 150 155 160 <br>Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser <br>165 170 175 <br>Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr <br>180 185 190 <br>Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser <br>195 200 205 <br>Phe Asn Arg Gly Glu Cys <br>210 <br><210> 28 <br><211> 214 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 28 <br>Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly <br>l 5 10 15 <br>Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Asp Asn Tyr <br>20 25 30 <br>Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Il e <br>35 40 45 <br>Tyr Tyr Thr Ser Glu Tyr His Ser Gly Val Pro Ser Arg Phe Ser Gly <br>50 55 60 <br>Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro <br>65 70 75 80 <br>Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ala Leu Pro Pro <br>85 90 95 <br>13 <br>EP 2 579 894 B l ME 11 3448 <br>Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala <br>100 105 110 <br>Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly <br>115 120 125 <br>Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala <br>130 135 140 <br>Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln <br>145 150 155 160 <br>Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser <br>165 170 175 <br>Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr <br>180 185 190 <br>Ala Cys Gl u Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser <br>195 200 205 <br>Phe Asn Arg Gly Glu Cys <br>210 <br><210> 29 <br><211> 21 4 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 29 <br>Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly <br>l 5 10 15 <br>Asp Arg Va l Thr Ile Thr Cys Arg Ala Ser Lys Asp Ile Ser Lys Tyr <br>20 25 30 <br>Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile <br>35 40 45 <br>Tyr Tyr Thr Ser Gly Tyr His Ser Gly Val Pro Ser Arg Phe Ser Gly <br>50 55 60 <br>Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro <br>14 <br>EP 2 579 894 Bl ME 113448 <br>65 70 75 80 <br>Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ala Leu Pro Pro <br>85 90 95 <br>Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala <br>100 105 110 <br>Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly <br>115 120 125 <br>Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala <br>130 135 140 <br>Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln <br>145 150 155 160 <br>Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser <br>165 170 175 <br>Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr <br>180 185 190 <br>Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser <br>195 200 205 <br>Phe Asn Arg Gly Glu Cys <br>210 <br><210> 30 <br><211> 214 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 30 <br>Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly <br>l 5 10 15 <br>Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Arg Pro Ile Asp Lys Tyr <br>20 25 30 <br>Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile <br>35 40 45 <br>15 <br>EP 2 579 894 Bl ME 11 3448 <br>Tyr Tyr Thr Ser Glu Tyr His Ser Gly Val Pro Ser Arg Phe Ser Gly <br>50 55 60 <br>Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro <br>65 70 75 80 <br>Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ala Leu Pro Pro <br>85 90 95 <br>Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala <br>100 105 110 <br>Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly <br>115 120 125 <br>Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala <br>130 135 140 <br>Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln <br>145 150 155 160 <br>Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser <br>165 170 175 <br>Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr <br>180 185 190 <br>Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Va l Thr Lys Ser <br>195 200 205 <br>Phe Asn Arg Gly Glu Cys <br>210 <br><210> 31 <br><211> 214 <br><212> PRT <br><213> Umje t ni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 31 <br>Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly <br>l 5 10 15 <br>Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Asp Lys Tyr <br>20 25 30 <br>16 <br>EP 2 579 894 Bl ME 11 3448 <br>Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile <br>35 40 45 <br>Tyr Tyr Thr Ser Gly Tyr His Ser Gly Val Pro Ser Arg Phe Ser Gly <br>50 55 60 <br>Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro <br>65 70 75 80 <br>Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ala Leu Pro Pro <br>85 90 95 <br>Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala <br>100 105 110 <br>Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly <br>115 120 125 <br>Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala <br>130 135 140 <br>Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln <br>145 150 155 160 <br>Glu Ser Val Thr Glu Gl n Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser <br>165 170 175 <br>Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr <br>180 185 190 <br>Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser <br>195 200 205 <br>Phe Asn Arg Gly Glu Cys <br>210 <br><210> 32 <br><211> 445 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 32 <br>Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala <br>l 5 10 15 <br>17 <br>EP 2 579 894 Bl ME 11 3448 <br>Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Gly Asn Tyr <br>20 25 30 <br>Trp Met Gln Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met <br>35 40 45 <br>Gly Ala Ile Tyr Glu Gly Thr Gly Asp Thr Arg Tyr Ile Gln Lys Phe <br>50 55 60 <br>Ala Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr <br>65 70 75 80 <br>Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys <br>85 90 95 <br>Ala Arg Leu Ser Asp Tyr Val Ser Gly Phe Ser Tyr Trp Gly Gln Gly <br>100 105 110 <br>Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe <br>115 120 125 <br>Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu <br>130 135 140 <br>Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp <br>145 150 155 160 <br>Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu <br>165 170 175 <br>Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser <br>180 185 190 <br>Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro <br>195 200 205 <br>Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro <br>210 215 220 <br>Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe <br>225 230 235 240 <br>Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro <br>245 250 255 <br>18 <br>EP 2 579 894 Bl ME 11 3448 <br>Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val <br>260 265 270 <br>Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr <br>275 280 285 <br>Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val <br>290 295 300 <br>Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys <br>305 310 315 320 <br>Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser <br>325 330 335 <br>Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro <br>340 345 350 <br>Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val <br>355 360 365 <br>Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly <br>370 375 380 <br>Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp <br>385 390 395 400 <br>Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp <br>405 410 415 <br>Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His <br>420 425 430 <br>Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gl y <br>435 440 445 <br><210> 33 <br><211> 445 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 33 <br>Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala <br>l 5 10 15 <br>19 <br>EP 2 579 894 Bl ME 11 3448 <br>Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Gly Asn Tyr <br>20 25 30 <br>Trp Met Gln Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met <br>35 40 45 <br>Gly Ala Ile Tyr Glu Gly Thr Gly Lys Thr Val Tyr Ile Gln Lys Phe <br>50 55 60 <br>Ala Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr <br>65 70 75 BO <br>Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys <br>85 90 95 <br>Ala Arg Leu Ser Asp Tyr Val Ser Gly Phe Ser Tyr Trp Gly Gln Gly <br>100 105 110 <br>Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe <br>115 120 125 <br>Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu <br>130 135 140 <br>Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp <br>145 150 155 160 <br>Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu <br>165 170 175 <br>Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser <br>180 185 190 <br>Ser Ser Leu Gl y Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro <br>195 200 205 <br>Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro <br>210 215 220 <br>Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe <br>225 230 235 240 <br>Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro <br>245 250 255 <br>20 <br>EP 2 579 894 Bl ME 11 3448 <br>Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val <br>260 265 270 <br>Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr <br>275 280 285 <br>Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val <br>290 295 300 <br>Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys <br>305 310 315 320 <br>Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser <br>325 330 335 <br>Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro <br>340 345 350 <br>Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val <br>355 360 365 <br>Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly <br>370 375 380 <br>Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp <br>385 390 395 400 <br>Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp <br>405 410 415 <br>Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His <br>420 425 430 <br>Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly <br>435 440 445 <br><210> 34 <br><211> 445 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 34 <br>Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser <br>l 5 10 15 <br>2 1 <br>EP 2 579 894 Bl ME 11 3448 <br>Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Gly Asn Tyr <br>20 25 30 <br>Trp Met Gln Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met <br>35 40 45 <br>Gly Ala Ile Tyr Glu Gly Thr Gly Lys Thr Val Tyr Ile Gln Lys Phe <br>50 55 60 <br>Ala Asp Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr <br>65 70 75 80 <br>Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys <br>85 90 95 <br>Ala Arg Leu Ser Asp Tyr Val Ser Gly Phe Gly Tyr Trp Gly Gln Gly <br>100 105 110 <br>Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe <br>115 120 125 <br>Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu <br>130 135 140 <br>Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp <br>145 150 155 160 <br>Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu <br>165 170 175 <br>Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser <br>180 185 190 <br>Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro <br>195 200 205 <br>Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro <br>210 215 220 <br>Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe <br>225 230 235 240 <br>Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro <br>245 250 255 <br>22 <br>EP 2 579 894 Bl ME 11 3448 <br>Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val <br>260 265 270 <br>Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr <br>275 280 285 <br>Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val <br>290 295 300 <br>Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys <br>305 310 315 320 <br>Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser <br>325 330 335 <br>Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro <br>340 345 350 <br>Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val <br>355 360 365 <br>Lys Gly Phe Tyr Pro Ser Asp I l e Ala Val Glu Trp Glu Ser Asn Gly <br>370 375 380 <br>Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp <br>385 390 395 400 <br>Gly Ser Ph e Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp <br>405 410 415 <br>Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His <br>420 425 430 <br>Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly <br>435 440 445 <br><210> 35 <br><211> 445 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 35 <br>Gln Val Gl n Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gl y Ala <br>l 5 10 15 <br>23 <br>EP 2 579 894 Bl ME 11 3448 <br>Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Gly Asn Tyr <br>20 25 30 <br>Trp Met Gln Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met <br>35 40 45 <br>Gly Ala Ile Tyr Glu Gly Thr Gly Lys Thr Val Tyr Ile Gln Lys Phe <br>50 55 60 <br>Ala Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr <br>65 70 75 80 <br>Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys <br>85 90 95 <br>Ala Arg Leu Ser Asp Tyr Val Ser Gly Phe Gly Tyr Trp Gly Gln Gly <br>100 105 110 <br>Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe <br>115 120 125 <br>Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu <br>130 135 140 <br>Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp <br>145 150 155 160 <br>Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu <br>165 170 175 <br>Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser <br>180 185 190 <br>Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro <br>195 200 205 <br>Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro <br>210 215 220 <br>Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe <br>225 230 235 240 <br>Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro <br>245 250 255 <br>24 <br>EP 2 579 894 B l ME 11 3448 <br>Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val <br>260 265 270 <br>Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr <br>275 280 285 <br>Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val <br>290 295 300 <br>Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys <br>305 310 315 320 <br>Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser <br>325 330 335 <br>Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro <br>340 345 350 <br>Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val <br>355 360 365 <br>Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly <br>370 375 380 <br>Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp <br>385 390 395 400 <br>Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp <br>405 410 415 <br>Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His <br>420 425 430 <br>Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly <br>435 440 445 <br><210> 36 <br><211> 445 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 36 <br>Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser <br>l 5 10 15 <br>25 <br>EP 2 579 894 Bl ME 11 3448 <br>Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Gly Asn Tyr <br>20 25 30 <br>Trp Met Gln Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met <br>35 40 45 <br>Gly Ala Ile Tyr Glu Gly Thr Gly Lys Thr Val Tyr Ile Gln Lys Phe <br>50 55 60 <br>Ala Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr <br>65 70 75 80 <br>Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys <br>85 90 95 <br>Ala Arg Leu Ser Asp Tyr Val Ser Gly Phe Gly Tyr Trp Gly Gln Gly <br>100 105 110 <br>Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe <br>115 120 125 <br>Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu <br>130 135 140 <br>Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp <br>145 150 155 160 <br>Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu <br>165 170 175 <br>Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser <br>180 185 190 <br>Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro <br>195 200 205 <br>Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro <br>210 215 220 <br>Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe <br>225 230 235 240 <br>Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro <br>245 250 255 <br>26 <br>EP 2 579 894 Bl ME 11 3448 <br>Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val <br>260 265 270 <br>Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr <br>275 280 285 <br>Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val <br>290 295 300 <br>Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys <br>305 310 315 320 <br>Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser <br>325 330 335 <br>Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro <br>340 345 350 <br>Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val <br>355 360 365 <br>Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly <br>370 375 380 <br>Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp <br>385 390 395 400 <br>Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp <br>405 410 415 <br>Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His <br>420 425 430 <br>Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly <br>435 440 445 <br><210> 37 <br><211> 17 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><220> <br><221> Miješana svojstva <br><222> (8) .. (8) <br><223> Xaa na položaju 8 je Lys ili Asp <br>27 <br>EP 2 579 894 Bl ME 11 3448 <br><220> <br><221> Miješana svojstva <br><222> (lO) o o (lO) <br><223> X aa na položaju lO je Val ili Arg <br><220> <br><221> Miješana svojstva <br><222> (17) o o (17) <br><223> X aa na položaju 17 je As p ili Gly <br><400> 37 <br>Ala Ile Tyr Glu Gly Thr Gly Xaa Thr Xaa Tyr Ile Gln Lys Phe Ala <br>l 5 10 15 <br>X aa <br><210> 38 <br><211> 10 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><220> <br><221> Miješana svojstva <br><222> (9) oo (9) <br><223> Xaa na položaju 9 je Gly ili Ser <br><400> 38 <br>Leu Ser Asp Tyr Val Ser Gly Phe Xaa Tyr <br>l 5 10 <br><210> 39 <br><211> lO <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><400> 39 <br>Leu Ser Asp Tyr Va l Ser Gly Phe Gly Tyr <br>l 5 10 <br><210> 40 <br><211> 107 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br>28 <br>EP 2 579 894 Bl ME 11 3448 EP 2 579 894 Bl <br><400> 40 <br>Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly <br>l s 10 lS <br>Glu Arg Ala Thr Leu Ser Cys Lys Ala Ser Lys Arg Va l Thr Thr Tyr <br>20 2S 30 <br>Val Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile <br>3S 40 45 <br>Tyr Gly Al a Ser Asn Arg Tyr Leu Gly Ile Pro Ala Ar g Phe Ser Gly <br>so 55 60 <br>Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro <br>65 70 75 80 <br>Glu Asp Phe Ala Val Tyr Tyr Cys Ser Gln Ser Tyr Asn Tyr Pro Tyr <br>8S 90 95 <br>Thr Phe Gly Gln Gly Thr Lys Le u Glu Ile Lys <br>100 105 <br><210> 41 <br><211> 122 <br><212> PRT <br><213> Umj etni sli j ed <br><220> <br><223> Si ntetski konstrukt <br><400> 41 <br>Glu Va l Gl n Leu Val Glu Ser Gly Gly Gly Leu Val Gl n Pro Gl y Gly <br>l 5 10 lS <br>Ser Leu Ar g Leu Ser Cys Ala Al a Ser Gl y Phe Thr Phe Ser Asn Tyr <br>20 25 30 <br>Trp Ile Se r Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Tr p Val <br>35 40 45 <br>Ala Glu Ile Arg Ser Glu Ser Asp Ala Ser Ala Thr His Tyr Ala Glu <br>so 55 60 <br>Ala Va l Lys Gly Arg Phe Thr I le Ser Arg Asp Asn Al a Lys Asn Ser <br>6S 70 7S 80 <br>29 ME 113448 EP 2 579 894 Bl <br>Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr <br>85 90 95 <br>Tyr Cys Leu Ala Tyr Phe Asp Tyr Gly Leu Ala Ile Gln Asn Tyr Trp <br>100 105 110 <br>Gly Gln Gly T hr Leu Val T hr Val Ser Ser <br>115 120 <br><210> 42 <br><211> 107 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><220> <br><221> Miješana svojstva <br><222> (27) . . (27) <br><223> X aa na položaju 27 je Gl n , Lys ili Arg <br><220> <br><221> Miješana svojstva <br><222> (28) .. (28) <br><223> X aa na položaju 28 je As p ili Pro <br><220> <br><221> Miješana svojstva <br><222> (30) .. (30) <br><223> X aa na položaju 30 je As p ili Ser <br><220> <br><221> Miješana svojstva <br><222> ( 31) .. ( 31) <br><223> X aa na položaju 31 je Lys ili Asn <br><220> <br><221> Miješana svojstva <br><222> (53) .. (53) <br><223> X aa na položaju 53 je Gl u ili Gly <br><220> <br><221> Miješana svojstva <br><222> (73) .. (73) <br><223> X aa na položaju 73 je P he ili Leu <br><220> <br><221> Miješana svojstva <br><222> (83) . . (83) <br><223> X aa na položaju 83 je Ile ili P he <br><220> <br><221> Miješana svojstva <br><222> (100) .. (100) <br><223> X aa na položaju 100 je Gl n ili Gly <br><220> <br>30 ME 113448 <br><221> Miješana svojstva <br><222> (104) . . (104) <br><223> Xaa na položaju 104 je Leu ili Val <br><400> 42 <br>Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly <br>l 5 10 15 <br>Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Xaa Xaa Ile Xaa Xaa Tyr <br>20 25 30 <br>Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile <br>35 40 45 <br>Tyr Tyr Thr Ser Xaa Tyr His Ser Gly Val Pro Ser Arg Phe Ser Gly <br>50 55 60 <br>Ser Gly Ser Gly Thr Asp Phe Thr Xaa Thr Ile Ser Ser Leu Gln Pro <br>65 70 75 80 <br>Glu Asp Xaa Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ala Leu Pro Pro <br>85 90 95 <br>Thr Phe Gly Xaa Gly Thr Lys Xaa Glu Ile Lys <br>100 105 <br><210> 43 <br><211> 119 <br><212> PRT <br><213> Umjetni slijed <br><220> <br><223> Sintetski konstrukt <br><220> <br><221> Miješana svojstva <br><222> ( 16) . . ( 16) <br><223> X aa na položaju 16 je Ala ili Ser <br><220> <br><221> Miješana svojstva <br><222> ( 57) .. ( 57) <br><223> X aa na položaju 57 je Lys ili Asp <br><220> <br><221> Miješana svojstva <br><222> (59) .. (59) <br><223> X aa na položaju 59 je Val ili Arg <br><220> <br><221> Miješana svojstva <br><222> ( 66) .. ( 66) <br><223> X aa na položaju 66 je Gly ili Asp <br>3 1 <br>EP 2 579 894 B l ME J J3448 EP 2 579 894 B J <br><220> <br><221> Miješana svojstva <br><222> ( 70) . . ( 70) <br><223> X aa na položaju 70 je Met ili Ile <br><220> <br><221> Miješana svojstva <br><222> (72) . . ( 72) <br><223> X aa na položaju 72 je Arg ili Ala <br><220> <br><221> Miješana svojstva <br><222> ( 74) .. ( 7 4) <br><223> X aa na položaju 74 je T hr ili Lys <br><220> <br><221> Miješana svojstva <br><222> (7 9) .. (79) <br><223> X aa na položaju 79 je Val ili Ala <br><220> <br><221> Miješana svojstva <br><222> (107) .. (107) <br><223> X aa na položaju 107 je Gly ili Ser <br><220> <br><221> Miješana svojstva <br><222> (114) .. (114) <br><223> X aa na položaju 114 je Leu ili T hr <br><400> 43 <br>Gl n Val Gl n Leu Val Gl n Ser Gly Ala Gl u Val Lys Lys Pro Gly X aa <br>l 5 lO 15 <br>Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Gly Asn Tyr <br>20 25 30 <br>Trp Met Gln Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met <br>35 40 45 <br>Gly Ala Ile Tyr Glu Gly Thr Gly Xaa Thr Xaa Tyr Ile Gln Lys Phe <br>50 55 60 <br>Ala Xaa Arg Val Thr Xaa Thr Xaa Asp Xaa Ser Thr Ser Thr Xaa Tyr <br>65 70 75 80 <br>Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys <br>85 90 95 <br>Ala Arg Leu Ser Asp Tyr Val Ser Gly Phe Xaa Tyr Trp Gly Gln Gly <br>100 105 110 <br>32 ME 113448 <br>Thr Xaa Val Thr Val Ser Ser <br>11 5 <br>EP 2 579 894 Bl <br>33 </ll>
Claims (8)
1. Ljudsko konstruirano protutijelo protiv CGRP, naznačeno time što sadrži varijabilno područje lakog lanca (LCVR) i varijabilno područje teškog lanca (HCVR), gdje navedeni LCVR sadrži aminokiselinske sljedove LCDR1, LCDR2, LCDR3, a HCVR sadrži aminokiselinske sljedove HCDR1, HCDR2, HCDR3, gdje je LCDR1 RASKDISKYLN (SEQ ID NO: 6), LCDR2 je YTSGYHS (SEQ ID NO: 7), LCDR3 je QQGDALPPT (SEQ ID NO: 5), HCDR1 je GYTFGNYWMQ (SEQ ID NO: 12), HCDR2 je AIYEGTGKTVYIQKFAD (SEQ ID NO: 16), a HCDR3 je LSDYVSGFGY (SEQ ID NO: 39).
2. Ljudsko konstruirano protutijelo protiv CGRP u skladu s patentnim zahtjevom 1, naznačeno time što je aminokiselinski slijed navedenog LCVR SEQ ID NO: 19, a aminokiselinski slijed navedenog HCVR je SEQ ID NO: 24.
3. Ljudsko konstruirano protutijelo protiv CGRP u skladu s patentnim zahtjevom 2, naznačeno time što navedeno protutijelo sadrži laki lanac i teški lanac, gdje je aminokiselinski slijed lakog lanca SEQ ID NO: 29, a aminokiselinski slijed teškog lanca je SEQ ID NO: 34.
4. Ljudsko konstruirano protutijelo protiv CGRP u skladu s patentnim zahtjevom 3, naznačeno time što navedeno protutijelo sadrži dva laka lanca i dva teška lanca, gdje je svaki aminokiselinski slijed lakog lanca SEQ ID NO: 29, a svaki aminokiselinski slijed teškog lanca je SEQ ID NO: 34.
5. Farmaceutski pripravak, naznačen time što sadrži ljudsko konstruirano protutijelo protiv CGRP u skladu s bilo kojim od patentnih zahtjeva 1-4, kao i farmaceutski prihvatljiv nosač, razrjeđivač ili pomoćnu tvar.
6. Ljudsko konstruirano protutijelo protiv CGRP u skladu s bilo kojim od patentnih zahtjeva 1-4, naznačeno time što je namijenjeno upotrebi u terapiji.
7. Ljudsko konstruirano protutijelo protiv CGRP u skladu s bilo kojim od patentnih zahtjeva 1-4, naznačeno time što je namijenjeno upotrebi u liječenju migrena.
8. Antigenski vežući fragment, naznačen time što je antigenski vežući fragment ljudskog konstruiranog protutijela protiv CGRP u skladu s bilo kojim od patentnih zahtjeva 1-4 ili 6-7.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US35332310P | 2010-06-10 | 2010-06-10 | |
| EP11792989.3A EP2579894B1 (en) | 2010-06-10 | 2011-06-07 | Cgrp antibodies |
| PCT/US2011/039381 WO2011156324A1 (en) | 2010-06-10 | 2011-06-07 | Cgrp antibodies |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ME02862B true ME02862B (me) | 2018-04-20 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MEP-2017-280A ME02862B (me) | 2010-06-10 | 2011-06-07 | Protutijela protiv cgrp |
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| Country | Link |
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| US (3) | US9073991B2 (me) |
| EP (2) | EP3318272B1 (me) |
| JP (2) | JP6021806B2 (me) |
| KR (1) | KR101489566B1 (me) |
| CN (2) | CN104292332B (me) |
| AR (1) | AR081434A1 (me) |
| AU (1) | AU2011265050B2 (me) |
| BR (1) | BR112012031501B1 (me) |
| CA (1) | CA2802102C (me) |
| CY (2) | CY1119789T1 (me) |
| DK (1) | DK2579894T3 (me) |
| EA (1) | EA022931B1 (me) |
| ES (2) | ES2930321T3 (me) |
| HR (1) | HRP20171992T1 (me) |
| HU (2) | HUE038135T2 (me) |
| IL (2) | IL222885B (me) |
| JO (1) | JO3330B1 (me) |
| LT (2) | LT2579894T (me) |
| LU (1) | LUC00112I2 (me) |
| ME (1) | ME02862B (me) |
| MX (2) | MX363209B (me) |
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| AU2010288194B2 (en) | 2009-08-28 | 2013-08-29 | Teva Pharmaceuticals International Gmbh | Methods for treating visceral pain by administering antagonist antibodies directed against calcitonin gene-related peptide |
| JO3330B1 (ar) * | 2010-06-10 | 2019-03-13 | Lilly Co Eli | الأجسام المضادة cgrp |
| KR101965461B1 (ko) | 2011-05-20 | 2019-04-04 | 앨더바이오 홀딩스 엘엘씨 | 필요한 대상체, 특히 편두통 환자의 광선공포증 또는 광선 혐오증을 예방 또는 억제하기 위한 항-cgrp 항체 및 항체 단편의 용도 |
| CN103748111B (zh) | 2011-05-20 | 2018-04-27 | 奥尔德生物控股有限责任公司 | 抗cgrp组合物及其用途 |
| EP2709662B1 (en) | 2011-05-20 | 2019-07-31 | AlderBio Holdings LLC | Use of anti-cgrp or anti-cgrp-r antibodies or antibody fragments to treat or prevent chronic and acute forms of diarrhea |
| MX362456B (es) | 2012-08-24 | 2019-01-18 | Univ California | Anticuerpos y vacunas para utilizarse en el tratamiento de canceres por ror1 y para inhibir la metastasis. |
| US20170114122A1 (en) | 2015-10-23 | 2017-04-27 | Alderbio Holdings Llc | Regulation of glucose metabolism using anti-cgrp antibodies |
| MX378344B (es) | 2014-03-21 | 2025-03-10 | Teva Pharmaceuticals Int Gmbh | Anticuerpos antagonistas dirigidos contra el peptido relacionado con el gen de calcitonina y metodos que usan los mismos. |
| US10556945B2 (en) | 2014-03-21 | 2020-02-11 | Teva Pharmaceuticals International Gmbh | Antagonist antibodies directed against calcitonin gene-related peptide and methods using same |
| EP3209682B1 (en) | 2014-10-24 | 2020-12-30 | Merck Sharp & Dohme Corp. | Co-agonists of the glucagon and glp-1 receptors |
| TWI595006B (zh) * | 2014-12-09 | 2017-08-11 | 禮納特神經系統科學公司 | 抗ｐｄ－１抗體類和使用彼等之方法 |
| JOP20200116A1 (ar) | 2015-04-24 | 2017-06-16 | Amgen Inc | طرق لعلاج أو الوقاية من الصداع النصفي |
| AR104847A1 (es) * | 2015-06-17 | 2017-08-16 | Lilly Co Eli | Formulación de anticuerpo anti-cgrp |
| CN108135983A (zh) * | 2015-10-30 | 2018-06-08 | 伊莱利利公司 | 抗cgrp /抗il-23双特异性抗体及其用途 |
| CN105483091A (zh) * | 2015-12-29 | 2016-04-13 | 天津三箭生物技术股份有限公司 | 小鼠抗人Calcitonin单克隆抗体及分泌该单克隆抗体的杂交瘤细胞株 |
| US20190031748A1 (en) * | 2016-01-28 | 2019-01-31 | Eli Lilly And Company | Cgrp antibodies and uses thereof |
| JP6815407B2 (ja) | 2016-02-01 | 2021-01-20 | イーライ リリー アンド カンパニー | 副甲状腺ホルモン−抗ｒａｎｋｌ抗体融合化合物 |
| KR20230047507A (ko) | 2016-06-27 | 2023-04-07 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | 암 치료 조합 |
| WO2018055573A1 (en) | 2016-09-23 | 2018-03-29 | Teva Pharmaceuticals International Gmbh | Treating cluster headache |
| PE20191148A1 (es) * | 2016-09-23 | 2019-09-02 | Teva Pharmaceuticals Int Gmbh | Tratamiento de la migrana refractaria |
| RU2770066C2 (ru) | 2017-03-02 | 2022-04-14 | Бет Изрейэл Диконисс Медикал Сентер, Инк. | Отбор пациентов с головной болью, восприимчивых к антителам, направленным против кальцитонин ген-родственного пептида |
| AR111845A1 (es) | 2017-05-03 | 2019-08-28 | Lilly Co Eli | Anticuerpos biespecíficos anti-cgrp / anti-il-23 y usos de los mismos |
| EP3642218A4 (en) * | 2017-06-21 | 2021-04-07 | Cephalon, Inc. | WASH BUFFER FOR CATION EXCHANGE CHROMATOGRAPHY |
| TWI754772B (zh) * | 2017-09-06 | 2022-02-11 | 美商美國禮來大藥廠 | 用於治療偏頭痛之拉米迪坦(lasmiditan)與cgrp拮抗劑之組合療法 |
| AU2019207915B2 (en) | 2018-01-12 | 2025-09-04 | Amgen Inc. | PAC1 antibodies and uses thereof |
| WO2019231800A1 (en) | 2018-05-31 | 2019-12-05 | Eli Lilly And Company | Anti-cgrp antibodies for treating menstrual-related migraines |
| WO2020041468A1 (en) | 2018-08-22 | 2020-02-27 | Eli Lilly And Company | Anti-cgrp antibodies for treatment-resistant patients |
| BR112020018192A2 (pt) | 2019-01-08 | 2021-08-24 | H. Lundbeck A/S | Tratamento agudo e tratamento rápido de dor de cabeça com o uso de anticorpos anti-cgrp |
| EP3744400A1 (en) * | 2019-05-28 | 2020-12-02 | Etablissement Français du Sang | Car-t cells targeting il-1rap and their use in acute myeloid leukemia (aml) |
| CN114127110B (zh) * | 2019-05-30 | 2022-07-01 | 山东博安生物技术股份有限公司 | 抗cgrp抗体及其应用 |
| AU2020368369A1 (en) | 2019-10-15 | 2022-05-12 | Eli Lilly And Company | Recombinantly engineered, lipase/esterase-deficient mammalian cell lines |
| AU2020202454A1 (en) | 2020-04-06 | 2021-10-21 | H. Lundbeck A/S | Treatment of most bothersome symptom (MBS) associated with migraine using anti-CGRP antibodies |
| JP2024509165A (ja) | 2021-03-02 | 2024-02-29 | シージーアールピー ダイアグノスティクス ゲーエムベーハー | 片頭痛の治療及び／又は発生の低減 |
| KR20240153599A (ko) | 2022-02-28 | 2024-10-23 | 트리뎀 바이오사이언스 게엠베하 & 씨오 케이지 | 적어도 β-글루칸 또는 만난으로 구성되거나 또는 이를 포함하는 접합체 |
| CN117586390A (zh) * | 2022-08-11 | 2024-02-23 | 上海君实生物医药科技股份有限公司 | 抗cgrp抗体及用途 |
| CN118271438B (zh) * | 2024-05-27 | 2024-08-30 | 上海宏成药业有限公司 | 抗cgrp抗体或其抗原结合片段及其用途 |
| CN119320450B (zh) * | 2024-12-13 | 2025-07-25 | 中国人民解放军军事科学院军事医学研究院 | 针对降钙素基因相关肽的抗体 |
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| DE122004000008I1 (de) * | 1991-06-14 | 2005-06-09 | Genentech Inc | Humanisierter Heregulin Antikörper. |
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| US8293239B2 (en) * | 2008-03-04 | 2012-10-23 | Pfizer Limited | Methods of treating chronic pain |
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