RU2009133784A - АНТИ-Robo4-АНТИТЕЛА И ИХ ПРИМЕНЕНИЯ - Google Patents
АНТИ-Robo4-АНТИТЕЛА И ИХ ПРИМЕНЕНИЯ Download PDFInfo
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- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims abstract 6
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 4
- 125000000539 amino acid group Chemical group 0.000 claims abstract 2
- 238000012217 deletion Methods 0.000 claims abstract 2
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- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims 2
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- NKIJBSVPDYIEAT-UHFFFAOYSA-N 1,4,7,10-tetrazacyclododec-10-ene Chemical compound C1CNCCN=CCNCCN1 NKIJBSVPDYIEAT-UHFFFAOYSA-N 0.000 claims 1
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- WDLRUFUQRNWCPK-UHFFFAOYSA-N Tetraxetan Chemical compound OC(=O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1 WDLRUFUQRNWCPK-UHFFFAOYSA-N 0.000 claims 1
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- WKPWGQKGSOKKOO-RSFHAFMBSA-N maytansine Chemical compound CO[C@@H]([C@@]1(O)C[C@](OC(=O)N1)([C@H]([C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(C)=O)CC(=O)N1C)C)[H])\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 WKPWGQKGSOKKOO-RSFHAFMBSA-N 0.000 claims 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
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- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P27/02—Ophthalmic agents
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- A61P35/00—Antineoplastic agents
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- C07K2317/55—Fab or Fab'
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Abstract
1. Анти-Robo4-антитело, содержащее: по меньшей мере одну, две, три, четыре, пять или шесть последовательностей гипервариабельных областей (HVR), выбранных из группы, состоящей из: ! (i) HVR-L1, содержащей последовательность A1-A11, где A1-A11 является RASQDVSTAVA (SEQ ID NO:1), ! (ii) HVR-L2, содержащей последовательность B1-B7, где B1-B7 является SASFLYS (SEQ ID NO:2), ! (iii) HVR-L3, содержащей последовательность C1-C9, где C1-C9 является QQSYTTPPT (SEQ ID NO:3), ! (iv) HVR-H1, содержащей последовательность D1-D10, где D1-D10 является GFTINGYYIH (SEQ ID NO:17), ! (v) HVR-H2, содержащей последовательность E1-E18, где E1-E18 является GFIYPAGGDTDYADSVKG (SEQ ID NO:18), ! (vi) HVR-H3, содержащей последовательность F1-F17, где F1-F17 является ARLIGNKFGWSSYGMDY (SEQ ID NO:19) и ! (vii) по меньшей мере одного вариантного HVR, где вариантный HVR содержит инсерцию, делецию или замену по меньшей мере одного аминокислотного остатка последовательности, изображенной в SEQ ID NO:1, 2, 3, 17, 18 или 19. ! 2. Антитело по п.1, содержащее вариабельный домен легкой цепи, содержащий аминокислотную последовательность, выбранную из группы, состоящей из: SEQ ID NO:72-97, показанных на фиг.1А и 2А. ! 3. Антитело по п.1, содержащее вариабельный домен тяжелой цепи, содержащий аминокислотную последовательность, выбранную из группы, состоящей из: SEQ ID NO:140-165, показанных на фиг.1B и 2B. ! 4. Антитело по п.1, содержащее вариабельный домен легкой цепи, содержащий ! HVR-L1, содержащий SEQ ID NO:1, ! HVR-L2, содержащий SEQ ID NO:2, и ! HVR-L3, содержащий SEQ ID NO:20. ! 5. Антитело по п.1, содержащее вариабельный домен тяжелой цепи, содержащий ! HVR-Н1, содержащий SEQ ID NO:17, ! HVR-Н2, содержащий SEQ ID NO:18, и ! HVR-Н3, содержащий SEQ ID NO:19. ! 6. Антитело по п.1, содержащее ! (i) вариабельный домен легкой цепи, содержащий ! HVR-L1, содержащий SEQ ID NO:1, ! HVR-L2, содержащий SEQ ID NO:2, и ! HVR-L3, соде�
Claims (27)
1. Анти-Robo4-антитело, содержащее: по меньшей мере одну, две, три, четыре, пять или шесть последовательностей гипервариабельных областей (HVR), выбранных из группы, состоящей из:
(i) HVR-L1, содержащей последовательность A1-A11, где A1-A11 является RASQDVSTAVA (SEQ ID NO:1),
(ii) HVR-L2, содержащей последовательность B1-B7, где B1-B7 является SASFLYS (SEQ ID NO:2),
(iii) HVR-L3, содержащей последовательность C1-C9, где C1-C9 является QQSYTTPPT (SEQ ID NO:3),
(iv) HVR-H1, содержащей последовательность D1-D10, где D1-D10 является GFTINGYYIH (SEQ ID NO:17),
(v) HVR-H2, содержащей последовательность E1-E18, где E1-E18 является GFIYPAGGDTDYADSVKG (SEQ ID NO:18),
(vi) HVR-H3, содержащей последовательность F1-F17, где F1-F17 является ARLIGNKFGWSSYGMDY (SEQ ID NO:19) и
(vii) по меньшей мере одного вариантного HVR, где вариантный HVR содержит инсерцию, делецию или замену по меньшей мере одного аминокислотного остатка последовательности, изображенной в SEQ ID NO:1, 2, 3, 17, 18 или 19.
2. Антитело по п.1, содержащее вариабельный домен легкой цепи, содержащий аминокислотную последовательность, выбранную из группы, состоящей из: SEQ ID NO:72-97, показанных на фиг.1А и 2А.
3. Антитело по п.1, содержащее вариабельный домен тяжелой цепи, содержащий аминокислотную последовательность, выбранную из группы, состоящей из: SEQ ID NO:140-165, показанных на фиг.1B и 2B.
4. Антитело по п.1, содержащее вариабельный домен легкой цепи, содержащий
HVR-L1, содержащий SEQ ID NO:1,
HVR-L2, содержащий SEQ ID NO:2, и
HVR-L3, содержащий SEQ ID NO:20.
5. Антитело по п.1, содержащее вариабельный домен тяжелой цепи, содержащий
HVR-Н1, содержащий SEQ ID NO:17,
HVR-Н2, содержащий SEQ ID NO:18, и
HVR-Н3, содержащий SEQ ID NO:19.
6. Антитело по п.1, содержащее
(i) вариабельный домен легкой цепи, содержащий
HVR-L1, содержащий SEQ ID NO:1,
HVR-L2, содержащий SEQ ID NO:2, и
HVR-L3, содержащий QQSRSDHPT (SEQ ID NO:20); и
(ii) вариабельный домен тяжелой цепи, содержащий
HVR-H1, содержащий SEQ ID NO:17,
HVR-H2, содержащий SEQ ID NO:18, и
HVR-H3, содержащий SEQ ID NO:19.
7. Антитело по п.1, где антитело является гуманизированным.
8. Антитело по п.1, где антитело выбрано из группы, состоящей из Fab, Fab' и (Fab')2.
9. Антитело по п.1, дополнительно содержащее цитотоксическое средство.
10. Антитело по п.9, где цитотоксическое средство выбрано из группы, состоящей из: N2'-деацетил-N2'-(3-меркапто-1-оксопропил)майтансина (DM1), монометилауристатина E (MMAE), монометилауристатина F (MMAF) и их комбинаций.
11. Антитело по п.10, дополнительно содержащее детектируемую метку.
12. Антитело по п.11, где детектируемая метка выбрана из группы, состоящей из: биотина, флуоресцентного красителя, радионуклида, хелатообразующего средства 1,4,7,10-тетраазациклододекан-N,N',N",N'"-тетрауксусной кислоты (DOTA), микропузырька, эмульсии перфторуглеродных наночастиц, металлической частицы и их комбинаций.
13. Антитело по п.11, где детектируемая метка ковалентно присоединена к антителу к остатку цистеина.
14. Антитело по п.13, где остаток цистеина находится в положении 118 Fc-области тяжелой цепи согласно EU-нумерации.
15. Способ модуляции ангиогенеза, предусматривающий контактирование клетки или ткани с эффективным количеством антитела по п.1.
16. Способ по п.15, где антитело дополнительно содержит цитотоксическое средство.
17. Способ по п.15, в котором ингибируется ангиогенез.
18. Способ по п.15, где ангиогенез ассоциирован с нарушением, выбранным из группы, состоящей из: рака, атеросклероза, ретролентальной фиброплазии, гемангиом, хронического воспаления, внутриглазных неоваскулярных заболеваний, пролиферативных ретинопатий, диабетической ретинопатии, связанной со старением дегенерации желтого пятна (AMD), неоваскулярной глаукомы, иммунного отторжения трансплантированной корнеальной ткани и других тканей, ревматоидного артрита, псориаза и их комбинаций.
19. Способ по п.15, где ангиогенез ассоциирован с раком.
20. Способ по п.19, где рак выбран из группы, состоящей из: плоскоклеточного рака, рака легкого, рака брюшины, печеночно-клеточного рака, рака ЖКТ или рака желудка, в том числе желудочно-кишечного рака, рака поджелудочной железы, глиобластомы, рака шейки матки, рака яичников, рака печени, рак мочевого пузыря, рака мочевых путей, гепатомы, рака молочной железы, рака ободочной кишки, рака прямой кишки, рака ободочной и прямой кишки, эндометриального рака или карциномы матки, карциномы слюнных желез, рака почки или почечного рака, рака предстательной железы, рака вульвы, рака щитовидной железы, рака печени, анального рака, рака, относящегося к половому члену, меланомы, множественной миеломы и В-клеточной лимфомы, рака головного мозга, рака головы и шеи, остеогенной саркомы и ангиосаркомы и их ассоциированных метастазов и комбинаций.
21. Способ по п.15, где клетка или ткань находится в млекопитающем.
22. Способ по п.21, где млекопитающим является человек.
23. Способ по п.15, дополнительно предусматривающий контактирование клетки со средством, выбранным из группы, состоящей из: противоопухолевого средства, химиотерапевтического средства, ингибирующего рост средства, цитотоксического средства и их комбинаций.
24. Способ по п.23, где средством является анти-VEGF-антитело.
25. Способ визуализации in vivo, предусматривающий введение антитела по п.11 млекопитающему.
26. Способ по п.25, где млекопитающим является человек.
27. Способ по п.25, где млекопитающее предположительно имеет заболевание или нарушение, выбранное из группы, состоящей из: рака, атеросклероза, ретролентальной фиброплазии, гемангиом, хронического воспаления, внутриглазных неоваскулярных заболеваний, пролиферативных ретинопатий, диабетической ретинопатии, связанной со старением дегенерации желтого пятна (AMD), неоваскулярной глаукомы, иммунного отторжения трансплантированной корнеальной ткани, ревматоидного артрита, псориаза и их комбинаций.
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- 2008-02-08 CL CL200800420A patent/CL2008000420A1/es unknown
- 2008-02-08 BR BRPI0806403-2A patent/BRPI0806403A2/pt not_active IP Right Cessation
- 2008-02-08 KR KR1020097018734A patent/KR20090114443A/ko not_active Withdrawn
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- 2008-02-08 US US12/028,124 patent/US7834154B2/en not_active Expired - Fee Related
- 2008-02-08 NZ NZ578701A patent/NZ578701A/en not_active IP Right Cessation
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- 2008-02-08 CN CN200880011514A patent/CN101652389A/zh active Pending
- 2008-02-08 JP JP2009549247A patent/JP2010518115A/ja active Pending
- 2008-02-08 PE PE2008000289A patent/PE20081760A1/es not_active Application Discontinuation
- 2008-02-08 EP EP11195237A patent/EP2468776A3/en not_active Withdrawn
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- 2008-02-08 RU RU2009133784/10A patent/RU2009133784A/ru not_active Application Discontinuation
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Also Published As
| Publication number | Publication date |
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| NZ578701A (en) | 2012-02-24 |
| MX2009008430A (es) | 2009-10-28 |
| WO2008100805A3 (en) | 2008-10-09 |
| PE20081760A1 (es) | 2009-01-01 |
| CO6220835A2 (es) | 2010-11-19 |
| CL2008000420A1 (es) | 2008-06-27 |
| AR065271A1 (es) | 2009-05-27 |
| CN101652389A (zh) | 2010-02-17 |
| ECSP099619A (es) | 2009-10-30 |
| JP2010518115A (ja) | 2010-05-27 |
| BRPI0806403A2 (pt) | 2011-09-06 |
| US20110059013A1 (en) | 2011-03-10 |
| KR20090114443A (ko) | 2009-11-03 |
| CR11017A (es) | 2009-10-09 |
| AU2008216495A1 (en) | 2008-08-21 |
| WO2008100805A2 (en) | 2008-08-21 |
| US20110059112A1 (en) | 2011-03-10 |
| EP2468776A2 (en) | 2012-06-27 |
| US7834154B2 (en) | 2010-11-16 |
| IL200012A0 (en) | 2010-04-15 |
| EP2468776A3 (en) | 2012-11-14 |
| CA2676766A1 (en) | 2008-08-21 |
| MA31231B1 (fr) | 2010-03-01 |
| US20080247951A1 (en) | 2008-10-09 |
| EP2125896A2 (en) | 2009-12-02 |
| TW200840822A (en) | 2008-10-16 |
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