RU2010126539A - Антитела против фактора роста эндотелия сосудов (vegf) - Google Patents
Антитела против фактора роста эндотелия сосудов (vegf) Download PDFInfo
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- 210000003989 endothelium vascular Anatomy 0.000 title 1
- 239000003102 growth factor Substances 0.000 title 1
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 53
- 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
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims abstract 6
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims abstract 6
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims abstract 6
- 238000006467 substitution reaction Methods 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims 12
- 210000004027 cell Anatomy 0.000 claims 10
- 239000013598 vector Substances 0.000 claims 5
- 206010028980 Neoplasm Diseases 0.000 claims 4
- 102000040430 polynucleotide Human genes 0.000 claims 3
- 108091033319 polynucleotide Proteins 0.000 claims 3
- 239000002157 polynucleotide Substances 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 210000003527 eukaryotic cell Anatomy 0.000 claims 2
- 230000002401 inhibitory effect Effects 0.000 claims 2
- 210000001236 prokaryotic cell Anatomy 0.000 claims 2
- 230000002062 proliferating effect Effects 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 230000033115 angiogenesis Effects 0.000 claims 1
- 239000012472 biological sample Substances 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 239000013604 expression vector Substances 0.000 claims 1
- 208000005017 glioblastoma Diseases 0.000 claims 1
- 229940127121 immunoconjugate Drugs 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 210000004962 mammalian cell Anatomy 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000008728 vascular permeability Effects 0.000 claims 1
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Abstract
1. Выделенное антитело против фактора роста эндотелия сосудов (VEGF), содержащее шесть HVR, выбранных из: ! (i) HVR-L1, содержащей аминокислотную последовательность X1X2RX3SL, причем HVR-L1 содержит 1, 2 или 3 замены в любой комбинации следующих положений: X1 обозначает G или А; Х2 обозначает V или I; и/или Х3 обозначает Т или R; ! (ii) HVR-L2, содержащей аминокислотную последовательность DASSLA (SEQ ID NO: 6); ! (iii) HVR-L3, содержащей аминокислотную последовательность SYKSPL (SEQ ID NO: 7); ! (iv) HVR-H1, содержащей аминокислотную последовательность SISGSWIF (SEQ ID NO: 1); ! (v) HVR-H2, содержащей аминокислотную последовательность GAIWPFGGYTH (SEQ ID NO: 2); и ! (vi) HVR-H3, содержащей аминокислотную последовательность RWGHSTSPWAMDY (SEQ ID NO: 3). ! 2. Выделенное антитело против VEGF, содержащее: ! (1) HVR-H1, содержащую аминокислотную последовательность SEQ ID NO: 1; ! (2) HVR-H2, содержащую аминокислотную последовательность SEQ ID NO: 2; ! (3) HVR-H3, содержащую аминокислотную последовательность SEQ ID NO: 3; ! (4) HVR-L1, содержащую аминокислотную последовательность SEQ ID NO: 4; ! (5) HVR-L2, содержащую аминокислотную последовательность SEQ ID NO:6; и ! (6) HVR-L3, содержащую аминокислотную последовательность SEQ ID NO: 7. ! 3. Выделенное антитело против VEGF, содержащее: ! (1) HVR-H1, содержащую аминокислотную последовательность SEQ ID NO: 1; ! (2) HVR-H2, содержащую аминокислотную последовательность SEQ ID NO: 2; ! (3) HVR-H3, содержащую аминокислотную последовательность SEQ ID NO: 3; ! (4) HVR-L1, содержащую аминокислотную последовательность SEQ ID NO: 5; ! (5) HVR-L2, содержащую аминокислотную последовательность SEQ ID NO: 6; и ! (6) HVR-L3, содержащую аминокислотную последовательность SEQ ID NO: 7. ! 4. Выделенное антитело против VEGF, у которого вариабельный домен легкой цепи содержит аминокислотную последовательность SEQ
Claims (34)
1. Выделенное антитело против фактора роста эндотелия сосудов (VEGF), содержащее шесть HVR, выбранных из:
(i) HVR-L1, содержащей аминокислотную последовательность X1X2RX3SL, причем HVR-L1 содержит 1, 2 или 3 замены в любой комбинации следующих положений: X1 обозначает G или А; Х2 обозначает V или I; и/или Х3 обозначает Т или R;
(ii) HVR-L2, содержащей аминокислотную последовательность DASSLA (SEQ ID NO: 6);
(iii) HVR-L3, содержащей аминокислотную последовательность SYKSPL (SEQ ID NO: 7);
(iv) HVR-H1, содержащей аминокислотную последовательность SISGSWIF (SEQ ID NO: 1);
(v) HVR-H2, содержащей аминокислотную последовательность GAIWPFGGYTH (SEQ ID NO: 2); и
(vi) HVR-H3, содержащей аминокислотную последовательность RWGHSTSPWAMDY (SEQ ID NO: 3).
2. Выделенное антитело против VEGF, содержащее:
(1) HVR-H1, содержащую аминокислотную последовательность SEQ ID NO: 1;
(2) HVR-H2, содержащую аминокислотную последовательность SEQ ID NO: 2;
(3) HVR-H3, содержащую аминокислотную последовательность SEQ ID NO: 3;
(4) HVR-L1, содержащую аминокислотную последовательность SEQ ID NO: 4;
(5) HVR-L2, содержащую аминокислотную последовательность SEQ ID NO:6; и
(6) HVR-L3, содержащую аминокислотную последовательность SEQ ID NO: 7.
3. Выделенное антитело против VEGF, содержащее:
(1) HVR-H1, содержащую аминокислотную последовательность SEQ ID NO: 1;
(2) HVR-H2, содержащую аминокислотную последовательность SEQ ID NO: 2;
(3) HVR-H3, содержащую аминокислотную последовательность SEQ ID NO: 3;
(4) HVR-L1, содержащую аминокислотную последовательность SEQ ID NO: 5;
(5) HVR-L2, содержащую аминокислотную последовательность SEQ ID NO: 6; и
(6) HVR-L3, содержащую аминокислотную последовательность SEQ ID NO: 7.
4. Выделенное антитело против VEGF, у которого вариабельный домен легкой цепи содержит аминокислотную последовательность SEQ ID NO: 44 или 45.
5. Выделенное антитело против VEGF, у которого вариабельный домен тяжелой цепи содержит аминокислотную последовательность SEQ ID NO: 43, а вариабельный домен легкой цепи содержит аминокислотную последовательность SEQ ID NO: 44 или 45.
6. Антитело по п.5, у которого вариабельный домен тяжелой цепи содержит аминокислотную последовательность SEQ ID NO: 43, а вариабельный домен легкой цепи содержит аминокислотную последовательность SEQ ID NO: 44.
7. Антитело по п.5, у которого вариабельный домен тяжелой цепи содержит аминокислотную последовательность SEQ ID NO: 43, а вариабельный домен легкой цепи содержит аминокислотную последовательность SEQ ID NO: 45.
8. Антитело по любому из пп.1-7, представляющее собой моноклональное антитело.
9. Антитело по любому из пп.1-7, представляющее собой "гуманизированное" антитело.
10. Антитело по любому из пп.1-7, представляющее собой человеческое антитело.
11. Антитело по любому из пп.1-7, у которого по меньшей мере участок каркасной последовательности представляет собой человеческую консенсусную каркасную последовательность.
12. Полинуклеотид, кодирующий антитело по любому из пп.1-7.
13. Вектор, содержащий полинуклеотид по п.12.
14. Вектор по п.13, представляющий собой экспрессирующий вектор.
15. Клетка-хозяин, содержащая вектор по п.13 или 14.
16. Клетка-хозяин по п.15, представляющая собой прокариотическую клетку.
17. Клетка-хозяин по п.15, представляющая собой эукариотическую клетку.
18. Клетка-хозяин по п.15, представляющая собой клетку млекопитающего.
19. Способ получения антитела против VEGF, включающий (а) экспрессию вектора по п.14 в подходящей клетке-хозяине и (б) выделение антитела.
20. Способ получения иммуноконъюгата антитела против VEGF, включающий (а) экспрессию вектора по п.14 в подходящей клетке-хозяине и (б) выделение антитела.
21. Способ по п.19 или 20, при котором клетка-хозяин является прокариотической клеткой.
22. Способ по п.19 или 20, при котором клетка-хозяин является эукариотической клеткой.
23. Композиция, содержащая антитело против VEGF по любому из пп.1-7.
24. Композиция, содержащая полинуклеотид по любому из пп.12-14.
25. Композиция по п.23 или 24, дополнительно содержащая носитель.
26. Способ обнаружения VEGF, включающий обнаружение комплекса VEGF-антитело против VEGF в биологическом образце, причем аминокислотная последовательность антитела против VEGF содержит вариабельный домен тяжелой цепи, включающий аминокислотную последовательность SEQ ID NO: 43, и вариабельный домен легкой цепи, включающий аминокислотную последовательность SEQ ID NO: 44 или 45.
27. Способ по п.26, при котором аминокислотная последовательность антитела против VEGF содержит вариабельный домен тяжелой цепи, включающий аминокислотную последовательность SEQ ID NO: 43, и вариабельный домен легкой цепи, включающий аминокислотную последовательность SEQ ID NO: 44.
28. Способ по п.26, при котором аминокислотная последовательность антитела против VEGF содержит вариабельный домен тяжелой цепи, включающий аминокислотную последовательность SEQ ID NO: 43, и вариабельный домен легкой цепи, включающий аминокислотную последовательность SEQ ID NO: 45.
29. Способ по любому из пп.26-28, при котором антитело против VEGF является меченным детектируемой меткой.
30. Способ лечения опухоли, рака или клеточно-пролиферативного заболевания, заключающийся во введении эффективного количества антитела против VEGF по любому из пп.1-7 субъекту, нуждающемуся в таком лечении.
31. Способ по п.30, при котором субъектом является человек.
32. Способ по п.30, при котором опухоль, рак или клеточно-пролиферативное заболевание представляет собой рак толстой кишки, рак легкого, рак молочной железы или глиобластому.
33. Способ ингибирования ангиогенеза у субъекта, заключающийся во введении субъекту эффективного количества антитела против VEGF по любому из пп.1-7.
34. Способ ингибирования сосудистой проницаемости, заключающийся во введении субъекту эффективного количества антитела против VEGF по любому из пп.1-7.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US99130207P | 2007-11-30 | 2007-11-30 | |
| US60/991,302 | 2007-11-30 | ||
| PCT/US2008/013248 WO2009073160A1 (en) | 2007-11-30 | 2008-12-01 | Anti-vegf antibodies |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2013138711A Division RU2639506C2 (ru) | 2007-11-30 | 2013-08-21 | Антитела против фактора роста эндотелия сосудов (vegf) |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2010126539A true RU2010126539A (ru) | 2012-01-10 |
| RU2514148C2 RU2514148C2 (ru) | 2014-04-27 |
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| RU2010126539/10A RU2514148C2 (ru) | 2007-11-30 | 2008-12-01 | Антитела против фактора роста эндотелия сосудов (vegf) |
| RU2013138711A RU2639506C2 (ru) | 2007-11-30 | 2013-08-21 | Антитела против фактора роста эндотелия сосудов (vegf) |
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| RU2013138711A RU2639506C2 (ru) | 2007-11-30 | 2013-08-21 | Антитела против фактора роста эндотелия сосудов (vegf) |
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| EP (3) | EP2851372B1 (ru) |
| JP (2) | JP5577254B2 (ru) |
| KR (2) | KR20100100914A (ru) |
| CN (2) | CN103893759B (ru) |
| AR (1) | AR069501A1 (ru) |
| AU (1) | AU2008331874B2 (ru) |
| BR (1) | BRPI0819165A2 (ru) |
| CA (1) | CA2703790A1 (ru) |
| CO (1) | CO6331344A2 (ru) |
| DK (1) | DK2220114T3 (ru) |
| ES (1) | ES2534905T3 (ru) |
| HK (2) | HK1147269A1 (ru) |
| HU (1) | HUE025141T2 (ru) |
| IL (2) | IL205249A (ru) |
| MX (1) | MX2010005856A (ru) |
| MY (2) | MY156315A (ru) |
| NZ (2) | NZ586047A (ru) |
| PH (1) | PH12013501652A1 (ru) |
| PL (1) | PL2220114T3 (ru) |
| RU (2) | RU2514148C2 (ru) |
| SG (1) | SG186616A1 (ru) |
| SI (1) | SI2220114T1 (ru) |
| TW (2) | TWI580694B (ru) |
| WO (1) | WO2009073160A1 (ru) |
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Effective date: 20181202 |