RU2012127351A - Композиции и способы для диагностики и лечения опухоли - Google Patents
Композиции и способы для диагностики и лечения опухоли Download PDFInfo
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- RU2012127351A RU2012127351A RU2012127351/10A RU2012127351A RU2012127351A RU 2012127351 A RU2012127351 A RU 2012127351A RU 2012127351/10 A RU2012127351/10 A RU 2012127351/10A RU 2012127351 A RU2012127351 A RU 2012127351A RU 2012127351 A RU2012127351 A RU 2012127351A
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- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Abstract
1. Выделенное антитело, которое связывается с ТАТ211, содержащее:a. CDR-L1 последовательность, любую из SEQ ID NO:21-34;b. CDR-L2 последовательность, любую из SEQ ID NO:35-38;с. CDR-L3 последовательность, любую из SEQ ID NO:39-41;d. CDR-H1 последовательность, любую из SEQ ID NO:42-45;е. CDR-H2 последовательность, любую из SEQ ID NO:46-60; иf. CDR-H3 последовательность, любую из SEQ ID NO:61-65.2. Выделенное антитело по п.1, содержащее:а. CDR-L1 последовательность SEQ ID NO:22;b. CDR-L2 последовательность SEQ ID NO:36;с. CDR-L3 последовательность SEQ ID NO:41;d. CDR-H1 последовательность SEQ ID NO:43;е. CDR-H2 последовательность SEQ ID NO:47; иF. CDR-H3 последовательность SEQ ID NO:62.3. Выделенное антитело по п.1, содержащее:а. CDR-L1 последовательность SEQ ID NO:23;b. CDR-L2 последовательность SEQ ID NO:36;с. CDR-L3 последовательность SEQ ID NO:41;d. CDR-H1 последовательность SEQ ID NO:43;е. CDR-H2 последовательность SEQ ID NO:47; иF. CDR-H3 последовательность SEQ ID NO:62.4. Выделенное антитело по п.1, содержащее:а. CDR-L1 последовательность SEQ ID NO:23;b. CDR-L2 последовательность SEQ ID NO:36;с. CDR-L3 последовательность SEQ ID NO:41;d. CDR-H1 последовательность SEQ ID NO:43;e. CDR-H2 последовательность SEQ ID NO:48; иF. CDR-H3 последовательность SEQ ID NO:65.5. Выделенное антитело по п.1, содержащее:a. CDR-L1 последовательность SEQ ID NO:23;b. CDR-L2 последовательность SEQ ID NO:36;с. CDR-L3 последовательность SEQ ID NO:41;d. CDR-H1 последовательность SEQ ID NO:43;e. CDR-H2 последовательность SEQ ID NO:49; иF. CDR-H3 последовательность SEQ ID NO:65.6. Выделенное антитело по п.1, содержащее:а. CDR-L1 последовательность SEQ ID NO:24;b. CDR-L2 последовательность SEQ ID NO:36;с. CDR-L3 последовательность SEQ ID NO:41;d. CDR-H1 последовательность SEQ ID NO:43;e. CDR-H2 последовательность SEQ ID NO:47; иF. CDR-H3 последовательность SEQ ID NO:65.7. Выделенное антитело по п.1, содержащее:а. CDR-L1 последовательность SEQ ID NO:25;b. CDR-L2 последовательность SEQ ID NO:36;с. CDR-L3 по
Claims (72)
1. Выделенное антитело, которое связывается с ТАТ211, содержащее:
a. CDR-L1 последовательность, любую из SEQ ID NO:21-34;
b. CDR-L2 последовательность, любую из SEQ ID NO:35-38;
с. CDR-L3 последовательность, любую из SEQ ID NO:39-41;
d. CDR-H1 последовательность, любую из SEQ ID NO:42-45;
е. CDR-H2 последовательность, любую из SEQ ID NO:46-60; и
f. CDR-H3 последовательность, любую из SEQ ID NO:61-65.
2. Выделенное антитело по п.1, содержащее:
а. CDR-L1 последовательность SEQ ID NO:22;
b. CDR-L2 последовательность SEQ ID NO:36;
с. CDR-L3 последовательность SEQ ID NO:41;
d. CDR-H1 последовательность SEQ ID NO:43;
е. CDR-H2 последовательность SEQ ID NO:47; и
F. CDR-H3 последовательность SEQ ID NO:62.
3. Выделенное антитело по п.1, содержащее:
а. CDR-L1 последовательность SEQ ID NO:23;
b. CDR-L2 последовательность SEQ ID NO:36;
с. CDR-L3 последовательность SEQ ID NO:41;
d. CDR-H1 последовательность SEQ ID NO:43;
е. CDR-H2 последовательность SEQ ID NO:47; и
F. CDR-H3 последовательность SEQ ID NO:62.
4. Выделенное антитело по п.1, содержащее:
а. CDR-L1 последовательность SEQ ID NO:23;
b. CDR-L2 последовательность SEQ ID NO:36;
с. CDR-L3 последовательность SEQ ID NO:41;
d. CDR-H1 последовательность SEQ ID NO:43;
e. CDR-H2 последовательность SEQ ID NO:48; и
F. CDR-H3 последовательность SEQ ID NO:65.
5. Выделенное антитело по п.1, содержащее:
a. CDR-L1 последовательность SEQ ID NO:23;
b. CDR-L2 последовательность SEQ ID NO:36;
с. CDR-L3 последовательность SEQ ID NO:41;
d. CDR-H1 последовательность SEQ ID NO:43;
e. CDR-H2 последовательность SEQ ID NO:49; и
F. CDR-H3 последовательность SEQ ID NO:65.
6. Выделенное антитело по п.1, содержащее:
а. CDR-L1 последовательность SEQ ID NO:24;
b. CDR-L2 последовательность SEQ ID NO:36;
с. CDR-L3 последовательность SEQ ID NO:41;
d. CDR-H1 последовательность SEQ ID NO:43;
e. CDR-H2 последовательность SEQ ID NO:47; и
F. CDR-H3 последовательность SEQ ID NO:65.
7. Выделенное антитело по п.1, содержащее:
а. CDR-L1 последовательность SEQ ID NO:25;
b. CDR-L2 последовательность SEQ ID NO:36;
с. CDR-L3 последовательность SEQ ID NO:41;
d. CDR-H1 последовательность SEQ ID NO:43;
e. CDR-H2 последовательность SEQ ID NO:47; и
F. CDR-H3 последовательность SEQ ID NO:65.
8. Выделенное антитело, которое связывается с антигенным эпитопом, расположенным между аминокислотами 320-361 последовательности полипептида ТАТ211, показанной на Фигуре 2 (SEQ ID NO:2).
9. Выделенное антитело по любому из пп.1-7, дополнительно содержащее любую акцепторную VH консенсусную каркасную последовательность человека из SEQ ID NO:66-75.
10. Выделенное антитело по любому из пп.1-7, дополнительно содержащее любую акцепторную VL консенсусную каркасную последовательность человека из SEQ ID NO:76-79.
11. Выделенное антитело по любому из пп.1-7, дополнительно содержащее любую акцепторную VH консенсусную каркасную последовательность человека из SEQ ID NO:66-75 и любую акцепторную VL консенсусную каркасную последовательность человека из SEQ ID NO:76-79.
12. Антитело по любому из пп.1-7, которое представляет собой фрагмент антитела.
13. Антитело по любому из пп.1-7, которое представляет собой химерное или гуманизированное антитело.
14. Антитело по любому из пп.1-7, которое является конъюгированным с агентом, ингибирующим рост.
15. Антитело по любому из пп.1-7, которое является конъюгированным с цитотоксическим агентом.
16. Антитело по п.15, где цитотоксический агент выбирают из группы, состоящей из токсинов, антибиотиков, радиоактивных изотопов и нуклеолитических ферментов.
17. Антитело по п.15, где цитотоксический агент представляет собой токсин.
18. Антитело по п.17, где токсин выбран из группы, состоящей из майтансиноида и калихеамицина.
19. Антитело по п.17, где токсин представляет собой ауристатин.
20. Антитело по п.19, где токсин представляет собой монометилауристатин Е (ММАЕ).
21. Антитело по п.19, где токсин представляет собой монометилауристатин F (MMAF).
22. Антитело по п.2, которое является конъюгированным с малеимидокапроил-валин-цитруллин-п-аминобензилоксикарбонил-монометилауристатином Е (MC-val-cit-PAB-MMAE).
23. Антитело по п.3, которое является конъюгированным с MC-val-cit-PAB-MMAE.
24. Антитело по п.4, которое является конъюгированным с MC-val-cit-PAB-MMAE.
25. Антитело по п.5, которое является конъюгированным с MC-val-cit-PAB-MMAE.
26. Антитело по п.6, которое является конъюгированным с MC-val-cit-PAB-MMAE.
27. Антитело по п.7, которое является конъюгированным с MC-val-cit-PAB-MMAE.
28. Антитело по п.1, которое продуцируется в бактериях.
29. Антитело по п.1, которое продуцируется в СНО клетках.
30. Антитело по любому из пп.1-8 или 22-29, которое индуцирует смерть клетки, с которой оно связывается.
31. Антитело по п.30, где указанная клетка представляет собой клетку рака яичника.
32. Антитело по п.30, где указанная клетка представляет собой клетку рака легкого.
33. Антитело по любому из пп.1-7, которое метят для обнаружения.
34. Выделенное антитело по п.1, содержащее:
(a) CDR-L1 с последовательностью SEQ ID NO:22;
(b) CDR-L2 с последовательностью SEQ ID NO:36;
(c) CDR-L3 с последовательностью SEQ ID NO:40;
(d) CDR-H1 с последовательностью SEQ ID NO:43;
(e) CDR-H2 с последовательностью SEQ ID NO:47; и
(f) CDR-H3 с последовательностью SEQ ID NO:62.
35. Выделенное антитело, содержащее последовательность VL из любых, показанных в SEQ ID NO:6-11.
36. Выделенное антитело, содержащее последовательность VH из любых, показанных в SEQ ID NO:15-20.
37. Выделенное антитело, содержащее последовательность VL из SEQ ID NO 6 и последовательность VH из SEQ ID NO:15.
38. Выделенное антитело, содержащее последовательность VL из SEQ ID NO:7 и последовательность VH из SEQ ID NO:16.
39. Выделенное антитело, содержащее последовательность VL из SEQ ID NO:8 и последовательность VH из SEQ ID NO:17.
40. Выделенное антитело, содержащее последовательность VL из SEQ ID NO:9 и последовательность VH из SEQ ID NO:18.
41. Выделенное антитело, содержащее последовательность VL из SEQ ID NO:10 и последовательность VH из SEQ ID NO:19.
42. Выделенное антитело, содержащее последовательность VL из SEQ ID NO:11 и последовательность VH из SEQ ID NO:20.
43. Выделенное антитело, содержащее последовательность с тяжелой цепью из SEQ ID NO:80.
44. Выделенное антитело, содержащее последовательность с легкой цепью из SEQ ID NO:81.
45. Выделенное антитело, содержащее последовательность с тяжелой цепью из SEQ ID NO:80 и последовательность с легкой цепью из SEQ ID NO:81.
46. Антитело по п.37, которое является конъюгированным с MC-val-cit-PAB-MMAE.
47. Антитело по п.38, которое является конъюгированным с MC-val-cit-PAB-MMAE.
48. Антитело по п.39, которое является конъюгированным с MC-val-cit-PAB-MMAE.
49. Антитело по п.40, которое является конъюгированным с MC-val-cit-PAB-MMAE.
50. Антитело по п.41, которое является конъюгированным с MC-val-cit-PAB-MMAE.
51. Антитело по п.42, которое является конъюгированным с MC-val-cit-PAB-MMAE.
52. Антитело по п.45, которое является конъюгированным с MC-val-cit-PAB-MMAE.
53. Клетка, которая продуцирует антитело по любому из пп.1-7 и 35-45.
54. Выделенная нуклеиновая кислота, которая кодирует антитело по любому из пп.1-7 и 35-45.
55. Способ идентификации первого антитела, которое связывается с ТАТ211 антигенным эпитопом, связанным со вторым антителом, где указанное второе антитело представляет собой антитело по п.1, указанный способ включает определение способности указанного первого антитела блокировать связывание указанного второго антитела с полипептидом ТАТ211, где способность указанного первого антитело блокировать связывание указанного второго антитела с указанным полипептидом ТАТ211 на по меньшей мере 40%, и при равных концентрациях антитела указывает на то, что указанное первое антитело обладает способностью к связыванию с эпитопом, связанным с указанным вторым антителом.
56. Способ ингибирования роста клетки, которая экспрессирует полипептид ТАТ211, где указанный способ включает приведение в контакт указанной клетки с антителом по любому из пп.1-27 и 35-52, где связывание указанного антитела с указанным полипептидом ТАТ211 вызывает ингибирование роста указанной клетки.
57. Способ по п.56, где указанный полипептид ТАТ211 содержит аминокислотную последовательность SEQ ID NO:2 или ее внеклеточный домен.
58. Способ по п.56, где указанная клетка представляет собой клетку рака яичника.
59. Способ по п.56, где указанная клетка представляет собой клетку рака легких.
60. Способ терапевтического лечения млекопитающего, имеющего раковую опухоль, содержащую клетки, которые экспрессируют полипептид ТАТ211, где указанный способ включает введение указанному млекопитающему терапевтически эффективного количества антитела по любому из пп.1-27 и 35-45, посредством чего эффективно излечивая указанное млекопитающее.
61. Способ по п.60, где указанный полипептид ТАТ211 содержит аминокислотную последовательность SEQ ID NO:2 или ее внеклеточный домен.
62. Способ по п.60, где указанные клетки представляют собой клетки рака яичника.
63. Способ по п.60, где указанные клетки представляют собой клетки рака легких.
64. Способ определения присутствия ТАТ211 белка в образце, подозреваемом на содержание указанного белка, где указанный способ включает подвергание указанного образца воздействию антитела по любому из пп.1-8 и 34-45 и определение связывания указанного антитела с указанным белком в указанном образце, где связывание антитела с указанным белком указывает на присутствие указанного белка в указанном образце.
65. Способ по п.64, где указанный образец содержит клетку, подозреваемую на экспрессию указанного белка.
66. Способ по п.65, где указанная клетка представляет собой клетку рака яичника.
67. Способ по п.65, где указанная клетка представляет собой клетку рака легких.
68. Способ по п.65, где указанное антитело является меченым для обнаружения.
69. Способ диагностики присутствия опухоли у млекопитающего, включающий приведение в контакт тестируемого образца клеток ткани, полученных от указанного млекопитающего, с антителом по любому из пп.1-8 и 34-45 и обнаружение образования комплекса между указанным антителом и ТАТ211 белком в тестируемом образце, где образование комплекса указывает на присутствие опухоли у указанного млекопитающего.
70. Способ по п.69, где указанный тестируемый образец клеток ткани получают от индивидуума, подозреваемого на наличие раковой опухоли.
71. Способ по п.70, где указанная опухоль представляет собой опухоль яичника или легкого.
72. Способ по п.69, где указанный полипептид ТАТ211 содержит аминокислотную последовательность SEQ ID NO:2 или ее внеклеточный домен.
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