RU2011134500A - Антитела и иммуноконъюгаты и их применения - Google Patents

Антитела и иммуноконъюгаты и их применения Download PDF

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RU2011134500A
RU2011134500A RU2011134500/10A RU2011134500A RU2011134500A RU 2011134500 A RU2011134500 A RU 2011134500A RU 2011134500/10 A RU2011134500/10 A RU 2011134500/10A RU 2011134500 A RU2011134500 A RU 2011134500A RU 2011134500 A RU2011134500 A RU 2011134500A
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seq
amino acid
hvr
acid sequence
antibody
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Аллен Дж Мл. ЭБЕНС
Алан М. ГРЭЙ
Вэй-Чин ЛЯН
Янь У
Шан-Фань ЮЙ
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Дженентек, Инк.
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Abstract

1. Антитело, связывающееся с CD22, содержащее (a) HVR-L1, содержащую аминокислотную последовательность, выбранную из SEQ ID NO:9, 10, 19-23, 32 и 33, и (b) по меньшей мере, одну, две, три, четыре или пять HVR, выбранных из(1) HVR-H1, содержащей аминокислотную последовательность SEQ ID NO:2;(2) HVR-H2, содержащей аминокислотную последовательность SEQ ID NO:4;(3) HVR-H3, содержащей аминокислотную последовательность SEQ ID NO:6;(4) HVR-L2, содержащей аминокислотную последовательность SEQ ID NO:12; и(5) HVR-L3, содержащей аминокислотную последовательность SEQ ID NO:14.2. Антитело по п.1, содержащее HVR-L1, содержащую аминокислотную последовательность, которая соответствует консенсусной последовательности SEQ ID NO:10.3. Антитело по п.2, дополнительно содержащее HVR-H1, содержащую аминокислотную последовательность SEQ ID NO:2; HVR-H2, содержащую аминокислотную последовательность SEQ ID NO:4; и HVR-H3, содержащую аминокислотную последовательность SEQ ID NO:6.4. Антитело по п.1, где HVR-L1 содержит SEQ ID NO:9, и антитело дополнительно содержит HVR-H1, содержащую аминокислотную последовательность SEQ ID NO:2; HVR-H2, содержащую аминокислотную последовательность SEQ ID NO:4; и HVR-H3, содержащую аминокислотную последовательность SEQ ID NO:6.5. Антитело по п.1, где HVR-L1 содержит SEQ ID NO:19, и антитело дополнительно содержит HVR-H1, содержащую аминокислотную последовательность SEQ ID NO:2; HVR-H2, содержащую аминокислотную последовательность SEQ ID NO:4; и HVR-H3, содержащую аминокислотную последовательность SEQ ID NO:6.6. Антитело по п.1, где HVR-L1 содержит SEQ ID NO:20, и антитело дополнительно содержит HVR-H1, содержащую аминокислотную последовательность SEQ ID NO:2; HVR-H2, содержащую аминокислотную последовательность SEQ ID NO:4; и HVR-H3, содержащую аминокислотную последовательность SEQ ID NO:6.7. Антител

Claims (25)

1. Антитело, связывающееся с CD22, содержащее (a) HVR-L1, содержащую аминокислотную последовательность, выбранную из SEQ ID NO:9, 10, 19-23, 32 и 33, и (b) по меньшей мере, одну, две, три, четыре или пять HVR, выбранных из
(1) HVR-H1, содержащей аминокислотную последовательность SEQ ID NO:2;
(2) HVR-H2, содержащей аминокислотную последовательность SEQ ID NO:4;
(3) HVR-H3, содержащей аминокислотную последовательность SEQ ID NO:6;
(4) HVR-L2, содержащей аминокислотную последовательность SEQ ID NO:12; и
(5) HVR-L3, содержащей аминокислотную последовательность SEQ ID NO:14.
2. Антитело по п.1, содержащее HVR-L1, содержащую аминокислотную последовательность, которая соответствует консенсусной последовательности SEQ ID NO:10.
3. Антитело по п.2, дополнительно содержащее HVR-H1, содержащую аминокислотную последовательность SEQ ID NO:2; HVR-H2, содержащую аминокислотную последовательность SEQ ID NO:4; и HVR-H3, содержащую аминокислотную последовательность SEQ ID NO:6.
4. Антитело по п.1, где HVR-L1 содержит SEQ ID NO:9, и антитело дополнительно содержит HVR-H1, содержащую аминокислотную последовательность SEQ ID NO:2; HVR-H2, содержащую аминокислотную последовательность SEQ ID NO:4; и HVR-H3, содержащую аминокислотную последовательность SEQ ID NO:6.
5. Антитело по п.1, где HVR-L1 содержит SEQ ID NO:19, и антитело дополнительно содержит HVR-H1, содержащую аминокислотную последовательность SEQ ID NO:2; HVR-H2, содержащую аминокислотную последовательность SEQ ID NO:4; и HVR-H3, содержащую аминокислотную последовательность SEQ ID NO:6.
6. Антитело по п.1, где HVR-L1 содержит SEQ ID NO:20, и антитело дополнительно содержит HVR-H1, содержащую аминокислотную последовательность SEQ ID NO:2; HVR-H2, содержащую аминокислотную последовательность SEQ ID NO:4; и HVR-H3, содержащую аминокислотную последовательность SEQ ID NO:6.
7. Антитело по п.1, где HVR-L1 содержит SEQ ID NO:21, и антитело дополнительно содержит HVR-H1, содержащую аминокислотную последовательность SEQ ID NO:2; HVR-H2, содержащую аминокислотную последовательность SEQ ID NO:4; и HVR-H3, содержащую аминокислотную последовательность SEQ ID NO:6.
8. Антитело по п.1, где HVR-L1 содержит SEQ ID NO:22, и антитело дополнительно содержит HVR-H1, содержащую аминокислотную последовательность SEQ ID NO:2; HVR-H2, содержащую аминокислотную последовательность SEQ ID NO:4; и HVR-H3, содержащую аминокислотную последовательность SEQ ID NO:6.
9. Антитело по п.1, где HVR-L1 содержит SEQ ID NO:23, и антитело дополнительно содержит HVR-H1, содержащую аминокислотную последовательность SEQ ID NO:2; HVR-H2, содержащую аминокислотную последовательность SEQ ID NO:4; и HVR-H3, содержащую аминокислотную последовательность SEQ ID NO:6.
10. Антитело по п.1, где HVR-L1 содержит SEQ ID NO:32, и антитело дополнительно содержит HVR-H1, содержащую аминокислотную последовательность SEQ ID NO:2; HVR-H2, содержащую аминокислотную последовательность SEQ ID NO:4; и HVR-H3, содержащую аминокислотную последовательность SEQ ID NO:6.
11. Антитело по п.1, где HVR-L1 содержит SEQ ID NO:33, и антитело дополнительно содержит HVR-H1, содержащую аминокислотную последовательность SEQ ID NO:2; HVR-H2, содержащую аминокислотную последовательность SEQ ID NO:4; и HVR-H3, содержащую аминокислотную последовательность SEQ ID NO:6.
12. Антитело по п.1, дополнительно содержащее, по меньшей мере, один каркас, выбранный из консенсусного каркаса подгруппы III VH и консенсусного каркаса подгруппы I VL.
13. Антитело по п.1, дополнительно содержащее вариабельный домен тяжелой цепи, по меньшей мере, с 90% идентичности последовательности с аминокислотной последовательностью, выбранной из SEQ ID NO:16.
14. Антитело по п.1, содержащее вариабельный домен легкой цепи, по меньшей мере, с 90% идентичности последовательности с аминокислотной последовательностью, выбранной из SEQ ID NO:17.
15. Антитело по п.1, содержащее вариабельный домен легкой цепи, по меньшей мере, с 90% идентичности последовательности с аминокислотной последовательностью, выбранной из SEQ ID NO:18.
16. Антитело по п.1, содержащее вариабельный домен тяжелой цепи, содержащий одну, две, три или четыре каркасные аминокислотные последовательности, выбранные из SEQ ID NO:1, 3, 5 и 7.
17. Антитело по п.1, содержащее вариабельный домен легкой цепи, содержащий одну, две, три или четыре каркасные аминокислотные последовательности, выбранные из SEQ ID NO:8, 11, 13 и 15.
18. Антитело по п.13, дополнительно содержащее вариабельный домен легкой цепи, который, по меньшей мере, на 90% идентичен последовательности с аминокислотной последовательностью, выбранной из SEQ ID NO:17.
19. Антитело по п.13, дополнительно содержащее вариабельный домен легкой цепи, который, по меньшей мере, на 90% идентичен последовательности с аминокислотной последовательностью, выбранной из SEQ ID NO:18.
20. Антитело по п.1, содержащее тяжелую цепь, которая, по меньшей мере, на 90% идентична последовательности с аминокислотной последовательностью, выбранной из SEQ ID NO:88.
21. Антитело по п.1, содержащее легкую цепь, которая, по меньшей мере, на 90% идентична последовательности с аминокислотной последовательностью, выбранной из SEQ ID NO:87.
22. Антитело по п.1, содержащее тяжелую цепь с аминокислотной последовательностью SEQ ID NO:88 и легкую цепь с аминокислотной последовательностью SEQ ID NO:87.
23. Антитело, связывающееся с CD22, содержащее вариабельный домен тяжелой цепи, который, по меньшей мере, на 90% идентичен последовательности с аминокислотной последовательностью SEQ ID NO:16.
24. Антитело по п.23, дополнительно содержащее вариабельный домен легкой цепи, который, по меньшей мере, на 90% идентичен последовательности с аминокислотной последовательностью SEQ ID NO:17.
25. Антитело по п.23, дополнительно содержащее вариабельный домен легкой цепи, который, по меньшей мере, на 90% идентичен последовательности с аминокислотной последовательностью SEQ ID NO:18.
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