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RU2018125624A - Антитела к с5 и способы их применения - Google Patents

Антитела к с5 и способы их применения Download PDF

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RU2018125624A
RU2018125624A RU2018125624A RU2018125624A RU2018125624A RU 2018125624 A RU2018125624 A RU 2018125624A RU 2018125624 A RU2018125624 A RU 2018125624A RU 2018125624 A RU2018125624 A RU 2018125624A RU 2018125624 A RU2018125624 A RU 2018125624A
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seq
amino acid
antibody
hvr
sequence
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RU2018125624A
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RU2742606C2 (ru
RU2018125624A3 (ru
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Дзэндзиро Сампэй
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Чугаи Сейяку Кабусики Кайся
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Claims (15)

1. Выделенное антитело, которое связывается с С5, где антитело содержит (а) HVR-H3, содержащий аминокислотную последовательность DX1GYX2X3PTHAMX4X5, в которой X1 обозначает G или А, Х2 обозначает V, Q или D, Х3 обозначает Т или Y, Х4 обозначает Y или Н, Х5 обозначает L или Y (SEQ ID NO: 128), (б) HVR-L3, содержащий аминокислотную последовательность QX1TX2VGSSYGNX3, в которой X1 обозначает S, С, N или Т, Х2 обозначает F или K, Х3 обозначает А, Т или Н (SEQ ID NO: 131), и (в) HVR-H2, содержащий аминокислотную последовательность X1IX2TGSGAX3YX4AX5WX6KG, в которой X1 обозначает С, А или G, Х2 обозначает Y или F, Х3 обозначает Т, D или Е, Х4 обозначает Y, K или Q, Х5 обозначает S, D или Е, обозначает А или V (SEQ ID NO: 127).
2. Выделенное антитело, которое связывается с С5, где антитело содержит (a) HVR-H1, содержащий аминокислотную последовательность SSYYX1X2, в которой X1 обозначает М или V, Х2 обозначает С или A (SEQ ID NO: 126), (б) HVR-H2, содержащий аминокислотную последовательность X1IX2TGSGAX3YX4AX5WX6KG, в которой X, обозначает С, А или G, Х2 обозначает Y или F, Х3 обозначает Т, D или Е, Х4 обозначает Y, K или Q, Х5 обозначает S, D или Е, Х6 обозначает А или V (SEQ ID NO: 127), и (в) HVR-H3, содержащий аминокислотную последовательность DX1GYX2X3PTHAMX4X5, в которой X1 обозначает G или А, Х2 обозначает V, Q или D, Х3 обозначает Т или Y, Х4 обозначает Y или Н, Х5 обозначает L или Y (SEQ ID NO: 128).
3. Антитело по п. 2, которое дополнительно содержит (a) HVR-L1, содержащий аминокислотную последовательность X1ASQX2IX3SX4LA, в которой X1 обозначает Q или R, Х2 обозначает N, Q или G, Х3 обозначает G или S, Х4 обозначает D, K или S (SEQ ID NO: 129); (б) HVR-L2, содержащий аминокислотную последовательность GASX1X2X3S, в которой X1 обозначает K, Е или Т, Х2 обозначает L или Т, Х3 обозначает А, Н, Е или Q (SEQ ID NO: 130); и (в) HVR-L3, содержащий аминокислотную последовательность QX1TX2VGSSYGNX3, в которой X1 обозначает S, С, N или Т, Х2 обозначает F или K, Х3 обозначает А, Т или Н (SEQ ID NO: 131).
4. Выделенное антитело, которое связывается с С5, содержащее (a) HVR-L1, содержащий аминокислотную последовательность X1ASQX2IX3SX4LA, в которой X1 обозначает Q или R, Х2 обозначает N, Q или G, Х3 обозначает G или S, Х4 обозначает D, K или S (SEQ ID NO: 129); (б) HVR-L2, содержащий аминокислотную последовательность GASX1X2X3S, в которой X1 обозначает K, Е или Т, Х2 обозначает L или Т, Х3 обозначает А, Н, Е или Q (SEQ ID NO: 130); и (в) HVR-L3, содержащий аминокислотную последовательность QX1TX2VGSSYGNX3, в которой X1 обозначает S, С, N или Т, Х2 обозначает F или K, Х3 обозначает А, Т или Н (SEQ ID NO: 131).
5. Антитело по п. 2, которое дополнительно содержит каркасный участок вариабельного домена тяжелой цепи FR1, содержащий одну из аминокислотных последовательностей SEQ ID NO: 132-134; FR2, содержащий одну из аминокислотных последовательностей SEQ ID NO: 135-136; и FR3, содержащий одну из аминокислотных последовательностей SEQ ID NO: 137-139; и FR4, содержащий одну из аминокислотных последовательностей SEQ ID NO: 140-141.
6. Антитело по п. 2, которое дополнительно каркасный участок вариабельного домена легкой цепи FR1, содержащий одну из аминокислотных последовательностей SEQ ID NO: 142-143; FR2, содержащий одну из аминокислотных последовательностей SEQ ID NO: 144-145; FR3, содержащий одну из аминокислотных последовательностей SEQ ID NO: 146-147; и FR4, содержащий аминокислотную последовательность SEQ ID NO: 148.
7. Выделенное антитело, которое связывается с С5, содержащее (а) последовательность VH, идентичную по меньшей мере на 95% одной из аминокислотных последовательностей SEQ ID NO: 10, 106-110; (б) последовательность VL, идентичную по меньшей мере на 95% одной из аминокислотных последовательностей SEQ ID NO: 20, 111-113; или (в) последовательность VH, указанную в подпункте (а), и последовательность VL, указанную в подпункте (б).
8. Антитело по п. 7, содержащее последовательность VH, представленную в одной из SEQ ID NO: 10, 106-110.
9. Антитело по п. 7, содержащее последовательность VL, представленную в одной из SEQ ID NO: 20, 111-113.
10. Антитело, содержащее последовательность VH, представленную в одной из SEQ ID NO: 10, 106-110, и последовательность VL, представленную в одной из SEQ ID NO: 20, 111-113.
11. Антитело по одному из пп. 1-10, которое представляет собой полноразмерное антитело IgG1-класса или IgG4-класса.
12. Выделенная нуклеиновая кислота, кодирующая антитело по одному из пп. 1-11.
13. Клетка-хозяин, содержащая нуклеиновую кислоту по п. 12.
14. Способ получения антитела, включающий культивирование клетки-хозяина по п. 13, в результате чего получают антитело.
15. Фармацевтическая композиция, содержащая антитело по одному из пп. 1-11 и фармацевтически приемлемый носитель.
RU2018125624A 2015-12-18 2016-12-16 Антитела к с5 и способы их применения RU2742606C2 (ru)

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JP2015-247069 2015-12-18
JP2015247069 2015-12-18
PCT/JP2016/087481 WO2017104779A1 (en) 2015-12-18 2016-12-16 Anti-c5 antibodies and methods of use

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RU2018125624A true RU2018125624A (ru) 2020-01-20
RU2018125624A3 RU2018125624A3 (ru) 2020-03-27
RU2742606C2 RU2742606C2 (ru) 2021-02-09

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