RU2020107917A - Конъюгаты цитокинов для лечения пролиферативных и инфекционных заболеваний - Google Patents

Конъюгаты цитокинов для лечения пролиферативных и инфекционных заболеваний Download PDF

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RU2020107917A
RU2020107917A RU2020107917A RU2020107917A RU2020107917A RU 2020107917 A RU2020107917 A RU 2020107917A RU 2020107917 A RU2020107917 A RU 2020107917A RU 2020107917 A RU2020107917 A RU 2020107917A RU 2020107917 A RU2020107917 A RU 2020107917A
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daltons
polypeptide
positions
poly
seq
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RU2020107917A
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RU2020107917A3 (ru
RU2786116C2 (ru
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Джерод Птацин
Каролина Е. КАФФАРО
Маркос МИЛЛА
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Синторкс, Инк.
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    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
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Claims (25)

1. Модифицированный полипептид интерлейкин 2 (IL-2), содержащий:
a. по меньшей мере одну неприродную аминокислоту;
b. конъюгирующий фрагмент, ковалентно присоединенный через линкер к по меньшей мере одной неприродной аминокислоте;
причем конъюгирующий фрагмент представляет собой водорастворимый полимер,
причем положение по меньшей мере одной неприродной аминокислоты выбрано из К35, Т37, R38, Т41, F42, К43, F44, Y45, Е60, Е61, E62, K64, P65, E68, V69, N71, L72, M104, C105 и Y107,
причем положения остатков соответствуют положениям 35, 37, 38, 41, 42, 43, 44, 45, 60, 61, 62, 64, 65, 68, 69, 71, 72, 104, 105 и 107, как представлено в SEQ ID NO: 1, и
причем модифицированный полипептид интерлейкин-2 (IL-2) характеризуется по меньшей мере 80%-й идентичностью последовательности по отношению к SEQ ID NO: 1.
2. Модифицированный полипептид интерлейкин-2 (IL-2) по п. 1, характеризующийся по меньшей мере 90%-й идентичностью последовательности по отношению к SEQ ID NO: 1.
3. Модифицированный полипептид интерлейкин-2 (IL-2) по п. 1, в котором положение по меньшей мере одной неприродной аминокислоты выбрано из F42, K43, F44, E62 и P65, причем положения остатков соответствуют положениям 42, 43, 44, 62 и 65, как представлено в SEQ ID NO: 1.
4. Модифицированный полипептид интерлейкин-2 (IL-2) по п. 3, в котором положение по меньшей мере одной неприродной аминокислоты представляет собой E62, причем положения остатков соответствуют положению 62, как представлено в SEQ ID NO: 1.
5. Модифицированный полипептид интерлейкин-2 (IL-2) по п. 3, в котором положение по меньшей мере одной неприродной аминокислоты представляет собой P65, причем положения остатков соответствуют положению 65, как представлено в SEQ ID NO: 1.
6. Модифицированный полипептид интерлейкин-2 (IL-2) по п. 1, в котором по меньшей мере одна неприродная аминокислота представляет собой аналог лизина или содержит ароматическую боковую цепь.
7. Модифицированный полипептид интерлейкин-2 (IL-2) по п. 1, в котором водорастворимый полимер содержит полиэтиленгликоль (PEG), поли(пропиленгликоль) (PPG), сополимеры этиленгликоля и пропиленгликоля, поли(оксиэтилированный полиол), поли(олефиновый спирт), поли(винилпирролидон), поли(гидроксиалкилметакриламид), поли(гидроксиалкилметакрилат), поли(сахариды), поли(α-гидроксикислоту), поли(виниловый спирт), полифосфазен, полиоксазолины (POZ), поли(N-акрилоилморфолин), поли[олиго(этиленгликоль)метилметакрилат] (POEGMA) или их комбинацию.
8. Модифицированный полипептид интерлейкин-2 (IL-2) по п. 7, в котором водорастворимый полимер содержит полиэтиленгликоль (PEG).
9. Модифицированный полипептид интерлейкин-2 (IL-2) по п. 8, в котором полиэтиленгликоль (PEG) имеет средневесовую молекулярную массу от около 10000 Дальтон до около 85000 Дальтон.
10. Модифицированный полипептид интерлейкин-2 (IL-2) по п. 9, в котором полиэтиленгликоль (PEG) имеет средневесовую молекулярную массу, выбранную из около 20,000 Дальтон, около 25000 Дальтон, около 30000 Дальтон, около 35000 Дальтон, около 40000 Дальтон, около 45000 Дальтон или около 50000 Дальтон.
11. Модифицированный полипептид интерлейкин-2 (IL-2) по п. 1, в котором:
a. положение по меньшей мере одной неприродной аминокислоты выбрано из F42, K43, F44, Y45, E62 и P65, причем положения остатков соответствуют положениям 42, 43, 44, 45, 62 и 65 как представлено в SEQ ID NO: 1;
b. модифицированный полипептид IL-2 содержит N-концевую делецию, включающую делецию первых 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25 или 30 остатков с N-конца, причем положения остатков относятся к положениям в SEQ ID NO: 1;
c. конъюгирующий фрагмент представляет собой полиэтиленгликоль (PEG), имеющий средневесовую молекулярную массу от около 20000 Дальтон до около 85000 Дальтон; и
d. модифицированный полипептид интерлейкин-2 (IL-2) характеризуется по меньшей мере 90%-й идентичностью последовательности по отношению к SEQ ID NO: 1.
12. Модифицированный полипептид интерлейкин-2 (IL-2) по п. 11, содержащий N-концевую делецию, включающую делецию первых 1, 2, 3, 4 или 5 остатков с N-конца, причем положения остатков относятся к положениям в SEQ ID NO: 1.
13. Модифицированный полипептид интерлейкин-2 (IL-2) по п. 12, в котором полиэтиленгликоль (PEG) имеет средневесовую молекулярную массу, выбранную из около 20000 Дальтон, около 25000 Дальтон, около 30000 Дальтон, около 35000 Дальтон, около 40000 Дальтон, около 45000 Дальтон или около 50000 Дальтон.
14. Фармацевтическая композиция, содержащая модифицированный полипептид IL-2 по любому из пп. 1-13 и фармацевтически приемлемое вспомогательное вещество.
15. Фармацевтическая композиция по п. 14, причем фармацевтическая композиция составлена для системной или парентеральной доставки.
RU2020107917A 2017-08-03 2018-08-03 Конъюгаты цитокинов для лечения пролиферативных и инфекционных заболеваний RU2786116C2 (ru)

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