RU2021101502A - ХИМЕРНЫЙ АНТИГЕННЫЙ РЕЦЕПТОР (CAR) С АНТИГЕНСВЯЗЫВАЮЩИМИ ДОМЕНАМИ К КОНСТАНТНОЙ ОБЛАСТИ β Т-КЛЕТОЧНОГО РЕЦЕПТОРА - Google Patents

ХИМЕРНЫЙ АНТИГЕННЫЙ РЕЦЕПТОР (CAR) С АНТИГЕНСВЯЗЫВАЮЩИМИ ДОМЕНАМИ К КОНСТАНТНОЙ ОБЛАСТИ β Т-КЛЕТОЧНОГО РЕЦЕПТОРА Download PDF

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RU2021101502A
RU2021101502A RU2021101502A RU2021101502A RU2021101502A RU 2021101502 A RU2021101502 A RU 2021101502A RU 2021101502 A RU2021101502 A RU 2021101502A RU 2021101502 A RU2021101502 A RU 2021101502A RU 2021101502 A RU2021101502 A RU 2021101502A
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cell
bispecific
activator
malignant
cell activator
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Мартен Пюле
Пол МАСИОСИЯ
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ЮСиЭл БИЗНЕС ЛТД
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Priority claimed from GB201416908A external-priority patent/GB201416908D0/en
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Claims (27)

1. Биспецифический Т-клеточный активатор, содержащий:
a) первый домен, который селективно связывает либо константную область 1 TCR бета (TRBC1), либо TRBC2; и
b) второй домен, способный активировать Т-клетку.
2. Биспецифический Т-клеточный активатор по п. 1, где указанный первый и второй домены представляют собой одноцепочечные вариабельные фрагменты (scFv).
3. Биспецифический Т-клеточный активатор по любому из пп. 1 или 2, где указанный первый домен селективно связывает TRBC1.
4. Биспецифический Т-клеточный активатор по п. 3, где первый домен содержит вариабельную область тяжелой цепи (VH) и вариабельную область легкой цепи (VL), которые содержат следующие определяющие комплементарность области (CDR):
VH CDR1: SEQ ID No. 7;
VH CDR2: SEQ ID No. 8;
VH CDR3: SEQ ID No. 9;
VL CDR1: SEQ ID No. 10;
VL CDR2: SEQ ID No. 11; и
VL CDR3: SEQ ID No. 12.
5. Биспецифический Т-клеточный активатор по п. 3, где первый домен содержит вариабельную область тяжелой цепи (VH), который имеет последовательность, SEQ ID No. 1, и вариабельную область легкой цепи (VL), который имеет последовательность SEQ ID No. 2.
6. Биспецифический Т-клеточный активатор по п. 3, где первый домен содержит scFv, имеющий последовательность SEQ ID No. 3.
7. Биспецифический Т-клеточный активатор по любому из пп. 1 или 2, где первый домен селективно связывает TRBC2.
8. Нуклеиновая кислота, кодирующая биспецифический Т-клеточный активатор по любому из пп. 1-7.
9. Вектор, содержащий нуклеиновую кислоту по п. 8.
10. Биспецифический Т-клеточный активатор по любому из пп. 1-7 для применения в способе лечения Т-клеточной лимфомы или лейкемии у субъекта, который включает этап введения указанного биспецифического Т-клеточного активатора субъекту для того чтобы вызвать селективное истощение популяции злокачественных T-клеток, вместе с нормальными T-клетками, экспрессирующими ту же TRBC, что и злокачественные T-клетки, но не вызвать истощение популяции нормальных T-клеток, экспрессирующих TRBC, которая не экспрессируется злокачественными T-клетками.
11. Биспецифический Т-клеточный активатор для применения по п. 10, где указанный способ также включает этап исследования константной области TCR бета (TCRB) злокачественной Т-клетки от субъекта, чтобы определить, экспрессирует ли она TRBC1 или TRBC2.
12. Биспецифический Т-клеточный активатор для применения по любому из пп. 10 или 11, где Т-клеточная лимфома или лейкемия выбрана из периферической Т-клеточной лимфомы, неуточненной (ПТКЛ-НУ); ангиоиммунобластной Т-клеточной лимфомы (АИТКЛ), анапластической крупноклеточной лимфомы (АККЛ), Т-клеточной лимфомы, ассоциированной с энтеропатией (ТКЛЭ), гепатоспленической Т-клеточной лимфомы (ГСТЛ), экстранодальной NK/Т-клеточной лимфомы назального типа, Т-клеточной лимфомы кожи, первичной АККЛ кожи, Т-клеточной пролимфоцитарной лейкемии и Т-клеточной острой лимфобластной лейкемии.
13. Фармацевтическая композиция, содержащая биспецифический Т-клеточный активатор по любому из пп. 1-7 и фармацевтически приемлемый носитель, разбавитель, вспомогательное вещество или адъювант.
14. Способ выбора подходящей терапии для лечения субъекта, страдающего Т-клеточной лимфомой или лейкемией, который включает:
i) определение того, экспрессирует ли злокачественная Т-клетка в образце, выделенном у субъекта, TRBC1 или TRBC2; и
ii) выбор биспецифического Т-клеточного активатора для применения по любому из пп. 10-12 на основе экспрессии TRBC1 или TRBC2 в указанной злокачественной Т-клетке.
15. Способ выбора субъекта, страдающего Т-клеточной лимфомой или лейкемией, для получения терапии на основе биспецифического Т-клеточного активатора для применения по любому из пп. 10-12, который включает:
i) определение того, экспрессирует ли злокачественная Т-клетка в образце, выделенном у субъекта, TRBC1 или TRBC2; и
ii) выбор указанного субъекта для получения терапии на основе биспецифического Т-клеточного активатора для применения по любому из пп. 10-12 на основе экспрессии TRBC1 или TRBC2 в указанной злокачественной Т-клетке.
RU2021101502A 2014-03-05 2015-03-05 ХИМЕРНЫЙ АНТИГЕННЫЙ РЕЦЕПТОР (CAR) С АНТИГЕНСВЯЗЫВАЮЩИМИ ДОМЕНАМИ К КОНСТАНТНОЙ ОБЛАСТИ β Т-КЛЕТОЧНОГО РЕЦЕПТОРА RU2021101502A (ru)

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RU2021101502A RU2021101502A (ru) 2014-03-05 2015-03-05 ХИМЕРНЫЙ АНТИГЕННЫЙ РЕЦЕПТОР (CAR) С АНТИГЕНСВЯЗЫВАЮЩИМИ ДОМЕНАМИ К КОНСТАНТНОЙ ОБЛАСТИ β Т-КЛЕТОЧНОГО РЕЦЕПТОРА
RU2018140694A RU2018140694A (ru) 2014-03-05 2015-03-05 ХИМЕРНЫЙ АНТИГЕННЫЙ РЕЦЕПТОР (CAR) С АНТИГЕНСВЯЗЫВАЮЩИМИ ДОМЕНАМИ К КОНСТАНТНОЙ ОБЛАСТИ β Т-КЛЕТОЧНОГО РЕЦЕПТОРА

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