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RU2423383C2 - Антитела к ox40l - Google Patents

Антитела к ox40l Download PDF

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RU2423383C2
RU2423383C2 RU2009126723/10A RU2009126723A RU2423383C2 RU 2423383 C2 RU2423383 C2 RU 2423383C2 RU 2009126723/10 A RU2009126723/10 A RU 2009126723/10A RU 2009126723 A RU2009126723 A RU 2009126723A RU 2423383 C2 RU2423383 C2 RU 2423383C2
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nucleic acid
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Йозеф ЭНДЛЬ (DE)
Йозеф ЭНДЛЬ
Элси ЮГИ (US)
Элси ЮГИ
Мария ФЮНТЕС (US)
Мария ФЮНТЕС
Иво ГРАУС (NL)
Иво Граус
Аран ЛАБРИЙН (NL)
Аран ЛАБРИЙН
Мартин ЛАНЦЕНДЁРФЕР (DE)
Мартин Ланцендёрфер
Паул ПАРРЕН (NL)
Паул Паррен
Франк РЕБЕРС (NL)
Франк РЕБЕРС
Ральф ШУМАХЕР (DE)
Ральф Шумахер
Штефан ЗЕБЕР (DE)
Штефан ЗЕБЕР
Ян ВАН-ДЕ-ВИНКЕЛ (NL)
Ян ВАН-ДЕ-ВИНКЕЛ
Мартине ВАН-ВУГТ (NL)
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    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
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Abstract

Изобретение относится к биотехнологии и представляет собой антитела к OX40L, которые содержат Fc-фрагмент, полученный из организма человека, и не связываются с фактором комплемента C1q. Кроме того представлены вектора, клетки, способы получения антитела, композиции и применения антитела для приготовления лекарственного средства. Антитела обладают новыми и патентоспособными признаками, в частности, преимуществом для пациента, который страдает воспалительными заболеваниями. 17 н. и 2 з.п. ф-лы, 7 табл., 12 ил.

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Claims (19)

1. Антитело, которое связывается с OX40L человека, отличающееся тем, что содержит Fc-фрагмент, полученный из организма человека, и не связывается с фактором комплемента C1q, а также включает комбинацию вариабельных областей, независимо друг от друга выбранных из группы, включающей следующие комбинации:
а) вариабельная область легкой цепи, которая имеет аминокислотную последовательность SEQ ID NO:1, и вариабельная область тяжелой цепи, которая имеет последовательность SEQ ID NO:2;
б) вариабельная область легкой цепи, которая имеет аминокислотную последовательность SEQ ID NO:3, и вариабельная область тяжелой цепи, которая имеет последовательность SEQ ID NO:4;
в) вариабельная область легкой цепи, которая имеет аминокислотную последовательность SEQ ID NO:5, и вариабельная область тяжелой цепи, которая имеет последовательность SEQ ID NO:6;
г) вариабельная область легкой цепи, которая имеет аминокислотную последовательность SEQ ID NO:7, и вариабельная область тяжелой цепи, которая имеет последовательность SEQ ID NO:8;
д) вариабельная область легкой цепи, которая имеет аминокислотную последовательность SEQ ID NO:9, и вариабельная область тяжелой цепи, которая имеет последовательность SEQ ID NO:10;
е) вариабельная область легкой цепи, которая имеет аминокислотную последовательность SEQ ID NO:11 или 16, и вариабельная область тяжелой цепи, которая имеет последовательность SEQ ID NO:12.
2. Антитело, которое связывается с OX40L человека, отличающееся тем, что содержит Fc-фрагмент, полученный из организма человека, и не связывается с фактором комплемента C1q, и включает в качестве
а) тяжелой γ-цепи SEQ ID NO:58 и легкой каппа-цепи SEQ ID NO:61,
б) тяжелой γ-цепи SEQ ID NO:62 и легкой каппа-цепи SEQ ID NO:65 или
в) тяжелой γ-цепи SEQ ID NO:66 и легкой каппа-цепи SEQ ID NO:69.
3. Антитело по п.1, отличающееся тем, что антитело представляет собой Fab-, F(ab')2- или одноцепочечный фрагмент.
4. Антитело по п.2, отличающееся тем, что антитело представляет собой Fab-, F(ab')2- или одноцепочечный фрагмент.
5. Вектор, предназначенный для обеспечения экспрессии молекулы антитела, которое связывается с OX40L человека, и содержащий нуклеиновую кислоту, кодирующую антитело по п.1.
6. Вектор, предназначенный для обеспечения экспрессии молекулы антитела, которое связывается с OX40L человека, и содержащий молекулу нуклеиновой кислоты, кодирующую антитело по п.2.
7. Клетка-хозяин, предназначенная для получения молекулы антитела, которое связывается с OX40L человека, и включающая вектор, который содержит молекулу нуклеиновой кислоты, кодирующую антитело по п.1.
8. Клетка-хозяин, предназначенная для получения молекулы антитела, которое связывается с OX40L человека, и включающая вектор, который содержит молекулу нуклеиновой кислоты, кодирующую антитело по п.2.
9. Способ получения антитела, которое связывается с OX40L человека и содержит Fc фрагмент, полученный из организма человека, отличающийся тем, что культивируют клетку-хозяина, включающую вектор, содержащий молекулу нуклеиновой кислоты, кодирующую антитело по п.1 или 2,
в условиях, которые обеспечивают синтез молекулы антитела, и выделяют молекулу антитела из культуры.
10. Способ получения антитела, которое связывается с OX40L человека, отличающийся тем, что последовательность нуклеиновой кислоты, кодирующую антитело по п.1, модифицируют таким образом, чтобы это модифицированное антитело не связывалось с фактором комплемента C1q и/или человеческим Fcγ-рецептором на NK-клетках, встраивают указанную модифицированную первую нуклеиновую кислоту и вторую нуклеиновую кислоту, кодирующую легкую цепь антитела, в экспрессионный вектор, встраивают вектор в прокариотическую или эукариотическую клетку-хозяина, культивируют клетку-хозяина в условиях, которые обеспечивают синтез антитела, и выделяют антитело из культуры.
11. Способ получения антитела, которое связывается с OX40L человека, отличающийся тем, что последовательность нуклеиновой кислоты, кодирующую антитело по п.2, модифицируют таким образом, чтобы это модифицированное антитело не связывалось с фактором комплемента C1q и/или человеческим Fсγ-рецептором на NK-клетках, встраивают указанную модифицированную первую нуклеиновую кислоту и вторую нуклеиновую кислоту, кодирующую легкую цепь антитела, в экспрессионный вектор, встраивают вектор в прокариотическую или эукариотическую клетку-хозяина, культивируют клетку-хозяина в условиях, которые обеспечивают синтез антитела, и выделяют антитело из культуры.
12. Композиция, предназначенная для индукции иммунного ответа к OX40L человека и содержащая молекулу антитела по п.1 в дозовом количестве 0,1 мг/кг.
13. Композиция, предназначенная для индукции иммунного ответа к OX40L человека и содержащая молекулу антитела по п.2 в дозовом количестве 0,1 мг/кг.
14. Диагностическая композиция для обнаружения воспалительных заболеваний, содержащая молекулу антитела по п.1 в дозовом количестве 0,1 мг/кг.
15. Диагностическая композиция для обнаружения воспалительных заболеваний, содержащая молекулу антитела по п.2 в дозовом количестве 0,1 мг/кг.
16. Фармацевтическая композиция для лечения и профилактики воспалительных заболеваний, содержащая антитело по п.1 в дозовом количестве 0,1 мг/кг, и по меньшей мере один фармацевтически приемлемый эксципиент.
17. Фармацевтическая композиция для лечения и профилактики воспалительных заболеваний, содержащая антитело по п.2 в дозовом количестве 0,1 мг/кг, и по меньшей мере один фармацевтически приемлемый эксципиент.
18. Применение антитела по п.1 для приготовления лекарственного средства, предназначенного для профилактики и лечения воспалительных заболеваний.
19. Применение антитела по п.2 для приготовления лекарственного средства, предназначенного для профилактики и лечения воспалительных заболеваний.
RU2009126723/10A 2004-09-17 2005-09-16 Антитела к ox40l RU2423383C2 (ru)

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