RU2395523C2 - Антитела к ох40l - Google Patents

Антитела к ох40l Download PDF

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RU2395523C2
RU2395523C2 RU2007114328/13A RU2007114328A RU2395523C2 RU 2395523 C2 RU2395523 C2 RU 2395523C2 RU 2007114328/13 A RU2007114328/13 A RU 2007114328/13A RU 2007114328 A RU2007114328 A RU 2007114328A RU 2395523 C2 RU2395523 C2 RU 2395523C2
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Йозеф ЭНДЛЬ (DE)
Йозеф ЭНДЛЬ
Элси ЮГИ (US)
Элси ЮГИ
Мария ФЬЮНТЕС (US)
Мария ФЬЮНТЕС
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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Abstract

Изобретение относится к биотехнологии и представляет собой антитело, которое связывается с OX40L, и варианты этого антитела, которые содержат определенные Fc-фрагменты, полученные из организма человека, и не связываются с фактором комплемента C1q. При этом моноклональное антитело продуцируется линией клеток, выбранной из группы, включающей линии клеток, депонированные в Немецкой коллекции микроорганизмов и клеточных культур (DSMZ) под инвентарными №№DSM АСС 2685, DSM АСС 2686, DSM АСС 2688, DSM АСС 2689. Также изобретение относится к способу получения такого антитела, к молекулам нуклеиновой кислоты, кодирующим антитела по изобретению. Кроме того, антитело по изобретению используется в диагностической композиции для выявления OX40L in vitro, в фармацевтической композиции для профилактики и лечения воспалительных заболеваний, а также в приготовлении лекарственного средства для профилактики и лечения воспалительных заболеваний. Антитела по изобретению обладают преимуществом для пациентов, страдающих воспалительными заболеваниями. 9 н.п. ф-лы, 20 ил., 7 табл.

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Claims (9)

1. Антитело, которое связывается с OX40L человека, отличающееся тем, что содержит 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 оно продуцируется линией клеток, выбранной из группы, включающей линии клеток
hu-Mab<hOX40L>LC.001,
hu-Mab<hOX40L>LC.005,
hu-Mab<hOX40L>LC010,
hu-Mab<hOX40L>LC.019,
hu-Mab<hOX40L>LC.029
и hu-Mab<hOX40L>LC.033.
3. Антитело, которое связывается с OX40L, отличающееся тем, что относится к классу человеческого IgG1 и содержит 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.
4. Молекула нуклеиновой кислоты, кодирующая молекулу антитела, отличающаяся тем, что указанное антитело связывается с OX40L человека и содержит 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.
5. Молекула нуклеиновой кислоты, кодирующая антитело, которое связывается с OX40L человека, отличающаяся тем, что она кодирует антитело, включающее:
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.
6. Способ получения антитела, которое связывается с OX40L и содержит Fc фрагмент, полученный из организма человека, отличающийся тем, что культивируют клетку-хозяина, включающую вектор, содержащий молекулу нуклеиновой кислоты по п.4 или 5 в условиях, которые обеспечивают синтез антитела и выделяют антитело из культуры.
7. Диагностическая композиция, для выявления OX40L in vitro содержащая молекулу антитела по любому из пп.1-3 в дозовом количестве 0,1 мг/кг и, по меньшей мере, один диагностически приемлемый экципиент.
8. Фармацевтическая композиция, предназначенная для профилактики или лечения воспалительных заболеваний, содержащая молекулу антитела по любому из пп.1-3 в дозовом количестве 0,1 мг/кг и, по меньшей мере, один диагностически приемлемый экципиент.
9. Применение антитела по любому из пп.1-3 для приготовления лекарственного средства, предназначенного для профилактики и лечения воспалительных заболеваний.
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