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RU2013120318A - Антитела, связывающие il-4 и/или il-13, и их применение - Google Patents

Антитела, связывающие il-4 и/или il-13, и их применение Download PDF

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RU2013120318A
RU2013120318A RU2013120318/10A RU2013120318A RU2013120318A RU 2013120318 A RU2013120318 A RU 2013120318A RU 2013120318/10 A RU2013120318/10 A RU 2013120318/10A RU 2013120318 A RU2013120318 A RU 2013120318A RU 2013120318 A RU2013120318 A RU 2013120318A
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Эрколе Рао
Венсан Миколь
Даньси ЛИ
Йохен КРУЙП
Меттью ДЭВИСОН
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Abstract

1. Биспецифическое антитело или функциональный фрагмент этого антитела, которое специфически связывается с IL-13 и IL-4,где биспецифическое антитело или его функциональный фрагмент содержит две легких и две тяжелых цепи;где легкие цепи содержат внешний вариабельный домен легкой цепи, связанный с внутренним вариабельным доменом легкой цепи, который связан с константным доменом легкой цепи (CL), а тяжелые цепи содержат внешний вариабельный домен тяжелой цепи, связанный с внутренним вариабельным доменом тяжелой цепи, который связан с константным доменом легкой цепи (CH1); игде:(а) внешний вариабельный домен легкой цепи содержит аминокислотную последовательность SEQ ID NO:1, внутренний вариабельный домен легкой цепи содержит аминокислотную последовательность SEQ ID NO:3, внешний вариабельный домен тяжелой цепи содержит аминокислотную последовательность SEQ ID NO:2, внутренний вариабельный домен тяжелой цепи содержит аминокислотную последовательность SEQ ID NO:4;(b) внешний вариабельный домен легкой цепи содержит аминокислотную последовательности SEQ ID NO:1, внутренний вариабельный домен легкой цепи содержит аминокислотную последовательность SEQ ID NO:3, внешний вариабельный домен тяжелой цепи содержит аминокислотную последовательность SEQ ID NO:2, и внутренний вариабельный домен тяжелой цепи содержит аминокислотную последовательность SEQ ID NO:5;(c) внешний вариабельный домен легкой цепи содержит аминокислотные последовательности RASESVDSYGQSYMH (SEQ ID NO:8), LASNLES (SEQ ID NO:9) и QQNAEDSRT (SEQ ID NO:10), внутренний вариабельный домен легкой цепи содержит аминокислотные последовательности HASQNIDVWLS (SEQ ID NO:14), KASNLHTG (SEQ ID NO:15) и QQAHSYPFT (SEQ ID NO:16), наружный вариабельный домен тяжел�

Claims (17)

1. Биспецифическое антитело или функциональный фрагмент этого антитела, которое специфически связывается с IL-13 и IL-4,
где биспецифическое антитело или его функциональный фрагмент содержит две легких и две тяжелых цепи;
где легкие цепи содержат внешний вариабельный домен легкой цепи, связанный с внутренним вариабельным доменом легкой цепи, который связан с константным доменом легкой цепи (CL), а тяжелые цепи содержат внешний вариабельный домен тяжелой цепи, связанный с внутренним вариабельным доменом тяжелой цепи, который связан с константным доменом легкой цепи (CH1); и
где:
(а) внешний вариабельный домен легкой цепи содержит аминокислотную последовательность SEQ ID NO:1, внутренний вариабельный домен легкой цепи содержит аминокислотную последовательность SEQ ID NO:3, внешний вариабельный домен тяжелой цепи содержит аминокислотную последовательность SEQ ID NO:2, внутренний вариабельный домен тяжелой цепи содержит аминокислотную последовательность SEQ ID NO:4;
(b) внешний вариабельный домен легкой цепи содержит аминокислотную последовательности SEQ ID NO:1, внутренний вариабельный домен легкой цепи содержит аминокислотную последовательность SEQ ID NO:3, внешний вариабельный домен тяжелой цепи содержит аминокислотную последовательность SEQ ID NO:2, и внутренний вариабельный домен тяжелой цепи содержит аминокислотную последовательность SEQ ID NO:5;
(c) внешний вариабельный домен легкой цепи содержит аминокислотные последовательности RASESVDSYGQSYMH (SEQ ID NO:8), LASNLES (SEQ ID NO:9) и QQNAEDSRT (SEQ ID NO:10), внутренний вариабельный домен легкой цепи содержит аминокислотные последовательности HASQNIDVWLS (SEQ ID NO:14), KASNLHTG (SEQ ID NO:15) и QQAHSYPFT (SEQ ID NO:16), наружный вариабельный домен тяжелой цепи содержит аминокислотные последовательности GFSLTDSSIN (SEQ ID NO:11), DGRID (SEQ ID NO:12) и DGYFPYAMDF (SEQ ID NO:13) и внутренний вариабельный домен тяжелой цепи содержит аминокислотные последовательности GYSFTSYWIH (SEQ ID NO:17), IDPSDGETR (SEQ ID NO:18) и LKEYGNYDSFYFDV (SEQ ID NO:19); или
(d) внешний вариабельный домен легкой цепи содержит аминокислотные последовательности RASESVDSYGQSYMH (SEQ ID NO:8), LASNLES (SEQ ID NO:9) и QQNAEDSRT (SEQ ID NO:10), внутренний вариабельный домен легкой цепи содержит аминокислотные последовательности HASQNIDVWLS (SEQ ID NO:14), KASNLHTG (SEQ ID NO:15) и QQAHSYPFT (SEQ ID NO:16), наружный вариабельный домен тяжелой цепи содержит аминокислотные последовательности GFSLTDSSIN (SEQ ID NO:11), DGRID (SEQ ID NO:12) и DGYFPYAMDF (SEQ ID NO:13) и внутренний вариабельный домен тяжелой цепи содержит аминокислотные последовательности GYSFTSYWIH (SEQ ID NO:20), IDASDGETR (SEQ ID NO:21) и LKEYGNYDSFYFDV (SEQ ID NO:22).
2. Биспецифическое антитело или его функциональный фрагмент по п.1, где пептидый линкер связывает внешний вариабельный домен легкой цепи и внутренний вариабельный домен легкой цепи, и пептидный линкер связывает наружный вариабельный домен тяжелой цепи и внутренний вариабельный домен тяжелой цепи.
3. Биспецифическое антитело или его функциональный фрагмент по п.2, где пептидный линкер состоит из аминокислотной последовательности SEQ ID NO:6.
4. Биспецифическое антитело или его функциональный фрагмент по п.1, которое необязательно содержит дополнительные константные домены.
5. Биспецифическое антитело или его функциональный фрагмент по п.4, где дополнительные константные домены состоят из CH2 и CH3.
6. Биспецифическое антитело или его функциональный фрагмент по любому из пп.1-5, которое необязательно конъюгировано с эффекторной молекулой.
7. Биспецифическое антитело или его функциональный фрагмент по п.6, где эффекторная молекула представляет собой гетерологический полипептид, лекарственное средство, радионуклеотид и токсин.
8. Фармацевтическая композиция для лечения заболеваний или расстройств, связанных с функцией или метаболизмом IL-4 и/или IL-13, содержащая биспецифическое антитело или его функциональный фрагмент по любому из пп.1-7 и фармацевтически приемлемый носитель.
9. Молекула нуклеиновой кислоты, кодирующая биспецифическое антитело или его функциональный фрагмент по любому из пп.1-5.
10. Вектор, содержащий молекулу нуклеиновой кислоты, по п.9.
11. Выделенная клетка-хозяин, содержащая вектор по п.10.
12. Способ лечения аллергического заболевания у млекопитающего, включающий стадию введения млекопитающему терапевтически эффективного количества биспецифического антитела или его функционального фрагмента по любому из пп.1 или 4.
13. Способ лечения злокачественного новообразования у млекопитающего, включающий стадию введения млекопитающему терапевтически эффективного количества биспецифического антитела или его функционального фрагмента по любому из пп.1 или 4.
14. Способ лечения астмы у млекопитающего, включающий стадию введения млекопитающему терапевтически эффективного количества биспецифического антитела или его функционального фрагмента по любому из пп.1 или 4.
15. Способ лечения заболевания, связанного с патологической продукцией IL-4 и/или IL-13 у млекопитающего, предусматривающий стадию введения млекопитающему терапевтически эффективного количества биспецифического антитела или его функционального фрагмента по любому из пп.1 или 4.
16. Применение биспецифического антитела или его функционального фрагмента по любому из пп.1-7 для получения лекарственного средства для лечения идиопатического легочного фиброза у млекопитающего.
17. Способ подавления TH-2 опосредованного ответа у млекопитающего, включающий стадию введения млекопитающему терапевтически эффективного количества биспецифического антитела или его функционального фрагмента по любому из пп. 1 или 4.
RU2013120318/10A 2007-10-15 2008-10-14 Антитела, связывающие il-4 и/или il-13, и их применение RU2580049C2 (ru)

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Application Number Priority Date Filing Date Title
EP07291259A EP2050764A1 (en) 2007-10-15 2007-10-15 Novel polyvalent bispecific antibody format and uses thereof
EP07291259.5 2007-10-15
US3712808P 2008-03-17 2008-03-17
US61/037,128 2008-03-17

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RU2015141428A Division RU2705551C2 (ru) 2007-10-15 2015-09-29 Антитела, связывающие il-4 и/или il-13, и их применение
RU2015141418A Division RU2721236C2 (ru) 2007-10-15 2015-09-29 Антитела, связывающие il-4 и/или il-13, и их применение

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