RU2009127805A - АНТИТЕЛА-АНТАГОНИСТЫ ПРОТИВ Notch3 И ИХ ПРИМЕНЕНИЕ ДЛЯ ПРОФИЛАКТИКИ И ЛЕЧЕНИЯ СВЯЗАННЫХ С Notch3 ЗАБОЛЕВАНИЙ - Google Patents
АНТИТЕЛА-АНТАГОНИСТЫ ПРОТИВ Notch3 И ИХ ПРИМЕНЕНИЕ ДЛЯ ПРОФИЛАКТИКИ И ЛЕЧЕНИЯ СВЯЗАННЫХ С Notch3 ЗАБОЛЕВАНИЙ Download PDFInfo
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Abstract
1. Вариабельная область тяжелой цепи («VH»), содержащая аминокислотную последовательность, обладающую, по меньшей мере, 95% идентичностью с последовательностью, представленной в SEQ ID NO: 2. ! 2. Область цепи VH по п.1, дополнительно содержащая константную область. ! 3. Область цепи VH по п.2, содержащая CH1-, CH2- и CH3-домены константной области. ! 4. Область цепи VH по п.2, где константная область получена из антитела IgG. ! 5. Область цепи VH по п.4, где антитело IgG представляет собой антитело IgG1, антитело IgG2, антитело IgG3 или антитело IgG4. ! 6. Вариабельная область тяжелой цепи («VH»), содержащая аминокислотную последовательность, обладающую, по меньшей мере, 95% идентичностью с последовательностью, представленной в SEQ ID NO: 4. ! 7. Область цепи VH по п.6, дополнительно содержащая константную область. ! 8. Область цепи VH по п.7, содержащая CH1-, CH2- и CH3-домены константной области. ! 9. Область цепи VH по п.7, где константная область получена из антитела IgG. ! 10. Область цепи VH по п.9, где антитело IgG представляет собой антитело IgG1, антитело IgG2, антитело IgG3 или антитело IgG4. ! 11. Последовательность цепи VH, содержащая SEQ ID NO: 32, 33 и 34. ! 12. Последовательность цепи VH, содержащая SEQ ID NO: 38, 39 и 40. ! 13. Нуклеиновая кислота, кодирующая одну или несколько из SEQ ID NO: 2, 4, 32-34 и 38-40. ! 14. Вектор, содержащий одну или несколько нуклеиновых кислот по п.13. ! 15. Клетка, содержащая вектор по п.14. ! 16. Антитело, содержащее область цепи VH, содержащую (a) аминокислотную последовательность, обладающую, по меньшей мере, 95% идентичностью с последовательностью, представленной в SEQ ID NO: 2, или (b) аминокислотную последовательность, обладающую, по меньшей мере, 95% идентичностью с последовательностью, представленной в
Claims (39)
1. Вариабельная область тяжелой цепи («VH»), содержащая аминокислотную последовательность, обладающую, по меньшей мере, 95% идентичностью с последовательностью, представленной в SEQ ID NO: 2.
2. Область цепи VH по п.1, дополнительно содержащая константную область.
3. Область цепи VH по п.2, содержащая CH1-, CH2- и CH3-домены константной области.
4. Область цепи VH по п.2, где константная область получена из антитела IgG.
5. Область цепи VH по п.4, где антитело IgG представляет собой антитело IgG1, антитело IgG2, антитело IgG3 или антитело IgG4.
6. Вариабельная область тяжелой цепи («VH»), содержащая аминокислотную последовательность, обладающую, по меньшей мере, 95% идентичностью с последовательностью, представленной в SEQ ID NO: 4.
7. Область цепи VH по п.6, дополнительно содержащая константную область.
8. Область цепи VH по п.7, содержащая CH1-, CH2- и CH3-домены константной области.
9. Область цепи VH по п.7, где константная область получена из антитела IgG.
10. Область цепи VH по п.9, где антитело IgG представляет собой антитело IgG1, антитело IgG2, антитело IgG3 или антитело IgG4.
11. Последовательность цепи VH, содержащая SEQ ID NO: 32, 33 и 34.
12. Последовательность цепи VH, содержащая SEQ ID NO: 38, 39 и 40.
13. Нуклеиновая кислота, кодирующая одну или несколько из SEQ ID NO: 2, 4, 32-34 и 38-40.
14. Вектор, содержащий одну или несколько нуклеиновых кислот по п.13.
15. Клетка, содержащая вектор по п.14.
16. Антитело, содержащее область цепи VH, содержащую (a) аминокислотную последовательность, обладающую, по меньшей мере, 95% идентичностью с последовательностью, представленной в SEQ ID NO: 2, или (b) аминокислотную последовательность, обладающую, по меньшей мере, 95% идентичностью с последовательностью, представленной в SEQ ID NO: 4, где антитело связывается специфически с Notch3.
17. Антитело по п.16, дополнительно содержащее область цепи VL, содержащую (a) аминокислотную последовательность, обладающую, по меньшей мере, 95% идентичностью с последовательностью, представленной в SEQ ID NO: 3, или (b) аминокислотную последовательность, обладающую, по меньшей мере, 95% идентичностью с последовательностью, представленной в SEQ ID NO: 5.
18. Антитело по п.17, где область цепи VL содержит SEQ ID NO: 3, и область цепи VH содержит SEQ ID NO: 2.
19. Антитело по п.17, где область цепи VL содержит SEQ ID NO: 5, и область цепи VH содержит SEQ ID NO: 4.
20. Антитело по любому из пп.16-19, дополнительно содержащее константную область легкой цепи и константную область тяжелой цепи.
21. Антитело, содержащее последовательность цепи VH по п.11, где антитело связывается специфически с Notch3.
22. Антитело по п.21, дополнительно содержащее последовательность цепи VL, содержащую SEQ ID NO: 35, 36 и 37.
23. Антитело, содержащее последовательность цепи VH по п.12, где антитело связывается специфически с Notch3.
24. Антитело по п.23, дополнительно содержащее последовательность цепи VL, содержащую SEQ ID NO: 41, 42 и 43.
25. Антитело по любому из пп.21-24, дополнительно содержащее константную область легкой цепи и/или константную область тяжелой цепи.
26. Антитело по любому из пп.16-19, 24-26 и 21-24, где антитело представляет собой одноцепочечный Fv.
27. Антитело по любому из пп.16-19 и 21-24, дополнительно содержащее метку.
28. Антитело, которое связывается с конформационным эпитопом Notch3, содержащим домен LIN12, обладающий, по меньшей мере, 90% идентичностью последовательности с SEQ ID NO: 9, и димеризационный домен 2, обладающий, по меньшей мере, 90% идентичностью последовательности с SEQ ID NO: 18.
29. Антитело по п.28, где домен LIN12 состоит из SEQ ID NO 9.
30. Антитело по п.28, где димеризационный домен состоит из SEQ ID NO 18.
31. Антитело, которое связывается с конформационным эпитопом Notch3, содержащим аминокислотные остатки 1395-1396, 1402-1404 и 1420-1422 домена L1 LIN12 Notch3 (SEQ ID NO: 1) и аминокислотные остатки 1576-1578 и 1626-1628 димеризационного домена D2 Notch3 (SEQ ID NO: 1).
32. Применение антитела по п.27 для детекции связанного с Notch3 заболевания.
33. Способ получения антитела, включающий культивирование клетки по п.15 в условиях, подходящих для продукции антитела и выделения полученного антитела.
34. Антитело против Notch3, которое связывается специфически с Notch3 человека, где антитело ингибирует передачу сигнала Notch3.
35. Антитело по любому из пп.16-19, 21-24, 28-31 и 34, где антитело представляет собой фрагмент антитела.
36. Гуманизированная форма антитела по любому из пп.16-19, 21-24, 28-31 и 34.
37. Применение антитела по любому из пп.16-31 и 34-36 для получения лекарственного средства.
38. Применение антитела по любому из пп.16-31 и 34-36 для лечения связанного с Notch3 заболевания или нарушения.
39. Применение по п.38, где заболевание представляет собой T-клеточный острый лимфобластный лейкоз, лимфому, заболевание печени, при котором имеет место патологическая васкуляризация, диабет, рак яичника, заболевания, при которых имеет место определение судьбы клеток сосудов, ревматоидный артрит, рак поджелудочной железы, немелкоклеточный рак легкого, новообразования из плазматических клеток (такие как множественная миелома, плазмоклеточный лейкоз и экстрамедуллярная плазмацитома) и нейробластому.
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US87559706P | 2006-12-18 | 2006-12-18 | |
US60/875,597 | 2006-12-18 | ||
US87921807P | 2007-01-06 | 2007-01-06 | |
US60/879,218 | 2007-01-06 | ||
PCT/US2007/087723 WO2008076960A2 (en) | 2006-12-18 | 2007-12-17 | Antagonist anti-notch3 antibodies and their use in the prevention and treatment of notch3-related diseases |
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US6984522B2 (en) | 2000-08-03 | 2006-01-10 | Regents Of The University Of Michigan | Isolation and use of solid tumor stem cells |
WO2005111072A2 (en) | 2004-04-29 | 2005-11-24 | The Trustees Of Columbia University In The City Of New York | Notch-based fusion proteins and uses thereof |
PL2032166T3 (pl) | 2006-06-13 | 2013-09-30 | Oncomed Pharm Inc | Kompozycje i sposoby diagnozowania i leczenia nowotworów |
CL2007002989A1 (es) | 2006-10-19 | 2008-05-16 | Genentech Inc | Anticuerpos anti-notch3; acido nucleico que los codifica; vector y celula que lo comprende; metodo de produccion; y su uso para el diagnostico de enfermedades relacionadas con notch3. |
PE20081264A1 (es) * | 2006-10-19 | 2008-10-01 | Genentech Inc | Anticuerpos agonistas anti-notch3 |
BRPI0719409A2 (pt) | 2006-12-18 | 2014-02-11 | Genentch Inc | "regiões variáveis da cadeia pesada ("vh"), sequências da cadeia vh, ácido nucléico, vetor, célula, anticorpos, uso do anticorpo, método para produzir um anticorpo, anticorpo anti-notch3 e forma humanizada do anticorpo" |
US8148147B2 (en) | 2007-01-24 | 2012-04-03 | The Regents Of The University Of Michigan | Compositions and methods for treating and diagnosing pancreatic cancer |
JP5618544B2 (ja) | 2007-01-24 | 2014-11-05 | オンコメッドファーマシューティカルズ インコーポレイテッド | 癌の診断および処置のための組成物および方法 |
US20090208491A1 (en) * | 2007-02-14 | 2009-08-20 | Austin Gurney | Compositions and Methods for Diagnosing and Treating Cancer |
PE20090321A1 (es) * | 2007-06-04 | 2009-04-20 | Genentech Inc | Anticuerpos anti-notch1 nrr, metodo de preparacion y composicion farmaceutica |
WO2009036167A1 (en) * | 2007-09-14 | 2009-03-19 | Vanderbilt University | Targeting of notch3 receptor function for cancer therapy |
RS53924B1 (en) * | 2008-07-08 | 2015-08-31 | Oncomed Pharmaceuticals, Inc. | NOTCH-BINDING AGENTS AND ANTAGONISTS AND PROCEDURES FOR THEIR USE |
US9132189B2 (en) | 2008-07-08 | 2015-09-15 | Oncomed Pharmaceuticals, Inc. | Notch1 binding agents and methods of use thereof |
WO2010039832A1 (en) * | 2008-10-01 | 2010-04-08 | Genentech, Inc. | Anti-notch2 antibodies and methods of use |
JP5113812B2 (ja) * | 2009-08-31 | 2013-01-09 | 清 中川 | コロニーピッキング装置、コロニーピッキング方法、及び融合細胞クローン作製方法 |
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