RU2007133660A - Ингибирование шеддинга her2 антагонистами матриксной металлопротеиназы - Google Patents

Ингибирование шеддинга her2 антагонистами матриксной металлопротеиназы Download PDF

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RU2007133660A
RU2007133660A RU2007133660/13A RU2007133660A RU2007133660A RU 2007133660 A RU2007133660 A RU 2007133660A RU 2007133660/13 A RU2007133660/13 A RU 2007133660/13A RU 2007133660 A RU2007133660 A RU 2007133660A RU 2007133660 A RU2007133660 A RU 2007133660A
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mmp
her2
mammal
antagonist
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Кендалл Д. КЭРИ (US)
Кендалл Д. КЭРИ
Ральф Х. СКВОЛ (US)
Ральф Х. СКВОЛ
Марк К. СЛИВКОВСКИ (US)
Марк К. СЛИВКОВСКИ
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Дженентек, Инк. (Us)
Дженентек, Инк.
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Claims (21)

1. Способ ингибирования шеддинга HER2, включающий в себя обработку клеток, экспрессирующих HER2, антагонистом матриксной металлопротеазы (MMP) в количестве, эффективном для ингибирования шеддинга HER2.
2. Способ по п.1, где антагонист MMP представляет собой антагонист мембраносвязанной MMP (MT-MMP).
3. Способ по п.2, где MT-MMP выбрана из группы, состоящей из MMP-15 (MT2-MMP), MMP-16 (MT3-MMP), MMP-24 (MT5-MMP), MMP-17 (MT4-MMP) и MMP-25 (MT6-MMP).
4. Способ по п.3, где MT-MMP представляет собой MMP-15.
5. Способ по п.1, где клетка демонстрирует гиперэкспрессию HER2, амплификацию или активацию.
6. Способ по п.5, где клетка демонстрирует гиперэкспрессию или амплификацию HER2.
7. Способ по п.1, дополнительно включающий в себя обработку клетки ингибитором HER.
8. Способ по п.7, где ингибитор HER представляет собой антитело к HER2.
9. Способ по п.8, где антитело к HER2 представляет собой трастузумаб или пертузумаб.
10. Способ по п.7, где ингибитор HER выбран из группы, состоящей из трастузумаба, пертузумаба, цетуксимаба, ABX-EGF, EMD7200, гефитиниба, эрлотиниба, CP724714, CI1033, GW572016, IMC-11F8 и TAK165.
11. Способ уменьшения сывороточного уровня внеклеточного домена (ECD) HER2 у млекопитающего, включающий в себя введение млекопитающему антагониста матриксной металлопротеазы (MMP) в количестве, эффективном для снижения сывороточного уровня ECD HER2 у млекопитающего.
12. Способ по п.11, где у млекопитающего повышенный уровень MMP.
13. Способ лечения злокачественного заболевания у млекопитающего, включающий в себя введение млекопитающему антагониста матриксной металлопротеазы (MMP) в количестве, эффективном для лечения злокачественного заболевания.
14. Способ по п.13, где при злокачественном заболевании обнаруживается экспрессия, амплификация или активация HER.
15. Способ по п.14, где при злокачественном заболевании обнаруживается гиперэкспрессия или амплификация HER2.
16. Способ по п.13, где у млекопитающего повышен сывороточный уровень сброшенного HER2 или повышен уровень p95 HER2.
17. Способ лечения у млекопитающего злокачественного заболевания, устойчивого к действию ингибитора HER, включающий в себя введение млекопитающему антагониста матриксной металлопротеазы (MMP) в количестве, эффективном для лечения этого злокачественного заболевания.
18. Способ по п.17, где ингибитором HER является трастузумаб.
19. Способ снижения уровня p95 HER2 в клетке, включающий в себя воздействие на эту клетку антагонистом матриксной металлопротеазы (MMP) в количестве, эффективном для снижения уровня p95 HER2.
20. Способ диагностики, включающий в себя исследование MMP-15 (MT2-MMP) в образце, полученном от пациента, страдающего злокачественным заболеванием, где повышенный уровень MMP-15 или повышенная активность указывает на наличие у пациента повышенного сывороточного уровня p95 HER2 или сброшенного HER2, или на плохой клинический исход.
21. Способ по п.20, где повышенный уровень MMP-15 указывает на то, что у пациента будет плохой клинический исход.
RU2007133660/13A 2005-02-09 2006-02-09 Ингибирование шеддинга her2 антагонистами матриксной металлопротеиназы RU2007133660A (ru)

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US (1) US20060177448A1 (ru)
EP (1) EP1846558A2 (ru)
JP (1) JP2008530123A (ru)
KR (1) KR20070100968A (ru)
CN (1) CN101115836A (ru)
AU (1) AU2006213659A1 (ru)
BR (1) BRPI0606557A2 (ru)
CA (1) CA2595395A1 (ru)
IL (1) IL184564A0 (ru)
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