RU2015144097A - Gla домены в качестве терапевтических агентов - Google Patents
Gla домены в качестве терапевтических агентов Download PDFInfo
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- RU2015144097A RU2015144097A RU2015144097A RU2015144097A RU2015144097A RU 2015144097 A RU2015144097 A RU 2015144097A RU 2015144097 A RU2015144097 A RU 2015144097A RU 2015144097 A RU2015144097 A RU 2015144097A RU 2015144097 A RU2015144097 A RU 2015144097A
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Claims (48)
1. Способ нацеливания на фосфатидилсерин (PtdS) клеточной мембраны, который включает:
(а) обеспечение изолированного полипептида, включающего домен гамма-карбоксиглутаминовой кислоты (Gla) и который не имеет домен протеазы или гормонсвязывающий домен; и
(б) приведение в контакт указанного пептида с поверхностью клетки,
где указанный полипептид связывается с PtdS на указанной клеточной мембране.
2. Способ по п. 1, где указанная клеточная мембрана представляет собой мембрану кардиомиоцита, мембрану нейронной клетки, мембрану эндотелиальной клетки, мембрану инфицированной вирусом клетки, мембрану апоптической клетки, мембрану тромбоцита или мембрану раковой клетки.
3. Способ по п. 1, где указанный полипептид дополнительно включает домен, связывающий EGF.
4. Способ по п. 1, где указанный полипептид дополнительно включает Крингл домен.
5. Способ по п. 1, где указанный полипептид дополнительно включает домен блока ароматической аминокислоты.
6. Способ по п. 1, где указанный Gla домен представляет собой Gla домен из фактора II, фактора VII, фактора IX, фактора X, белка S или белка С.
7. Способ по п. 1, где указанный полипептид дополнительно включает способную к определению метку.
8. Способ по п. 7, где указанная способная к определению метка представляет собой флуоресцентную метку, хемилюминисцентную метку, радиоактивную метку, фермент, краситель или лиганд.
9. Способ по п. 1, где указанный полипептид представляет собой 300 остатков или меньше.
10. Способ по п. 1, в котором указанный полипептид представляет собой 200 остатков или меньше.
11. Способ по п. 1, в котором указанный полипептид представляет собой 100 остатков или меньше.
12. Способ по п. 1, в котором указанный полипептид содержит 5-15 Gla остатков.
13. Способ по п. 1, в котором указанный полипептид содержит 9-13 Gla остатков.
14. Способ по п. 1, в котором указанный полипептид содержит более чем 13 GLA доменов, но меньше, чем 30% общего количества остатков Gla.
15. Способ по п. 1, в котором указанный полипептид составляет примерно от 4,5 до 30 кДа в размере.
16. Способ по п. 1, в котором указанный полипептид содержит, по меньшей мере, одну дисульфидную связь.
17. Способ по п. 1, в котором указанный полипептид содержит 2-5 дисульфидных связей.
18. Способ по п. 1, в котором указанный полипептид содержит белок S Gla домена.
19. Способ по п. 1, в котором указанный полипептид содержит белок S Gla домена и белок S EGF домена.
20. Способ по п. 1, где указанный полипептид содержит домен Gla протромбина.
21. Способ по п. 1, где указанный полипептид включает Gla домен протромбина плюс Крингл домен протромбина.
22. Способ по п. 1, где указанный полипептид включает Gla домен белка Z.
23. Способ по п. 1, где указанный полипептид включает Gla домен белка Z плюс Крингл домен протромбина.
24. Способ по п. 1, где указанный полипептид включает Gla домен фактора VII.
25. Способ по п. 1, где указанный полипептид включает Gla домен фактора VII плюс Крингл домен протромбина.
26. Способ по п. 1, где указанный полипептид дополнительно включает Fc участок антитела.
27. Способ лечения рака у субъекта, включающий введение изолированного полипептида указанному субъекту, который имеет домен гамма-карбоксиглутаминовой кислоты (Gla) и который не имеет домен протеазы или гормон-связывающий домен.
28. Способ по п. 27, где указанный рак представляет собой рак молочной железы, рак мозга, рак желудка, рак легких, рак предстательной железы, рак яичников, рак яичек, рак толстой кишки, рак кожи, рак прямой кишки, рак шейки матки, рак матки, рак печени, рак поджелудочной железы, рак головы и шеи или рак пищевода.
29. Способ по п. 27, дополнительно включающий лечение указанного субъекта с помощью второй терапии рака.
30. Способ по п. 28, в котором указанная вторая терапия против рака представляет собой иммунотерапию, радиотерапию, химиотерапию, токсиновую терапию, цитокиновую терапию или гормональную терапию.
31. Способ лечения аутоиммунного заболевания у субъекта, включающий введение изолированного полипептида указанному субъекту, который имеет домен гамма-карбоксиглутаминовой кислоты (Gla) и не имеющего домена протеазы или гормон-связывающего домена, где указанный полипептид является связанным с противовирусным агентом.
32. Способ по п. 31, где указанное аутоиммунное заболевание представляет собой следующие: спондилоартропатия, анкилозирующий спондилит, псориатический артрит, реактивный артрит, энтеропатический артрит, язвенный колит, болезнь Крона, синдром раздраженной толстой кишки, воспалительные заболевания кишечника, ревматоидный артрит, ювенильный ревматоидный артрит, семейная средиземноморская лихорадка, боковой амиотрофический склероз, синдром Шегрена, ранний артрит, вирусный артрит, рассеянный склероз, системная красная волчанка, псориаз, васкулит, гранулематоз Вегенера, болезнь Аддисона, алопеция, антифосфолипидный синдром, болезнь Бехчета, целиакия, синдром хронической усталости, язвенный колит, диабет типа I, фибромиалгия, аутоиммунные гастриты, синдром Гудпасчера, болезнь Грейвса, идиопатическая тромбоцитопеническая пурпура (ITP), тяжелая миастения, пузырчатка обыкновенная, первичный билиарный цирроз печени, ревматизм, саркоидоз, склеродермия, витилиго, васкулит, небольшой васкулит сосудов, гепатит, первичный билиарный цирроз печени, саркоидоз, склеродермия, реакция трансплантат против хозяина (острый и хронический), апластическая анемия, или циклическая нейтропения.
33. Способ по п. 31, дополнительно включающий лечение указанного субъекта с помощью второго терапевтического агента для аутоиммунного заболевания.
34. Способ по п. 33, в котором указанный второй терапевтический агент для аутоиммунного заболевания включает следующие: преднизолон, метилпреднизон, венипред, целестон, гидрокортизон, триамциноклон, внутрисуставная инъекция арстонпана, метапред, Райос перорально, бетаметазон или этанерцепт.
35. Способ лечения вирусного заболевания у субъекта, включающий введение выделенного полипептида указанному субъекту, который имеет домен гамма-карбоксиглутаминовой кислоты (Gla) и при отсутствии протеазы или гормон-связывающего домена.
36. Способ по п. 35, где указанное вирусное заболевание представляет собой вирус гриппа, вирус иммунодефицита человека, вирус лихорадки денге, вирус Западного Нила, вирус оспы, респираторно-синцитиальный вирус, вирус корейской геморрагической лихорадки, авипоксивирус, вирус ветряной оспы, вирус простого герпеса 1 или 2, вирус Эпштейна-Барр, вирус марбургской болезни, хантавирус, вирус желтой лихорадки, вирус гепатита А, В, С или Е, вирус Эбола, вирус папилломы человека, риновирус, вирус Коксаки, вирус полиомиелита, вирус кори, вирус краснухи, вирус бешенства, вирус ньюкаслской болезни, ротавирус, HTLV-1 и -2.
37. Способ по п. 35, дополнительно включающий лечение указанного субъекта с помощью второго антивирусного терапевтического агента.
38. Способ по п. 37, где указанный второй антивирусный терапевтический агент представляет собой авакавир, акикловир, ацикловир, адефовир, амантадин, ампренавир, амплиген, арбидол, атазанавир, атрипла, боцепревирертет, цидофовир, комбивир, дарунавир, делавирдин, диданозин, докозанол, эдоксудин, эфавиренц, эмтрицитабин, энфувиртид, энтекавир, ингибиторы проникновения, фамцикловир, фомивирсен, фосампренавир, фоскарнет, фосфонет, ганцикловир, ибацитабин, имуновир, идоксуридин, имиквимод, индинавир, инозин, ингибитор интегразы, интерферон типа III, интерферон типа II, интерферон типа I, интерферон, ламивудин, лопинавир, ловирид, маравирок, мороксидин, метисазон, нелфинавир, невирапин, нексавир, аналоги нуклеозидов, озелтамивир, пегинтерферон альфа-2а, пенцикловир, перамивир, плеконарил, подофиллотоксин, ингибитор протеазы, ралтегравир, ингибитор обратной транскриптазы, рибавирин, ремантадин, ритонавир, пирамидин, саквинавир, ставудин, синергетический усилитель (антиретровирусный), масло чайного дерева, телапревир, тенофовир, дизопроксилфумарат, типранавир, трифлуридин, тризивир, тромантадин, трувада, валацикловир, валганцикловир, викривироц, видарабин, вирамидин, зальцитабин, занамивир или зидовудин.
39. Способ лечения расстройства гиперкоагуляции у субъекта, включающий введение выделенного полипептида указанному субъекту, который имеет домен гамма-карбоксиглутаминовой кислоты (Gla) и при отсутствии протеазы или гормон-связывающего домена.
40. Способ по п. 39, дополнительно включающий лечение указанного субъекта с помощью второго антикоагулянта.
41. Способ модуляции свертывания у субъекта, включающий введение выделенного полипептида указанному субъекту, который имеет домен гамма-карбоксиглутаминовой кислоты (Gla) и при отсутствии протеазы или гормон-связывающего домена.
42. Способ по п. 41, дополнительно включающий введение указанному субъекту фактора свертывания.
43. Способ лечения сепсиса у субъекта, включающий введение указанному выделенного полипептида субъекту, который имеет домен гамма-карбоксиглутаминовой кислоты (Gla) и при отсутствии протеазы или гормон-связывающего домена.
44. Способ лечения сосудисто-окклюзионного кризиса у субъекта с серповидно-клеточной болезнью, включающий введение выделенного полипептида указанному субъекту, который имеет домен гамма-карбоксиглутаминовой кислоты (Gla) и при отсутствии протеазы или гормон-связывающего домена.
45. Способ лечения расстройства, характеризующегося патологической экспрессией фосфатидилсерина на поверхности клетки, включающий введение выделенного полипептида указанному субъекту, который имеет домен гамма-карбоксиглутаминовой кислоты (Gla) и при отсутствии протеазы или гормон-связывающего домена.
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WO2017118764A1 (en) | 2016-01-07 | 2017-07-13 | Thomas Brocker | Novel approaches for the in vivo and in vitro visualization of dying cells |
CN111051500A (zh) | 2017-09-05 | 2020-04-21 | 角斗士生物科学公司 | 有效载荷递送至干细胞 |
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