ДЕФРИЗ Шон (US),СТЕЕНСТРУП Томас Док (DK),ВАНДАЛЬ Бриан Берг Стидсен (DK),БОЛТ Герт (DK),СТЕННИКЕ Хэннинг Ральф (DK),ТИМ Ларс (DK)
申请号：
RU2010137743/15
公开号：
RU2010137743A
申请日:
2009.02.26
申请国别(地区):
RU
年份:
2012
代理人:
摘要：
1. A shortened B-domain Factor VIII molecule having an altered half-life in the bloodstream, said molecule being covalently conjugated to a hydrophilic polymer via an O-linked oligosaccharide in a shortened B-domain, wherein activation of Factor VIII removes the covalently conjugated hydrophilic polymer. ! 2. The molecule of claim 1, wherein the O-linked oligosaccharide is attached at the O-glycosylation site obtained by shortening the B domain. ! 3. The molecule according to claim 1, where the hydrophilic polymer is PEG. ! 4. The molecule according to claim 3, where the size of the PEG is approximately from 10,000 to 160,000 Da. ! 5. The molecule according to claim 4, where the size of the PEG is about 40,000 Da. ! 6. The molecule according to any one of claims 1 to 5, comprising the amino acid sequence shown in SEQ ID NO 2.! 7. A pharmaceutical composition comprising a molecule according to any one of claims 1 to 6. ! 8. The method of producing molecules according to any one of claims 1 to 6, comprising conjugating a Factor VIII molecule containing a truncated B domain to a hydrophilic polymer by means of an O-linked oligosaccharide in a truncated B domain. ! 9. A molecule that can be obtained by the method according to claim 8. ! 10. A method for treating hemophilia, comprising administering to a patient in need of treatment a therapeutically effective amount of molecules according to any one of claims 1 to 6. ! 11. The use of a molecule according to any one of claims 1 to 6 as a medicine. ! 12. The use of a molecule according to any one of claims 1 to 6 for the manufacture of a medicament for the treatment of hemophilia. ! 13. The method of creating a Factor VIII molecule with a shortened B-domain according to any one of claims 1 to 6, including (i) shortening the B-domain and, possibly, analyzing the amino acid sequence of such a shortened1. Молекула Фактора VIII с укороченным В-доменом, имеющая измененное время полужизни в кровотоке, причем указанная молекула
