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1. 发明申请

WO1997040145A1 INACTIVATION RESISTANT FACTOR VIII 审中-公开
标题翻译：灭绝因子VIII
公开(公告)号：WO1997040145A1
公开(公告)日：1997-10-30
申请号：PCT/US1997006563
申请日：1997-04-24
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , KAUFMAN, Randal, J. , PIPE, Steven, W. , AMANO, Kagehiro
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
IPC分类号： C12N09/48
CPC分类号： C07K14/755 , A61K38/00
摘要： The present invention provides novel purified and isolated nucleic acid sequences encoding procoagulant-active FVIII proteins. The nucleic acid sequences of the present invention encode amino acid sequences corresponding to known human FVIII sequences, wherein residue Phe309 is mutated. The nucleic acid sequences of the present invention also encode amino acid sequences corresponding to known human FVIII sequences, wherein the APC cleavage sites, Arg336 and Ile562, are mutated. The nucleic acid sequences of the prsent invention further encode amino acid sequences corresponding to known human FVIII sequences, wherein the B-domain is deleted, the von Willebrand factor binding site is deleted, a thrombin cleavage site is mutated and an amino acid sequence spacer is inserted between the A2- and A3-domains. Methods of producing the FVIII proteins of the invention, nucleotide sequences encoding such proteins, pharmaceutical compositions containing the nucleotide sequences or proteins, as well as methods of treating patients suffering from hemophilia, are also provided.
摘要翻译：本发明提供了编码促凝血活性FVIII蛋白的新型纯化和分离的核酸序列。本发明的核酸序列编码对应于已知人FVIII序列的氨基酸序列，其中残基Phe309被突变。本发明的核酸序列还编码对应于已知人FVIII序列的氨基酸序列，其中APC切割位点Arg336和Ile562突变。本发明的核酸序列进一步编码对应于已知人FVIII序列的氨基酸序列，其中缺失B结构域，缺失血管性血友病因子结合位点，突变凝血酶切割位点，氨基酸序列间隔物为插入在A2-和A3-域之间。还提供了产生本发明的FVIII蛋白的方法，编码这种蛋白质的核苷酸序列，含有核苷酸序列或蛋白质的药物组合物，以及治疗患有血友病的患者的方法。

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