单链因子viii分子

文档序号:1835805 发布日期:2021-11-12 浏览:30次 >En<

阅读说明:本技术 单链因子viii分子 (Single chain factor VIII molecules ) 是由 S·基斯特纳 C·昂格雷尔 J·道芬巴赫 P·赫伯纳 于 2020-05-08 设计创作,主要内容包括:本发明涉及重组因子VIII蛋白,其在单链中包括包含因子VIII的A1和A2结构域的重链部分和包含因子VIII的A3、C1和C2结构域的轻链部分,其中B-结构域在两个缺失中部分缺失,第一个导致存在可被凝血酶切割的确定的加工序列,并且第二个导致在位置R1664-R1667处不存在弗林蛋白酶切割识别位点。B-结构域的内部片段被保留。还提供了编码所述蛋白的核酸、宿主细胞和制备该蛋白的方法,以及包含所述蛋白、核酸或宿主细胞的药物组合物,其可用于治疗A型血友病。(The present invention relates to a recombinant factor VIII protein comprising in single chain a heavy chain portion comprising the a1 and a2 domains of factor VIII and a light chain portion comprising the A3, C1 and C2 domains of factor VIII, wherein the B-domain is partially deleted in two deletions, the first resulting in the presence of a defined processing sequence cleavable by thrombin and the second resulting in the absence of a furin cleavage recognition site at positions R1664-R1667. The internal fragment of the B-domain is retained. Also provided are nucleic acids encoding the proteins, host cells and methods of making the proteins, as well as pharmaceutical compositions comprising the proteins, nucleic acids or host cells, which are useful for treating hemophilia a.)

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