公开(公告)号：EP3033097A4

公开(公告)日：2017-01-25

申请号：EP14835828

申请日：2014-08-14

申请人： BIOGEN MA INC ,  AMUNIX OPERATING INC

发明人： LIU TONGYAO ,  CHANG PEI-YUN ,  KULMAN JOHN ,  SCHELLENBERGER VOLKER ,  JIANG HAIYAN ,  PETERS ROBERT T ,  CHHABRA EKTA SETH

IPC分类号： A61K38/36 ,  A61K35/14 ,  A61K38/37 ,  C07K1/00 ,  C07K14/745 ,  C07K14/755

CPC分类号： A61K38/37 ,  A61K9/0019 ,  A61K38/00 ,  C07K14/00 ,  C07K14/755 ,  C07K2319/31

摘要： The present invention provides chimeric proteins comprising a Factor VIII (FVIII) polypeptide and XTEN polypeptides. The FVIII polypeptide can have a reduced affinity for von Willebrand Factor (VWF). XTEN polypeptides of appropriate sizes are inserted into the FVIII polypeptide at particular locations in order to extend the half-life of the FVIII polypeptide. The invention also includes nucleotides, vectors, host cells, and methods of using the chimeric proteins, e.g., to treat bleeding diseases and disorders.

公开(公告)号：EP2882450A4

公开(公告)日：2016-06-22

申请号：EP13816031

申请日：2013-07-10

申请人： AMUNIX OPERATING INC ,  BIOGEN MA INC

发明人： CHHABRA EKTA SETH ,  LIU TONGYAO ,  CHANG PEI-YUN ,  PETERS ROBERT T ,  KULMAN JOHN

IPC分类号： A61K38/37 ,  A61K38/36 ,  C07K14/755 ,  C12N15/00 ,  C12N15/62 ,  C12P21/08

CPC分类号： C07K14/755 ,  A61K38/36 ,  A61K38/37 ,  A61K47/481 ,  A61K47/55 ,  C07K16/00 ,  C07K2319/00 ,  C07K2319/30 ,  C07K2319/31 ,  C07K2319/35 ,  C07K2319/50 ,  C12N15/11

摘要： The present invention includes a chimeric protein comprising a VWF protein with D′ domain and D3 domain of VWF, one or more XTEN sequence, and a FVIII protein, wherein the VWF fragment, the XTEN sequence, or the FVIII protein are linked to or associated with each other. The chimeric protein can further comprise one or more Ig constant region or a portion thereof (e.g., an Fc region). A polypeptide chain of a VWF fragment is associated with a FVIII polypeptide chain linked to an XTEN sequence. The VWF fragment polypeptide chain can prevent or inhibit binding of endogenous VWF to FVIII protein linked to the XTEN sequence. By preventing or inhibiting binding of endogenous VWF to FVIII protein, VWF fragment can extend half-life of chimeric protein comprising FVIII protein. The invention includes nucleotides, vectors, host cells, use of VWF fragment, or chimeric proteins.

公开(公告)号：EP3013358A4

公开(公告)日：2017-03-22

申请号：EP14817900

申请日：2014-06-27

申请人： BIOGEN MA INC

发明人： CHHABRA EKTA SETH ,  KULMAN JOHN ,  LIU TONGYAO

IPC分类号： C07K14/755 ,  A61K38/00 ,  A61K38/37 ,  A61K48/00

CPC分类号： C07K14/755 ,  A61K38/00 ,  A61K38/37 ,  A61K48/00 ,  C07K2319/00 ,  C07K2319/30 ,  C07K2319/35 ,  C07K2319/50 ,  C07K2319/70 ,  C07K2319/90

公开(公告)号：EP3013359A4

公开(公告)日：2017-01-25

申请号：EP14818050

申请日：2014-06-27

申请人： BIOGEN MA INC

发明人： CHHABRA EKTA SETH ,  KULMAN JOHN ,  LIU TONGYAO

IPC分类号： A61K38/37 ,  A61P7/04

CPC分类号： C07K14/755 ,  A61K38/00 ,  A61K38/36 ,  A61K38/37 ,  C07K2319/30 ,  C12P21/02

公开(公告)号：EP2804623A4

公开(公告)日：2015-12-02

申请号：EP13735649

申请日：2013-01-12

申请人： BIOGEN MA INC

发明人： CHHABRA EKTA SETH ,  LIU TONGYAO ,  PETERS ROBERT ,  JIANG HAIYAN

IPC分类号： A61K38/37

CPC分类号： C07K14/755 ,  A61K38/37 ,  A61K47/62 ,  C07K16/00 ,  C07K2317/94 ,  C07K2319/00 ,  C07K2319/31

摘要： The present invention provides a VWF fragment comprising the D′ domain and D3 domain of VWF, a chimeric protein comprising the VWF fragment and a heterologous moiety, or a chimeric protein comprising the VWF fragment and a FVIII protein and methods of using the same. A polypeptide chain comprising a VWF fragment of the invention binds to or is associated with a polypeptide chain comprising a FVIII protein and the polypeptide chain comprising the VWF fragment can prevent or inhibit binding of endogenous VWF to the FVIII protein. By preventing or inhibiting binding of endogenous VWF to the FVIII, which is a half-life limiting factor for FVIII, the VWF fragment can induce extension of half-life of the FVIII protein. The invention also includes nucleotides, vectors, host cells, methods of using the VWF fragment, or the chimeric proteins.

摘要翻译： 本发明提供了包含VWF的D'结构域和D3结构域的VWF片段，包含VWF片段和异源部分的嵌合蛋白质，或包含VWF片段和FVIII蛋白质的嵌合蛋白质及其使用方法。 包含本发明的VWF片段的多肽链与包含FVIII蛋白的多肽链结合或相关，并且包含VWF片段的多肽链可以预防或抑制内源性VWF与FVIII蛋白的结合。 通过预防或抑制内源VWF与作为FVIII的半衰期限制因子的FVIII的结合，VWF片段可诱导FVIII蛋白的半衰期延长。 本发明还包括核苷酸，载体，宿主细胞，使用VWF片段或嵌合蛋白的方法。