公开(公告)号：US20140370035A1

公开(公告)日：2014-12-18

申请号：US14371931

申请日：2013-01-12

申请人： Biogen Idec MA Inc. ,  Puget Sound Blood Center

发明人： Haiyan Jiang ,  Tongyao Liu ,  Sriram Krishnamoorthy ,  Neil Josephson ,  Glenn Pierce

IPC分类号： A61K47/48 ,  C12Q1/68 ,  A61K38/37

CPC分类号： C12Q1/6883 ,  A61K38/21 ,  A61K38/37 ,  A61K39/0008 ,  A61K47/6811 ,  A61K47/6815 ,  A61K2039/6031 ,  A61K2039/6056 ,  C07K14/755 ,  C07K2319/30 ,  C12Q2600/156 ,  A61K2300/00

摘要： The present disclosure provides methods of administering chimeric and hybrid Factor VIII (FVIII) polypeptides comprising FVIII and Fc to subjects at risk of developing inhibitory FVIII immune responses, including anti-FVIII antibodies and/or cell-mediated immunity. The administration is sufficient to promote coagulation and to induce immune tolerance to FVIII. The chimeric polypeptide can comprise full-length FVIII or a FVIII polypeptide containing a deletion, e.g., a full or partial deletion of the B domain.

摘要翻译： 本公开提供了将具有FVIII和Fc的嵌合和杂合因子VIII（FVIII）多肽施用于具有发展抑制性FVIII免疫应答风险的受试者的方法，所述风险包括抗FVIII抗体和/或细胞介导的免疫。 该施用足以促进凝血并诱导对FVIII的免疫耐受。 嵌合多肽可以包含全长FVIII或含有缺失的FVIII多肽，例如B结构域的完整或部分缺失。

公开(公告)号：US11286528B2

公开(公告)日：2022-03-29

申请号：US16246225

申请日：2019-01-11

申请人： Bioverativ Therapeutics Inc. ,  Puget Sound Blood Center

发明人： Haiyan Jiang ,  Tongyao Liu ,  Sriram Krishnamoorthy ,  Neil Josephson ,  Glenn Pierce

IPC分类号： C07K14/755 ,  C12Q1/6883 ,  A61K38/21 ,  A61K39/00 ,  A61K38/37 ,  A61K47/68

摘要： The present disclosure provides methods of administering chimeric and hybrid Factor VIII (FVIII) polypeptides comprising FVIII and Fc to subjects at risk of developing inhibitory FVIII immune responses, including anti-FVIII antibodies and/or cell-mediated immunity. The administration is sufficient to promote coagulation and to induce immune tolerance to FVIII. The chimeric polypeptide can comprise full-length FVIII or a FVIII polypeptide containing a deletion, e.g., a full or partial deletion of the B domain.

公开(公告)号：US10221455B2

公开(公告)日：2019-03-05

申请号：US14371931

申请日：2013-01-12

申请人： Bioverativ Therapeutics Inc. ,  Puget Sound Blood Center

发明人： Haiyan Jiang ,  Tongyao Liu ,  Sriram Krishnamoorthy ,  Neil Josephson ,  Glenn Pierce

IPC分类号： C07K14/755 ,  C12Q1/6883 ,  A61K38/37 ,  A61K38/21 ,  A61K39/00 ,  A61K47/68

摘要： The present disclosure provides methods of administering chimeric and hybrid Factor VIII (FVIII) polypeptides comprising FVIII and Fc to subjects at risk of developing inhibitory FVIII immune responses, including anti-FVIII antibodies and/or cell-mediated immunity. The administration is sufficient to promote coagulation and to induce immune tolerance to FVIII. The chimeric polypeptide can comprise full-length FVIII or a FVIII polypeptide containing a deletion, e.g., a full or partial deletion of the B domain.

公开(公告)号：US20190241960A1

公开(公告)日：2019-08-08

申请号：US16246225

申请日：2019-01-11

申请人： Bioverativ Therapeutics Inc. ,  Puget Sound Blood Center

发明人： Haiyan Jiang ,  Tongyao Liu ,  Sriram Krishnamoorthy ,  Neil Josephson ,  Glenn Pierce

IPC分类号： C12Q1/6883 ,  C07K14/755 ,  A61K47/68 ,  A61K39/00 ,  A61K38/21 ,  A61K38/37

CPC分类号： C12Q1/6883 ,  A61K38/21 ,  A61K38/37 ,  A61K39/0008 ,  A61K47/6811 ,  A61K47/6815 ,  A61K2039/6031 ,  A61K2039/6056 ,  C07K14/755 ,  C07K2319/30 ,  C12Q2600/156 ,  A61K2300/00

摘要： The present disclosure provides methods of administering chimeric and hybrid Factor VIII (FVIII) polypeptides comprising FVIII and Fc to subjects at risk of developing inhibitory FVIII immune responses, including anti-FVIII antibodies and/or cell-mediated immunity. The administration is sufficient to promote coagulation and to induce immune tolerance to FVIII. The chimeric polypeptide can comprise full-length FVIII or a FVIII polypeptide containing a deletion, e.g., a full or partial deletion of the B domain.

公开(公告)号：US20150023959A1

公开(公告)日：2015-01-22

申请号：US14371948

申请日：2013-01-12

申请人： BIOGEN IDEC MA INC.

发明人： Ekta Seth Chhabra ,  Tongyao Liu ,  Robert T. Peters ,  Haiyan Jiang

IPC分类号： C07K14/755 ,  C07K16/00

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联，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性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。