公开(公告)号：US20160199454A1

公开(公告)日：2016-07-14

申请号：US14912047

申请日：2014-08-14

Applicant: BIOGEN MA INC. ,  AMUNIX OPERATING INC.

Inventor： Tongyao LIU ,  Pei-Yun CHANG ,  John KULMAN ,  Volker SCHELLENBERGER ,  Haiyan JIANG ,  Robert T. PETERS ,  Ekta Seth CHHABRA

IPC: A61K38/37 ,  A61K9/00 ,  C07K14/00 ,  C07K14/755

Abstract: 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.

Abstract translation: 本发明提供了包含因子VIII（FVIII）多肽和XTEN多肽的嵌合蛋白。 FVIII多肽可以对血管性血友病因子（VWF）具有降低的亲和力。 适当大小的XTEN多肽在特定位置插入FVIII多肽中，以延长FVIII多肽的半衰期。 本发明还包括核苷酸，载体，宿主细胞和使用嵌合蛋白的方法，例如治疗出血疾病和病症。

公开(公告)号：US20160376344A1

公开(公告)日：2016-12-29

申请号：US15163561

申请日：2016-05-24

Applicant: Amunix Operating Inc.

Inventor： Volker SCHELLENBERGER ,  Pei-Yun CHANG ,  Fatbardha VARFAJ ,  John KULMAN ,  Tongyao LIU ,  Garabet G. TOBY ,  Haiyan JIANG ,  Robert PETERS ,  Deping WANG ,  Baisong MEI ,  Joshua SILVERMAN ,  Chia-Wei WANG ,  Benjamin SPINK ,  Nathan GEETHING

IPC: C07K14/755 ,  C07K14/00

CPC classification number: C07K14/755 ,  A61K38/00 ,  C07K14/001 ,  C07K2319/00 ,  C07K2319/21 ,  C07K2319/31 ,  C07K2319/41 ,  C07K2319/50 ,  C07K2319/95

Abstract: The present invention relates to compositions comprising factor VIII coagulation factors linked to extended recombinant polypeptide (XTEN), isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of making and using such compositions in treatment of factor VIII-related diseases, disorders, and conditions.

公开(公告)号：US20160185817A1

公开(公告)日：2016-06-30

申请号：US14910555

申请日：2014-08-08

Applicant: Biogen MA Inc.

Inventor： Lily ZHU ,  Anxhela KOLE ,  John KULMAN ,  Marisol ACOSTA

IPC: C07K1/36 ,  C07K14/755

CPC classification number: C07K1/36 ,  C07K14/755 ,  C07K2319/31

Abstract: The invention is directed to methods of purifying a chimeric protein comprising subjecting the chimeric protein to a factor VIII-specific affinity chromatography, and subjecting the chimeric protein to an AEX chromatography; wherein the chimeric protein comprises a factor VIII protein or a fragment thereof. The chimeric protein purified by the present methods shows improved factor VIII activity.

Abstract translation: 本发明涉及纯化嵌合蛋白的方法，包括使嵌合蛋白进行因子VIII特异性亲和层析，并使嵌合蛋白进行AEX色谱; 其中所述嵌合蛋白包含因子VIII蛋白或其片段。 通过本方法纯化的嵌合蛋白显示出改善的因子VIII活性。

公开(公告)号：US20160251408A1

公开(公告)日：2016-09-01

申请号：US14894108

申请日：2014-06-27

Applicant: BIOGEN MA INC.

Inventor： Ekta Seth CHHABRA ,  John KULMAN ,  Tongyao LIU

IPC: C07K14/755 ,  A61K38/37

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

Abstract: The present invention provides a chimeric molecule comprising a VWF protein fused to a heterologous moiety via a VWF linker. The invention provides an efficient VWF linker that can be cleaved in the presence of thrombin. The chimeric molecule can further comprise a polypeptide chain comprising a FVIII protein and a second heterologous moiety, wherein the chain comprising the VWF protein and the chain comprising the FVIII protein are associated with each other. The invention also includes nucleotides, vectors, host cells, methods of using the chimeric proteins.

Abstract translation: 本发明提供了包含通过VWF接头与异源部分融合的VWF蛋白质的嵌合分子。 本发明提供了可在凝血酶存在下被切割的有效的VWF接头。 嵌合分子可进一步包含含有FVIII蛋白和第二异源部分的多肽链，其中包含VWF蛋白的链和包含FVIII蛋白的链彼此相关联。 本发明还包括核苷酸，载体，宿主细胞，使用嵌合蛋白的方法。

公开(公告)号：US20160229903A1

公开(公告)日：2016-08-11

申请号：US14895264

申请日：2014-06-27

Applicant: Biogen MA Inc.

Inventor： Ekta Seth CHHABRA ,  John KULMAN ,  Tongyao LIU

IPC: C07K14/755 ,  C12P21/02

CPC classification number: C07K14/755 ,  A61K38/00 ,  A61K38/36 ,  A61K38/37 ,  C07K2319/30 ,  C12P21/02

Abstract: The present invention provides a chimeric molecule comprising a VWF protein fused to a heterologous moiety via a VWF linker. The invention provides an efficient VWF linker that can be cleaved in the presence of thrombin. The chimeric molecule can further comprise a polypeptide chain comprising a FVIII protein and a second heterologous moiety, wherein the chain comprising the VWF protein and the chain comprising the FVIII protein are associated with each other. The invention also includes nucleotides, vectors, host cells, methods of using the VWF fragment, or the chimeric proteins.

Abstract translation: 本发明提供了包含通过VWF接头与异源部分融合的VWF蛋白质的嵌合分子。 本发明提供了可在凝血酶存在下被切割的有效的VWF接头。 嵌合分子可进一步包含含有FVIII蛋白和第二异源部分的多肽链，其中包含VWF蛋白的链和包含FVIII蛋白的链彼此相关联。 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。

公开(公告)号：US20160130361A1

公开(公告)日：2016-05-12

申请号：US14894155

申请日：2014-06-13

Applicant: BIOGEN MA INC.

Inventor： John KULMAN

IPC: C07K16/36 ,  G01N33/86 ,  C07K14/755

CPC classification number: C07K16/36 ,  A61K38/00 ,  C07K14/755 ,  C07K2317/52 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  G01N33/86 ,  G01N2333/755 ,  G01N2800/224

Abstract: The present invention provides anti-FVIII antibodies and antigen-binding molecules thereof which specifically bind FVIII epitopes. The antibodies and antigen-binding molecules can be used to purify FVIII. The invention also includes nucleic acid molecules and methods of making the anti-FVIII antibodies or antigen binding molecules thereof.

Abstract translation: 本发明提供了特异性结合FVIII表位的抗FVIII抗体及其抗原结合分子。 抗体和抗原结合分子可用于纯化FVIII。 本发明还包括核酸分子和制备抗FVIII抗体或其抗原结合分子的方法。