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公开(公告)号:US20220275057A1
公开(公告)日:2022-09-01
申请号:US17519719
申请日:2021-11-05
Applicant: Bioverativ Therapeutics Inc.
Inventor: Ekta Seth CHHABRA , Tongyao LIU , Robert T. PETERS , John KULMAN
IPC: C07K14/755 , C07K16/00
Abstract: The present invention provides a chimeric protein comprising a first polypeptide which comprises a FVIII protein and a first Ig constant region or a portion thereof and a second polypeptide which comprises a VWF protein comprising the D′ domain and D3 domain of VWF, a XTEN sequence having less than 288 amino acids in length, and a second Ig constant region or a portion thereof, wherein the first polypeptide and the second polypeptide are associated with each other. The invention also includes nucleotides, vectors, host cells, methods of using the chimeric proteins.
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公开(公告)号:US20190169267A1
公开(公告)日:2019-06-06
申请号:US16154310
申请日:2018-10-08
Applicant: Bioverativ Therapeutics Inc.
Inventor: Ekta Seth CHHABRA , Tongyao LIU , Pei-yun CHANG , Robert T. PETERS , John KULMAN
Abstract: The present invention provides a chimeric protein comprising a VWF protein comprising the 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 comprising a VWF fragment of the invention binds to or is associated with a polypeptide chain comprising a FVIII protein linked to an XTEN sequence and the polypeptide chain comprising the VWF fragment can prevent or inhibit binding of endogenous VWF to the FVIII protein linked to the XTEN sequence. By preventing or inhibiting binding of endogenous VWF to the FVIII protein, which is a half-life limiting factor for FVIII, the VWF fragment can induce extension of half-life of the chimeric protein comprising a FVIII protein. The invention also includes nucleotides, vectors, host cells, methods of using the VWF fragment, or the chimeric proteins.
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公开(公告)号:US20220106383A1
公开(公告)日:2022-04-07
申请号:US17479705
申请日:2021-09-20
Applicant: Bioverativ Therapeutics Inc.
Inventor: Ekta Seth CHHABRA , John KULMAN , Tongyao LIU
IPC: C07K14/755 , A61K38/37
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.
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公开(公告)号:US20230322901A1
公开(公告)日:2023-10-12
申请号:US18068288
申请日:2022-12-19
Applicant: BIOVERATIV THERAPEUTICS INC.
Inventor: John KULMAN
IPC: C07K14/755 , C07K14/59 , C07K14/79 , A61K38/37 , A61K35/14 , C07K14/00 , C07K14/435 , C07K14/705 , C07K14/76
CPC classification number: C07K14/755 , C07K14/59 , C07K14/79 , A61K38/37 , A61K35/14 , C07K14/00 , C07K14/43504 , C07K14/705 , C07K14/76 , C07K2319/00 , C07K2319/30 , C07K2319/31 , C07K2319/60 , A61K38/00
Abstract: Provided are recombinant Factor VIII proteins, e.g., human Factor VIII proteins with heterologous moieties inserted into flexible permissive loops located in the Factor VIII A domains, while retaining the procoagulant activity of Factor VIII.
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公开(公告)号:US20210261607A1
公开(公告)日:2021-08-26
申请号:US17155935
申请日:2021-01-22
Applicant: Bioverativ Therapeutics Inc.
Inventor: Lily ZHU , Anxhela KOLE , John KULMAN , Marisol ACOSTA
IPC: C07K1/36 , C07K14/755
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.
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公开(公告)号:US20210238259A1
公开(公告)日:2021-08-05
申请号:US16478747
申请日:2018-01-31
Applicant: BIOVERATIV THERAPEUTICS INC.
Inventor: Arjan VAN DER FLIER , Zhiqian LIU , David R. LIGHT , Ekta Seth CHHABRA , Tongyao LIU , Robert T. PETERS , John KULMAN , Ayman ISMAIL
IPC: C07K14/745 , C12N9/64
Abstract: The present disclosure provides Factor IX (FIX) fusion proteins comprising at least one heterologous moiety, such as an XTEN. The present disclosure further discloses methods of making and using the FIX fusion proteins.
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公开(公告)号:US20240083975A1
公开(公告)日:2024-03-14
申请号:US18358601
申请日:2023-07-25
Applicant: Bioverativ Therapeutics Inc.
Inventor: Ekta Seth CHHABRA , John KULMAN , Tongyao LIU
IPC: C07K14/755 , A61K38/37
CPC classification number: C07K14/755 , A61K38/37 , A61K38/00
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.
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公开(公告)号:US20230192896A1
公开(公告)日:2023-06-22
申请号:US16462878
申请日:2017-11-22
Applicant: Bioverativ Therapeutics Inc.
Inventor: Robert T. PETERS , Nina LEKSA , Bradley R. PEARSE , John KULMAN , Maria ALEMAN , Allison GOODMAN
CPC classification number: C07K16/468 , A61P7/04 , C07K2317/565 , C07K2317/31 , C07K2317/34
Abstract: The present disclosure provides antibodies that selectively binds to specific forms of clotting factors, in particular, antibodies that specifically binds to activated factor IX (FIXa) wherein the anti-FIXa antibody or an antigen binding portion thereof preferentially binds to FIXa in the presence of FIXa and factor IX zymogen (FIXz), and antibodies that specifically bind to factor X zymogen (FXz) wherein the anti-FXz antibody or antigen binding portion thereof preferentially binds to FXz in the presence of FXz and activated factor X (FXa). Also provided are bispecific molecules (e.g., antibodies) comprising, e.g., an anti-FIXa antibody or antigen binding portion thereof and/or an anti-FXz antibody or antigen binding portion thereof. The disclosure also provides compositions encoding the disclosed antibodies and bispecific molecules, vectors, cells, pharmaceutical and diagnostic compositions, kits, methods of manufacture, methods of use, and immunoconjugates.
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公开(公告)号:US20200048327A1
公开(公告)日:2020-02-13
申请号:US16516816
申请日:2019-07-19
Applicant: BIOVERATIV THERAPEUTICS INC.
Inventor: John KULMAN
IPC: C07K14/755 , C07K14/59 , C07K14/79 , A61K38/37 , A61K35/14 , C07K14/00 , C07K14/435 , C07K14/705 , C07K14/76
Abstract: Provided are recombinant Factor VIII proteins, e.g., human Factor VIII proteins with heterologous moieties inserted into flexible permissive loops located in the Factor VIII A domains, while retaining the procoagulant activity of Factor VIII.
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公开(公告)号:US20180355341A1
公开(公告)日:2018-12-13
申请号:US15750119
申请日:2016-08-03
Applicant: Bioverativ Therapeutics Inc.
Inventor: Zhiqian LIU , Ajan VAN DER FLIER , David R. LIGHT , Ekta Seth CHHABRA , Tongyao LIU , Robert T. PETERS , John KULMAN , Ayman ISMAIL
CPC classification number: C12N9/644 , A61K9/0019 , A61K38/00 , A61P7/04 , C07K14/00 , C07K2319/00 , C07K2319/30 , C12Y304/21022
Abstract: The present invention provides Factor IX (FIX) fusion proteins comprising at least one heterologous moiety, such as an XTEN. The present invention further discloses methods of making and using the FIX fusion proteins.
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