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    CHIMERIC FACTOR VIII POLYPEPTIDES AND USES THEREOF
    41.
    发明申请
    CHIMERIC FACTOR VIII POLYPEPTIDES AND USES THEREOF 有权

    公开(公告)号：US20230011438A1

    公开(公告)日：2023-01-12

    申请号：US17826932

    申请日：2022-05-27

    Applicant: BIOVERATIV THERAPEUTICS INC.

    Inventor： Ekta Seth CHHABRA ,  Tongyao LIU ,  Robert T. PETERS ,  Haiyan JIANG

    IPC: C07K14/755 ,  A61K47/62 ,  C07K16/00

    Abstract: 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.

    PROCOAGULANT COMPOUNDS
    42.
    发明申请
    PROCOAGULANT COMPOUNDS 有权

    公开(公告)号：US20220243189A1

    公开(公告)日：2022-08-04

    申请号：US17577684

    申请日：2022-01-18

    Applicant: Bioverativ Therapeutics Inc.

    Inventor： Vu Phong HONG ,  Adam R. MEZO ,  Joe SALAS ,  Robert PETERS

    IPC: C12N9/64 ,  A61K38/02 ,  A61K38/36 ,  A61K38/48

    Abstract: The present disclosure provides protease-activatable procoagulant compounds comprising a procoagulant polypeptide, e.g., a procoagulant peptide and/or clotting factor, and a linker comprising a protease-cleavable substrate (e.g., a synthetic thrombin substrate) and a self-immolative spacer (e.g., p-amino benzyl carbamate). Upon cleavage of the protease-cleavable substrate by a protease (e.g., thrombin), the self-immolative spacer cleaves itself from the procoagulant polypeptide such that the polypeptide is in an underivatized and active form. Also provided are pharmaceutical compositions, methods for treating bleeding disorders using the disclosed compounds, methods of enhancing in vivo efficacy of procoagulant polypeptides, methods of increasing the efficacy of proteolytic cleavage of compounds comprising procoagulant polypeptides, methods of activating procoagulant polypeptides, and methods of releasing a procoagulant polypeptide from a heterologous moiety such as PEG.

    Chimeric factor VIII polypeptides and uses thereof
    44.
    发明授权
    Chimeric factor VIII polypeptides and uses thereof 有权

    公开(公告)号：US11370827B2

    公开(公告)日：2022-06-28

    申请号：US14371948

    申请日：2013-01-12

    Applicant: BIOVERATIV THERAPEUTICS INC.

    Inventor： Ekta Seth Chhabra ,  Tongyao Liu ,  Robert T Peters ,  Haiyan Jiang

    IPC: A61K38/37 ,  C07K14/755 ,  A61K47/62 ,  C07K16/00

    Abstract: 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.

    Factor VIII chimeric proteins and uses thereof
    45.
    发明授权
    Factor VIII chimeric proteins and uses thereof 有权

    公开(公告)号：US11192936B2

    公开(公告)日：2021-12-07

    申请号：US15110673

    申请日：2015-01-09

    Applicant: Bioverativ Therapeutics Inc.

    Inventor： Ekta Seth Chhabra ,  Tongyao Liu ,  Robert T. Peters ,  John Kulman

    IPC: C07K14/755 ,  C07K16/00 ,  A61K38/00

    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.

    USE OF LENTIVIRAL VECTORS EXPRESSING FACTOR VIII
    49.
    发明申请
    USE OF LENTIVIRAL VECTORS EXPRESSING FACTOR VIII 有权

    公开(公告)号：US20210038744A1

    公开(公告)日：2021-02-11

    申请号：US16965895

    申请日：2019-01-31

    Applicant: BIOVERATIV THERAPEUTICS INC.

    Inventor： Andrea ANNONI ,  Alessio CANTORE ,  Douglas DRAGER ,  Tongyao LIU ,  Michela MILANI ,  Jeff MOFFIT ,  Luigi NALDINI ,  Susannah PATARROYO-WHITE ,  Robert T. PETERS ,  Alexey SEREGIN

    IPC: A61K48/00 ,  A61K38/37

    Abstract: The present disclosure provides lentiviral vectors comprising codon optimized Factor VIII sequences, and methods of using such lentiviral vectors. The liver-targeted lentiviral vectors disclosed herein can be used for gene therapy, wherein the lentiviral gene delivery enables stable integration of the transgene expression cassette into the genome of targeted cells (e.g., hepatocytes) of pediatric (e.g., neonatal) or adult subjects, achieving an improvement in FVIII expression (for example, a 100-fold improvement) at low lentiviral vector doses (e.g., 5×1010 or lower, such as 1.5×109 or lower, or 1×108 TU/kg or lower). The present disclosure also provides methods of treating bleeding disorders such as hemophilia (e.g., hemophilia A) comprising administering to a subject in need thereof a liver-targeted lentiviral vector comprising a codon optimized Factor VIII nucleic acid sequence at low dosages (1×108 TU/kg or lower to 1.5×1010 TU/kg).

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