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    OPTIMIZED FACTOR VIII GENE
    112.
    发明申请
    OPTIMIZED FACTOR VIII GENE 审中-公开

    公开(公告)号：US20200024327A1

    公开(公告)日：2020-01-23

    申请号：US16452010

    申请日：2019-06-25

    Applicant: BIOVERATIV THERAPEUTICS INC.

    Inventor： Siyuan TAN ,  Robert T. PETERS

    IPC: C07K14/755 ,  C12N9/64

    Abstract: The present invention provides codon optimized Factor VIII sequences, vectors and host cells comprising codon optimized Factor VIII sequences, polypeptides encoded by codon optimized Factor VIII sequences, and methods of producing such polypeptides.The present invention also provides methods of treating bleeding disorders such as hemophilia comprising administering to the subject a codon optimized Factor VIII nucleic acid sequence or the polypeptide encoded thereby.

    CHIMERIC CLOTTING FACTORS
    114.
    发明申请
    CHIMERIC CLOTTING FACTORS 审中-公开

    公开(公告)号：US20190225957A1

    公开(公告)日：2019-07-25

    申请号：US16228144

    申请日：2018-12-20

    Applicant: Bioverativ Therapeutics Inc.

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

    IPC: C12N9/64 ,  A61K38/36 ,  A61K38/48 ,  A61K47/62

    Abstract: The invention provides chimeric clotting factors comprising an activatable clotting factor and an enhancer moiety. The activatable clotting factor allows the chimeric clotting factor to be activated at the site of coagulation. The enhancer moiety can additionally improve procoagulation activities of the chimeric clotting factors. The chimeric clotting factors can further be improved by fusion to a half-life extender, which improves a pharmacokinetics property of the chimeric clotting factor. The invention also includes methods of making and methods of using these chimeric clotting factors.

    FACTOR VIII COMPLEX WITH XTEN AND VON WILLEBRAND FACTOR PROTEIN, AND USES THEREOF
    116.
    发明申请
    FACTOR VIII COMPLEX WITH XTEN AND VON WILLEBRAND FACTOR PROTEIN, AND USES THEREOF 审中-公开

    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

    IPC: C07K14/755 ,  A61K47/55 ,  C12N15/11 ,  C07K16/00 ,  A61K38/36 ,  A61K38/37

    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.

    Procoagulant compounds
    117.
    发明授权
    Procoagulant compounds 有权

    公开(公告)号：US10287564B2

    公开(公告)日：2019-05-14

    申请号：US14406163

    申请日：2013-06-07

    Applicant: Bioverativ Therapeutics Inc.

    Inventor： Vu Phong Hong ,  Adam R. Mezo ,  Joe Salas ,  Robert T. Peters

    IPC: C12N9/64 ,  A61K47/62 ,  A61K38/36 ,  A61K38/48 ,  A61K38/02

    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.

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