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    Procoagulant compounds
    6.
    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.

    Procoagulant compounds
    9.
    发明授权
    Procoagulant compounds 有权

    公开(公告)号：US11261437B2

    公开(公告)日：2022-03-01

    申请号：US16357153

    申请日：2019-03-18

    Applicant: Bioverativ Therapeutics Inc.

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

    Chimeric clotting factors
    10.
    发明授权
    Chimeric clotting factors 有权

    公开(公告)号：US11168316B2

    公开(公告)日：2021-11-09

    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 ,  A61K47/62 ,  A61K38/36 ,  A61K38/48

    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.

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