FACTOR VIII CHIMERIC PROTEINS AND USES THEREOF

    公开(公告)号:US20220275057A1

    公开(公告)日:2022-09-01

    申请号:US17519719

    申请日:2021-11-05

    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.

    FACTOR VIII COMPLEX WITH XTEN AND VON WILLEBRAND FACTOR PROTEIN, AND USES THEREOF

    公开(公告)号:US20190169267A1

    公开(公告)日:2019-06-06

    申请号:US16154310

    申请日:2018-10-08

    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.

    THROMBIN CLEAVABLE LINKER WITH XTEN AND ITS USES THEREOF

    公开(公告)号:US20220106383A1

    公开(公告)日:2022-04-07

    申请号:US17479705

    申请日:2021-09-20

    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.

    THROMBIN CLEAVABLE LINKER WITH XTEN AND ITS USES THEREOF

    公开(公告)号:US20240083975A1

    公开(公告)日:2024-03-14

    申请号:US18358601

    申请日:2023-07-25

    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.

    BISPECIFIC ANTIBODIES BINDING TO COAGULATION FACTOR IX AND COAGULATION FACTOR X

    公开(公告)号:US20230192896A1

    公开(公告)日:2023-06-22

    申请号:US16462878

    申请日:2017-11-22

    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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