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    BISPECIFIC ASYMMETRIC HETERODIMERS COMPRISING ANTI-CD3 CONSTRUCTS
    4.
    发明公开
    BISPECIFIC ASYMMETRIC HETERODIMERS COMPRISING ANTI-CD3 CONSTRUCTS 审中-公开
    非对称双特异性异源二聚体与抗CD3构建

    公开(公告)号：EP2872170A2

    公开(公告)日：2015-05-20

    申请号：EP13816697.0

    申请日：2013-07-13

    申请人： Zymeworks, Inc.

    发明人： DIXIT, Surjit Bhimarao ,  SPRETER VON KREUDENSTEIN, Thomas ,  NG, Gordon, Yiu Kon ,  WEISSER, Nina E.

    IPC分类号： A61K39/00 ,  A61K39/395 ,  C12P21/08

    CPC分类号： C07K16/2809 ,  C07K16/2803 ,  C07K16/2887 ,  C07K16/32 ,  C07K2317/31 ,  C07K2317/35 ,  C07K2317/52 ,  C07K2317/524 ,  C07K2317/526 ,  C07K2317/528 ,  C07K2317/622 ,  C07K2317/64 ,  C07K2317/71 ,  C07K2317/72 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/74 ,  C07K2317/92 ,  C07K2317/94 ,  C07K2319/31

    摘要： Disclosed herein are isolated multispecific heteromultimer constructs comprising multispecific heteromultimer construct comprising: a first polypeptide construct comprising a first heavy chain polypeptide and a CD3 binding polypeptide construct that binds to a CD3 complex on at least one CD3 expressing cell; a second polypeptide construct comprising a second heavy chain polypeptide which is different from said first heavy chain polypeptide, and an antigen binding polypeptide construct that binds to a target antigen on at least one B cell; wherein: said multispecific heteromultimer construct simultaneously engages said at least one B cell and said at least one CD3 expressing cell such that the CD3 expressing cell is activated, thereby inducing killing of the B cell; and said first and second heavy chain polypeptides form a heterodimeric Fc region comprising a variant immunoglobulin CH3 region comprising at least one amino acid mutation that promotes the formation of said heterodimeric Fc with stability at least comparable to a native homodimeric Fc, and with high purity. Also provided are isolated multispecific heteromultimer construct comprising: a first polypeptide construct comprising a first transporter polypeptide fused to at least one CD3 binding polypeptide construct that binds to a CD3 complex on at least one CD3 expressing cell; a second polypeptide construct comprising a second transporter polypeptide which is different from said first transporter polypeptide, fused to at least one antigen binding polypeptide construct that binds to a target antigen on at least one B cell; wherein said first and second transporter polypeptides are derived from a protein by segmentation of said protein, each transporter polypeptide comprising an amino acid sequence with at least 90% identity to a segment of said protein, and wherein said transporter polypeptides self-assemble to form a quasi-native structure of said monomeric protein.

    BISPECIFIC HER2 AND HER3 ANTIGEN BINDING CONSTRUCTS
    6.
    发明公开
    BISPECIFIC HER2 AND HER3 ANTIGEN BINDING CONSTRUCTS 审中-公开
    BISPEZIFISCHE HER2- UND HER3-ANTIGENBINDENDE KONSTRUKTE

    公开(公告)号：EP2994164A1

    公开(公告)日：2016-03-16

    申请号：EP14794897.0

    申请日：2014-05-08

    申请人： Zymeworks, Inc.

    发明人： NG, Gordon, Yiu Kon ,  CHAN, Peter, Wing Yiu ,  WICKMAN, Grant, Raymond

    IPC分类号： A61K39/395

    摘要： Described herein are isolated bi-specific antigen binding constructs, e.g., antibodies. The bi-specific antigen binding constructs include two antigen binding polypeptide constructs, e.g., a Fab and an scFv. The first antigen-binding polypeptide construct monovalently and specifically binds to extracellular domain 4 (ECD4) of HER2 (human epidermal growth factor receptor 2); the second antigen-binding polypeptide construct monovalently and specifically binds to an extracellular domain (ECD) of HER3 (human epidermal growth factor receptor 3). One antigen binding polypeptide construct is a Fab format and the other antigen binding polypeptide construct is an scFv format. The bi-specific antigen binding constructs includes an Fc having two Fc polypeptides each having a CH3 domain for dimerization. Each Fc polypeptide is linked to the C-terminus of one of the antigen binding polypeptide constructs with or without a linker.

    摘要翻译： 本文描述的是分离的双特异性抗原结合构建体，例如抗体。 双特异性抗原结合构建体包括两个抗原结合多肽构建体，例如Fab和scFv。 第一抗原结合多肽构建物与HER2（人表皮生长因子受体2）的细胞外结构域4（ECD4）单价并特异性结合; 第二抗原结合多肽构建物单独且特异性结合HER3（人表皮生长因子受体3）的细胞外结构域（ECD）。 一个抗原结合多肽构建体是Fab格式，另一个抗原结合多肽构建体是scFv格式。 双特异性抗原结合构建体包括具有两个Fc多肽的Fc，每个Fc多肽具有用于二聚化的CH3结构域。 每个Fc多肽与具有或不具有接头的抗原结合多肽构建体之一的C-末端连接。