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    SINGLE-ARM MONOVALENT ANTIBODY CONSTRUCTS AND USES THEREOF
    51.
    发明公开
    SINGLE-ARM MONOVALENT ANTIBODY CONSTRUCTS AND USES THEREOF 审中-公开
    EINZELARM-MONOVALENTEANTIKÖRPERKONSTRUKTEUND VERWENDUNGEN DAVON

    公开(公告)号：EP2847224A4

    公开(公告)日：2016-04-27

    申请号：EP13788508

    申请日：2013-05-08

    申请人： ZYMEWORKS INC

    发明人： NG GORDON YIU KON ,  DIXIT SURJIT BHIMARAO ,  SPRETER VON KREUDENSTEIN THOMAS

    IPC分类号： C07K16/46 ,  A61K39/00 ,  A61K39/395 ,  A61K47/48 ,  C07K16/28 ,  C07K16/30 ,  C07K16/32

    CPC分类号： C07K16/32 ,  A61K39/39558 ,  A61K47/48584 ,  A61K47/6803 ,  A61K47/6855 ,  A61K2039/505 ,  C07K16/3015 ,  C07K2317/35 ,  C07K2317/41 ,  C07K2317/51 ,  C07K2317/515 ,  C07K2317/52 ,  C07K2317/526 ,  C07K2317/55 ,  C07K2317/622 ,  C07K2317/64 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2317/94 ,  C12P21/02

    摘要： Provided herein are monovalent antibody constructs. In specific embodiments is a monovalent antibody construct comprising: an antigen-binding polypeptide construct which monovalently binds an antigen; and a dimeric Fc polypeptide construct comprising a CH3 domain, said construct comprising two monomeric Fc polypeptides, wherein one said monomeric Fc polypeptide is fused to at least one polypeptide from the antigen-binding polypeptide construct. These therapeutically novel molecules encompass monovalent constructs that display an increase in binding density and Bmax (maximum binding at a target to antibody ratio of 1:1) to a target cell displaying said antigen as compared to a corresponding monospecific bivalent antibody construct with two antigen binding regions. Provided herein are methods for creation of monovalent antibody constructs that shows superior effector efficacy as compared to the corresponding bivalent antibody construct at equimolar concentrations. Provided herein are methods for creation of monovalent antibody constructs that unexpectedly inhibit tumor cell growth and can be internalized and show greater efficacy compared to a bivalent antibody construct at equimolar saturating concentrations. Provided are monovalent antibody constructs for the treatment of HER2 expressing diseases.

    摘要翻译： 本文提供单价抗体构建体。 在具体实施方案中是单价抗体构建体，其包含：单价结合抗原的抗原结合多肽构建体; 和包含CH3结构域的二聚Fc多肽构建体，所述构建体包含两个单体Fc多肽，其中一个所述单体Fc多肽与来自抗原结合多肽构建物的至少一种多肽融合。 与具有两个抗原结合的相应的单特异性二价抗体构建体相比，这些治疗性新颖的分子包括显示结合密度和Bmax（目标与抗体比例为1:1的最大结合）与显示所述抗原的靶细胞的增加的单价构建体 区域。 本文提供了用于产生与等摩尔浓度相对于相应的二价抗体构建体相比优异的效应子功效的单价抗体构建体的方法。 本文提供了产生意想不到的抑制肿瘤细胞生长并且可以内化的单价抗体构建体的方法，并且在等摩尔浓度下与二价抗体构建体相比显示更大的功效。 提供用于治疗表达HER2的疾病的单价抗体构建体。

    BISPECIFIC HER2 AND HER3 ANTIGEN BINDING CONSTRUCTS
    52.
    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。

    SYSTEMS AND METHODS FOR IDENTIFYING THERMODYNAMICALLY RELEVANT POLYMER CONFORMATIONS
    53.
    发明公开
    SYSTEMS AND METHODS FOR IDENTIFYING THERMODYNAMICALLY RELEVANT POLYMER CONFORMATIONS 审中-公开
    系统和用于鉴定THERMO动态关联POLYMERKONFORMATIONEN

    公开(公告)号：EP2864917A4

    公开(公告)日：2015-12-16

    申请号：EP13807096

    申请日：2013-06-21

    申请人： ZYMEWORKS INC

    发明人： LAKATOS GREGORY ,  SRINIVASAN SIDDHARTH ,  DIXIT SURJIT BHIMARAO

    IPC分类号： G06F19/16 ,  C07K1/00 ,  C40B30/02 ,  G01N33/68 ,  G06F19/00

    CPC分类号： G06F19/16 ,  C07K1/00 ,  C07K2299/00 ,  G01N33/68 ,  G06F19/704 ,  G06F19/707

    摘要： Systems, methods and non-transitory computer readable media identify favored polymer conformations. One or more residues are identified and may be replaced in the polymer, or the original primary sequence of the polymer may be retained. The conformations of residues in a subset of residues in a region of the identified one or more residues are altered. This conformational adjustment is repeated for other subsets of residues in the region of the identified one or more residues, and for other conformations, thereby deriving a plurality of polymer structures. A set of clusters is generated for each residue of the polymer using the conformationally adjusted structures, thereby creating sets of clusters. Structures in the plurality of structures are grouped into subgroups when the structures fall into the same clusters across a threshold number of the sets of clusters. One or more physical properties are determined for structures in subgroups, thereby identifying one or more thermodynamically relevant polymer conformations for the polymer.