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    CRYSTAL STRUCTURES OF HETERODIMERIC FC DOMAINS
    9.
    发明公开
    CRYSTAL STRUCTURES OF HETERODIMERIC FC DOMAINS 有权
    KRISTALLSTRUKTUREN AUS HETERLDEREN FC-DOMÄNEN

    公开(公告)号：EP2914634A4

    公开(公告)日：2016-05-11

    申请号：EP13851307

    申请日：2013-10-31

    申请人： ZYMEWORKS INC

    发明人： SPRETER VON KREUDENSTEIN THOMAS ,  DIXIT SURJIT BHIMARAO ,  LARIO PAULA IRENE ,  ESCOBAR-CABRERA ERIC ,  BOULANGER MARTIN J ,  SUITS MICHAEL D L

    IPC分类号： C07K16/46 ,  A61K39/395 ,  C07K16/28 ,  G06F19/16

    CPC分类号： C07K16/00 ,  C07K16/2887 ,  C07K16/32 ,  C07K2299/00 ,  C07K2317/524 ,  C07K2317/526 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/92 ,  C07K2317/94 ,  G06F19/16

    摘要： Disclosed are the atomic coordinates of compositions comprising Fc heterodimer proteins in crystalline form derived from high resolution x-ray diffraction. Further disclosed are systems and methods for using all or a portion of these atomic coordinates to identify and design improved Fc heterodimer proteins. Further disclosed are compositions comprising a mixture of (i) a solubilized Fc heterodimer protein and (ii) a mother liquor solution. The mother liquor solution comprises between 2% and 10% (v/v) ethylene glycol, between 10% and 25% (w/v) polyethylene glycol having an average molecular weight of between 2000 Daltons and 10000 Daltons, and between 0.05 M and 0.40 M ammonium iodide. Further disclosed are systems and methods of identifying a mutation which promotes heterodimeric Fc chain pair formation in which structure based modeling is performed to identify a candidate mutation to an Fc chain using all or a portion of the disclosed three-dimensional atomic coordinates.

    摘要翻译： 公开了包含衍生自高分辨率x射线衍射的结晶形式的Fc异二聚体蛋白质的组合物的原子坐标。 进一步公开的是使用这些原子坐标的全部或部分来鉴定和设计改进的Fc异二聚体蛋白的系统和方法。 还公开了包含（i）溶解的Fc异二聚体蛋白和（ii）母液溶液的混合物的组合物。 母液溶液包含2％至10％（v / v）乙二醇，10％至25％（w / v）的平均分子量介于2000道尔顿与10000道尔顿之间的聚乙二醇和0.05M至 0.40M碘化铵。 进一步公开的是鉴定促进异源二聚体Fc链对形成的突变的系统和方法，其中使用所公开的三维原子坐标的全部或一部分进行基于结构的建模来鉴定到Fc链的候选突变。

    SINGLE-ARM MONOVALENT ANTIBODY CONSTRUCTS AND USES THEREOF
    10.
    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。