公开(公告)号：EP3068430A2

公开(公告)日：2016-09-21

申请号：EP14861805.1

申请日：2014-11-13

申请人： Zymeworks Inc.

发明人： NG, Gordon Yiu Kon ,  WEISSER, Nina E. ,  WICKMAN, Grant Raymond

IPC分类号： A61K39/395

CPC分类号： C07K16/32 ,  A61K39/39558 ,  A61K47/6855 ,  A61K2039/505 ,  A61K2039/507 ,  C07K16/30 ,  C07K16/3069 ,  C07K2317/24 ,  C07K2317/30 ,  C07K2317/52 ,  C07K2317/524 ,  C07K2317/526 ,  C07K2317/53 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/622 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2317/94

摘要： Provided herein are methods of use and treatment using a first or a first and second monovalent antigen-binding constructs targeting HER2. The monovalent antigen- binding constructs can include at least one antigen-binding polypeptide comprising a heavy chain variable domain, wherein the antigen-bind polypeptide specifically binds HER2; and a heterodimeric Fc, the Fc comprising at least two CH3 sequences, wherein the Fc is coupled, with or without a linker, to the antigen-binding polypeptide.

摘要翻译： 本文提供使用靶向HER2的第一或第一和第一单价抗原结合构建体的使用和治疗方法。 一价抗原结合构建体可以包括至少一种包含重链可变结构域的抗原结合多肽，其中所述抗原结合多肽特异性结合HER2; 和异源二聚体Fc，所述Fc包含至少两个CH3序列，其中所述Fc与或不具有接头偶联至所述抗原结合多肽。

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.

公开(公告)号：EP3223848A1

公开(公告)日：2017-10-04

申请号：EP15862509.5

申请日：2015-11-26

申请人： Zymeworks Inc.

发明人： WICKMAN, Grant Raymond ,  NG, Gordon Yiu Kon ,  WEISSER, Nina E.

IPC分类号： A61K39/395 ,  A61P35/00 ,  C07K16/28 ,  C07K16/30

CPC分类号： C07K16/32 ,  A61K39/395 ,  A61K47/6803 ,  A61K47/6855 ,  A61K47/6869 ,  A61K47/6879 ,  A61K2039/505 ,  C07K16/28 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/41 ,  C07K2317/522 ,  C07K2317/526 ,  C07K2317/55 ,  C07K2317/622 ,  C07K2317/64 ,  C07K2317/72 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2317/94

摘要： Described herein methods of using antigen-binding constructs to treat HER2+ tumors in a subject such as breast, lung, or head and neck tumors. In some aspects, the tumor volume in the subject after receiving at least seven doses of the antigen binding construct is less than the tumor volume of a control subject receiving an equivalent amount of trastuzumab. In some aspects, the survival of the subject receiving the antigen binding construct is increased as compared to a control subject receiving an equivalent amount of a non-specific control antibody or as compared to a control subject not receiving treatment.

摘要翻译： 本文描述了使用抗原结合构建体来治疗受试者（例如乳腺癌，肺癌或头颈部肿瘤）中的HER2 +肿瘤的方法。 在一些方面，接受至少7个剂量的抗原结合构建体后，受试者的肿瘤体积小于接受等量曲妥珠单抗的对照受试者的肿瘤体积。 在一些方面，与接受等量非特异性对照抗体的对照受试者相比，或与未接受治疗的对照受试者相比，接受抗原结合构建体的受试者的存活率增加。

公开(公告)号：EP3074424A1

公开(公告)日：2016-10-05

申请号：EP14866161.4

申请日：2014-11-27

申请人： Zymeworks Inc.

发明人： WEISSER, Nina E. ,  NG, Gordon Yiu Kon ,  WICKMAN, Grant Raymond ,  DIXIT, Surjit Bhimarao ,  ESCOBAR-CABRERA, Eric ,  SANCHES, Mario

IPC分类号： C07K16/46 ,  A61K39/395 ,  A61K47/48 ,  A61P35/00 ,  C07K16/28 ,  C12N15/13 ,  C12N5/10 ,  C40B40/08

CPC分类号： C07K16/32 ,  A61K39/39558 ,  A61K45/06 ,  A61K47/6803 ,  A61K47/6851 ,  A61K47/6855 ,  A61K47/6869 ,  A61K2039/505 ,  C07K16/3015 ,  C07K16/3069 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/35 ,  C07K2317/41 ,  C07K2317/52 ,  C07K2317/524 ,  C07K2317/526 ,  C07K2317/55 ,  C07K2317/622 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2317/94 ,  G01N33/57492

摘要： Provided herein are biparatopic antigen-binding constructs that specifically bind HER2. The biparatopic antigen-binding constructs comprise one antigen-binding moiety that binds to ECD2 of HER2, a second antigen-binding moiety that binds to ECD4 of HER2, and an Fc. At least one of the antigen-binding moieties is an scFv. The biparatopic antigen-binding constructs can be used in the treatment of cancer.

摘要翻译： 本文提供了特异性结合HER2的二互补位的抗原结合构建体。 双互补位抗原结合构建体包含结合HER2的ECD2的一个抗原结合部分，其结合HER2的ECD4的第二抗原结合部分和Fc。 至少一个抗原结合部分是scFv。 两性反应性抗原结合构建体可用于治疗癌症。