公开(公告)号：US09771573B2

公开(公告)日：2017-09-26

申请号：US14432153

申请日：2013-10-03

申请人： Zymeworks Inc. ,  National Research Council of Canada

发明人： Anders Ohrn ,  Adam Louis Corper ,  Gordon Yiu Kon Ng ,  Antonios Samiotakis ,  Yang-Chieh Chou ,  Jason Baardsnes ,  Maureen O'Connor-McCourt

IPC分类号： G01N33/53 ,  C12N15/10 ,  A61K39/00 ,  C07K16/46 ,  G01N21/64

CPC分类号： C12N15/1055 ,  A61K39/00 ,  C07K16/468 ,  C07K2317/55 ,  G01N21/6486

摘要： Provided is a method of quantitatively determining the ability of individual IgG heavy chains to selectively pair with a particular IgG light chain when the heavy chains and two unique light chains are co-expressed. The method provides results with reasonable throughput and is robust and accurate. The co-expressed heavy and light chains do not need to be isolated and purified which enables more efficient screening.

公开(公告)号：US20140200331A1

公开(公告)日：2014-07-17

申请号：US14092804

申请日：2013-11-27

申请人： Zymeworks Inc.

发明人： Adam Louis Corper ,  Dunja Urosev ,  Stacey A.L. Tom-Yew ,  Dustin Weyland Blue Bleile ,  Thomas Spreter Von Kreudenstein ,  Surjit Dixit ,  Paula Irene Lario

IPC分类号： C07K16/28

CPC分类号： C07K16/36 ,  C07K2317/55 ,  C07K2317/94

摘要： The present invention provides heterodimer pairs comprising a first heterodimer and a second heterodimer wherein each heterodimer comprises an immunoglobulin heavy chain or fragment thereof and an immunoglobulin light chain. At least one of the heterodimers comprises amino acid modifications in the CH1 and/or CL domains, amino acid modifications in the VH and/or VL domains or a combination thereof. The modified amino acid residues are part of the interface between the light chain and heavy chain and are modified in order to create preferential pairing between each heavy chain and a desired light chain such that when the two heavy chains and two light chains of the heterodimer pair are co-expressed in a mammalian cell, the heavy chain of the first heterodimer preferentially pairs with one of the light chains rather than the other. Likewise, the heavy chain of the second heterodimer preferentially pairs with the second light chain rather than first.

摘要翻译： 本发明提供包含第一异二聚体和第二异二聚体的异二聚体对，其中每个异二聚体包含免疫球蛋白重链或其片段和免疫球蛋白轻链。 至少一个异源二聚体包括CH1和/或CL结构域中的氨基酸修饰，VH和/或VL结构域中的氨基酸修饰或其组合。 修饰的氨基酸残基是轻链和重链之间的界面的一部分，并且被修饰以在每个重链和所需的轻链之间产生优先配对，使得当异源二聚体对的两条重链和两条轻链 在哺乳动物细胞中共表达，第一个异二聚体的重链优先与轻链之一而不是另一个重合。 同样，第二异源二聚体的重链优先与第二轻链配对，而不是首先。