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2. 发明申请

WO2007124077A2 IMMUNOGLOBULIN CONSTANT REGION DOMAINS WITH ENHANCED STABILITY 审中-公开
标题翻译：具有增强稳定性的免疫球蛋白恒定区域
公开(公告)号：WO2007124077A2
公开(公告)日：2007-11-01
申请号：PCT/US2007009693
申请日：2007-04-20
申请人： AMGEN INC , MATSUMURA MASAZUMI , JACOB JABY
发明人： MATSUMURA MASAZUMI , JACOB JABY
IPC分类号： C07K19/00 , A61P35/00 , A61P37/00 , C07K16/00
CPC分类号： C07K16/00 , C07K2317/52
摘要： The invention provides an isolated polypeptide including an immunoglobulin C H 3 region domain polypeptide, or functional fragment thereof, having at least one Pro to GIy substitution and exhibiting enhanced stability, including an enhanced folding rate, compared to an unsubstituted C H 3 domain, wherein the at least one Pro to GIy substitution comprises C H 3 residue Pro38 or a C H 3 domain equivalent thereof. Multimeric complexes of an immunoglobulin C H 3 region domain polypeptide, or functional fragment thereof, having at least one Pro to GIy substitution with a second immunoglobulin C H 3 region domain polypeptide also are provided by the invention. The multimeric complexes can include antibodies, antibody functional fragments such as Fd, Fv, Fab, F(ab'), F(ab) 2 , F(ab') 2 , single chain Fv (scFv), chimeric antibodies, diabodies, triabodies, tetrabodies or minibody and other binding polypeptides having an immunoglobulin C H 3 region domain polypeptide such as a peptibody or an Fc fusion polypeptide. An isolated population of polypeptides including a plurality of immunoglobulin C H 3 region domain polypeptides, or functional fragments thereof, is further provided. Each C H 3 region domain polypeptide within the populations includes at least one Pro to GIy substitution and exhibits enhanced stability, including an enhanced folding rate, compared to an unsubstituted C H 3 domain, wherein the at least one Pro to GIy substitution comprises C H 3 residue Pro38 or a C H 3 domain equivalent thereof. The invention further provides a method of producing a multimeric binding polypeptide and a method of treating a pathological condition characterized by aberrant cell growth.
摘要翻译：本发明提供了一种分离的多肽，其包含免疫球蛋白C 3区域结构域多肽或其功能片段，其具有至少一个Pro至Gly取代并表现出增强的稳定性，包括增强的折叠率，与未取代的C 3 H 3结构域，其中至少一个Pro至Gly取代包括C 3 H 3残基Pro38或其C 3 H 3结构域等同物。具有与第二免疫球蛋白C区域结构域多肽进行至少一个Pro至Gly取代的免疫球蛋白C H 3区域多肽或其功能片段的多聚体复合物也由本发明提供。多聚体复合物可以包括抗体，抗体功能片段，例如Fd，Fv，Fab，F（ab'），F（ab）2，F（ab'）2 ，单链Fv（scFv），嵌合抗体，双抗体，三抗体，四体抗体或微型抗体以及其它具有免疫球蛋白C H 3区域结构域多肽的结合多肽，例如肽型或Fc融合多肽。还提供了分离的多肽包括多个免疫球蛋白C 3区域结构域多肽或其功能片段。与未取代的C 3 H 3相比，群体内的每个C 3 H 3域结构域多肽包含至少一个Pro至Gly取代并表现出增强的稳定性，包括增强的折叠率其中所述至少一个Pro至Gly取代包括C 3 H 3残基Pro38或其C 3 H 3结构域等同物。本发明进一步提供了一种制备多聚结合多肽的方法和一种治疗以异常细胞生长为特征的病理状态的方法。

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