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    Methods of humanizing immunoglobulin variable regions through rational modification of complementarity determining residues
    10.
    发明授权
    Methods of humanizing immunoglobulin variable regions through rational modification of complementarity determining residues 有权
    通过合理修饰互补决定残基来人源化免疫球蛋白可变区的方法

    公开(公告)号：US07678371B2

    公开(公告)日：2010-03-16

    申请号：US11369641

    申请日：2006-03-06

    申请人： Alexey Alexandrovich Lugovskoy ,  Karl Hanf ,  You Li ,  Kenneth Simon ,  Herman Van Vlijmen

    发明人： Alexey Alexandrovich Lugovskoy ,  Karl Hanf ,  You Li ,  Kenneth Simon ,  Herman Van Vlijmen

    IPC分类号： A61K39/00

    CPC分类号： C07K1/00 ,  C07K16/00 ,  C07K16/2842 ,  C07K16/30 ,  C07K16/465 ,  C07K2317/24 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/92

    摘要： The present invention is based, at least in part, on the discovery that strategic modifications of non-human donor antibody CDR residue(s) can be used to humanize antibodies. Such modifications modulate the 3D structural fit between donor antibody CDRs and human acceptor antibody framework regions that comprise the variable domains of a CDR-grafted antibody. Whereas prior art methods of humanization have relied on making framework substitutions (in which selected human framework residues are backmutated to the corresponding amino acid residue present in the non-human donor antibody), the instant invention is based, at least in part, on a method of humanizing antibodies in which selected CDR residues, and optionally adjacent FR residues, are changed in order to accommodate differences in FR amino acid sequences between donor and acceptor antibodies.

    摘要翻译： 本发明至少部分地基于以下发现，即可以使用非人供体抗体CDR残基的战略修饰来使抗体人源化。 这样的修饰调节供体抗体CDR和包含CDR移植抗体的可变结构域的人受体抗体框架区之间的3D结构拟合。 而现有技术的人源化方法依赖于进行框架取代（其中所选择的人类框架残基反向到存在于非人供体抗体中的相应氨基酸残基），本发明至少部分地基于 人源化抗体的方法，其中选择的CDR残基和任选相邻的FR残基被改变以适应供体和受体抗体之间的FR氨基酸序列的差异。