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    Altered antibodies having improved antigen-binding affinity
    3.
    发明申请
    Altered antibodies having improved antigen-binding affinity 审中-公开
    改变的抗体具有改善的抗原结合亲和力

    公开(公告)号：US20070135998A1

    公开(公告)日：2007-06-14

    申请号：US11338942

    申请日：2006-01-24

    申请人： Herman Van Vlijmen ,  Brian Sherman ,  Alexey Lugovskoy

    发明人： Herman Van Vlijmen ,  Brian Sherman ,  Alexey Lugovskoy

    IPC分类号： G06F19/00

    CPC分类号： C07K16/00 ,  C07K16/2842 ,  C07K16/2875 ,  C07K2299/00 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  G16B15/00 ,  G16B20/00

    摘要： The invention relates to methods of modulating the antigen-binding affinity of an antibody by determining, using data corresponding to the structure of a complex between the antibody and an antigen in a solvent, a representation of a charge distribution of the CDRs of the antibody which minimizes electrostatic contribution to binding free energy between the antibody and the antigen in a solvent. Guided by these determinations, the antibody is accordingly modified (altered) to improve upon, e.g., antibody/antigen binding by modifying at least one amino acid residue to decrease the binding free energy between the antibody and antigen when bound in a solvent.

    摘要翻译： 本发明涉及通过使用与溶剂中的抗体和抗原之间的复合物的结构相对应的数据来确定抗体的CDR的电荷分布的表示来调节抗体的抗原结合亲和力的方法，所述抗体的CDR的电荷分布 使溶剂中抗体与抗原之间的结合自由能的静电贡献最小化。 在这些测定的指导下，通过修饰至少一个氨基酸残基以减少结合于溶剂中的抗体与抗原之间的结合自由能，相应地修饰（改变）抗体以改善例如抗体/抗原结合。

    Methods of humanizing immunoglobulin variable regions through rational modification of complementarity determining residues
    5.
    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：US08349324B2

    公开(公告)日：2013-01-08

    申请号：US12628898

    申请日：2009-12-01

    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： A61K39/395

    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。