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Humanization method based on three-dimensional structure

机译:基于三维结构的人性化方法

摘要

PROBLEM TO BE SOLVED: To provide a method for humanization of a non-human antibody using a structure-based scoring matrix. A method comprising the following steps: (a) aligning the amino acid sequence of a non-human heavy chain or light chain variable domain with a first humanized variant of the non-human heavy chain or light chain variable domain, ( b) An aligned framework position in which the non-human heavy or light chain variable domain and the first humanized variant of the non-human heavy or light chain variable domain have different amino acid residues, and because of the difference. , The step of identifying the position affecting the antigen binding and / or three-dimensional structure of the variable domain; (c) the non-human heavy chain or light chain variable by substituting the amino acid residue identified in step (b). The step of modifying the first humanized variant of the domain; (d) the step of producing a nucleic acid sequence encoding the modified variable domain, thereby producing a nucleic acid sequence encoding the humanized immunoglobulin variable domain. [Selection diagram] None
机译:要解决的问题:提供使用基于结构的评分基质的非人抗体的人性化方法。一种方法,其包含以下步骤:(a)将非人重链或轻链可变域的氨基酸序列与非人重链或轻链可变结构域的第一人源化变体对准,(b)对齐非人重链或轻链可变结构域和第一个非人重链可变结构域的框架位置,具有不同的氨基酸残基,并且由于差异。 ,识别影响可变域的抗原结合和/或三维结构的位置的步骤; (c)非人重链或轻链可变通过代替步骤(b)中鉴定的氨基酸残基。修改域的第一个人源化变体的步骤; (d)制备编码改性可变结构域的核酸序列的步骤,从而产生编码人源化免疫球蛋白可变结构域的核酸序列。 [选择图]无

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