PROBLEM TO BE SOLVED: To provide a method for purifying a multi-specific polypeptide comprising a first polypeptide and a second polypeptide, which have variable regions of antibodies.SOLUTION: According to the present invention, a method for purifying a multi-specific polypeptide including a first polypeptide and a second polypeptide, which have variable regions of antibodies comprises: modifying a nucleic acid that encodes the polypeptide including at least one amino acid residue that can be exposed on a CDR region of each of the polypeptide to modify the charge of the amino acid residue, where the modification of the nucleic acid modifies both or any of a nucleic acid encoding the amino acid residue of the first polypeptide a nucleic acid encoding the amino acid residue of the second polypeptide so as to increase the difference between the isoelectric points of the first polypeptide and the second polypeptide as compared with that before the modification； culturing a host cell in which any of the nucleic acids is modified so as to express the nucleic acids； and purifying a multi-specific polypeptide from the culture using chromatography.SELECTED DRAWING: NoneCOPYRIGHT: (C)2017,JPO&INPIT【課題】抗体の可変領域を有する第１のポリペプチドおよび第２のポリペプチドを含む多重特異性ポリペプチドの精製方法を提供する。【解決手段】抗体の可変領域を有する第１のポリペプチドおよび第２のポリペプチドを含む多重特異性ポリペプチドの精製方法であって、当該ポリペプチドのCDR領域の表面に露出し得る少なくとも１つのアミノ酸残基の電荷が改変するように、当該アミノ酸残基を含むポリペプチドをコードする核酸を改変し、当該核酸の改変が、改変前と比較して、第１のポリペプチドと第２のポリペプチドの等電点の差が増大するように第１のポリペプチドのアミノ酸残基をコードする核酸および第２のポリペプチドのアミノ酸残基をコードする核酸の両方またはいずれかを改変し、前記いずれかの核酸が改変された核酸を含む宿主細胞を、該核酸が発現するように培養し、培養物からクロマトグラフィーにより多重特異性ポリペプチドを精製する方法。【選択図】なし
