Method for modifying the isoelectric point of an antibody by amino acid substitution in CDR

By performing amino acid replacement in the CDR region of the antibody and adjusting the heteroelectric point, the problems of high production costs and short half-life of antibody drugs are solved, and half-life control and drug performance are achieved.

JP7651031B2Active Publication Date: 2025-03-25CHUGAI PHARMA CO LTD
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Patent Information

Application Number
JP2024026124
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Priority Date
2007-09-28
Filing Date
2024-02-26
Publication Date
2025-03-25
Estimated Expiration
2028-09-26

AI Technical Summary

Technical Problem

Due to the high production cost and short half-life of existing antibody drugs, it limits their application in chronic autoimmune diseases, and it is difficult to effectively control the plasma half-life and immunogenicity of the antibodies.

Method used

By performing amino acid substitutions in variable regions of the antibody, especially the CDR regions, the heteroelectric point of the antibody is adjusted to control its plasma half-life and maintain antigen binding activity.

Benefits of technology

It realizes the half-life control of antibody drugs, reduces production costs, improves the stability and immunogenicity of drugs, and is suitable for long-term treatment of chronic autoimmune diseases.

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Abstract

To provide a method for purifying a multispecific polypeptide comprising a first polypeptide and a second polypeptide each having an antibody variable region.SOLUTION: A method for purifying a multispecific polypeptide comprising a first polypeptide and a second polypeptide having a variable region of an antibody comprises modifying a nucleic acid encoding a polypeptide comprising an amino acid residue so that the charge of at least one amino acid residue which may be exposed on a surface of a CDR region of the polypeptide concerned is modified; modifying both or either of the nucleic acid encoding the amino acid residue of the first polypeptide and the nucleic acid encoding the amino acid residue of the second polypeptide so that a difference of an isoelectric point between the first polypeptide and the second polypeptide increases as compared to that before modifying; culturing a host cell comprising the nucleic acid in which either of the nucleic acid is modified so that the nucleic acid expresses; and purifying the multispecific polypeptide from a culture by chromatography.SELECTED DRAWING: None
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