Determination method for modification degree of polymer modified antibody drug

Abstract

The invention discloses a method for determining the modification degree of a polymer modified antibody drug, and particularly relates to a method for determining the modification degree of a PEG modified monoclonal antibody. According to the determination method, the modification degree of a polymer (such as PEG) on a monoclonal antibody chain is calculated by utilizing LC-Q-TOF, complete physical separation or chromatographic separation does not need to be carried out on the monoclonal antibody chains with different modification degrees, and the modification degrees of the polymer (such as PEG) on a light chain and a heavy chain can be simultaneously obtained by utilizing a molecular weight difference rule obtained by deconvolution; moreover, physical separation is not needed, MALDI-TOF is used for carrying out molecular weight detection on hundreds of thousands of polymer modified antibodies, molecular weight detection can also be carried out on light chains and heavy chains after reduction resolution, and the modification degree of the polymer (such as PEG) is calculated; the LC-Q-TOF and the MALDI-TOF are used in a combined mode, complement each other and verify each other, more modification information of heavy chains and light chains can be obtained, and the result is more reliable.

Description

technical field [0001] The invention relates to the technical field of drug analysis, in particular to a method for determining the degree of modification of a polymer-modified antibody drug (especially a PEG-modified monoclonal antibody) and its application. Background technique [0002] Protein drugs mainly include proteins with special functions such as peptides, enzymes, cytokines, hormones, antibodies, etc. With the development of biotechnology, people can obtain the desired drugs through fermentation engineering, genetic engineering, protein engineering, and enzyme engineering. protein. However, after a large number of clinical studies, it has been found that protein drugs without any modification have defects such as short half-life, strong immunogenicity, poor stability, and easy degradation by enzymes in vivo, which reduces the clinical effect. To this end, people try to transform protein drugs to adapt to clinical applications through a variety of ways. [0003] ...

AI Technical Summary

Problems solved by technology

However, in the enzymatic hydrolysis method, the release of PEG may not be complete. In order to avoid the interference of free PEG, it is often necessary to purify the enzymatic hydrolysis sample.

Patent document CN109682901A discloses a method for determining the average degree of modification of PEGylated protein drugs, which includes the use of multiple types of detection methods that are linearly related to the concentrations of unmodified protein drug standards and polyethylene glycol standards. detector, the steps of establishing the standard curve of the concentration of unmodified protein drug standard, polyethylene glycol standard and the response value of each type of detector corresponding to their respective concentrations, the steps are cumbersome, and the workload in actual detection is relatively large

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