Preparation method of antibody with thiol group site specific modification and application of TCEP

By using TCEP and transition metal ions to reduce the interchain disulfide bonds in antibodies, site-specific modification of thiol groups of antibody drug conjugates (ADCs) is achieved, which solves the problem of insufficient uniformity of existing ADCs and achieves High uniformity and optimized safety and effectiveness.

CN119325482APending Publication Date: 2025-01-17SUZHOU BIOREINNO BIOTECHNOLOGY LTD CO
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Patent Information

Application Number
CN202380045305.1
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Priority Date
2023-01-19
Filing Date
2023-08-22
Publication Date
2025-01-17

AI Technical Summary

Technical Problem

Existing antibody drug conjugates (ADCs) have problems with uneven mixing during drug adhesion, resulting in complex pharmacokinetic, toxic and effective characteristics and difficulty in efficient characterization and purification.

Method used

By using tris(2-carboxyethyl)phosphine (TCEP) or its salts and transition metal ions, the interchain disulfide bonds in antibodies are selectively reduced to achieve site-specific modification of the thiol group, thereby preparing multiple A kind of high uniformity ADC, such as D2 type, D1 type, D2+D6 type, etc.

Benefits of technology

The uniformity of the ADC has been improved. The uniformity of the D2 type ADC has reached 55%, 60%, 65%, or even 70%, 75%, 80% or 83%. At the same time, the operating complexity and cost have been reduced, and the generated ADC has optimized safety and effectiveness.

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Abstract

The invention provides a preparation method of an antibody with thiol group site specific modification and application of TCEP. The present invention relates to a method for reducing a thiol group from an interchain disulfide bond within an antibody, and the method comprises the use of TCEP or a salt thereof and a transition metal ion wherein the molar ratio of TCEP to the transition metal ion is from 1: 0.4 to 1: 200. The antibody with the thiol group site specific modification is a D1 type ADC (Analog to Digital Converter), a D2 type ADC, a D1 + D6 type ADC, a D1 + D3 type ADC, a D2 + D6 type ADC, a D2 + D3 type ADC, a D0 + D6 type ADC or a D0 + D3 type ADC. Compared with the conventional coupling method, the homogeneity of the ADC produced by the method disclosed by the invention is remarkably improved. Specifically, the D2 type ADC content is generally greater than 55%, 60%, 65%, and even up to 70%, 75%, 80% or 83%.
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Citation Information

Patent Citations

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