A systematic approach for analysis and characterization of mispairing in bispecific antibodies with asymmetric architecture

MAbs
Chunlei WangDengfeng Liu

Abstract

Immunoglobulin G-like bispecific antibodies with asymmetric architecture are among the most widely used bispecific antibody formats for diagnostic and therapeutic applications. The primary technical challenge for this format is how to achieve correctly paired assembly of four unique polypeptide chains. Advances in protein engineering and process development are being used to overcome these challenges and are driving a corresponding demand for sensitive analytical tools to monitor and control mispaired species. Here, we report a systematic approach for analysis and characterization of mispairing in asymmetric bispecific antibodies. This approach consists of three orthogonal components, the first of which is a liquid chromatography (LC)-mass spectrometry (MS)-based method to measure the mass of intact antibodies. This method is used for fast analysis of mispairing and requires minimal method development, which makes it an ideal choice for early-stage development. The second component is a hydrophobic interaction chromatography (HIC)-based mispairing method that is suitable for lot release testing. The HIC method is robust and quality control friendly, and offers great linearity, precision, and accuracy. The third component is a t...Continue Reading

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Citations

Jun 17, 2020·Methods : a Companion to Methods in Enzymology·Yujia Ying, Huilin Li
Apr 23, 2021·Journal of the American Society for Mass Spectrometry·Iain D G Campuzano, Wendy Sandoval
Aug 21, 2021·Protein Expression and Purification·Yifeng Li
Sep 9, 2021·Mass Spectrometry Reviews·Guinevere S M Lageveen-KammeijerManfred Wuhrer
Oct 24, 2021·Biotechnology and Bioengineering·Siddharth S ParasnavisSteven M Cramer

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Methods Mentioned

BETA
affinity capture
amidation
glycosylation

Software Mentioned

MaxEnt I
DuetMab

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