Assessing the Impact of CDR Deamidation and Isomerization on mAb Target Binding Using Affinity-Resolved 2D-SEC-SCX-MS Analysis.

ABSTRACT: Post-translational modifications (PTMs) within the Complementarity-Determining Regions (CDRs) of monoclonal antibodies (mAbs) can impact their target-binding capabilities, making them potential critical quality attributes (CQAs) during therapeutic mAb development. Conventional methods for assessing PTM criticality often involve variant enrichment followed by target-binding testing, which face limitations in throughput and complexity. To address these challenges, affinity enrichment-based strategies have emerged, offering a valuable alternative for PTM assessment. Notably, the combination of competitive binding, size exclusion chromatography (SEC) separation, and MS detection, has proven highly effective in assessing the criticality of PTMs in a multiplexed fashion. Recently, we introduced

SUBMITTER: Yan Y 

PROVIDER: S-EPMC12679624 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature