About This Webinar

Analyzing structural changes upon aggregation as a strategy for resolution

Aggregation of antibody therapeutics is a major consideration in their developability, safety, and immunogenicity. While detection of antibody aggregates and analysis of their basic properties is fairly routine, elucidating the mechanism of their formation and mapping the sequences that are involved is much more challenging. Structural mass spectrometry techniques such as hydroxyl radical protein footprinting (HRPF) are well suited for this application, as they can be rapidly employed to characterize higher-order structure of proteins in solution. Here, we demonstrate the use of plasma induced modification of biomolecules (PLIMB), an HRPF technology, to investigate a readily observed bispecific antibody (bsAb) dimer. These data, combined with those previously collected, were used to gain structural and mechanistic understanding of the bsAb dimer formation. This work demonstrates the use of hydroxyl radical protein footprinting data for gaining structural and mechanistic understanding of antibody dimerization.

This session was recorded in June 2023.

Key Learning Objectives

• What is antibody aggregation and how can it affect drug development and process engineering?
• How to leverage hydroxyl radical footprinting to understand the mechanism of aggregation and potentially resolve these issues
• Methods for analyzing footprinting data in the context of aggregation to arrive at actionable insights