Predicting stability of antibody therapeutics by unfolded-state studies with high-throughput dynamic light scattering
August 18, 2020
1 pm to 2 pm EDT



Webinar Description:

The presentation will highlight recent applications of high-throughput dynamic light scattering (HT-DLS) for quantifying the colloidal stability of antibody therapeutics, and the relationship to storage stability. Aggregation driven by association of partially-folded or unfolded states is the main degradation route of such molecules, but its characterization is difficult due to the transient nature and low abundance of these states. Overcoming this difficulty requires orthogonal approaches for measuring self-association over a range of native and stressed formulation conditions.

HT-DLS is the ideal tool to screen colloidal stability in these studies, thanks to its speed, low sample consumption, ease of use, reproducibility, and versatility. In this webinar, we show how measurements made under native conditions, with thermal stress, and in the presence of chemical denaturants, can be used to improve predictions of aggregation propensity and storage stability.

Learning Objectives:

  • How colloidal stability of mAb unfolded states, measured by HT-DLS under accelerated stress conditions with chemical denaturation, helps predict storage stability
  • How orthogonal measurements of native-state and unfolded-state colloidal stability performed with HT-DLS relate to aggregation propensity of marginally-stable scFv domain antibodies
  • How the protein-protein interaction parameter k_D, measured by high-throughput DLS, is used for elucidating effects of buffers and salts on mAb colloidal stability


Robin Curtis

Robin Curtis, Ph.D.
Senior Lecturer, School of Chemical Engineering and Analytical Science
University of Manchester

Robin Curtis is a Senior Lecturer in the School of Chemical Engineering and Analytical Science at the University of Manchester. He obtained his PhD from UC Berkeley and completed post-doctoral work Rice University and UCLA. His expertise includes molecular approaches to understanding protein solution behavior, directly relevant to liquid formulations and downstream bioprocessing unit operations. Current projects focus on refolding and protein aggregation under chemically denaturing conditions, protein phase diagrams, novel excipients to prevent aggregation, and methods for measuring protein-protein interactions by light scattering. Dr. Curtis collaborates with several biopharmaceutical companies including Medimmune, Fujifilm Diosynth Novozymes and Novaliq.