March 14, 2018
11 am to 12 pm EST
Investigations of thermal behavior are essential during the development of therapeutic proteins. Understanding the link between thermal unfolding and aggregation might help develop approaches to minimizing conformational and colloidal instabilities. In this study, a therapeutic monoclonal antibody (MAb) and its Fab and Fc fragments were investigated by differential scanning fluorimetry, temperature-ramped dynamic light scattering and turbidity measurements.
Repulsive net charges at low pH increased colloidal stability, although a concomitant reduction of conformational stability was observed. Aggregation was driven by hydrophobic interactions. Coupling of differently charged hydrophobic payloads affected colloidal stability mostly based on the charge effects. The three experimental methods described and explained the thermal behavior of the protein, demonstrating significant value for the development of pharmaceutical protein products. This combination of orthogonal methods provides for a better understanding of the conformational and colloidal stability of mAbs and mAb-conjugates.
- How light scattering combines with other biophysical techniques to provide a comprehensive description of the factors influencing mAb stability
- How the tradeoff between conformational and colloidal stability plays out in a full mAb vs. Fab and Fc domains
- How drug conjugation may affect conformation and colloidal stability of mAbs
Prof. Dr. Wolfgang Friess
Professor of Pharmaceutics and Biopharmaceutics
Department of Pharmacy, Pharmaceutics and Biopharmaceutics
Dr. Wolfgang Frieß is Professor of Pharmaceutical Technology and Biopharmaceutics at Ludwig Maximilians University of Munich in Germany. He received his PhD in Pharmaceutical Technology in 1993 and his Pharmacy degree in 1989 from the University of Erlangen, and has held academic positions in both Germany and the US.
His primary research interests are protein formulation, drug delivery and biomaterials, in particular new analytical tools for protein formulations; freeze-drying of proteins; and different local delivery routes. He is co-editor of the European Journal of Pharmaceutics and Biopharmaceutics, and has published over 150 research papers, patents and book chapters.