Simulation of high-concentration self-interactions for monoclonal antibodies from well-behaved to poorly-behaved systems
Attractive self-interactions of therapeutic proteins are linked to problematic solution behaviors at high protein concentrations such as reversible or irreversible aggregation, high viscosity, opalescence, phase separation, and low solubility. Prediction of attractive self-interactions early in development can improve the processes of formulation development and candidate selection. To that end, a coarse-grained model with explicit representation of charged sites was used to accurately predict a broad range of protein self-interactions at high protein concentrations (up to 160 mg/ml) for multiple monoclonal antibodies and formulations, including strong electrostatic attractions, with static light scattering measurements at low protein concentrations as the only experimental input. In addition, Mayer-weighted electrostatic energies for charged residues from these simulations can contribute to understanding of electrostatic interactions and guide the development of protein variants.
This is the peer reviewed version of the following article: Forder, JK, Ilott, AJ, Sahin, E, Roberts, CJ. Simulation of high-concentration self-interactions for monoclonal antibodies from well-behaved to poorly-behaved systems. AIChE J. 2022;e17965. doi:10.1002/aic.17965, which has been published in final form at https://doi.org/10.1002/aic.17965. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. This article will be embargoed until 11/21/2023.
monoclonal antibodies, protein formulation, protein self-interactions, static light
Forder, JK, Ilott, AJ, Sahin, E, Roberts, CJ. Simulation of high-concentration self-interactions for monoclonal antibodies from well-behaved to poorly-behaved systems. AIChE J. 2022;e17965. doi:10.1002/aic.17965