(159e) Predicting Protein Interactions to Enhance Stability and Solubility of Therapeutic Antibodies

Therapeutic proteins are one of the fastest growing classes of innovator drug candidates. However, proteins are often problematic with respect to (mis)folding, aggregation, and practical limitations for solubility and solution viscosity at high protein concentrations. This presentation focuses on a combined experimental and computational approach to quantifying and predicting protein-protein interactions that can determine the physical stability of proteins such as therapeutic antibodies. Examples will highlight coarse-grained models to quantitatively or semi-quantitatively predict well-behaved vs. poorly behaved candidate molecules, spanning from antibody fragments to full-length monoclonal antibodies. Outstanding challenges will also be illustrated that underlie a number of common assumptions regarding how protein-protein interactions mitigate key pharmaceutical product attributes such as solution viscosity and aggregation rates.