(51g) Applying Machine Learning to Predict Therapeutic Antibody Aggregation??

In the present study, we developed a general machine learning feature selection protocol to predict antibody stabilities. These features only require information from sequences and molecular structures of antibodies. In addition, the physically relevant features are easily interpretable and help to design experiments to understand the underlying mechanisms of antibody stabilities. Two case studies are demonstrating using this protocol. First, we applied this framework to predict aggregation behaviors of 21 approved monospecific monoclonal antibodies at high concentration (150 mg/mL), yielding an accuracy of 97% on validation tests with only three features. Models trained using structural features, rather than sequence features, correlated better with aggregation. Second, the concentration dependent viscosity behavior of 27 FDA approved antibody drugs was measured in concentrated solutions at high concentration (150 mg/mL). Combining molecular modeling and machine learning feature selection, we found that the net charge in the antibodies and the amino acid composition in the variable region are key features which govern the viscosity behavior. We presented two predictive models for aggregation and viscosity based on machine learning trained models, facilitating early stage design.