Physicochemical Rules for Identifying Monoclonal Antibodies with Drug-like Specificity

• DOI: 10.1021/acs.molpharmaceut.0c00257
• Publication Date: 2020-05-26T23:09:05Z
• Authors: Yulei Zhang; Lina Wu; Priyanka Gupta; Alec A. Desai; Matthew D. Smith; Lilia A. Rabia; Seth D. Ludwig; Peter M. Tessier
• Keywords: 0303 health sciences; 03 medical and health sciences; Drug Development; Models, Chemical; Solubility; Viscosity; Immunoglobulin Variable Region; Antibodies, Monoclonal; High-Throughput Nucleotide Sequencing; Bioengineering; Sensitivity and Specificity; 3. Good health

The ability of antibodies to recognize their target antigens with high specificity is fundamental natural function. Nevertheless, therapeutic display variable and difficult-to-predict levels nonspecific self-interactions that can lead various drug development challenges, including antibody aggregation, abnormally viscosity, rapid clearance. Here we report a method for predicting the overall in terms relative risk displaying or at physiological conditions. We find individual combined sets chemical rules limit maximum minimum numbers certain solvent-exposed amino acids regions are strong predictors large panels preclinical clinical-stage antibodies. also demonstrate how be used identify sites mediate interactions suboptimal guide design targeted sublibraries yield variants specificity. These findings readily improve selection engineering drug-like