The effect of hydrophobicity on antibody aggregation is well understood, and it has been shown that charge calculations can be useful for high-concentration viscosity and pharmacokinetic (PK) clearance predictions. In this work, structure-based charge descriptors are evaluated for their predictive performance on recently published antibody pI, viscosity, and clearance data. From this, we devised four rules for therapeutic antibody profiling which address developability issues arising from hydrophobicity and charged-based solution behavior, PK, and the ability to enrich for those that are approved by the U.S. Food and Drug Administration. Differences in strategy for optimizing the solution behavior of human IgG1 antibodies versus the IgG2 and IgG4 isotypes and the impact of pH alterations in formulation are discussed.
