The development of a precipitation or crystallization step requires knowing the solubility of the target protein and its crystallization behavior in aqueous solutions at different pH, temperatures and in the presence of precipitating agents, especially salts. Within this work, a solubility model for proteins based on the second osmotic virial coefficient B-22 is developed. For this, a relation between protein solubility and B-22 was combined with the extended DLVO model. This solubility model was then used to model and also predict the protein solubility of lysozyme and monoclonal antibody for different salts, salt concentrations, and pH. The modeled as well predicted B-22 and protein solubility data of lysozyme in the presence of sodium chloride and sodium p-toluenesulfonate and of a monoclonal antibody in the presence of ammonium sulfate at different pH shows good agreement with experimental data. (C) 2016 Elsevier B.V. All rights reserved.