In vitro and in silico assessment of the developability of a designed monoclonal antibody library.

摘要: Despite major advances in antibody discovery technologies, the successful development of monoclonal antibodies (mAbs) into effective therapeutic and diagnostic agents can often be impeded by developability liabilities, such as poor expression, low solubility, high viscosity aggregation. Therefore, strategies to predict at early phases risk late-stage failure candidates are highly valuable. In this work, we employ silico solubility predictor CamSol design a library 17 variants humanized mAb predicted span broad range values, examine their potential with battery commonly used vitro assays. Our results demonstrate ability rationally enhance developability, provide quantitative comparison measurements each other more resource-intensive measurements, well predictors that offer potentially faster cheaper alternative. We observed strong correlation between experimentally determined obtained using panel assays probe non-specific interactions. These indicate computational methods have reduce or eliminate need carrying out laborious quality controls for large numbers lead candidates. Overall, our study provides support emerging view implementation tools campaigns ensure rapid selection optimal potential.