High throughput cross-interaction measures for human IgG1 antibodies correlate with clearance rates in mice

摘要: Although improvements in technology for the isolation of potential therapeutic antibodies have made process increasingly predictable, development biologically active monoclonal (mAbs) into drugs can often be impeded by developability issues such as poor expression, solubility, and promiscuous cross-reactivity. Establishing early stage screening assays capable predicting late behavior is therefore high value to minimize risks. Toward this goal, we selected a panel 16 representing different profiles, terms self- cross-interaction propensity, examined their downstream from expression titer accelerated stability pharmacokinetics mice. Clearance rates showed significant rank-order correlations 2 related assays, with closest correlation non-specificity assay on surface yeast. Additionally, self-association correlated each other but not mouse clearance rate. This case study suggests that combining throughput discovery could significantly lower