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