The Therapeutic Antibody Profiler for Computational Developability Assessment

The need to consider an antibody's "developability" (immunogenicity, solubility, specificity, stability, manufacturability, and storability) is now well understood in therapeutic antibody design. Predicting these properties rapidly and inexpensively is critical to industrial workflows, to avoid devoting resources to non-productive candidates. Here, we describe a high-throughput computational developability assessment tool, the Therapeutic Antibody Profiler (TAP), which assesses the physicochemical "druglikeness" of an antibody candidate. Input variable domain sequences are converted to three-dimensional structural models, and then five developability-linked molecular surface descriptors are calculated and compared to advanced-stage clinical therapeutics. Values at the extremes of/outside of the distributions seen in therapeutics imply an increased risk of developability issues. Therefore, TAP, starting only from sequence information, provides a route to rapidly identifying drug candidate antibodies that are likely to have poor developability. Our web application ( opig.stats.ox.ac.uk/webapps/tap ) profiles input antibody sequences against a continually updated reference set of clinical therapeutics.