Integrating In Silico and In Vitro Tools for Optimized Antibody Development-Design of Therapeutic Anti-oxMIF Antibodies.

Background: Rigorous assessment of antibody developability is crucial for optimizing lead candidates before progressing to clinical studies. Recent advances in predictive tools for protein structures, surface properties, stability, and immunogenicity have streamlined the development of new biologics. However, accurate prediction of the impact of single amino acid substitutions on antibody structures remains challenging, due to the diversity of complementarity-determining regions (CDRs), particularly CDR3s.

Beyond affinity: selection of antibody variants with optimal biophysical properties and reduced immunogenicity from mammalian display libraries.

The early phase of protein drug development has traditionally focused on target binding properties leading to a desired mode of therapeutic action. As more protein therapeutics pass through the development pipeline; however, it is clear that non-optimal biophysical properties can emerge, particularly as proteins are formulated at high concentrations, causing aggregation or polyreactivity. Such late-stage "developability" problems can lead to delay or failure in traversing the development process.