Strategies for automated affinity purification-resin screening for non-traditional biopharmaceuticals in the discovery space.

Abstract

Biotherapeutics occupy a significant portion of the pharmaceutical pipeline and are projected to continue growing in sales and scope. Further, the field is advancing novel and more complex molecules beyond monoclonal antibodies including multi-target proteins, engineered proteins and bioconjugates. In this aspect, the development of increasingly advanced and challenging therapies necessitates a commiserate degree of innovation to develop automated methods for resin screening, purification, and analytics in the discovery space to quickly identify liabilities and rank candidates with minimal impact on developmental resources. In this work, we introduce an automated resin screening platform tailored to small scale production runs for clone evaluation and process development in the biologics discovery space. The complex characteristics of these novel therapies requires empirical testing of resin to ensure optimal recovery of high-quality material for evaluation to inform on cell line development and future downstream process and analytical method development. This workflow enables the purification of milligrams of protein material for analytical testing and identifies ideal resins to leverage downstream as a candidate quickly progresses. This workflow was validated using a research monoclonal antibody and applied to a novel bispecific fusion protein to evaluate resin performance with respect to recovery, purity and impact on higher-order structure.