Research Project
10134745
Project Summary This Fast-Track SBIR project will address voice of customer needs for chromatography products that rapidly purify therapeutic proteins with high selectivity over closely related species such as isoforms, variants, and product aggregates. Therapeutic proteins are among the most effective treatment modalities for severe and chronic conditions such as cancers and autoimmune disorders. As protein titers increase and numerous non- monoclonal antibody molecules are developed and enter clinical trials, purifications are becoming more complex and challenging. Coincidental with these challenges, biomanufacturers are moving towards small batch production runs in multidrug facilities to increase flexibility and counteract market risks. This is particularly true for emerging orphan drugs and personalized medicines. Current multimodal cation-exchange (MM-CEX) chromatography products are limited to resin media. They offer high selectivity but require long residence times that lead to long purification runs and associated product losses at production scale. The products of this SBIR Fast-Track project will be first-in-market, disposable MM-CEX membrane columns and cassettes for bind-and-elute polishing step purification of mAbs and primary capture step purification of non- mAbs. They will have major impact on the industry and contribute to improving human health by purifying proteins rapidly and selectively, supporting faster changeovers in multidrug facilities due to their disposability, and improving patient accessibility to treatments. The overall aims of the Fast-Track study are (i) to develop MM-CEX membranes with the above-stated, sought-after performance characteristics using scalable production strategies and (ii) to determine membrane column operating ranges and conduct field research on prototypes. Research will be done in partnership with Clemson University to understand membrane structure- performance relationships. Field research will be done with industry partners to study purification schemes, build demonstration cases for broad applicability to purifying biologics, and compare performance against commercial products. The Specific Aims of the Phase I research are to confirm the technical feasibility of two innovative, patentable synthetic approaches to MM-CEX membrane fabrication and to quantify performance for polishing step purification of a mAb and a non-mAb produced by a commercial cell line. The Specific Aims of the Phase II research are to comprehensively evaluate the roles played by synthesis conditions and membrane pore size on performance; to finalize a production process for MM-CEX membrane columns with defined product shelf life and reusability; and to determine column operating ranges, demonstrate tunable selectivity and aggregate impurity removal, and conduct the field research on prototypes. Market entry for the new column products will be sales to purification scientists and engineers in biopharmaceutical companies who seek this enabling new technology. These individuals are end-users, influencers and decision makers.
