SBIR Phase I: Non-Chromatographic Method for the Purification of Monoclonal Antibodies

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to improve manufacturing technology for the purification of monoclonal antibodies, which are important therapeutics as well as valuable tools in research and diagnostics. Approximately four new antibody drugs are approved every year, and while they can have tremendous clinical outcomes and are sometimes heralded as "magic bullets," they often come with a significant price tag. This puts a strain on patients and insurance companies, limiting the accessibility of antibody-based drugs. Furthermore, antibodies are critical research tools that enhance the understanding of biology. The technology developed in this research project will provide a completely novel method for the purification of antibodies from cell culture that will lower cost, increase manufacturing throughput, and accelerate the time to market for new therapeutics. Commercially, this technology will disrupt the current gold standard - Protein A resin - making antibody purification simpler, faster, and cheaper at all scales: research, clinical, and industrial. The intellectual merit of this SBIR Phase I project is to develop technology for improved purification of monoclonal antibodies. Although upstream production of antibodies in cell culture has improved dramatically, downstream purification has not kept pace, resulting in a production bottleneck and a major market opportunity. The objectives of this SBIR Phase I project are to demonstrate technical and commercial feasibility of a new technology that combines affinity with liquid-liquid phase separation to separate antibodies from cell culture contaminants. It involves an antibody-binding domain fused to a biopolymer with stimulus responsive phase behavior. When this fusion protein is added to cell culture harvest, it binds the antibody and, after triggering the phase separation with salt, pulls the antibody out of solution. The purified antibody can then be eluted from the fusion by lowering the pH. This project aims to 1) optimize regeneration conditions so that the fusion can be reused, 2) evaluate long-term stability, and 3) validate the technology at scale and conduct a head-to-head comparison to the industry gold standard, Protein A resin. The goal is to identify storage conditions that provide a long shelf life for a product that can be reused 10-100 times without compromising antibody yield or purity. The focus of the project is to demonstrate promising capabilities of the technology for use in industrially manufactured monoclonal antibodies, replacing conventional chromatography steps with a simpler and more cost-effective method. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.