PFI:AIR-TT: Translation of multimodal membrane adsorbers for protein purifications

Clemson University, Clemson SC

Investigators

Abstract

This PFI: AIR Technology Translation project focuses on translating multimodal membranes towards commercialization to fill the market need for products that increase purification speeds during biologics drug discovery and preclinical research and development efforts. The multimodal membranes are important because they will help to get biologics to market faster where they are needed to service the large and growing population of patients with long-term, chronic conditions such as cancers, cardiovascular diseases, and autoimmune disorders. The project will result in research-scale, cation-exchange multimodal membrane chromatography (CEX-MMC) column prototypes. This CEX-MMC column has the following unique features: rapid purification of biologics, tolerance of feedstock ionic strength, high biologics binding capacity, and disposability. These features increase productivity and decrease purification costs of biologics by reducing processing times and number of steps, the costs of consumables, and fixed capital expenses when compared to the leading competing chromatography columns in this market space. Market entry will result from use of these products in research and early stage development laboratories, where purification speed is essential and customers are willing to try new technologies. This project addresses remaining technology gaps as it translates from research discovery toward commercial application. The first generation CEX-MMC developed in the NSF lineage award demonstrated unprecedented protein binding capacity at high ionic strength. Dynamic binding capacity results showed that the CEX-MMC column has high productivity; however, protein binding kinetics must be improved. In this project, new membrane coatings will be designed to enhance protein binding kinetics. In addition, nearly all performance data have been collected using pure-component protein solutions and low titer cell culture supernatant, and almost no work has been done to quantify biological activity of the product or removal of aggregates and other impurities. In this project, antibody media will be prepared using commercial cell lines and used to collect these essential performance data. Two biopharmaceutical companies have committed to collaboration for assessing the performance of the prototypes using industry representative process parameters and monoclonal antibody feed streams. Evaluation of protein recovery, purity, and removal of protein aggregates will be measured following the CEX-MMC column purification step. These are critical performance measures that need to be determined for the Minimally Viable Product (MVP) prior to commercialization. Strategic commercialization and educational plans are designed to validate remaining parts of the business model canvas and create new networks among inventors, entrepreneurs, potential investors and potential customers. Broader impacts also include training graduate and undergraduate students to better understand technology commercialization and entrepreneurship and pursue careers developing new purification technologies for biomanufacturing. Graduate and undergraduate students will attend lectures on technology commercialization held at CUBEInC, Clemson University's life science incubator. A collateral benefit of these lectures is that they will give all project personnel regular opportunities for direct communication with business leaders; entrepreneurs; and potential partners, customers, and investors in the life sciences. Students also will complete a course on technology commercialization designed for engineering students. MBA students will advance understanding of the market value, space, potential customers, and competition landscape and seek collaborations for launch with selected industry partners; and evaluate potential distribution channels and estimate the associated costs. The team will use this knowledge continually to refine the overall strategy for translation of the research discoveries onto a path towards commercialization.