R.M. Booth, R.E. Skouby, A.M. Jons, C.L. Parham, J. Mike and D.W. Howell
Bondwell BioPure,
United States
Keywords: Antibody purification, membrane, biomaterial
Summary:
The development of novel antibody therapies, combined with identification of novel mAb applications for diseases such as Alzheimer’s disease, Parkinson’s disease, infectious diseases, diabetes, and some coronary heart disease or atherosclerosis products, are creating an explosive demand for therapeutic monoclonal antibodies (mAbs). However, downstream processing (mAb purification) is not keeping pace with demand, creating a significant bottleneck in manufacturing. Currently, 93% of downstream operations use a Protein A-based method for antibody purification. Protein A resins offer high binding capacity but are limited by low flow rate and high costs. On the other hand, Protein A membranes combine high flow rates with low recovery volumes but lack antibody binding capacity. No current matrix has both high binding capacity and tolerance of high flow velocity. Bondwell Technologies (BT) has developed a platform technology that combines the high binding capacities achievable with resins with the high flow rates associated with membranes into a single product produced at sufficiently low cost to allow application as a single-use technology. Unlike other matrices, BT can incorporate large multi-domain proteins into unique, stable materials. Active, uniformly oriented proteins are distributed evenly throughout BT materials. This pre-functionalization method overcomes the limitations of other supports that rely on post-functionalization chemical crosslinking steps. As a result, the ligand density and stability are significantly improved. Our first-generation prototype demonstrated a static binding capacity of 66 mg/mL and a DBC10 of 35 mg/mL at a 2-minute residence time. These prototypes are undergoing third-party testing with several large players in the bioprocessing market. Feedback from these tests will be incorporated into a second-generation protype with optimized performance. Early data indicates that our second-generation prototype will compete with current resin capacities (>70 mg/mL) while also reducing the residence time. Bondwell Technologies is leveraging the unique properties of our biomaterials to develop a Protein A membrane that far exceeds the current mAb purification technologies.