Biopolymers for Relevant Recombinant Protein Puification

Phase Bioscience, Inc., Morrisville NC

Investigators

Abstract

DESCRIPTION (provided by applicant): The long-term objective of this application is to develop a novel protein purification technology, which will eliminate the need for chromatography. This technology, the deltaPhase TM Technology, has greater selectivity, is simpler to operate and is much less expensive than chromatography. In short, the deltaPhase Technology will change the economics of protein purification. The impact of the technology will be in two health related areas: Development of Novel Medicines. As unique pharmaceutical targets are identified through functional genomics, they will need to be expressed and purified for evaluation (target validation) and screening (high-throughput screening and X-ray crystallography). The PhaseBio technology will rapidly expand the pool of target proteins by 1) enabling first-time expression of proteins in expression systems of choice (e.g., E. coli) due to the significant solubility enhancement properties of the technology and 2) increasing the throughput of purification by the simple, one step purification method which can be readily automated. Lower Cost of Bio-therapeutics. The use of the deltaPhase TM technology by innovative biopharmaceutical companies will reduce the purification costs by an estimated 10-fold. Given the pricing pressures by managed care, biopharmaceutical companies will have more pricing flexibility when the cost of goods is reduced. In addition, the biogeneric market has not fully developed because the cost of manufacturing has been so high, and the price differential between the generic and the original has not warranted development of the generic substitute. The ability of the deltaPhase TM technology to reduce purification costs could be an important catalyst in the development of a biogeneric market. The technology relies on the use of an Elastin-Like Polypeptide (ELP) fused to the protein of interest. These tags are fused using recombinant DNA techniques. The Specific Aims of the project include 1. Design and Synthesis of deltaPhase TM ELP tags for Optimized Purification 2. Expression and Characterization of ELPs and 3. Expression and Purification of Four Pharmaceutically Relevant Recombinant ELP Fusion Proteins. The Milestones for the project include: 1. Purify two of the four proteins to at least 90 percent purity, as measured by SDS-PAGE. 2. For the two purified proteins, one protein will have equal activity to that protein purified by conventional means. 3. Demonstrate at least a two-fold decrease in purification costs (time and material) for one of the purified proteins.