The GenNext Phase II SBIR submssion entitled “FoxWare™, an Advanced Data Analysis Package for Hydroxyl Radical Foot-printing Higher Order Structural Analysis” is responsive to the ackowledged need for new and improved tools for higher order structural analysis (HOS) of biopharmaceuticals. Biopharmaceuticals are complex, heterogeneous mixtures of 3-dimensional biomolecules, whose safety and efficacy is reliant upon proper HOS. The presence of proteins with improper HOS has been linked to severe adverse drug reactions (ADR), establishing the need for new and improved HOS analytics. An emerging HOS analysis technique is hydroxyl radical foot-printing (HRPF). HRPF involves the irreversible labeling of a protein's exterior by reaction with hydroxyl radicals with subsequent MS analysis to identify the outer portions of the protein. The most widely used method for generating OH radicals employs a quick burst of UV light, and is appropriately called fast photochemical oxidation of proteins (FPOP). Academic laboratories have demonstrated the utility of FPOP for HOS analysis; however adoption in pharma has been minuscule at best. Guided by the critiques of scientists at leading biopharmaceutical companies, we have identified barriers that have limited pharma's adoption of FPOP HRPF. A substantial barrier is the absence of data processing tools to facilitate HRPF analysis. Today there are no commercial solutions for FPOP analysis, despite the demonstrated market need for its HOS analytical power. Today's proteomics data analysis products fail to adequately address specific work-flow, chemical labeling / artifacts, and comparative study requirements of HRPF HOS analysis. Researchers are compelled to use a piece-meal approach, arduously stitching together results from multiple packages and manually manipulating data in home-brew spreadsheets. As such, data processing represents a significant bottleneck that greatly complicates and delays progress in HRPF HOS studies. Our FoxWare™ software addresses data processing demands of HRPF HOS analysis. Our proposal vastly improves HRPF data analysis by replacing laborious and agonizing present-day practices with an integrated, seamless solution to interpret and amplify the value of HRPF HOS studies. Upon completion of our envisioned program, FoxWare will make an indelible mark upon HOS analysis and impart a transformative shift in analytics and HRPF throughput, addressing the market demands of the biopharmaceutical industry.

The importance of large protein drugs (biopharmaceuticals) and their generic counterparts, know as biosimilars, has created a need for improved analytics to facilitate biopharmaceutical research and to combat adverse drug reactions. The biopharmaceutical industry acknowledges the critical role that protein structure plays in the safety and function of biotherapeutics. Consequently, the U.S. government has issued guidelines that call for the use and development of state-of-the-art technology for evaluating bipharmaceutical protein structure. The GenNext Phase II SBIR will create an improved data processing software program to analyze protein higher order structure. Upon successful completion of our program, we will demonstrate the transformative nature of our new technology to positively impact biopharmaceutical research.