GENNEXT TECHNOLOGIES, INC. SBIR Phase I Award, April 2018

The GenNext submssion entitledMetal oxide Photo Oxidation of ProteinsMoPOPfor Biopharmaceutical Higher Order Structural Analysisis responsive to the ackowledged need for new and improved tools for higher order structural analysisHOSof biopharmaceuticalsBiopharmaceuticals are complexheterogeneous mixtures ofdimensional biomoleculeswhose safety and efficacy is reliant upon proper HOSThe presence of proteins with improper HOS has been linked to severe adverse drug reactionsADRestablishing the need for new and improved HOS analyticsAn emerging HOS analysis technique is hydroxyl radical foot printingHRPFHRPF involves the irreversible labeling of a protein s exterior by reaction with hydroxyl radicalsOHgenerated from UV photolysis of hydrogen peroxideH Owith subsequent MS analysis to identify the outer portions of the proteinAcademic laboratories have demonstrated the utility of HRPF for HOS analysishowever adoption in pharma has been minuscule at bestGuided by the critiques of scientists at leading biopharmaceutical companieswe have identified barriers that have limited pharma s adoption of FPOP HRPFA substantial barrier is artifacts created by H OWhile H Ois a fine source ofOHits potential for protein oxidation under ambient conditions is well described and represents a limitation for HRPF adoptionIn our experiencebiopharmaceutical exposure to H Omust be limited to less thanminutes to avoid labeling artifactsSuch temporal limitations constrain the number of samples that can be queued in microplatesplacing H OHRPF at odds with market desires of throughput and productivityMoreoverclients have expressed the need for a rapid screening technique that could serve to triage their HOS studiesThis proposal aims to replace photolysis of H Owith a novel metal oxide photo catalytic process that producesOH from waterOur proprietarypatent pending process has been coined Metal oxide Photo Oxidation of ProteinsMoPOPMoPOP theoreticalOH yields are predicted to support HRPF experimentationeliminating the use of H Oand its associated complicationsWhen irradiated with an economical continuous waveCWdiode sourceMoPOP provides a facileinexpensiveandreagent freemeans to label biopharmaceuticalsIn addition to LC MS analysisMoPOP oxidative products can be detected and quantified using selective fluorescence dyes for carbonylated proteinsaddressing the market need for HOS screening The importance of large protein drugsbiopharmaceuticalsand their generic counterpartsknow as biosimilarshas created a need for improved analytics to facilitate biopharmaceutical research and to combat adverse drug reactionsThe biopharmaceutical industry acknowledges the critical role that protein structure plays in the safety and function of biotherapeuticsConsequentlythe U Sgovernment has issued guidelines that call for the use and development of state of the art technology for evaluating bipharmaceutical protein structureThe GenNext Phase I SBIR will demonstrate feasibility of an improved and high throughput means to screen for and analyze protein structure using a novel metal oxide photo catalysis approachUpon successful completion of our programwe will demonstrate the transformative nature of our new technology to positively impact biopharmaceutical research