Reclaim Pharmaceutical Waste Management, LLC — Department of Health and Human Services SBIR Phase II: 400

Description

Project Summary Abstract Protein therapeutics are the fastest growing segment of the pharmaceutical marketyet there are two important challenges associated with the discovery and development of biologic drugsepitope paratope mapping andD structural analysisEpitope and paratope mapping are essential parts of identifying the most therapeutically relevant lead candidates for advancement to in vivo testingAccurately mapping epitopes can help identify therapeutic candidates that bind to the desired region of an antigen based on the mechanism of actionwhile characterizing paratopes frequently forms the basis for intellectual property strategiesProteinD structural analysis is crucial for many downstream activities throughout the drug development processand it most often is required to ensure that manufacturingshippingstorageand formulation do not have an unintended impact on protein structureIn additionD structural analysis plays a critical role in ensuring biosimilars under development are structurally similar to their branded originator drugCurrent analytical strategies for epitope paratope mapping andD structural analysis of protein therapeutics are often inadequate for the early stages of drug discovery and developmentIn responseQuarryBio and its research partners at Indiana University and the University of Massachusetts Amherst have developed a new mass spectrometry based method that uses covalent labeling to identify epitopes and paratopes and can detect changes in proteinD structure accurately and sensitivelyResearch during Phase I demonstrated that this method is quickeasy to use and provides sufficient resolution for both epitope mapping andD structural analysis of protein therapeuticsSuccess during Phase I was possible because of the creation of a customized data analysis software pipeline that could successfully identify and quantify covalently labeled sites in proteinsallowing the needed protein structural information to be obtainedPhase II will build off these successful preliminary studiesthereby preparing this technology for commercializationThree specific aims will be pursuedwe will demonstrate the ability of our covalent labeling technology to provide robust structural information and to map epitopes and paratopes in mAb antigen complexeswe will automate data analysis and visualization by creating protocols that minimize the manual manipulations associated with our customized softwareandwe will develop laboratory automation for sample preparation activities to improve the reproducibility of our measurementsAt the end of Phase IIwe expect that our covalent labeling technology and data analysis software pipeline will be fully ready for commercializationQuarryBio has fee for service contracts in place with seven biotech clientsdemonstrating the commercial potential of this technologyThe work proposed here will significantly improve the qualityreproducibilityand throughput of our approach and demonstrate how our methodology can be used for key decision steps during early stage biologic drug discovery and development Project Narrative Epitope mapping and high resolution biophysical characterization are critical elements for identifying biologic drug lead candidatesUnfortunatelycurrent analytical strategies are inadequate for obtaining epitope mapping data until after lead candidate selection and are not able to deliver high resolution analyses of proteinD structure quickly and cheaply enough for the early stages of drug discovery and developmentIn this SBIR Phase II projectQuarryBioLLC will develop a mass spectrometry method that uses labeling to identify epitopes and paratopes as well as detect changes in proteinD structureproviding high resolution protein structure analyses without the limitations of existing methods