GLSynthesis Inc. — Department of Health and Human Services SBIR Phase II: 300

Description

DESCRIPTION provided by applicant In Phase I as proposed we successfully demonstrated proof of principle for the Flurosome trans abcg assay This innovative assay characterizes how compounds interact with the important ATP dependent drug efflux transporter ABCG BCRP Breast Cancer Resistance Protein i e the susceptibility of drug candidates to be extruded from their target tissue A successful Phase I forms the basis for this Phase II proposal The goal of Phase II is to bring the Fluorosome trans abcg assay to commercialization providing a fully validated high throughput solution for ABCG transporter studies to drug development groups worldwide Our ultimate goal is to commercialize a complete suite of assay reagents for all FDA and EMA mandated transporters enabling the pharmaceutical industry to efficiently evaluate the suitability of drug candidates for continued development The andquot Fluorosome trans abcg andquot reagent will be one of this suite of reagents We were able to successfully accomplish all the proof of principle goals of our Phase I proposal In brief we were able to produce purified human ABCG reconstitute the ABCG transporter in a functional form into lipid bilayers test and confirm the reconstituted ABCG andapos s ATPase activity use the reconstituted ABCG to construct lipid vesicles containing encapsulated drug sensor andquot Fluorosome trans abcg andquot demonstrate that ABCG is functional in the resulting Fluorosome trans abcg construct demonstrate the ability of Fluorosome trans abcg to detect the active transport of test substrates and demonstrate that the assay is sensitive to known inhibitors of ABCG In addition to succeeding in these initial goals we have made a significant advance over what was proposed in Phase I in that instead of relying on an external vendor for the purification and reconstitution of the ABCG protein we have both improved these procedures and brought them entirely in house For Phase II we will bring the Fluorosome trans abcg assay to a commercial stage When successful this assay will be the first off the shelf high throughput assay available to drug developers that is unambiguously specific for the ABCG transporter The assay uses small amounts of test material and is simple to use With respect to instrumentation it requires only a standard injecting multiwell fluorescence plate reader which generates real time data in under a minute To bring this assay to commercialization we propose the development of various in house processes technologies that enable the large scale production of purified ABCG protein and its incorporation into our Flurosome trans abcg reagent the necessary extensive validation of the assay using drugs known to interact with ABCG establishment of rigorous quality control methods required for reagent manufacture and storage and finally the implementation of an extensive plan which includes an Early Adopter Program followed by product launch and revenue generation Accomplishing these goals will result in a unique easy to use rapid cost effective and highly specific assay for characterizing the interaction of drugs and drug candidates with the ABCG transporter The Fluorosome trans abcg assay will be poised to enter the market as a highly competitive and useful product This will greatly facilitate us in bringing our other two current Fluorosome assays those for the human pgp and BSEP into the marketplace PUBLIC HEALTH RELEVANCE This project will result in a commercial level technique to determine if drugs will be expelled from their target tissue by the Breast Cancer Resistance Protein andquot ABCG andquot The test will allow the pharmaceutical industry to evaluate at an early stage the suitability of drug candidates for continued development The test will be highly specific reliable simple rapid inexpensive and amenable to robotics