?sHLA Protein Chip? The class I [A, B, C] and class II HLA proteins [DRB1, DQ, DP] comprise the heart of the inducible human immune system. For organ, marrow and stem cell transplantation, the development of serum-born antibodies against one or more of those many HLA proteins comprises the best and earliest test for transplant rejection. Because of the enormous medical importance of transplantation, serum testing for the appearance of anti-HLA antibodies has emerged as one of the premier tests in all of laboratory medicine. The present $300M/yr market for HLA-based transplantation serology is dominated by a single supplier: Thermo-One Lambda, who has configured an anti-HLA antibody screening test that is based on the use of membrane extracts coupled to Luminex beads. That pairing of cell extracts and Luminex beads comprises 15-year old technology which, although still the dominant market leader, is felt by Key Opinion Leaders in Transplantation Medicine to produce poor sensitivity and specificity relative to other kinds of serum immunoassay. There is thus a clear and present need for a new and better alternative to the current test method for anti-HLA antibody screening. The Phase IIb plan presented here provides a fundamentally new alternative to the dominant Thermo-One Lambda test: based on the convergence of two highly innovative technology platforms: I. Cloning and expression of an enormously diverse family of recombinant HLA proteins, the sHLAs, which was invented and developed by Pure Protein: class I = 120; class II = 117. II. Deployment of complex immunoassays such as those for the 237 sHLAs, in a simple, low-cost protein microarray format, which was invented and developed by GMSbiotech. The commercial focus of the proposed Phase IIb plan, to be executed as a Pure Protein + GMS collaboration, is to create a pair of microarray based tests, EZScreenTM I & EZScreenTM II, to be provided as a kit with all ancillary reagents and turn-key analytical software: wherein EzScreenTM I can interrogate in parallel, as a single test, serum antibodies against 120 different recombinant class I sHLA proteins; and EZScreenTM II can interrogate, also in parallel as a single test, serum antibodies against 117 different recombinant class II sHLA proteins. Each EZScreenTM test is performed on 20uL of raw serum at room temperature, using only simple laboratory pipetting, by staff with no special expertise in bioinformatics.
Specific Aims of the Present Phase IIb Study. SA1: Complete Cloning, Expression and Manufacture of the Remaining Class II sHLA Proteins (Yr. 1). SA2: Complete Validation of EZScreenTM Manufacture at a Third Party OEM Supplier (Yr 1). SA3: Complete EZScreenTM Analysis Software Validation (Yrs. 1-3). SA4: EZScreenTM Kit Manufacture (Yrs. 1-3). SA5. EZScreenTM Beta Testing using ASHI Reference Labs (3 labs).
?sHLA Protein Chip? A three-year Phase IIB SBIR plan is proposed, focused on the development of a pair of microarray-based tests for sera antibody detection which emerge against HLA proteins, comprising a fundamental improvement in the diagnostic side of Transplantation Rejection. Upon completion of this plan, both tests and the companion software will be ready for Research Use only (RUO) product launch and to begin the FDA review process.