Technology
MOLECULAR DIAGNOSTIC PRODUCT DEVELOPMENT

Molecular Diagnostics Development Gene Express, Inc. was formed in 1992 to standardize multi-gene expression measurement and to create reliable molecular diagnostic products. Gene Express's StaRT-PCR technology and pharmacogenomics are developing biomarkers, theranostics and clinical molecular diagnostics that are transforming the practice of medicine. Major Molecular Diagnostic products have already been developed which focus on accurately diagnosing and treating cancer and other diseases. Multi-center clinical testing has begun on the product diagnosing lung cancer. To address the primary commercial product objective of the Company, Molecular Diagnostic Products, Gene Express has developed or is developing the following Products:

  • Lung Cancer Molecular Diagnostics Products (A battery of molecular diagnostic products focused on accurately diagnosing and treating lung cancer) Based on a National Cancer Institute grant of $1.2 one of these products, providing a more accurate diagnosis of lung cancer, is in multi-center clinical trials at the New York University Hospital, the Memorial Sloan Kettering Cancer Center, the University of Pittsburgh and the Medical University of Ohio.

  • Lung Cancer Gene Express has already developed molecular diagnostic tests for lung cancer. Each comprising transcript abundance (TA) measurement of different sets of genes in a signature or indices. These molecular diagnostics are ready for evaluation in multi-institutional trials using StaRT-PCR. The tests provide, respectively, (1) more accurate diagnosis of cancers (listed above in multi-center clinical trials), (2) the identification of Non-Small Cell, Small Cell & poor outcome lung cancers, (3) the third test, nearly ready for clinical trial, identifies lung cancers with resistance to chemotherapy (cisplatin) and (4) the identification of individuals at high risk for lung cancer. Patents are pending on these molecular diagnostic tests. Other promising tests in development will measure TA levels in panels of genes from peripheral blood cells before and after therapy to determine biological effect of treatment, and predict response.

  • Bladder Cancer In cooperative efforts with the University of Southern California and Genetic Squared, Inc., stages or the disease progression in bladder cancer has been molecularly identified with StaRT-PCR. Interactive Transcript Abundance Index (indices) or ITAI for each stage (Ta, T1, T2, T3 & T4) of bladder cancer have been developed as can be seen in the ITAI� example listed below for stage Ta: [(KDR >= ((if (MAPK29 > sqr (FGFR4)) then GSTP1 else PDGFB) + MMP16))] THEN Ta. This will allow the rapid development of specific tests to identify disease stages or progression in bladder cancer. These interactive signatures or indices can be developed with the high quality, reproducible numerical data from StaRT-PCR. This is ground breaking technology, the only method that provides reliable measurement of number of molecules of a gene transcript, and the only technology that supports the FDA's Pharmacogenomics Guidance for use in new drug development.

  • Other Cancer Molecular Diagnostics Products Gene Express has the technological capability of developing clinical molecular diagnostic tests for all the different types of cancers and other genetically related diseases. In addition Gene Express is searching for biomarker and theranostic gene sets to license and develop into Interactive Transcript Abundance Index (indices) or ITAI.

  • Whole Blood Analysis In a recent study commissioned by Pfizer, Gene Express defined normal ranges of gene transcript values and identified significant correlation between gene transcript abundance values and important clinical endpoint associations with healthy normal subjects in whole blood. Variation attributed to analytical factors (assay replicates, sample-to-sample and visit-to-visit) was less than 5% of total combined variation. A change of one standard deviation in the group mean response is often taken as clinically relevant change. The results of this study indicate that using the StaRT-PCR Method in a blood study would require 17 subjects per group to detect a one standard deviation level of change with 80% power using a 2-sided α = 0.05 statistical test for mean differences. A group of this size should produce a mean Transcript Abundance Measurement estimate with %CV <26%. This study also indicates that the StaRT-PCR Method could enable the molecular definition of diseases such as rheumatoid arthritis, osteoarthritis, inflammation, cardiovascular, diabetes and other diseases to be determined from gene expression measurement in blood.

  • Blood Cultures Using StaRT-PCR, Gene Express is developing measurement for blood cultures in hours, not days and will identify infection from all 100 bacteria and viruses that attack humans.

Creating Molecular Diagnostic Indices Gene Express, Inc. has created a clinical molecular diagnostics and pharmacogenomics process that can generate medical diagnostic rules for many types of diseases. In addition to the company's technology, Gene Express is working with two strategic partners. First, on the front end of our StaRT-PCR technology, one partner has access to normal and diseased tissues samples and has the most experience with RNA extraction in different types of tissues. Second, on the back end of our technology, after Gene Express produces the number of standardized molecules of gene expression, we are beginning to co-market analytical software. This machine learning software is producing molecular diagnostic, predictive and pharmacogenomics rules for innovative molecular diagnostic tests and individually designed pharmacogenomics drugs. These innovated treatment diagnostics are expected to change the practice of medicine including reducing both the cost and time for the development of new drugs.

Commercialization of Molecular Diagnostic Products Currently, Gene Express is seeking strategic partners to help commercialize these molecular diagnostic tests. We will offer initially our lung cancer molecular diagnostic tests as home brew tests only as a service in a CLIA (Clinical Laboratory Improvement Amendments) SEM Center. This strategy will allow earlier market entry and allow early capital resources to be used for purposes other than the regulatory approval process. Molecular Diagnostics tests that are successful in the SEM service Center, and/or are promising from the beginning, will be converted to kits and submitted for FDA approval.

New StaRT-PCR Assays The sequencing of the genome facilitated the Company's efforts to develop and commercialize its StaRT-PCR assay reagents since the sequence is a prerequisite to the preparation of the StaRT-PCR gene's Internal Standard. The component reagents to conduct StaRT-PCR assays are gene specific forward and reverse primers and competitive template internal standards that are formulated into Standardized Mixtures of Internal Standards (SMIS). These StaRT-PCR reagents are manufactured under controlled Good Laboratory Practice (GLP) with stringent quality control (QC) and quality assurance (QA) performed and in addition to the quality assurance (QA) tests conducted on new SMIS in the Standardized Expression Measurement (SEM) Center. Gene Express is currently developing additional gene expression StaRT-PCR tests. It is estimated that 5000 to 10,000 genes could have commercial application and thus patented StaRT-PCR assay reagents would be produced for these genes.

Analysis of Protein and Gene Transcript Abundance Measurements in the Same Sample Gene Express is currently developing methods that will be able to conduct protein and gene expression tests on the same sample in the near future. Both of these measurements may be important in developing clinical biomarkers and molecular diagnostic products. A patent has been submitted for a method that enables these analyses. The method enables measurement of proteins, drugs and other clinically important molecules with all of the performance characteristics of StaRT-PCR. Specifically, the linear dynamic range will be greater than 8 orders of magnitude and the lower detection threshold will be less than 10 molecules. This lower detection threshold is three orders of magnitude better than that for mass spec or microarrays, and 5 orders of magnitude better than for classic immunoassays.

 

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