Geron Corporation, a biopharmaceutical company focused on developing and commercializing therapeutic and diagnostic products, announced that it has been granted U.S. Patent No. 6,610,839, by the U.S. Patent and Trademark Office, with claims covering the promoter that regulates expression of the human telomerase reverse transcriptase gene (the "hTERT promoter"). Geron had non-exclusively licensed the hTERT promoter to Genetic Therapy, Inc. (GTI), a subsidiary of Novartis AG, for use in the development of viruses that are designed to target cancer cells. Cell Genesys, Inc. recently acquired rights to the GTI product portfolio and intellectual property in the field of c, including the hTERT promoter licensed non-exclusively from Geron. This granted patent triggers a milestone payment.
"This U.S. patent for the hTERT promoter is significant because pre-clinical animal data reported by us, GTI and others, are confirming that the promoter can confer both selective expression of effector genes and selective viral replication in cancer cells across a wide range of tumor types," noted David J. Earp, J.D., Ph.D., Geron's vice president of Intellectual Property. "These data suggest that the promoter can be used therapeutically to drive anti-cancer genes in cancer-killing viruses."
In June, 2003, GTI presented data from its work in oncolytic viruses at the annual American Society for Gene Therapy (ASGT) conference, held in Washington D.C. The studies used an oncolytic virus in which two genes essential for replication of the virus were controlled by separate tumour specific promoters -- the first by the E2F-1 promoter (primarily active in Rb-pathway defective cancer cells) and the second by the hTERT promoter. Based on studies with mice carrying human liver and prostate cancers, GTI reported that a single intravenous injection of the virus led to significant anti-tumor efficacy and improved survival, without significant toxicity. Moreover, the combination of the oncolytic virus with widely used chemotherapy drugs was synergistic in human tumor cell cultures of hepatocellular, prostate, small cell lung and colon carcinomas. Continuing the synergy studies in an in vivo liver cancer model, GTI reported that significantly improved anti-tumor efficacy was observed when the oncolytic virus was combined with doxorubicin, compared to either treatment alone.
"We have been pleased with the progress made by GTI," said Thomas B. Okarma, Ph.D., M.D., Geron's president and chief executive officer. "Internally, we tested oncolytic viruses driven by the hTERT promoter and the data we obtained suggested that the specificity of this promoter for cancer cells of many types would enable these viruses for use as mono-therapy as well as in combination with other therapeutic modalities. We made a decision to out-license this technology for development by companies with a principal business focus and IP in the oncolytic virus field. We look forward now to Cell Genesys' efforts to continue the development of this product."
"Oncolytic viruses may represent an important therapeutic alternative for cancer patients in the future," said Robert Tidwell, Cell Genesys' senior vice president of Corporate Development. "Our scientists have a strong interest in the telomerase promoter and we are eager to continue working with it in our oncolytic virus research in order to identify a clinical candidate as quickly as possible."
The telomerase enzyme must be turned on for cancer cells to replicate indefinitely and enable tumor growth and metastasis. Geron's proprietary telomerase technology is now the foundation for the development of three distinct approaches to treating cancer. Geron's telomerase inhibitors, GRN163 and GRN719, drugs that block the telomerase enzyme and send cancer cells into crisis, are in pre-clinical testing. Geron's cancer vaccine, which induces an immune response specific to telomerase-bearing cancer cells, is in a phase I/II clinical trial for hormone-refractory metastatic prostate cancer at Duke University. Finally, Cell Genesys will continue the development of cancer-killing oncolytic viruses that employ the hTERT promoter to drive selective expression of a gene required for viral replication in cancer cells.