Maxim Pharmaceuticals have announced the United States Patent and Trademark Office issued U.S. patent number 6,828,091 B2, entitled "Method of Identifying Immunosuppressive Agents."
The patent covers a method for identifying therapeutically active immunosuppressive agents by screening for compounds that induce apoptosis in activated T or B cells. Apoptosis is detected by measuring the activity of caspase-3, an enzyme essential in programmed cell death.
"Overly aggressive immune responses have become associated with many serious diseases such as arthritis, graft versus host disease, inflammatory bowel disease, and other conditions. As our understanding of these diseases has progressed, the need for targeted immunosuppressive therapeutics has become more apparent. Our proprietary screening technology allows Maxim to find compounds that selectively suppress activated T or B cells and identify those holding promise as potential immunosuppressive drugs," commented Ben Tseng, Ph.D., Vice President of Research for Maxim Pharmaceuticals. "While our primary focus will remain on the research and development of compounds that induce apoptosis in cancer cells, we will also work to exploit the broader applications of our technology platform."
Cancer is characterized by uncontrolled cell growth (e.g., tumor formation). One reason for this unchecked growth is the disabling, or absence, of the natural process of programmed cell death called apoptosis. Apoptosis is normally triggered when a cell outlives its purpose or it is seriously damaged. One of the most promising approaches in the fight against cancer is to selectively induce apoptosis in cancerous cells, thereby checking, and perhaps reversing, the improper cell growth.
Maxim researchers can efficiently identify new cancer drug candidates and molecular targets that selectively induce apoptosis in cancer cells through the use of chemical genetics and our proprietary live cell high-throughput caspase-3 screening technology. Chemical genetics is a research approach investigating the effect of small molecule drug candidates on the cellular activity of a protein, enabling researchers to determine the protein's function. Using this approach with its proprietary caspase-3 screening technology, Maxim researchers can focus their investigation on the cellular activity of small molecule drug candidates and their relationship to apoptosis. The focus on apoptosis is achieved by screening for the activity of caspase-3, an enzyme with an essential role in cleaving other important proteins necessary to cause cell death through apoptosis. This combination of chemical genetics and Maxim's screening technology, allows researchers to discover and rapidly test the effect of small molecules on pathways and molecular targets crucial to apoptosis, and gain insights into their potential as new anticancer agents.
Maxim's screening technology is also particularly versatile since it can adapt its assays for almost any tumor type that can be cultured, and it can measure caspase activation inside multiple cell types (e.g. cancer cells, immune cells, or cell lines from different organ systems or genetically engineered cells). This allows Maxim researchers to find potential drug candidates that are selective for specific cancer types, which may help identify candidates that provide increased therapeutic benefit and reduced toxicity.
Maxim's high-throughput screening capabilities allow researchers to screen approximately 30,000 compounds per day. To date, this program has identified several families of compounds with potentially novel mechanisms that induce apoptosis in cancer cells. Four compounds from within these families have progressed to lead drug candidate status with proven pre-clinical efficacies in tumor models and identified molecular targets. The most advanced candidate from this program is entering a Phase 1 trial through collaboration with Myriad Genetics.