Project BriefOpen Competition 1 - BiotechnologyRational Design of Non-Immunogenic ProteinsRedesign and re-engineer therapeutic proteins to be less immunogenic by using innovative computational methods to identify and replace antigenic protein regions (epitopes) for improved safety and efficacy. Sponsor: Xencor111 W. Lemon AvenueMonrovia, CA 91016
As a result of unprecedented opportunities brought about by the Human Genome Project, pharmaceutical companies have expanded their efforts to develop protein therapeutics -- proteins designed to treat disease. The market for protein-based products is now greater than $17 billion. The advantages of protein therapeutics over conventional therapeutics include faster development times and lower development costs. Unfortunately, many promising candidates fail to reach the market because of the over-reaction of human immune systems, which attack the therapeutic proteins as though they were foreign tissue. Excessive immune responses have been observed even with approved products that have been on the market for several years. Immune responses against non-therapeutic products, including allergic reactions to proteins in detergents, cosmetics, toiletries, and genetically modified organisms (such as corn) are also of serious concern. Testing such products typically involves using animals, but this method is costly and not predictive of human immunogenicity. Xencor plans to overcome the immunogenicity problem by coupling its proprietary Protein Design Automation (PDATm) technology with immunogenicity prediction methods as well as the development of new high-throughput validation assays. The new technology, referred to as ImmunoPDATm, will identify specific immunogenic protein regions (epitopes) known to elicit immune responses and replace them in the protein with rationally designed protein fragments that do not disrupt protein structure and function. The result will be the design, generation, testing, and production of non-immunogenic proteins that are no longer recognized as foreign objects by the human immune system. Current methods that rely on chemical modification of immunogenic proteins are inefficient and unsystematic. Poor market conditions make venture capital firms and pharmaceutical companies unwilling to invest in a high-risk biotech project that will not produce near-term revenues or late-stage product candidates. Funds from the ATP to supplement Xencor's commitment of $2.6 million would significantly hasten the speed and expand the scope and scale of the research. Researchers from the Mayo Clinic (Rochester, Minn.) and the Johns Hopkins University (Baltimore, Md.) will be engaged as consultants. If successful, this technology will accelerate the discovery of new non-immunogenic proteins for treating a variety of diseases and will decrease development costs, perhaps by millions of dollars per drug candidate. Researchers will also have better chances of finding solutions to immunogenicity problems of protein products now on the market. The growth of the U.S. pharmaceutical business will be stimulated, and the net result will be safer, lower-cost treatments for patients.
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