EXECUTIVE SUMMARY

Novel Type I Interferon Antagonists

SUMMARY:  Dr. Jerome A. Langer in the Department of Molecular Genetics, Microbiology & Immunology at the University of Medicine & Dentistry of New Jersey (UMDNJ) has produced variants of interferon that block the action of active Type I interferons.  These Type I interferon antagonists may have therapeutic potential for the treatment of autoimmune diseases such as systemic lupus erythematosus and Sjögren’s syndrome.  Siuta Consulting has been retained by UMDNJ to identify pharmaceutical or biotechnology company partners for the further development of these antagonists.

BACKGROUND:  Type I interferons are a family of proteins that constitute a rapid and broad-spectrum defensive response to viral infections and some intracellular parasites.  These proteins have therapeutic use against some viral diseases, several tumors, and multiple sclerosis.  However, there is recent evidence that Type I interferons are involved in the cause or progression of autoimmune disease states such as systemic lupus erythematosus and Sjögren’s syndrome.  In such instances, pharmacologic blockade of interferon action might be an effective method of slowing or stopping the disease progression.  There may also be other situations in humans where blocking Type I interferon action is desirable.  In addition, there are a number of studies in animals, including mouse strains that are susceptible to autoimmune disease, demonstrating that Type I interferon may be involved in promoting pathogenesis.  Therefore, therapeutic approaches to blocking the action of native Type I interferon are required both for humans and for experimental species such as mice.  Type I interferon antagonists also have diverse in vitro applications.

TECHNOLOGY:  Dr. Langer has demonstrated that novel antagonists of Type I interferon can be derived from native Type I interferons by mutational disruption of the site for interaction with the interferon receptor subunit IFNAR-1, while maintaining the strong interaction with the interferon receptor subunit IFNAR-2.  In his current prototype antagonists, he has demonstrated that several variants derived from IFN-α2b can inhibit the action of native Type I interferons in vitro.  These first-generation Type I interferon antagonists are being further characterized.  Modified interferon antagonists provide a useful alternative to other cytokine inhibitory molecules, such as antibodies or soluble receptors. 

Based on this overall design, Dr. Langer will improve and expand the potential applications by: (1) increasing the potency of the human interferon antagonists, which is important for human therapeutic applications; and (2) engineering analogous modifications in one or more murine Type I interferons by a similar strategy to provide relatively inexpensive antagonists for use in murine in vitro and in vivo applications.  Knowledge of structure/function relationships gained from these Type I interferon antagonists can provide the basis for the design of peptidic or non-peptidic mimetics that act as Type I interferon antagonists.

PATENT STATUS:  A United States Provisional Patent Application was filed in September 2007.