Methods for treating or preventing the inflammatory response of IBDs by intrarectally or intraperitoneally administering a therapeutic effective amount of NF-KB decoy oligodeoxynucleotides

Inflammatory Bowel Diseases (IBDs; Crohn's disease and ulcerative colitis) are chronic inflammatory disorders affecting almost 1 million people in the developed world at an estimated annual cost of one billion dollars in lost work days. Current treatments include corticosteroids, 5-aminosalicylates and immunomodulators but novel and more effective therapies without adverse side effects continue to be needed. NIH researchers have previously shown that a variety of immunomodulators affecting the Th1 and Th2 T cell responses which underlie Inflammatory Bowel Diseases can be used to treat IBD disease models and have now extended this work by inhibiting NF-KB transcriptional activity in a variety of animal models using decoy oligodeoxynucleotides (decoy ODNs). Dr. Strober and colleagues at the National Institute of Allergy and Infectious Diseases (NIAID) have shown that intrarectal (i.r.) or intraperitoneal (i.p.) administration of decoy ODNs encapsulated in a viral envelope (HVJ-E) prevented and treated a model of acute trinitrobenzene sulfonic acid-induced (TNBS-induced) colitis, a model for Crohn's disease, as assessed by clinical course and the effect on Th1 cytokine production. NF-KB decoy ODNs were also shown to be an effective treatment of a model of chronic TNBS-colitis, inhibiting both the production of IL-23/Il-17 and the development of fibrosis that characterizes this model. Treatment of TNBS-induced inflammation by i.r. administration of NF-KB decoy ODNs did not inhibit NF-KB in extraintestinal organs and resulted in CD4+ T cell apoptosis, suggesting that such treatment is highly focused and durable. Additionally, NF- KB decoy ODNs also prevented and treated oxazolone-colitis, a mouse model for ulcerative colitis, and thus affected a Th2- mediated inflammatory process. In each case, decoy administration led to inflammation clearing effects, suggesting a therapeutic potency applicable to human IBD [J. Clin. Invest. (2005) 115, 3057-3071]. Available for licensing are methods for treating or preventing the inflammatory response of IBDs by intrarectally or intraperitoneally administering a therapeutic effective amount of NF-KB decoy ODN. Claims are directed to treatment of Th1 and Th2 inflammatory response and these studies suggest that NF-KB decoy ODNs targeting the consensus NF-KB binding site and encapsulated in a viral envelope represent an effective approach for the treatment of IBDs.

U.S. Patent Application No. 11/125,919 filed 10 May 2005 (HHS Reference No. E-108-2005/0-US-01); PCT International Application filed 10 May 2006 (HHS Reference No. E-108- 2005/0-PCT-02) Inventors: Warren Strober (NIAID), Ivan Fuss (NIAID), Atsushi Kitani (NIAID), and Stefan Fichtner-Feigl (NIAID) Related IBD technologies available for licensing also include IL- 13 modulators and inhibitors (HHS Reference No. E-131-2002/0- PCT-02, WO 2004/001655, filed 14 June 2002) and IL-13 mutant and chimeric molecules (HHS Reference No. E-003-2005/ 0-US- 01, U.S. Provisional Patent Application No. 60/671,624 filed 15 April 2005).

Licensees sought. In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.