[Federal Register Volume 71, Number 124 (Wednesday, June 28, 2006)]
[Notices]
[Pages 36816-36817]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 06-5868]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, HHS.

ACTION: Notice.

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SUMMARY: The inventions listed below are owned by an agency of the U.S. 
Government and are available for licensing in the U.S. in accordance 
with 35 U.S.C. 207 to achieve expeditious commercialization of results 
of Federally-funded research and development. Foreign patent 
applications are filed on selected inventions to extend market coverage 
for companies and may also be available for licensing.

ADDRESSES: Licensing information and copies of the U.S. patent 
applications listed below may be obtained by writing to the indicated 
licensing contact at the Office of Technology Transfer, National 
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, 
Maryland 20852-3804; telephone: 301/496-7057; fax: 301/402-0220. A 
signed Confidential Disclosure Agreement will be required to receive 
copies of the patent applications.

Treatment of Inflammatory Bowel Disease (IBD) Using NF-KB Decoy 
Polynucleotides

Warren Strober (NIAID), Ivan Fuss (NIAID), Atsushi Kitani (NIAID), and 
Stefan Fichtner-Feigl (NIAID)
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)
Licensing Contact: Susan Carson, D. Phil; 301/435-5020; 
[email protected].
    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

[[Page 36817]]

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

Treatment and Prevention of Inflammatory Bowel Disease (IBD) using 
Mutant and Chimeric IL-13 Molecules

Warren Strober (NIAID), Ivan Fuss (NIAID), Peter Mannon (NIAID), Jan 
Preiss (NIAID), Raj Puri (FDA), Koji Kawakami (FDA), Stefan Fichtner-
Feigl (NIAID), and Atsushi Kitani (NIAID)
U.S. Provisional Patent Application No. 60/671,624 filed 15 April 2005 
(HHS Reference No. E-003-2005/ 0-US-01); PCT International Application 
filed 14 April 2006 (HHS Reference No. E-003-2005/0-PCT-02)
Licensing Contact: Susan Carson, D. Phil; 301/435-5020; 
[email protected].
    Ulcerative colitis (UC) is a chronic inflammatory disease of the 
colorectum and affects approximately 400,000 people in the United 
States. The cause of UC is not known, although an abnormal 
immunological response to bacterial antigens in the gut microflora is 
thought to be involved. Present treatments for UC include anti-
inflammatory therapy using aminosalicylates or corticosteroids, as well 
as immunomodulators and diet. However, 25-40% of ulcerative colitis 
patients must eventually have their colons removed due to massive 
bleeding, severe illness, rupture of the colon, risk of cancer or due 
to side effects of corticosteroids and novel treatments are still 
actively being sought. NIH scientists and their collaborators have used 
a mouse model of experimental colitis (oxazolone colitis, OC) to show 
that IL-13, a Th2 cytokine, is a significant pathologic factor in OC 
and that neutralizing IL-13 in these animals effectively prevents 
colitis [Immunity (2002) 17, 629-638].
    OC is a colitis induced by intrarectal administration of a 
relatively low dose of the haptenating agent oxazolone subsequent to 
skin sensitization with oxazolone. A highly reproducible and chronic 
colonic inflammation is obtained that is histologically similar to 
human ulcerative colitis. Studies show that Natural Killer T (NKT) 
cells, rather than conventional CD4+T cells, mediate oxazolone colitis 
and are the source of IL-13 as well as being activated by CD1-
expressing intestinal epithelial cells. Tissue removed from ulcerative 
colitis patients were also shown to contain increased numbers of 
nonclassical NKT cells that produce markedly increased amounts of IL-13 
and that in keeping with epithelial damage being a key factor in UC, 
these NKT cells are cytotoxic for epithelial cells [J. Clin. Invest. 
(2004) 113, 1490-1497]. Building on their previous work, scientists at 
NIAID and FDA have shown that an Il-13 chimeric fusion protein linked 
to an effector molecule was able to prevent colitis in a mouse model of 
ulcerative colitis.
    Available for licensing are methods for treating or preventing the 
inflammatory response of IBD by inhibiting the binding of IL-13 to IL-
13 receptors on NKT cells. Additionally, these mutant and chimeric Il-
13 molecules are able to block the chronic inflammatory response that 
results in fibrosis as seen in Crohn's disease. Preventing the 
inflammatory response of colitis by either modulating or blocking IL-13 
and NKT cell activity continues to be an effective therapeutic approach 
in animal models of colitis with implications for the treatment of 
human ulcerative colitis and for the treatment of fibrosis associated 
with Crohn's disease.
    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 NF-kappa B decoy oligonucleotides 
[HHS Reference No. E-108-2005/0-US-01, U.S. Patent Application No. 11/
125,919, filed 10 May 2005; J. Clin. Invest. (2005) 115, 3057-3071].
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

    Dated: June 21, 2006.
David R. Sadowski,
Acting Director, Division of Technology Development and Transfer, 
Office of Technology Transfer, National Institutes of Health.
[FR Doc. 06-5868 Filed 6-27-06; 8:45 am]
BILLING CODE 4140-01-P