[Federal Register Volume 72, Number 89 (Wednesday, May 9, 2007)]
[Notices]
[Pages 26404-26406]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-8894]


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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.

New Compounds and Methods for the Treatment of Spinal Muscular Atrophy 
and Other Diseases

    Description of Technology: Spinal muscular atrophy (SMA) is caused 
by mutations in the SMN1 gene that result in reduced expression of the 
survival motor neuron (SMN) protein and a loss of spinal motor neurons. 
An SMN2 gene paralog that differs from SMN by a single base pair has 
inadequate expression of SMN to support motor neuron survival. 
Alternative splicing caused by the single base substitution in the SMN2 
gene results in a slightly truncated and highly unstable SMN protein. 
Drugs that allow translational read through of the stop codons 
introduced by the alternative splice event have been shown to stabilize 
the mutant protein, resulting in increased levels of SMN.
    A chemical library screen identified indoprofen, a nonsteroidal 
anti-inflammatory drug, as an inducer of SMN expression in cultured 
cells. However, indoprofen cannot enter the brain in satisfactory 
amounts, has a relatively low level of activity and can cause 
substantial side-effects in part due to its cyclooxygenase inhibitory 
activity. NIH inventors designed indoprofen derivatives without 
cyclooxygenase activity that can enter the CNS and increase expression 
of a SMN protein from the SMN2 gene with increased potency and 
efficacy. The mechanism of action of these indoprofen analogs appears 
to be translational readthrough of stop codons introduced by the 
alternative SMN2 splicing event. In addition to treating SMA, novel 
drugs that allow read through of stop codons could potentially treat 
many other diseases caused by such mutations such as cystic fibrosis 
and muscular dystrophy.
    Available for licensing are compounds and methods useful for the 
treatment of spinal muscular atrophy by increasing SMN expression and 
increasing the expression from any nucleic acid that encodes a 
translational stop codon.
    Applications: Efficacious treatment for SMA, utilizing indoprofen 
analogs that increase SMN protein expression; Treatment of any genetic 
disease caused by premature termination of protein translation.
    Market: SMA is a rare genetic disease that affects approximately 1 
in 6,000 live births, and is the leading genetic cause of death in 
infants and toddlers. The projected market size for SMA is between $250 
million and $750 million.
    Development Status: Clinical candidate selection scheduled for June 
2007.
    Inventors: Jill Heemskerk (NINDS), et al.
    Publication: MR Lunn, DE Root, AM Martino, SP Flaherty, BP Kelley, 
DD Coovert, AH Burghes, NT Man, GE Morris, J Zhou, EJ Androphy, CJ 
Sumner, BR Stockwell. Indoprofen upregulates the survival motor neuron 
protein through a cyclooxygenase-independent mechanism. Chem. Biol. 
2004 Nov;11(11):1489-1493.
    Patent Status: U.S. Provisional Application No. 60/783,292 filed 17 
Mar 2006 (HHS Reference No. E-133-2006/0-US-01); PCT Application No. 
PCT/2007/006772 filed 16 Mar 2007 (HHS Reference No. E-133-2006/1-PCT-
01)
    Licensing Availability: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: Norbert Pontzer, J.D., Ph.D.; 301/435-5502; 
<a href="/cdn-cgi/l/email-protection#a4d4cbcad0dec1d6cae4c9c5cdc88acacdcc8ac3cbd2"><span class="__cf_email__" data-cfemail="ed9d82839997889f83ad808c8481c3838485c38a829b">[email protected]</span></a>.

STAMP, a Novel Cofactor and Possible Steroid Sparing Agent, Modulates 
Steroid-Induced Induction or Repression of Steroid Receptors

    Description of Technology: Steroid hormones such as androgens, 
glucocorticoids, and estrogens are used in the treatments of many 
diseases. They act to regulate many physiological responses by binding 
to steroid

[[Page 26405]]

receptors. However, because steroid receptors are expressed in many 
tissues, efforts to therapeutically modify the effects of steroid 
hormones on a specific tissue or on a specific receptor of the steroid 
receptor family often cause undesirable effects in other tissues or on 
other receptors. STAMP (SRC-1 and TIF-2 Associated Modulatory Protein), 
a novel protein that acts to lower the concentration of steroid hormone 
needed to induce (or repress) selected target genes by regulating 
steroid receptor synthesis, offers an novel approach for reducing the 
severity of unwanted side-effects, thereby increasing the ability to 
use steroid hormone therapies.

Applications

    1. Diseases requiring chronic steroid treatment such as rheumatoid 
arthritis, psoriatic arthritis, asthma, inflammatory and auto-immune 
diseases;
    2. Diseases characterized by excess or deficiency of 
glucocorticoids such as obesity, diabetes, hypertension, Cushing's 
Syndrome, Parkinson's Disease, Addison's Disease;
    3. Diseases in which glucocorticoid-responsive gene expression is 
deranged, so deranging carbohydrate, protein or lipid metabolism;
    4. Cancers responsive to androgen or estrogen, such as breast 
cancer or prostate cancer;
    5. Therapeutic applications related to male or female hormone 
replacement, symptoms related to menopause, birth control, menstrual 
cycle/amenorrhea, fertility or endometriosis.

Advantages

    1. STAMP reduces the severity of unwanted side-effects of steroid 
hormone therapies;
    2. STAMP modulates the gene induction properties of androgen and 
progesterone receptors;
    3. STAMP modulates both induction and repression properties of 
glucocorticoid receptors;
    4. STAMP is inactive toward alpha and beta estrogen receptors, 
thyroid receptor beta, PPAR gamma 2, retinoid receptor alpha or RXR 
alpha;
    5. The siRNAs could be useful as therapeutics.
    Market: The protein, STAMP, offers a novel approach for reducing 
the severity of unwanted side-effects of steroid hormone therapies. 
Therefore, STAMP would be helpful in the treatment of diseases 
requiring chronic steroid treatments, those characterized by excess or 
deficiency of glucocorticoid response, therapies related to male or 
female hormone replacement or cancers responsive to androgen or 
estrogen.

Development Status

    1. STAMP, a protein which is a novel nuclear receptor cofactor, has 
been identified;
    2. STAMP siRNAs have been shown to change the dose response curve 
of endogenous glucocorticoid receptor induced genes;
    3. A STAMP antibody has been prepared.

Further Research & Development Required

    1. Further in-vivo studies into the role of STAMP in glucocorticoid 
receptor-mediated repression;
    2. Further study into the activity of STAMP in androgen receptor-
mediated responses;
    3. Investigation into the mechanism of action of STAMP;
    4. Development of STAMP knockout mouse.
    Inventors: Drs. S. Stoney Simons Jr (NIDDK) and Yuanzheng He 
(NIDDK)
    Publication: Y He and SS Simons Jr. STAMP: A Novel Predicted Factor 
Assisting TIF2 Actions in Glucocorticoid Receptor-mediated Induction 
and Repression. Mol Cell Biol. 2007 Feb;27(4);1467-1485.
    Patent Status: PCT International No. PCT/US2005/006393 filed 25 Feb 
2005 (priority date 26 Feb 2004), which published as WO 2005/082935 on 
09 Sep 2005, entitled ``A Novel Cofactor that Modulates Steroid 
Receptor Activities''; National Stage U.S., Europe, Canada, Australia 
(HHS Reference No. E-056-2004/0).
    Related Technologies: HHS Reference No. E-015-2000/0, 
``Antiprogestins with Partial Agonist Activity.'' Global IP pending: 
US, Europe, Australia, Canada, Japan.
    Licensing Status: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: Dr. Susan Carson; 301/435-5020; 
<a href="/cdn-cgi/l/email-protection#cfacaebdbca0a1bcba8fa2aea6a3e1a1a6a7e1a8a0b9"><span class="__cf_email__" data-cfemail="e68587949589889593a68b878f8ac8888f8ec8818990">[email protected]</span></a>.
    Collaborative Research Opportunity: The National Institute of 
Diabetes, Digestive and Kidney Diseases, Laboratory of Molecular and 
Cellular Biology is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate or commercialize this technology. Please contact Dr. Stoney 
Simons, Chief, Steroid Hormones Section (NIDDK) at 
<a href="/cdn-cgi/l/email-protection#0b787f6e7964626f784b636e67627325656263256c647d"><span class="__cf_email__" data-cfemail="1665627364797f7265567e737a7f6e38787f7e38717960">[email protected]</span></a>; Tel: 301-4960-6796 for more information.

TMC1, a Deafness-Related Gene

    Description of Technology: Hearing loss is a common communication 
disorder affecting nearly 1 in 1,000 children in the United States 
alone, and nearly 50% of adults by the age of eighty. Hearing loss can 
be caused by environmental and disease-related factors; however, 
hearing loss due to genetic factors accounts for approximately 50% of 
cases.
    The NIH announces the isolation of two novel genes involved in 
hearing; TMC1, short for transmembrane channel-like gene 1. The 
inventors have discovered that dominant and recessive mutations in TMC1 
underlie two forms of hereditary deafness, known as DFNA36 and DFNB7/
11. TMC1 encodes a protein required for normal function of the 
mammalian hair cell, which plays a critical role within the hearing 
pathway that detects sound in the inner ear.
    The invention discloses TMC1 nucleic acids, vectors, and cells. 
Also disclosed are methods of detecting hearing loss, or a 
predisposition to hearing loss, due to a mutation in TMC1, as well as 
methods for identifying agents that interact with the TMC1 gene in a 
cell. Nucleic acids and methods of use for TMC2, a gene closely related 
to TMC1, are also disclosed.
    Applications: Development of a genetic diagnostic test for hearing 
loss; Development of pharmaceuticals to treat hearing loss.
    Market: Hearing loss with a genetic component accounts for 50% of 
all cases of hearing loss.
    Development Status: Early stage.
    Inventors: Andrew J. Griffith et al. (NIDCD).
    Publication: K Kurima et al. Dominant and recessive deafness caused 
by mutations of a novel gene, TMC1, required for cochlear hair-cell 
function. Nat Genet. 2002 Mar;30(3):277-284.

Patent Status

    1. HHS Reference No. E-168-2001/0:
    a. U.S. Provisional Application No. 60/323,275 filed 19 Sep 2001.
    b. PCT Application No. PCT/US02/29614 filed 19 Sep 2002, which 
published as WO 03/025140 on 27 Mar 2003.
    c. U.S. Patent No. 7,192,705 issued 20 Mar 2007.
    d. U.S. Patent Application No. 11/615,250 filed 22 Dec 2006.
    e. Foreign counterparts in Australia, Canada, Europe, and Japan.
    2. HHS Reference No. E-168-2001/1:
    a. U.S. Patent No. 7,116,433 issued 23 Jan 2007.
    b. Foreign counterparts in Australia and Canada.
    Licensing Status: Available for non-exclusive licensing.
    Licensing Contact: Tara L. Kirby, Ph.D.; 301/435-4426; 
<a href="/cdn-cgi/l/email-protection#2a5e4b584b416a474b434604444342044d455c"><span class="__cf_email__" data-cfemail="fc889d8e9d97bc919d9590d2929594d29b938a">[email protected]</span></a>.

[[Page 26406]]

    Collaborative Research Opportunity: The NIDCD Otolaryngology Branch 
is seeking statements of capability or interest from parties interested 
in collaborative research to further develop, evaluate, or 
commercialize this technology as well as collaborate on further pre-
clinical and clinical studies with the TMC2 gene mutations. Please 
contact Ms. Marianne Lynch at 301-402-5579 or via e-mail at 
<a href="/cdn-cgi/l/email-protection#791500171a1114391711151b1057171011571e160f"><span class="__cf_email__" data-cfemail="0b6772656863664b656367696225656263256c647d">[email protected]</span></a> for more information.

    Dated: April 30, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E7-8894 Filed 5-8-07; 8:45 am]
BILLING CODE 4140-01-P


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