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[Federal Register Volume 74, Number 130 (Thursday, July 9, 2009)]
[Notices]
[Pages 32940-32943]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-16299]

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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.

qPCR Assay for Detection of JC Virus

    Description of Invention: JC Virus causes a fatal disease in the 
brain called progressive multifocal leukoencephalopathy (PML) that 
occurs in many patients with immunocompromised conditions. For example, 
more than five percent (5%) of AIDS patients develop PML. Additionally, 
these conditions include, but are not limited to, cancers such as 
leukemias and lymphomas, organ transplants such as kidney, heart and 
autoimmune conditions with treatment that modulates the immune system 
such as Multiple Sclerosis (MS), rheumatoid arthritis, psoriasis, and 
systemic lupus erythematosus. The finding of JCV DNA in the patients 
with neurological symptoms of PML is a diagnostic criterion and is 
needed to confirm the diagnosis of PML to rule out other neurological 
conditions.
    This technology describes a qPCR assay that utilizes viral DNA 
standards and testing samples to detect the presence of the JC viral 
genome in patients' cerebrospinal fluid and blood, blood products, and 
tissue samples from biopsy or autopsy.
    Application: Development of JC Virus (JCV) diagnostics, calibration 
of existing JCV assays.
    Advantages: Assay is sensitive, reproducible and highly specific 
because the amount of JCV DNA in cerebrospinal fluid or blood or blood 
product samples may be very small.
    Development Status: Materials and assay have been developed and 
tested.
    Inventors: Eugene O. Major and Caroline Ryschkewitsch (NINDS).

Publications

    1. ML Landry et al. False negative PCR despite high levels of JC 
virus DNA in spinal fluid: Implications for diagnostic testing. J Clin 
Virol. 2008 Oct;43(2):247-249.
    2. C Ryschkewitsch et al. Comparison of PCR-southern hybridization 
and quantitative real-time PCR for the detection of JC and BK viral 
nucleotide sequences in urine and cerebrospinal fluid. J Virol Methods. 
2004 Nov;121(2):217-221.
    3. T Yousry et al. Evaluation of patients treated with natalizumab 
for progressive multifocal leukoencephalopathy. N Engl J Med. 2006 Mar 
2;354(9):924-933.
    Patent Status: HHS Reference No. E-152-2009/0--Research Material. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; 
[email protected].

A Locking Device for Permanently Securing Surgical Suture Loops

    Description of Invention: This technology relates to a device that 
can be used to non-invasively secure surgical suture loops when 
combined with a percutaneous delivery system. It has been shown to be 
effective in correcting mitral valve regurgitation (MVR) in an animal 
model. During the procedure, a guidewire is percutaneously conveyed to 
the atrium of the heart and is used to secure the ``cerclage'' suture 
encircling the mitral valve annulus, which is delivered using a 
delivery catheter. The locking device is advanced over the suture by 
the delivery catheter and it permanently secures the suture and 
maintains the tension on the annulus once the delivery system is 
removed. This locking device, in combination with the percutaneous 
procedure, allows for more complete coaptation of the valve leaflets 
and correction of MVR without the need for open heart surgery and its 
associated risks. The locking device is also adjustable, allowing the 
user to vary the tension on the suture if further tightening or 
loosening is required. It is also MRI compatible and all follow-up 
studies can be performed under MRI.
    This invention has demonstrated its ability to correct MVR in 
animals where the locking device was observed to maintain the correct 
position and tension after implantation. This device has the potential 
to replace the traditional loop and knot method used for surgical 
correction of MVR, and may also be useful for other conditions that 
require permanently secured suture loops.
    Applications: Non-invasive and effective correction of MVR and 
other conditions; Tensioning device for securing suture loops.
    Advantages: Technology amenable to a non-invasive technique; 
Control of tension on surgical sutures.
    Development Status: Early stage.
    Inventor: Ozgur Kocaturk (NHLBI).
    Patent Status: U.S. Provisional Application No. 61/157,267 filed 04 
Mar 2009 (HHS Reference No. E-048-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Jeffrey A. James, Ph.D.; 301-435-5474; 
[email protected].
    Collaborative Research Opportunity: The National Heart, Lung and 
Blood Institute Cardiac Catheterization Lab is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize the

[[Page 32941]]

tension fixation device. Please contact Peg Koelble at 301-594-4095 or 
[email protected] for more information.

Modulators of Pregnane X Receptor (PXR) as Therapeutics for Bowel 
Disorders (BD)

    Description of Invention: This technology is based on the novel 
findings that susceptibility to BD is strongly associated with genetic 
variation in the PXR gene, a member of the nuclear receptor family, and 
rifaximin is a specific activator of human PXR. PXR is an integral 
component of the body's defense mechanism involved in endogenous and 
xenobiotic detoxication. Based on these novel findings, the present 
technology provides (a) methods of screening for compositions that 
modulate inflammatory bowel disease (IBD), (b) methods of inhibiting 
inflammation of the bowel and related tissues and organs, and (c) 
methods of treatment of inflammatory bowel disease.
    Applications: Therapeutics for bowel disorders; Screening assays 
for candidate drugs to treat bowel disorders.
    Development Status: Early stage.
    Market: It is estimated that as many as one (1) million Americans 
have IBD, with that number evenly split between Crohn's disease and 
Ulcerative Colitis (UC). Further, it is estimated that the IBD 
therapeutic market will grow to reach four (4) billion U.S. dollars in 
2017.
    Inventors: Frank J. Gonzalez (NCI), Xiaochao Ma (NCI), et al.
    Publication: X Ma, Y Shah, C Cheung, GL Guo, L Feigenbaum, KW 
Krausz, JR Idle, FJ Gonzalez. The PREGnane X receptor gene-humanized 
mouse: a model for investigating drug-drug interactions mediated by 
cytochromes P450 3A. Drug Metab Dispos. 2007 Feb;35(2):194-200.
    Patent Status: U.S. Provisional Application No. 60/999,234 filed 17 
Oct 2007 (HHS Reference No. E-002-2008/0-US-01); PCT Patent Application 
(HHS Reference No. E-002-2008/0-PCT-02).
    Licensing Status: Available for licensing.
    Licensing Contact: Suryanarayana (Sury) Vepa, PhD, J.D.; 301-435-
5020; [email protected].
    Collaborative Research Opportunity: The Laboratory of Metabolism, 
Center for Cancer Research, NCI, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize compounds that ameliorate bowel 
disorders through the PXR pathway. Please contact Lisa Finkelstein, PhD 
at 301-451-7458 or [email protected] for more information.

The Protein Cyanovirin Inactivates HIV and Influenza

    Description of Invention: Cyanovirin-N (CV-N) potently and 
irreversibly inactivates diverse primary strains of HIV-1, including M-
tropic forms involved in sexual transmission of HIV, as well as T-
tropic and dual-tropic forms. CV-N also blocks cell-to-cell 
transmission of HIV infection. CV-N interacts in an unusual manner with 
the viral envelope, binding with extremely high affinity to poorly 
immunogenic epitopes on gp120. Further, CV-N and homologous proteins 
and peptides potently inhibit diverse isolates of influenza viruses A 
and B, the two major types of influenza virus that infect humans.
    The described technology includes glycosylation-resistant mutants, 
which code sequences to enable ultra large-scale recombinant production 
of functional CV-Ns in non-bacterial (yeast or insect) host cells or in 
transgenic animals or plants. Therefore, these glycosylation-resistant 
mutants may allow industry to produce CV-Ns on a large scale and make 
CV-Ns cheap enough for developing countries to benefit from this 
invention.
    CV-N was benign in vivo when tested in the rabbit/monkey vaginal 
toxicity/irritancy model and was not cytotoxic in vitro against human 
immune cells and lactobacilli. CV-N is readily soluble in aqueous 
media, is remarkably resistant to physicochemical degradation and is 
amenable to very large-scale production by a variety of genetic 
engineering approaches.

Applications

     Therapeutics and prevention of HIV and influenza 
infections.
     Topical microbicide to protect HIV infection.
     Ex vivo devices incorporating CV-N to remove or inactivate 
HIV from fluid samples.

Advantages

     Potent anti-HIV and anti-influenza activity.
     Can be applied both systematically or locally.
     Can be applied both in vivo and ex vivo.
     Inexpensive and large scale manufacturing.

Development Status

     Preclinical (rabbit/monkey) data in microbicide field are 
available at this time.
     Initial animal efficacy studies (both mouse and ferret) 
against influenza (H1N1) have been completed and published.
    Market: For HIV therapeutics market, a published report by the 
financial services firm Griffin Securities suggested that sales of HIV/
AIDS drugs reached $13 billion annually in 2007 (http://www.hivandhepatitis.com).
    For microbicide market, it has been estimated that the global 
market size of microbicide will reach to $900 million by 2011 and will 
reach the sales of over $1.8 billion by 2020). ``Promising 
microbicides'' Frontline (Volume 21--Issue 14, Jul. 03-16, 2004).
    For influenza market, based on Report Buyer which is a UK-based 
independent online store supplying business information on major 
industry sectors: By 2010, the worldwide influenza market is likely to 
reach $7.1 billion, with average annual growth estimated at 19.8%.
    Inventors: Michael R. Boyd (NCI), Barry R. O'Keefe (NCI), et al.

Publications

    1. B Giomarelli, R Provvedi, F Meacci, T Maggi, D Medaglini, G 
Pozzi, T Mori, JB McMahon, R Gardella, MR Boyd. The microbicide 
cyanovirin-N expressed on the surface of commensal bacterium 
Streptococcus gordonii captures HIV-1. AIDS. 2002 Jul 5;16(10):1351-
1356.
    2. CC Tsai, P Emau, Y Jiang, MB Agy, RJ Shattock, A Schmidt, WR 
Morton, KR Gustafson, MR Boyd. Cyanovirin-N inhibits AIDS virus 
infections in vaginal transmission models. AIDS Res Hum Retroviruses. 
2004 Jan; 20(1):11-18.
    3. DF Smee, KW Bailey, MH Wong, BR O'Keefe, KR Gustafson, VP 
Mishin, LV Gubareva. Treatment of influenza A (H1N1) virus infections 
in mice and ferrets with cyanovirin-N. Antiviral Res. 2008 
Dec;80(3):266-271.

Patent Status

     E-117-1995/0--US Patent Numbers 5,843,882; 6,015,876; 
5,962,653; 6,245,737 and 6,586,392.
     E-117-1995/1--US Patent Numbers 5,821,081; 5,998,587; 
6,987,096; and 5,962,668.
     E-117-1995/2-PCT-01 (WO 96/34107)--entered in AU with 
Patent Numbers 707781 and 746809; in CA with Patent application Numbers 
2219105; in JP with Patent Numbers 3803115 and 4081484; and in EP with 
Patent Number 836647 and registration GB, FR, DE, BE and CH.
     E-117-1995/3-PCT-02 (WO 00/11036)--entered in USA with 
Patent Number 6,193,982; in AU with Patent Number 746313; in CA with 
Patent Application Number 2340787; in JP

[[Page 32942]]

with Patent Application Number 566308/2000; and in EP with Patent 
Application Number 99943784.1.
     E-074-1999/0--US Patent Numbers 6,420,336 and 6,743,577.
     E-074-1999/1--US Patent Numbers 7,105,169; 7,048,935; and 
6,428,790.
     E-074-1999/2-PCT-01 (WO 00/53213)--entered in AU with 
Patent Numbers 762704 and 2003252207; in CA with Patent Application 
Numbers 2364500; in JP with Patent Application Number 603702/2000; and 
in EP with Patent Number 1162992 and registration GB, FR, DE, BE and 
CH.
     E-074-1999/3-PCT-02 (WO 02/077189)--entered in USA with 
Patent Numbers 7,339,037 & 6,780,847 and Patent Application Number 10/
857,265; in AU with Patent Number 2002254382; in CA with Patent 
Application Number 2441287; in JP with Patent Application Number 
576632/2002; and in EP with Patent Number 1456382 and registration GB, 
FR, DE, BE and CH.
     E-198-2006/0-PCT-02 (WO 2008/022303)--entered in USA with 
Patent Application Number 12/377875; and in EP with Patent Application 
Number 07814209.8.
    Licensing Status: Available for licensing.
    Licensing Contact: Sally Hu, PhD, 301-435-5606, [email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Molecular Targets Development Program, is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize this 
technology. Please contact John D. Hewes, PhD at 301-435-3121 or 
[email protected] for more information.

Novel Osteobiologic Proteins for Treatment of Osteoporosis, Rheumatoid 
and Neurologic Diseases

    Description of Invention: In an effort to find effective strategies 
for treatment of body tissue and structural damage as the result of 
trauma, cancer and other diseases, scientists at the National 
Institutes of Health (NIH) and the Food and Drug Administration (FDA) 
have identified proteins and associated pathways instrumental in 
replacing or regenerating damaged tissue. The identified proteins 
include Cartilage-Derived Morphogenetic Proteins (CDMP), Bone 
Morphogenetic Proteins (BMPs) and a tissue fate modifying FRZB Protein. 
Each has unique activities likely to be useful as stand alone agents or 
in construction of engineered tissues.
    CDMPs appear helpful in the healing of bone and joint surface 
lesions, and also for the repair or reconstruction of cartilaginous 
tissues, tendons and ligaments. BMP antagonists will be useful in the 
study of stem cell differentiation. FRZB Protein, a tissue fate 
modifying secretable antagonist of Wnt signaling, is involved in the 
formation of cartilage, bone, neural and muscle tissue.

Potential Areas of Application

     Rheumatic diseases of the bone.
     Osteoporosis and osteoarthritis.
     Wound healing.
     Neurodegenerative disorders.
     Growth and repair of musculoskeletal tissues.
     Tissue engineering.

Cartilage-Derived Morphogenetic Proteins (HHS Reference No. E-138-1994/
0)

     Useful in the therapeutic induction, repair, and 
maintenance of skeletal tissues and cartilage growth.
     Polynucleotides encoding these proteins are effective 
diagnostic reagents for detecting genetic abnormalities associated with 
poor skeletal development.

Tissue Fate Modifying FRZB Protein (HHS Reference Nos. E-127-1995/0/1/
2)

     Involved in the formation of cartilage, bone, neural and 
muscle tissue.
     Regenerative agent to treat degenerative disorders (i.e., 
Huntington's, Alzheimer's or spinal cord injuries), myodegenerative 
disorders (i.e., muscular dystrophy, myasthenia gravis or myotonic 
myopathies) and osteodegenerative disorders (i.e., osteoporosis or 
osteoarthritis)
     Selectively blocks diseases associated with Wnt family of 
signaling molecules including neoplasias.

Bone Morphogenetic Protein Variants (HHS Reference No. E-196-2004/0)

     Promote repair of menisci, cruciate and collateral 
ligaments of the knee, and rotator cuff or other tendons and/or 
ligaments.
     Induce the proliferation and differentiation of progenitor 
cells into functional bone, cartilage, tendon, or ligament tissue.
    Advantages: Osteobiologics, such as BMPs, have the ability to 
stimulate musculo-skeletal repair instead of using donated human tissue 
allografts and synthetic materials.
    Market Size: Ankylosing spondylitis afflicts least half a million 
people in the United States. Currently, there remains a need for the 
development of effective therapeutics for treating 
spondyloarthropathies that could overcome the disadvantages of current 
drugs.
    Osteoarthritis overall affects an estimated 30 million US adults. 
Direct medical expenses for arthritis and other rheumatic conditions 
are estimated at $80.8 billion. In the United States, 10 million people 
have Osteoporosis. Osteoporosis related fractures attributed for $21 
billion with the number expected to rise to $26 billion in 2025.
    Inventors: Malcolm C. Moos Jr. (FDA), Frank P. Luyten (NIDCR), et 
al.

Related Publications

    1. K Lin, S Wang, MA Julius, J Kitajewski, M Moos Jr., FP Luyten. 
The cysteine-rich frizzled domain of Frzb-1 is required and sufficient 
for the modulation of Wnt signaling. Proc Natl Acad Sci. USA 1997 Oct 
14;94(21):11196-11200.
    2. B Hoang, M Moos Jr, S Vukicevic, FP Luyten. Primary structure 
and tissue distribution of FRZB, a novel protein related to Drosophila 
frizzled, suggests a role in skeletal morphogenesis. J Biol Chem. 1996 
Oct 18;271(42):26131-26137.

Patent Status

Cartilage-Derived Morphogenetic Proteins (HHS Reference No. E-138-1994/
0)
     U.S. Patent 7,148,036 issued 12 Dec 2006.
     U.S. Patent 7,220,558 issued 22 May 2007.
     U.S. Patent Application No. 11/592,811 (allowed).
Tissue Growth-Inducing FRZB Protein (HHS Reference Nos. E-127-1995/0/1/
2)
     U.S. Patent 6,884,871 issued 26 Apr 2005.
     U.S. Patent 6,924,367 issued 02 Aug 2005.
     U.S. Patent 7,049,291 issued 23 May 2006.
     U.S. Patent Application No. 11/184,005 (allowed).
     U.S. Patent Application No. 11/369,089 (pending).
Bone Morphogenetic Variants (HHS Reference No. E-196-2004/0)
     U.S. Patent Application No. 11/916,990 (pending).
    Licensing Status: Available for licensing.
    Licensing Contact: Surekha Vathyam, PhD; 301-435-4076; 
[email protected].

[[Page 32943]]

    Dated: June 30, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E9-16299 Filed 7-8-09; 8:45 am]
BILLING CODE 4140-01-P
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