[Federal Register Volume 75, Number 18 (Thursday, January 28, 2010)]
[Notices]
[Pages 4573-4575]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-1665]


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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

[[Page 4574]]

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.

Preventing Oral Mucositis With Hybrid Adenoretroviral Vectors

    Description of Invention: Researchers at the National Institutes of 
Health have recently developed a novel method utilizing adenoretroviral 
vectors to safely and swiftly prevent oral mucositis induced by 
radiotherapy. This clever new method developed by National Institute of 
Dental and Craniofacial Research (NIDCR) researchers combines the 
advantages of adenoviral and retroviral vectors to efficiently shuttle 
into salivary glands a non-integrating vector that can produce a 
therapeutic protein for intermediate to long-term treatment. This 
approach is anticipated to result in fewer side-effects than current 
therapies.
    The market for the treatment of mucositis, the painful inflammation 
and ulceration of the mucous membranes lining the digestive tract, is 
estimated to be in excess of $5 billion worldwide. Up to 80% of all 
patients receiving radiotherapy and approximately 40% of all 
chemotherapy patients develop oral mucositis, and almost all patients 
receiving radiotherapy for head and neck cancer and those undergoing 
stem cell transplantation develop mucositis.

Applications

     Prevention of radiation-induced oral mucositis.
     Transduction of genes encoding secretory proteins with 
clinical uses for intermediate to long-term treatment (e.g., 4-8 
weeks).

Advantages

     Safe.
     Reduced potential for side-effects.
     Efficient production of transduced genes.
     Efficient in vivo/in vitro transduction.
     Extra-chromosomal location.

    Development Status: Pre-clinical.
    Inventor: Changyu Zheng et al. (NIDCR).
    Patent Status: U.S. Provisional Application No. 61/176,210 filed 07 
May 2009 (HHS Reference No. E-185-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Patrick McCue, Ph.D.; 301-435-5560; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Dental and Craniofacial Research is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize this technology. Please contact 
David Bradley, Ph.D. at 301-402-0540 or [email protected] for 
more information.

Mutations of the ERBB4 Gene in Melanoma

    Description of Invention: Cutaneous malignant melanoma is the most 
common fatal skin cancer, and the incidence of this disease increases 
each year. The average survival time for patients diagnosed with 
malignant melanoma is less than ten months. Consequently, it is 
important to identify and understand genetic alterations leading to 
malignant melanoma so that new treatment strategies can be developed.
    Protein tyrosine kinases (PTKs) have been associated with a wide 
variety of cancers, including melanoma. Using high-throughput gene 
sequencing, the NIH inventors have analyzed PTKs in melanoma and have 
identified several novel somatic alterations, including alterations in 
ERBB4. This invention provides methods of identifying specific 
inhibitors to ERBB4 that could be used to treat patients with ERBB4 
mutations. Given the recent success of small molecule protein kinase 
inhibitors and specifically inhibitors to EGFR, this invention could be 
used to further the development of specific inhibitors to ERBB4 and 
improve existing melanoma treatments for patients with these mutations.

Applications

     Diagnostic array for the detection of ERBB4 mutations.
     Method of identifying ERBB4 inhibitors as therapeutic 
agents to treat malignant melanoma patients.
    Development Status: The technology is currently in the pre-clinical 
stage of development.

Market

     Approximately 160,000 new cases of melanoma are diagnosed 
worldwide each year. Malignant melanoma is increasing faster than any 
other cancer.
     Melanoma is the most prevalent cancer among women between 
the ages of 25 and 29 and the second most prevalent cancer among women 
ages 30-34.
     Cutaneous malignant melanoma is the most serious form of 
skin cancer and accounts for about 75% of all skin cancer deaths.
     One person dies from melanoma every hour.
    Inventors: Yardena R. Samuels et al. (NHGRI).
    Related Publication: Prickett TD, Agrawal NS, Wei X, Yates KE, Lin 
JC, Wunderlich JR, Cronin JC, Cruz P, Rosenberg SA, Samuels Y. Analysis 
of the tyrosine kinome in melanoma reveals recurrent mutations in 
ERBB4. Nature Genet. 2009 October; 41(10):1127-1132. [PubMed: 
19718025].
    Patent Status: PCT Application No. PCT/US2009/053005 filed 06 Aug 
2009 (HHS Reference No. E-272-2008/ 0-PCT-02).
    Licensing Status: Available for licensing.
    Licensing Contact: Whitney Hastings, 301-451-7337; 
[email protected].
    Collaborative Research Opportunity: The Cancer Genetics Branch, 
National Human Genome Research Institute (NHGRI), National Institutes 
of Health (NIH) is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate and/or commercialize an ERBB4-based diagnostic, prognostic 
and/or theranostic test as well as identify and/or evaluate ERBB4 
inhibitor compounds for testing as possible candidate malignant 
melanoma therapeutic drugs. Please contact Claire Driscoll at 
[email protected] or Dr. Yardena Samuels at [email protected] 
for more information.

Genetically Modified Stem Cells for Personalized Therapy of Single Gene 
Disorders

    Description of Invention: This technology is directed to 
individualized therapies of single gene disorders by introducing a 
patient's own genetically modified adult stem cells to the damaged 
tissue. Diseases arising from single gene disorders affect 
approximately 1% of the human population. Unlike most current 
treatments for such diseases, which are non-specific and symptom-based, 
this technology specifically addresses the underlying pathology of the 
disorder.
    Many single gene diseases are accompanied by tissue damage and 
inflammation. This technology exploits the inflammatory response, which 
includes homing of mesenchymal stem cells to the site of damage, for 
therapeutic purposes. The inventors have genetically modified adult 
stem cells to produce silencing RNA specific to the defective protein 
in the damaged tissue. The silencing RNA can inhibit the source of the 
pathology and promote the growth and differentiation of genetically 
modified stem cells adjacent to the damaged tissue which can support 
the tissue healing process.

[[Page 4575]]

Additionally, the risk of developing Graft Versus Host Disease is 
eliminated by utilizing the patient's own stem cells.
    Proof of concept has been demonstrated in the vascular type of the 
Ehlers-Danlos Syndrome (VEDS). Using tissues isolated from VEDS 
patients, siRNA was shown to correct the mutational defect. The siRNA 
not only inhibited the production of the mutant protein but also 
restored the normal, non-pathological structure of the wild-type 
protein in the tissue.
    This technology may be particularly applicable to patients with 
mutations in structural proteins of the extracellular matrix, as 
presented in diseases such as osteogenesis imperfecta, Marfan syndrome, 
and Ehlers-Danlos syndrome (EDS).

Potential Applications and Advantages

     Therapeutic for diseases arising from single gene 
disorders.
     Specific to the underlying disease unlike most current 
treatments.
     Therapeutic cells are recruited to the specific site of 
damage.
     Subsequent differentiation and localization of stem cells 
is therapeutic to the damaged tissue.
    Development Status: Pre-clinical; however, patients with vascular 
type of the Ehlers-Danlos syndrome (VEDS) are being recruited for 
observational studies.
    Inventors: Wilfried M. Briest and Mark I. Talan (NIA).
    Patent Status: U.S. Provisional Application No. 61/233,537 filed 13 
Aug 2009 (HHS Reference No. E-171-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Fatima Sayyid, M.H.P.M.; 301-435-4521; 
[email protected].

HIV-1 Infection Detection Assay for Seroconverted HIV-1 Vaccine 
Recipients

    Description of Invention: Available for licensing and commercial 
distribution is a serological test specifically designed to distinguish 
between antibodies generated in HIV vaccine recipients and those 
generated in a natural HIV infection. The method is useful in HIV 
vaccine development and clinical studies as it can readily detect early 
breakthrough infections in seroconverted vaccine recipients, thus 
providing the information required to determine vaccine efficacy. The 
test kit includes diagnostic peptide fragments derived from human 
immunodeficiency virus-1 (HIV-1). The peptide epitopes are primarily 
derived from the GAG-p6 and gp41 genes. These epitopes are broadly 
reactive with early sera from HIV infected individuals, but do not 
illicit protective antibodies, or immunologic cytotoxicity, and thus 
can readily be excluded from current and future HIV-1 vaccine 
candidates.

Applications

     Vaccine efficacy studies; Detection of early 
seroconversion in vaccine recipients.
     Distinguishing between healthy vaccine recipients and 
natural HIV infection.
     Blood bank screening.
    Advantages: Cost effective method to determine vaccines efficacy in 
clinical studies.
    Market: In spite of the more than twenty years of efforts to 
develop HIV vaccine, such vaccine does not yet exist. While treatment 
of HIV/AIDS with antiretroviral drugs can reduce viral load and extend 
life, this approach does not provide a true cure and cannot stop the 
HIV/AIDS pandemic. The medical community therefore fully recognizes the 
urgency to develop an effective vaccine for HIV/AIDS. In spite of the 
many challenges in the development of such vaccine (out of the 75 
vaccine candidates that entered clinical trials over the years only 3 
have reached the stage of large-scale efficacy trials and to date none 
have prove efficacious) the efforts in this area will continue to 
receive high priority by the public sector and high level of research 
funding. In order to make progress in this area, public sectors in many 
countries as well as not-for-profit NGOs have in recent years developed 
strategies and provided incentives to the private sector to continue 
with the efforts through the creation of public-private partnerships. 
Development of tools that can facilitate clinical trials, such as the 
present invention, may therefore be a good commercial opportunity, in 
particular in light of the potential market for HIV/AIDS vaccine. While 
the market for therapeutic drugs against HIV/AIDS across the seven 
major markets is now approaching $11.0 billion annually and growing at 
about 12.8% a year, the International AIDS Vaccine Initiative (IAVI) 
projects $2.5 billion to $5.5 billion in peak annual revenues of any 
new vaccine. This projection is based on peak demand of between 38 and 
152 million courses (two doses per one course) depending on the vaccine 
profile. The projection also takes into consideration a tiered pricing 
and this projected revenue represents 5% to 13% of the total global 
vaccine market.
    Inventors: Hana Golding and Surender Khurana (FDA).

Related Publications

    1. S Khurana et al. Human immunodeficiency virus (HIV) vaccine 
trials: A novel assay for differential diagnosis of HIV infections in 
the face of vaccine-generated antibodies. J Virol. 2006 March;80(5): 
2092-2099. [PubMed: 16474117].
    2. S Khurana et al. Novel approach for differential diagnosis of 
HIV infections in the face of vaccine-generated antibodies: Utility for 
detection of diverse HIV-1 subtypes. J Acquir Immune Defic Syndr. 2006 
Nov 1;43(3):304-312. [PubMed: 17019363].
    3. S Khurana et al. HIV-SELECTEST EIA and rapid test: Ability to 
detect seroconversion following HIV-1 infection. J Clin Microbiol. 2009 
Nov 11. Epub ahead of print. doi:10.1128/JCM.01573-09. [PubMed: 
19906903].

Patent Status

     U.S. Provisional Application No. 60/607,579 filed 08 Sep 
2004 (HHS Reference No. E-259-2004/0-US-01).
     U.S. Provisional Application No. 60/676,931 filed 03 May 
2005 (HHS Reference No. E-259-2004/1-US-01).
     PCT Application No. PCT/US2005/031287, which published as 
WO/2007/018550 on 15 Feb 2007 (HHS Reference No. E-259-2004/2-PCT-01); 
and related applications: U.S. Patent Application No. 11/662,370 filed 
02 Sep 2005, published 27 Jun 2007; Australia Patent Application No. 
2005335203, published 04 Apr 2007; Canadian Patent Application No. 
2579676; European Patent Application No. 2005858397, published 27 Jun 
2007.
     U.S. Provisional Application No. 61,180,233 filed 21 May 
2009 (HHS Reference No. E-259-2004/3-US-01).
    Licensing Status: Available for licensing.
    Licensing Contacts: Uri Reichman, Ph.D., M.B.A.; 301-435-4616; 
[email protected]; or Michael Shmilovich, Esq.; 301-435-5019; 
[email protected].

    Dated: January 21, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-1665 Filed 1-27-10; 8:45 am]
BILLING CODE 4140-01-P