[Federal Register Volume 74, Number 27 (Wednesday, February 11, 2009)]
[Notices]
[Pages 6910-6912]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-2822]


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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.

Prognostic Test for Breast Cancer Based on a 12 Gene Expression 
Signature

    Description of Technology: The clinical course and survival times 
of patients with breast cancer varies greatly, consequently it is 
difficult to establish a prognosis for the disease. To improve patient 
prognosis, much effort has been made to identify biological markers 
that would allow precise staging of the cancer. When cells cannot 
repair minor damage to their DNA it leads to genetic instability which 
can produce gross abnormalities in chromosomes and the onset of a 
cancer. It is known that the magnitude of the abnormalities is strongly 
correlated with a negative prognosis for cancer. Thus, genetic 
instability can serve as a useful biomarker for establishing a 
prognosis for breast cancer patients. Presently, genetic instability is 
not directly accounted for in established prognostic tests.
    Investigators at the National Cancer Institute (NCI) have developed 
a compact gene signature that detects genome instability in breast 
cancer cells. By comparing changes in expression levels of only 12 
genes in malignant tissue to levels in normal breast tissue it is 
possible to detect the genetic abnormalities that are indicative of a 
poor prognosis. This method has potential to improve markedly the 
forecasting of clinical outcomes for breast cancer and help improve 
treatment of this disease.
    Applications:
     Precise staging of women with breast cancer prior to 
commencing treatment.

[[Page 6911]]

     Discovery of therapeutics that alter genomic instability 
and improve breast cancer prognosis.
    Advantages:
     Reduced number of genes to measure compared to available 
technologies.
     Prognosis independent of other cancer indicators, such as 
lymph node status.
     Improved prediction in low risk patients.
    Market: It is estimated that in 2008 more than 184,000 Americans 
would be diagnosed with breast cancer. After lung cancer, breast cancer 
is the second most lethal cancer in women.
    Development Status: Pre-clinical or clinical data available.
    Inventors: Thomas Ried (NCI) et al.
    Publications: Presently, none related to this invention.
    Patent Status: U.S. Provisional Application No. 61/097,101 filed 15 
Sep 2008 (HHS Reference No. E-215-2008/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Surekha Vathyam, PhD; 301-435-4076; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
Genetics Branch is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize Prognostic Test for Breast Cancer Based on a 
12 Gene Expression Signature. Please contact John D. Hewes, Ph.D. at 
301-435-3121 or [email protected] for more information.

HMGN Polypeptides as Immune Enhancers and HMGN Antagonists as Immune 
Suppressants

    Description of Technology: HMGN polypeptides are multidomain 
proteins known to function by binding DNA to regulate the transcription 
of certain genes inside cells. However, when a HMGN polypeptide is 
released extracellularly, it distinctly acts as a potent activator of 
the immune system. Because of this activity, it has potential use as a 
biological therapeutic for stimulating an immune response as well as a 
promising target for antagonist drugs to suppress a pathological 
inflammatory response.
    Secreted HMGN acts as a potent recruiter and activator of dendritic 
cells, the cell principally responsible for initiating the immune 
response. Furthermore, it enables dendritic cells to preferentially 
induce a Th1-type T lymphocyte response that leads to enduring cellular 
immunity. Therefore, HMGN has potential use as a clinically effective 
immunoadjuvant for use in vaccines against tumors and many 
intracellular pathogens.
    Investigators at the National Institutes of Health have developed 
compositions and methods for using HMGN and its derivatives as 
immunoadjuvants in combination, as mixtures or as chemical conjugates, 
with microbial or tumor antigens. HMGN has the advantage of being gene 
encoded so it can be fused to an antigen gene to produce recombinant 
fusion proteins or administered as a DNA vaccine. Conversely, HMGN 
could be exploited as a drug target to treat diseases that would 
benefit from shifting away the Th1-type immune response towards a Th2-
type or humoral immune response. This would be beneficial for treatment 
of parasitic infections and inflammatory or autoimmune disorders.
    Applications:
     As an immunostimulatory adjuvant to increase efficacy of 
preventive or therapeutic vaccinations against microbes or cancers.
     As an attractant and activator of dendritic cells.
     Antagonist drug development for suppressing Th1-type 
response.
    Advantages:
     Less adverse effects expected compared to current 
immunoadjuvants since HMGN is produced by the human body.
     Highly effective polarizer of the immune response towards 
Th1-type immunity.
    Development Status: Pre-clinical data available.
    Market: Very few immunoadjuvants have reached clinical approval 
since the introduction of alum over half a decade ago. Currently, there 
is a need for safe and effective vaccine adjuvants to increase the 
effectiveness of preventive and therapeutic vaccines.
    Inventors: De Yang et al. (NCI).
    Publications: Presently, none related to this invention.
    Patent Status: U.S. Provisional Patent No. 61/083,781 filed 25 Jul 
2008 (DHHS Reference No. E-185-2008/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Surekha Vathyam, Ph.D.; 301-435-4076; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
Laboratory of Molecular Immunoregulation is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize HMGN1. Please 
contact John D. Hewes, Ph.D. at 301-435-3121 or [email protected] for 
more information.

Substituted IL-15

    Description of Technology: Interleukin-15 (IL-15) is an immune 
system modulating protein (cytokine) that stimulates the proliferation 
and differentiation of T-lymphocytes. In the clinical context, IL-15 is 
being investigated for use in the treatment of diseases such as cancer. 
In vitro manufacture of IL-15 can be problematic.
    The invention relates to substituted IL-15 amino acid sequences of 
one or more amino acids that are predicted to reduce or eliminate 
deamidation of a specific aspargine amino acid residue found within the 
IL-15 protein. Deamidation can lead to protein degradation and 
interfere with the pharmaceutical purification and processing of IL-15. 
The invention also provides potential substituted gene sequences that 
encode the substituted IL-15 amino acid sequences. The substituted IL-
15 amino acid sequences may advantageously facilitate the refolding, 
purification, storage, characterization, and clinical testing of IL-15.
    Applications: IL-15 immunotherapies.
    Advantages: Potential decreased immunogenicity of pharmacologically 
active IL-15 expressed in E. coli.
    Development Status: Concept Development Phase.
    Market: Cancer immunotherapy; IL-15 based immunotherapies.
    Inventors: David F. Nellis et al. (NCI/SAIC).
    Patent Status: U.S. Provisional Application No. 61/049,165 filed 30 
Apr 2008 (HHS Reference No. E-123-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Kevin W. Chang, Ph.D.; 301-435-5018; 
[email protected]
    Collaborative Research Opportunity: The National Cancer Institute 
Biological Research Branch is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize the topic of this U.S. Provisional 
Patent Application. Please contact John D. Hewes, Ph.D. at 301-435-3121 
or [email protected] for more information.

Novel Protein Delivery System for Mammalian Cells

    Description of Technology: Virus-like particles (VLPs) consist of 
viral structural proteins that are capable of

[[Page 6912]]

self-assembly into a nanoparticle, but are non-infectious because they 
lack viral nucleic acids. VLPs have been used in viral vaccines, such 
as those for human papilloma virus and hepatitis B. However, they also 
have great potential in other applications, such as cancer vaccines, 
transport of nucleic acids into target cells (gene therapy), and 
transport of biologics or other large molecules into target cells for 
therapeutic purposes. The present technology discloses a chimeric VLP 
containing a GAG-Cre recombinase fusion protein. This recombinase 
fusion protein retains Cre recombinase activity, and can excise a LOX-
flanked gene in a transduced target cell. Experiments by Drs. 
Kaczmarczyk and Chatterjee have demonstrated that chimeric VLPs can be 
used to deliver functional fusion proteins into cells. The technology 
also provides for a two-VLP protein delivery system designed to deliver 
a protein of interest into a target cell. The present technology also 
discloses VLPs containing GAG-protein of interest (ex. GAG-Cre) co-
packaged with GAG-protease to deliver protein of interest in target 
site as a fully-processed protein rather than as a fusion protein.
    The claims in the pending patent application provide for virus-like 
particles, methods of making virus-like particles, and methods of using 
virus-like particles to deliver proteins to a cell. The claims also 
provide for methods of targeting a protein to a cell, methods of 
protein therapy and methods of treating diseases or disorders.
    Applications:
     Intracellular targeted delivery of therapeutic proteins.
     Ex vivo use for expansion of stem cells for 
transplantation.
     Antigen loading of dendritic cells for cancer vaccination.
    Market: The therapeutic protein market segment will have a 
projected $52.2 billion in sales in 2010.
    Development Status: In vivo feasibility studies are in progress.
    Patent Status: U.S. Patent Application No. 61/195,084 filed 03 Oct 
2008 (HHS Reference No. E-010-2008/0-US-01).
    Inventors: Deb K. Chatterjee and Stanislaw J. Kaczmarcyk (NCI/
SAIC).
    Licensing Status: Available for licensing.
    Licensing Contact: Suryanarayana (Sury) Vepa, Ph.D., J.D.; 301-435-
5020; [email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
Advanced Technology Program, Protein Expression Laboratory, 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, Ph.D. at 301-435-3121 or 
[email protected] for more information.

    Dated: January 30, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E9-2822 Filed 2-10-09; 8:45 am]
BILLING CODE 4140-01-P