Notice: Government-Owned Inventions; Availability for Licensing

Federal Register: June 15, 2009 (Volume 74, Number 113)            
                  Page 28256-28258

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

ACTION: Notice.

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.

Improved Antibodies Against ErbB4/Her4

    Description of Technology: ErbB4/Her4 is a receptor tyrosine kinase 
that regulates cell proliferation, cell differentiation and cell 
survival. ErbB4 has been implicated in the pathology of numerous 
cancers (e.g., breast cancer, non-small cell lung carcinoma, 
adenocarcinoma), as well as psychiatric disorders (e.g., 
schizophrenia). As a result, ErbB4 is an excellent target for 
developing therapies against these diseases. Unfortunately, the study 
of ErbB4 has been slowed by the lack of highly specific and functional 
antibodies against the receptor.
    In order to overcome the deficiencies with current ErbB4 
antibodies, NIH inventors have generated three rabbit monoclonal 
antibodies with improved properties and versatility. Specifically, the 
mAb-6, mAb-7 and mAb-10 hybridomas produce antibodies with a high 
degree of specificity and affinity for ErbB4. These antibodies 
recognize specific epitopes on the intracellular domains of ErbB4 
without cross-reaction against other proteins, and can be used 
successfully in the immunostaining of fixed tissue. Each antibody 
recognizes both human and mouse ErbB4, whereas only mAb-7 and mAb-10 
recognize rat ErbB4.
    Applications:
     Basic research tool for the study of ErbB4;

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     Reagent for diagnostic applications such as Western 
Blotting, ELISA, immunofluorescence and immunohistochemistry in fixed 
tissue samples;
     Reagent for biochemical techniques such as 
immunoprecipitation.
    Advantages:
     Potential to be the gold standard for ErbB4 antibodies due 
to its specificity and affinity;
     Greater affinity for ErbB4 than currently available 
antibodies, giving them superior properties in diagnostic and 
biochemical applications;
     Unlike currently available polyclonal antibodies to ErbB4, 
the monoclonal antibodies do not cross-react with other proteins;
     Unlike currently available antibodies, these antibodies 
are capable of immunostaining fixed tissue samples;
     The epitopes on ErbB4 that are recognized by each 
monoclonal antibody have been mapped.
    Relevant Publications:
    1. G Carpenter. ErbB-4: mechanism of action and biology. Exp Cell 
Res. 2003 Mar 10;284(1):66-77.
    2. S Britsch. The neruregulin-1/ErbB signaling system in 
development and disease. Adv Anat Embryol Cell Biol. 2007;190:1-65.
    Inventors: Andres Buonanno and Detlef Vullhorst (NICHD)
    Patent Status: HHS Reference No. E-171-2009/0--Research Material. 
Patent protection is not being pursued for this technology.
    Licensing Status: The technology is available under a biological 
materials license.
    Licensing Contact: David A. Lambertson, PhD; 301-435-4632; 
lambertsond@mail.nih.gov.
    Collaborative Research Opportunity: The Eunice Kennedy Shriever 
National Institute of Child Health and Human Development, Section on 
Molecular Neurobiology, is seeking statements of capability or interest 
from parties interested in collaborative research to further evaluate 
or commercialize specific rabbit monoclonal antibodies generated 
against the ErbB4 receptor (also known as HER4). Please contact Joseph 
Conrad III, PhD at 301-435-3107 or jmconrad@mail.nih.gov for more 
information.

Mouse Model of Individual Unresponsive to Interferon

    Description of Technology: NIAID has developed a mouse model that 
produces very high levels of Interferon-alpha-receptor 2 (IFNAR2), both 
in liver cells and free-floating in serum.
    Chronic co-infection of HIV and hepatitis C virus (HCV) is 
associated with increased overall morbidity and mortality compared to 
those infected with just one virus. Recent data further suggests that 
co-infection is also associated with a more rapid progression of liver 
disease, higher HCV RNA viral levels, decreased cure rate of HCV, and 
increased toxicities of anti-HCV therapy. Finally, clinical trials have 
shown that many patients infected with both viruses do not respond to 
Interferon-based therapy. Research strongly suggests that non-
responding patients have an increased level of a free-floating form of 
IFNAR2, which could block Interferon activity.
    Resistance to Interferon therapy also occurs in other diseases, 
such as autoimmune diseases (e.g., lupus, scleroderma, psoriasis, 
vasculitis) and certain forms of cancer (e.g., Kaposi's sarcoma, 
follicular lymphoma). The various means by which resistance arises is 
currently being researched.
    Applications: Study of mechanisms of resistance to Interferon 
therapy in selected diseases, such as HCV/HIV co-infection and certain 
cancers; study of Interferon-alpha in auto-immune diseases such as 
lupus, scleroderma, psoriasis, and vasculitis; drug design and 
screening.
    Advantages:
     A model to screen, develop, and test drugs for HCV among 
HCV/HIV co-infected patients not responding to Interferon;
     A model for basic research, to study the biology and role 
of IFNAR2 and its function, along with the role of the Interferon 
receptor in the development of disease resulting from activation of the 
immune system.
    Development Status: Proof-of-principle studies showing that the 
mice represent HCV/HIV co-infected individuals not responding to 
Interferon treatment.
    Market: HIV/HCV co-infection is documented in one-third of all HIV-
infected persons in the United States, an estimated 250,000 people. 
Moreover, certain cancers (e.g., Kaposi's sarcoma, follicular lymphoma) 
normally treated with Interferon-alpha either show initial resistance 
or develop resistance during therapy, but the mechanism of resistance 
is highly complex; this mouse model will be useful in learning the 
paths through which resistance develops, and perhaps in designing 
strategies to overcome resistance. Finally, autoimmune diseases known 
to be caused (in whole or in part) by Interferon-alpha include lupus, 
scleroderma, psoriasis, and vasculitis.
    Inventors: Shyamasundaran Kottilil (NIAID), Howard Young (NCI), 
Michael Polis (NIAID), Anthony Suffredini (NIHCC).
    Patent Status: HHS Reference No. E-106-2009/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for non-exclusive Biological Materials 
Licensing.
    Licensing Contact: Bruce Goldstein, J.D., M.S.; 301-435-5470; 
goldsteb@mail.nih.gov.
    Collaborative Research Opportunity: The National Institute of 
Allergy and Infectious Diseases, Laboratory of Immunoregulation, is 
interested in collaborative research directed toward molecular 
strategies for vaccine and antiviral development, and animal models of 
viral hepatitis C. For more information, please contact Rick Williams 
at 301-402-0960.

Enhanced Immune Response Against Influenza Virus by Priming With a DNA-
based Vaccine

    Description of Technology: Available for licensing and commercial 
development are compositions and methods for enhancing an immune 
response to influenza viruses by priming with DNA-based vaccines 
encoding influenza proteins. The priming compositions contain DNA 
constructs with inserted nucleic acids encoding influenza virus 
hemagglutinin (HA) or an epitope-bearing domain thereof, while the 
boosting compositions are inactivated influenza vaccines. The DNA 
constructs are based on proprietary expression systems that increase 
protein expression relative to commonly used alternatives.
    A potential influenza pandemic caused by H5N1 strains of avian 
influenza virus (bird flu) is a major global concern. The seasonal 
influenza caused by other subtypes of influenza is also a cause of 
concern. Vaccination is one of the most effective ways to minimize 
suffering and death from influenza. However, influenza vaccination does 
not reduce the risk of community-acquired pneumonia in elderly nor does 
it decrease the rate of influenza infection in children aged 6-23 
months. Strategies to elicit protective immunity with greater potency 
and breadth therefore remain a priority. The present invention 
discloses the ability of gene-based priming with influenza 
hemagglutinin (HA) to prime for an increase in titer and cross-
reactivity of the neutralizing antibody response after inactivated 
influenza virus vaccine boost. After priming with a DNA vaccine 
encoding HA from a H1N1 strain, boosting with a seasonal influenza 
vaccine containing this

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inactivated virus stimulated a 100-fold increase in the titer of H1 
neutralizing antibodies. Of note, this combination immunization, in 
contrast to either component alone, elicited heterotypic neutralizing 
antibodies against a H5N1 strain. Similar priming was also observed 
with a DNA vaccine encoding an HA from a H5N1 strain, with the H5N1 
subvirion vaccine boost. These results show that gene-based priming 
prior to vaccinating with the traditional influenza vaccine boost 
induced humoral immunity against different subtypes of influenza 
viruses that increases the potency and breadth of the neutralizing 
antibody response.
    Applications: This invention provides a vaccine strategy for 
potentially controlling influenza epidemics, including avian flu should 
it cross over to humans, and seasonal flu strains.
    Development Status: Animal studies
    Inventors: Gary J. Nabel and Chih-jen Wei (VRC/NIAID)
    Patent Status: U.S. Provisional Application No. 61/100,621 filed 26 
Aug 2008, entitled ``DNA Prime/Inactivated Vaccine Boost Immunization 
to Influenza Virus'' (HHS Reference No. E-341-2008/0-US-01).
    Related Technology: U.S. Patent No. 7,094,598 issued 22 Aug 2006 
and associated foreign rights (proprietary expression system with CMV/R 
promoter) (HHS Reference No. E-241-2001).
    Licensing Status: Available for licensing.
    Licensing Contact: Cristina Thalhammer-Reyero, PhD, MBA; 301-435-
4507; thalhamc@mail.nih.gov.

Use of MMP-8 as a Prognostic Marker for Melanoma

    Description of Technology: 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 treatments strategies can be developed.
    Matrix Metalloproteinases (MMPs) have been associated with 
increased metastasis and several small molecule inhibitors have been 
developed as potential anticancer agents. Unfortunately, these 
inhibitors have been largely unsuccessful despite the research 
suggesting otherwise and it is clear that additional analyses are 
warranted. The NIH inventors have recently performed a mutational 
analysis of the MMP gene family in human cutaneous metastatic melanoma 
and have identified several novel somatic mutations, most notably 
mutations in MMP-8. This invention provides methods of identifying 
specific inhibitors to MMP-8 that could be used to treat patients with 
MMP-8 mutations. It also provides methods for predicting the prognosis 
of patients with MMP-8 mutations. Thus, this invention could not only 
help identify the roles of specific MMPs in melanoma, but also help 
further the development MMP inhibitors to treat melanoma patients.
    Applications:
     Diagnostic array for the detection of MMP-8 mutations.
     Method of predicting the prognosis of melanoma patients.
     Method of identifying MMP-8 activators 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 25-29 and the second most prevalent cancer among woman 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 (NHGRI).
    Publication: LH Palavalli et al: Analysis of the matrix 
metalloproteinase family reveals that MMP8 is often mutated in 
melanoma. Nat Genet 2009 May;41(5):518-520.
    Patent Status: U.S. Provisional Application No. 61/198,384 filed 03 
Nov 2008 (HHS Reference No. E-273-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Whitney Hastings; 301-451-7337; 
hastingw@mail.nih.gov.
    Collaborative Research Opportunity: The National Human Genome 
Research Institute's Cancer Genetics Branch is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, and/or commercialize this newly 
identified candidate melanoma diagnostic and prognostic marker as well 
as to identify and develop possible MMP-8 activators for testing as 
possible anti-melanoma agents. Please contact NHGRI's Technology 
Development Coordinator (TDC) Claire T. Driscoll at 
cdriscol@mail.nih.gov for more information.

Methods for Preparing Immunogenic Conjugates

    Description of Technology: This technology describes improved 
methods of synthesis for conjugate vaccines, specifically those against 
anthrax. The inventors' method is designed to synthesize immunogenic 
conjugates (i.e., a protein carrier conjugated to a bacterially derived 
synthetic peptide) that are prepared at a physiological pH, not 
reversible and do not require reduction with borohydride. The 
inventors' method comprises reacting the protein carrier with a 
dihydrazide, and the peptide with a benzaldehyde, or the reverse, then 
reacting the derivatized peptide and the derivatized protein with each 
other to form an immunogenic conjugate.
    Application: Methods for making conjugate vaccines and reagents.
    Advantages: More efficient conjugation methods, higher conjugate 
yields.
    Development Status: Vaccine candidates have been synthesized and 
preclinical studies have been performed.
    Inventors: Rachel Schneerson (NICHD), Joanna Kubler-Kielb (NICHD), 
Fathy Majadly (NICHD), Stephen Leppla (NIAID), John Robbins (NICHD), 
Darrel Liu (NICHD), Joseph Shiloach (NIDDK).
    Related Publication: J Kubler-Kielb et al. Additional conjugation 
methods and immunogenicity of Bacillus anthracis poly-gamma-D-glutamic 
acid-protein conjugates. Infect Immun. 2006 Aug;74(8):4744-4749.
    Patent Status: U.S. Patent Application No. 11/005,851 filed 06 Dec 
2004 (HHS Reference No. E-040-2005/0-US-01); Foreign Rights Available.
    Licensing Status: Available for licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; 
soukasp@mail.nih.gov.

    Dated: June 8, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E9-13943 Filed 6-12-09; 8:45 am]

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