[Federal Register Volume 72, Number 59 (Wednesday, March 28, 2007)]
[Notices]
[Pages 14589-14591]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-5670]


-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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

[[Page 14590]]

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.

Microarray for Detection and Subtyping of Human Influenza Viruses

    Description of Technology: Available for licensing and commercial 
development are a novel influenza virus microarray and methods for 
using the microarray for the identification of existing and new types 
and subtypes of human influenza viruses. There are three types of 
influenza viruses, type A, B and C. Influenza types A or B viruses 
cause epidemics of disease almost every winter, with type A causes 
major pandemic periodically. Influenza type A viruses are further 
divided into subtypes based on two proteins on the surface of the 
virus. These proteins are called hemagglutinin (H) and neuraminidase 
(N). There are 16 known HA subtypes and 9 known NA subtypes of 
influenza A viruses. Each subtype may have different combination of H 
and N proteins. Although there are only three known A subtypes of 
influenza viruses (H1N1, H1N2, and H3N2) currently circulating among 
humans, many other different strains are circulating among birds and 
other animals and these viruses do spread to humans occasionally. There 
is a requirement for sensitive and rapid diagnostic techniques in order 
to improve both the diagnosis of infections and the quality of 
surveillance systems. This microarray platform tiles the genomes of all 
types/subtypes of influenza viruses, and is capable of correctly 
identifying all 3 types/subtypes of influenza viruses from an influenza 
vaccine sample.
    More specifically, the invention consists of: (1) Microarrays 
comprising a solid support with a plurality of n-mer influenza viral 
nucleotide segments of influenza Types A, B and C, including each 
respective subtypes, and (2) methods of detecting and identifying known 
and unknown influenza viral types and subtypes by: (a) Using 
hybridization microarrays to known influenza viral nucleotide 
sequences, (b) sequencing the nucleotides which hybridize to the 
microarrays and (c) analyzing the hybridized sequences using existing 
databases, thus identifying existing or new subtypes of influenza 
viruses.
    Applications: Detection and identification of human influenza 
viruses; Efficient discovery of new subtypes of influenza viruses; 
Diagnosis of influenza outbreaks.
    Development Status: This microarray platform was capable of 
correctly identifying all 3 types/subtypes of influenza viruses from an 
influenza vaccine sample.
    Inventors: Xiaolin Wu, Cassio S. Baptista, Elizabeth Shannon, and 
David J. Munroe (NCI).
    Patent Status: U.S. Provisional Application No. 60/857,695 filed 07 
Nov 2006 (HHS Reference No. E-208-2006/0-US-01).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Cristina Thalhammer-Reyero, PhD, MBA; 301/435-
4507; [email protected].

Improved Interleukin Expression for Immunogenic Compositions and 
Vaccine Adjuvant

    Description of Technology: The NIH is pleased to announce as 
available for licensing a technology that provides for optimized 
nucleic acids for improved expression of interleukin-15 (IL-15) and IL-
15 receptor alpha (IL-15Ralpha) in mammalian cells. IL-15 is a cytokine 
important for both the innate and adaptive immune systems. Based on its 
many functions and relative safety in animal models, IL-15 finds use in 
vaccines, cancer immunotherapeutics, and autoimmune disease and as a 
vaccine adjuvant.
    The present technology enhances the production and bioavailability 
of IL-15 through use of optimized nucleic acid sequences. Native IL-15 
coding sequences do not express IL-15 optimally for several reasons, 
and the optimized sequences of the subject technology overcome these 
deficiencies. The nucleic acids can be part of expression vectors, 
which could be utilized either in vitro or in vivo. The expression 
vectors express IL-15 alone, IL-15Ralpha alone, or both molecules 
together from a single vector. Further enhanced expression of IL-15 
and/or IL-15Ralpha can be achieved through the use of signal peptides 
or propeptides from heterologous proteins. These nucleic acids can be 
administered to enhance the immune response of an individual against 
one or more antigens. Primate studies have shown that co-administration 
of IL-15 and IL-15Ralpha increased antigen specific cells, cells 
expressing IL-2, and/or cells expressing IL-2 and IFN-gamma (i.e. 
multifunctional cells). The present compositions are useful for the 
increased bioavailability and therefore biological effects of IL-15 
after its administration to humans or other mammals.
    Applications: Vaccines; Improved protein expression; Cancer 
immunotherapeutics; Autoimmune disease; Vaccine adjuvant.
    Inventors: Barbara K. Felber and George N. Pavlakis (NCI).
    Related Publication: MA Kutzler et al. Coimmunization with an 
optimized IL-15 plasmid results in enhanced function and longevity of 
CD8 T cells that are partially independent of CD4 T cell help. J 
Immunol. 2005 Jul 1;175(1):112-123.
    Patent Status: U.S. Provisional Application No. 60/758,819 filed 13 
Jan 2006 (HHS Reference No. E-254-2005/0-US-01); U.S. Provisional 
Application No. 60/812,566 filed 09 Jun 2006 (HHS Reference No. E-254-
2005/1-US-01); PCT Application filed 13 Jan 2007 (HHS Reference No. E-
254-2005/2-PCT-01).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Susan Ano, PhD; 301/435-5515; [email protected].

Potent Activation of Antigen Presenting Cells by the Hepatitis A Virus 
Cellular Receptor 1 and Its Role in the Regulation of Immune Responses

    Description of Technology: Available for licensing and commercial 
development are compositions and methods to regulate various immune 
responses through the hepatitis A virus cellular receptor 1 (HAVCR1). 
HAVCR1 (also known as TIM-1) is a member of the TIM family of receptors 
that is usurped by the hepatitis A virus (HAV) to infect cells. The 
gene encoding HAVCR1 has been shown to be an important asthma and 
allergy susceptibility gene. HAVCR1 plays a critical role in regulating 
T cell differentiation and the development of atopy. HAVCR1 is over-
expressed in kidney ischemic cells and malignant renal tumors. The 
invention describes a ligand of HAVCR1 in antigen presenting cells 
(APCs) that is unrelated to murine Tim-4, a TIM family member reported 
as the ligand of murine Tim-1. The ligand was identified using an 
expression cloning strategy. The specific binding of HAVCR1 to this 
ligand on APCs causes activation and induces the expression of co-
stimulatory receptors at the cell surface of the APCs and the secretion 
of cytokines such as IL-6, IL-10, and TNF-a. Furthermore, treatment of 
APCs with soluble forms of HAVCR1 induced T cell proliferation. The 
invention describes a novel mechanism by which HAVCR1 regulates immune 
responses, in which the activation of APCs is mediated by HAVCR1 
binding to ligands on APCs. The association of HAVCR1 with the ligand 
identified in

[[Page 14591]]

APCs also enhances the interaction of HAVCR1 with HAV.
    Aspects of the technology are further described in Tami et al., 
2007. J. Virol., in press.
    Applications: Therapies that target the interaction of HAVCR1 with 
the ligand on APCs, such as small molecules or monoclonal antibodies, 
can control immune responses, the development of asthma, allergies and 
other atopic diseases, hepatitis A, kidney regeneration, and cancer.
    Development Status: The technology is in early stages of 
development.
    Inventors: Gerardo Kaplan (CBER/FDA), et al.
    Patent Status: U.S. Provisional Application No. 60/865,631 filed 13 
Nov 2006 (HHS Reference No. E-035-2005/0-US-01).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Cristina Thalhammer-Reyero, PhD, M.B.A.; 301/
435-4507; [email protected].
    Collaborative Research Opportunity: The Food and Drug 
Administration, Center of Biologics Research and Evaluation, Laboratory 
of Hepatitis and Related Emerging Agents, is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize the hepatitis A 
virus cellular receptor as a potent activator of antigen presenting 
cells. Please contact Beatrice Droke, 301/872-7008 or 
[email protected], for more information.

Cyanovirins and Related Conjugates, Compositions, Nucleic Acids, 
Vectors, Host Cells, Methods of Production and Methods of Use for 
Microbicide Development

    Description of Technology: The development of an effective anti-HIV 
topical microbicide, especially a female-controlled, vaginal 
microbicide, has been deemed an urgent global priority by numerous 
international agencies, including the World Health Organization, the 
U.S. Department of Health and Human Services, the National Institute of 
Allergy and Infectious Diseases, and others. The present invention 
provides antiviral proteins (collectively referred to as cyanovirins), 
conjugates thereof, DNA sequences encoding such agents, host cells 
containing such DNA sequences, antibodies directed to such agents, 
compositions comprising such agents, and methods of obtaining and using 
such agents for the production of microbicides.
    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 is 
directly virucidal, interacting in an unusual manner with the viral 
envelope, apparently binding with extremely high affinity to poorly 
immunogenic epitopes on gp120. Further, cyanovirin-N (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 
of CV-N, which code sequences to enable ultra large-scale recombinant 
production of functional cyanovirins 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 vaginal toxicity/
irritancy model, and was not cytotoxic in vitro against human immune 
cells and lactobacilli (unpublished). 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: Development of microbicides against HIV and 
influenza.
    Development Status: Preclinical data is available at this time.
    Inventors: Michael Boyd (NCI), Robert Shoemaker (NCI), Barry 
O'Keefe (NCI), Toshiyuki Mori (NCI), Angela Gronenborn (NIDDK).
    Related 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.
    Patent Status:
    1. Patent Cooperation Treaty Serial No. PCT/US00/06247 filed 10 Mar 
2000; National Stage Filing in United States, Japan, Australia, Europe, 
Germany, France, China, United Kingdom, and Belgium (HHS Reference No. 
E-074-1999/2).
    2. Patent Cooperation Treaty Serial No. PCT/US99/18975 filed 19 Aug 
1999; National Stage Filing in United States, Japan, Australia, Europe, 
Germany, France, China, United Kingdom, and Belgium (HHS Reference No. 
E-117-1995/3).
    Licensing Status: Available for licensing and commercial 
development.
    Licensing Contact: Sally Hu, PhD; 301/435-5606; [email protected].
    Collaborative Research Opportunity: The National Cancer Institute's 
Molecular Targets Development Program is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize microbicides 
for HIV and influenza. Please contact John D. Hewes at (301) 435-3121 
or [email protected] for more information.

    Dated: March 16, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E7-5670 Filed 3-27-07; 8:45 am]
BILLING CODE 4140-01-P