[Federal Register: March 28, 2007 (Volume 72, Number 59)]
[Notices]
[Page 14589-14591]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr28mr07-81]
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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
[[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; thalhamc@mail.nih.gov.
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; anos@mail.nih.gov.
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; thalhamc@mail.nih.gov.
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
beatrice.droke@fda.hhs.gov, 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; HuS@mail.nih.gov.
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 hewesj@mail. nih.gov 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