[Federal Register Volume 69, Number 80 (Monday, April 26, 2004)]
[Notices]
[Pages 22540-22542]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-9465]


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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.

Reactivity of Human Sera in a Sensitive, High Throughput Pseudovirus-
Based Papillomavirus Neutralization Assay for HPV 16 and HPV 18

John Schiller (NCI), Douglas Lowy (NCI), Chris Buck (NCI),
Diana Pastrana (NCI), Richard Roden (EM), DHHS Reference No. E-137-
2004/0--Research Material
Licensing Contact: Peter Soukas; (301) 435-4646; [email protected].

    This invention is a research tool for measuring protective antibody 
responses generated by prophylactic Human Papilloma Virus (HPV) 
vaccines. Sensitive high-throughput neutralization assays, based upon 
pseudoviruses carrying a secreted alkaline phosphatase (SEAP) reporter 
gene, were developed and validated by the inventors for HPV 16, HPV 18, 
and bovine papillomavirus 1 (BPV1). In a 96-well plate format, the 
assay was reproducible and appears to be as sensitive as, but more 
specific than, a standard papillomavirus-like particle (VLP)-based 
enzyme-linked immunosorbent assay (ELISA). The SEAP pseudovirus-based 
neutralization assay should be a practical method for quantifying 
potentially protective antibody responses in HPV natural history and 
prophylactic vaccine studies.
    This assay is available nonexclusively through a biological 
materials license. The assay is further described in Pastrana et al., 
``Reactivity of human sera in a sensitive, high-throughput pseudovirus-
based papillomavirus neutralization assay for HPV16 and HPV18,'' 
Virology. 2004 Apr 10;321(2):205-16.

[[Page 22541]]

Enzymatically-Active RNA-Dependent RNA Polymerase From a Human 
Norovirus (Calicivirus)

Gael Belliot, Stanislav Sosnovtsev, Kyeong-Ok Chang, Kim Green (NIAID),
DHHS Reference No. E-283-2003/0--Research Material.
    Licensing Contact: Peter Soukas; (301) 435-4646; 
[email protected].

    The noroviruses (formerly known as ``Norwalk-like viruses'') are 
associated with gastroenteritis outbreaks, affecting large numbers of 
individuals each year. Emerging data are supporting their increasing 
recognition as important agents of diarrhea-related morbidity and 
mortality. The frequency with which noroviruses are associated with 
gastroenteritis as ``food and water-borne pathogens'' has led to the 
inclusion of caliciviruses as Category B Bioterrorism Agents/Diseases. 
Because the noroviruses cannot be propagated by any means in the 
laboratory, an important strategy in their study is to development of 
molecular biology-based tools and replication systems. This invention 
reports the isolation of the first recombinant, enzymatically-active 
proteinase and RNA dependent RNA polymerase (RdRp) complex for a human 
norovirus. This enzyme should facilitate studies aimed at developing 
therapeutic drugs for norovirus disease.
    The materials embodied in this invention are available 
nonexclusively through a biological materials license. The materials 
are further described in Wei L et al., ``Proteinase-polymerase 
precursor as the active form of feline calicivirus RNA-dependent RNA 
polymerase,'' J. Virol. 2001 Feb;75(3):1211-9.

Construction of an Infectious Full-Length cDNA Clone of the Porcine 
Enteric Calicivirus RNA Genome

    Kyeong-Ok Chang (NIAID), Stanislav Sosnovtsev (NIAID), Gael Belliot 
(NIAID), Linda Saif (EM), Kim Green (NIAID) DHHS Reference No. E-214-
2003/0--Research Material
    Licensing Contact: Peter Soukas; 301/435-4646; 
[email protected].
    Porcine enteric calicivirus (PEC) is a member of the genus 
Sapovirus in the family Caliciviridae. This virus causes diarrheal 
illness in pigs, and is presently the only enteric calicivirus that can 
be grown in cell culture. In addition to its relevance to veterinary 
medicine as a diarrheal agent in pigs, PEC serves as an important model 
for the study of enteric caliciviruses that cause diarrhea and that 
cannot be grown in cell culture (including the noroviruses represented 
by Norwalk virus). The development of an infectious cDNA clone is 
important because it enables the use of ``reverse genetics'' to 
engineer mutations of interest into the genome of PEC and to study 
their effects. In addition, it allows the introduction of foreign 
coding sequences into the genome of PEC that could be useful for 
vaccine development in swine and possibly humans. This discovery has 
both basic research applications such as mapping mutations involved in 
tissue culture adaptation, tissue tropism, and virulence as well as 
practical applications such as providing a genetic backbone for the 
development of chimeric vaccine viruses.
    The materials embodied in this invention are available 
nonexclusively through a biological materials license. The materials 
are further described in Chang K-O et al., ``Cell-culture propagation 
of porcine enteric calicivirus mediated by intestinal contents is 
dependent on the cyclic AMP signaling pathway,'' Virology. 2002 Dec 
20;304(2):302-10.

Construction of Recombinant Baculoviruses Carrying the Gene Encoding 
the Major Capsid Protein, VP1, From Calicivirus Strains (Including 
Norovirus Strains Toronto, Hawaii, Desert Shield, Snow Mountain, and 
Md145-12)

    Kim Green, Judy F. Lew, Adriene D. King, Stanislav Sosnovtsev, Gael 
Belliot (NIAID) DHHS Reference No. E-198-2003/0--Research Material
    Licensing Contact: Peter Soukas; 301/435-4646; 
[email protected].
    The noroviruses (known as ``Norwalk-like viruses'') are associated 
with an estimated 23,000,000 cases of acute gastroenteritis in the 
United States each year. Norovirus illness often occurs in outbreaks, 
affecting large numbers of individuals, illustrated recently by well-
publicized reports of gastroenteritis outbreaks on several recreational 
cruise ships and in settings such as hospitals and schools. Norovirus 
disease is clearly important in terms of medical costs and missed 
workdays, and accumulating data support its emerging recognition as 
important agents of diarrhea-related morbidity.
    Because the noroviruses cannot be propagated by any means in the 
laboratory, an important strategy in their study is the development of 
molecular biology-based tools. This invention reports the development 
of recombinant baculoviruses carrying the capsid gene from several 
caliciviruses associated with human disease. Growth of these 
baculovirus recombinants in insect cells results in the expression of 
virus-like particles (VLPs) that are antigenically indistinguishable 
from the native calicivirus particle. These VLPs can be purified in 
large quantities for use as diagnostic reagents and potential vaccine 
candidates.
    The materials embodied in this invention are available 
nonexclusively through a biological materials license. An example of 
the application of these materials is further described in Green KY et 
al., ``A predominant role for Norwalk-like viruses as agents of 
epidemic gastroenteritis in Maryland nursing homes for the elderly,'' 
J. Infect. Dis. 2002 Jan. 15;185(2):133-46.

MVA Expressing Modified HIV envelope, gag, and pol Genes

    Bernard Moss (NIAID), Patricia Earl (NIAID), Linda Wyatt (NIAID), 
Leigh Anne Steinmeyer (EM), Thomas VanCott (EM), Matthew Harris (EM) 
U.S. Provisional Application No. 60/459,175 filed 28 Mar 2003 (DHHS 
Reference No. E-023-2003/0-US-01); PCT Application filed 28 Mar 2004 
(DHHS Reference No. E-023-2003/0-PCT-02)
    Licensing Contact: Peter Soukas; 301/435-4646; 
[email protected].
    This invention claims Modified Vaccinia Ankara (MVA), a 
replication-deficient strain of vaccinia virus, expressing Human 
Immunodeficiency Virus (HIV) env, gag, and pol genes, where the genes 
are isolated from Ugandan Clade D isolates, Kenyan Clade A isolates, 
and Tanzanian Clade C isolates. In a rhesus macaque SHIV model, DNA 
priming followed by a recombinant MVA (rMVA) booster controlled a 
highly pathogenic immunodeficiency challenge. Both the DNA and the rMVA 
components of the vaccine expressed multiple immunodeficiency virus 
proteins. Two DNA inoculations at zero (0) and eight (8) weeks and a 
single rMVA booster at twenty-four (24) weeks effectively controlled an 
intrarectal challenge administered seven (7) months after the booster. 
Additionally, the inventors have generated data showing that 
inoculations of rMVA induce good immune responses even without DNA 
priming.
    The inventors are continuing preclinical work on the vaccine, and 
have generated further data on the vaccine. Furthermore, the inventors 
are continuing to optimize the vaccine by genetically modifying the 
genes. This vaccine will be the subject of an upcoming Phase I clinical 
trial. These findings provide hope that a relatively simple 
multiprotein DNA/MVA vaccine can help to control the Acquired Immune 
Deficiency Syndrome (AIDS) epidemic.

[[Page 22542]]

Reagents to Produce Purified Human 14-3-3 Zeta and 14-3-3 Epsilon as 
Glutathione-S-Transferase Fusion Protein

    David Klein, Surajit Ganguly (NICHD), DHHS Reference No. E-142-
2002--Research Material.
    Licensing Contact: Peter Soukas; 301/435-4646; 
[email protected].
    14-3-3 proteins are thought to be involved in some way in prion-
based diseases, including Bovine Spongiform Encephalopathy (BSE). The 
preparations described in this invention can be used to make large 
amounts of two human forms of 14-3-3 proteins, zeta and epsilon. These 
proteins can be used to raise antisera against human 14-3-3 proteins 
and in assays of proteins that bind 14-3-3 proteins to monitor prion-
caused diseases. Additionally, the 14-3-3 proteins described in this 
invention may be used as vaccines to immunize against proteins involved 
in prion diseases.
    The materials described in this invention are available 
nonexclusively through a biological materials license. The materials 
are further described in Ganguly S. et al., ``Role of a pineal cAMP-
operated arylalkylamine N-acetyltransferase/14-3-3-binding switch in 
melatonin synthesis,'' Proc. Natl. Acad. Sci. U.S.A. 2001 Jul 
3;98(14):8083-8 and Obsil T. et al., ``Crystal structure of the 14-3-
3zeta:serotonin N-acetyltransferase complex. a role for scaffolding in 
enzyme regulation,'' Cell. 2001 Apr 20;105(2):257-67.

    Dated: April 18, 2004.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 04-9465 Filed 4-23-04; 8:45 am]
BILLING CODE 4140-01-P