[Federal Register Volume 73, Number 118 (Wednesday, June 18, 2008)]
[Notices]
[Pages 34762-34765]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-13672]


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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.

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)

    Description of Technology: 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.
    Inventors: Kim Y. Green, Judy F. Lew, Adriene D. King, Stanislav V. 
Sosnovtsev, Gael M. Belliot (NIAID).
    Publication: An example of the application of these materials is 
further described in KY Green 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):133-146.
    Patent Status: HHS Reference No. E-198-2003/0--Research Material.
    Licensing Status: The materials embodied in this invention are 
available

[[Page 34763]]

nonexclusively through a biological materials license.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].
    Collaborative Research Opportunity: The Laboratory of Infectious 
Diseases, NIAID, NIH, is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize norovirus VLP antigens. Please contact Kim 
Y. Green at [email protected] for more information.

Full-Length cDNA Clone Representing the Consensus Sequence of the RNA 
Genome of a Human Norovirus (Strain MD145-12) That Encodes Biologically 
Active Proteins

    Description of Technology: The invention provides for a full-length 
cloned cDNA copy of the RNA genome of a predominant norovirus strain 
(Genogroup II.4) designated MD145-12 that was associated with human 
gastrointestinal illness. The noroviruses, which were formerly known as 
``Norwalk-like'' viruses are estimated to cause 23 million cases of 
acute gastroenteritis in the USA each year. The virus has been 
designated into category B of the CDC biodefense-related priority 
pathogens because it can be used as an agent of bioterrorism. The 
subject cDNA clone of the virus encodes proteins of the MD145-12 strain 
that, when expressed in vitro, exhibit properties that would be 
expected from those produced by the original infectious virus. This 
cDNA clone is presently the only source to obtain norovirus proteins to 
facilitate studies aimed at developing control strategies such as 
vaccines and therapeutic drugs.
    Inventors: Gael M. Belliot, Kim Y. Green, Stanislav V. Sosnovtsev 
(NIAID).
    Patent Status: HHS Reference No. E-212-2003/0--Research Material.
    Licensing Status: The cDNA clone for norovirus strain MD145-12 is 
available for licensing via a biological material license (BML).
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].
    Collaborative Research Opportunity: The Laboratory of Infectious 
Diseases, NIAID, NIH, is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize reagents derived from a cDNA clone of the 
genome of a predominant human norovirus strain, Genogroup II.4. Please 
contact Kim Y. Green at [email protected] for more information.

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

    Description of Technology: Porcine enteric calicivirus (PEC) is a 
member of the genus Sapovirus in the family Caliciviridae. This virus 
causes diarrheal illness in pigs. In addition, 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 and the sapoviruses 
represented by Sapporo 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.
    Inventors: Kyeong-Ok Chang (NIAID), Stanislav V. Sosnovtsev 
(NIAID), Gael M. Belliot (NIAID), Kim Y. Green (NIAID), et al.
    Publication: The materials are further described in KO Chang 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):302-310.
    Patent Status: HHS Reference No. E-214-2003/0--Research Material.
    Licensing Status: The materials embodied in this invention are 
available nonexclusively through a biological materials license.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].
    Collaborative Research Opportunity: The Laboratory of Infectious 
Diseases, NIAID, NIH, is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize reagents derived from an infectious cDNA 
copy of the genome of porcine enteric calicivirus. Please contact Kim 
Y. Green at [email protected] for more information.

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

    Description of Technology: 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 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.
    Inventors: Gael M. Belliot, Stanislav V. Sosnovtsev, Kyeong-Ok 
Chang, Kim Y. Green (NIAID).
    Publication: The materials are further described in L Wei et al., 
``Proteinase-polymerase precursor as the active form of feline 
calicivirus RNA-dependent RNA polymerase,'' J. Virol. 2001 
Feb;75(3):1211-1219.
    Patent Status: HHS Reference No. E-283-2003/0--Research Material.
    Licensing Status: The materials embodied in this invention are 
available nonexclusively through a biological materials license.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].
    Collaborative Research Opportunity: The Laboratory of Infectious 
Diseases, NIAID, NIH, is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize an active human norovirus proteinase-
polymerase enzyme. Please contact Kim Y. Green at [email protected] 
for more information.

A Sensitive, High Throughput Pseudovirus-Based Papillomavirus 
Neutralization Assay for HPV 16 and HPV 18

    Description of Technology: This invention is a research tool for 
measuring protective antibody responses against Human Papilloma Viruses 
(HPV). 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

[[Page 34764]]

96-well plate format, the assay was reproducible and appears to be as 
sensitive as, but more type-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.
    Inventors: John T. Schiller (NCI), Douglas R. Lowy (NCI), 
Christopher Buck (NCI), Diana V. Pastrana (NCI), et al.
    Publication: 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):205-216.
    Patent Status: HHS Reference No. E-137-2004/0--Research Material.
    Licensing Status: This assay is available nonexclusively through a 
biological materials license.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].

Methods for Preparing Complex Multivalent Immunogenic Conjugates

    Description of Invention: Claimed in this application are novel 
methods for preparing complex multivalent immunogenic conjugates and 
conjugate vaccines. The multivalent conjugates and conjugate vaccines 
are synthesized by conjugating mixtures of more than one polysaccharide 
at a desired ratio of the component polysaccharides to at least one 
carrier protein using hydrazide chemistry. Because of the high 
efficiency of hydrazide chemistry in conjugation, the polysaccharides 
are effectively conjugated to the carrier protein(s) so that the 
resulting complex synthesized vaccine conjugate products, without 
requiring tedious and complicated purification procedures such as 
chromatography and/or ammonium sulfate precipitation, are efficacious 
in inducing antibodies in mice against each component polysaccharide. 
The methods claimed in this application simplify the preparation of 
multivalent conjugate vaccines by utilizing simultaneous conjugation 
reactions in a single reaction mixture or batch that includes at least 
two immunogenic-distinct polysaccharides. This single-batch 
simultaneous reaction eliminates the need for multiple parallel 
synthesis processes for each polysaccharide vaccine conjugate component 
as employed in conventional methods for making multivalent conjugate 
vaccines.
    Application: Cost effective and efficient manufacturing of 
conjugate vaccines.
    Inventors: Che-Hung Robert Lee (CBER/FDA).
    Patent Status: PCT Application No. PCT/US2007/006627 filed 16 Mar 
2007 (HHS Reference No. E-085-2005/0-PCT-02).
    Licensing Status: Available for exclusive or non-exclusive 
licensing. The technology is not available for licensing in the field 
of use of multivalent meningitis vaccines.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].

Human Neutralizing Monoclonal Antibodies to Respiratory Syncytial Virus 
and Human Neutralizing Antibodies to Respiratory Syncytial Virus

    Description of Technology: This invention is a human monoclonal 
antibody fragment (Fab) discovered utilizing phage display technology. 
It is described in Crowe et al., Proc Natl Acad Sci USA. 1994 Feb 
15;91(4):1386-1390 and Barbas et al., Proc Natl Acad Sci USA. 1992 Nov 
1;89(21):10164-10168. This MAb binds an epitope on the RSV F 
glycoprotein at amino acid 266 with an affinity of approximately 
10\9\M-\1\. This MAb neutralized each of 10 subgroup A and 9 
subgroup B RSV strains with high efficiency. It was effective in 
reducing the amount of RSV in lungs of RSV-infected cotton rats 24 
hours after treatment, and successive treatments caused an even greater 
reduction in the amount of RSV detected.
    Applications: Research and drug development for treatment of 
respiratory syncytial virus.
    Inventors: Robert M. Chanock (NIAID), Brian R. Murphy (NIAID), 
James E. Crowe Jr. (NIAID), et al.
    Patent Status: U.S. Patent 5,762,905 issued 09 Jun 1998 (HHS 
Reference No. E-032-1993/1-US-01); U.S. Patent 6,685,942 issued 03 Feb 
2004 (HHS Reference No. E-032-1993/1-US-02); U.S. Patent Application 
No. 10/768,952 filed 29 Jan 2004 (HHS Reference No. E-032-1993/1-US-
03).
    Licensing Status: Available for non-exclusive licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].

Neutralizing Monoclonal Antibodies to Respiratory Syncytial Virus

    Description of Technology: Respiratory syncytial virus (RSV) is the 
most common cause of bronchiolitis and pneumonia among infants and 
children under 1 year of age. Illness begins most frequently with 
fever, runny nose, cough, and sometimes wheezing. During their first 
RSV infection, between 25% and 40% of infants and young children have 
signs or symptoms of bronchiolitis or pneumonia, and 0.5% to 2% require 
hospitalization. Most children recover from illness in 8 to 15 days. 
The majority of children hospitalized for RSV infection are under 6 
months of age. RSV also causes repeated infections throughout life, 
usually associated with moderate-to-severe cold-like symptoms; however, 
severe lower respiratory tract disease may occur at any age, especially 
among the elderly or among those with compromised cardiac, pulmonary, 
or immune systems.
    This invention is a human monoclonal antibody fragment (Fab) 
discovered utilizing phage display technology. The neutralizing 
monoclonal antibody was isolated and its binding site was identified. 
Fab F2-5 is a broadly reactive fusion (F) protein-specific recombinant 
Fab generated by antigen selection from a random combinatorial library 
displayed on the surface of filamentous phage. In an in vitro plaque-
reduction test, the Fab RSVF2-5 neutralized the infectivity of a 
variety of field isolates representing viruses of both RSV subgroups A 
and B. The Fab recognized an antigenic determinant that differed from 
the only other human anti-F monoclonal antibody (RSV Fab 19) described 
thus far. A single dose of 4.0 mg of Fab RSVF2-5/kg of body weight 
administered by inhalation was sufficient to achieve a 2000-fold 
reduction in pulmonary virus titer in RSV-infected mice. The antigen-
binding domain of Fab RSVF2-5 offers promise as part of a prophylactic 
regimen for RSV infection in humans.
    Application: Respiratory Syncytial Virus prophylaxis/therapeutic.
    Development Stage: The antibodies have been synthesized and 
preclinical studies have been performed.
    Inventors: Brian Murphy (NIAID), Robert Chanock (NIAID), James 
Crowe (NIAID), et al.
    Publication: JE Crowe et al. Isolation of a second recombinant 
human respiratory syncytial virus monoclonal antibody fragment (Fab 
RSVF2-5) that exhibits therapeutic efficacy in vivo. J Infect Dis. 1998 
Apr;177(4):1073-1076.
    Patent Status: HHS Reference No. E-001-1996/0--U.S. and Foreign 
Rights Available.
    Licensing Status: Available for exclusive or non-exclusive 
licensing.

[[Page 34765]]

    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].

Murine Monoclonal Antibodies Effective To Treat Respiratory Syncytial 
Virus

    Description of Technology: Available for licensing through a 
Biological Materials License Agreement are the murine MAbs described in 
Beeler et al., ``Neutralization epitopes of the F glycoprotein of 
respiratory syncytial virus: effect of mutation upon fusion function,'' 
J Virol. 1989 Jul;63(7):2941-2950. The MAbs that are available for 
licensing are the following: 1129, 1153, 1142, 1200, 1214, 1237, 1112, 
1269, and 1243. One of these MAbs, 1129, is the basis for a humanized 
murine MAb (see U.S. Patent 5,824,307 to humanized 1129 owned by 
MedImmune, Inc.), recently approved for marketing in the United States. 
MAbs in the panel reported by Beeler et al. have been shown to be 
effective therapeutically when administered into the lungs of cotton 
rats by small-particle aerosol. Among these MAbs several exhibited a 
high affinity (approximately 10\9\M-\1\) for the RSV F 
glycoprotein and are directed at epitopes encompassing amino acid 262, 
272, 275, 276 or 389. These epitopes are separate, nonoverlapping and 
distinct from the epitope recognized by the human Fab of U.S. Patent 
5,762,905 owned by The Scripps Research Institute.
    Applications: Research and drug development for treatment of 
respiratory syncytial virus.
    Inventors: Robert M. Chanock, Brian R. Murphy, Judith A. Beeler, 
and Kathleen L. van Wyke Coelingh (NIAID).
    Patent Status: HHS Reference No. B-056-1994/1--Research Tool.
    Licensing Status: Available for non-exclusive licensing under a 
Biological Materials License Agreement.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].

    Dated: June 10, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E8-13672 Filed 6-17-08; 8:45 am]
BILLING CODE 4140-01-P