[Federal Register Volume 71, Number 238 (Tuesday, December 12, 2006)]
[Notices]
[Pages 74549-74551]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-21029]


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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.

Noncovalent HIV Env-CD4 Complexes as HIV Vaccines

    Description of Technology: HIV vaccine technology based on HIV 
envelope protein (Env) have been less successful than anticipated to 
date. One possible reason for this is the potential conformational 
masking of neutralizing epitopes. The current technology combines HIV 
Env and cell surface polypeptides CD4 in non-covalent complexes to 
expose epitopes not present on the uncomplexed Env molecules. These 
complexes can thus be used to elicit neutralizing antibodies when used 
as vaccines, immunogenic compositions or immunotherapies. The CD4 
inducing epitopes found in regions of the virus that are most conserved 
across clades are unmasked and immune sera generated with this 
technology neutralized primary HIV-1 viruses from several clades. 
Additionally, cell surface polypeptide CD4 is in its native 
conformation and masked by Env, therefore it is unlikely to induce 
autoantibodies.
    Applications and Advantages: (1) HIV vaccine based on 
conformationally masked epitopes; (2) Presents epitopes to immune 
system that are the same or similar as with actual HIV infection; (3) 
Multiple copies of Env may enhance immune response and limit dosage.
    Inventors: Jinhai Wang and Michael Norcross (CDER/FDA).
    Patent Status: U.S. Provisional Application No. 60/711,985 filed 25 
Aug 2005 (HHS Reference No. E-173-2005/0-US-01); PCT Application filed 
25 Aug 2006 (HHS Reference No. E-173-2005/1-PCT-01).
    Licensing Contact: Susan Ano, PhD; 301-435-5515; [email protected].
    Collaborative Research Opportunity: The FDA Center for Drug 
Evaluation and Research is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize this HIV Env-CD4 technology. Please contact 
Beatrice A. Droke at 301/827-7008 or [email protected] for more 
information.

Modified Bacterial Strain for Otitis Media Vaccine

    Description of the Technology: This invention relates to a strain 
of Moraxella catarrhalis containing a gene mutation that prevents 
endotoxic lipooligosaccharide (LOS) synthesis and potential use of the 
mutant for developing novel vaccines against the pathogen, for which 
there is currently

[[Page 74550]]

no licensed vaccine. M. catarrhalis is one of the causative agents of 
otitis media (middle ear infection), sinusitis, and lung infections. 
The mutant is defective in the lpxA gene, whose enzyme product is 
relevant in lipid A biosynthesis (lipid A is part of the LOS). The 
nontoxic mutant was found to elicit high levels of antibodies with 
bactericidal activity and provided protection against wild type 
bacterial challenge. Use of this mutant bacterium is envisioned as a 
new approach for vaccines against M. catarrhalis.
    Applications: Otitis media vaccine, sinusitis, and lung infections.
    Inventors: Xin-Xing Gu and Daxin Peng (NIDCD).
    Patent Status: U.S. Provisional Application No. 60/577,244 filed 04 
Jun 2004 (HHS Reference No. E-174-2004/0-US-01); U.S. Provisional 
Application No. 60/613,139 filed 23 Sep 23 (HHS Reference No. E-174-
2004/1-US-01); PCT Application No. PCT/US2005/019479 filed 03 Jun 2005 
(HHS Reference No. E-174-2004/2-PCT-01).
    Licensing Status: Available for non-exclusive licensing--biological 
materials.
    Licensing Contact: Susan Ano, PhD; 301/435-5515; [email protected].
    Collaborative Research Opportunity: The Vaccine Research Section in 
the National Institute on Deafness and Other Communication Disorders 
(NIDCD) is seeking statements of capability or interest from parties 
interested in collaborative research. NIDCD is interested in developing 
outer membrane proteins (OMP), outer membrane vesicle (OMV), and whole 
cell vaccines generated from the mutant. The mutant strain can also be 
used as an effective vehicle to express and deliver protective antigens 
from other important human pathogens. Please contact Dr. Xin-Xing Gu by 
phone (301-402-2456) or e-mail ([email protected]) for more 
information.

A Method With Increased Yield for Production of Polysaccharide-Protein 
Conjugate Vaccines Using Hydrazide Chemistry

    Description of Technology: Current methods for synthesis and 
manufacturing of polysaccharide-protein conjugate vaccines employ 
conjugation reactions with low efficiency (about twenty percent). This 
means that up to eighty percent of the added activated polysaccharide 
(PS) is lost. In addition, inclusion of a chromatographic process for 
purification of the conjugates from unconjugated PS is required.
    The present invention utilizes the characteristic chemical property 
of hydrazide groups on one reactant to react with aldehyde groups or 
cyanate esters on the other reactant with an improved conjugate yield 
of at least sixty percent. With this conjugation efficiency the 
leftover unconjugated protein and polysaccharide would not need to be 
removed and thus the purification process of the conjugate product can 
be limited to diafiltration to remove the by-products of small 
molecules. The new conjugation reaction can be carried out within one 
or two days with reactant concentrations between 1 and 25 mg/mL at PS/
protein ratios from 1:2 to 3:1, at temperatures between 4 and 40 
degrees Centigrade, and in a pH range of 5.5 to 7.4, optimal conditions 
varying from PS to PS.
    Application: Cost effective and efficient manufacturing of 
conjugate vaccines.
    Inventors: Che-Hung Robert Lee and Carl E. Frasch (CBER/FDA).
    Patent Status: U.S. Patent Application No. 10/566,899 filed 01 Feb 
2006, claiming priority to 06 Aug 2003 (HHS Reference No. E-301-2003/0-
US-10); U.S. Patent Application No. 10/566,898 filed 01 Feb 2006, 
claiming priority to 06 Aug 2003 (HHS Reference No. E-301-2003/1-US-
02); International rights available.
    Licensing Status: Available for non-exclusive licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].

HIV Entry Inhibitor

    Description of Technology: The technology relates to a chimeric 
molecule, NCCG-gp41, in which the internal trimeric helical 
coiled-coil of the ectodomain of gp41 is fully exposed and stabilized 
by both fusion to a minimal ectodomain core of gp41 and by engineered 
intersubunit disulfide bonds. NCCG-gp41 inhibits HIV 
envelope mediated cell fusion at nanomolar concentrations with an 
IC50 of 16 nM. It is proposed that NCCG-gp41 
targets the exposed C-terminal region of the gp41 ectodomain in its 
pre-hairpin intermediate state, thereby preventing the formation of the 
fusogenic form of the gp41 ectodomain that comprises a highly stable 
trimer of hairpins arranged in a six-helix bundle. Antibodies have been 
raised against NCCG-gp41 that inhibit HIV envelope mediated 
cell fusion.
    Applications: (1) Entry inhibitor HIV therapeutic; (2) HIV/AIDS 
vaccine; (3) As a component of a high throughput screening assay for 
small molecule inhibitors of HIV envelope mediated cell fusion.
    Development Status: The technology is currently in pre-clinical 
stage of development.
    Inventors: G. Marius Clore et al. (NIDDK).
    Publications:
    1. JM Louis et al. Design and properties of NCCG-gp41, a 
chimeric gp41 molecule with nanomolar HIV fusion inhibitory activity. J 
Biol Chem. 2001 Aug 3;276(31):29485-29489.
    2. CA Bewley et al. Design of a novel peptide inhibitor of HIV 
fusion that disrupts the internal trimeric coiled-coil of gp41. J Biol 
Chem. 2002 Apr 19;277(16):14238-14245.
    3. JM Louis et al. Covalent trimers of the internal N-terminal 
trimeric coiled-coil of gp41 and antibodies directed against them are 
potent inhibitors of HIV envelope-mediated cell fusion. J Biol Chem. 
2003 May 30;278(22):20278-20285.
    4. JM Louis et al. Characterization and HIV-1 fusion inhibitory 
properties of monoclonal Fabs obtained from a human non-immune phage 
library selected against diverse epitopes of the ectodomain of HIV-1 
gp41. J Mol Biol. 2005 Nov 11;353(5):945-951.
    Patent Status: U.S. Patent Application No. 10/499,094 filed 14 Jun 
2004 (HHS Reference No. E-252-2001/0-US-03); EP application 02795951.9 
and IN application 1535/CHENP/2004.
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Susan Ano, Ph.D.; 301/435-5515; 
[email protected].

Subgenomic Replicons of the Flavivirus Dengue

    Description of Technology: Dengue virus, with its four serotypes 
Den-1 to Den-4, is the most important member of the Flavivirus genus 
with respect to infection of human producing diseases that range from 
flu-like symptoms of dengue fever (DF) to severe or fatal illness of 
dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Dengue 
outbreaks continue to be a major public health problem in densely 
populated areas of the tropical and subtropical regions, where mosquito 
vectors are abundant. This invention relates to the construction of all 
four types of dengue subgenomic replicons (chromosome and plasmid which 
contain genetic information necessary for their own replication) 
containing large deletions in the structural region (C-preM-E) of the 
genome. Immunization using these replicons should be effective in 
eliciting not only a humoral-mediated immune response but also a cell-
mediated

[[Page 74551]]

immune response. These replicons should be safer than a live attenuated 
vaccine because they cannot cause disease in the host and they should 
be better than subunit vaccines because they can replicate in the host.
    Applications: Prevention of severe and/or fatal human disease 
caused by dengue virus, a major health concern in tropical and 
subtropical regions.
    Inventor: Xiaowu Pang (CBER/FDA).
    Patent Status: U.S. Patent Application 10/656,721 filed 05 Sep 
2003, claiming priority to 09 Mar 2001 (HHS Reference No. E-228-2000/0-
US-03).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].

    Dated: December 1, 2006.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E6-21029 Filed 12-11-06; 8:45 am]
BILLING CODE 4140-01-P