[Federal Register Volume 74, Number 108 (Monday, June 8, 2009)]
[Notices]
[Pages 27150-27152]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-13284]


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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.

Interactive Venn Diagram Software Designed for Microarray Analysis

    Description of Technology: Multiple conditions from any source, but 
designed for experiments involving microarrays, will produce 
(significant gene lists for arrays) lists from each condition, thus 
multiple lists. This Java[reg] based software provides investigators 
with a method of displaying multiple conditions in a single graphic 
along with producing a text output of genes that are the product of 
these conditional intersections along with each conditions unique list. 
A standard Venn diagram is limited to only display three (3) 
comparisons; this software can display any number of comparisons and 
will automatically create lists from all intersections even if not able 
to be displayed along with each conditions unique list.
    Applications:
     Microarray analysis.
     Genomics.
     Bioinformatics.
     Any environment creating multiple lists (Business, 
Accounting, Inventory Control, etc.).
    Inventor: Daniel E. Sturdevant (NIAID).
    Patent Status: HHS Reference No. E-189-2009/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for licensing.
    Licensing Contact: Michael A. Shmilovich, Esq.; 301-435-5019; 
[email protected].

Axenically-Produced Coxiella burnetii and Methods for Producing Axenic 
Coxiella burnetii

    Description of Technology: Coxiella burnetii is the causative agent 
of Q (Query) fever. Currently, there is a need for a safe Q fever 
vaccine. It is anticipated that axenically-produced C. burnetii, which 
is free of host cell related impurities, could provide either the basis 
for a whole-cell Q fever vaccine or advance the development of a safe 
recombinant Q fever vaccine. Currently, there are no licensed Q-fever 
vaccines except for a whole-cell, formalin inactivated, vaccine which 
is available in Australia (Q-Vax). Individuals with a previous exposure 
to C. burnetii may, however, have a severe allergic reaction to this 
vaccine and other individuals may experience a headache or flu-like 
symptoms after vaccination. It is anticipated that axenically-produced 
C. burnetii could provide the basis for a less reactogenic whole-cell 
vaccine or facilitate the development of a recombinant vaccine that 
does not cause an allergic reaction. Additionally, the inability to 
propagate obligate intracellular pathogens under axenic (host cell-
free) culture conditions imposes severe experimental constraints that 
have negatively impacted progress in understanding pathogen virulence 
and disease mechanisms.
    Q fever is a zoonotic disease and farm animals, pets, and rodents 
are significant reservoirs for C. burnetii. C. burnetii persists in the 
soil for a long time and typically humans are exposed to Q fever by the 
inhalation of the bacterium deposited with animal waste such as urine, 
feces, and amniotic fluid. The epidemiology of Q fever is diverse and 
the disease does not discriminate between developed and developing 
countries. Additionally, urban outbreaks have been known to occur due 
to windborne C. burnetii. C. burnetii is listed as a select agent by 
the Department of Health and Human Services (HHS) because of its 
potential as an agent of bioterrorism. Deployed military personnel are 
also at risk of contracting Q fever and thousands of cases of Q fever 
have been reported among military personnel since the disease was first 
reported in the 1930s.
    Advantages:
     The ability to propagate, previously unpropagatable, C. 
burnetii without a hostcell.
     The ability to study C. burnetii virulence using axenic 
conditions or conditions free of host cell-related impurities.
     This technology is ready for use in drug/vaccine 
discovery, production, and development.
     Potential licensees of this invention include companies 
that are: 1) seeking vaccine production platforms based on host cell-
free (axenic) media, 2) seeking to develop recombinant vaccines for 
obligate, intracellular, bacteria; or 3) seeking to lower costs and 
ease scale-up would be potential licensees of this technology.
    Development Status: This technology has been demonstrated with C. 
burnetii. Currently, the inventors are testing this technology for 
support of axenic growth of other obligate, intracellular, bacteria of 
public health significance.
    Inventors: Robert A. Heinzen, Anders Omsland, Diane C. Cockrell, 
Dale Howe (NIAID).
    Publication: A Omsland et al. Host cell-free growth of the Q fever 
bacterium Coxiella burnetii. Proc Natl Acad Sci USA. 2009 Mar 
17;106(11):4430-4434.
    Patent Status: U.S. Provisional Application No. 61/154,330 filed 20 
Feb 2009 (HHS Reference No. E-114-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; 
[email protected].

[[Page 27151]]

Self-Expanding Stent for Valve Replacement

    Description of Technology: Aortic stenosis and aortic regurgitation 
are the most common types of aortic valvular diseases. Such diseased 
aortic valves in the body are traditionally replaced with valve 
prosthesis by an open surgical implantation. Available for licensing 
and commercial development is intellectual property covering stents for 
use with valve prostheses. One possible embodiment of the invention 
includes a self-expandable stent with an elastic tubular latticework 
having radial and longitudinal direction. The stent geometry and 
mechanical parameters provide more anatomically-correct placement and 
the flexible scaffolding of the valve (using an interconnected four-
sided polygons and longitudinal rods comprising a self-expanding stent 
with a plurality of struts connecting a plurality of rods) allow for 
secure implantation with adaptable apposition of the prosthesis in the 
aorta.
    Applications: Cardiac Surgery; Cardiology; Surgery; Stent 
implantation.
    Inventors: Keith Horvath, Dumitru Mazilu, Ming Li (NHLBI).
    Publications:
    1. M Li, D Mazilu, KA Horvath. Robotic system for transapical 
aortic valve replacement with MRI guidance. Med Image Comput Comput 
Assist Interv Int Conf Med Image Comput Comput Assist Interv. 
2008;11(Pt 2):476-484.
    2. KA Horvath, M Li, D Mazilu, MA Guttman, ER McVeigh. Real-time 
magnetic resonance imaging guidance for cardiovascular procedures. 
Semin Thorac Cardiovasc Surg. 2007 Winter;19(4):330-335. Review.
    Patent Status: U.S. Provisional Application No. 61/172,568 filed 24 
Apr 2009 (HHS Reference No. E-337-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Michael A. Shmilovich, Esq.; 301-435-5019; 
[email protected].
    Collaborative Research Opportunity: The National Heart, Lung, and 
Blood Institute, Cardiothoracic Surgery Research Program, is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
this technology. Please contact Peg Koelbe at 301-594-4095 or 
[email protected] for more information.

Method of Diagnosing Multidrug Resistant Tuberculosis

    Description of Technology: The invention can be used to develop 
tests that are much more rapid than conventional tests for determining 
drug resistance. It relates to the discovery that a putative gene of 
Mycobacterium tuberculosis (MTb) with no previously identified function 
is responsible for the ability of the bacteria to activate a class of 
second line thioamide drugs used for MTb infections. The gene, termed 
``etaA,'' codes for the synthesis of a monooxygenase, the enzyme 
responsible for the oxidative activation of the drugs. Mutation in the 
etaA gene leads to the expression of mutated, inactivated enzyme, thus 
resulting in thioamide drug-resistant bacteria. The significance of 
this discovery is that now, resistance to the class of thioamide drugs 
in clinical isolates can be identified in a relatively short time, 
eliminating the need to perform lengthy culturing procedures.
    The invention claims test methods for determining resistance to 
thioamide drugs by detecting gene mutation. These include (a) 
amplifying the etaA gene or a portion of it containing the mutation, 
with a set of primers which provide amplified product, and sequencing 
the amplified product to compare the sequence with a known sequence of 
the wild-type etaA; a difference in sequence patterns indicates 
mutation; (b) subjecting the amplified gene product to digestion by 
restriction enzymes and comparing the cleaved DNA gel pattern to the 
one obtained from digestion of the wild-type etaA gene; a difference 
indicates mutation in etaA; and (c) detecting the mutations by probe 
hybridization techniques, where the amplified product hybridizes to a 
nucleic acid of known sequence under stringent conditions, and the 
hybridized product is detected. In addition to the above, the invention 
proposes other detection methods such as commonly used for SNPs. Other 
methods claimed in the invention are immunoassay (i.e., ELISA) for the 
etaA gene product or mutated versions of it, or immunoassay and 
chemical analysis of the drug metabolites, whereby the absence of the 
metabolites indicates gene mutation and impaired activating ability.
    Applications: Infectious diseases, diagnostics (bacterial); 
Infectious diseases, therapeutics (anti-bacterial).
    Advantages: Novel methods for diagnosing multidrug resistant 
tuberculosis that are much more rapid than conventional tests.
    Inventors: Clifton E. Barry III (NIAID), Andrea E. DeBarber 
(NIAID), Khisimuzi Mdluli (NIAID), et al.
    Publication: AE DeBarber et al. Ethionamide activation and 
sensitivity in multidrug-resistant Mycobacterium tuberculosis. Proc 
Natl Acad Sci U S A. 2000 Aug 15;97(17):9677-9682.
    Patent Status:
     U.S. Patent No. 6,905,822 issued 14 Jun 2005 (HHS 
Reference No. E-093-2000/0-US-02).
     U.S. Patent Application No. 11/058,484 filed 14 Feb 2005 
and allowed 17 Feb 2009 (HHS Reference No. E-093-2000/0-US-03).
    Licensing Status: Available for licensing.
    Licensing Contact: RC Tang, JD, LLM; 301-435-5031; 
[email protected]

A Novel Chimeric Protein for Prevention and Treatment of HIV Infection

    Description of Technology: This invention relates to bifunctional 
fusion proteins effective in HIV neutralization. Specifically, the 
invention is a genetically engineered chimeric protein composed of a 
soluble extracellular region of human CD4 (sCD4) attached via a 
flexible polypeptide linker to a single-chain construct of a human 
monoclonal antibody directed against a CD4-induced, highly conserved 
gp120 determinant involved in co-receptor interaction and virus entry. 
Mechanistically, the binding of the sCD4 moiety to the HIV gp120 Env 
glycoprotein induces a conformational change that enables the antibody 
moiety to bind, thereby blocking Env function and virus entry. This 
novel design provides the protein with unique characteristics that 
enable its extremely strong binding to gp120, thus rendering it a 
potential effective antiviral agent against HIV. Recent studies 
indicate that this novel bispecific protein displays extremely broad 
neutralizing activity against genetically diverse primary HIV-1 
isolates, with breadth much greater than previously described (Dey et 
al. J. Virology 2003). The potency is generally at least 10-fold 
greater than the best described HIV-1 neutralizing monoclonal 
antibodies, and the protein is highly active against many HIV-1 
isolates that are refractory to neutralization by these antibodies. 
Importantly, the protein is composed of almost entirely human 
sequences.
    The chimeric protein of this invention has considerable potential 
for prevention of HIV-1 infection, both as a topical microbicide and as 
a systemic agent to protect during and after acute exposure (e.g. 
vertical transmission, post exposure prophylaxis). It also has 
potential utility for treatment of chronic infection, including gene 
therapy strategies involving hematopoietic stem cells and/or viral 
vectors. Such proteins, nucleic acid molecules encoding them, and their 
production and use in

[[Page 27152]]

preventing or treating viral infections are claimed in the patents 
issued for this invention.
    Applications:
     Prophylactic and/or therapeutic treatment for HIV 
infection.
     Topical microbicide treatment to protect against HIV 
infection.
     Imaging of HIV infected cells in tissues.
    Advantages:
     High neutralization efficiency due to unique bifunctional 
binding characteristics.
     Potentially minimally immunogenic or toxic (human 
sequences and possibly low treatment doses).
     Broad neutralizing activity.
     Mechanism of action less susceptible to resistance.
    Development Status:
     Reproducible production and scale-up of chimeric protein 
has been demonstrated.
     Potent and broad neutralization of genetically diverse 
HIV-1 clinical isolates was demonstrated.
    Market: The race to develop effective antiviral strategies against 
HIV infection is ongoing. The problems exhibited by conventional drugs 
(i.e. toxicity and resistance) have triggered the pursuit of 
alternative approaches to HIV/AIDS prevention and treatment. One of the 
new approaches is the development of neutralizing antibodies against 
the HIV envelope proteins. This approach has not yet yielded any 
commercially viable treatment. It is believed that the approach 
presented in the subject invention will circumvent many of the 
shortcomings of the existing drugs and other pursued approaches. If 
this approach is successful the commercial rewards will be huge because 
of the global magnitude of HIV epidemics.
    Inventor: Edward A. Berger (NIAID).
    Publication: B Dey, CS Del Castillo, EA Berger. Neutralization of 
human immunodeficiency virus type 1 by sCD4-17b, a single-chain 
chimeric protein, based on sequential interaction of gp120 with CD4 and 
coreceptor. J Virol. 2003 March;77(5):2859-2865.
    Patent Status:
    HHS Reference No. E-039-1999/0--
     U.S. Patent No. 7,115,262, issued 03 October 2006.
     U.S. Application No. 11/535,957, filed 27 September 2006, 
published 18 October 2007 as 20070243208.
     Australian Patent No. 765218, issued 30 July 2003.
     Applications pending in Canada, France, Germany, Great 
Britain, Italy, Japan, Spain.
    Licensing Status: Available for licensing.
    Licensing Contacts: Uri Reichman, Ph.D, MBA; 301-435-4616; 
[email protected]; RC Tang, JD, LLM; 301-435-5031; [email protected].
    Collaborative Research Opportunity: The NIAID Office of Technology 
Development is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize ``A Novel Chimeric Protein for Prevention 
and Treatment of HIV Infection.'' Please contact Rick Williams at 301-
402-0960 for more information.

    Dated: June 1, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E9-13284 Filed 6-5-09; 8:45 am]
BILLING CODE 4140-01-P