[Federal Register Volume 74, Number 27 (Wednesday, February 11, 2009)]
[Notices]
[Pages 6906-6909]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-2820]


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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.

HTLV-II Vector and Methods of Use

    Description of Technology: The invention hereby offered for 
licensing is in the field of vaccines and vaccine vectors. More 
specifically the invention provides compositions and methods of use of 
HTLV-II viral vector. The vector comprises at least a portion of the 
HTLV-II genome encoding the gag, pro, and pol genes and lacking all or 
a portion of the pX region. A heterologous gene is inserted within the 
deletion of the pX region. The gene of interest may encode all or a 
portion of a protein that corresponds to a viral protein of a foreign 
virus. The viral vectors thus constructed are useful for inducing 
immune response to the viral protein from the foreign virus. In 
particular the invention claims vaccines against HIV and SIV.
    Applications: The technology can be used for DNA-based vaccines.
    Advantages:
     Vaccines based on HTLV-II vectors have exhibited the 
capability to eliciting T cell response effectively. In particular they 
induce specific CD4+ and CD8+ T cell response. Antibody response to the 
HTLV-II vector is almost undetectable. The vector is infectious, but 
highly attenuated, with respect to the wild type HTLV-II. Desirably, 
the HTLV-II viral vector induces antibodies that can participate in 
Antibody-Dependent-Cell-Mediated Cytotoxicity (ADCC), a mechanism that 
enhances its effectiveness.
     Most of the T-cell vaccines developed for HIV are based on 
microbial vectors that have limited replication capacity and do not 
persist in the host. Such vaccines do not protect macaques from SIV 
infection and their ability to protect against high virus load is 
merely transient (approximately six months). They are perceived to 
elicit too ``small T-cell responses'' that expand ``too late''. In 
addition, few of these vectors target mucosal sites, the first portal 
of HIV entry. In contrast, an HTLV-II based vaccine is anticipated to 
infect macaques and replicate at very low level in lymphoid tissue and 
particularly in the gut which may enable them to maintain sufficient 
level of effectors CD8 memory cells to decrease early seeding of the 
virus, and sufficient level of central memory cells in lymph nodes that 
may limit the broadcasting of the virus at distal sites. These features 
make an HTLV-II based vaccine for HIV an excellent unique candidate to 
target mucosal tissues and provide long lasting mucosal immunity to 
HIV. In addition, the HTLV-II infects dendritic cells both in vivo and 
in vitro, and the HTLV-II infected dendritic cells have a mature 
phenotype, suggesting that HIV antigens expressed within dendritic 
cells could be effectively presented to the immune system.
     HTLV-II is a human retrovirus with no clear disease 
associations neither in healthy nor in HIV infected individuals.
     HTLV shares many biological and molecular characteristics 
of HIV, including routes of transmission, a T-cell tropism and gut 
tropism.
     Based on the above, it is believed that HIV vaccines based 
on HTLV-II vector will exhibit superiority compared to other vaccines 
in development.
    Development Status: At the present only in vitro as well as animal 
(macaques) data that demonstrate the

[[Page 6907]]

proof of concept are available. The data indicates that an HTLV-II 
based vaccine could replicate in the appropriate body compartment and 
confer immunity in humans. The inventors continue to work on the 
development of this approach.
    Market: In spite of major global efforts of more than 25 years in 
developing a vaccine against HIV/AIDS, such a vaccine is still not in 
existence but yet very much needed for the fight against the global 
epidemic of HIV/AIDS. The market for HIV/AIDS drugs is currently at the 
level of approximately $6 billion a year and is expected to grow to $13 
billion by the year 2015. Should an effective vaccine be developed the 
market for such a vaccine may exceed this level. The instant technology 
may offer superiority to existence approaches in the area of HIV 
vaccines and thus a huge commercial opportunity for pharmaceutical/
vaccine enterprises as well as a major contribution for global public 
health.
    Inventors: Genoveffa Franchini, Izabela Bialuk, Vibeke Andresen, 
Shari Gordon, Valentina Cecchinato, Francis Ruscetti, Kathryn Jones 
(NCI).
    Publications: Paper in preparation.
    Patent Status: U.S. Provisional Application No. 61/081,994 filed 18 
Jul 2008 (HHS Reference No. E-269-2008/0-US-01).
    Related Technologies: RhCMV SIV vaccine (Picker et al.).
    Licensing Status: The technology is available for exclusive or non-
exclusive licensing.
    Licensing Contact: Uri Reichman, Ph.D., MBA; 301-435-4616; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Animal Models & Retroviral Vaccine Section, is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize HTLV-II 
vectored HIV vaccines. Please contact John D. Hewes, Ph.D. at 301-435-
3121 or [email protected] for more information.

Adoptive Immunotherapy for Reestablishing HIV-specific Cytotoxic T-cell 
(CD8 T-cell) Function in HIV and AIDS Patients and Methods for 
Assessing the Reestablishment of CD8 T-cell Function

    Description of Technology: This technology includes methods and 
compositions for rescuing or reestablishing the ability of HIV-
specific, cytotoxic T-cells (CD8 T-cells) to proliferate and kill HIV-
infected cells such as CD4 cells. Additionally, this invention provides 
a means for evaluating the ability of therapeutic vaccines or other 
therapies to reestablish CD8 T-cell function during HIV infection. As 
an immunotherapy, this technology involves treating peripheral blood 
mononuclear cells (PBMCs) from an HIV or AIDS patient to reestablish 
CD8 T-cell function and returning the treated cells to the patient. It 
is anticipated that this technology could provide an alternative to 
antiretroviral therapy (ART).
    Background: This technology arose from research aimed at 
understanding why HIV infection does not progress in a subset of HIV-
infected individuals, called long-term nonprogressors (LTNP). During 
the course of HIV infection HIV-specific CD8 T-cells from HIV 
progressors lose the ability to proliferate and kill HIV-infected cells 
using cytotoxins such as perforin and granzymes A and B. Unlike HIV 
progressors, it has been shown that CD8 T-cells from LTNP retain the 
ability to proliferate and use cytotoxins to kill HIV-infected cells. 
This technology provides a means for rescuing HIV-specific CD8 T-cell 
proliferation and cytotoxic functions in HIV progressors.
    Applications:
     Treatment of HIV infection
     Assessing the effectiveness of therapeutic vaccines or 
other immune therapies
    Advantages:
     Novel strategy for treating HIV infection
     Direct measure of the reestablishment of CD8 T-cell 
function
     Alternative to ART
    Development Status: In vitro data available. Primate studies are 
underway.
    Market:
     HIV therapeutics
     Immunotherapy and therapeutic vaccine development
    Inventors: Mark Connors and Stephen Migueles (NIAID).
    Publication: SA Migueles et al. Lytic granule loading of CD8+ T 
cells is required for HIV-infected cell elimination associated with 
immune control. Immunity. 2008 Dec 29;29(6):1009-1021.
    Patent Status: U.S. Provisional Application No. 61/070,849 filed 27 
Mar 2008 (HHS Reference No. E-146-2008/0-US-01).
    Licensing Status: This invention is available for exclusive or non-
exclusive licensing.
    Licensing Contact: Sally Hu, Ph.D.; 301-435-5606, [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 this technology. Please contact Richard 
Williams at 301-451-3522 for more information.

Humanized Monoclonal Antibodies That Specifically Bind Japanese 
Encephalitis Virus (JEV) and Their Use

    Description of Technology: Japanese encephalitis virus (JEV) is the 
prototype virus of the Japanese encephalitis (JE) group belonging to 
the Flavivirus genus of the Flaviviridae family. Other members of the 
group include Kunjin virus, St. Louis encephalitis virus, and West Nile 
encephalitis virus (WNV). JEV is widely distributed in South Asia, 
Southeast Asia, and the Asian Pacific Rim. In recent years, JE 
epidemics have spread to previously unaffected areas, such as northern 
Australia, Pakistan, India and Indonesia. The JE outbreak in India 
during July to November of 2005 was the longest and most severe in 
recent years, affecting more than 5,000 persons and causing more than 
1,000 deaths. It is estimated that JEV causes 35,000 to 50,000 cases of 
encephalitis, including 10,000 deaths and as many neurologic sequelae, 
each year. The wide geographical distribution and the existence of 
multiple strains, coupled with the high rate of mortality and residual 
neurological complications in survivors, make JEV infection an 
important public health problem. Until a JEV vaccine becomes generally 
available, passive immunization with potently neutralizing anti-JEV 
antibodies remains an attractive strategy for short-term prevention of 
and therapeutic intervention in encephalitic JEV infections.
    From a panel of 11 Fabs recovered by different panning strategies, 
three highly potent neutralizing antibodies, termed Fabs A3, B2, and 
E3, which recognized spatially separated regions on the JEV virion were 
identified. These antibodies reacted with epitopes in different 
domains: The major determinant for Fab A3 was Lys179 (domain I), that 
for Fab B2 was Ile126 (domain II), and that for Fab E3 was Gly302 
(domain III) in the envelope protein, suggesting that these antibodies 
neutralize the virus by different mechanisms. These three Fabs and 
derived humanized monoclonal antibodies (MAbs) exhibited high 
neutralizing activities against a broad spectrum of JEV genotype 
strains. In preclinical testing, the monoclonal antibodies of the 
technology significantly prolonged the average survival time compared 
to the control group, suggesting a therapeutic potential for use of MAb 
B2 in humans.
    This application claims the antibodies described above, methods of 
preventing

[[Page 6908]]

and/or treating JEV with the antibodies, and diagnostics using the 
antibodies of the technology.
    Application: Development of Japanese Encephalitis Virus (JEV) 
vaccines, therapeutics and diagnostics.
    Development Status: Monoclonal antibodies have been synthesized and 
preclinical studies have been performed.
    Inventors: Ana P. Goncalvez, Robert H. Purcell, Ching-Juh Lai 
(NIAID).
    Publication: AP Goncalvez et al. Humanized monoclonal antibodies 
derived from chimpanzee Fabs protect against Japanese encephalitis 
virus in vitro and in vivo. J Virol. 2008 Jul;82(14):7009-7021.
    Patent Status: U.S. Provisional Application No. 61/123,905 filed 10 
Apr 2008 (HHS Reference No. E-142-2008/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; 
[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 ``Humanized Monoclonal Antibodies that 
Specifically Bind Japanese Encephalitis Virus (JEV) and Their Use''. 
Please contact Percy Pan at 301-451-3523 for more information.

Sialostatin Mediation Controls Blood-Feeding Success of the Tick Ixodes 
scapularis

    Description of Technology: This invention offers an environmentally 
friendly alternative to existing acaricides (pesticides), and relates 
to vaccines against tick bites and the pathogens that the ticks may 
transmit.
    Bites from the nymphal stage of Ixodes scapularis are associated 
with Lyme disease transmission in disease-endemic areas of central and 
eastern US. Ixodes scapularis nymphs are the key vector stage 
implicated in Lyme disease transmission, mainly due to their small size 
that makes timely detection difficult. Guinea pig vaccination against 
sialostatin L2, a secreted Ixodes scapularis salivary protein, can 
confer nymphal recognition and protection against the tick. Increased 
rejection rates, prolonged feeding time, and inflammation were observed 
in the vaccine group, indicating that a protective host immune response 
was elicited. Moreover, anti-sialostatin L2 titers correlate with 
weight reduction of nymphs by the end of feeding. These studies suggest 
that an essential action of sialostatin L2 can be blocked by host 
humoral immunity.
    Applications: Use of Sialostatin L2 in a multi-component vaccine to 
protect against tick bites, and the pathogens that the ticks may 
transmit.
    Advantages:
     Sialostatin L2 as an anti-tick vaccine will target the 
vector and therefore confer protection against all the pathogens that 
may be transmitted by the vector.
     An environmentally friendly alternative to acaricides.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Market: Tick-borne diseases have alarmingly increased over the past 
years worldwide, affecting both human and animal populations. Lyme 
borreliosis is the most common and prevalent vector-borne human illness 
throughout the northern hemisphere. In the U.S., Lyme disease cases are 
steadily on the rise, exceeding the 23,000 reported to the CDC in 2005; 
while in Europe, the estimated cases are more than 50,000, making it a 
growing public health problem. Apart from transmitting the Lyme agent, 
the same tick species, of the genus Ixodes, serve as vectors for a 
repertoire of other human disease pathogens, such as viruses that cause 
tick-borne encephalitis, protozoa that cause babesiosis, and bacteria 
that cause granulocytic anaplasmosis, Q-fever, and Mediterranean 
spotted fever.
    Inventors: Michalis Kotsyfakis (NIAID), Jos[eacute] M.C. Ribeiro 
(NIAID), Jesus G. Valenzuela (NIAID), John Andersen (NIAID), Jennifer 
Anderson (NIAID), et al.
    Publications:
    1. M Kotsyfakis et al. Cutting edge: Immunity against a ``silent'' 
salivary antigen of the Lyme vector Ixodes scapularis impairs its 
ability to feed. J Immunol. 2008 Oct 15;181(8):5209-5212.
    2. M Kotsyfakis et al. Selective cysteine protease inhibition 
contributes to blood-feeding success of the tick Ixodes scapularis. J 
Biol Chem. 2007 Oct 5;282(40):29256-29263.
    3. M Kotsyfakis et al. Antiinflammatory and immunosuppressive 
activity of sialostatin L, a salivary cystatin from the tick Ixodes 
scapularis. J Biol Chem. 2006 Sep 8;281(36):26298-26307.
    Patent Status:
     U.S. Provisional Application No. 60/963,332 filed 02 Aug 
2007 (HHS Reference No. E-289-2007/0-US-01).
     PCT Patent Application No. PCT/US08/09075 filed 25 Jul 
2008 (HHS Reference No. E-289-2007/1-PCT-01).
    Licensing Status: Available for licensing.
    Licensing Contact: RC Tang, JD, LLM; 301-435-5031; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Allergy and Infectious Diseases/Laboratory of Malaria and Vector 
Research/Vector Biology Section is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize potential applications based on the 
above mentioned patent and in regard to the protection from tick bites 
and the pathogens they transmit. Please contact Charles Rainwater, 
NIAID/OTD at 301-435-8617/or [email protected] for more 
information.

A Parameterized Model for Simulating Microarrays

    Description of Invention: The current invention describes a 
simulation procedure in which several parameters can be used to model 
microarray image formation. Over 20 model parameters, each governed by 
a probability distribution, control the signal intensity, spot 
geometry, spot drift, background effects, and the many kinds of noise 
that affect microarray images as a result of the manner in which they 
are formed. In practice, a simulated microarray image is generated 
according to a number of defined parameters and can be compared to a 
known value. An imaging procedure is then applied to the simulated 
microarray image to generate observed values. The known values can then 
be compared to the observed values to evaluate the imaging procedure.
    The model can be used to measure the performance of imaging 
procedures designed to measure the true intensity of spots on 
microarrays. Modeling and simulation of microarray image formation is a 
key to benchmarking various signal processing tools being developed to 
estimate cDNA signal spots. Using a model to describe the true signal 
intensity not only helps in evaluating these tools, but also 
facilitates the understanding of various process interactions. The 
simulation program has been used extensively in the design of the 
microarray image-analysis program used at the National Human Genome 
Research Institute (NHGRI). This has been done by testing the accuracy 
of the analysis program on simulated images exhibiting troublesome 
noise conditions and then tuning the program to achieve better results.
    The simulation procedure can be incorporated into hardware/software 
for

[[Page 6909]]

ease of use. The levels of foreground noise, background noise, and spot 
distortion can be set, and algorithms can be evaluated under varying 
conditions.
    Applications:
     Microarray imaging
     Evaluation of gene expression
    Advantages:
     Efficient and accurate microarray signal analysis
     Improved detection of weak targets and improved local 
background estimation for microarray spots
    Development Status: Late stage.
    Inventors: Yidong Chen (NHGRI) et al.
    Publication: Y Balagurunathan, ER Dougherty, Y Chen, ML Bittner, JM 
Trent. Simulation of cDNA microarrays via a parameterized random signal 
model. J Biomed Opt. 2002 Jul;7(3):507-523.
    Patent Status: U.S. Patent No. 7,363,169 issued 22 Apr 2008 (HHS 
Reference No. E-089-2003/0-US-03).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Jeffrey A. James, PhD; 301-435-5474; 
[email protected].

System for Synergistic Combination of Multiple Automatic Induction 
Methods and Automatic Re-Representation of Data

    Description of Invention: The present application describes a 
unique prototype of an advanced framework which relates to the field of 
multidimensional data mining, machine learning, and analysis that has 
been named COEV (for COEVolutional). COEV synergistically combines 
different methods of statistical analysis, neural networks, decision 
trees and genetic algorithms for the resolution of data queries. COEV 
automatically determines the optimal methods and data representations 
to apply at each step of inquiry and, as a result, can provide outcomes 
that are significantly more accurate than can be achieved by use of any 
one methodology alone. The invention uses an evolutionary learning 
technology to improve predictive outcomes with continued use. COEV is 
designed to advance the accuracy, flexibility, speed and ease of use of 
advanced data analysis technologies.
    Characteristics of problems that are appropriate for the 
application of the COEV method are: (1) Appropriate for machine 
learning, in that there is a well-defined set of input variables and a 
clear prediction target; (2) difficult for traditional methods, and 
where a modest improvement in accuracy over existing machine learning 
methods (e.g., neural networks) would be significant; (3) there is a 
large amount of training data, ideally thousands of cases.
    Possible application areas of interest include the analysis of 
high-throughput screening data for pharmaceutical discovery, detecting 
patterns of fraud in insurance claims, or automating screening of 
medical images.
    This invention requires further R&D and testing to make it a 
practical system for widespread use.
    Applications:
     Machine learning
     High throughput screening analysis for pharmaceutical, 
biotechnology, and other industries
    Advantages:
     More accurate interpretation and analysis of complex data 
networks
     Improved predictive outcomes with continued use 
(evolutionary learning)
    Development Status: Early stage.
    Inventors: Lawrence Hunter (NLM).
    Patent Status: U.S. Patent No. 6,449,603 issued 10 Sep 2002 (HHS 
Reference No. E-118-1996/0-US-03).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Jeffrey A. James, PhD; 301-435-5474; 
[email protected].

Computational Analysis of Nucleic Acid Information Defines Binding 
Sites

    Description of Invention: Many approaches to determine whether a 
nucleotide change is a benign polymorphism or is associated with a 
genetic disease rely on sequence comparisons of a substantial number of 
individuals. This invention embodies a computational method that is 
able to predict whether a nucleotide change will have a deleterious 
effect. The claims of this invention relate to a computer program which 
has the novel feature in that it is designed to calculate the relative 
importance of a given nucleotide change. This program is unique in that 
it is capable of predicting the effect that a given nucleotide change 
would have on a particular sequence such as a known binding site. The 
method has been successfully applied to predicting the effects of 
changes at human splice junctions.
    Further information is available at http://www.ccrnp.ncifcrf.gov/
~toms/walker/index.html.
    Applications:
     Predictive outcomes for genetic mutations
     Biomedical research
    Development Status: Late stage.
    Inventors: Thomas D. Schneider (NCI) et al.
    Patent Status: U.S. Patent 5,867,402 issued 02 Feb 1999 (HHS 
Reference No. E-080-1995/0-US-01).
    Licensing Status: Available for non-exclusive licensing.
    Licensing Contact: Jeffrey A. James, PhD; 301-435-5474; 
[email protected].

    Dated: January 30, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E9-2820 Filed 2-10-09; 8:45 am]
BILLING CODE 4140-01-P