[Federal Register Volume 72, Number 150 (Monday, August 6, 2007)]
[Notices]
[Pages 43647-43650]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-15208]


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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.

Immortalized Cell Line for Retroviral Studies

    Description of Technology: This technology describes immortalized 
human umbilical cord-blood T lymphocytes transformed with the 
retrovirus human T-cell leukemia-lymphoma virus (HTLV). These cells 
contain the HTLV genome and synthesize viral RNA but are restricted in 
their expression of viral structure proteins. This cell line should be 
useful in the study of retrovirus expression. Please visit the NIH AIDS 
Research and Reference Reagent Program Web site (http://www.aidsreagent.org; catalog #404) for additional information.
    Applications: Viral expression studies; Study of viral proteins and 
nucleic acids involved in T-cell immortalization.
    Inventors: Genoveffa Franchini (NCI).
    Publications:
    1. SZ Salahuddin et al. Restricted expression of human T-cell 
leukemia--lymphoma virus (HTLV) in transformed human umbilical cord 
blood lymphocytes. Virology 1983 Aug;129(1):51-64.
    2. NIH AIDS Research and Reference Reagent Program Web site.
    Patent Status: HHS Reference No. E-272- 2007/0--Research Tool.
    Licensing Status: Available for licensing.
    Licensing Contact: Susan Ano, Ph.D.; 301/435-5515; 
[email protected].

Device and Method for Protecting Against Coronary Artery Compression 
During Transcatheter Mitral Valve Annuloplasty

    Description of Technology: Catheter-based mitral valve 
regurgitation treatments that use a coronary sinus trajectory or 
coronary sinus implant can have unwanted effects because the coronary 
sinus and its branches have been found to cross the outer diameter of 
major coronary arteries in a majority of humans. As a result, pressure 
applied by any prosthetic device in the coronary sinus (such as tension 
on the annuloplasty device) can compress the underlying coronary artery 
and induce myocardial ischemia or infarction.
    Available for licensing and commercial development are devices and 
methods that avoid constricting coronary artery branches during 
coronary sinus-based annuloplasty. These devices and methods protect 
coronary artery branches from constriction during trans-sinus mitral 
annuloplasty. The device protects a coronary vessel from compression 
during mitral annuloplasty in which an annuloplasty element, such as a 
tensioning device, extends at least partially through the coronary 
sinus over a coronary artery. The device is a surgically sterile bridge 
configured for placement within the coronary sinus at a location where 
the coronary sinus passes over a coronary artery, so that the 
protection device provides a support for a mitral annuloplasty element, 
such as a compressive prosthesis, including a tension element when it 
is placed under tension. The protection device has an arch of 
sufficient rigidity and dimensions to support the tensioning element 
over the coronary artery, redistribute tension away from an underlying 
coronary artery, and inhibit application of pressure to the underlying 
artery, for example when an annuloplasty tension element is placed 
under tension during mitral annuloplasty.
    In particular, the protective device can be a support interposed in 
the

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coronary sinus between the annuloplasty device and the coronary artery. 
The device may be substantially tubular so that the tensioning element 
is contained within the protective device and supported in spaced 
relationship to the coronary artery. An arch may be configured to 
extend between a proximal end and a distal end that are substantially 
collinear with one another so that the ends form stabilizing members 
such as feet that retain the bridge in position over the coronary 
artery.
    The device may be used in methods of improving the function of a 
mitral valve in a subject in which an annuloplasty element, for example 
an element that exerts compressive remodeling forces on the mitral 
valve (such as a tensioning element), is introduced at least partially 
around the mitral valve, for example at least partially through the 
coronary sinus and over a coronary artery. The protective device is 
placed between the annuloplasty element and the coronary artery, with 
the annuloplasty element supported by the bridge of the device. 
Compressive remodeling forces are exerted by the annuloplasty device 
(for example by applying tension to alter the shape or configuration of 
the mitral valve annulus to reduce its circumference) while supporting 
the annuloplasty element on the bridge to inhibit application of 
pressure to the coronary artery. The function of the mitral valve in 
the patient is thereby improved without impairing coronary blood flow.
    The annuloplasty element can be introduced at least partially 
around the mitral valve by advancing the annuloplasty element in an 
endovascular catheter through the vascular system to the heart and 
introducing the annuloplasty element and the protective device from the 
catheter into the coronary sinus through a coronary sinus ostium. In 
those embodiments in which the protective device includes an internal 
lumen, the annuloplasty element extends through the lumen of the 
protective device over the coronary artery so that the annuloplasty 
element is supported by the protective device. The protective device 
can be integrated directly into the annuloplasty element, such as a 
resilient or expandable device, or a tensioning element or tensioning 
material.
    In other embodiments, this disclosure provides a method of 
improving function of a mitral valve in a subject who has mitral 
regurgitation by performing a mitral valve cerclage annuloplasty. In a 
particular disclosed example of the procedure, a guiding catheter is 
percutaneously inserted through the vasculature of a subject. The 
guiding catheter is introduced through the coronary sinus into the 
great cardiac vein, and a steerable microcatheter or other coaxial 
guiding catheter or steering device introduces a guidewire into a basal 
blood vessel such as the first septal coronary vein. From there the 
guidewire traverses under imaging guidance the septal myocardium or 
annulus fibrosis and reenters the right ventricle or right atrium. The 
guidewire is then retrieved using a vascular snare and the guiding 
catheter and guidewire are replaced with a tensioning system. The 
protective device is then introduced through the guiding catheter over 
or in tandem with the tensioning system so as to protect an underlying 
coronary artery when tension is introduced to perform the annuloplasty.
    Applications: Cardiac valve repair; Interventional Cardiology; 
Cardiac Surgery.
    Development Status: Early-stage; Pre-clinical data available; 
Prototype.
    Inventors: June-Hong Kim, Robert J. Lederman, Ozgur Kocaturk 
(NHLBI).
    Patent Status: U.S. Provisional Application No. 60/858,716 filed 14 
Nov 2006. (HHS Reference No. E-249-2006/0-US-01); U.S. Provisional 
Application No. 60/932,611 filed 31 May 2007 (HHS Reference No. E-249-
2006/1-US-01); The issued and pending patent rights are solely owned by 
the United States Government.
    Licensing Status: Available for licensing on an exclusive or non-
exclusive basis.
    Licensing Contact: Michael A. Shmilovich, Esq.; 301/435-5019; 
[email protected].
    Collaborative Research Opportunity: The NHLBI Cardiovascular Branch 
is seeking statements of capability or interest from parties interested 
in collaborative research to further development, evaluate, or 
commercialize catheter-based cardiovascular devices. Please contact Peg 
Koelble, NHLBI Office of Technology Transfer and Development, at 301-
594-4095 or [email protected].

A Shuttle Plasmid, Recombinant MVA/HIV1 Clinical Vaccine Constructs and 
a Mechanism for Enhanced Stability of Foreign Gene Inserts by Codon 
Alternation and for Insertion of the Foreign Gene Between Two Vaccinia 
Virus Essential Genes

    Description of Technology: Since the onset of the AIDS epidemic 
more than two decades ago, enormous efforts have been directed to 
making a vaccine that will protect against human immunodeficiency 
virus-1 (HIV); an effective vaccine is thought to require the induction 
of cellular and humoral responses. Vaccine candidates have included a 
variety of HIV immunogens delivered as DNA, attenuated poxviruses, 
adenoviruses, vesicular stomatitis virus, proteins, and various 
combinations thereof. The inventors' efforts to design an HIV vaccine 
have focused on modified vaccinia virus Ankara (MVA) as a vector.
    The patent application describes (1) The shuttle plasmid, pLW73, 
used for insertion of a foreign gene between two essential vaccinia 
virus genes (in this case, I8R, G1L), (2) an MVA/Ugandan Clade D (UGD) 
construct, and (3) an MVA/HIV 75 AG construct using pLW73 as a vector. 
Additionally, the invention provides two methods: (1) A method useful 
for large-scale production of recombinant vaccinia viruses, and (2) a 
method for stabilizing foreign gene inserts that undergo mutation after 
repeated passages, again useful in large-scale production of 
recombinant vaccinia viruses.
    Application: Immunization against HIV.
    Developmental Status: Vaccine candidates have been synthesized and 
preclinical studies have been performed. The vaccine candidates of this 
invention are slated to enter Phase I clinical trials in the next year.
    Inventors: Bernard Moss, Patricia Earl, Linda Wyatt (NIAID).
    Patent Status: U.S. Patent Application No. 60/840,093 filed 25 Aug 
2006 (HHS Reference No. E-248-2006/0-US-01); U.S. Patent Application 
No. 60/840,755 filed 28 Aug 2006 (HHS Reference No. E-248-2006/1-US-
01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Peter J. Soukas, J.D.; 301/435-4646; 
[email protected].

Molecular Probes for Identification or Isolation of Membrane Proteins

    Description of Technology: This technology describes a new class of 
molecular probes designed around an iodonaphthyl succinate antigen that 
can be used to label and tag proteins using a variety of conventional 
protein modification chemistries. The technology is offered as a 
combination of probe + monoclonal antibodies against the probe (three 
clones). The probe can be used for labeling and tagging cell surface 
and integral membrane proteins as well as soluble proteins. The 
monoclonal antibodies were tested and found effective for 
immunoprecipitation, western blot, and

[[Page 43649]]

flow cytometry. Once tagged, the modified proteins can be detected or 
isolated using an antibody reactive with the probe. Several possible 
probes and monoclonal antibodies that react with them are described. 
These probes and their corresponding antibodies have significant 
advantages over the biotin-avidin system.
    Advantages: Reversibility of binding for protein isolation; Lack of 
high, non-specific binding to cell surfaces; Ability to incorporate 
isotopic 125 I label in the probe for tracking tagged 
proteins in vivo.
    Applications: Protein labeling; Protein isolation.
    Development Status: In vitro data available.
    Inventors: Yossef Raviv et al. (NCI).
    Patent Status: U.S. Provisional Application No. 60/906,166 filed 09 
Mar 2007 (HHS Reference No. E-162-2006/0-US-01).
    Licensing Contact: Susan Ano, Ph.D.; 301/435-5515; 
[email protected].

Cross-protective Influenza Vaccine That Protects Against Lethal H5N1 
Challenge

    Description of Technology: Concerns about a potential influenza 
pandemic and its prevention are a regular part of health news, with 
bird (avian) influenza (prominently including H5N1 strains) being a 
major concern. Vaccination is one of the most effective ways to 
minimize suffering and death from influenza. Currently, there is not an 
effective way to vaccinate against avian influenza without knowing what 
subtype and strain will circulate. The technology described here 
relates to use of influenza A matrix 2 (M2) protein of a sequence 
derived from one subtype to induce immunity protective against 
infection with other subtypes, an approach made possible by the fact 
that M2 is highly conserved among different influenza strains. The M2 
component can be expressed from a DNA vaccine or recombinant viral 
vector, can be a protein or peptide, or can involve immunizing with one 
form and boosting with another, for example a DNA or viral vector 
followed by or preceded by a polypeptide. The M2 component can be used 
either alone or in combination with other influenza components, and can 
be administered with or without adjuvant. Specifically, mouse studies 
showed that the DNA vaccine priming followed by recombinant adenoviral 
boosting with constructs expressing M2 from an H1N1 strain protected 
against a lethal challenge with an H5N1 strain. Such cross-protection 
would be beneficial in a seasonal or pandemic influenza vaccine 
product. The current approach offers several advantages over 
traditional influenza vaccine approaches, including (a) ease and speed 
of production without need for eggs, (b) vaccine manufacture not based 
upon surveillance to determine dominant strain(s), and (c) 
effectiveness despite antigenic shift for the components HA and NA of 
circulating viruses.
    Application: Influenza vaccine.
    Development Status: Animal (mouse) data available.
    Inventors: Suzanne L. Epstein et al. (CBER/FDA).
    Patent Status: U.S. Provisional Application No. 60/786,152 filed 27 
Mar 2006 (HHS Reference No. E-076-2006/0-US-01); PCT Application No. 
PCT/US2007/007679 filed 27 Mar 2007 (HHS Reference No. E-076-2006/1-
PCT-01).
    Licensing Contact: Susan Ano, PhD; 301/435-5515; [email protected].
    Collaborative Research Opportunity: The Center for Biologics 
Evaluation and Research, Office of Cellular, Tissue, and Gene 
Therapies, Division of Cellular and Gene Therapies, Gene Therapy and 
Immunogenicity Branch, is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize matrix 2 (M2) vaccines protective against 
influenza A subtypes, including high-pathogenicity avian strains, 
differing from the strain from which the vaccine was derived. Please 
contact Dr. Suzanne Epstein at 301-827-0450 or 
[email protected] for more information.

Targeting Poly-Gamma-Glutamic Acid To Treat Staphylococcus Epidermidis 
and Related Infections

    Description of Invention: Over the past decade, Staphylococcus 
epidermidis has become the most prevalent pathogen involved in 
nosocomial infections. Usually an innocuous commensal microorganism on 
human skin, this member of the coagulase-negative group of 
staphylococci can cause severe infection after penetration of the 
epidermal protective barriers of the human body. In the U.S. alone, S. 
epidermidis infections on in-dwelling medical devices, which represent 
the main type of infection with S. epidermidis, cost the public health 
system approximately $1 billion per year. Importantly, S. epidermidis 
is frequently resistant to common antibiotics.
    Immunogenic compositions and methods for eliciting an immune 
response against S. epidermidis and other related staphylococci are 
claimed. The immunogenic compositions can include immunogenic 
conjugates of poly-[gamma]-glutamic acid (such as [gamma]DLPGA) 
polypeptides of S. epidermidis, or related staphylococci that express a 
[gamma]PGA polypeptide. The [gamma]PGA conjugates elicit an effective 
immune response against S. epidermidis, or other staphylococci, in 
subjects to which the conjugates are administered. A method of treating 
an infection caused by a Staphylococcus organism that expresses CAP 
genes is also disclosed. The method can include selecting a subject who 
is at risk of or has been diagnosed with the infection by the 
Staphylococcus organism which expresses [gamma]PGA from the CAP genes. 
Further, the expression of a [gamma]PGA polypeptide by the organism can 
then be altered.
    Application: Prophylactics against S. epidermidis.
    Developmental Status: Preclinical studies have been performed.
    Inventors: Michael Otto, Stanislava Kocianova, Cuong Vuong, Jovanka 
Voyich, Yufeng Yao, Frank DeLeo (NIAID).
    Publication: S Kocianova et al. Key role of poly-gamma-DL-glutamic 
acid in immune evasion and virulence of Staphylococcus epidermidis. J 
Clin Invest. 2005 Mar;115(3):688-694.
    Patent Status: PCT Patent Application No. PCT/US2006/026900 filed 
10 Jul 2006 (HHS Reference No. E-263-2005/0-PCT-02).
    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 National Institute of 
Allergy and Infectious Diseases, Laboratory of Human Bacterial 
Pathogenesis, is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize the use of poly-[gamma]-glutamic acid of 
staphylococci. Please contact Dr. Michael Otto at [email protected] 
for more information.

Improved Expression Vectors for Mammalian Use

    Description of Technology: This technology relates to improving 
levels of gene expression using a combination of a constitutive RNA 
transport element (CTE) with a mutant form of another RNA transport 
element (RTE). The combination of these elements results in a 
synergistic effect on stability of mRNA transcripts, which in turn 
leads to increased expression levels. Using HIV-1 gag as reporter mRNA, 
one mutated RTE in combination with a CTE was

[[Page 43650]]

found to improve expression of unstable mRNA by about 500-fold. 
Similarly this combination of elements led to synergistically elevated 
levels of HIV-1 Env expression. The function of CTEs and RTEs is 
conserved in mammalian cells, so this technology is a simple and useful 
way of obtaining high levels of expression of otherwise poorly 
expressed genes and can be used in a number of applications such as but 
not limited to improvements of gene therapy vectors, expression vectors 
for mammalian cells.
    Applications: Gene therapy; DNA vaccines; Protein expression.
    Development Status: In vitro data available.
    Inventor: Barbara Felber et al. (NCI).
    Patent Status: U.S. Utility Application No. 10/557,129, filed 16 
Nov 2005, from PCT Application No. PCT/US04/15776 filed 19 May 2004, 
which published as WO2004/113547 on 29 Dec 2004 (HHS Reference No. E-
223-2003/1-US-03).
    Licensing Status: Available for licensing.
    Licensing Contact: Susan Ano, PhD; 301/435-5515; [email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
Vaccine Branch is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize this technology. Please contact John D. 
Hewes, PhD at 301-435-3121 or [email protected] for more information.

    Dated: July 31, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E7-15208 Filed 8-3-07; 8:45 am]
BILLING CODE 4140-01-P