[Federal Register Volume 71, Number 65 (Wednesday, April 5, 2006)]
[Notices]
[Pages 17119-17121]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-4869]


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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.

Live Tissue Imaging Gel

Emily Rothstein (NHLBI).

[[Page 17120]]

HHS Reference No. E-328-2005/0--Research Tool.
Licensing Contact: Chekesha Clingman; 301/435-5018; 
[email protected].

    The National Heart Lung and Blood Institute (NHLBI), Laboratory of 
Cardiac Energetics, has created a gel with 0.3%-0.5% carbomer 940 which 
is easily used as an imaging immersion medium for confocal and two 
photon fluorescence emission microscopy and second harmonic generation 
imaging. This thick, but transparent, gel can be layered on tissue for 
microscopic analysis and retain the connection between the objective 
and tissue at a large working distance without supplementary retention. 
The thickness of the gel allows for optimal positioning on tissue for 
imaging in the living animal, which eliminates the frustrations 
associated with imaging using thinner gels and fluid.
    This thick gel can be used by microscopists and pathologists for 
imaging tissue in a living animal. Also, this gel can be used for skin 
screening as an alternative to biopsy for image analysis of tissue 
structure, thus saving diagnosis time and patient discomfort.

The Medusa\TM\ Sequencer: A Sequencing Machine the Size of a Molecule 
That Could Sequence RNA in a Living Cell

Thomas D. Schneider, Ilya G. Lyakhov, and Danielle Needle (NCI).
U.S. Provisional Application No. 60/749,729 filed December 12, 2005, 
entitled ``Probe for Nucleic Acid Sequencing and Methods of Use'' (HHS 
Reference No. E-194-2005/0-US-01).
Licensing Contact: Cristina Thalhammer-Reyero; 301/435-
4507;[email protected].

    Available for licensing and commercial development is the 
Medusa\TM\ Sequencer, a single-molecule sequencing device that consists 
of a DNA (or RNA) polymerase attached to a set of four flexible arms. 
The tip of each arm carries a nonhydrolyzable nucleotide and a 
spectrally distinct Forster Resonance Energy Transfer (FRET) acceptor 
fluorophore. A donor fluorophore attached to the polymerase can excite 
the acceptor fluorophores by FRET. A Medusa\TM\ Sequencer binds to a 
DNA primer hybridized to the DNA or RNA to be sequenced. The four arms 
with nucleotide tips ``test'' the polymerase pocket and the arm that 
has the nucleotide tip complementary to the unknown base of the 
sequence will dwell longer than the other three that are not 
complementary. However, the polymerase will not incorporate the 
nucleotide on the tip of the arm into the nascent strand because the 
nucleotide is nonhydrolyzable. FRET between the donor and the acceptor 
fluorophore at the arm tip produces a characteristic spectrum that 
identifies the bound base. Free hydrolyzable dNTPs (or NTPs) allow the 
Medusa\TM\ Sequencer to step forward. The series of FRET signals 
reveals the unknown nucleotide sequence. A Medusa\TM\ Sequencer could 
also be injected into a cell to read mRNA sequences inside a living 
organism. Coded versions of the Medusa\TM\ Sequencer can signal when 
the device has been damaged.
    The benefits of the Medusa\TM\ Sequencer include: (a) Simplicity, 
only one reagent required; (b) accuracy for counting individual mRNAs 
or DNAs; (c) low error rate per base, and this can be improved by 
modifying the polymerase; (d) speed, a single microscope can be used to 
obtain many sequences in parallel; (e) exceptionally low cost per 
sequencing device; and (d) could be used in the clinic along with 
sequence walkers to analyze patient's genetic diseases (e.g. Medical 
Applications of Sequence Walkers: ABCR Mutation G863A, http://
www.ccrnp.ncifcrf.gov/~toms/g863a.html).
    The technology is further described at http://
www.ccrnp.ncifcrf.gov/~toms/patent/medusa.
    The National Institutes of Health, National Cancer Institute, 
Center for Cancer Research Nanobiology Program is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize the Medusa\TM\ 
Sequencer. Please contact Melissa Maderia at 301/846-5465 (phone), 301/
846-6820 (fax), [email protected] (e-mail) for more information.

Nanoprobes for Detection or Modification of Molecules

Ilya G. Lyakhov, Thomas D. Schneider, and Danielle Needle (NCI).
U.S. Provisional Application No. 60/749,858 filed December 12, 2005 (E-
195-2005/0-US-01).
Licensing Contact: Cristina Thalhammer-Reyero; 301/435-4507; [email protected].

    Available for licensing and commercial development are the ``Rod-
tether Nanoprobes'', devices consisting of a rigid molecular rod with a 
flexible molecular tether attached at each end that can be used to 
detect and/or modify molecules. Each tether tip has a functional group, 
such as an antibody or oligonucleotide, that recognizes a target 
molecule. In addition, one tip carries a donor fluorophore and the 
other carries an acceptor fluorophore. The fluorophores form a pair for 
Forster Resonance Energy Transfer (FRET). In the absence of the target 
molecule, the rod keeps the tether arms apart most of the time, while 
in the presence of the target molecule, both recognizers bind to the 
target. This holds the donor and acceptor fluorophores close together. 
Illumination with light excites the donor and the energy is transferred 
by FRET to the nearby acceptor, which emits a detectable signal. By 
reducing an ELISA-like assay entirely to the molecular level, complex 
macroscopic or microfluidic washing and pumping systems can be 
eliminated. Rod-tether Nanoprobes can detect a wide variety of clinical 
and biowarfare reagents. The nanoprobes can also be used to rapidly and 
simply detect, modify and/or destroy endogenous molecules such as 
proteins and mRNA involved in a broad range of diseases. The simplest 
ssDNA-detecting nanoprobe has been created.
    The benefits of the Rod-Tether Nanoprobes include: (a) Simplicity, 
only one reagent required and complicated and expensive microfluidic 
chips are eliminated (see BioTechniques Jan 2006, 40:1:85-90); (b) 
reduction of ELISA, Southern, Northern and Western assays to single 
molecules; (c) speed, only a single molecular reaction is required to 
detect a target molecule; (d) exceptionally low cost per device; (e) 
could be used in the clinic to instantaneously analyze patient's blood 
and detect genetic diseases; and (f) could be used to detect biowarfare 
agents instantaneously.
    The technology is further described at http://
www.ccrnp.ncifcrf.gov/~toms/patent/nanoprobe/.
    The National Institutes of Health, National Cancer Institute, 
Center for Cancer Research Nanobiology Program is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize Rod-Tether 
Nanoprobes. Please contact Melissa Maderia at 301/846-5465 (phone), 
301/846-6820 (fax), [email protected] (e-mail) for more 
information.

A Novel MRI Adiabatic T2 Preparation Sequence With Reduced 
B1 Sensitivity

Reza Nezafat (NHLBI).
U.S. Patent Application No. 11/147,151 filed June 6, 2005 (HHS 
Reference No. E-073-2005/0-US-02).
Licensing Contact: Chekesha Clingman; 301/435-5018; 
[email protected].


[[Page 17121]]


    This invention relates to a novel magnetic resonance angiography 
(MRA) method that accomplishes uniform contrast enhancement between 
coronary arteries and the surrounding tissue across the entire imaging 
volume. The disclosed technique utilizes an adiabatic refocusing 
transverse relaxation time (T2)-preparation pulse sequence, 
in which the magnetization is tipped into the transverse plane with a 
hard radio-frequency (RF) pulse and refocused using a pair of adiabatic 
fast-passage RF pulses. The isochromats are subsequently returned to 
the longitudinal axis using a hard RF pulse. Simulations and in vivo 
images acquired with the T2-Prep sequence illustrate 
excellent suppression of artifacts originating from B1 
inhomogeneity while achieving contrast-to-noise (CNR) enhancement 
between coronary arteries and surrounding tissues. Furthermore, images 
acquired with the T2-Prep sequence show suppression of the 
banding artifacts and improvement of the visual sharpness of distal 
segments of the coronaries as compared to images acquired without the 
T2-Prep sequence.

Novel Methods and Compositions for Diagnosing AIDS and Other Diseases 
Involving Immune System Activation

Gene M. Shearer and Jean-Philippe Herbeuval (NCI).
U.S. Provisional Application No. 60/564,588 filed April 23, 2004 (HHS 
Reference No. E-045-2004/0-US-01) and U.S. Provisional Application No. 
60/634,255 filed December 12, 2004 (HHS Reference No. E-045-2004/1-US-
01), combined into PCT/US2005/13554 filed April 21, 2005 (HHS Reference 
No. E-045-2004/2-PCT-01).
Licensing Contact: Cristina Thalhammer-Reyero; 301/435-4507; 
[email protected].

    Available for licensing and commercial development are methods and 
compositions suitable for monitoring the progression of AIDS and other 
diseases whose progression involves immune system activation in 
mammals, such as cancer, atherosclerosis, Alzheimer's disease, 
inflammation, autoimmune disorder, allergic asthma, Crohn's disease, 
Grave's disease, lupus, multiple sclerosis, Parkinson's disease, 
allograft transplant rejection, and graft vs. host disease.
    In particular, the invention relates to the use of the TRAIL (TNF-
related apoptosis-inducing ligand) and TRAIL compounds to monitor the 
progression of AIDS, and such other diseases. This is accomplished by 
assessing the presence or concentration of TRAIL, especially mTRAIL, 
sTRAIL, the TRAIL DR5 receptor molecule, and biological molecules that 
activate TRAIL or its receptor. These biological molecules include p53, 
alpha- and beta-interferon, as well as additional compounds such as 
CD69 and HLA-DR. Also claimed are kits for immunoassays to determine 
the presence or concentration of a TRAIL compound in a biological 
fluid, suitable for determining whether the mammal suffers from any of 
the above diseases.
    TRAIL can be used as a new surrogate biomarker to monitor the 
progression of HIV infection and other conditions and diseases 
associated with immune system activation. In the case of HIV infection, 
measuring levels of this biomarker can distinguish among infected 
individuals with high viral load, infected individuals with low viral 
load, and uninfected individuals. Only two surrogate markers are 
currently recognized by the Food and Drug Administration as clinically 
relevant to HIV progression, HIV viral load and the absolute number of 
peripheral CD4+ T cells. Tests for assessing HIV viral load employ PCR, 
the use of which has drawbacks, including cross-contamination. TRAIL 
has mechanistic implications for HIV-1 pathogenesis and directly 
correlates to viral load but not necessarily inversely with CD4+ T cell 
count. Other surrogate markers have been proposed but do not 
consistently reflect AIDS progression in all individuals or may result 
in overlooking possible treatments that may affect disease progression 
but do not affect the chosen marker. Therefore, use of this new 
biomarker to assess disease progression in infected individuals and to 
evaluate the effectiveness of various treatment regimens has several 
advantages over currently used methods, since TRAIL is a death molecule 
involved in CD4+ T cell depletion in HIV/AIDS. TRAIL, its receptor, and 
activating molecules can all be used as sensitive markers for CD4 T 
cell activation and apoptosis.
    The technology is further described at:
    1. Herbeuval JP, Hardy AW, Boasso A, Anderson SA, Dolan MJ, Dy M, 
Shearer GM. Regulation of TNF-related apoptosis-inducing ligand on 
primary CD4+ T cells by HIV-1: role of type I IFN-producing 
plasmacytoid dendritic cells. Proc Natl Acad Sci U S A. September 27, 
2005;102(39):13974-9.
    2. Herbeuval JP, Grivel JC, Boasso A, Hardy AW, Chougnet C, Dolan 
MJ, Yagita H, Lifson JD, Shearer GM ``CD4+ T-cell death induced by 
infectious and noninfectious HIV-1: role of type 1 interferon-
dependent, TRAIL/DR5-mediated apoptosis'' Blood. November 15, 
2005;106(10):3524-31.
    3. Herbeuval JP, Boasso A, Grivel JC, Hardy AW, Anderson SA, Dolan 
MJ, Chougnet C, Lifson JD, Shearer GM ``TNF-related apoptosis-inducing 
ligand (TRAIL) in HIV-1-infected patients and its in vitro production 
by antigen-presenting cells'' Blood. March 15, 2005;105(6):2458-64.

Vessel Delineation in Magnetic Resonance Angiographic Images

Peter Yim (CC).
U.S. Patent No. 7,003,144 issued February 21, 2006 (HHS Reference No. 
E-229-1999/0-US-04).
Licensing Contact: Michael Shmilovich; 301/435-5019; 
[email protected].
    This invention relates to advances in magnetic resonance 
angiography (MRA) or the imaging of blood vessels in the body for the 
evaluation of vascular pathology. Presented are new methods for 
processing magnetic resonance angiographic images, or angiograms, to 
delineate certain vessels in an angiogram. These methods find 
particular utility in highly vascular regions of the body such as the 
cerebrum, heart, abdomen and extremities where there is extensive 
overlapping and variation in the size of the vessels. Current MRA 
methods are unable to generate high-resolution images of complex vessel 
geometries in these dynamic environments. The patent application for 
this invention covers algorithms and computer-implemented methods for 
tracking the paths of vessels in magnetic resonance angiography. Also 
covered are similar methods for digital image processing in alternative 
imaging technologies such as tomography and X-ray angiography.

    Dated: March 28, 2006.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E6-4869 Filed 4-4-06; 8:45 am]
BILLING CODE 4140-01-P