[Federal Register Volume 69, Number 90 (Monday, May 10, 2004)]
[Notices]
[Pages 25913-25915]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-10495]


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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, DHHS.

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/

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496-7057; fax: 301/402-0220. A signed Confidential Disclosure Agreement 
will be required to receive copies of the patent applications.

Rapid Integration Site Mapping

Shawn Burgess (NHGRI).
U.S. Provisional Application filed 20 Apr 2004 (DHHS Reference No. E-
027-2004/0-US-01).
Licensing Contact: Michael Ambrose; 301/594-6565; 
[email protected].

    This invention describes a novel method for mapping retroviral 
integration sites within genomic DNA. The invention provides for rapid 
integration profiling with reduced labor and time required and reduces 
the inherent biases resulting from other techniques.
    The technology uses pre-selected frequent cutting restriction 
enzymes and proprietary linkers to produce smaller amplicons that, in 
practice, reduce the bias effects of other more commonly used mapping 
techniques that often include linear amplification as a first step. 
Further, the technology does not require the use of measurable 
phenotypic characteristics to analysis or distinguish integration 
events. Thus, knowledge of potential cellular changes is not required. 
This invention can be used to provide rapid, cost-effective screening 
of cells treated with retroviruses for gene therapy. The ability to 
identify potentially harmful integrations and eliminating them from 
therapeutic use is essential for safer gene therapy applications.
    Additional information may be found in X. Wu et al., 
``Transcription Start Regions in the Human Genome are Favored Targets 
for MLV Integration'', Science Jun 13 2003 300:1749-1751.

Novel Method of Fat Suppression in Steady State Free Precession (SSFP) 
Based Magnetic Resonance Imaging (MRI)

John Derbyshire, Daniel Herzka, Elliot McVeigh (NHLBI).
U.S. Provisional Application filed 08 Mar 2004 (DHHS Reference No. E-
237-2003/0-US-01).
Licensing Contact: Michael Shmilovich; 301/435-5019; 
[email protected].

    Available for licensing is a technique for improving magnetic 
resonance imaging (MRI) that employs steady state free precession 
(SSFP). One such technique, fast imaging with steady-state free 
precession (FISP), is a well established and is a fast MR imaging 
method commonly used to evaluate cardiovascular anatomy and function. 
FISP provides high signal to noise ratio (SNR) images with excellent 
contrast between blood and the myocardium. However, these images are 
often contaminated with high signal from fatty tissue resulting in 
image artifacts. Conventional methods of fat signal suppression in FISP 
are often inefficient and result in a loss of temporal resolution. The 
present pulse sequence provides intrinsic chemical selectivity and 
significant attenuation of fat-based signals (by a factor of four 
compared to conventional FISP imaging) while maintaining the preferred 
high SNR for water-based tissues provided by standard FISP. In 
addition, the pulse sequence design is such that the high temporal 
resolution of FISP is not compromised. Thus, this technology offers a 
valuable improvement to standard cardiac MRI methods.

[gamma]PGA Conjugates for Eliciting Immune Responses Directed Against 
Bacillus Anthracis and Other Bacilli

Rachel Schneerson (NICHD), Stephen Leppla (NIAID), John Robbins 
(NICHD), Joseph Shiloach (NIDDK), Joanna Kubler-Kielb (NICHD), Darrell 
Liu (NIDCR), Fathy Majadly (NICHD).
U.S. Provisional Application No. 60/476,598 filed 05 Jun 2003 (DHHS 
Reference No. E-343-2002/0-US-01).
Licensing Contact: Peter Soukas; 301/435-4646; [email protected].

    This invention claims immunogenic conjugates of a poly-[gamma]-
glutamic acid ([gamma]PGA) of B. anthracis, or of another bacillus that 
expresses a [gamma]PGA that elicit a serum antibody response against B. 
anthracis, in mammalian hosts to which the conjugates are administered. 
The invention also relates methods which are useful for eliciting an 
immunogenic response in mammals, particularly humans, including 
responses which provide protection against, or reduce the severity of, 
infections caused by B. anthracis. The vaccines claimed in this 
application are intended for active immunization for prevention of B. 
anthracis infection, and for preparation of immune antibodies. The 
vaccines of this invention are designed to confer specific immunity 
against infection with B. anthracis, and to induce antibodies specific 
to B. anthracis [gamma]PGA. The B. anthracis vaccine is composed of 
non-toxic bacterial components, suitable for infants, children of all 
ages, and adults.
    This vaccine is further described in Schneerson R. et al., 
``Poly(gamma-D-glutamic acid) protein conjugates induce IgG antibodies 
in mice to the capsule of Bacillus anthracis: a potential addition to 
the anthrax vaccine,'' Proc. Natl. Acad. Sci. U. S. A. 2003 Jul 
22;100(15):8945-50.

Contrast Agent Enhancement of Chemical Exchange Dependent Saturation 
Transfer (CEDST) MRI

Robert S. Balaban, Kathleen Ward, Anthony H. Aletras (NHLBI).
U.S. Patent Application No. 09/959,138 filed 17 Oct 2001 (DHHS 
Reference No. E-240-1998/0-US-04).
Licensing Contact: Michael Shmilovich; 301/435-5019; 
[email protected].

    Available for licensing is an MRI image improving system wherein at 
least one contrast agent is administered to a subject in amounts 
effective to perform chemical exchange dependent saturation transfer 
(CEDST) MRI analysis.
    Examples of contrast agents suitable for administration as 
exogenous contrast agents include at least one functional group bearing 
a proton capable of chemical exchange. Examples of these functional 
groups include, without limitation, amides, amines, and carboxyl, 
hydroxyl, and sulfhydryl groups.
    The contrast agent can be administered as a solid, as a dispersion 
or solution, such as an aqueous composition, as a mixture of two or 
more agents, etc. The contrast agent may also be in the form of a 
polymer.
    One feature of the present invention involved identifying contrast 
agents, which contain the functional groups having the appropriate 
proton exchange and chemical shift properties at physiological pH and 
temperature to function effectively for performing CEDST MRI analyses 
in vivo. A number of different contrast agents can be used to practice 
the present method for performing CEDST MRI analyses in vivo can be 
selected from the group consisting of: Sugars, including 
oligosaccharides and polysaccharides, such as dextran; amino acids, 
such as 5-hydroxy-tryptophan (which also includes an indole -NH) and 
including oligomers of amino acids and proteins; nitrogen-containing 
heterocycles generally; indoles, purines and pyrimidines; nucleosides; 
imidazole and derivatives thereof, such as 2-imidazolidone and 2-
imidazoldinethione; imino acids, including azetidines, such as 
azetidine-2-carboxylic acid, pyrolidines, such as 4-trans-hydroxy-
proline, and piperidines, such as pipecolinic acid; barbituric acid and 
analogs thereof, such as 2-thio-barbituric acid and 5,5-
diethylbarbituric acid; miscellaneous materials, such as guanidine, 
hydantoin, parabanic acid, and biologically active salts thereof; and 
mixtures of these contrast agents.

[[Page 25915]]

    Working embodiments of the invention used the all of above 
materials at a variety of concentration levels for in-vitro experiments 
and, using a 500 mM solution of barbituric acid, in an in-vivo rabbit 
model.
    The method of the present invention is useful for enhancing the 
contrast of MRI images, including images produced in vivo, using CEDST.
    A second feature of the present invention involved identifying 
contrast agents which contained the functional groups which could be 
used, either alone or in combination, to function effectively at 
performing pH measurement using CEDST in vivo.
    Working embodiments of this feature of the invention used either 
dihydrouracil or a combination solution of 5-Hydroxytryptophan and 2-
Imidazolidinethione as the contrast agent, which was provided as an 
aqueous composition having about 62.5 mM of each chemical in the 
solution. Other chemicals with more than one chemical exchange site or 
mixtures of other contrast agents may also be used to practice the 
second feature of the present invention. A standard pH curve is 
prepared by performing in vitro CEDST MRI analyses of the contrast 
agent, which is then used to evaluate the in vivo pH measurement 
results.
    A third feature of the present invention involved identifying 
contrast agents which contained the functional groups which could be 
used to function effectively at performing temperature measurement 
using CEDST in vivo.
    Working embodiments of this feature of the invention used 
barbituric acid as the contrast agent, which was provided as an aqueous 
composition having about 62.5 mM of chemical in the solution. Other 
chemicals may be used to practice the third feature of the present 
invention. A standardized temperature curve is prepared performing in 
vitro CEDST MRI analyses of the contrast agent, which is then used to 
evaluate the in vivo temperature results.
    A fourth feature of the present invention involved identifying 
contrast agents which contained the function groups which could be used 
to function effectively at measuring a metabolite of interest using 
CEDST in vivo.
    Working embodiments of this feature of the invention used 
dihydrouracil as the contrast agent, which was provided as an aqueous 
composition having about 62.5 mM with phosphate as the metabolite of 
interest. Other chemicals may be used to practice the third feature of 
the present invention. A standardized metabolite curve is prepared 
performing in vitro CEDST MRI analyses of the contrast agent, which is 
then used to evaluate the in vivo metabolite results.

    Dated: May 3, 2004.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 04-10495 Filed 5-7-04; 8:45 am]
BILLING CODE 4140-01-P