National Institutes of Health, Public Health Service, DHHS.
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.
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/Start Printed Page 25914496-7057; 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; firstname.lastname@example.org.
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@example.com.
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.
γPGA 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; firstname.lastname@example.org.
This invention claims immunogenic conjugates of a poly-γ-glutamic acid (γPGA) of B. anthracis, or of another bacillus that expresses a γPGA 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 γPGA. 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@example.com.
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. Start Printed 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.Start Signature
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