Federal Tech Transfer Opportunities

During the past week, the following agencies have published notice of government-owned inventions available for licensing.

NATIONAL INSTITUTES OF HEALTH 
SUMMARY: The inventions listed below are owned by agencies 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.

Enhanced Homologous Recombination Mediated by Lambda Recombination Proteins

Donald L. Court, Daiguan Yu, E-Chaing Lee, Hilary Ellis, Nancy A. Jenkins, Neal G. Copeland (NCI), DHHS Reference No. E-177-00/0 filed 14 Aug 2000, Licensing Contact: Dennis Penn; 301/496-7056 ext. 211; e-mail: pennd@od.nih.gov.

The present invention concerns methods to enhance homologous recombination in bacteria and eukaryotic cells using recombination proteins derived from bacteriophage lambda. It also concerns methods for promoting homologous recombination using other recombination proteins.

Concerted use of restriction endonucleases and DNA ligases allows in vitro recombination of DNA sequences. The recombinant DNA generated by restriction and ligation may be amplified in an appropriate microorganism such as E. coli, and used for diverse purposes including gene therapy. However, the restriction-ligation approach has two practical limitations: first, DNA molecules can be precisely combined only if convenient restriction sites are available; second, because useful restriction sites often repeat in a long stretch of DNA, the size of DNA fragments that can be manipulated are limited, usually to less than about 20 kilobases.

Homologous recombination, generally defined as an exchange of homologous segments anywhere along a length of two DNA molecules, provides an alternative method for engineering DNA. In generating recombinant DNA with homologous recombination, a microorganism such as E. coli, or a eukaryotic cell such as a yeast or vertebrate cell, is transformed with an exogenous strand of DNA. The center of the exogenous DNA contains the desired transgene, whereas each flank contains a segment of homology with the cell's DNA. The exogenous DNA is introduced into the cell with standard techniques such as electroporation or calcium phosphate-mediated transfection, and recombines into the cell's DNA, for example with the assistance of recombination-promoting proteins in the cell.

In generating recombinant DNA by homologous recombination, it is often advantageous to work with short linear segments of DNA. For example, a mutation may be introduced into a linear segment of DNA using polymerase chain reaction (PCR) techniques. Under proper circumstances, the mutation may then be introduced into cellular DNA by homologous recombination. Such short linear DNA segments can transform yeast, but subsequent manipulation of recombinant DNA in yeast is laborious. It is generally easier to work in bacteria, but linear DNA fragments do not readily transform bacteria (due in part to degradation by bacterial exonucleases). Accordingly, recombinants are rare, require special poorly-growing strains (such as RecBCD-strains) and generally require thousands of base pairs of homology. This invention teaches an improved method of promoting homologous recombination in bacteria. In eukaryotic cells, targeted homologous recombination provides a basis for targeting and altering essentially any desired sequence in a duplex DNA molecule, such as targeting a DNA sequence in a chromosome for replacement by another sequence. This invention teaches methods useful for treating human genetic diseases, the creation of transgenic animals, or modifying the germline of other organisms.

Amelogenin Knockout Mice and Use as Models for Tooth Disease

Dr. Ashok Kulkarni et al. (NIDCR), DHHS Reference No. E-167-00/0, Licensing Contact: John Rambosek; 301/496-7056 ext. 270; e-mail: rambosej@od.nih.gov

This technology relates to transgenic knockout mice that may serve as an animal model for dental disease. Using gene-targeting techniques, mice have been created which are disrupted for the amelogenin gene. These mice lack the amelogenin protein, which is normally expressed only in the teeth. Since these mice lack this protein, they are expected to mimic an inherited tooth disorder called ``amelogenesis imperfecta (AI)''. AI is an inherited condition that is transmitted as a dominant trait and causes the enamel of the tooth to be soft and thin resulting in discoloration, disintegration and disfigurement of the teeth. The damaged teeth are also susceptible to decay. The amelogenin knockout mice display an interesting tooth phenotype. Their maxillary incisors are chalky white in color and opaque in appearance. These changes are associated with mild attrition of incisor tips and molar cusps. Detailed analysis of this phenotype is in progress. The amelogenin knockout mice may be used as an animal model to develop therapeutic approaches to AI.

Transgenic Mouse Model for Tooth Disorders Such as Dentin Dysplasia and Dentinogenesis Imperfecta

Drs. Thyagarajan, Sreenath, and Kulkarni (NIDCR), DHHS Reference No. E-150-00/0, Licensing Contact: John Rambosek, Ph.D.; 301/496-7056; e-mail: rambosej@od.nih.gov.

This technology describes transgenic mice that selectively overexpress transforming growth factor beta-1 (TGF-beta1) in odontoblast and ameloblast cells of teeth. Ameloblasts mainly make enamel, whereas odontoblasts make dentin. These transgenic mice mimic dental symptoms similar to those seen in common tooth disorders such as dentin dysplasia and dentinogenesis imperfecta. Both of these human dentin defects are inherited in an autosomal dominant manner and appear to be caused by abnormal dentin production by odontoblasts and associated poor mineralization of the dentin matrix. In both diseases, teeth are discolored and fractured, causing difficulties in eating food. Experimentally, these mice display discolored and fractured teeth with defective dentin. This transgenic mice model will be valuable to advance our understanding of the molecular pathogenesis underlying dentin dysplasia and dentinogenesis imperfecta and also for developing therapeutic strategies. This material is available for licensing through a PHS Biological Materials License.


ADDRESSES: Licensing information and copies of the U.S. patent applications listed below may be obtained by contacting Dale Berkley, Ph.D., J.D., at the Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: 301/496-7735 ext. 223; fax: 301/402-0220; e-mail: berkleyd@od.nih.gov. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

Automated Core Biopsy Instrument

Erik Kass, Carter Vanwaes (NIDCD), DHHS Reference No. E-269-00/0 filed 20 Sep 2000.

The invention is an automated core biopsy instrument that may be operated with one hand. The instrument has a single activation element that causes a stylet to advance into the tissue of interest as a cutting cannula disposed around the stylet is fired to shear off the tissue into specimen notches disposed in the stylet. The invention is constructed so that the stylet and cutting cannula may be separately driven and biased. The cocking mechanism of the automated core biopsy instrument is used to cock both the stylet assembly and cutting cannula assemblies against separate biasing springs. Manipulation of the cocking mechanism permits the exposure of tissue in the specimen notches when desired. The instrument has a locking mechanism that is used to prevent inadvertent firing of the automated core biopsy instrument.

EZ Navigator and EZ Forms Software

Andrew Schwartz, William K. Jones, Michelle R. Ugas, Ta-Jen Hu (CIT), DHHS Reference No. E-236-00/0.

The EZStart invention is a method of accessing a database management system that can be used to convert non-relational data to relational data and create and manage relational data over a network such as the Internet. The invention provides user-friendly access to data stored in a database management system, allowing users with little or no knowledge of database management systems to access, store and manage data using only a web browser. EZStart provides a generic platform from which any user can select, insert, update and delete data without creating a custom software application for each user. The invention automatically generates navigation and data forms, allowing access to a Relational Database Management System (RDBMS) while masking the complexity of the RDBMS. Using a function of EZStart coined EZNavigator, users can easily maneuver through the RDBMS, view lists of objects, drill-down into column, view and index definitions, and manage object privileges. A separate function of EZStart, known as EZForms, allows a user to select, insert, update and delete rows in tables. No Structured Query Language (SQL) knowledge is required to perform these functions, but advanced users can use EZForms to generate SQL into a text area for modification and execution of the SQL. The SQL can be saved into and retrieved from a repository.

Integrated Low Field MRI/RF EPRI for Co-Registering Imaging of In Vivo Physiology and Anatomy in Living Objects

Murali K. Cherukuri et al. (NCI), DHHS Reference No. E-120-99/0 
filed 01 Nov 1999.

Obtaining physiological information in a non-invasive manner from living tissue will provide valuable information, rather than invasive methods that are sometimes not available and also may damage living tissue. EPRI (Electron Paramagnetic Resonance Imaging) is the technique to investigate physiological information such as oxygen imaging and pharmacokinetic imaging in a non-invasive manner after non-toxic infusion of the spin probe.

However, the disadvantage of EPRI is the lack of proper orientation of the physiological image with respect to anatomy. On the contrary, Magnetic Resonance Imaging (MRI) methods are excellent for providing images with fine anatomical detail, but are often not possible methods that provide physiological information co-registered with anatomy with clinically relevant resolution.

The current invention complements a MRI with EPRI methods to solve each method's problem described above. A low-field MRI(5-30 mT) module is integrated into an EPRI(5--20 mT) system to provide an MRI scout image to properly orient the EPRI physiological information with respect to anatomy (A common magnet/gradient coil assembly is used for both MRI and EPRI scans).

Therefore, the EPR images contain spectral information regarding the local physiological conditions such as oxygen status. This data, when overlaid with anatomical images of MRI (Magnetic Resonance Imaging), co-register anatomical MR images and EPR physiological images.

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