Government-Owned Inventions; Availability for Licensing

AGENCY:

National Institutes of Health, Public Health Service, HHS.

ACTION:

Notice.

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.

Erythroid Progenitor Cells and Methods for Producing Parvovirus B19 Therein

Description of Technology: The present technology offers novel methods of cell culture for production of human parvovirus B19 (B19). B19, a common infection of children adults, is the cause of fifth disease. Symptoms of B19 infection are usually mild in otherwise healthy individuals, but some adults can suffer chronic arthopathy. Severe health conditions and mortality may result from B19 infection of immunocompromised individuals and patients with chronic hemolytic anemia such as sickle cell disease. In addition, B19 infection during pregnancy may cause hydrops fetalis and fetal death. There is no specific antiviral drug for B19, and some forms of chronic infection are difficult to diagnose. Vaccination is an effective strategy for other animal parvoviruses and is feasible for B19 in humans.

B19 selectively infects erythroid progenitor cells of bone marrow, fetal liver and a small number of specialized cell lines. These specific cell lines demonstrate limited infectability and commonly produce little or no virus following initial inoculation with B19. Current methods for producing infectious B19 require phlebotomy of infrequently available infected donors.

The available technology describes a method of producing pure populations of human erythroid progenitor cells that are fully permissive to B19 infection. This discovery uses CD34+ hematopoietic stem cells present in peripheral blood to supply erythroid progenitor cells, which demonstrate a significant increase in viral production after initial inoculation. The ability to efficiently generate significant amounts of infectious B19V in cells is useful for the development of killed or attenuated vaccines, therapeutics and efficient diagnostic tools for prevention and treatment of B19V. Furthermore, this technology would allow development of new diagnostic assays, which use the entire virus as the antigenic target, thus providing more sensitive and accurate results than current diagnostic tools, which rely on antibodies against a single viral protein.

Applications: (1) Diagnosis of human parvovirus B19; (2) Vaccination of individuals at risk for severe effects of parvovirus infection; (3) Research and development of anti-parvovirus agents.

Development Status: Preclinical data is available at this time.

Inventors: Susan Wong and Neal Young (NHLBI).

Related Publications: 1. MC Giarratana, L Kobari, H Lapillonne, D Chalmers, L Kiger, T Cynober, MC Marden, H Wajcman, L Douay. Ex vivo generation of fully mature human red blood cells from hematopoietic stem cells. Nat Biotechnol. 2005 Jan; 23(1):69-74.

2. JM Freyssinier, C Lecoq-Lafon, S Amsellem, F Picard, R Ducrocq, P Mayeux, C Lacombe, S Fichelson. Purification, amplification and characterization of a population of human erythroid progenitors. Br J Haematol. 1999 Sep; 106(4):912-922.

Patent Status: U.S. Provisional Application No. 60/808,904 filed 26 May 2006 (HHS Reference No. E-188-2006/0-US-01).

Licensing Status: Available for non-exclusive or exclusive licensing and commercial development.

Licensing Contact: Chekesha S. Clingman, Ph.D.; 301/435-5018; clingmac@mail.nih.gov.

Collaborative Research Opportunity: The NHLBI Hematology Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize novel methods to produce parvovirus B19 and use as diagnostic or vaccine. Please contact Dr. Neal Young at 301-496-5093, YoungNS@mail.nih.gov for more information.

Small Molecules for Imaging Protein-Protein Interactions

Description of Technology: Imaging techniques like positron emission tomography and photon emission computerized tomography are often used with imaging agents to detect the presence and accumulation of amyloid plaques within the human brain. These imaging agents have high specificity for beta amyloid peptides, and administration of such agents aids in the early detection of amyloid plaques in brains of Alzheimer's victims. However, currently available imaging agents have limited success for detecting pre-plaque beta amyloid proteins because they are small and reside within the tissue for a short period of time. Therefore, new imaging agents are needed for enhanced identification of amyloid deposits.

Available for licensing and commercial development are small molecules for imaging protein-protein interactions in Alzheimer's disease. This technology describes a bifunctional molecule with high specificity for beta amyloid proteins that is applicable for in vivo imaging. The molecule contains two moieties with different binding affinities, one moiety has an affinity for amyloid beta proteins, and the other moiety has an affinity for a tissue-specific chaperone. The different moieties of the subject invention are conjoined by an inert linkage group, typically comprised of a hydrocarbon chain, peptide, or carbohydrate. The subject invention is affixed with a label, such as a fluorophore or radioisotope, which adheres to the binding site of the beta amyloid protein, the chaperone, or the linkage group. The choice of label makes the subject invention versatile and employable in several types of imaging modalities such as single photon emission computed tomography (SPECT), positron emission tomography (PET), magnetic resonance imaging (MRI), and computerized tomography (CT) scans.

Applications: (1) Applicable for identification of beta amyloid plaques in patients with or at risk for Alzheimer's disease and pre-plaque amyloid beta proteins; (2) Applicable for in vivo imaging protein-protein interactions using small molecules; (3) Applicable for image guided therapy of Alzheimer's disease.

Market: (1) Alzheimer's disease affects approximately 4.5 million people within the United States; (2) The direct and indirect annual costs associated with Alzheimer's disease are at least $100 billion.

Development Status: Pre-clinical data is available.

Inventors: King C. Li and S. Narasimhan Danthi (CC).

Patent Status: U.S. Provisional Application No. 60/815,740 filed 21 Jun 2006 (HHS Reference No. E-046-2006/0-US-01).

Licensing Status: Available for exclusive or non-exclusive licensing.

Licensing Contact: Chekesha S. Clingman , Ph.D.; 301-435-5018; clingmac@mail.nih.gov.

Collaborative Research Opportunity: The National Institutes of Health Clinical Center, Laboratory of Diagnostic Radiology Research, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Small Molecules for Imaging Protein-Protein Interactions. Please contact Betty Tong, Ph.D. at 301-594-4263 for more information.

Methods and Systems for Identifying and Classifying Drug Targets

Description of Technology: Available for licensing and commercial development is a novel method for a-priori evaluation of the therapeutic relevance of gene products for various diseases, in order to make drug development more cost-efficient. In addition, this technology may be used to identify novel therapeutic uses for known drugs. For example, the current invention has the potential to uncover the role of an established cancer drug target, in an alternative disorder such as Alzheimer's disease, thus providing an additional use for the available cancer drug.

The multivariable model used by the method, which is based on a training set of targets that have already passed FDA review, is capable of ranking drug targets in terms of prospective clinical success. This innovative approach integrates multiple datasets that describe each single gene product from a broad range of analyses, such as microarrays, x-ray crystallography, and phylogenetics, to rapidly characterize a proteins structure, function, and gene regulation information. An algorithm subsequently scores a protein's potential as a drug target for use in future drug design studies. The resulting set of targets is enriched 28-fold as compared to randomly selected gene products.

Applications: (1) Early evaluation of a candidate drug target's potential to yield a therapeutic effect, given the target's inhibitor is provided; (2) Efficient discovery of novel drugs and drug targets; (3) Classification of genes according to their involvement in specific diseases.

Development Status: The technology is ready to be used in drug discovery and development.

Inventors: Anatoly L. Mayburd (NCI), James L. Mulshine (NCI), et al.

Patent Status: U.S. Provisional Application No. 60/788,522 filed 31 Mar 2006 (HHS Reference No. E-268-2005/0-US-01).

Licensing Status: Available for non-exclusive or exclusive licensing.

Licensing Contact: Cristina Thalhammer-Reyero, Ph.D., M.B.A.; 301-435-4507; thalhamc@mail.nih.gov.

Systems and Methods for Intelligent Quality Control of Instruments and Processes

Description of Technology: Available for licensing and commercial development is a cost-effective system and method for evaluation of instruments and processes for real-time detection of error. The subject invention includes the capacity to identify imprecision in a variety of data analysis tools, which may be susceptible to malfunction. Such processes include instrumental analysis of patient specimens, assembly line manufacturing and general plant or factory operation. This system provides an automated platform for the dual purpose of (1) monitoring data to detect unusual events in real time and (2) enhancement of human and machine recognition and analysis of improper occurrences based on time-varying patterns of measured values.

The scheme of the current system is straightforward and in general the method involves the following steps: (1) Collection of data elements from an instrument or process (2) counting data elements having values within predetermined intervals of the data range (3) applying counts of data to a neural network that monitors data trends and (4) production of an output based on the neural network, which demonstrates whether the instrument or process is generating results within an appropriate range. This system is advantageous because output is generated in real time and thus available without delay for immediate correction of malfunctions.

Applications: (1) Quality control for processes and instruments; (2) Automated system for real time notification of malfunctions in an instrument or process for immediate correction of the procedure.

Development Status: The technology is fully developed.

Inventors: James M. Deleo (CIT) and Alan T. Remaley (CC).

Patent Status: U.S. Patent No. 6,556,951 issued 29 Apr 2003 (HHS Reference No. E-042-1997/0-US-03).

Licensing Status: Available for non-exclusive and exclusive licensing.

Licensing Contact: Cristina Thalhammer-Reyero, Ph.D., M.B.A.; 301-435-4507; thalhamc@mail.nih.gov.

Collaborative Research Opportunity: The National Institutes of Health Clinical Center, Radiologic and Imaging Sciences, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Intelligent Quality Control of Instruments. Please contact Elaine Ayres at 301/594-3019 for more information.

Sample Delivery System With Laminar Mixing for Microvolume Biosensing

Description of Invention: The invention is a sample delivery system with at least two microchannels connected to a sample chamber containing a biosensor. Biosensing for studying molecular recognition has become an important biophysical tool for biomedical research. The system aspirates a small sample volume into the microfluidic channels and applies a periodic oscillatory flow pattern to the sample. This prevents sample depletion in the stagnant layer across the sensor surface and results in efficient mixing of the sample during the biosensor measurement. Because the oscillatory flow pattern does not produce a net transport of the sample with time, there is a very long incubation time of the sensor surfaces with a very small sample volume. The new sample delivery system uses sample volumes of only 3 to 8 microliters, compared to the 25 to 200 microliter volumes of conventional systems, which use cuvette principles or continuous flow microfluidics. The present invention is substantially better than existing systems with respect to biosensor contact time and required sample volume.

Application: Sample delivery for biosensing.

Development Status: A prototype of the technology is currently being implemented in inventor's lab and technology is ready for commercialization.

Inventor: Peter Schuck (ORS).

Publication: M Abrantes, MT Magone, LF Boyd, P Schuck. Adaptation of a surface plasmon resonance biosensor with microfluidics for use with small sample volumes and long contact times. Anal Chem. 2001 Jul 1;73(13):2828-2835.

Patent Status: U.S. Patent Application No. 10/415,909 filed 05 May 2003, claiming priority to 06 Nov 2000 (HHS Reference No. E-143-2000/0-US-03); European Patent Application No. 01990651.0 filed 11 Jun 2001 (HHS Reference No. E-143-2000/0-EP-04).

Licensing Status: Available for non-exclusive or exclusive licensing.

Licensing Contact: Michael A. Shmilovich, Esq.; 301/435-5019; shmilovm@mail.nih.gov.

Collaborative Research Opportunity: The NIH Office of Research Services, Division of Bioengineering and Physical Science, Protein Biophysics Resource, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this Sample Delivery System technology. Please contact Dr. Peter Schuck at 301-435-1950 or pschuck@helix.nih.gov for more information.

Vaccine for Dengue Virus

Description of Technology: The claimed invention relates to viable chimeric dengue viruses or their derived recombinant mutants for use as vaccines against dengue and other flavivirus diseases, including tick-borne encephalitis and West Nile encephalitis. Dengue is a mosquito-transmitted viral disease which occurs in tropical and subtropical regions throughout the world. Inactivated whole dengue virus vaccines have been shown to be insufficiently immunogenic and live dengue virus vaccines prepared by serial passage in cell culture have not been shown to be consistently attenuated. A dengue vaccine is still not available. The present invention represents a technical breakthrough, which provides new approaches to dengue vaccines by construction of chimeric dengue viruses of all four serotypes and strategic modification to produce attenuated virus strains. Several fields of use remain available for licensing.

Applications: Prevention of dengue outbreaks, severe and fatal dengue caused by dengue viruses, a major public health problem in tropical and subtropical regions.

Inventors: Ching-juh Lai, et al. (NIAID).

Patent Status: U.S. Patent 6,184,024 issued 06 Feb 2001 (HHS Reference No. E-171-1988/1-US-02); U.S. Patent 6,676,926 issued 13 Jan 2004 (HHS Reference No. E-171-1988/1-US-03).

Licensing Status: Available for non-exclusive licensing.

Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; soukasp@mail.nih.gov.

Murine Monoclonal Antibodies Effective To Treat Respiratory Syncytial Virus

Description of Technology: Available for licensing through a Biological Materials License Agreement are the murine MAbs described in Beeler et al, “Neutralization epitopes of the F glycoprotein of respiratory syncytial virus: effect of mutation upon fusion function,” J Virol. 1989 Jul;63(7):2941-2950. The MAbs that are available for licensing are the following: 1129, 1153, 1142, 1200, 1214, 1237, 1112, 1269, and 1243. One of these MAbs, 1129, is the basis for a humanized murine MAb (see U.S. Patent 5,824,307 to humanized 1129 owned by MedImmune, Inc.), recently approved for marketing in the United States. MAbs in the panel reported by Beeler et al. have been shown to be effective therapeutically when administered into the lungs of cotton rats by small-particle aerosol. Among these MAbs several exhibited a high affinity (approximately 109M-1) for the RSV F glycoprotein and are directed at epitopes encompassing amino acid 262, 272, 275, 276 or 389. These epitopes are separate, nonoverlapping and distinct from the epitope recognized by the human Fab of U.S. Patent 5,762,905 owned by The Scripps Research Institute.

Applications: Research and drug development for treatment of respiratory syncytial virus.

Inventors: Robert M. Chanock, Brian R. Murphy, Judith A. Beeler, and Kathleen L. van Wyke Coelingh (NIAID).

Patent Status: HHS Reference No. B-056-1994/1—Research Tool.

Licensing Status: Available for non-exclusive licensing under a Biological Materials License Agreement.

Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; soukasp@mail.nih.gov.