E5-7249. 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: [phone]; fax: [phone]. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

Tri-Functional Nanospheres

Yun-bo Shi (NICHD) et al.

U.S. Patent Application No. 11/135,380 filed 24 May 2005 (HHS Reference No. E-145-2005/0-US-01).

Licensing Contact: Cristina Thalhammer-Reyero; 301/435-4507; [e-mail].

Available for licensing and commercial development is an invention related to “biofunctional” tri-functional nanospheres (TFNs) or multi-functional nanospheres (MFNs) obtained by binding one or more biomaterials, such as folate, IgG, biotin or streptavidin, to fluorescent-magnetic bifunctional nanospheres (BFNs). Unlike other BFNs available, which are virtually all based on having a magnetic core, the present invention is based on mesoporous BFNs with hydrophobic inner cavities. The properties of the TFNs of the subject invention have superior qualities for use for the various applications that require aqueous solutions.

Nanospheres are becoming the materials of choice for a rapidly increasing number of pharmaceutical and biomedical applications, including the use of quantum dots (QDs) and magnetic nanoparticles. Materials with the combined function of fluorescent labeling and magnetic separation have many applications in biomedical science, including those resulting from the encapsulation of both particles in polymer microcapsules. However, these related prior technologies are predominantly dependent on core-shell type technologies. Typically, a magnetic material such as magnetite or a fluorescent particle such as a QD is used as a core. Such a core-shell structure is chemically unstable and disadvantageous for fluorescence applications because the shell tends to absorb either or both of the excitation and emission lights, thus dimming the fluorescent signal. The nanoparticles of this invention are composed of a mesoporous copolymer, a magnetic material embedded into the mesoporous copolymer, a fluorescent nanomaterial concurrently embedded into the mesoporous copolymer, and one or more biomaterials coupled to the mesoporous copolymer.

TFNs and MFNs have multiple uses. When the TFNs are labeled by a single biomaterial, the nanoparticles may specifically bind to a cell, or a protein or any other moiety that to which the biomaterial specifically binds. For instance, the biomaterial may be a small molecule ligand that is specifically bound by a cell surface receptor. MFNs in which two bioagents are coupled to single BFNs allow using one bioagent to target a macromolecule or a cell and using the second one to alter the function/properties of the macromolecule or cell, e.g., using a protein to target a cell and using a toxin or cell death protein to kill the targeted cell, or using a chemical or protein to target a protein within a complex and another one to alter the function of a different component of the complex.

The technology is further described in “Biofunctionalization of fluorescent-magnetic-biofunctional nanospheres and their applications,” Guo-Ping Wang, Er-Qun Song, Hai-Yan Xie, Zhi-Ling Zhang, Zhi-Quan Tian, Chao Zuo, Dai-Wen Pang, Dao-Cheng Wu and Yun-Bo Shi; Chemical Communications, 2005, (34), 4276-4278; DOI: 10.1039/b508075d.

In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.

Efficient Growth of Wild-Type Hepatitis A Virus in Cell Culture for Development of Live Vaccines

Gerarado Kaplan and Krishnamurthy Konduru (FDA).

U.S. Provisional Application No. 60/684,526 filed 28 Jun 2005 (HHS Reference No. E-151-2004/0-US-01).

Licensing Contact: Chekesha S. Clingman; 301/435-5018; [e-mail].

This technology relates to the development of recombinant wild-type and attenuated Hepatitis A Virus (HAV) vectors capable of growing in cell culture and useful for development of a live HAV vaccine. This technology also encompasses HAV vectors coding for markers that allow the selection of cell lines that support the efficient growth of wild-type and attenuated HAV in culture for diagnostic and environmental monitoring purposes. The currently available killed HAV vaccines are expensive and require a two dose schedule to confer immunity for approximately two decades. Inability of wild-type (wt) HAV to grow efficiently in cell culture has been the major roadblock to developing a live HAV vaccine, which could confer lifelong immunity, be cost-effective and allow eradication of the virus. The inventors have developed recombinant infectious HAV coding for resistance genes against antibiotics that inhibits translation in mammalian cells and provides a selective phenotype that allows selection of cells expressing the phenotype within one week. Also, the inventors have created methods of selecting cells permissive for replication of wild-type and not overly attenuated HAV by utilizing selective or screened phenotypes and antibiotic resistant cell techniques.

In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.

Internal Control Nucleic Acid Molecule for Real-Time Polymerase Chain Reaction

Michael Vickery, Angelo DePaola, George Blackstone (FDA).

U.S. Provisional Application No. 60/471,121 filed 16 May 2003 (HHS Reference No. E-213-2003/0-US-01);

PCT Application No. PCT/US04/15175 filed 14 May 2004 (HHS Reference No. E-213-2003/0-PCT-02).

Licensing Contact: Michael Shmilovich; 301/435-5019; [e-mail].

The invention provides a PCR internal control system for use in both real-time PCR (also known as kinetic or Q-PCR) and conventional PCR. This flexible system has a number of novel design qualities which make it universally adaptable for use in virtually any real-time or conventional PCR assay, including RT-PCR and multiplex PCR applications, regardless of the organism/gene/nucleic acid being targeted. It provides the user/assay developer a choice of control product sizes, fluorogenic probe reporting systems, and thermal cycling options, allowing ease of incorporation into various assay formats and instrument platforms. This unique internal control also can be readily incorporated into virtually any existing quantitative multiplex real-time PCR assay. The invention also provides methods of using the internal control system and kits of the invention.

Additional information may be found in Vickery et al., “Detection and Quantification of Total and Potentially Virulent Vibrio parahaemolyticus Using a 4-Channel Multiplex Real-Time PCR Targeting the tl, tdh, and trh Genes and a Novel PCR Internal Control,” published abstract, 103rd General Meeting of the American Society for Microbiology, May 18-23, 2003, Washington, DC.

In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.

Bisubstrate Inhibitors of Acetyltransferases

Dr. David Klein et al. (NICHD).

HHS Reference No. E-205-1999/0-PCT-02 filed 08 Aug 2000.

Licensing Contact: Marlene Shinn-Astor; 301/435-4426; [e-mail].

The present invention provides methods of inhibiting acetyletransferase enzymes, such as arylalkylamine-N-acetyltransferase (AANAT), by producing a bisubstrate inhibitor in a cell. AANAT catalyzes the transfer of acetyl groups from Acetyl coenzyme A (AcCoA) to substrates such as serotonin. Bisubstrate inhibitors are compounds which share characteristics of AcCoA and of the specific acetyl group acceptors. A highly potent bisubstrate inhibitor of AANAT is CoA-S-N-acetyltryptamine. That inhibitor may be formed in vitro by the reaction of alkylating derivatives of the acetyl acceptor and AcCoA. However, the inhibitor thus formed does not cross the cell membranes and is expensive to produce using AcCoA.

The present invention is based on the surprising discovery that a bisubstrate inhibitor which is specific for a particular acetyltransferase can be formed in a cell by introducing into the cell an alkylating derivative of an acetyl acceptor. Formation of the bisubstrate inhibitor occurs efficiently at very low concentrations of introduced drug because the enzyme to be inhibited positions and catalyzes the reactants favorably to form the inhibitor. The bisubstrate inhibitor is likely to accumulate in the cell because it is stable, highly charged and thus will not pass through cell membranes. The targeted acetyltransferase will thus be inhibited and therapeutic actions realized.

The varied actions of acetyltransferases in biochemical processes offer many potential therapeutic targets. Acetylation inactivates drugs and endogenous ligands so inhibitors could, for example, enhance the effectiveness of antibiotics where antibiotic resistance is due to a high level of acetylation. In the case of AANAT, acetylation inactivates serotonin and is the rate limiting step in the formation of melatonin. Inhibition of AANAT will thus decrease melatonin production and increase serotonin levels. Melatonin is a pineal hormone that has endocrinological, neurophysiological, and behavioral functions. Since melatonin and serotonin are implicated in several types of mood disorders, inhibition of AANAT could have valuable therapeutic uses. Specific inhibitors of melatonin synthesis are not yet available and serotonin antagonists have unacceptable side effects in many patients.

In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.

Imaging With Positron-Emitting Taxanes, Camptothecins, and Other Drugs as a Guide to Antitumor Therapy

Jerry M. Collins, Raymond W. Klecker, Lawrence Anderson (FDA).

U.S. Patent Application No. 10/088,561 filed 19 Mar 2002 (HHS Reference No. E-263-1998/0-US-03);

U.S. Patent Application No. 10/319,812 filed 16 Dec 2002 (HHS Reference No. E-263-1998/1-US-01).

Licensing Contact: Michael Shmilovich; 301/435-5019; [e-mail].

Available for licensing and commercial development is a method for using of positron-emitting compounds to label taxane type drugs. This invention also relates to the use, synthesis and structure of three radio-labeled probe molecules,¹¹ C-SN-38,¹¹ C-imatinib, and¹¹ C-mitoxantrone. SN-38 is a major active metabolite of Camptosar, a product marketed by Pharmacia for the treatment of colorectal cancer. Imatinib is a compound that is used to treat chronic myeloid leukemia (CML) and is marketed under the tradename Gleevec. Mitoxantrone is also used to treat certain types of cancers and multiple sclerosis. For all of these compounds the FDA approved new and expanded uses and there is intense interest in determining whether and where each of the compounds actually collects in the body, and especially whether they are taken up by the targeted tumor. Traditional approaches to determine drug uptake and retention have been invasive. Advantages of using this technology include: (1) Avoidance of exposing patients to toxic drugs that have no potential for benefit; (2) ability to rapidly determine whether a given tumor will be likely to respond to a particular drug; and (3) the ability to monitor the impact of various dosages, schedules, and modulators for delivery, in situ, at the actual tumor under treatment conditions. Further, methods to guide treatment of solid tumors, with labeled taxanes, are also disclosed in the present application.

Additional information may be found in: Ravert et al., “Radiosynthesis of [11C]paclitaxel,” J Label Compd and Radiopharm, 2002, 45(6):471-477.

In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.

Dated: December 1, 2005.

Steven M. Ferguson,

Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.