04-10607. 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.

Eosinophil-Derived Neurotoxin, an Antimicrobial Protein With Ribonuclease Activity, is an Immunostimulant

De Yang et al. (NCI).

U.S. Provisional Patent Application Nos. 60/466,797 and 60/466,796, filed 29 Apr 2003 (DHHS Reference Nos. E-175-2003/0-US-01 and E-191-2003/0-US-01).

Licensing Contact: Brenda Hefti; 301/435-4632; [e-mail].

Eosinophil-derived neurotoxin (EDN) has in vitro anti-viral activity that is dependent on its ribonuclease activity. This invention discloses that EDN is a selective chemoattractant and activator of dendritic cells, resulting in dendritic cell migration, maturation, and a production of a wide variety of cytokines. Based on these potent chemotactic and activating effects on dendritic cells, EDN might be useful as a clinical immunoadjuvant for the promotion of immune responses to specific antigens of tumors or pathogenic organisms.

Detection of Antigen-Specific T Cells and Novel T Cell Epitopes by Acquisition of Peptide/HLA-GFP Complexes

Steven Jacobson, Utano Tomaru, and Yoshihisa Yamano (NINDS).

U.S. Provisional Application No. 60/457,006 filed 24 Mar 2003 (DHHS Reference No. E-084-2003/0-US-01); U.S. Provisional Application No. 60/480,083 filed 20 Jun 2003 (DHHS Reference No. E-084-2003/1-US-01); PCT Application filed 24 Mar 2004 (DHHS Reference No. E-084-2003/2-PCT-01).

Licensing Contact: Brenda Hefti; 301/435-4632; [e-mail].

This invention relates to a method for identifying specific T cell epitopes and antigen-specific T cells through labeling with an HLA-GFP complex expressed on an antigen-presenting cell. The T cells acquired the peptide-HLA-GFP complex through T cell mediated endocytosis upon specific antigen stimulation. This basic method can be used for several purposes. First, it can be used to generate a T-cell immune response through the attachment of a reporter peptide to the antigen-presenting cell. It can also be used as a way to assay a population of cells to determine whether any T cells specific for a particular antigen are present. This might be useful in applications related to autoimmunity, infectious disease, or cancer. Third, it can be used as a therapeutic to eliminate antigen-specific T cells associated with disease, if coupled to a toxic moiety.

Protein Kinase C Inhibitor, Related Composition, and Method of Use

Shaomeng Wang, Peter Blumberg (NCI), Nancy Lewin (NCI).

U.S. Provisional Patent Application No. 60/451,214 filed 28 Feb 2003 (DHHS Reference No. E-073-2003/0-US-01); PCT Application No. PCT/US04/05855 filed 26 Feb 2004 (DHHS Reference No. E-073-2003/0-PCT-02).

Licensing Contact: Brenda Hefti; 301/435-4632; [e-mail].

Protein kinase C is a critical component in cellular signaling, involved in cellular growth, differentiation, and apoptosis. It has been identified as a promising therapeutic target for cancer, diabetic retinopathy, and Alzheimer's disease, among other indications. This invention relates to lead compounds that can inhibit protein kinase C isoforms through disruption of their C1 domains. The inventors also found that these compounds possess isoform selectivity, an important feature for therapeutic specificity. Finally, although the disclosed compounds are previously known molecules, novel structures are described in the invention that have further improved specificity.

Recombinant Immunotoxin and Use in Treating Tumors

Ira Pastan (NCI), Masanori Onda (NCI), Nai-Kong Cheung (EM).

PCT Application No. PCT/US03/38227 filed 01 Dec 2003 (DHHS Reference No. E-051-2003/0-PCT-02).

Licensing Contact: Brenda Hefti; 301/435-4632; [e-mail].

The current invention relates to the 8H9 monoclonal antibody (MAb), which is highly reactive with a cell surface glycoprotein expressed on human breast cancers, childhood sarcomas, and neuroblastomas but is not reactive with the cell surface of normal human tissues. This specific reactivity suggests that this antibody could be useful as a diagnostic, or as a therapeutic molecule to treat breast cancer, osteosarcoma, and neuroblastoma. The PCT application claims the 8H9 protein, 8H9 antibodies, 8H9 immunotoxins, pharmaceutical compositions, and methods of use.

More information can be found in a recent publication: M. Onda et al., “In vitro and in vivo cytotoxic activities of recombinant immunotoxin 8H9(Fv)-PE38 against breast cancer, osteosarcoma, and neuroblastoma,” Cancer Res. 2004 Feb 15;64(4):1419-1424.

Methods of Diagnosing Potential for Developing Hepatocellular Carcinoma or Metastasis and of Identifying Therapeutic Agents

Xin Wei Wang et al. (NCI).

U.S. Provisional Application No. 60/370,895 filed 05 Apr 2002 (DHHS Reference No. E-125-2002/0-US-01); PCT Application No. PCT/US03/10783 filed 04 Apr 2003 (DHHS Reference No. E-125-2002/0-PCT-02).

Licensing Contact: Brenda Hefti; 301/435-4632; [e-mail].

Expression of nearly 10,000 genes was analyzed in hepatocellular carcinoma (HCC) tumors, and a molecular signature was identified that targets genes that are most likely relevant to the prediction outcome of metastases, including patient survival. A specific therapeutic target protein was also identified, and antibodies against this protein prevent invasion of metastatic HCC cells in vitro. These data identify this target protein both as a diagnostic marker and a therapeutic target for metastatic HCC. In addition, by analyzing premalignant cirrhotic liver tissues from high risk liver disease patients, a molecular signature were identified that may be useful in diagnosing early onset of HCC. Some of the biomarkers have been validated with serum samples to have potentially predictive values.

This invention may be useful in diagnosing early onset of HCC and HCC metastatic tumors, evaluating risk for development of HCC and HCC metastatic tumors, and identifying HCC therapeutic targets. This invention also identifies a specific therapeutic target protein, and identifies methods of identifying antagonists to this protein, which might be useful in developing a variety of HCC therapeutics.

p-Toluemesulfonhydrazide Derivatization for Separation and Measurement of Endogenous Estrogen Metabolites by High-Pressure Liquid Chromatography-Electrospray-Mass Spectrometry

Xia Xu, David Waterhouse, Joseph Saavedra, Larry Keefer, Regina Ziegler (NCI).

U.S. Provisional Patent Application 60/372,848 filed 15 Apr 2002 (DHHS Reference No. E-103-2002/0-US-01); PCT Application No. PCT/US03/11562 filed 15 Apr 2003, which published as WO 03/089921 on 30 Oct 2003 (DHHS Reference No. E-103-2002/0-PCT-02).

Licensing Contact: Brenda Hefti; 301/435-4632; [e-mail].

The current invention relates to a method for measuring endogenous estrogen levels, and this technology may be generalizable to all endogenous ketolic steroids, including estrogens, androgens, and phytoestrogens.

Specifically, the current invention is a derivatization technique that forms estrogen-p-toluenesulfonhydrazones, which can be separated and then measured using high-pressure liquid chromatography-electrospray-mass spectrometry (HPLC-ESI-MS). This method offers a number of improvements over current methods. It is more sensitive, it is faster, it is more accurate, and it requires a smaller sample size.

Cloning and Mutational Analysis of the Hyperparathyroidism-Jaw Tumor Syndrome (HPT-JT) Gene

John D. Carpten et al. (NHGRI).

U.S. Provisional Application No. 60/378,022 filed 13 May 2002 (DHHS Reference No. E-004-2002/0-US-01); PCT Application No. PCT/US03/15081 filed 13 May 2003, which published as WO 03/094860 on 20 Nov 2003 (DHHS Reference No. E-004-2002/0-PCT-02).

Licensing Contact: Brenda Hefti; 301/435-4632; [e-mail].

Hyperparathyroidism is a key feature of some hereditary endocrine neoplasias and the autosomal dominant disorder HPJT, all of which are characterized by the presence of tumors in endocrine tissues. The current invention identifies a series of mutations in chromosome 1 open reading frame 28 (C10RF28)—the HPT-JT gene. Linkage analysis and physical mapping studies of clinical samples from multiple families with HPT-JT syndrome were used to identify these mutations. These genomic changes are predicted to result in truncated gene products.

This new technology might be useful for: (1) Diagnosis of HPT-JT and/or a predisposition to HPT-JT; (2) development of a treatment for HPT-JT; and (3) determination of the effectiveness of various potential HPT-JT therapies.

Additional information may be found in: J.D. Carpten et al., “HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome,” Nat. Genet. (2002 Dec) 32(4):676-80, Epub 2002 Nov 18.; J.D. Chen et al., “Hyperparathyroidism-jaw tumour syndrome,” J. Int. Med. (2003 Jun) 253(6):634-642, doi: 10.1046/j.1365-2796.2003.01168.x; T.M. Shattuck et al., “Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma,” N. Engl. J. Med. (2003 Oct) 349(18):1722-1729; W.F. Simonds et al., “Familial isolated hyperparathyroidism is rarely caused by germline mutation in HRPT2, the gene for the hyperparathyroidism-jaw tumor syndrome,” J. Clin. Endocrinol. Metab. (2004 Jan) 89(1):96-102, doi: 10.1210/jc.2003-030675; A. Villablanaca et al., “Germline and de novo mutations in the HRPT2 tumour suppressor gene in familial isolated hyperparathyroidism (FIHP),” J. Med. Genet. (2004 Mar) 41(3):e32, doi: 10.1136/jmg.2003.012369.

Dated: May 4, 2004.

Steven M. Ferguson,

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