NIH Invention Disclosures, Aug. 22, 1996

NIH invention disclosures, forwarded for publication in the Federal Register, August 22, 1996



Expression Of Early Lung Cancer Detection Marker P31 In Neoplastic And Non-Neoplastic Respiratory Epithelium

Description of Invention:
Lung cancer is the most frequent cause of cancer death in both males and females in the United States. Metastatic lung cancer is almost uniformly fatal. Methods for earlier detection of lung carcinoma may help increase survival rates by allowing earlier treatment. Recently, there have been efforts to detect antigens associated with lung carcinoma in the sputum of patients. The basis of this approach is the identification of early, potentially pre-neoplastic changes in cells shed from bronchial epithielium. This invention identifies P31 as a candidate for a lung carcinoma associated antigen which can be detected in sputum using immunological methods. This invention describes production and use of antibodies specific for P31 antigen which are highly correlated with patients having increased age and prolonged smoking history, and is selective for neoplastic tissue or tissue proximally associated with neoplasms. This invention further defines a method by which other candiate early lung cancer detection markers can be evaluated. Issuance of a patent on this invention is currently pending.

Inventor:
JL Mulshine (NCI)

Patent Status:
Serial No. 08/538,711 filed 02 Oct 95

Portfolios:
Cancer - Diagnostics, in vitro, MAb based
Cancer - Research Reagents, MAb based

For additional information, please contact:
Ken Hemby
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 265
Fax: 301/402-0220


Colon Mucosa Gene Having Down-Regulated Expression In Colon Adenomas And Adenocarcinomas

Description of Invention:
Tumor suppressor genes that are down-regulated in colon adenomas and adenocarcinomas have been identified and isolated that may be valuable for the study and treatment of these disorders as well as for detecting and identifying other tumor suppressor genes. Colorectal cancer is a significant problem in the U.S., with 130,000 new cases per year and more than 65,000 deaths per year. Colorectal cancer is a multistep process involving the loss of function of so-called tumor suppressor genes as well as the activation of oncogenes. Studies in cell cultures have shown that the transfer of wild-type tumor suppressor genes to colon cancer cells lacking this gene suppresses tumorigenicity. cDNAs encoding an mRNA that is down-regulated in adenocarcinomas and adenomas of the colon have been isolated and cloned. The mRNA encodes a polypeptide of about 84,500 daltons. This down-regulated in adenoma (DRA) gene maps to chromosome 7, in which abnormalities have previously been linked to colorectal carcinomas. The polypeptide product of the cDNA may be used for studying the process of tumorigenesis and suppression. In addition, the DRA gene and/or polypeptide may be valuable as therapy for colon cancer or for staging colon tumors. Finally, this invention includes nucleotide probes for detecting and isolating other tumor suppressor genes.

Inventors:
CW Schweinfest, TS Papas (NCI)

Patent Status:
Serial No. 08/424,567 filed 17 Apr 95 (FWC of 08/026,045)

Portfolios:
Cancer - Diagnostics, in vitro, DNA based
Gene-Based Therapies - Diagnostics

For additional information, please contact:
Ken Hemby
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 265
Fax: 301/402-0220


Screening Assays For Compounds That Cause Apoptosis

Description of Invention:
This application discloses a method for screening compounds for those which have the property of inducing programmed cell death, or "apoptosis", and which therefore are candidates for treating cancers caused by a loss of ability to induce apoptosis. Apoptosis is a normal body mechanism for controlling the growth of cells; the loss of ability to induce apoptosis in cells with defective DNA replication is associated with the formation of certain cancers. One major pathway for monitoring cells for transformation and for inducing apoptosis in transformed cells involves the nuclear protein coded for by the p53 tumor suppressor gene. Mutations in the p53 gene have been linked to a number of human cancers. The screening assays are based on the knowledge that the p53 dependent apoptosis pathway involves the interaction of the p53 protein with XPB or XPD proteins of the disease Xeroderma pigmentosum (XP), or both. The application discloses in vitro diagnostic assays for two of the eight genetic forms of XP, specifically those related to defects in the B or D groups. The assays capitalize on the p53/XP protein interaction by using the ability of compounds with certain binding properties to induce apoptosis to detect the defects indicative of XP. The application also describes a peptide which interferes with the binding of p53 to XPB or XPD protein and may thus be capable of inducing apoptosis in cells susceptible to p53-mediated apoptosis. Issuance of a patent for this invention is currently pending.

Inventors:
CC Harris, XW Wang, JH Hoeijmakers (NCI)

Patent Status:
Serial No. 08/359,316 filed 19 Dec 94

Portfolio:
Cancer - Diagnostics, in vitro, DNA based
Cancer - Research Reagents, DNA based
Gene-Based Therapies - Diagnostics

For additional information, please contact:
Ken Hemby
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 265
Fax: 301/402-0220


Cancer-Related Autocrine Motility Factor, Autotaxin

Description of Invention:
Many types of tumor cells have been found to produce proteins termed "autocrine motility factors". Cell motility plays an important role in the metastasis of tumor cells. The present novel motility factor autotaxin has been isolated and molecular cloned. The cDNA encoding the entire autotaxin protein contains 3251 base pairs, and has an mRNA size of approximately 3.3 kb. The full-length deduced amino acid sequence of autotaxin comprises a protein of 915 amino acids. Autotaxin was found to hydrolyze the type I phosphodiesterase substrate p-nitrophenyl thymidine-5' monophosphate. Autotaxin stimulates both random and directed migration of human A2058 melanoma cells at picomolar concentrations.

The patent application includes claims to the autotaxin protein and cDNA and antibodies thereto. These materials may be useful in the development of cancer diagnostics and therapeutics.

Inventors:
ML Stracke, LA Liotta, E Schiffmann, HC Krutzsch (NCI)

Patent Status:
Serial No. 08/346,455 filed 28 Nov 94

Portfolios:
Cancer - Diagnostics, in vitro, MAb based
Cancer - Therapeutics, biological response modifiers
Cancer - Therapeutics, immunoconjugates, MAb

For additional information, please contact:
Ken Hemby
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 265
Fax: 301/402-0220


The IRS Family Of Genes

Description of Invention:
Insulin Receptor Substrate (IRS) is a polypeptide that has recently been shown to play a role in activation of downstream responses to insulin as well as a possible role in models of obesity or insulin resistance. This invention discloses IRS-2 polypeptide. An IRS-2 polypeptide, insulin receptor substrate-2, specifically binds the insulin receptor, the interleukin-4 receptor, interleukin-13 receptor, insulin-like growth factor, or IL-15 receptor. Disclosed is a method of diagnosis of an insulin-related disorder, such as diabetes, or immune related diseases relating in human or other mammals. A method of measuring the effect of treatment, using a cell or tissue sample that misexpresses the IRS-2 gene. The invention also discloses the manufacture of a transgenic animal that expresses a mutant form of the IRS-2 gene and is useful as a model for the study of insulin-related disorders or other disorders characterized by unwanted cell growth.

Inventors:
MF White, XJ Sun, JH Pierce (NCI)

Patent Status:
Serial No. 08/317,310 filed 03 Oct 94

Portfolios:
Cancer - Diagnostics, in vitro, DNA based
Cancer - Diagnostics, in vivo, other
Cancer - Therapeutics, gene therapy, vectors
Cancer - Therapeutics, gene therapy, genes
Cancer - Therapeutics, biological response modifiers, growth factors
Gene-Based Therapies - Therapeutics, gene therapy, therapeutic genes

For additional information, please contact:
Ken Hemby
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 265
Fax: 301/402-0220


Antigenic Matrix Metalloproteinase Peptides

Description of Invention:
Inhibitory synthetic peptides have been made which incorporate various regions of the type IV collagenase purified from human melanoma cells. These peptides have been used to generate antibodies against specific domains within the type IV collagenase molecule. These peptides have also been shown to inhibit matrix metalloproteinases, and therefore may be useful in the treatment of matrix metalloproteinase-related disease states such as arthritis, tumor growth, invasion and metastasis, inappropriate angiogenesis, and certain inflammatory conditions, such as sarcoidosis. The peptides are suitable for administration by any means which provides ready transmission into the circulation, such as injection, infusion, inhalation, or buccal or sublingual administration. Opthalmologic administration via eye drops may also be possible. In addition to their inhibitory properties, the peptides may also be used to generate antibodies that recognize matrix metalloproteinases and antibodies that recognize collagenase IV specifically. Collagenase IV-specific antibodies are particularly advantageous, since the enzyme shares significant sequence homology with other matrix metalloproteinases. Antibodies made with certain of the peptides are capable of distinguishing activated and non-activated forms of collagenase IV. Hence, the peptides have potential applications as both therapeutic and diagnostic agents.

Inventors:
LA Liotta, W Stetler-Stevenson, H Krutzch (NCI)

Patent Status:
Serial No. 07/830,313 filed 26 Feb 90; U.S. Patent 5,372,809 issued 13 Dec 94

Portfolios:
Cancer - Research Reagents
Cancer - Diagnostics, in vitro, DNA based

For additional information, please contact:
Ken Hemby
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 265
Fax: 301/402-0220


Cell Matrix Receptor System And Use In Cancer Diagnosis And Management

Description of Invention:
A method of diagnosis and management of cancer, particularly breast cancer, is provided. The method involves interfering with the mechanism by which tumor cells adhere to the various membranes and tissues of the body, enabling replication, using cell receptors specific for the laminin molecule. The laminin molecule normally adheres to collagen IV of the membranes and tissues. The novel laminin molecule disclosed binds the cell receptor of the tumor cell because it has an affinity for the receptor but it does not have an affinity for collagen IV which is part of the membranes and tissues of the body.

Other applications include possible burn therapy through the promotion of adhesion and growth of epithelial cells, which form the covering of most internal organs and outer surface layers of skin.

Secondly, this invention provides a method for evaluating the effectiveness of chemotherapeutic agents designed to affect the receptor in cancer cells. the invention discloses a kit for detecting the presence of metastasizing cancer cells having this cell receptor. A method of separation of metastatic cancer cells expressing the cell receptor from a mixed population of cells is also provided.

Also provided is a method of detecting breast cancer using radiolabelled antibodies specific to the cell receptor.

Inventors:
LA Liotta, NC Rao, V Terranova (NCI)

Patent Status:
Serial No. 06/481,934 filed 04 Apr 83; U.S. Patent No. 4,565,789 issued 21 Jan 86

Portfolios:
Cancer - Diagnostics, in vitro, MAb based
Cancer - Diagnostics, in vivo, conjugate chemistry
Cancer - Diagnostics, in vitro, other
Cancer - Research Reagents, MAb based
Cancer - Miscellaneous
Cancer - Therapeutics, biological response modifiers, growth factors
Internal Medicine - Therapeutics, anti-inflammatory

For additional information, please contact:
Ken Hemby
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 265
Fax: 301/402-0220