[Federal Register Volume 61, Number 180 (Monday, September 16, 1996)]
[Notices]
[Pages 48712-48714]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-23634]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, HHS.

ACTION: Notice.

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    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 U.S. companies and may also be available for licensing.

ADDRESSES: Licensing information and copies of the U.S. patent 
applications and issued patents listed below may be obtained by 
contacting Ken Hemby at the Office of Technology Transfer, National 
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, 
Maryland 20852-3804; telephone: 301/496-7735 ext 265; fax: 301/402-
0220). A signed Confidential Disclosure Agreement will be required to 
receive copies of the patent applications.

Expression of Early Lung Cancer Detection Market P31 in Neoplastic and 
Non-Neoplastic Respiratory Epithelium

JL Mulshine (NCI)
Filed 02 Oct 95
Serial No. 08/538,711

    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. (portfolio: Cancer--Diagnostics, in vitro, MAb 
based; Cancer--Research Reagents, MAb based)

Colon Mucosa Gene Having Down-Regulated Expression in Colon Adenomas 
and Adenocarcinomas

CW Schweinfest, TS Papas (NCI)
Filed 17 Apr 95
Serial No. 08/424,567 (FWC of 08/026,045)


[[Page 48713]]


    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. (portfolio: 
Cancer--Diagnostics, in vitro, DNA based; Gene-Based Therapies--
Diagnostics)

Screening Assays for Compounds That Cause Apoptosis

CC Harris, XW Wang, JH Hoeijmakers (NCI)
Filed 19 Dec 94
Serial No. 08/359,316

    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. (portfolio: Cancer--Diagnostics, in vitro, DNA 
based; Cancer--Research Reagents, DNA based; Gene-Based Therapies--
Diagnostics)

Cancer-Related Autocrine Motility Factor, Autotaxin

ML Stracke, LA Liotta, E Schiffmann, HC Krutzsch (NCI)
Filed 28 Nov 94
Serial No. 08/346,455

    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. (portfolio: 
Cancer--Diagnostics, in vitro, MAb based; Cancer--Therapeutics, 
biological response modifers; Cancer--Therapeutics, immunoconjugates, 
MAb)

The IRS Family of Genes

MF White, XJ Sun, JH Pierce (NCI)
Filed 03 Oct 94
Serial No. 08/317,310

    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 the 
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. 
(portfolio: 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)

Antigenic Matrix Metalloproteinase Peptides

LA Liotta, W Stetler-Stevenson, H Krutzch (NCI)
Serial No. 07/830,313 filed 26 Feb 90
U.S. Patent 5,372,809 issued 13 Dec 94

    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

[[Page 48714]]

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. 
(portfolio: Cancer--Research Reagents; Cancer--Diagnostics, in vitro, 
DNA based)

Cell Matrix Receptor System And Use In Cancer Diagnosis And Management

LA Liotta, NC Rao, V Terranova (NCI)
Serial No. 06/481,934 filed 04 Apr 83
U.S. Patent No. 4,565,789 issued 21 Jan 86

    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. (Portfolio: 
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.)

    Dated: August 21, 1996.
Maria C. Freire,
Director, Office of Technology Transfer.
[FR Doc. 96-23634 Filed 9-13-96; 8:45 am]
BILLING CODE 4140-01-M