Invention disclosures forwarded by NIH on Sept. 25, 1997 for publication in the Federal Register
Methods and Compositions for Inhibiting Inflammation and Angiogenesis
Description of Invention:
The invention provides compositions and methods directed to isolated a
subunits of the 7TM protein CD97. CD97 is a heterodimer existing in
three isoforms, namely three forms of a subunit and one invariant b
subunit. The invention provides compositions and methods for detecting
a subunit of CD97, a T-cell protein which is upregulated in activated
T-cells and is involved in the onset and maintenance of inflammation and
angiogenesis. The invention provides an isolated protein comprising a
soluble CD97 a subunit, and an isolated nucleic acid encoding a soluble
CD97 a subunit protein. The invention also provides methods for
identifying compounds which inhibit soluble CD97 a subunit expression.
The invention may be used to inhibit angiogenesis associated with
chronic inflammation in a mammal by administering a therapeutically
effective amount of a CD97 antagonist. Another application includes
determining the degree of inflammation at a site in a mammal with an
antibody composition specifically reactive to a soluble CD97 a subunit.
Further, it should be noted that these compositions and methods further
have in vitro utility in the construction of proteins and subsequences
thereof for the construction of antibodies, and nucleic acids and
subsequences thereof for use as probes.
Inventor:
K Kelly (NCI)
Patent Status:
Serial No. 60/027,871 filed 25 Oct 96
Portfolios:
Internal Medicine - Diagnostics, anti-inflammatory
Internal Medicine - Therapeutics
For additional information, please contact:
J. Peter Kim
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7056, ext. 264
Fax: 301/402-0220
E-mail: JK141N@NIH.GOV
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Genes for Niemann-Pick Type C Disease
Description of Invention:
Niemann-Pick disease is a class of inherited lipid storage diseases. Niemann-Pick Type C disease is an autosomal recessive neurovisceral lipid storage disorder which leads to systemic and neurological abnormalities including ataxia, seizures, and loss of speech. Patients with the disease typically die as children. The biochemical hallmark of Niemann-Pick Type C cells is the abnormal accumulation of unesterified cholesterol in lysosomes, which results in the delayed homeostatic regulation of both uptake and esterification of low density lipoprotein (LDL) cholesterol. Niemann-Pick Type C is characterized by phenotypic variability. The disease appears at random in families that have no history of the disorder, making diagnosis problematic. This invention provides the human gene for Niemann-Pick Type C disease and the nucleic acid sequences corresponding to the human gene for Niemann-Pick Type C disease. Also provided is the mouse homolog of the human gene. The invention could lead to improved diagnosis and the design of therapies for the disease and improved means of detection of carriers of the gene. In addition, this invention may contribute to the understanding and development of treatments for atherosclerosis, a more common disorder associated with cholesterol buildup that involves the accumulation of fatty tissue inside arteries that blocks blood flow, leading to heart disease and stroke. The invention may also lead to additional discoveries concerning how cholesterol is processed in the body.
Inventors:
DA Tagle, ED Carstea, JA Morris, PG Pentchev, WJ Pavan, MA Rosenfeld, SK Loftus (NINDS/NHGRI)
Patent Status:
Serial No. 60/051,682 filed 03 Jul 97
Portfolios:
Internal Medicine - Diagnostics, other
Central Nervous System - Diagnostics, in vitro, other
Gene-Based Therapies - Diagnostics
For additional information, please contact:
Leopold J. Luberecki, Jr., J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext. 223
Fax: 301/402-0220
E-mail: LL87A@NIH.GOV
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AIB-1, A Steroid Receptor Co-Activator Amplified in Breast and Ovarian Cancer
Description of Invention:
Breast cancer is the number one cancer in U.S. women, with over 185,000 cases in 1996 and an estimated 44,560 deaths in the past year. Breast cancer arises from estrogen-responsive breast epithelial cells. Estrogen activity is thought to promote the development of breast cancer, and many breast cancers are initially dependent on estrogen at the time of diagnosis. Anti-estrogen compositions have therefore been used to treat breast cancer.
AIB-1 (Amplified in Breast Cancer-1) is a novel gene that is pivotal to a crucial metabolic pathway linked to the growth and progression of human breast cancer. In many cancers, especially breast cancer, tumor cells have amplified copies of genes that can give the cancer a growth advantage. AIB-1, located on the long arm of chromosome 20, is one such amplified gene. High-level AIB-1 amplification and overexpression have been observed in several estrogen receptor (ER) positive breast and ovarian cancer cell lines, as well as in uncultured breast cancer specimens. AIB-1 has also been found to be expressed in prostate epithelial cells.
AIB-1 is the most recently identified member of a gene family known as SRC-1 (steroid receptor coactivator), all of which interact with genes for steroid hormone receptors, ultimately enhancing tumor cell growth.
This invention provides the gene for AIB-1, a novel steroid receptor co-activator which is overexpressed in breast cancer cells. It also encompasses diagnostic assays for steroid hormone-responsive cancers and screening assays to identify compounds which could inhibit interactions of the co-activator with steroid hormone receptors and other proteins in this pathway.
Inventors:
PS Meltzer, JM Trent (NHGRI)
Patent Status:
OTT Reference No. E-018-97/0 filed 17 Jun 97
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
E-mail: JH259B@NIH.GOV
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Methods and Compositions for Inhibiting Inflammation and Angiogenesis
Description of Invention:
The invention provides compositions and methods directed to isolated ( subunits of the 7TM protein CD97. CD97 is a heterodimer existing in three isoforms, namely three forms of ( subunit and one invariant ( subunit. The invention provides compositions and methods for detecting a subunit of CD97, a T-cell protein which is upregulated in activated T-cells and is involved in the onset and maintenance of inflammation and angiogenesis. The invention provides an isolated protein comprising a soluble CD97 ( subunit, and an isolated nucleic acid encoding a soluble CD97 ( subunit protein. The invention also provides methods for identifying compounds which inhibit soluble CD97 ( subunit expression. The invention may be used to inhibit angiogenesis associated with chronic inflammation in a mammal by administering a therapeutically effective amount of a CD97 antagonist. Another application includes determining the degree of inflammation at a site in a mammal with an antibody composition specifically reactive to a soluble CD97 ( subunit. Further, it should be noted that these compositions and methods further have in vitro utility in the construction of proteins and subsequences thereof for the construction of antibodies, and nucleic acids and subsequences thereof for use as probes.
Inventor:
K Kelly (NCI)
Patent Status:
Serial No. 60/027,871 filed 25 Oct 96
Portfolios:
Internal Medicine - Diagnostics, anti-inflammatory
Internal Medicine - Therapeutics
For additional information, please contact:
J. Peter Kim
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7056, ext. 264
Fax: 301/402-0220
E-mail: JK141N@NIH.GOV
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Peptides With Laminin Activity
Description of Invention:
Peptides with laminin activity, including YIGSR, are claimed. These peptides block angiogenesis, alter the formation of capillary structures by endothelial cells, prevent the formation of excess blood vessels in tissue and inhibit in vivo tumor cell colonization of tissues. These peptides can be used, among other things, to inhibit metastasis.
Potential Areas of Application:
* cancer therapeutic
* research reagent
Main Advantages of Invention:
* encourage cell adhesion
* inhibits metastasis and angiogenesis
Inventors:
Y Yamada, JO Graf, Y Iwamoto, F Robey, HK Kleinman, M Sasaki, GR Martin (NIDR)
Patent Status:
* Serial No. 07/272,165; U.S. Patent 5,092,885 issued 03 Mar 92
* Canadian Patent No. 1,329,446 issued 10 May 94
* Australian Patent No. 600112 issued Feb 91
* European Patent No. 0278781 granted 03 Nov 93
Related Technology:
Serial No. 07/267,564 filed 07 Nov 88; U.S. Pat. No. 5,211,657 issued 18 May 93, entitled "Laminin A Chain Deduced Amino Acid Sequence, Expression Vectors and Active Synthetic Peptides"
Relevant Publications:
* Iwamoto Y; Nomizu M; Yamada Y; Ito Y; Tanaka K; Sugioka Y. Inhibition of angiogenesis, tumor growth and experimental metastasis of human fibrosarcoma cell HT 1080 by a multimeric form of the laminin sequence Tyr-Ile-Ser-Arg (Y-I-G-S-R). B.J. Cancer 73:589, 1996.
* Kim WH; Schnaper HW; Nomizu M; Yamada Y; Kleinman HK. Apoptosis in human fibrosarcoma cells is induced by a multimeric synthetic YIGSR-containing polypeptide from laminin. Cancer Res 54:5005, 1994.
* Yamamura K; Kibbey MC; Jun SH; Kleinman HK. Effect of Matrigel and laminin peptide YIGSR on tumor growth and metastasis. Semin Cancer Biol 1993 Aug; 4(4):259-65
* Nomizu M; Yamamura K; Kleinman HK; Yamada Y. Multimeric forms of Tyr-Ile-Gly-Ser-Arg (YIGSR) peptide enhance the inhibition of tumor growth and metastasis. Cancer Res 1993 Aug 1;53(15):3459-61
* Graf J; Iwamoto Y; Sasaki M; Martin GR; Kleinman HK; Robey FA; Yamada Y. Identification of an amino acid sequence in laminin mediating cell attachment, chemotaxis, and receptor binding. Cell 1987 Mar 27;48(6):989-9
Portfolio:
Cancer - Therapeutics
Licensing Status:
Available for exclusive or non-exclusive licensing
For additional information, please ontact:
Jaconda Wagner, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735, ext. 284
Fax: 301/402-0220
E-mail: Jaconda_Wagner@nih.gov
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Laminin A Peptides
Description of Invention:
This invention relates to peptides and derivatives thereof having laminin-like activity, as well as a pharmaceutical composition of the peptide. The peptides claimed include Serine-Isoleucine-Lysine-Valine-Alanine-Valine (SIKVAV). Methods for promoting increased adhesion and migration of epithelial cells is also disclosed. The peptides have wide usage in research, nerve regeneration and cancer treatment. For example, this invention may be useful as an adhesion and regeneration agent for nerve guides and as an adhesion agent for vascular prosthesis.
Potential Areas of Application:
* adhesion agent
* cancer therapeutic
* research reagent
Main Advantages of Invention:
* key extraceullular matrix component
* widespread biological activity
Inventors:
Y Yamada, HK Kleinman, M Sasaki, GR Martin (NIDR)
Patent Status:
* Serial No. 07/267,564 filed 07 Nov 88; U.S. Patent 5,211,657 issued 18 May 93
* No foreign rights available
Related Technology:
Serial No. 07/272,165 filed 16 Nov 88; U.S. Patent 5,092,885 issued 03 Mar 92, entitled "Peptides with Laminin Activity"
Recent Relevant Publications:
* Barchi JJ; Russ P; Johnson B; Otaka A; Nomizu M; Yamada Y. Glycosylation of the active sequence Ser-Ile-Lys-Val-Ala-Val from (1 chain of laminin reduces tumor cell attachment activity. Bioorganic Medinal Chem Lett 5:711, 1995.
* Kibbey MC; Johnson B; Petryshyn R; Jucker M; Kleinman HK. A 110-kD nuclear shuttling protein, nucleolin, binds to the neurite-promoting IKVAV site of laminin-1. J Neurosci Res 1995 Oct 15;42(3):314-22
* Bresalier RS; Schwartz B; Kim YS; Duh QY; Kleinman HK; Sullam PM. The laminin alpha 1 chain Ile-Lys-Val-Ala-Val (IKVAV)-containing peptide promotes liver colonization by human colon cancer cells. Cancer Res 1995 Jun 1;55(11):2476-80
* Nomizu M; Weeks BS; Weston CA; Kim WH; Kleinman HK; Yamada Y. Structure-activity study of a laminin alpha 1 chain active peptide segment Ile-Lys-Val-Ala-Val (IKVAV). FEBS Lett 1995 May 29;365(2-3):227-3
* Kibbey MC; Corcoran ML; Wahl LM; Kleinman HK. Laminin SIKVAV peptide-induced angiogenesis in vivo is potentiated by neutrophils. J Cell Physiol 1994 Jul;160(1):185-93
* Weeks BS; Holloway E; Klotman PE; Akiyama SK; Schnaper HW; Kleinman HK. 12-O-tetradecanoylphorbol 13-acetate stimulates human T-lymphocyte adherence to the fibronectin RGD domain and the laminin IKVAV domain. Cell Immunol 1994 Jan;153(1):94-104
Portfolios:
Cancer - Research Materials, other
Internal Medicine - Other
Devices - Research Tools and Materials, biologicals and chemicals
Licensing Status:
Available for exclusive or non-exclusive licensing
For additional information, please contact:
Jaconda Wagner, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735, ext. 284
Fax: 301/402-0220
E-mail: Jaconda_Wagner@nih.gov
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Dvl1-Deficient Mice
Description of Invention:
Genetic factors are important modifiers of a variety of simple and complex behaviors in virtually all organisms. Genetic effects have been inferred from inbred strain analysis in rodents and from linkage analysis in rodents and humans. More recently, genes influencing specific behaviors have been identified by analyzing behavioral abnormalities in mice with targeted gene disruption.
In the present invention, mice completely deficient for Dvl1, a mouse homolog of the Drosophila segment polarity gene Dishevelled, were created by gene targeting. These mice demonstrate that Dvl1 participates in complex behaviors in mammals. Dvl1-deficient mice exhibit reduced social interaction, including differences in whisker-trimming, deficits in nest-building, less huddling contact during home cage sleeping, and subordinate responses in a social dominance test. In addition, Dvl1-deficient mice display striking abnormalities in sensorimotor gating, as indicated by attenuation of prepulse startle inhibition in the mutant mice. Prepulse inhibition is abnormal in several human neuropsychiatric disorders including schizophrenia, schizotypal personality disorders, obsessive-compulsive disorders, Huntington's disease, and Tourette syndrome. In addition, many of these disorders (as well as autism) are characterized by abnormal social interaction. Hence, Dvl1-deficient mice provide a genetic animal model of aspects of several human psychiatric disorders and serve as a useful model for screening drugs that modify abnormal social interaction and sensorimotor gating.
Potential Areas of Application:
Genetic animal model for investigating psychiatric disorders
Animal model for screening behavior-modifying therapeutics
Inventors:
AJ Wynshaw-Boris, N Lijam, D Sussman, R Paylor, J Crawley (NHGRI)
Patent Status:
OTT Reference No. E-100-97/0
Relevant Publication:
N Lijam, R. Paylor, MP McDonald, JN Crawley, CX Deng, K Herrup, KE Stevens, G Maccaferri, CJ McBain, DJ Sussman, A Wynshaw-Boris," Social Interaction and Sensorimotor Gating Abnormalities in Mice Lacking DVl1,: Cell 1997 Sep 5;90(5):895-905.
Portfolio:
Central Nervous System - Research Materials, transgenics
For additional information, please contact:
David Sadowski
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext. 288
Fax: 301/402-0220
E-mail: DS27A@NIH.GOV