[Federal Register Volume 64, Number 222 (Thursday, November 18, 1999)]
[Notices]
[Pages 63049-63050]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-30065]


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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, Public Health Service, DHHS.

ACTION: Notice.

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SUMMARY: 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 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: 301/496-7057; fax: 301/402-0220. A 
signed Confidential Disclosure Agreement will be required to receive 
copies of the patent applications.

Peptide Inhibitor of Cyclin Dependent Kinase 4 (cdk4) Derived from 
MyoD

BM Paterson, J Zhang (NCI).
Serial No. 60/139,934 filed 18 Jun 1999.
Licensing Contact: Susan S. Ricker; 301/496-7056 ext. 245; e-mail: 
[email protected].

    This invention pertains to cell cycle regulation and the activity 
of the GI cyclin-dependent kinase 4 (CDK4). The invention describes a 
15 amino acid peptide and variants thereof derived from MyoD, which is 
an inhibitor of the CDK4. CDK4 is one of a number of cyclin-dependent 
kinases which control progression through the cell cycle through their 
ability to phosphorylate particular substrates at the correct phase of 
the cell cycle. CDK4 has been shown to be involved in cell cycle 
control through its ability to regulate the activity of the 
retinoblastoma protein, pRb, an activator of genes essential for cell 
division.
    Inhibitors of the cyclin-dependent kinases (CKIs), such as the 
peptides described in this invention, prevent cell cycle progression 
and induce cells to exit the cell cycle into the Go state. The peptides 
described in this invention prevent the phosphorylation of pRb by cdk4, 
an obligate step for entry into the cell cycle. Osteosarcomas and 
habdosarcomas are two types of tumors known to over-express pRb. The 
inhibitor described in this invention may be useful in treating these 
cancers or other diseases which have been specifically linked to over-
expression of active pRb.
    Background material related to this invention has been published 
[Zhang. J. et al. EMBO J 18(4): 926-33 (Feb. 15, 1999)].

Chromatographic Separation of Proteins by Ammonium Sulfate 
Precipitation

Yoichiro Ito (NHLBI)
Serial No. 09/263,609 filed 05 Mar. 99
Licensing Contact: John Fahner-Vihtelic; 301/496-7735 ext.
270; e-mail: [email protected]

    Recently, a field flow fractionation apparatus and method for the 
chromatographic separation of proteins have been developed. Unique in 
design, the fractionation apparatus contains two spiral channels, a 
reagent channel and a sample channel carved into two mating disks 
separated by a semi-permeable membrane. The primary advantage to this 
design is that it allows proteins passing through the sample channel to 
be fractioned according to their ability to precipitate out in the 
presence of an exponential ammonium sulfate concentration gradient in 
the reagent channel. Protein elution is achieved by repetitive 
precipitation, and takes place along the sample channel without the 
tedious manual labor required by conventional fractionation procedures. 
This method can also utilize other precipitation reagents such as NaCl, 
ethanol and polyethylene glycols. Applications would include 
purification of monoclonal antibodies (IgM and IgG) from a culture 
medium and ascitic fluid and affinity separation of recombinant enzymes 
from E. coli  lysate. A working prototype is undergoing additional 
refinement.

Calcium Channel Compositions and Methods of Use Thereof

Michael I. Lerman et al. (NCI)
Serial No. 60/114,359 filed 30 Dec 1998
Licensing Contact: Susan S. Rucker; 301/496-7056 ext. 245;
e-mail [email protected]

    The invention described in this patent application relates to the 
identification, isolation and cloning of a three cDNAs identified 
during a search of the short arm of chromosome 3 for a tumor suppressor 
gene (TSG) associated with lung, breast and other cancers. The cDNAs 
are alternate isoforms which encode a protein which functions as a

[[Page 63050]]

L-type voltage-dependent calcium channel. Type L-voltage dependent 
calcium channels represent one of five families of calcium channels, L, 
R, P, N, Q, which have been identified. Type L voltage-dependent 
calcium channels are found in a wide variety of tissues including the 
brain, muscle and the endocrine system.
    The gene has been mapped to the short arm of chromosome 3 at 
3p21.3. The gene, which corresponds to this cDNAs is an alpha2delta 
(2) subunit, and has been shown to be deleted in lung 
and breast cancer. The scientists have demonstrated that the expression 
of this calcium channel has been shut off in lung cancer cells and 
hypothesize that this may lead to a malignant phenotype. Possible 
applications of this technology include its use in drug screening 
assays; its use as an early diagnostic marker and/or as a prognostic or 
treatment indicator; its use in gene therapy where defective cells 
would be reconstructed with the gene and as a therapeutic agent for 
clearing autoantibodies which develop toward the alpha2delta subunit in 
the disease Lambert-Eton myasthenia syndrome.

Hepatitus C Virus (HCV) Envelope Protein Modified for Expression on 
the Host Cell Surface and Use of DNA Constructs Encoding the 
Modified Protein as a Vaccine and of Host Cells Expressing the 
Protein in Diagnostic and Screening Assays

Xavier Forns, Suzanne U. Emerson, Jens Bukh, Robert H. Purcell (NIAID)
Serial No. 60/089,779 filed 18 Jun 1998
Licensing Contact: J. Peter Kim; 301/496-7056 ext. 264;
e-mail: [email protected]

    Hepatitis C virus (HCV) is a single stranded RNA virus responsible 
for the majority of non-A non-B hepatitis. Hepatitis C virus (HCV) has 
a worldwide distribution and is a major cause of liver cirrhosis and 
hepatocellular carcinoma in the U.S., Europe, and Japan. For this 
reason, development of a vaccine against hepatitis C is of great 
importance.
    The present invention provides for hepatitis C virus (HCV) vaccines 
and diagnostic assays. The invention provides chimeric genes, 
expression vectors which comprise these chimeric genes, and DNA based 
vaccines which employ the expression vectors as immunogens to produce 
protective antibodies to HCV in a mammal. The invention further 
provides for diagnostic assays to screen sera for the presence of 
antibodies to HCV envelope proteins, as antigens in the screening of 
phage display combinatorial libraries, and as reagents to develop 
tissue culture systems suitable for testing anti-HCV envelope 
antibodies for neutralizing activity.

Human FRP and Fragments Thereof Including Methods for Using Them

US Rubin (NCI), PW Finch, SA Aaronson, and X He
Serial No. 09/087, 031 field 29 May 1998
Licensing Contact: Susan S. Rucker; 301/496-7056 ext 245; e-mail: 
[email protected]

    This application relates to signal transduction pathways and 
mechanisms. More particularly, the application describes the isolation, 
cloning of the cDNA encoding, and characterization of a human protein 
denoted ``Frizzled Related Protein'' or FRP. FRP, also known as sFRP-1, 
is a secreted protein which contains an N-terminal cysteine-rich domain 
(CRD) which is a similar to the CRDs of the frizzled family of membrane 
anchored Wnt receptors. sFRP-1 lacks any transmembrane region or 
cytoplasmic domain characteristic of molecules capable of transducing a 
signal within a cell but is preferentially distributed to the cell 
surface or matrix.
    Wnt signaling has been implicated in the development of cancers and 
various organs. sFRP-1 has been demonstrated to antagonize Wnt 
signaling and therefore may function as an inhibitor of Wnt activity or 
otherwise modulate Wnt signaling. In addition, others have suggested 
that sFRP-1 plays a role in regulating apoptosis by sensitizing cells 
to apoptotic agents and modulating levels of -catenin. The 
gene encoding sFRP-1 is found on the short arm of chromosome 8 at 
8p11.1-12. RNA transcripts have been identified in multiple adult 
tissues such as the heart, kidney, ovary, prostate, testis, small 
intestine and colon but have not been detected in a number of other 
tissues.
    In view of this sFRP-1 derived products may be useful in further 
study of sFRP-1--Wnt interactions, drug screening assays, the 
development of diagnostics for cancer or other conditions which are 
related to Wnt signaling, or may be developed as therapeutic agents 
themselves. Recombinant FRP, expression vectors containing FRP cDNA and 
cDNA containing the full length FRP coding sequence are available. 
Limited quantities of rabbit polyclonal antisera which specifically 
binds FRP is also available.
    This work has appeared, in part, in Finch, PW, et al. PNAS 94(13): 
6770-75 (June 24, 1997) and has been published as WO 98/54325 (Dec. 3, 
1998).

Use of Lipoxygenase Inhibitors as Anti-Cancer Therapeutic and 
Intervention Agents

James L. Mulshine, Marti Jett (NCI)
Serial No. 08/704,569 filed 03 Dec 96
Licensing Contact: Girish Barua; 301/496-7056 ext. 263; email 
[email protected]

    We have reported that S-Lipoxygenase inhibitors can treat or 
prevent certain epithelial cancers such as lung cancer, breast cancer, 
and head and neck cancer. This is believed to occur from the 
interruption of the 5-lipoxygenase pathway which results in increased 
tumor cell apoptosis. We have demonstrated this effect for the growth 
factor-induced stimulation in several model systems so we propose this 
as a robust anti-promotional chemoprevention approach as well.
    Suitable 5-lipoxygenase inhibitors useful for the methods of the 
present invention include 2-(12-Hydroxydodeca-5, 10-dinyl) 3,5,6-
trimethyl-1,4benzoquinone and derivatives thereof; Nordihydroguiaretic 
acid and derivatives and 3-[1-(4-chlorobenzy)-3-t-butylthio-t-
isopropyl-indol-2-yl] -2, 2-dimethylpropionic acid and derivatives 
thereof. Also intended to be encompassed by this are hydroxyurea 
derivatives as inhibitors of 5-lipoxygenase for use in the prevention 
and treatment of the cancers mentioned above.

    Dated: November 9, 1999.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 99-30065 Filed 11-17-99; 8:45 am]
BILLING CODE 4140-01-M