[Federal Register Volume 65, Number 174 (Thursday, September 7, 2000)]
[Notices]
[Pages 54285-54286]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-22880]


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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.

Use of Cumulative Distribution Functions To Determine Protein 
Purity and Homogeneity

Alfred L. Yergey, Paul S. Blank, Christin M. Sjomeling (NICHD)
DHHS Reference No. E-163-00/0 filed 28 Apr 2000
Licensing Contact: Vasant Gandhi; 
301/496-7056 ext. 224; 
e-mail:[email protected]

    Successful solutions to numerous problems in the biochemical 
sciences depend on the ability to produce ``pure'' proteins and 
recognize the degree to which proteins might be modified. Current 
methods used for assessing purity are relatively nonspecific and 
insensitive to small differences in molecular weight. The inventors 
have developed a computer-implemented method and system for 
nonparametric statistical analysis of matrix-assisted laser desorption 
ionization (MALDI) protein spectra but is equally applicable to 
deconvoluted electrospray ionization (ESI) spectra. The invention 
facilitates assessing protein heterogeneity and detection of otherwise 
indistinguishable differences in the distribution of molecular weight. 
A principal advantage is that no additional instrumentation is required 
beyond that typically included in a mass spectrometry analysis system.

Hsp70-Like ATPase Peptide Binds Chap1/Dsk2

Frederic J. Kaye (NCI)
DHHS Reference No. E-282-99/0 filed 15 Sep 1999
Licensing Contact: Elaine White; 301/496-7056 ext. 282; e-mail: 
[email protected]

    The current invention embodies the identification of a novel gene 
and protein, Chap1/Dsk2, a ubiquitin-linked protein which appears to 
play a vital role in regulating mitosis. Identified also is the 
conserved 20 amino acid region within the ATPase domain of the protein 
chaperone STCH, an Hsp70-like protein, which is the binding site for 
Chap1/Dsk2 and other ubiquitin-linked proteins.
    Protein chaperones are essential for cell viability, regulating 
various cell cycle events including the biosynthesis, folding and 
unfolding, transport, multiunit assembly, and degradation of cell 
proteins. Overexpression of protein chaperones, such as STCH, can serve 
to suppress tumorigenesis and apoptosis. It therefore is believed that 
the peptide identified as the binding domain of STCH may have potential 
for use as a therapeutic agent against cancer or various infectious 
diseases, via modulation of tumorigenesis, apoptosis, or the multiunit 
assembly of viral particles such as HIV.

Polypeptides Comprising IL-6 Ligand Binding Receptor Domains and 
Related Nucleic Acids, Antibodies, Compositions and Methods

W. Carl Saxinger (NCI)
DHHS Reference No. E-061-99/0 filed 27 Aug 1999
Licensing Contact: Richard Rodriguez; 301/496-7056 ext. 287; e-mail: 
[email protected]

    The biological activities of IL-6 include the stimulation of B and 
T cell growth and differentiation, production of acute-phase proteins 
by hepatocytes, multilineage hematopoiesis, osteoblast formation, 
maturation of megakaryocytes and platelet production. An abnormal 
expression of IL-6 may be involved in the pathogenesis of a variety of 
diseases, among which are multiple myeloma, rheumatoid arthritis, 
postmenopausal osteoporosis, chronic autoimmune diseases, Castleman's 
disease and AIDS. Methods of abrogating the effects of abnormal 
expression of IL-6 can be made at its site of production or at its 
target. The inventors of this technology have focused on the latter 
technique. Using a unique, newly patented, automated peptide array 
system, the inventors have studied specific sequences potentially 
involved in protein-protein interactions at the molecular level. This 
system was used to identify and isolate potential target peptide 
sequences within the IL-6 receptor molecule. Candidate peptide 
sequences were identified by direct binding to the IL-6 ligand by 
optimally displayed IL-6 receptor peptide segments in solid phase form. 
The specific binding properties of the peptide sequences were verified 
by using IL-6 heteroantisera, and the peptides have been shown to 
mitigate or reverse the effects of the above referenced properties of 
IL-6 in tissue culture.

Receptor-Mediated Uptake of an Extracellular Bcl-XL Fusion Protein 
Inhibits Apoptosis

Richard J. Youle, Xiuhuai Liu, JoAnn Castelli (NINDS)
DHHS Reference No. E-073-99/0 filed 16 Aug 1999

[[Page 54286]]

Licensing Contact: Richard Rodriguez; 301/496-7056 ext. 287; e-mail: 
[email protected]

    The present invention relates to the field of apoptosis, in 
particular, it relates to apoptosis-modifying fusion proteins with at 
least two domains, one of which targets the fusion proteins to a target 
cell, and another of which modifies an apoptotic response of the target 
cell. For example, fusing various cell-binding domains to Bcl-XL and 
Bad allows targeting to specific subsets of cells in vivo, permitting 
treatment and/or prevention of cell-death related consequences of 
various diseases and injuries. This technology could be used to 
minimize or prevent apoptotic damage that can be caused by 
neurodegenerative disorders, e.g., Alzheimer's disease, Huntington's 
disease or spinal-muscular atrophy, stroke episodes or transient 
ischemic neuronal injury, e.g., spinal cord injuries. Additionally, 
apoptotic-enhancing fusion proteins of the current invention could be 
used to inhibit cell growth, e.g., uncontrolled cellular proliferation.

DNA Binding Protein and Sequence as Insulators Having Specific 
Enhancer Blocking Activity for Regulation of Gene Expression

Adam C. Bell, Adam G. West, Gary Felsenfeld (NIDDK)
DHHS Reference Nos. E-220-98/0 filed 30 Jun 1999 and E-220-98/1 filed 
19 Apr 2000
Licensing Contact: Girish Barua; 301/496-7735 ext. 263; e-mail: 
[email protected]

    This patent application has two components. The first is the 
identification of a functional 50bp fragment of a previously known 
chicken chromatin insulator protein. The second component is the 
identification of the REBL (Required for Enhancer Blocking) CTCF 
protein (CCCTC-binding factor) which binds to the 50bp fragment. [The 
relationship between these two can be analogized as a receptor (50 bp 
fragment) and its ligand (the REBL CTCF protein).] These two elements 
can be used separately or together to regulate gene expression.
    An insulator is a DNA sequence which is capable of acting as a 
barrier to neighboring cis-acting elements, preventing gene activation 
when juxtaposed between an enhancer and a promoter (i.e., when the 
insulator is placed between the enhancer and the promoter gene 
activation is blocked). An insulator will also act to protect a stably 
integrated reporter gene from position effects. This 50 bp fragment 
represents a functionally active domain of the chicken insulator 
protein which is both necessary and sufficient for enhancer blocking 
activity in human cells. The previously described chicken chromatin 
insulator is a 1.2 kb fragment which, where overall size of the vector 
to be delivered is a concern, for example, in gene therapy, may be too 
large for some applications. The identification of this active 50 bp 
fragment may therefore be a preferred alternative.
    The identification of the REBL CTCF protein as an agent which binds 
to the 50 bp insulator fragment and whose binding activity is necessary 
for blocking of enhancer activity provides an additional element which 
may be used to more specifically control gene regulation. As most gene 
expression is dependent on the activity of multiple components the 
identification of a specific binding factor which functions as a 
blocking enhancer activity may permit more precise control of gene 
expression. The human REBL protein has regions which share homology 
with previously disclosed partial human cDNAs. It has a molecular 
weight of 135 kDa. A chicken homolog has also been identified. CTCF was 
originally identified as a repressor of the chicken c-myc gene.

    Dated: August 29, 2000.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 00-22880 Filed 9-6-00; 8:45 am]
BILLING CODE 4140-01-U