[Federal Register Volume 66, Number 66 (Thursday, April 5, 2001)]
[Notices]
[Pages 18098-18099]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-8375]


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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 contacting John Rambosek, 
Ph.D., Technology Licensing Specialist, Office of Technology Transfer, 
National Institutes of Health, 6011 Executive Boulevard, Suite 325, 
Rockville, Maryland 20852-3804; telephone: 301/496-7056 ext. 270; fax: 
301/402-0220; e-mail: [email protected]. A signed Confidential 
Disclosure Agreement will be required to receive copies of the patent 
applications.

Enhanced Homologous Recombination Mediated by Lambda Recombination 
Proteins

Drs. E. Lee, N. Copeland, N. Jenkins, and D. Court (NCI)
DHHS Reference No. E-077-01/0 filed 26 Feb 2001

    The present invention concerns methods to enhance homologous 
recombination in bacterial and eukaryotic cells using recombination 
proteins derived from bacteriophage lambda. It also concerns methods 
for promoting homologous recombination using other recombination 
proteins. Concerted use of restriction endonucleases and DNA ligases 
allows in vitro recombination of DNA sequences. The recombinant DNA 
generated by restriction and ligation may be amplified in an 
appropriate microorganism such as E. coli, and used for diverse 
purposes including gene therapy. However, practical limitations imposed 
by this system generally results in DNA fragments with an upper limit 
of approximately 20 kilobases. The present invention utilizes 
homologous recombination instead of restriction enzymes to build DNA 
constructs. These DNA constructs may be several hundreds of kilobases 
in size. Using this invention, small linear fragments of DNA (such as a 
gene of interest) may be inserted efficiently and precisely into very 
large cloned fragments of DNA. These DNA constructs may be used for a 
variety of purposes, including generation of transgenic animals in 
which appropriate tissue specific regulation of gene expression is 
maintained.

Biologically Active FLAG-Epitope-Tagged Transforming Growth Factor 
Beta (TGF-beta) Protein

Lawrence A. Wolfraim, John J. Letterio, Kathleen Flanders, Lalage 
Wakefield, Anita B. Roberts (NCI)

[[Page 18099]]

DHHS Reference No. E-149-00/0 filed 20 Oct 2000

    The current invention discloses an epitope-tagged TGF-beta that can 
be expressed in mammalian cells while still maintaining complete 
biological activity. An epitope is a region of a protein that can be 
recognized by an antibody. Although there are currently TGF-beta 
antibodies available, their usefulness is limited by cross reactivity 
amongst all members of the TGF family, as well as by an inability to 
distinguish between endogenous and exogenous TGFs. The current 
invention provides a means for distinguishing between these variations 
by epitope tagging of TGF-beta. The tag of this invention is the FLAG 
tag, an 8 amino acid sequence consisting of DYKDDDDK (D=aspartate, 
Y=tyrosine, K=lysine). Two FLAG tagged TGF constructs have been 
generated: the first inserts the tag at the amino terminus of the 
mature polypeptide and the second inserts the tag between amino acids 
11 and 12 of the mature polypeptide. The core of the invention is that 
the insertion of the tag into these specific regions of the TGF 
molecule still allows for the retention of complete biological 
activity. Thus the tagged TGF may be monitored and distinguished by 
various biochemical means (through the FLAG epitope) from endogenous 
TGFs while at the same time the physiological effects of the tagged TGF 
may be analyzed as though it were a natural TGF. The TGF of the current 
invention may also be used to study TGF receptor expression levels, the 
loss of which has been correlated with various disease states, 
including cancers and autoimmune diseases. In addition, in the future 
the FLAG tag may permit the development of therapeutic compounds which 
could be used to ``ferry'' the TGFs to target tissues, thereby reducing 
side effects associated with systemic administration of TGF family 
proteins.

    Dated: March 29, 2001.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 01-8375 Filed 4-4-01; 8:45 am]
BILLING CODE 4140-01-P