[Federal Register Volume 66, Number 83 (Monday, April 30, 2001)]
[Notices]
[Pages 21405-21406]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-10580]



[[Page 21405]]

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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.

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 Feb 26, 2001
Licensing Contact: John Rambosek; 301/496-7056 ext. 270; e-mail: 
[email protected]

    The present invention concerns a method to enhance homologous 
recombination in bacteria using the Red recombination system derived 
from a defective lambda prophage. This lambda system, like the RecET 
system, uses homologous recombination proteins to protect and recombine 
the electroporated linear DNA. However, the lambda system is at least 
50 to 100 times more efficient than the RecET system. The high 
recombination efficiency offered by this system makes it possible to 
manipulate DNA without drug selection. Point mutations, deletions, or 
insertions can be engineered into any gene on plasmids or bacterial 
artificial chromosomes (BACs) for gene functional analysis. This 
recombination system also can be used to subclone DNA fragments as 
large as 80 kb from BACs by gap repair. Targeting vectors for embryonic 
stem cells or transgenic constructs by BAC engineering can now be 
subcloned with ease, and virtually any region of the engineered BAC may 
be included in the final subclone. The ability to efficiently and 
precisely modify genes or regulatory sequences on BACs, combined with 
the ability to include or exclude them during the subcloning process, 
should make it possible to dissect the function of these sequences in 
the whole animal at a high-through-put level not previously possible.
    This lambda recombination system has been used to introduce a Cre 
recombinase gene into the coding region of the mouse neural-specific 
enolase gene carried on a 250 kb mouse BAC after transfer of the mouse 
BAC into DY380 E. coli cells which carry the lambda recombination 
system. Transgenic mice that were subsequently generated which carry 
this modified BAC specifically expressed Cre in all mature neurons and 
Cre expression mirrored that of the mouse neural-specific enolase gene.
    This abstract modifies an abstract for this technology published in 
the Federal Register on Thursday, April 5, 2001 (66 FR 18098).

Use of Endogenous Vertebrate Phytase to Increase Capacity To 
Utilize Phytic Acid in Livestock Feed

Stephen Shears (NIEHS), Paul Reynolds, Jim Petitte
DHHS Reference No. E-139-00/0 filed Aug 11, 2000
Licensing Contact: John Rambosek; 301/496-7056 ext. 270; e-mail: 
[email protected]

    This invention discloses the concept of creating transgenic farm 
animals that secrete a native phytase enzyme into their digestive 
tracts. It has long been recognized that monogastric animals (e.g. pigs 
and chickens) do not utilize dietary phosphorus as efficiently as 
possible. This is because a high percentage of total phosphorus (70% in 
cereals, 50% in legume seeds) is present as phytic acid and its salts--
phytate. Monogastric animals utilize phytate inefficiently because they 
lack the enzyme phytase in their digestive systems. Phytase liberates 
the phosphorus from phytate, thereby making dietary phosphorus 
available to the animals. This has the dual effect of both promoting 
more efficient growth of the animals, as well as imposing less of an 
environmental burden in the form of excess phosphorus in water streams.
    Use of phytase as a growth feed supplement is well known. However, 
in the past the focus has always been on adding exogenous phytase to 
animal feed, or to increase the level of phytase expression in the 
seeds making up the feed. The inventors' novel concept is to redirect 
expression of a naturally occurring phytase gene so that the enzyme 
will be secreted into the intestinal lumen. This will create farm 
animals that can more efficiently utilize unsupplemented feeds. Another 
problem with existing phytases that the present invention overcomes is 
that phytase tends to be unstable during the heat treatment used to 
process feed. This invention overcomes this limitation because the 
phytase does not have to incorporated into feed at all.

Cloning of the Human Nuclear Receptor Co-Repressor Gene

Dr. Johnson M. Liu (NHLBI)
DHHS Reference Number E-088-99/0 filed Aug 3, 1999
Licensing Contact: John Rambosek; 301/496-7056 ext. 270; e-mail: 
[email protected]

    Alteration in the expression of human genes is critical to the 
development and progression of many diseases. These include, among 
others, cancer, inflammation, cardiovascular disease, 
hypercholesterolemia, blood pressure, and diabetes. The Human Nuclear 
Receptor Co-Repressor (HuN-Cor) gene represents a technology that may 
be used to alter the transcription of genes. It provides a general 
mechanism by which many genes may be modulated throughout the entire 
range of being turned on to being completely turned off. The HuN-Cor 
gene encodes for a ubiquitously expressed protein that silences other 
genes. It does this by specifically recruiting an enzyme complex that 
causes local folding of chromatin, not allowing other transcription 
factors to access the DNA. HuN-Cor represents a powerful research tool 
that can be used to study gene expression and characterization of many 
different genes. It may ultimately have great utility in controlling 
gene expression via gene therapy technology, and may also be useful as 
a target for the isolation of pharmaceutical compounds that enhance or 
inhibit expression of genes. For example, it may be possible to 
engineer mutations of the HuN-Cor gene that dominantly inhibit its 
function; these mutants could then be expressed in appropriate target 
tissues or cells in order to control gene expression. Finally, the gene 
product may have utility in the discovery of therapeutic compounds that 
modulate gene expression via HuN-Cor.

Antibodies That Selectively Detect the Human Nestin Protein

Conrad Messam et al. (NINDS)

[[Page 21406]]

DHHS Reference Nos. E-145-99/0 and E-009-01/0
Licensing Contact: Norbert Pontzer; 301/496-7736, ext. 284; e-mail: 
[email protected]

    Nestin is an intermediate filament protein first described in early 
embryonic neuroepithelial stem cells. Although not found in most cells 
of the mature CNS, nestin is the predominant marker used to detect the 
small population of undifferentiated cells. The presence of nestin 
identifies stem, progenitor and some tumor cells in the CNS, and also 
labels areas of reactive gliosis in the CNS. Available methods to 
detect nestin use antibodies generated against rat nestin protein. 
Since rat and human nestin have only about fifty percent sequence 
homology, these antibodies may not be optimal for detecting nestin in 
human cells.
    NIH scientists used a novel human nestin immunogen to generate 
polyclonal and monoclonal antibodies that bind with high affinity and 
specificity to human nestin. The immunogen was expressed from a 450 
base-pair segment of human nestin mRNA, which has 11 nucleotide 
differences from previously published human nestin. These antibodies 
increase the specificity to accurately detect human nestin in all 
stages of brain development and will increase our understanding of 
glial differentiation. In addition, this technology may be useful for 
detecting glioblastomas or other early stage neuroectodermal tumors and 
for following transplanted stem cells.

    Dated: April 20, 2001.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 01-10580 Filed 4-27-01; 8:45 am]
BILLING CODE 4140-01-P