[Federal Register Volume 65, Number 97 (Thursday, May 18, 2000)]
[Notices]
[Pages 31577-31578]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-12546]


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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.

Mutant Aequorea Victoria Fluorescent Proteins Having Increased 
Cellular Fluorescence

George N. Pavlakis, George A. Gaitanaris, Roland H. Stauber, John N. 
Vournakis (NCI)
U.S. Patent 6,027,881 issued 22 February 2000
Licensing Contact: Girish C. Barua; 301/406-7056 ext. 263; e-mail: 
<a href="/cdn-cgi/l/email-protection#bddadf8c85c9fdd3d4d593dad2cb"><span class="__cf_email__" data-cfemail="c7a0a5f6ffb387a9aeafe9a0a8b1">[email protected]</span></a>

    The Green Fluorescent Protein (GFP) from the jellyfish Aequorea 
victoria is rapidly becoming an important reporter molecule for 
monitoring gene expression in vivo, in situ and in real time. GFP can 
be used to tag proteins, cellular compartments, or cells, and has found 
many uses in the study of biological processes. Unlike other 
bioluminescent reporters, GFP fluoresces in the absence of any other 
proteins, substrates, or cofactors. Improved signal to noise ratio is 
important for several applications using GFP. We have generated GFP 
mutants that increase the fluorescent signal by at least tenfold over 
the wild-type GFP in mammalian cells. These mutants emit either green 
or blue light, detectable when single copy genes are inserted into the 
cell.

Method for Refolding Recombinant Endostatin

Dong Xie, Paul Grulich, John W. Erickson (NCI)
DHHS Reference No. E-260-99/0 filed 18 Feb 2000
Licensing Contact: Richard Rodriguez; 301/496-7056 ext. 287; e-mail 
<a href="/cdn-cgi/l/email-protection#7b09094a4e4f213b151213551c140d"><span class="__cf_email__" data-cfemail="f78585c6c2c3adb7999e9fd9909881">[email protected]</span></a>

    Endostatin is a naturally occurring collagen-derived fragment that 
has been the subject of intense interest due to its reported anti-tumor 
and anti-metastatic properties. Endostatin's exact mode of action is 
unknown, and a detailed analysis of this mode of action has been 
hampered by the inability to consistently produce large quantities of 
refolded recombinant endostatin. While endostatin can be recombinantly 
produced, the isolated protein is found in an unfolded state. Thus a 
need exists to produce recombinant endostatin in a biologically active 
form for continuing clinical development and studying specific motifs 
or structures associated with endostatin which may be responsible for 
its anti-angiogenic/metastatic properties. The current invention 
comprises a method of renaturing endostatin comprising contacting 
unfolded endostatin with an effective amount of cyclodextrin in an 
aqueous environment buffered at a neutral or acidic ph.

CpG Oligodeoxynucleotides Used To Improve Human Immune Responses

Dennis Klinman, Daniela Verthelyi, Kenji Ishii (FDA)
DHHS Reference No. E-078-00/0 filed 14 Jan 2000
Licensing Contact: Peter Soukas; 301-496-7056, ext. 268; e-mail: 
<a href="/cdn-cgi/l/email-protection#7e0e0d4f474d1d3e10171650191108"><span class="__cf_email__" data-cfemail="364645070f055576585f5e18515940">[email protected]</span></a>

    This invention concerns immune-activating oligonucleotides 
containing CpG motifs. Although it is known that certain CpG sequences 
can induce responses from human immune system cells, individual 
subjects show considerable heterogeneity in their response to different 
CpG sequences. These different responses make it difficult to induce a 
therapeutic immune response in all members of a diverse population 
using a single CpG sequence, even if such a sequence is repeated in a 
CpG oligonucleotide. The inventors have found that a broad-based 
immunomodulatory response scan be generated in a wide cross-section of 
subjects by using a mixture of multiple different CpG motifs. The 
mixture of oligodeoxynucleotides of the present invention can either be 
mixtures of different oligodeoxynucleotides expressing different CpG 
motif is or a

[[Page 31578]]

single oligodeoxynucleotide containing multiple different motifs. The 
oligodeoxynucleotides of the current invention have the capacity to 
stimulate humoral, cell-mediated immune responses or both humoral and 
cell-mediated immune responses, depending on the motifs utilized. The 
oligodeoxynucleotides of the present invention have uses including, but 
not limited to, treating allergies infectious diseases, cancer, and 
autoimmune disorders; furthermore, the obligodeoxynucleotides of the 
present invention have utility as vaccine adjutants for conventional 
and DNA vaccines, and as anti-sense therapeutics.

A Novel Neuropeptide Potentially Involved in Pain Regulation, Blood 
Pressure Control, and Other Physiological Functions

Dr. Ted. Usdin (NIMH)
DHHS Reference No. E-123-99/0 filed 15 Jun 1999
Licensing Contact: Norbert Pontzer; 301/496-7736 ext. 284; e-mail: 
<a href="/cdn-cgi/l/email-protection#afc1df9a96c1efc1c6c781c8c0d9"><span class="__cf_email__" data-cfemail="0a647a3f33644a646362246d657c">[email protected]</span></a>

    A 39 amino acid peptide which activates the newly discovered 
parathyroid 2 (PTH2) receptor has been isolated, sequenced and cloned. 
The PTH2 receptor is a member of the secretin receptor family which 
includes receptors for secretin, vasoactive intestinal polypeptide, 
calcitonin, glucagon, gastric inhibitory polypeptide and CRF. 
Immunohistochemical mapping of the PTH2 receptor shows a distribution 
of PTH2 receptor in: endocrine tissue including pancreatic islet 
somatostatin cells; thyroid parafollincular cells and peptide secreting 
cells in the intestine; heart muscle, and nervous tissue including 
areas of the hypothalamus involve din pituitary regulation and the 
somatic and visceral primary sensory neuron terminals in the dorsal 
horn of the spinal column. This distribution suggests that the ligand 
or an antagonist may be used to treat pain, high blood pressure, 
diabetes, GI disturbances, psychiatric disease and other pathologies.

Novel Disulfide Conjugated Cell Toxins and Methods of Making and 
Using Them

David Fitzgerald, Michael J. Iadarola (NCI)
DHHS Reference No. E-301-99/0 filed 22 Oct 1999
Licensing Contact: Marlene Shinn; 301/496-7056 ext. 285; e-mail: 
<a href="/cdn-cgi/l/email-protection#ddb0aee9e5efb09db3b4b5f3bab2ab"><span class="__cf_email__" data-cfemail="bed3cd8a868cd3fed0d7d690d9d1c8">[email protected]</span></a>

    Efforts to find more effective treatments of chronic pain with few 
unwanted side effects or which do not dampen acutely painful 
potentially dangerous stimuli remains a continuing challenge. Current 
analgesic therapies often fall short of therapeutic goals and typically 
have unacceptable side effects. Thus the discovery of a more 
efficacious and safe means to control chronic pain is unpredictable and 
therapeutically advantageous.
    The NIH announces a new technology which is an effective treatment 
for pain control directed at the local ablation of NK-1 receptor 
expressing cells. The NK-1 receptor is found on a variety of cell 
types, the predominant expressing cells being pain-mediating neurons. 
Other cell types include brain cells and neostriatum cells through the 
axon collaterals of spiny projection neurons to name a few. This 
technology is the discovery of a novel conjugate generated between TNB-
derivatized Substance P (SP) and a truncated version of Pseudomonas 
exotoxin, termed PE35. When administered to NK-1 receptor expressing 
cells, SP-PE35 induced cell death, while cells that expressed NK-2 and 
NK-3 receptors remained unaffected. This toxin allows for the killing 
of a specific category of cell types and is an effective means of 
treating a variety of conditions, in particular chronic pain or tumors 
that express NK-1 receptors. The toxin can be placed in a 
pharmaceutically acceptable excipient and can be combined with any 
method of procedure currently being used clinically, making it a 
versatile and superior form of treatment.

    Dated: April 25, 2000.
Jack Spiegel,
Director, Division of Technology Development and Transfer, National 
Institutes of Health.
[FR Doc. 00-12546 Filed 5-17-00; 8:45 am]
BILLING CODE 4140-01-M


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