00-12546. Government-Owned Inventions; Availability for Licensing

AGENCY:

National Institutes of Health, Public Health Service, DHHS.

ACTION:

Notice.

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: [phone]; fax: [phone]. 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: [e-mail]

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 [e-mail]

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: [e-mail]

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 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: [e-mail]

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: [e-mail]

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.