National Institutes of Health, Public Health Service, DHHS.
Notice.Start Printed Page 70266
The inventions listed below are owned by an agency 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.
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.
Adoptive Immunotherapy With Enhanced T-Lymphocyte Survival
Richard Morgan (NCI) and Steven Rosenberg (NCI)
U.S. Provisional Patent Application No. 60/617,340 filed 08 Oct 2004 (DHHS Reference No E-340-2004/0-US-01) and U.S. Provisional Patent Application filed 12 Oct 2004 (DHHS Reference No E-340-2004/1-US-01)
Licensing Contact: Jeff Walenta; (301) 435-4633; firstname.lastname@example.org.
Adoptive immunotherapy strategies have existed for several years now and many have proven to be highly successful in a limited subset of patients. This limited response rate among a diverse patient population may not be surprising, given the complexity of the immune system and the complicated evolution of a normal cell to a immune evading malignancy. A common observation amongst most patients that did not respond to adoptive therapy strategies is that the immune response to the cancer was not sustained.
A number of cytokines have been shown to sustain a T-cell response when administered systemically with autologous isolated T-cells. However, the systemic delivery of many cytokines, such as IL-2, will cause significant toxicity before the beneficial immunologic effects of the autologous T-cells can occur. This invention describes a method of transfecting isolated autologous T-Lymphocytes with endogenous cytokines, for example IL-7 and IL-15, to sustain an adoptive T-lymphocyte response without systemic toxicity. The invention also describes a method for improving expression of transfected cytokines via a codon optimized IL-15 vector.
This invention was developed at the NCI Surgery Branch. The Surgery Branch plans to initiate clinical studies utilizing this technology and collaborative opportunities may be available. Publications which may provide background information for this technology include:
1. Rosenberg, SA and Dudley, ME. Cancer regression in patients with metastatic melanoma after the transfer of autologous antitumor lymphocytes. Proc Natl Acad Sci U S A. 2004 Oct 5;101 Suppl 2:14639-45. Epub 2004 Sep 20.
2. Klebanoff CA, Finkelstein SE, Surman DR, Lichtman MK, Gattinoni L, Theoret MR, Grewal N, Spiess PJ, Antony PA, Palmer DC, Tagaya Y, Rosenberg SA, Waldmann TA, Restifo NP. IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells. Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1969-74. Epub 2004 Feb 04.
3. Dudley ME, Rosenberg SA. Adoptive-cell-transfer therapy for the treatment of patients with cancer. Nat Rev Cancer. 2003 Sep;3(9):666-75. Review.
4. Liu K, Rosenberg SA. Interleukin-2-independent proliferation of human melanoma-reactive T lymphocytes transduced with an exogenous IL-2 gene is stimulation dependent. J Immunother. 2003 May-Jun;26(3):190-201.
5. Liu K, Rosenberg SA. Transduction of an IL-2 gene into human melanoma-reactive lymphocytes results in their continued growth in the absence of exogenous IL-2 and maintenance of specific antitumor activity. J Immunol. 2001 Dec 1;167(11):6356-65.
A New Approach Toward Macrocyclization of Peptides
Terrence R. Burke, Jr. et al. (NCI)
DHHS Reference No. E-327-2004/0-US-01
Licensing Contact: George Pipia; (301) 435-5560; email@example.com
The invention relates to cyclic peptides for use as inhibitors of oncogenic signal transduction for cancer therapy. The current invention discloses novel cyclic peptides resulting from ring closure between the alpha and beta positions of C-terminal and N-terminal residues, respectively. This allows retention of key functionality needed for binding to target proteins, which results in increased affinity.
Cyclic peptides that retain key chemical functionality may be of particular importance in inhibiting oncogenic signaling cascades for therapeutic benefit. In many oncogenic signal transduction cascades, tyrosine protein kinases phosphorylated target proteins. Propagation of the signal is achieved when these phosphorylated tyrosyl residues are bound by proteins bearing SH2 domains. Cyclic peptides that disrupt the interaction between proteins with SH2 domains and proteins with phosphorylated tyrosyl residues could block oncogenic signals and serve as powerful cancer therapeutic agents. As several moieties are required for optimal recognition by SH2 domains, the cyclic peptides of the current invention could be more effective inhibitors of SH2 domain proteins, or of other proteins where increased specificity is desired. The inventors have determined that the peptides of the current invention bind to the Grb2-SH2 domain with high affinity, supporting their potential use as therapeutic agents. The current invention is related to U.S. Provisional Application No. 60/504,241; DHHS Reference No. E-315-2003/0-US-01.
cDNA for Murine PEDF
IR Rodriguez, GJ Chader, VK Singh (NEI)
DHHS Reference No. E-112-2004/0—Research Tool
Licensing Contact: Susan Rucker; (301) 435-4478; firstname.lastname@example.org.
This technology is a cDNA, obtained from mouse liver, which encodes the open reading frame of the murine homolog of pigment epithelium-derived factor (mPEDF). PEDF is a serpin protein that has not been demonstrated to have serine protease activity in a physiological setting but which exhibits diverse biologic properties including neurotrophic activity and anti-angiogenic activity. The mPEDF cDNA may be used to study PEDF function and may be particularly useful in research applications comparing mPEDF to hPEDF. The cDNA, provided as a plasmid designated pMOU12A, can be readily inserted into an expression vector. The cDNA is further described in Singh, VK et al. Mol Vision 4: 7 (April 20, 1998). No patent application has been or will be filed by the NIH for this technology. The cDNA is available through a biological materials license agreement.
Novel Compounds That Release Both Nitric Oxide (NO) and Nitroxyl (HNO) as Pharmacological Agents
Larry Keefer et al. (NCI)
U.S. Provisional Application No. 60/540,368 filed 30 Jan 2004 (DHHS Reference No. E-095-2004/0-US-01) Start Printed Page 70267
Licensing Contact: Norbert Pontzer; (301) 435-5502; email@example.com
The simple diatomic molecule nitric oxide (NO) is known to play a diverse and complex role in cellular physiology. NCI scientists have previously produced a number of nucleophile/nitric oxide adducts (diazeniumdiolates) that spontaneously dissociate at physiological pH to release nitric oxide by stable first order kinetics. These compounds are finding diverse therapeutic uses as pharmacological agents. Growing evidence suggests that redox related forms of NO such as nitroxyl (HNO) also have a rich pharmacological potential and may complement that of NO. The present invention provides compounds that release both NO and HNO under physiological conditions, compositions comprising those compounds and methods of using the compounds alone and in conjunction with medical devices such as stents to treat disease. Included among the compositions claimed is a glycosylated prodrug derivative that can be cleaved to active form by β-D-glucosidase (J. Am. Chem. Soc. 2004, 126, 12880-12887).
A Method With Increased Yield for Production of Polysaccharide-Protein Conjugate Vaccines Using Hydrazide Chemistry
Che-Hung Robert Lee and Carl Frasch (FDA), U.S. Provisional Application No. 60/493,389 filed 06 Aug 2003 (DHHS Reference No. E-301-2003/0-US-01)
Licensing Contact: Peter Soukas; (301) 435-4646; firstname.lastname@example.org.
Current methods for synthesis and manufacturing of polysaccharide-protein conjugate vaccines employ conjugation reactions with low efficiency (about twenty percent). This means that up to eighty percent of the added activated polysaccharide (PS) is lost. In addition, inclusion of a chromatographic process for purification of the conjugates from unconjugated PS is required.
The present invention utilizes the characteristic chemical property of hydrazide groups on one reactant to react with aldehyde groups or cyanate esters on the other reactant with an improved conjugate yield of at least sixty percent. With this conjugation efficiency the leftover unconjugated protein and polysaccharide would not need to be removed and thus the purification process of the conjugate product can be limited to diafiltration to remove the by-products of small molecules. The new conjugation reaction can be carried out within one or two days with reactant concentrations between 1 and 25 mg/mL at PS/protein ratios from 1:2 to 3:1, at temperatures between 4 and 40 degrees Centigrade, and in a pH range of 5.5 to 7.4, optimal conditions varying from PS to PS.
Therefore, this invention can reduce the cost of conjugate vaccine manufacture.Start Signature
Dated: November 24, 2004.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.
[FR Doc. 04-26596 Filed 12-2-04; 8:45 am]
BILLING CODE 4140-01-P