NIH Invention Disclosures, Aug. 19, 1996

NIH invention disclosures, forwarded for publication in the Federal Register, August 19, 1996


Immunization With Synthetic Peptides Generate Cytotoxic T Cell Responses Against The EWS/FL1 1 Ewing's Sarcoma Fusion Protein And The PAX-3/FKHR Alveolar Rhabdomysarcoma Fusion Protein

Description of Invention:
This invention provides novel methods of producing vaccines and therapeutics to viral infections or cancer(s). This method utilizes irradiated, peptide-pulsed antigen presenting cells (APCs) which are coated with synthetic or recombinant peptides. These APCs can be used to induce a tumor specific cytotoxic T lymphocyte (CTL) response. This broadly applicable method uses safe, non-toxic synthetic or recombinant peptides and does not utilize harmful adjuvants or live viral vectors. Peptides derived from viral or bacterial antigens or mutant oncogene or tumor suppressor gene products may be applied towards this method. For example, using this method, a synthetic peptide which corresponds to the site of the mutation in the tumor suppressor gene product p53 can be used to induce a CTL response which kills tumor cells endogenously expressing the mutant p53 gene.

Inventors:
TJ Goletz, LJ Helman, JA Berzofsky (NCI)

Patent Status:
Serial No. 08/528,129 filed 14 Sep 95

Portfolios:
Cancer - Therapeutics, biological response modifiers
Cancer - Therapeutics, vaccines

For additional information, please contact:
Allan Kiang, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 270
Fax: 301/402-0220


O-Malonlytyrosyl Compounds, O-Malonllytyrosyl Compound-Containing Peptides, And Uses Thereof

Description of Invention:
Phosphotyrosyl residues in signalling proteins, which appear to act as molecular switches in phosphotyrosyl-dependent cellular signal transduction pathways, are potential targets for therapeutic agents. The phosphotyrosol-dependent signal transduction pathway is composed of three elements: the protein kinases which add phosphates to tyrosine residues, the protein phosphatases which remove the phosphate, and the interaction of other signaling proteins with proteins containing phosphotyrosyl residues. This invention describes a phosphotyrosyl mimetic O-malonyltryosine (OMT) which uses a malonate moiety in place of phosphate that can be derivatized and thus potentially made permeable to cell membranes. Peptides containing OMT residues are therefore potential therapeutic agents for disease states with altered cellular signaling including cancer.

Inventors:
TR Burke, B Ye, M Akamatsu, X Yan, HK Kole, PR Roller (NCI)

Patent Status:
Serial No. 08/414,520 filed 31 Mar 95

Portfolio:
Cancer - Therapeutics, conventional chemotherapy, antimetabolites

For additional information, please contact:
Allan Kiang, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 270
Fax: 301/402-0220


Assay For Sensitivity Of Tumors To DNA-Platinating Chemotherapy

Description of Invention:
The invention provides a method for determining the sensitivity of a tumor tissue to treatment with platinum-based chemotherapy. The method is based on detecting high levels of the mRNA for ERCC1 which includes exon VIII or concurrent expression of ERCC1 and XPAC mRNAs in fresh tumor tissues. Studies show that this method clearly distinguishes between platinum-sensitive and platinum-resistant tumors (J. Clin. Invest. 94:703-708, 1994).

Inventors:
E Reed, M Dadholkar, F Bostick-Bruton (NCI)

Patent Status:
Serial No. 08/399,617 filed 07 Mar 95

Portfolio:
Cancer - Research Reagents, DNA based

For additional information, please contact:
Allan Kiang, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 270
Fax: 301/402-0220


Confirmationally Constrained Diacylglycerol Analogues

Description of Invention:
Diacylglycerol (DAG) is a member of the second messenger system in cell signal transduction. DAG is released from membrane phospholipids in response to the binding of a variety of agonists. Once released, DAG binds to the regulatory domain of protein kinase C (PK-C) and in doing so aids in the activation of the kinase. PK-C, when activated, is capable of phosphorlyating a variety of other proteins involved in cellular processes including growth, differentiation, inflammation, nerve function, tumor promotion, and ocogenic expression. Given the global action of PK-C, molecules that can activate or inactivate this enzyme would be very useful. The claims of this invention describe a series of a diaclyglycerol analogues, which act as potent pharmacological agonists of PK-C and can be easily synthesized.

Inventors:
VE Marquez, J Lee, R Sharma, S Wang, GWA Milne, MC Nicklaus, PM Blumberg, NE Lewin (NCI)

Patent Status:
Serial No. 08/372,602 filed 13 Jan 95

Portfolio:
Cancer - Therapeutics, conventional chemotherapy, antimetabolites

For additional information, please contact:
Allan Kiang, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 270
Fax: 301/402-0220


Treatment Of Cancer With Human Chorionic Gonadotropin

Description of Invention:
A major complication in treating tumors is that many of the known treatments, such as surgery, radiation or chemotherapy, have serious side effects. Other types of cancers are not amenable to conventional therapies due to the fact that the exact mechanism by which the disease develops is unknown. An example of this type of cancer is Kaposi's sarcoma. Kaposi's sarcoma is the most common malignancy in AIDS patients. Current therapies for Kaposi's sarcoma can cause myelotoxicity and neurotoxicity. In addition, these treatments can also induce immunosuppression. This invention describes the use of a naturally occurring human hormone, human chorionic gonadotropin, for the treatment of Kaposi's sarcoma. Human chorionic gonadotropin may also be useful for the treatment of breast, prostate, ovary, and stomach carcinomas, as well as neuroblastomas.

Inventors:
Y Lunardi-Iskandar, RC Gallo, JL Bryant (NCI)

Patent Status:
Serial No. 08/286,299 filed 05 Aug 94

Portfolio:
Infectious Diseases - Therapeutics, anti-virals, AIDS
Cancer - Therapeutics, conventional chemotherapy, hormonal compounds

For additional information, please contact:
Allan Kiang, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 270
Fax: 301/402-0220


Therapeutic Polyamines

Description of Invention:
Most previous attempts to retard the growth of tumor cells by depleting the intracellular polyamine pool have been directed at inhibiting enzymes in the polyamine biosynthetic pathway; a process that does not completely deplete endogenous stores of these molecules. To date, most attempts at using polyamine biosynthetic inhibitors have resulted in incomplete inhibition of cell growth. With this invention, analogs have been developed that, while binding physically to DNA, do not function like natural polyamines and indeed cause almost complete depletion of intracellular stores of these compounds. These compounds have shown great promise in vitro and in vivo against various tumors. Additionally, these synthetic polyamines have proven to be tumor sensitizers in conjunction with other conventional chemotherapeutics in vivo.

Inventors:
HS Basu, LJ Marton, BG Feuerstein, K Samejima (University of California; Josai University; NCI)

Patent Status:
Serial No. 08/147,527 filed 05 Nov 93; U.S. Patent 5,541,230 issued 30 Jul 96

Portfolio:
Cancer - Therapeutics, conventional chemotherapy, other

For additional information, please contact:
Allan Kiang, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 270
Fax: 301/402-0220


Topoisomerase II Inhibitors And Therapeutic Uses Therefor

Description of Invention:
DNA topology is maintained in all cells by the action of a class of enzymes termed topoisomerases. Many drugs used in cancer chemotherapy function by inhibiting the action of topoisomerases. This invention embodies a compound, azatoxin, which is a inhibitor of both topoisomerase II and tubulin polymerization. Azatoxin is unique compared to other topoisomerase inhibitors in that it inhibits the catalytic activity of the enzyme at specific sites of DNA. Certain derivatives of azatoxin are capable of inhibiting either topoisomerase activity or tubulin polymerization but not both. Therefore these derivatives are expected to be especially potent therapeutic compounds.

Inventors:
Y Pommier, T MacDonald, JS Madalengoitia (NCI and University of Virginia)

Patent Status:
Serial No. 07/965,922 filed 23 Oct 92 [CIP of 07/868,408 (Aban)]
Serial No. 08/460,754 filed 01 Jun 95 (DIV of 07/965,922)
Serial No. 08/460,742 filed 02 Jun 95 (DIV of 07/965,922)

Portfolio:
Cancer - Therapeutics, conventional chemotherapy, antimetabolites

For additional information, please contact:
Allan Kiang, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 270
Fax: 301/402-0220