COMPOSITIONS OF UCP INHIBITORS, FAS ANTIBODY, A FATTY ACID METABOLISM INHIBITOR AND/OR A GLUCOSE METABOLISM INHIBITOR

• US 20090258064A1
• Filed: 02/23/2009
• Published: 10/15/2009
• Est. Priority Date: 01/08/2004
• Status: Active Grant

• Current Assignee: The Board of Regents of the University of Colorado (University of Colorado System)
• Original Assignee: The Board of Regents of the University of Colorado (University of Colorado System)
• Inventors: Villalobos-Menuey, Elizabeth, Newell, M. Karen, Newell, Evan
• Granted Patent: US 8,293,240 B2
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 39/39541 against normal tissues, cells
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95

Abstract

Systems and methods for treating inflammatory and proliferative diseases, and wounds, using as a pharmacon a UCP and/or Fas antibody or other inhibitor, or combination thereof, and a therapeutically acceptable amount of a fatty acid metabolism inhibitor and/or a therapeutically acceptable amount of a glucose metabolism inhibitor, optionally in combination with one or more chemotherpeutic agents. In preferred embodiments, the invention combines an antibody against UCP and/or Fas antigen with an oxirane carboxylic acid, represented by etomoxir, and/or with a 2-deoxyglucose compound, represented by 2-deoxy-D-glucose. The systems and methods of the invention can be used to treat drug-resistant or multi-drug resistant cancers.

Claims

1. A method, comprising:

administering, to a subject susceptible to or exhibiting symptoms of drug-resistant cancer, a therapeutically acceptable amount of a composition of a fatty acid metabolism inhibitor and a pharmaceutically acceptable carrier wherein the subject is not otherwise indicated for treatment with the compound.

2. The method of claim 1 wherein the fatty acid metabolism inhibitor comprises at least one of etomoxir, oxfenicine, methyl palmoxirate, metoprolol, amiodarone, perhexyline, aminocarnitine, hydrazonopropionic acid, 4-bromocrotonic acid, trimetazidine, ranolazine, hypoglycin, dichloroacetate, methylene cyclopropyl acetic acid, or beta-hydroxy butyrate.

3. The method of claim 1 wherein the composition is formulated in a colloidal dispersion system that is a liposome.

4. The method of claim 1 in which the fatty acid metabolism inhibitor is an oxirane carboxylic acid compound capable of inhibiting fatty acid metabolism, or a pharmacologically acceptable salt thereof, wherein the subject is not otherwise indicated for treatment with the compound.

5. The method of claim 4 wherein the oxirane carboxylic acid compound has the formula:

6. The method of claim 5 wherein the oxirane carboxylic acid compound is etomoxir.

7. The method of claim 1 further comprising administering a glucose metabolism inhibitor.

8. The method of claim 7 wherein the glucose metabolism inhibitor is a 2-deoxyglucose compound.

9. The method of claim 8 wherein the 2-deoxyglucose compound has the formula:

10. The method of claim 9 wherein the 2-deoxyglucose compound is 2-deoxy-D-glucose

11. The method of claim 1 wherein the subject is not indicated for treatment of cardiac insufficiency.

12. The method of claim 1 wherein cells comprising the cancer derive a majority of their metabolic energy through fatty acid metabolism.

13. The method of claim 1 further comprising administering to the subject one or more chemotherapeutic agents.

14. The method of claim 13 wherein one or more of the chemotherapeutic agents is selected from the group consisting of methotrexate, trimetrexate, adriamycin, taxotere, doxorubicin, 5-fluorouracil, vincristine, vinblastine, pamidronate disodium, anastrozole, exemestane, cyclophosphamide, epirubicin, toremifene, letrozole, trastuzumab, megestrol, tamoxifen, paclitaxel, docetaxel, capecitabine, and goserelin acetate.

15. The method of claim 7 wherein the fatty acid metabolism inhibitor is dichloroacetate and the glucose metabolism inhibitor is 2-deoxy-D-glucose or the pharmaceutically acceptable salts thereof.