Methods and products for manipulating uncoupling protein expression

• US 20060247199A1
• Filed: 04/21/2006
• Published: 11/02/2006
• Est. Priority Date: 06/23/1999
• Status: Active Grant

• Current Assignee: University of Vermont & State Agricultural College
• Original Assignee: University of Vermont & State Agricultural College
• Inventors: Newell, Martha K.
• Granted Patent: US 7,816,319 B2
• Time in Patent Office: Days
• US Class Current: 514/44.R
• 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 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: G01N 2333/47 Assays involving proteins of known structure or function as defined in the subgroups
• CPC Class Codes: G01N 33/5011 : for testing antineoplastic activity
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention is based in part on the discovery that uncoupling proteins (UCPs) are expressed in the plasma membrane of rapidly dividing cells but not of growth arrested, chemotherapy resistant cells. It has also been found according to the invention that UCP is expressed in the lysosomal membrane under certain metabolic conditions. Thus the invention is methods, products, screening assays and kits relating to the manipulation of UCP expression within cellular and intracellular membranes.

Claims

1. A method for inhibiting plasma membrane UCP expression in a cell, comprising:

contacting a cell with a plasma membrane UCP inhibitor to inhibit plasma membrane UCP expression.

2. The method of claim 1, wherein the plasma membrane UCP inhibitor is selected from the group consisting of a UCP binding peptide or molecule, an anti-UCP antibody, a hydrophobic nucleotide analog, and a non-omega-3 fatty acid.

3. The method of claim 2, wherein the cell is a tumor cell, a lymphocyte, a pancreatic β

cell, a bacteria, or a B cell.

4. The method of claim 3, wherein the tumor cell is in a subject and wherein the plasma membrane targeted UCP inhibitor is administered in vivo.

5. The method of claim 3, wherein the tumor cell is in a subject and wherein the plasma membrane targeted UCP inhibitor is administered ex vivo.

6. The method of claim 3, further comprising the step of administering to the subject a cytotoxic anti-tumor therapy.

7-11. -11. (canceled)

12. A composition, comprising:

a plasma membrane targeted UCP inhibitor.

19. The composition of claim 12, further comprising a colloidal dispersion system, wherein the plasma membrane UCP inhibitor is incorporated into the colloidal dispersion system.

20. The composition of claim 19, wherein the colloidal dispersion system is a liposome.

21. The composition of claim 12 wherein the plasma membrane UCP inhibitor includes a hydrophobic moiety.

22. The composition of claim 21, wherein the plasma membrane UCP inhibitor is a modified nucleotide analog conjugated to a hydrophobic moiety.

23. The composition of claim 22, wherein the plasma membrane UCP inhibitor includes a membrane attachment domain

24. The composition of claim 23, wherein the plasma membrane UCP inhibitor is a membrane attachment domain conjugated to a nucleotide or nucleotide analog.

25. The composition of claim 24, wherein the membrane attachment domain is a Type I membrane attachment domain a Type II membrane attachment domain, or a Type III membrane attachment domain.

28. The composition of claim 24, wherein the membrane attachment domain is selected from the group consisting of P-Cadherin (FILPILGAVLALLLLLTLLALLLLV);

CD2 (IYLIIGICGGGSLLMVFVALLVFYIT);

CD40 (ALVVIPIIFGILFAILLVLVFI);

Contactin (ISGATAGVPTLLLGLVLPAP);

IL-4 receptor (LLLGVSVSCIVILAVCLLCYVSIT);

Mannose receptor (VAGVVIIVILLILTGAGLAAYFFY);

M-CSF receptor (FLFTPVVVACMSIMALLLLLLLLLL);

PDGFR .beta. chain (VVVISAILALVVLTIISLIILIMLWQKKPR);

PDGFR .alpha. chain (ELTVAAAVLVLLVIVSISLIVLVVTW);

P-Selectin (LTYFGGAVASTIGLIMGGTLLALL);

Rat Thy-1 (VKCGGISLLVQNTSWLLLLLLSLSFLQATDFISL);

TNFR-1 (TVLLPLVIFFGLCLLSLLFIGLM); and

VCAM-1 (LLVLYFASSLIIPAIGMIIYFAR).

29. A method for treating a cancer, comprising administering to a subject having a cancer the plasma membrane UCP inhibitor of claim 12, in an effective amount to treat the cancer.

13. The composition of 12, wherein the UCP inhibitor is a nucleotide or nucleotide analog.

14. The composition of claim 13, wherein the nucleotide analog is a purine analog.

16. The composition of claim 13, wherein the nucleotide analog is a pyrimidine analog.

15. (canceled)

17. (canceled)

18. The composition of 12, further comprising a pharmaceutically acceptable carrier.

26-27. -27. (canceled)

30-31. -31. (canceled)