Compositions and methods for the treatment and prevention of cancer, angiogenesis, and inflammation

• US 20040247603A1
• Filed: 04/07/2004
• Published: 12/09/2004
• Est. Priority Date: 12/22/2000
• Status: Active Grant

• Current Assignee: Apollo Endosurgery, Inc. (Boston Scientific Corporation)
• Original Assignee: Medlyte, Inc.
• Inventors: Sabbadini, Roger A.
• Granted Patent: US 7,169,390 B2
• Time in Patent Office: Days
• US Class Current: 424/155.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/7036 having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
• 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: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C12N 9/1205 Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases
• CPC Class Codes: C12N 9/1288 Transferases for other substituted phosphate groups (2.7.8)
• CPC Class Codes: C12N 9/80 acting on amide bonds in linear amides (3.5.1)
• CPC Class Codes: G01N 2800/32 Cardiovascular disorders
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere
• CPC Class Codes: G01N 33/92 involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743

Abstract

Methods and compositions are disclosed that are useful for the prevention and/or treatment of cancer, angiogenesis, and inflammation. The beneficial effects of the compositions and methods are achieved through the use of pharmaceutical compositions that include agents that bind spingolipids or sphingolipid metabolites. In one embodiment the agent is an antibody or antibody derivative. In some embodiments, the agent is a receptor of a sphingolipid or a sphingolipid metabolite. Also disclosed are methods for identifying and isolating therapeutic agents.

Claims

1. A method for treating or preventing a disease or disorder in a mammal comprising:

administering an agent to the mammal in an amount effective to treat or prevent the disease or disorder wherein the agent binds a sphingolipid or a sphingolipid metabolite and the disease or disorder is selected from the group consisting of;

cancer, angiogenesis, and inflammation.

2. The method of claim 1 wherein said agent is an antibody or antibody derivative.

3. The method of claim 1 wherein said agent is a non-catalytic derivative of an enzyme involved in the sphingolipid metabolic pathways.

4. The method of claim 1 wherein said agent is a soluble fragment of a receptor that binds a sphingolipid.

5. The method of claim 1, wherein said sphingolipid or a sphingolipid metabolite is selected from the group consisting of sphingomyelin, sphingosine, sphingolipid-1-phosphate (S-1-P), ceramide, sphingosylphosphorylcholine (SPC), 3-ketosphinganine, galactosylceramide and dihydroceramide.

6. The method of claim 1 wherein said sphingolipid is selected from the group consisting of ceramide, sphingosine and sphingolipid-1-phosphate (S-1-P).

7. The method of claim 4 wherein said sphingolipid is sphingolipid-1-phosphate (S-1-P).

8. The method of claim 7 wherein said receptor is selected from the group consisting of Edg-1, Edg-3, Edg-5, Edg-6, Edg-8, the Mil receptor, AXOR29, NRG1, SCaMPER and homologs and isoforms thereof.

9. The method of claim 7, wherein said receptor is an Edg receptor.

10. The method of claim 9, wherein said Edg receptor is rat Edg-3 receptor encoded by a nucleic acid having the sequence SEQ ID NO:

7.

11. The method of claim 10, wherein said receptor is a SCaMPER.

12. The method of claim 11, wherein said SCaMPER is encoded by a nucleic acid selected from the group consisting of SEQ ID NO:

3 and SEQ ID NO;

4.

13. The method of claim 1 wherein the disease or disorder is cancer.

14. The method of claim 1 wherein the disease or disorder is angiogenesis.

15. The method of claim 1 wherein the disease or disorder is inflammation.

17. The method of claim 13 wherein said agent is an antibody or antibody derivative.

18. The method of claim 13 wherein said receptor is selected from the group consisting of Edg-1, Edg-3, Edg-5, Edg-6, Edg-8, the Mil receptor, AXOR29, NRG1, SCaMPER and homologs and isoforms thereof.

19. The method of claim 13, wherein said receptor is an Edg receptor.

20. The method of claim 17, wherein said Edg receptor is rat edg-3 receptor encoded by a nucleic acid having the sequence SEQ ID NO:

7.

21. The method of claim 13, wherein said receptor is a SCaMPER.

22. The method of claim 18, wherein said SCaMPER is encoded by a nucleic acid selected from the group consisting of SEQ ID NO:

3 and SEQ ID NO;

4.

16. A method for treating or preventing a disease or disorder in a mammal comprising:

administering an agent to the mammal in an amount effective to treat or prevent the disease or disorder, wherein the agent binds a receptor of a sphingolipid or a sphingolipid metabolite and the disease or disorder is selected from the group consisting of;

cancer, angiogenesis, and inflammation.

23. The method of claim 16 wherein the disease or disorder is cancer.

24. The method of claim 16 wherein the disease or disorder is angiogenesis.

25. The method of claim 16 wherein the disease or disorder is inflammation.