METHODS OF PREVENTING OR TREATING CARDIOVASCULAR, CEREBROVASCULAR AND THROMBOTIC DISORDERS WITH TUMOR NECROSIS FACTOR ANTAGONISTS

• US 20020081306A1
• Filed: 02/16/1996
• Published: 06/27/2002
• Est. Priority Date: 02/16/1996
• Status: Active Grant

• Current Assignee: The Kennedy Institute Of Rheumatology (University of Oxford)
• Original Assignee: The Kennedy Institute Of Rheumatology (University of Oxford)
• Inventors: ELLIOTT, MICHAEL J., FELDMANN, MARC, MAINI, RAVINDER N.
• Granted Patent: US 7,608,262 B2
• Time in Patent Office: Days
• US Class Current: 424/184.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/4015 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• 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 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 14/7151 for tumor necrosis factor [TNF], for lymphotoxin [LT]
• CPC Class Codes: C07K 16/241 Tumor Necrosis Factors
• CPC Class Codes: C07K 16/248 IL-6
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

A method of treating or preventing a cardiovascular and/or a cerebrovascular disorder in an individual is disclosed. Also disclosed is a method for treating and/or preventing a thrombotic disorder in an individual. Further disclosed is a method of decreasing plasma fibrinogen in an individual.

Claims

1. A method for treating or preventing a cardiovascular disorder in an individual in need thereof comprising administering to the individual a therapeutically effective amount of a tumor necrosis factor antagonist.

2. A method of claim 1 wherein the cardiovascular disorder is selected from the group consisting of:

acute mycocardial infarction, deep vein thrombosis and thrombophlebitis.

3. A method of claim 2 wherein the cardiovascular disorder is acute mycocardial infarction.

4. A method for treating or preventing a cerebrovascular disorder in an individual in need thereof comprising administering to the individual a therapeutically effective amount of a tumor necrosis factor antagonist.

5. A method of claim 4 wherein the cerebrovascular disorder is stroke.

6. A method of treating or preventing a thrombotic disorder in an individual in need thereof comprising administering a therapeutically effective amount of a tumor necrosis factor antagonist to the individual.

7. A method of claim 6 wherein the thrombotic disorder is selected from the group consisting of:

a thromboembolic disorder, a ischemic event, stroke, acute mycocardial infarction, deep vein thrombosis and thrombophlebitis.

8. A method of claim 7 wherein the tumor necrosis factor antagonist is an anti-tumor necrosis factor antibody or fragment thereof.

9. A method of claim 8 wherein the antibody is selected from the group consisting of:

a chimeric antibody, a humanized antibody and a resurfaced antibody or fragment thereof.

10. A method of claim 9 wherein the antibody binds to one or more amino acids of hTNFα

selected from the group consisting of about 87-108 and about 59-80.

11. A method of claim 9 wherein the antibody binds to the epitope of A2.

12. A method of claim 9 wherein the antibody is a chimeric antibody.

13. A method of claim 12 wherein the antibody binds to one or more amino acids of hTNFα

selected from the group consisting of about 87-108 and about 59-80.

14. A method of claim 12 wherein the antibody binds to the epitope of cA2.

15. A method of claim 14 wherein the antibody is cA2.

16. A method of claim 7 wherein the tumor necrosis factor antagonist is a receptor molecule, derivative or a fragment thereof which binds to tumor necrosis factor.

17. A method of claim 16 wherein the receptor molecule is selected from the group consisting of:

p55 tumor necrosis factor receptor and p75 tumor necrosis factor receptor or functional portions thereof.

18. A method of claim 16 wherein the receptor molecule is selected from the group consisting of:

the extracellular domain of p55 tumor necrosis factor receptor and the extracellular domain of p75 tumor necrosis factor receptor.

19. A method of claim 16 wherein the receptor molecule is a TNF receptor multimeric molecule or a functional portion thereof.

20. A method of claim 19 wherein the tumor necrosis receptor multimeric molecule comprises all or a functional portion of two or more extracellular domains of tumor necrosis factor receptors linked via one or more polypeptide linkers.

21. A method of claim 16 wherein the receptor molecule is an immunoreceptor fusion molecule or functional portion thereof.

22. A method of claim 21 wherein the immunoreceptor fusion molecule comprises all or a functional portion of a tumor necrosis factor receptor and an immunoglobulin chain.

23. A method of claim 7 wherein the tumor necrosis factor antagonist prevents or inhibits tumor necrosis factor synthesis or tumor necrosis factor release.

24. A method of claim 23 wherein the tumor necrosis factor antagonist is a phosphodiesterase inhibitor.

25. A method of claim 24 wherein the phosphodiesterase inhibitor is selected from the group consisting of:

pentoxifylline and rolipram.

26. A method of claim 23 wherein the tumor necrosis factor antagonist is selected from the group consisting of:

thalidomide and tenidap.

27. A method of claim 23 wherein the tumor necrosis factor is selected from the group consisting of:

a A2b adenosine receptor agonist and a A2b adenosine receptor enhancer.

28. A method of claim 7 wherein the tumor necrosis factor antagonist prevents or inhibits tumor necrosis factor receptor signalling.

30. A method of claim 29 wherein the tumor necrosis factor antagonist is an anti-tumor necrosis factor antibody or fragment thereof.

31. A method of claim 30 wherein the antibody is selected from the group consisting of:

a chimeric antibody, a humanized antibody and a resurfaced antibody or fragment thereof.

32. A method of claim 31 wherein the antibody binds to one or more amino acids of hTNFα

selected from the group consisting of about 87-108 and about 59-80.

33. A method of claim 32 wherein the antibody binds to the epitope of A2.

34. A method of claim 31 wherein the antibody is a chimeric antibody.

35. A method of claim 34 wherein the antibody binds to one or more amino acids of hTNFα

selected from the group consisting of about 87-108 and about 59-80.

36. A method of claim 34 wherein the antibody binds to the epitope of cA2.

37. A method of claim 36 wherein the antibody is cA2.

38. A method of claim 29 wherein the tumor necrosis factor antagonist is a receptor molecule, derivative or a fragment thereof which binds to tumor necrosis factor.

39. A method of claim 38 wherein the receptor molecule is selected from the group consisting of:

p55 tumor necrosis factor receptor and p75 tumor necrosis factor receptor or functional portions thereof.

40. A method of claim 38 wherein the receptor molecule is selected from the group consisting of:

the extracellular domain of p55 tumor necrosis factor receptor and the extracellular domain of p75 tumor necrosis factor receptor.

41. A method of claim 40 wherein the receptor molecule is a tumor necrosis factor receptor multimeric molecule.

42. A method of claim 41 wherein the tumor necrosis factor receptor multimeric molecule comprises all or a functional portion of two or more extracellular domains of tumor necrosis factor receptors linked via one or more polypeptide linkers.

43. A method of claim 40 wherein the receptor molecule is an immunoreceptor fusion molecule or functional portion thereof.

44. A method of claim 43 wherein the immunoreceptor fusion molecule comprises all or a functional portion of a tumor necrosis factor receptor and an immunoglobulin chain.

45. A method of claim 29 wherein the tumor necrosis factor antagonist prevents or inhibits tumor necrosis factor synthesis or tumor necrosis factor release.

46. A method of claim 45 wherein the tumor necrosis factor antagonist is a phosphodiesterase inhibitor.

47. A method of claim 46 wherein the phosphodiesterase inhibitor is selected from the group consisting of:

pentoxifylline and rolipram.

48. A method of claim 45 wherein the tumor necrosis factor antagonist is selected from the group consisting of:

thalidomide and tenidap.

49. A method of claim 45 wherein the tumor necrosis factor antagonist is selected from the group consisting of:

a A2b adenosine receptor agonist and a A2b adenosine receptor enhancer.

50. A method of claim 29 wherein the tumor necrosis factor antagonist prevents or inhibits tumor necrosis factor receptor signalling.

29. A method of decreasing plasma fibrinogen in an individual comprising administering a therapeutically effective amount of a tumor necrosis factor antagonist to the individual.