CARDIOVASCULAR RELATED USES OF IL-1BETA ANTIBODIES AND BINDING FRAGMENTS THEREOF

• US 20100316651A1
• Filed: 05/28/2010
• Published: 12/16/2010
• Est. Priority Date: 05/29/2009
• Status: Abandoned Application

• Current Assignee: Xoma (US) LLC (Xoma Corp.)
• Original Assignee: Xoma Technology Ltd. (Xoma Corp.)
• Inventors: SOLINGER, ALAN M., SCANNON, PATRICK J., FELDSTEIN, JEFFREY D.
• Application Number:
  US12/790,738
• Publication Number:
  US 20100316651A1
• Time in Patent Office: Days
• US Class Current: 424/158.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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 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: A61P 9/12 Antihypertensives
• CPC Class Codes: C07K 16/245 IL-1

Abstract

Disclosed are methods for the reduction, prevention or treatment of cardiovascular events and/or cardiovascular diseases, including acute cardiovascular disease or chronic cardiovascular disease using anti-IL-1β binding molecules (e.g., IL-1β binding antibodies and fragments thereof). The present disclosure also relates to methods for prevention or treatment of cardiovascular events and/or cardiovascular diseases, including by reducing a cardiovascular event or disease.

Claims

1. A method of reducing a cardiovascular event in a subject, comprising administering to said subject a therapeutically effective amount of an anti-IL-1β

binding antibody or binding fragment thereof, wherein the subject is a subject with a history of a previous cardiovascular event or a history of at least one risk factor for cardiovascular disease, and wherein the cardiovascular event is myocardial infarction, stroke, cardiovascular death, congestive heart failure, cardiac arrest, acute coronary syndrome, angina, or a revascularization procedure.

2. The method of claim 1, wherein the subject is a subject with a history of a previous cardiovascular event, and wherein the cardiovascular event is myocardial infarction, stroke, acute coronary syndrome, angina or a revascularization procedure.

3. The method of claim 1, wherein the revascularization procedure is a coronary, carotid or peripheral arterial revascularization procedure.

4. The method of claim 3, wherein the coronary, carotid or peripheral arterial revascularization procedure is a percutaneous coronary intervention (PCI), a stent implant, coronary artery bypass graft (CABG), carotid endarterectomy, peripheral vascular disease bypass surgery, or peripheral angioplasty surgery.

5. The method of claim 2, wherein said subject also has a history of at least one risk factor for cardiovascular disease.

6. The method of claim 1, wherein the risk factor is manifest coronary heart disease, coronary artery disease, thrombosis, transient ischaemic attack, left ventricular hypertrophy, arteriosclerosis, restenosis, tobacco smoking or peripheral vascular disease.

7. The method of claim 1, wherein the risk factor is elevated triglycerides, systemic inflammation, high blood phosphorus levels, high parathyroid hormone levels, microalbuminuria, or high homocysteine levels.

8. The method of claim 1, wherein the risk factor is obesity, hyperglycemia, chronic renal failure, high blood glucose, chronic kidney disease, or metabolic syndrome.

9. The method of claim 1, wherein the risk factor is hypertension, dyslipidemia, hyperlipidemia, elevated total cholesterol, elevated LDL cholesterol, or low HDL cholesterol or atherosclerosis.

10. The method of claim 1, wherein the subject has elevated levels of C-reactive protein (CRP).

11. The method of claim 1, wherein the subject is older than 55 years.

12. The method of claim 1, wherein the subject is non-hypertensive.

13. The method of claim 1, wherein the subject has diabetes mellitus.

14. The method of claim 13, wherein said diabetes mellitus is Type 2 diabetes.

15. The method of claim 1, wherein the subject has a history of two or more said risk factors.

16. The method of claim 15, wherein the subject has a history of three or more said risk factors.

17. The method of claim 1, wherein administering said therapeutically effective amount of an anti-IL-1β

binding antibody or binding fragment thereof is sufficient to achieve a decrease in CRP levels.

69. The method of any one of claim 1, 18, 39, 58, 60, 62 or 65 further comprising administering at least one other pharmaceutical composition comprising an active agent other than an anti-IL-1β

binding antibody or binding fragment thereof.

79. The method of any one of claim 1, 18, 39, 58, 60, 62 or 65, wherein the anti-IL-1β

binding antibody or binding fragment thereof binds to human IL-1β

with a dissociation constant of about 500 pM or less.

89. The method of any one of claim 1, 18, 39, 58, 60, 62 or 65, wherein the anti-IL-1β

binding antibody or binding fragment thereof is administered in one or more doses of 1 mg/kg or less of antibody or fragment.

94. The method of any one of claim 1, 18, 39, 58, 60, 62 or 65, wherein the anti-IL-1β

binding antibody or binding fragment thereof is administered as a fixed dose, independent of a dose per subject weight ratio.

101. The method of any one of claim 1, 18, 39, 58, 60, 62 or 65, wherein the anti-IL-1β

binding antibody or binding fragment thereof is administered by subcutaneous, intravenous or intramuscular injection.

102. The method of any one of claim 1, 18, 39, 58, 60, 62 or 65, wherein administration of an initial dose of anti-IL-1β

binding antibody or binding fragment thereof is followed by the administration of one or more subsequent doses.

18. A method of reducing mortality following a cardiovascular event in a subject, comprising administering to said subject a therapeutically effective amount of an anti-IL-1β

binding antibody or binding fragment thereof.

19. The method of claim 18, wherein the cardiovascular event is myocardial infarction.

20. The method of claim 18, wherein the cardiovascular event is stroke.

21. The method of claim 18, wherein the cardiovascular event is congestive heart failure.

22. The method of claim 18, wherein the cardiovascular event is acute coronary syndrome.

23. The method of claim 18, wherein the cardiovascular event is angina.

24. The method of claim 18, wherein the cardiovascular event is a revascularization procedure.

25. The method of claim 24, wherein the revascularization procedure is a coronary, carotid or peripheral arterial revascularization procedure.

26. The method of claim 25, wherein the coronary, carotid or peripheral arterial revascularization procedure is a percutaneous coronary intervention (PCI), a stent implant, coronary artery bypass graft (CABG), carotid endarterectomy, peripheral vascular disease bypass surgery, or peripheral angioplasty surgery.

27. The method of claim 18, wherein the subject does not have Type 2 diabetes.

28. The method of claim 18, wherein the subject has survived a previous cardiovascular event of myocardial infarction or stroke.

29. The method of claim 18, wherein the occurrence of said cardiovascular event is a reoccurrence of a cardiovascular event of myocardial infarction or stroke.

30. The method of claim 18, wherein the subject has a history of one or more risk factors for cardiovascular disease.

31. The method of claim 30, wherein the risk factor is manifest coronary heart disease, coronary artery disease, thrombosis, transient ischaemic attack, left ventricular hypertrophy, arteriosclerosis, restenosis, tobacco smoking or peripheral vascular disease.

32. The method of claim 30, wherein the risk factor is elevated triglycerides, systemic inflammation, high blood phosphorus levels, high parathyroid hormone levels, microalbuminuria, or high homocysteine levels.

33. The method of claim 30, wherein the risk factor is obesity, hyperglycemia, chronic renal failure, high blood glucose, chronic kidney disease, or metabolic syndrome.

34. The method of claim 30, wherein the risk factor is hypertension, dyslipidemia, hyperlipidemia, elevated total cholesterol, elevated LDL cholesterol, or low HDL cholesterol or atherosclerosis.

35. The method of claim 18, wherein the subject is non-hypertensive.

36. The method of claim 30, wherein the subject has a history of two or more said risk factors.

37. The method of claim 36, wherein the subject has a history of three or more said risk factors.

38. The method of claim 18, wherein administering said therapeutically effective amount of an anti-IL-1β

binding antibody or binding fragment thereof is sufficient to achieve a decrease in CRP levels.

39. A method of reducing a cardiovascular event in a subject with a history of at least one risk factor for cardiovascular disease, comprising administering to said subject a therapeutically effective amount of an anti-IL-1β

binding antibody or binding fragment thereof, and wherein said risk factor is not Type 2 diabetes, obesity, hyperglycemia, dyslipidemia, hyperlipidemia, chronic renal failure, high blood glucose, chronic kidney disease, hypertension, atherosclerosis or metabolic syndrome.

40. The method of claim 39, wherein the risk factor is not Type 2 diabetes.

41. The method of claim 39, wherein the cardiovascular event is myocardial infarction.

42. The method of claim 39, wherein the cardiovascular event is stroke.

43. The method of claim 39, wherein the cardiovascular event is cardiac arrest.

44. The method of claim 39, wherein the cardiovascular event is congestive heart failure.

45. The method of claim 39, wherein the cardiovascular event is cardiovascular death.

46. The method of claim 39, wherein the cardiovascular event is acute coronary syndrome.

47. The method of claim 39, wherein the cardiovascular event is angina.

48. The method of claim 39, wherein the cardiovascular event is a revascularization procedure.

49. The method of claim 48, wherein the revascularization procedure is a coronary, carotid or peripheral arterial revascularization procedure.

50. The method of claim 49, wherein the coronary, carotid or peripheral arterial revascularization procedure is a percutaneous coronary intervention (PCI), a stent implant, coronary artery bypass graft (CABG), carotid endarterectomy, peripheral vascular disease bypass surgery, or peripheral angioplasty surgery.

51. The method of claim 39, wherein the risk factor is manifest coronary heart disease, coronary artery disease, thrombosis, transient ischaemic attack, left ventricular hypertrophy, arteriosclerosis, restenosis, tobacco smoking or peripheral vascular disease.

52. The method of claim 39, wherein the risk factor is elevated triglycerides, systemic inflammation, high blood phosphorus levels, high parathyroid hormone levels, microalbuminuria, or high homocysteine levels.

53. The method of claim 39, wherein the subject has elevated levels of C-reactive protein (CRP).

54. The method of claim 39, wherein the subject is older than 55 years.

55. The method of claim 39, wherein the subject has a history of two or more said risk factors.

56. The method of claim 55, wherein the subject has a history of three or more said risk factors.

57. The method of claim 39, wherein administering said therapeutically effective amount of an anti-IL-1β

binding antibody or binding fragment thereof is sufficient to achieve a decrease in CRP levels.

58. A method of treating a cardiovascular event in a subject, wherein the cardiovascular event is myocardial infarction, stroke, congestive heart failure, acute coronary syndrome or angina, comprising administering to said subject a therapeutically effective amount of an anti-IL-1β

binding antibody or binding fragment thereof and at least one other pharmaceutical composition comprising an active agent other than an IL-1β

antibody or fragment.

59. The method of claim 58, wherein the active agent of said at least one other pharmaceutical composition is a cholesterol lowering agent, a statin, an HMG-CoA reductase inhibitor, a calcium channel blocker, a beta blocker, an antihypertensive, a diuretic, aspirin, niacin, an angiotensin-converting enzyme (ACE) inhibitor, an angiotensin II receptor blocker, a vasodilator, an anticoagulant, a inhibitor of platelet aggregation, a thrombolytic or digitalis.

64. The method of claim 58, wherein administering said therapeutically effective amount of an anti-IL-1β

binding antibody or binding fragment thereof is sufficient to achieve a decrease in CRP levels.

60. A method for treating a cardiovascular event in a subject, wherein the cardiovascular event is myocardial infarction, stroke, congestive heart failure, acute coronary syndrome or angina, comprising administering to said subject a therapeutically effective amount of an anti-IL-1β

binding antibody or binding fragment thereof and a revascularization procedure.

61. The method of claim 60, wherein the revascularization procedure is a coronary, carotid or peripheral arterial revascularization procedure.

62. A method of reducing restenosis in a subject following a revascularization procedure, comprising administering to said subject a therapeutically effective amount of an anti-IL-1β

binding antibody or binding fragment thereof.

63. The method of claim 62, wherein the revascularization procedure is a coronary, carotid or peripheral arterial revascularization procedure.

65. A method of treating acute hypertension in a subject comprising administering to said subject a therapeutically effective amount of an anti-IL-1β

binding antibody or binding fragment thereof and one or more antihypertensive agents.

66. The method of claim 65, wherein the subject has a blood pressure of greater than or equal to 180/110 mm Hg.

67. The method of claim 65, wherein the antihypertensive agent is administered intravenously.

68. The method of claim 65, wherein the antihypertensive agent is labetalol, metoprolol, hydralazine, nitroglycerin, nicardipine, sodium nitroprusside or clevidipine.

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