MATERIALS AND METHODS FOR TREATING AND MANAGING PLAQUE DISEASE

• US 20110045054A1
• Filed: 09/13/2010
• Published: 02/24/2011
• Est. Priority Date: 12/08/2004
• Status: Abandoned Application

• Current Assignee: Shire Regenerative Medicine Incorporated (Shire plc)
• Original Assignee: Pervasis Therapeutics, Inc. (Shire plc)
• Inventors: Dalal, Anupam, Edelman, Elazer, Nugent, Helen Marie, Bollinger, Steve
• Application Number:
  US12/880,860
• Publication Number:
  US 20110045054A1
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 27/3808 Endothelial cells
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• 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

Abstract

Disclosed herein are materials and methods suitable for treating and managing plaque disease, including vulnerable plaque. An implantable material comprising cells, such as but not limited to endothelial cells, and a biocompatible matrix can reduce progression or deterioration of a plaque-associated lesion situated on the interior lumen of said blood vessel. The implantable material is implanted directly on an exterior surface of a blood vessel at or adjacent or in the vicinity of the site of a lesion on an interior lumen. Alternatively, the implantable material is deposited on an exterior surface at or adjacent or in the vicinity of the site of a lesion on an interior lumen by an intraluminal delivery device which traverses or penetrates the vessel wall or by a percutaneous delivery device which enters the perivascular space. Both modes of administration can be preceded by or coincident with an imaging step. The present invention can treat hemorrhage, erosion, fissure, plaque-associated thrombosis and occlusion, rupture, displacement and/or dislodgement of a plaque lesion.

Claims

1-29. -29. (canceled)

30. A method of treating a plaque-burdened site, the method comprising the step of:

contacting with an implantable material an exterior surface of a blood vessel at or adjacent or in the vicinity of a plaque-burdened site on an interior lumen of said vessel, wherein said implantable material comprises cells attached via cell to matrix interactions to a biocompatible matrix;

wherein said implantable material is in an amount effective to treat the plaque-burdened site; and

wherein the effective amount comprises at least about 2×

10⁵ to 4×

10⁵ cells/cm³ implantable material, wherein said cells are at least about 80% viable, wherein said cells produce at least about 0.5 to 1.0 micrograms heparan sulfate/10⁶ cells/day, wherein said cells produce at least about 200 to 300 picograms TGF-β

₁/ml/day, and wherein said cells produce no more than about 200 to 400 picograms b-FGF/ml/day.

31. The method of claim 30 wherein said effective amount reduces plaque hemorrhage at the plaque-burdened site.

32. The method of claim 30 wherein said effective amount reduces plaque fissure at the plaque-burdened site.

33. The method of claim 30 wherein said effective amount reduces plaque erosion at the plaque-burdened site.

34. The method of claim 30 wherein said effective amount reduces rupture, displacement or dislodgement of plaque at the plaque-burdened site.

36. The method of claim 30 or claim 35, wherein deposition of the implantable material is accomplished by first traversing or penetrating an interior wall of said blood vessel and then depositing the implantable material on the exterior surface of said blood vessel at or adjacent or in the vicinity of the plaque-burdened site.

37. The method of claim 30 or claim 35, wherein deposition of the implantable material is accomplished by entering the perivascular space by percutaneous administration and then depositing the implantable material at or adjacent or in the vicinity of the plaque-burdened site.

43. The method of claim 30 or claim 35, wherein the exterior surface of said blood vessel is a non-luminal surface selected from the group consisting of:

perivascular space, an adventitial site, a medial site, an intimal site, and a combination of any one of the foregoing.

44. The method of claim 30 wherein the total cell load per patient comprises about 1.6×

10⁴ to 2.6×

10⁴ cells per kilogram body weight.

45. The method of claim 30 or claim 35 wherein the contacting step is accomplished by depositing the implantable material on the exterior surface of said blood vessel either proximal or distal to a plaque-burdened site.

46. The method of claim 45 wherein the contacting step is accomplished by depositing the implantable material within about 2 to 20 mm of the plaque-burdened site.

47. The method of claim 45 wherein the contacting step is accomplished by depositing the implantable material within about 21 to 40 mm of the plaque-burdened site.

48. The method of claim 45 wherein the contacting step is accomplished by depositing the implantable material within about 41 to 60 mm of the plaque-burdened site.

49. The method of claim 45 wherein the contacting step is accomplished by depositing the implantable material within about 61 to 100 mm of the plaque-burdened site.

35. A method of diminishing clinical sequelae associated with vulnerable plaque in a patient in need thereof, the method comprising the step of:

contacting with an implantable material an exterior surface of said blood vessel at or adjacent or in the vicinity of a plaque-burdened site on the interior lumen of said vessel, wherein said implantable material comprises cells attached via cell to matrix interactions to a biocompatible matrix;

wherein said implantable material is in an amount effective to diminish clinical sequelae associated with vulnerable plaque, said clinical sequelae selected from the group consisting of;

acute coronary syndrome, myocardial infarction, sudden cardiac death; and

wherein the amount effective comprises a total cell load per patient no less than about 2×

10³ to no more than about 2×

10⁶ cells per kilogram body weight.

38. An effective amount of an implantable material suitable for use with the method of claim 35, wherein the effective amount comprises at least about 2×

10⁵ to 4×

10⁵ cells/cm³ implantable material, wherein said cells are at least about 80% viable, wherein said cells produce at least about 0.5 to 1.0 micrograms heparan sulfate/10⁶ cells/day, wherein said cells produce at least about 200 to 300 picograms TGF-β

₁/ml/day, and wherein said cells produce no more than about 200 to 400 picograms b-FGF/ml/day.

39. The implantable material of claim 38 wherein the implantable material is a flexible planar form.

40. The implantable material of claim 38 wherein the implantable material is a flowable composition.

41. The implantable material of claim 38 wherein said cells are endothelial cells or cells having an endothelial-like phenotype.

42. The implantable material of claim 41 wherein said cells are selected from the group consisting of:

a confluent population of cells;

a near confluent population of cells;

a post confluent population of cells;

a non-exponential population of cells; and

cells which have a phenotype of any one of the foregoing population of cells.