Medical device with coating that promotes endothelial cell adherence

• US 7,037,332 B2
• Filed: 03/15/2001
• Issued: 05/02/2006
• Est. Priority Date: 03/15/2000
• Status: Expired due to Term

• Current Assignee: OrbusNeich Medical Pte Ltd
• Original Assignee: Orbus Medical Technologies Inc. (OrbusNeich Medical Technology Co. Ltd.)
• Inventors: Rowland, Stephen Maxwell, Cottone, Robert John Jr., Kutryk, Michael John Bradley
• Primary Examiner(s): Isabella, David J.
• Assistant Examiner(s): Chattopadhyay, Urmi
• Application Number:
  US09/808,867
• Publication Number:
  US 20020049495A1
• Time in Patent Office: 1,874 Days
• Field of Search: 427 224- 225, 427/299, 427/322, 427/331, 427/402, 623/1.1, 623 144- 154, 623/2.1, 623/11.11, 623/66.1, 623/12, 623 2364- 2371, 623/23.76, 623/901, 623/916, 606191-198, 600/36, 435/174, 435/177
• US Class Current: 623/1.48
• CPC Class Codes: A61F 2/07 Stent-grafts
• CPC Class Codes: A61F 2/2412 with soft flexible valve members, e.g. tissue valves shaped like natural valves check valves with flexible valve members in general F16K15/14
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• 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 38/363 Fibrinogen
• CPC Class Codes: A61K 38/39 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61L 2300/256 Antibodies, e.g. immunoglobulins, vaccines
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/422 Anti-atherosclerotic agents
• CPC Class Codes: A61L 2300/432 Inhibitors, antagonists A61L2300/402 - A61L2300/43 take precedence
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2420/04 Coatings containing a composite material such as inorganic/organic, i.e. material comprising different phases
• CPC Class Codes: A61L 27/08 Carbon ; Graphite
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61L 27/303 Carbon
• CPC Class Codes: A61L 27/44 having a macromolecular matrix
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/103 Carbon
• CPC Class Codes: A61L 29/126 having a macromolecular matrix
• CPC Class Codes: A61L 29/16 : Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/022 : Metals or alloys
• CPC Class Codes: A61L 31/047 : Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
• CPC Class Codes: A61L 31/084 : Carbon; Graphite
• CPC Class Codes: A61L 31/10 : Macromolecular materials
• CPC Class Codes: A61L 31/125 : having a macromolecular matrix
• CPC Class Codes: A61L 31/148 : Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 : Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• 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: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C07K 16/2896 : against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 2317/55 : Fab or Fab'
• CPC Class Codes: C12N 2510/00 : Genetically modified cells
• CPC Class Codes: C12N 5/0692 : Stem cells; Progenitor cells; Precursor cells

Abstract

A medical device coated with one or more antibodies and one or more layers of a matrix is disclosed. The antibodies or fragments thereof react with an endothelial cell surface antigen. Also disclosed are compositions and methods for producing the medical device. The matrix coating the medical device may be composed of a synthetic material, such as a fullerene, or a naturally occurring material. The fullerenes range from about C60 to about C100. The medical device may be a stent or a synthetic graft. The antibodies promote the adherence of cells captured in vivo on the medical device. The antibodies may be mixed with the matrix or covalently tethered through a linker molecule to the matrix. Following adherence to the medical device, the cells differentiate and proliferate on the medical device. The antibodies may be different types of monoclonal antibodies. By facilitating adherence of cells to the surface of the medical device, the disclosed methods and compositions will decrease the incidence of restenosis as well as other thromboembolic complications resulting from implantation of medical devices.

Claims

1. A medical device comprising a coating rendering the medical device compatible for in vivo attachment and proliferation of cells on the surface thereof, wherein the coating comprises a therapeutically effective amount of a type of antibody which reacts with an endothelial cell surface antigen, and one or more layers of a matrix.

2. The medical device of claim 1, wherein the matrix is layered onto the surface of the medical device, and antibodies, or fragments thereof, of the type which reacts with an endothelial cell surface antigen are tethered covalently by a linker molecule to the matrix.

3. The medical device of claim 1, wherein the antibody is a monoclonal antibody.

4. The medical device of claim 3, wherein the monoclonal antibody reacts with endothelial cell surface antigen CD34.

5. The medical device of claim 3 or 8, wherein the monoclonal antibody comprises Fab or F(ab′

)₂ fragments.

6. The medical device of claim 1, wherein the medical device is a stent.

7. The medical device of claim 1, wherein the medical device is a synthetic graft.

8. The medical device of claim 1, wherein the endothelial cell is a human cell.

9. The medical device according to claim 1, wherein the matrix comprises a naturally occurring material or a synthetic material.

10. The medical device according to claim 1, wherein the matrix comprises a material selected from the group consisting of a fullerene, polyurethane, segmented polyurethane-urea/heparin, poly-L-lactic acid, cellulose ester, polyethylene glycol, collagen, laminin, heparin, fibrin, cellulose, carbon, polytetrafluoroethylene, and expanded polytetrafluoroethylene.

11. The medical device according to claim 10, wherein when the matrix material comprises a fullerene, the fullerene ranges from about C60 to about C100.

12. The medical device according to claim 10, wherein when the matrix material comprises a fullerene, the fullerene is C60O.

13. A coating composition for rendering a medical device compatible for in vivo attachment and proliferation of cells on the surface thereof, wherein the coating composition comprises a matrix and a therapeutically effective amount of a type of antibody which reacts with an endothelial cell surface antigen.

14. The coating composition of claim 13, wherein the matrix comprises a material selected from the group consisting of a fullerene, polyurethane, segmented polyurethane-urea/heparin, poly-L-lactic acid, cellulose ester, polyethylene glycol, collagen, laminin, heparin, fibrin, cellulose, carbon, polytetrafluoroethylene, and expanded polytetrafluoroethylene.

15. The coating composition according to claim 14, wherein when the matrix material comprises a fullerene, the fullerene ranges from about C60 to about C100.

16. The coating composition according to claim 14, wherein when the matrix material comprises a fullerene, the fullerene is C60O.

17. The coating composition of claim 13, wherein the antibody is a monoclonal antibody.

18. The coating composition of claim 17, wherein the monoclonal antibody reacts with endothelial cell surface antigen, CD34.

19. The coating composition of claim 17 or 18, wherein the monoclonal antibody comprises Fab or F(ab′

)₂ fragments.

20. The coating composition of claim 13, wherein the endothelial cell is a human cell.

21. The coating composition according to claim 13, wherein the matrix comprises a naturally occurring material or a synthetic material.

22. The coating composition of claim 13, wherein the coating composition comprises antibodies, or fragments thereof, of the type which reacts wit an endothelial cell surface antigen.

23. A method for rendering a medical device compatible for in vivo attachment and proliferation of cells on the surface thereof, comprising the steps:

(a) coating the medical device with one or more layers of a matrix; and

(b) adding to the matrix layer a therapeutically effective amount of a type of antibody which reacts with an endothelial cell surface antigen.

24. The method of claim 23, wherein the antibody is noncovalently coated on the matrix layer.

25. The method of claim 23, wherein the antibody is tethered covalently by a linker molecule to the matrix layer coating the medical device.

26. The method according to claim 23, wherein the matrix comprises a naturally occurring material or a synthetic material.

27. The method according to claim 23, wherein the matrix comprises a material selected from the group consisting of a fullerene, polyurethane, segmented polyurethane-urea/heparin, poly-L-lactic acid, cellulose ester, polyethylene glycol, collagen, laminin, heparin, fibrin, cellulose, carbon, polytetrafluoroethylene, and expanded polytetrafluoroethylene.

28. The method according to claim 27, wherein when the matrix material comprises a fullerene, the fullerene ranges from about C60 to about C100.

29. The method according to claim 27, wherein when the matrix material comprises a fullerene, the fullerene is C60O.

30. The method according to claim 23, wherein a therapeutically effective amount of antibodies, or fragments thereof, of the type which reacts with an endothelial cell surface antigen are added to the matrix layer.

31. A method of treating a mammal for atherosclerosis comprising inserting a medical device into an artery of the mammal, wherein the medical device comprises a coating rendering the medical device compatible for in vivo attachment and proliferation of cells on the surface thereof wherein the coating comprises a therapeutically effective amount of a type of antibody which reacts with an endothelial cell surface antigen, and one or mare layers of a matrix.

32. The method of treatment of claim 31, wherein the antibody is a monoclonal antibody.

33. The method of treatment of claim 32, wherein the monoclonal antibody comprises Fab or F(ab′

)₂ fragments.

34. The method of treatment of claim 31, wherein the atherosclerosis is coronary artery atherosclerosis.

38. The method according to claim 31 or 35, wherein the matrix comprises a naturally occurring material or a synthetic material.

39. The method according to claim 31 or 35, wherein the matrix comprises a material selected from the group consisting of a fullerene, polyurethane, segmented polyurethane-urea/heparin, poly-L-lactic acid, cellulose ester, polyethylene glycol, collagen, laminin, heparin, fibrin, cellulose, carbon, polytetrafluoroethylene, and expanded polytetrafluoroethylene.

40. The method according to claim 39, wherein when the matrix material comprises a fullerene, the fullerene ranges from about C60 to about C100.

41. The method according to claim 39, wherein when the matrix material comprises a fullerene, the fullerene is C60O.

42. The method of claim 31 or 35, wherein the coating composition comprises antibodies, or fragments thereof of the type which reacts with an endothelial cell surface antigen.

35. A method for treating a mammal for obstruction of a vessel comprising inserting a medical device into a vessel of the mammal, wherein the medical device comprises a coating rendering the medical device compatible for in vivo attachment and proliferation of cells on the surface thereof, wherein the coating comprises a type of antibody which reacts with an endothelial cell surface antigen, and one or more layers layer of a matrix.

36. The method of treatment of claim 35, wherein the vessel is an artery.

37. The method of treatment of claim 35, wherein the vessel is a vein.

43. A medical device comprising one or more layers of a matrix, wherein the matrix layer is covalently attached to the medical device and the matrix comprises a C60O fullerene.

44. The medical device of claim 43, wherein the matrix layer is noncovalently attached to the medical device.

45. The medical device of claim 43, wherein the medical device is a stent.

46. The medical device of claim 43, wherein the medical device is a synthetic graft.