MEDICAL DEVICE WITH COATING THAT PROMOTES ENDOTHELIAL CELL ADHERENCE

• US 20130035755A1
• Filed: 08/20/2012
• Published: 02/07/2013
• Est. Priority Date: 03/15/2000
• Status: Active Grant

• Current Assignee: OrbusNeich Medical Pte Ltd
• Original Assignee: Orbusneich Medical Incorporated (Orbusneich Medical)
• Inventors: Kutryk, Michael John Bradley, Cottone, Robert John Jr., Rowland, Stephen Maxwell
• Granted Patent: US 9,072,723 B2
• Time in Patent Office: Days
• US Class Current: 623/1.38
• 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

The invention relates to a method for healing blood vessels by stimulating the formation of a confluent endothelial autologous cell layer in vivo on an implantable metallic stent having a lumen and a luminal surface, and an exterior surface. More specifically, the method includes implanting the stent with a coating in a patient in need of thereof; wherein the coating includes one or more layers of a matrix covalently adherent on said luminal and exterior surface of said stent containing one or more pharmaceutical substances on said exterior surface and a therapeutically effective amount of a single type of antibody, antibody fragments or combinations thereof being compatible to binding selectively to a specific cell surface antigen of circulating autologous endothelial progenitor cells in peripheral blood. In addition, genetically engineered endothelial progenitor cells can be captured on said luminal surface of stent in vivo, to proliferate to form rapidly a confluent endothelium in situ.

Claims

1-32. -32. (canceled)

33. A method for stimulating the formation of a confluent endothelial autologous cell layer in vivo on an implantable metallic stent having a lumen and a luminal surface, and an exterior surface comprising the steps of:

implanting a metallic stent with a coating to a patient in need of said stent;

wherein said coating comprises one or more layers of a matrix covalently adherent on said luminal and exterior surface of said stent;

said one or more layers of the matrix containing one or more pharmaceutical substances on said exterior surface; and

a therapeutically effective amount of a single type of antibody, antibody fragments or combinations thereof tethered to said coating, said single type of antibody, antibody fragments or combinations thereof being compatible to binding selectively to a specific cell surface antigen of circulating autologous endothelial progenitor cells in peripheral blood and capturing endothelial progenitor cells or genetically engineered endothelial progenitor cells on said luminal surface of stent in vivo, and wherein said coating stimulates adherence and proliferation of said endothelial progenitor cells or genetically engineered endothelial progenitor cells on the luminal surface of said stent to form rapidly a confluent endothelium in situ.

34. The method of claim 33, wherein the antibody, antibody fragments or combinations thereof is/are immobilized to one or more layers of a biocompatible matrix.

35. The method of claim 33, wherein the antibody, antibody fragments or combinations thereof specifically binds to genetically engineered stem or progenitor cells.

36. The method of claim 33, further comprising providing molecules in said one or more layers of said matrix for inducing proliferation or differentiation of captured circulating stem cells or progenitor cells or genetically engineered cells, in situ.

37. The method of claim 33, wherein said one or more layers of said matrix is formed of a natural or synthetic polymer.

38. The method of claim 33, wherein said one or more layers of said matrix are a fibrous mesh.

39. The method of claim 33, wherein the specific antibody, antibody fragment or combination thereof bind an antigen selected from CD45, CD34, CD31, Flk-1, Tie-2, and E-selectin.

40. The method of claim 33, wherein the circulating stem or progenitor endothelial cells are transfected with a mammalian expression vector.

41. The method of claim 33, wherein the mammalian expression vector comprises one or more cloned genes encoding a protein selected from the group consisting of platelet derived growth factor (PDGF), fibroblast growth factor (FGF), and nitric oxide synthase.

42. The method of claim 34, wherein the one or more layers of said biocompatible matrix are bioabsorbable or non-absorbable.

43. The method of claim 33, wherein said one or more layers of said matrix comprises a synthetic polymer, naturally occurring polymer, fullerenes or amorphous carbon.

44. The method of claim 38, wherein said synthetic polymer is polyurethane, segmented polyurethane-urea/heparin, poly-lactic acid, cellulose ester, polyethylene glycol, or combinations thereof.

45. The method of claim 38, wherein said naturally-occurring polymer is collagen, laminin, heparin, fibrin, cellulose, elastin or combinations thereof.

46. The method of claim 33, wherein the antibodies and antibody fragments are derived from monoclonal antibodies or fragments thereof.

47. The method of claim 33, wherein the antibodies or antibody fragments have specificity to bind an endothelial cell membrane antigen.

48. The method of claim 33, wherein said coating promotes in vivo adherence of circulating endothelial cells to said medical device.

49. The method of claim 33, wherein the coating comprises at least one inner layer of a synthetic matrix and the antibodies are anti-CD34 antibodies.

50. The method of claim 33, wherein the stent polymer comprises stainless steel, nickel-titanium, tantalum, gold, platinum-iridium, Elgiloy, or MP35N.

51. A method of claim 33, wherein the antibodies, antibody fragments or combinations thereof comprise a plurality of different antibodies directed against different specific endothelial cell surface antigens.

52. The method of claim 33, wherein the one or more layers of the matrix comprise a material selected from the group consisting of a fullerene, polyurethane, segmented polyurethane-urea/heparin, poly (D,L-lactide) , poly-L-Iactic acid, cellulose ester, polyethylene glycol, collagen, elastin, laminin, heparin, fibrin, cellulose, carbon, polytetrafluoroethylene, and expanded polytetrafluoroethylene.