Claims for Patent: RE45500

Summary for Patent: RE45500

Title:	Polymeric network system for medical devices and methods of use
Abstract:	Methods of making a coating on a medical device are disclosed, including associating a composition with at least a portion of the device to form a layer. In some embodiments, a composition may include a copolymer prepared from a room temperature melt of a plurality of monomer units that comprises a first monomer unit and a second monomer unit, wherein the second monomer unit has a glass transition temperature that is at least about 30 degrees Centigrade higher than the glass transition temperature of the first monomer unit, with a glass transition temperature of a monomer unit being defined as a glass transition temperature of a homopolymer of that monomer unit.
Inventor(s):	Luthra; Ajay K. (Middlesex, GB), Sandhu; Shivpal S. (Farnham Common, GB)
Assignee:	BioInteractions Ltd. (Reading, Berkshire, GB)
Application Number:	13/365,092
Patent Claims:	1. A coating for a medical device for delivery of a therapeutic agent, the coating comprising a .Iadd.thermoplastic .Iaddend.layer with a thickness between about 0.1 .mu.m and about 1000 .mu.m and having a composition associated with at least a portion of the device, wherein the composition comprises the therapeutic agent associated with .Iadd.thermoplastic .Iaddend.copolymer free of covalent crosslinks that has a weight averaged molecular weight of at least about 2500, wherein the copolymer .Iadd.is made only of thermoplastic-forming monomers and .Iaddend.comprises a .Iadd.thermoplastic-forming .Iaddend.first monomer unit and a .Iadd.thermoplastic-forming .Iaddend.second monomer unit, wherein the second monomer unit has a glass transition temperature that is at least about 30 degrees Centigrade higher than the glass transition temperature of the first monomer unit, with a glass transition temperature of a monomer unit being defined as a glass transition temperature of a homopolymer of that monomer unit.Iadd., wherein the device is selected from the group consisting of an implantable device, a catheter, a guide-wire, an embolizing coil, a vascular graft, a heart valve, an implantable cardiovascular defibrillator, a pacemaker, a microsphere, a biosensor, an implantable sensor, an ex-vivo sensor, an ocular implant, a contact lens, a stent, and a tissue engineering scaffold; wherein the copolymer is made from a combination of monomer units and has a glass transition temperature in a range of about -70 to about 70 degrees Celsius as measured using differential scanning calorimetery.Iaddend.. 2. The coating of claim 1 wherein at least a portion of the first monomer units are organized into a plurality of blocks consisting essentially of repeats of the first monomer unit, and at least a portion of the second monomer units are organized into a plurality of blocks consisting essentially of repeats of the second monomer unit. 3. The coating of claim 2 wherein the copolymer further comprises regions of random copolymer bonding. 4. The .[.coaling.]. .Iadd.coating .Iaddend.of claim 1 wherein the copolymer comprises a third monomer unit and comprises at least three blocks, wherein each block consists essentially of repeats of one type of monomer unit. 5. The coating of claim 1 wherein the copolymer comprises acrylate blocks and methacrylate blocks. 6. The coating of claim 1 wherein the therapeutic agent associates with blocks within the copolymer. 7. The coating of claim 1 wherein the second monomer unit has a glass transition temperature that is at least about 50 degrees Centigrade higher than the glass transition temperature of the first monomer unit. 8. The coating of claim 1, wherein the second monomer unit has a glass transition temperature that is at least about 70 degrees Centigrade higher than the glass transition temperature of the first monomer unit. 9. The coating of claim 1 wherein the first monomer unit comprises an acrylate and the second monomer unit compromises a methacrylate. 10. The coating of claim 1 wherein the first monomer unit and the second monomer unit .Iadd.are .Iaddend.selected from .[.a member of.]. the group consisting of acrylic acid, acrlonitrile, allyamine, acrylates, methacrylates, methylmethacrylate, alkyl acrylates, alkyl methacrylate, .[.butadiene,.]. carbomethylsilane, (carbonate) urethane, .[.acrylates of polydimethyl siloxanes, methacrylates of polydimethyl siloxanes, ethylene,.]. ethylene glycol, propylene glycol, (ether) urethane, urethane, vinyl chloride, vinyl alcohol, maleic anhydride, cellulose nitrate, carboxy methyl cellulose, dextran, dextran sulphate, .[.propylene,.]. esters, carbonates, ethers, .[.butenes,.]. maleic acid, fluoropolymer monomeric units, unsaturated polymer monomeric units, .[.isoprene,.]. melamine, sulphone, ureas, biological polymer monomeric units, protein, gelatin, collagen, .[.elastin,.]. butyl methacrylate, hydroxyethyl methacrylate, methacrylate acid, polyethylene glycol dimethacrylate, polypropylene glycol .[.diglycidal.]. .Iadd.diglycidyl .Iaddend.ether, polyethylene glycol diglycidyl ether, isocyanatoethyl methacrylate, N-acryloxysuccinimide, glycidyl methacrylate, hexamethylene diisocyanate, acrolein, crotonaldehyde, glycerol monomethacrylate, heparin methacrylate, methacryloylethyl phosphorylcholine, .[.polymethacrylatea.]. .Iadd.polymethacrylate.Iaddend., polyacrylate, polyester, polyether, polyethylene glycol, butyl acrylate, polyethylene glycol monomethacrylate, isobutyl methacrylate, cyclohexyl methacrylate, ethyl acrylate, 2-hydroxyethyl acrylate, 2-ethylhexyl methacrylate, ethyl methacrylate, methyl acrylate, hexadecyl methacrylate, octadecyl methacrylate, styrene, methyl styrene, vinyl sterate, vinyl toluene, and tert-butyl acrylate. 11. The coating of claim 1 wherein the copolymer .[.father.]. .Iadd.further .Iaddend.comprises a third monomer unit, wherein the third monomer unit forms a homopolymer .[.wit.]. .Iadd.with .Iaddend.a glass transition temperature that is at least about 30 degrees Centigrade higher than the glass transition temperature of a homopolymer formed by the first monomer unit. 12. The coating of claim 11 wherein the first monomer unit comprises an acrylate, the second monomer unit compromises a methacrylate, and the third monomer unit comprises a methacrylate. 13. The coating of claim 11 wherein the copolymer comprises a homopolymer of the first monomer unit covalently joined to a homopolymer of the second monomer unit. 14. The coating of claim 13 wherein a first polymer comprises a first monomer unit and a second polymer comprises at least one member of the group consisting of the first monomer unit, the second monomer unit, and both the first monomer unit and the second monomer unit. 15. The coating of claim 1 wherein the copolymer comprises at least two methacrylate monomer units. 16. The coating of claim 1 wherein the copolymer comprises a member of the group consisting of poly(hydroxyethyl methacrylate-co-butylactylate-co-butylmethacrylate), poly(hydroxyethyl methacrylate-co-lauryl methacrylate), poly(polyethylene glycol monomethacrylate-co-butyl acrylate-co-butyl methacrylate), poly(heparin methacrylate-co-hydroxyethylmethacrylate-co-butyl acrylate-co-butyl methacrylate), poly(glycerol monomethacrylate-co-butyl acrylate-co-butyl methacrylate), poly(amino methacrylate hydrochloride-co-butyl acrylate-co-butyl methacrylate), poly(isocyanatoethyl methacrylate-co-butyl acrylate-co-butyl methacrylate) and poly (methoxy(polyethylene glycol) monomethacrylate-co-lauryl methacrylate-co-butyl methacrylate-co-ethylene glycol dimethacrylate). 17. The coating of claim 1 wherein the monomer units are polymerizable to form the copolymer after the monomer units have been associated with the medical device. 18. The coating of claim 1 wherein the medical device is a stent and the therapeutic agent is paclitaxel. 19. The coating of claim 1 wherein the copolymer is prepared and is subsequently associated with the therapeutic agent. 20. The coating of claim 1 wherein the copolymer is prepared from the monomer units from a melt of the monomers. 21. The coating of claim 1 wherein the first monomer unit and the second monomer unit are chosen so that the first monomer unit reacts to form a plurality of blocks consisting essentially of repeats of the first monomer unit and the second monomer unit reacts to form a plurality of blocks consisting essentially of repeats of the second monomer unit. 22. The coating of claim 1 further comprising a second layer that contacts at least a portion of the first layer, wherein the second layer and the first layer have a different composition. 23. The coating of claim 22 wherein the first layer is at least partially disposed between the device and the second layer. 24. The coaling of claim 22 wherein the second layer is at least partially disposed between the device and the first layer. 25. The coating of claim 22 wherein the second layer comprises a polymer that is covalently crosslinked to a polymer of the first layer. 26. The coating of claim 25 wherein the copolymer comprises reactive functional groups that are involved in forming covalent crosslinks with the second layer, and wherein the reactive functional groups are chosen from the group consisting of hydroxyl, amine, carboxylic, aldehyde, ketone, thiol, .[.ally).]. .Iadd.ally.Iaddend., acrylate, methacrylate, isocyanate, epoxide, azides, aziridines, acetals, ketals, alkynes, acyl halides, alky halides, hydroxy aldehydes and ketones, allenes, amides, bisamides, amino acids and esters, amino carbonyl compounds, mercaptans, amino mercaptans, anhydrides, azines, azo compounds, azoxy compounds, boranes, carbamates, carbodimides, carbonates, diazo compounds, isothionates, hydroxamic acid, hydroxy acids, hydroxy amines and amides, hydroxylamine, imines, lactams, nitriles, sulphonamides, sulphones, sulphonic acids, thiocyanates, and combinations thereof. 27. The coating of claim 25 wherein the second layer comprises a heparin macromer that comprises a second reactive functional group that is involved in forming the crosslinks with the first layer. 28. The coating of claim 25 wherein the polymer of the second layer comprises monomer units that comprise a heparin macromer. 29. The coating of claim 25 wherein the polymer of the second layer comprises a second functional group that forms at least one of the covalent crosslinks in response to exposure to light. 30. The coating of claim 29 wherein the second functional group comprises azide. 31. The coating of claim 22 wherein the first layer comprises the therapeutic agent and the second layer does not comprise the therapeutic agent. 32. The coating of claim 22 wherein the second layer reduces the rate of release of the therapeutic agent from the first layer. 33. The coating of claim 22 wherein the second layer is in contact with the medical device and comprises a polymer having at least one reactable monomer. 34. The coating of claim 33 wherein the at least one reactable monomer is a member of the group consisting of acrylates and methylmethacrylates. 35. The coating of claim 34 wherein the polymer in the second layer is a second copolymer that comprises monomer units of at least one member of the group consisting of vinyl chloride, vinyl acetate, and co-vinyl alcohol. 36. The coating of claim 34 wherein the polymer in the second layer comprises a hydrophillic polymer. 37. The coating of claim 36 wherein the polymer in the second layer comprises polyvinylpyrrolidone. 38. The coating of claim 22 further comprising a third layer having a composition different from the first layer and the second layer. 39. The coating of claim 1 wherein the therapeutic agent is a member of the group consisting of, vasoactive agents, neuroactive agents, hormones, growth factors, cytokines, anaesthetics, steroids, anticoagulants, anti-inflammatories, immunomodulating agents, cytotoxic agents, antibiotics, antivirals, antibodies, anti-thrombogenic agents such as heparin, heparin derivatives, urokinase, and PPack (dextrophenylalanine proline arginine chloromethylketone); anti-proliferative agents such as enoxaprin, angiopeptin, antibodies capable of blocking smooth muscle cell proliferation, hirudin, acetylsalicylic acid; anti-inflammatory agents, dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine, and mesalamine, 5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones, endostatin, angiostatin and thymidine kinase inhibitors; anesthetic agents such as lidocaine, bupivacaine, and ropivacaine; anti-coagulants, D-Phe-Pro-Arg chloromethyl ketone, an RGD peptide-containing compound, heparin, antithrombin compounds, platelet receptor antagonists, anti-thrombin, anti-platelet receptor antibodies, aspirin, prostaglandin inhibitors, platelet inhibitors, antiplatelet peptides, vascular cell growth promoters, growth factor inhibitors, growth factor receptor antagonists, transcriptional activators, translational promoters, vascular cell growth inhibitors, growth factor receptor antagonists, transcriptional repressors, translational repressors, replication inhibitors, inhibitory antibodies, antibodies directed against growth factors, cholesterol-lowering agents, vasodilating agents, agents which interfere with endogenous vasoactive mechanisms, a radiopharmaceutical, an analgesic drug, an anesthetic agent, an anorectic agent, an anti-anemia agent, an anti-asthma agent, an anti-diabetic agent, an anti-histamine, an anti-inflammatory drug, an antibiotic drug, an antimuscarinic drug, an anti-neoplastic drug, an antiviral drug, a cardiovascular drag, a central nervous system stimulator, a central nervous system depressant, an anti-depressant, an anti-epileptic, an anxyolitic agent, a hypnotic agent, a sedative, an anti-psychotic drug, a beta blocker, a hemostatic agent, a hormone, a vasodilator, a vasoconstrictor, and a vitamin. 40. The coating of claim 1 wherein the therapeutic agent comprises paclitaxel. .[.41. The coating of claim 1 wherein the device is selected from the group consisting of an implantable device, a device used topically on a patient, a device that contacts a living tissue, a catheter; a guide-wires, an embolizing coil; a vascular graft, a heart valve, an implantable cardiovascular defibrillator, a pacemaker, a surgical patch, a wound closure, a microsphere, a biosensors, an implantable sensor, an ex-vivo sensor, an ocular implant, a contact lens; and a tissue engineering scaffold..]. 42. The coating of claim 1 wherein the device comprises .[.a.]. .Iadd.the .Iaddend.stent. 43. The coating of claim 1 wherein the glass transition temperature of the first monomer unit is below about 37 degrees Centigrade and the glass transition temperature of the second monomer unit is above about 37 degrees Centigrade. 44. The coating of claim 1 wherein the copolymer is made from a combination of monomer units and has a glass transition temperature in a range of about 0 to about 60 degrees Celsius as measured using differential scanning calorimetery. 45. The coating of claim 1 wherein the copolymer is made from a combination of monomer units and has a glass transition temperature in a range of about 15 to about 40 degrees Celsius as measured using differential scanning calorimetery. .[.46. The coating of claim 1 wherein the copolymer is made from a combination of monomer units and has a glass transition temperature in a range of about -70 to about 70 degrees Celsius as measured using differential scanning calorimetery..]. 47. The coating of claim .[.46.]. .Iadd.1 .Iaddend.wherein the combination comprises at least one monomer unit selected from the group consisting of butyl acrylate, butyl methylmethacrylate, and hydroxyethylmethacrylate. 48. The coating of claim .[.46.]. .Iadd.1 .Iaddend.wherein the first monomer unit and the second monomer unit are selected from .[.a member of.]. the group consisting of acrylic acid, acrionitrile, allyamine, acrylates, methacrylates, methylmethacrylate, alkyl acrylates, alkyl methacrylate, .[.butadiene,.]. carbomethylsilane, (carbonate) urethane, .[.acrylates of polydimethyl siloxanes/methacrylates of polydimethyl siloxane ethylene,.]. ethylene glycol, propylene glycol, (ether) urethane, urethane, vinyl chloride, vinyl alcohol, maleic anhydride, cellulose nitrate, carboxy methyl cellulose, dextran, dextran sulphate, .[.propylene,.]. esters, carbonates, ethers, .[.butenes,.]. maleic acid, fluoropolymer monomeric units, unsaturated polymer monomeric units, .[.isoprene,.]. melamine, sulphone, ureas, biological polymer monomeric units, protein, gelatin, collagen, .[.elastin,.]. butyl methacrylate, hydroxyethyl methacrylate, acrylic acid, methacrylate acid, polyethylene glycol dimethacrylate, polypropylene glycol .[.diglycidal.]. .Iadd.diglycidyl .Iaddend.ether, polyethylene glycol diglycidyl ether, isocyanatoethyl methacrylate, N-acryloxysuccinimide, glycidyl methacrylate, hexamethylene diisocyanate, acrolein, crotonaldehyde, glycerol monomethacrylate, heparin methacrylate, methacryloyloxyethyl, methacryloylethyl phosphorylcholine polyacrylate, polyester, polyether, polyethylene glycol, butyl acrylate, polyethylene glycol monomethacrylate, isobutyl methacrylate, cyclohexyl methacrylate, ethyl acrylate, 2-hydroxyethyl acrylate, 2-ethylhexyl methacrylate, ethyl methacrylate, methyl acrylate, hexadecyl methacrylate, octadecyl methacrylate, styrene, methyl styrene, vinyl sterate, vinyl toluene, and tert-butyl acrylate. 49. The coating of claim .[.46.]. .Iadd.1 .Iaddend.wherein the copolymer further comprises a third monomer unit, wherein the third monomer unit forms a homopolymer with a glass transition temperature that is at least about 30 degrees Centigrade higher than the glass transition temperature of a homopolymer formed by the first monomer unit. 50. The coating of claim .[.46.]. .Iadd.1 .Iaddend.wherein the first monomer unit comprises an acrylate, the second monomer unit compromises a methacrylate, and the third monomer unit comprises a methacrylate. 51. The coating of claim .[.46.]. .Iadd.1 .Iaddend.wherein the copolymer comprises at least two methacrylate monomer units. 52. The coating of claim 42 wherein the coating is disposed essentially only on the solid portions of the stent. 53. The coating of claim 42 wherein the coating is disposed on both a lumen and exterior of the stent. 54. An expandable medical device associated with a material composition for delivery of a therapeutic agent, comprising: an expandable portion of an expandable .[.stern.]. .Iadd.stent .Iaddend.coated with a .Iadd.thermoplastic .Iaddend.composition comprising the therapeutic agent associated with a .Iadd.thermoplastic .Iaddend.copolymer free of covalent crosslinks that has a weight averaged molecular weight of at least about 2500, wherein the copolymer .Iadd.is made only of thermoplastic-forming monomers and .Iaddend.comprises a .Iadd.thermoplastic-forming .Iaddend.first monomer unit and a .Iadd.thermoplastic-forming .Iaddend.second monomer unit, wherein the second monomer unit has a glass transition temperature that is at least about 30 degrees Centigrade higher than the glass transition temperature of the first monomer unit, with a glass transition temperature of a monomer unit being defined as a glass transition temperature of a homopolymer of that monomer unit.Iadd.; wherein the copolymer comprises a third monomer unit and comprises at least three blocks, wherein each block consists essentially of repeats of one type of monomer unit.Iaddend.. 55. The device of claim 54 wherein at least a portion of the first monomer units are organized into a plurality of blocks consisting essentially of repeats of the first monomer unit, and at least a portion of the second monomer units are organized into a plurality of blocks consisting essentially of repeats of the second monomer unit. 56. The device of claim 55 wherein the copolymer further comprises regions of random copolymer bonding. 57. The device of claim 55 wherein the copolymer comprises acrylate blocks and methacrylate blocks. .[.58. The device of claim 54 wherein the copolymer comprises a third monomer unit and comprises at least three blocks, wherein each block consists essentially of repeats of one type of monomer unit..]. 59. The device of claim 54 wherein the therapeutic agent associates with blocks within the copolymer. 60. The device of claim 54, wherein the second monomer unit has a glass transition temperature that is at least about 70 degrees Centigrade higher than the glass transition temperature of the first monomer unit. 61. The device of claim 54 wherein the monomer units are polymerizable to form the copolymer after the monomer units have been associated with the medical device. 62. The device of claim 54 wherein the therapeutic agent is paclitaxel. 63. The device of claim 54 wherein the copolymer is prepared and is subsequently associated with the therapeutic agent. 64. The device of claim 54 wherein the copolymer is prepared from the monomer units from a melt of the monomers. 65. The device of claim 54 wherein the first monomer unit and the second monomer unit are chosen so that the first monomer unit reacts to form a plurality of blocks consisting essentially of repeats of the first monomer unit and the second monomer unit reacts to form a plurality of blocks consisting essentially of repeats of the second monomer unit. 66. The device of claim 54 further comprising a second layer that contacts at least a portion of the first layer, wherein the second layer and the first layer have a different composition. 67. The device of claim 66 wherein the second layer comprises a polymer that is covalently crosslinked to a polymer of the first layer. 68. The device of claim 67 wherein the polymer of the second layer comprises monomer units that comprise a heparin macromer. 69. The device of claim 66 wherein the polymer of the second layer comprises a second functional group that forms at least one of the covalent crosslinks in response to exposure to light. 70. The device of claim 54 wherein the copolymer glass transition temperature is between 26 and about 40 degrees Centigrade. 71. The device of claim 54 wherein the composition associated with the stent has a thickness ranging from about 0.1 .mu.m to about 30 .mu.m. 72. The coating of claim 1 wherein the thickness ranges from about 1 .mu.m to about 200 .mu.m. 73. The coating of claim 54 wherein the coating is disposed essentially only on the solid portions of the stent. 74. The coating of claim 54 wherein the coating is disposed on both a lumen and exterior of the stent. 75. A coating for a medical device for delivery of a therapeutic agent, the coating comprising a .Iadd.thermoplastic .Iaddend.layer having a composition associated with at least a portion of the device, wherein the composition comprises the therapeutic agent associated with a copolymer that has a weight averaged molecular weight of at least about 2500 and a glass transition temperature between 26 and about 40 degrees Centigrade as measured by differential scanning calorimetery, wherein the copolymer .Iadd.is made only of thermoplastic-forming monomers and .Iaddend.comprises a .Iadd.thermoplastic-forming .Iaddend.first monomer unit and a .Iadd.thermoplastic-forming .Iaddend.second monomer unit, wherein the second monomer unit has a glass transition temperature that is at least about 30 degrees Centigrade higher than the glass transition temperature of the first monomer unit, with a glass transition temperature of a monomer unit being defined as a glass transition temperature of a homopolymer of .[.tat.]. .Iadd.that .Iaddend.monomer unit, wherein the layer has a glass transition temperature between 26 and about 40 degrees Centigrade as measured by differential scanning calorimetery.Iadd., wherein the device is selected from the group consisting of an implantable device, a catheter; a guide-wire, an embolizing coil; a vascular graft, a heart valve, an implantable cardiovascular defibrillator, a pacemaker, a microsphere, a biosensor, an implantable sensor, an ex-vivo sensor, an ocular implant, a contact lens, a stent, and a tissue engineering scaffold.Iaddend.. 76. The coating of claim 75 wherein at least a portion of the first monomer units are organized into a plurality of blocks consisting essentially of repeats of the first monomer unit, and at least a portion of the second monomer units are organized into a plurality of blocks consisting essentially of repeats of the second monomer unit. 77. The coating of claim 75 wherein the copolymer further comprises regions of random copolymer bonding. 78. The coating of claim 75 wherein the copolymer comprises a third monomer unit and comprises at least three blocks, wherein each block consists essentially of repeats of one type of monomer unit. 79. The coating of claim 75 wherein the copolymer comprises acrylate blocks and methacrylate blocks. 80. The coating of claim 75 wherein the therapeutic agent associates with blocks within the copolymer. 81. The coating of claim 75, wherein the second monomer unit has a glass transition temperature that is at least about 70 degrees Centigrade higher than the glass transition temperature of the first monomer unit. 82. The coating of claim 75 wherein the monomer units are polymerizable to form the copolymer after the monomer units have been associated with the medical device. 83. The coating of claim 75 wherein the medical device is .[.a.]. .Iadd.the .Iaddend.stent and the therapeutic agent is paclitaxel. 84. The coating of claim 75 wherein the copolymer is prepared and is subsequently associated with the therapeutic agent. 85. The coating of claim 75 wherein the copolymer is prepared from the monomer units from a melt of the monomers. 86. The coating of claim 75 wherein the first monomer unit and the second monomer unit are chosen so that the first monomer unit reacts to form a plurality of blocks consisting essentially of repeats of the first monomer unit and the second monomer unit reacts to form a plurality of blocks consisting essentially of repeats of the second monomer unit. 87. The coating of claim 75 further comprising a second layer that contacts at least a portion of the first layer, wherein the second layer and the first layer have a different composition. 88. The coating of claim 87 wherein the second layer comprises a polymer that is covalently crosslinked to a polymer of the first layer. 89. The coating of claim 88 wherein the polymer of the second layer comprises .[.monomer wilts that comprise.]. a heparin macromer. 90. The coating of claim 88 wherein the polymer of the second layer comprises a second functional group that forms at least one of the covalent cross links in response to exposure to light. 91. The coating of claim 75 wherein the medical device is .[.a.]. .Iadd.the .Iaddend.stent, with the coating being applied to every expandable portion of the stent. .[.92. The coating of claim 75 wherein the medical device is a member of the group consisting of an implantable device, a device used topically on a patient, a device that contacts a living tissue, a catheter; a guide-wires, an embolizing coil, an implantable lead, an expandable balloon, a vascular graft, a heart valve, an implantable cardiovascular defibrillator, a pacemaker, a surgical patch, a wound closure, a microsphere, a biosensors, an implantable sensor, an ex-vivo sensor, an ocular implant, a contact lens, and a tissue engineering scaffold..]. 93. The coating of claim 75 having a thickness of between about 0.1 .mu.m and about 1000 .mu.m. 94. The coating of claim 75 having a thickness of between about 1 .mu.m and about 200 .mu.m. 95. The copolymer of claim 70 wherein the copolymer glass transition temperature is about 37.degree. C. 96. The coating of claim 75 wherein the layer glass transition temperature is about 37.degree. C. 97. A .[.coaling.]. .Iadd.coating .Iaddend.for a medical device for delivery of a therapeutic agent, the coating comprising a .Iadd.thermoplastic .Iaddend.layer having a composition associated .[.wit.]. .Iadd.with .Iaddend.at least a portion of the device, wherein the composition comprises the therapeutic agent associated with a copolymer free of covalent crosslinks that has a weight averaged molecular weight of at least about 2500, wherein the copolymer .Iadd.is made only of thermoplastic-forming monomers and .Iaddend.comprises a .Iadd.thermoplastic-forming .Iaddend.first monomer unit and a .Iadd.thermoplastic-forming .Iaddend.second monomer unit, wherein the second monomer unit has a glass transition temperature that is at least about 30 degrees Centigrade higher than the glass transition temperature of the first monomer unit, with a glass transition temperature of a monomer unit being defined as a glass transition temperature of a homopolymer of that monomer unit, wherein the device is selected from the group consisting of an implantable device, .[.a device used topically on a patient, a device that contacts a living tissue,.]. a catheter.[.;.]..Iadd., .Iaddend.a .[.guide-wires.]. .Iadd.guide-wire.Iaddend., an embolizing coil, an implantable lead, an expandable balloon, a vascular graft, a heart valve, an implantable cardiovascular defibrillator, a pacemaker, .[.a surgical patch, a wound closure,.]. a microsphere, a .[.biosensors.]. .Iadd.biosensor.Iaddend., an implantable sensor, an ex-vivo sensor, an ocular implant, a contact lens, and a tissue engineering scaffold.Iadd.; wherein the copolymer comprises a third monomer unit and comprises at least three blocks, wherein each block consists essentially of repeats of one type of monomer unit.Iaddend.. 98. The coating of claim 97 wherein at least a portion of the first monomer units are organized into a plurality of blocks consisting essentially of repeats of the first monomer unit, and at least a portion of the second monomer units are organized into a plurality of blocks consisting essentially of repeats of the second monomer unit. 99. The coating of claim 98 wherein the copolymer further comprises regions of random copolymer bonding. .[.100. The coating of claim 97 wherein the copolymer comprises a third monomer unit and comprises at least three blocks, wherein each block consists essentially of repeats of one type of monomer unit..]. 101. The coating of claim 97 wherein the copolymer comprises acrylate blocks and methacrylate blocks. 102. The coating of claim 97 wherein the therapeutic agent associates with blocks within the copolymer. 103. The coating of claim 97, wherein the second monomer unit has a glass transition temperature that is at least about 70 degrees Centigrade higher than the glass transition temperature of the first monomer unit. 104. The coating of claim 97 wherein the monomer units are polymerizable to form the copolymer after the monomer units have been associated with the medical device. 105. The coating of claim 97 wherein the copolymer is prepared and is subsequently associated with the therapeutic agent. 106. The coating of claim 97 wherein the copolymer is prepared from the monomer units from a melt of the monomers. 107. The coating of claim 97 wherein the first monomer unit and the second monomer unit are chosen so that the first monomer unit reacts to form a plurality of blocks consisting essentially of repeats of the first monomer unit and the second monomer unit reacts to form a plurality of blocks consisting essentially of repeats of the second monomer unit. 108. The coating of claim 97 further comprising a second layer that contacts at least a portion of the first layer, wherein the second layer and the first layer have a different composition. 109. The coating of claim 108 wherein the second layer comprises a polymer that is covalently crosslinked to a polymer of the first layer. 110. The coating of claim 109 wherein the polymer of the second layer comprises monomer units that comprise a heparin macromer. 111. The coating of claim 109 wherein the polymer of the second layer comprises a second functional group that forms at least one of the covalent crosslinks in response to exposure to light. 112. The coating of claim 97 wherein the copolymer has a glass transition temperature between 26 and about 40 degrees Centigrade. 113. The coating of claim 97 having a thickness of between about 0.1 .mu.m and about 1000 .mu.m. .Iadd.114. A coating for a medical device, the coating comprising a thermoplastic layer with a thickness between about 0.1 .mu.m and about 1000 .mu.m that comprises a thermoplastic copolymer free of covalent crosslinks that has a weight averaged molecular weight of at least about 2500, wherein the copolymer is made only of thermoplastic-forming monomers and comprises a first thermoplastic-forming monomer unit and a second thermoplastic-forming monomer unit, wherein the second monomer unit has a glass transition temperature that is at least about 30 degrees Centigrade higher than the glass transition temperature of the first monomer unit, with a glass transition temperature of a monomer unit being defined as a glass transition temperature of a homopolymer of that monomer unit, wherein the device is selected from the group consisting of an implantable device, a catheter, a guide-wire, an embolizing coil, a vascular graft, a heart valve, an implantable cardiovascular defibrillator, a pacemaker, a microsphere, a biosensor, an implantable sensor, an ex-vivo sensor, an ocular implant, a contact lens, a stent, and a tissue engineering scaffold; wherein the copolymer is made from a combination of monomer units and has a glass transition temperature in a range of about -70 to about 150 degrees Celsius as measured using differential scanning calorimetery..Iaddend. .Iadd.115. The coating of claim 114 wherein at least a portion of the first monomer units are organized into a plurality of blocks consisting essentially of repeats of the first monomer unit, and at least a portion of the second monomer units are organized into a plurality of blocks consisting essentially of repeats of the second monomer unit..Iaddend. .Iadd.116. The coating of claim 114 wherein the copolymer comprises a third monomer unit and comprises at least three blocks, wherein each block consists essentially of repeats of one type of monomer unit..Iaddend. .Iadd.117. The coating of claim 114 wherein the copolymer comprises vinyl blocks, acrylate blocks and methacrylate blocks..Iaddend. .Iadd.118. The coating of claim 114 wherein the second monomer unit has a glass transition temperature that is at least about 50 degrees Centigrade higher than the glass transition temperature of the first monomer unit..Iaddend. .Iadd.119. The coating of claim 114 wherein the second monomer unit has a glass transition temperature that is at least about 70 degrees Centigrade higher than the glass transition temperature of the first monomer unit..Iaddend. .Iadd.120. The coating of claim 114 wherein the first monomer unit comprises an acrylate or vinyl and the second monomer unit compromises a methacrylate or vinyl..Iaddend. .Iadd.121. The coating of claim 114 wherein the first monomer unit and the second monomer unit are selected from the group consisting of acrylic acid, acrylonitrile, allylamine, acrylates, methacrylates, methylmethacrylate, alkyl acrylates, alkyl methacrylate, butadiene, carbomethylsilane, (carbonate) urethane, ethylene glycol, propylene glycol, (ether) urethane, urethane, vinyl chloride, vinyl alcohol, vinyl pyrrolidone, maleic anhydride, cellulose nitrate, carboxy methyl cellulose, dextran, dextran sulphate, esters, carbonates, ethers, maleic acid, fluoropolymer monomeric units, unsaturated polymer monomeric units, melamine, sulphone, ureas, biological polymer monomeric units, protein, gelatin, collagen, butyl methacrylate, hydroxyethyl methacrylate, methacrylate acid, polyethylene glycol dimethylacrylate, polypropylene glycol diglycidyl ether, polyethylene glycol diglycidyl ether, isocyanatoethyl methacrylate, N-acryloxysuccinimide, glycidyl methacrylate, hexamethylene diisocyanate, acrolein, crotonaldehyde, glycerol monomethacrylate, heparin methacrylate, methacryloylethyl phosphorylcholine, polymethacrylate, polyacrylate, polyester, polyether, polyethylene glycol, butyl acrylate, polyethylene glycol monomethacrylate, isobutyl methacrylate, cyclohexyl methacrylate, ethyl acrylate, 2-hydroxyethyl acrylate, 2-ethylhexyl methacrylate, ethyl methacrylate, methyl acrylate, hexadecyl methacrylate, octadecyl methacrylate, styrene, methyl styrene, vinyl stearate, vinyl toluene, and tert-butyl acrylate..Iaddend. .Iadd.122. The coating of claim 114 wherein the copolymer further comprises a third monomer unit, wherein the third monomer unit forms a homopolymer with a glass transition temperature that is at least about 30 degrees Centigrade higher than the glass transition temperature of a homopolymer formed by the first monomer unit..Iaddend. .Iadd.123. The coating of claim 122 wherein the copolymer comprises a first homopolymer of the first monomer unit covalently joined to a second homopolymer of the second monomer unit..Iaddend. .Iadd.124. The coating of claim 123 wherein the first homopolymer comprises a first monomer unit and the second homopolymer comprises at least one member of the group consisting of the first monomer unit, the second monomer unit, and both the first monomer unit and the second monomer unit..Iaddend. .Iadd.125. The coating of claim 124 wherein the copolymer comprises at least two methacrylate monomer units or acrylate monomer units..Iaddend. .Iadd.126. The coating of claim 114 wherein the monomer units are polymerizable to form the copolymer after the monomer units have been associated with the medical device..Iaddend. .Iadd.127. The coating of claim 114 wherein the copolymer is prepared from the monomer units from a melt of the monomers..Iaddend. .Iadd.128. The coating of claim 114 wherein the copolymer is prepared from the monomer units from a solution (i.e. in a solvent) of the monomers..Iaddend. .Iadd.129. The coating of claim 114 wherein the glass transition temperature of the first monomer unit is below about 37 degrees Centigrade and the glass transition temperature of the second monomer unit is above about 37 degrees Centigrade..Iaddend. .Iadd.130. The coating of claim 114 wherein the first monomer unit and the second monomer unit are chosen so that the first monomer unit reacts to form a plurality of blocks consisting essentially of repeats of the first monomer unit and the second monomer unit reacts to form a plurality of blocks consisting essentially of repeats of the second monomer unit..Iaddend. .Iadd.131. The coating of claim 130 wherein the first layer is at least partially disposed between the device and the second layer..Iaddend. .Iadd.132. The coating of claim 130 wherein the second layer is at least partially disposed between the device and the first layer..Iaddend. .Iadd.133. The coating of claim 130 wherein the second layer comprises a polymer that is covalently crosslinked to a polymer of the first layer..Iaddend. .Iadd.134. The coating of claim 133 wherein the copolymer comprises reactive functional groups that are involved in forming covalent crosslinks with the second layer, and wherein the reactive functional groups are chosen from the group consisting of hydroxyl, amine, carboxylic, aldehyde, ketone, thiol, ally), acrylate, methacrylate, isocyanate, epoxide, azides, aziridines, acetals, ketals, alkenes, acyl halides, alky halides, hydroxy aldehydes and ketones, alkenes, amides, bisamides, amino acids and esters, amino carbonyl compounds, mercaptans, amino mercaptans, anhydrides, azines, azo compounds, azoxy compounds, boranes, carbamates, carbodimides, carbonates, diazo compounds, isothionates, hydroxamic acid, hydroxy acids, hydroxy amines and amides, hydroxylamine, imines, lactams, nitriles, sulphonamides, sulphones, sulphonic acids, thiocyanates, and combinations thereof..Iaddend. .Iadd.135. The coating of claim 133 wherein the second layer comprises a heparin macromer that comprises a second reactive functional group that is involved in forming the crosslinks with the first layer..Iaddend. .Iadd.136. The coating of claim 135 wherein the second functional group comprises azide or aziridine..Iaddend. .Iadd.137. The coating of claim 133 wherein the second layer comprises a hyaluronate macromer that comprises a second reactive functional group that is involved in forming the crosslinks with the first layer..Iaddend. .Iadd.138. The coating of claim 133 wherein the polymer of the second layer comprises a second functional group that forms at least one of the covalent crosslinks in response to exposure to light..Iaddend. .Iadd.139. The coating of claim 114 further comprising a second layer that contacts at least a portion of the first layer, wherein the second layer and the first layer have a different composition..Iaddend. .Iadd.140. The coating of claim 139 wherein the second layer is in contact with the medical device and comprises a polymer having at least one reactable monomer..Iaddend. .Iadd.141. The coating of claim 140 wherein the at least one reactable monomer is a member of the group consisting of vinyl, acrylates and methylmethacrylates..Iaddend. .Iadd.142. The coating of claim 141 wherein the polymer in the second layer is a second copolymer that comprises monomer units of at least one member of the group consisting of vinyl pyrrolidone, vinyl chloride, vinyl acetate, and co-vinyl alcohol..Iaddend. .Iadd.143. The coating of claim 141 wherein the polymer in the second layer comprises a hydrophilic polymer..Iaddend. .Iadd.144. The coating of claim 143 wherein the polymer in the second layer comprises polyvinylpyrrolidone..Iaddend. .Iadd.145. The coating of claim 114 wherein the copolymer is made from a combination of monomer units and has a glass transition temperature in a range of about 0 to about 60 degrees Celsius as measured using differential scanning calorimetery..Iaddend. .Iadd.146. The coating of claim 114 wherein the copolymer is made from a combination of monomer units and has a glass transition temperature in a range of about 15 to about 40 degrees Celsius as measured using differential scanning calorimetery..Iaddend. .Iadd.147. The coating of claim 114 wherein the copolymer is made from a combination of monomer units and has a glass transition temperature in a range of about 26 to about 40 degrees Centigrade as measured by differential scanning calorimetery..Iaddend. .Iadd.148. A coating for a medical device, the coating comprising a thermoplastic layer with a thickness between about 0.1 .mu.m and about 1000 .mu.m that comprises a thermoplastic copolymer free of covalent crosslinks that has a weight averaged molecular weight of at least about 2500, wherein the copolymer is made only of thermoplastic-forming monomers and comprises a first thermoplastic-forming monomer unit and a second thermoplastic-forming monomer unit, wherein the second monomer unit has a glass transition temperature that is at least about 30 degrees Centigrade higher than the glass transition temperature of the first monomer unit, with a glass transition temperature of a monomer unit being defined as a glass transition temperature of a homopolymer of that monomer unit, wherein the device is selected from the group consisting of an implantable device, a catheter, a guide-wire, an embolizing coil, a vascular graft, a heart valve, an implantable cardiovascular defibrillator, a pacemaker, a microsphere, a biosensor, an implantable sensor, an ex-vivo sensor, an ocular implant, a contact lens, a stent, and a tissue engineering scaffold; wherein the copolymer comprises a member of the group consisting of poly(hydroxyethyl methacrylate-co-butylacrylate-co-butylmethacrylate), poly(hydroxyethyl methacrylate-co-lauryl methacrylate), poly(polyethylene glycol monomethacrylate-co-butyl acrylate-co-butyl methacrylate), poly(heparin methacrylate-co-hydroxyethylmethacrylate-co-butyl acrylate-co-butyl methacrylate), poly(glycerol monomethacrylate-co-butyl acrylate-co-butyl methacrylate), poly(amino methacrylate hydrochloride-co-butyl acrylate-co-butyl methacrylate), poly(isocyanatoethyl methacrylate-co-butyl acrylate-co-butyl methacrylate), poly(methoxy(polyethylene glycol) monomethacrylate-co-lauryl methacrylate-co-butyl methacrylate-co-ethylene glycol dimethacrylate), and poly(hydroxyethyl methacrylate-co-hydroxypropyl methacrylate-co-butylmethacrylate)..Iaddend. .Iadd.149. The coating of claim 148 wherein the copolymer comprises poly(hydroxyethyl methacrylate-co-hydroxypropyl methacrylate-co-butylmethacrylate)..Iaddend. .Iadd.150. The coating of claim 148 wherein the copolymer comprises poly(hydroxyethyl methacrylate-co-lauryl methacrylate)..Iaddend. .Iadd.151. The coating of claim 1 wherein the copolymer comprises poly(hydroxyethyl methacrylate-co-butyl acrylate-co-butyl methacrylate)..Iaddend. .Iadd.152. The coating of claim 1 wherein the copolymer comprises poly(hydroxyethyl methacrylate-co-lauryl methacrylate)..Iaddend.

Details for Patent RE45500

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Microbix Biosystems Inc.	KINLYTIC	urokinase	For Injection	021846	01/16/1978		2022-06-26
Jubilant Hollisterstier Llc	N/A	positive skin test control-histamine	Injection	103891	03/13/1924		2022-06-26