Claims for Patent: 8,916,227

Summary for Patent: 8,916,227

Title:	Coating of the entire surface of endoprostheses
Abstract:	The present invention relates to methods for coating the entire surface of lattice-like or mesh-like endoprostheses, wherein the endoprostheses initially are being provided with a thin layer covering the material surface of the endoprosthesis and subsequently, the surface of the entire endoprosthesis is being coated, wherein said coating of the entire surface covers the struts as well as the interstices between the individual struts.
Inventor(s):	Horres; Roland (Stolberg, DE), Hoffmann; Michael (Eschweiler, DE), Hoffmann; Erika (Eschweiler, DE), Linssen; Marita (Aachen, DE), Caspers; Roger (Inden, DE), Styrnik; Michaela (Eschweiler, DE)
Assignee:	Hemoteq AG (Wurselen, DE)
Application Number:	11/913,545
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,916,227
Patent Claims:	1. Method for coating the entire surface of lattice-like or mesh-like endoprostheses, wherein in a first coating step the struts of the endoprosthesis which form the lattice-like or mesh-like structure are being covered completely or partially with a polymer coating and in a second coating step the entire surface of the interstices located between the struts which form the lattice-like or mesh-like structure is being coated with a polymer coating, wherein a protruding part is left on both ends, and said protruding part is folded over the edge of the endoprosthesis. 2. Method for coating the entire surface of lattice-like or mesh-like endoprostheses according to claim 1, comprising the following steps: a) providing a lattice-like or mesh-like endoprosthesis having a discontinuous surface with interstices between the struts forming the lattice or mesh, b) at least partially coating the struts with a polymer A, c) wetting the surface of the endoprosthesis coated with the polymer A with an organic solvent, d) coating the entire surface of the interstices between the struts which form the lattice-like or mesh-like structure with a polymer coating of a polymer B. 3. Method for coating the entire surface of lattice-like or mesh-like endoprostheses according to claim 1, comprising the following steps: a) providing a lattice-like or mesh-like endoprosthesis having a discontinuous surface and comprising struts with an inner surface and an outer surface with interstices between the individual struts, b) at least partially coating the inner as well as the outer surface of the struts with a polymer A, c) wetting the surface of the endoprosthesis coated with the polymer A with an organic solvent, d) coating the entire surface of the inner and/or outer surface as well as of the interstices between the struts with a polymer coating of a polymer B. 4. Method according to claim 2, wherein the coating step b) is performed by spray coating or electrospinning. 5. Method according to claim 2, wherein the interstices between the struts are not being covered with a polymer layer in the coating step b). 6. Method according to claim 2, wherein the wetting according to step c) is performed by dip coating or spray coating. 7. Method according to claim 2, wherein the organic solvent used for the wetting according to step c) contains the polymer B in a concentration lower than that of the polymer B in a solution used for coating according to step d). 8. Method according to claim 2, wherein the polymer A and/or the polymer B are/is selected from the group comprising: polyacrylic acid and polyacrylates such as polymethylmethacrylate, polybutylmethacrylate, polyacrylamide, polyacrylonitriles, polyamides, polyetheramides, polyethylene amine, polyimides, polycarbonates, polycarbourethanes, polyvinyl ketones, polyvinyl halides, polyvinylidene halides, polyvinyl ethers, polyvinylarenes, polyvinyl esters, polyvinyl pyrrollidones, polyoxymethylenes, polyethylene, polypropylene, polytetrafluoro-ethylene, polyurethanes, polyolefine elastomers, polyisobutylenes, EPDM gums, fluorosilicones, carboxymethyl chitosans, polyethylene terephthalate, polyvalerates, carboxymethylcellulose, cellulose, rayon, rayon triacetates, cellulose nitrates, cellulose acetates, hydroxyethyl cellulose, cellulose butyrates, cellulose acetate butyrates, ethyl vinyl acetate copolymers, polysulphones, polyethersulphones, epoxy resins, ABS resins, silicones such as polysiloxanes, polyvinyl halogens and copolymers, cellulose ethers, cellulose triacetates, chitosan, chitosan derivatives, polymerizable oils such as linseed oil and copolymers and/or mixtures thereof. 9. Method according to claim 2, wherein the polymer A and/or the polymer B are/is selected from the group comprising: polyvalerolactones, poly-.epsilon.-decalactones, polylactides, polyglycolides, copolymers of the polylactides and polyglycolides, poly-.epsilon.-caprolactone, polyhydroxybutyric acid, polyhydroxybutyrates, polyhydroxyvalerates, polyhydroxybutyrate-co-valerates, poly(1,4-dioxane-2,3-diones), poly(1,3-dioxane-2-one), poly-para-dioxanones, polyanhydrides such as polymaleic acid anhydrides, polyhydroxymethacrylates, fibrin, polycyanoacrylates, polycaprolactone-dimethylacrylates, poly-.beta.-maleic acid, polycaprolactonebutyl-acrylates, multiblock polymers such as from oligocaprolactonedioles and oligodioxanonedioles, polyetherester multiblock polymers such as PEG and poly(butyleneterephthalate), polypivotolactones, polyglycolic acid trimethyl-carbonates, polycaprolactone-glycolides, poly(.gamma.-ethylglutamate), poly(DTH-iminocarbonate), poly(DTE-co-DT-carbonate), poly(bisphenol-A-iminocarbonate), polyorthoesters, polyglycolic acid trimethyl-carbonates, polytrimethylcarbonates, polyiminocarbonates, poly(N-vinyl)-pyrrolidone, polyvinylalcohols, polyesteramides, glycolated polyesters, polyphosphoesters, polyphosphazenes, poly[p-carboxyphenoxy)propane], polyhydroxypentanoic acid, polyanhydrides, polyethylene oxide-propylene oxide, soft polyurethanes, polyurethanes with amino acid residues in the backbone, polyetheresters such as polyethylene oxide, polyalkeneoxalates, polyorthoesters as well as copolymers thereof, carrageenanes, fibrinogen, starch, collagen, protein based polymers, polyamino acids, synthetic polyamino acids, zein, modified zein, polyhydroxyalkanoates, pectic acid, actinic acid, modified and unmodified fibrin and casein, carboxymethyl sulphate, albumin, furthermore hyaluronic acid, heparan sulphate, heparin, chondroitine sulphate, dextran, .beta.-cyclodextrins, and copolymers with PEG and polypropylene glycol, gummi arabicum, guar, gelatine, collagen, collagen-N-Hydroxysuccinimide, modifications and copolymers and/or mixtures of the substances mentioned above. 10. Method according to claim 1, wherein the surface of the endoprosthesis is completely covered with a polymer coating by means of dip coating, electro spinning and/or micropippetting. 11. Method according to claim 2, wherein at least one antiproliferative, anti-migration, antiangiogenic, anti-inflammatory, antiphlogistic, cytostatic, cytotoxic and/or antithrombotic active agent is applied and/or incorporated beneath, in and/or on the layer of polymer A and/or beneath, in and/or on the layer of polymer B or portions of said layers. 12. Method according to claim 11, wherein the antiproliferative, anti-migration, anti-angiogenic, anti-inflammatory, antiphlogistic, cytostatic, cytotoxic and/or antithrombotic active agent is selected from the group comprising: sirolimus (rapamycin), everolimus, pimecrolimus, somatostatin, tacrolimus, roxithromycin, daunaimycin, ascomycin, bafilomycin, erythromycin, midecamycin, josamycin, concanamycin, clarithromycin, troleandomycin, folimycin, cerivastatin, simvastatin, lovastatin, fluvastatin, rosuvastatin, atorvastatin, pravastatin, pitavastatin, vinblastine, vincristine, vindesine, vinorelbine, etoposide, teniposide, nimustine, carmustine, lomustine, cyclophosphamide, 4-Hydroxyoxycyclophosphamide, estramustine, melphalan, ifosfamide, trofosfamide, chlorambucil, bendamustine, dacarbazine, busulfan, procarbazin, treosulfan, temozolomide, thiotepa, Doxorubicin, aclarubicin, epirubicin, mitoxantrone, idarubicin, bleomycin, mitomycin, dactinomycin, methotrexate, fludarabine, fludarabine-5'-dihydrogenphosphate, cladribine, mercaptopurine, thioguanine, cytarabine, fluorouracil, gemcitabine, capecitabine, Docetaxel, carboplatin, cisplatin, oxaliplatin, amsacrine, irinotecan, topotecan, hydroxycarbamide, miltefosine, pentostatin, aldesleukin, tretinoin, asparaginase, pegaspargase, anastrozole, exemestane, letrozole, formestane, aminoglutethimide, adriamycin, azithromycin, spiramycin, cepharanthin, 8-.alpha.-ergolines, dimethyl ergoline, agroclavin, 1-allyl lisuride, 1-allyl terguride, bromerguride, bromocriptine, elymoclavine, ergocristine, ergocristinine, ergocornine, ergocorninine, ergocryptine, ergocryptinine, ergometrine, ergonovine, ergosine, ergosinine, ergometrinine, ergotamine, ergotaminine, ergovaline, lergotrile, lisuride, lysergol, lysergic acid, lysergic acid amide, lysergic acid diethylamide, isolysergic acid, isolysergic acid amide, isolysergic acid diethylamide, mesulergine, metergoline, methergine, methylergometrine, methysergide, pergolide, proterguride and terguride, celecoxib, thalidomide, Fasudil.RTM., cyclosporine, inhibitor-2.omega. of SMC proliferation, epothilones A and B, mitoxanthrone, azathioprine, mycophenolate mofetil, c-myc antisense, b-myc antisense, betulinic acid, camptothecin, PI-88 (sulphated oligosaccharide), melanocyte stimulating hormone (.alpha.-MSH), activated protein C, IL1-.beta.-Inhibitor, Thymosin .alpha.-1, fumaric acid and esters thereof, calcipotriol, tacalcitol, lapachol, .beta.-lapachone, podophyllotoxin, betulin, 2-ethylhydrazide of podophyllic acid, molgramostim (rhuGM-CSF), peginterferon .alpha.-2b, lanograstim (r-HuG-CSF), filgrastim, macrogol, dacarbazine, basiliximab, daclizumab, selectin (cytokine antagonist), CETP inhibitor, cadherins, cytokine inhibitors, COX-2-Inhibitor, NFkB, angiopeptin, ciprofloxacin, fluoroblastin, monoclonal antibodies inhibiting the muscle cell proliferation, bFGF antagonists, probucol, prostaglandins, 1,11-dimethoxycanthin-6-one, 1-hydroxy-11-methoxycanthin-6-one, scopoletin, colchicine, NO donors such as pentaerythritol tetranitrate and sydnonimines, S-nitroso derivatives, tamoxifen, staurosporine, .beta.-estradiol, .alpha.-estradiol, estriol, estrone, ethinyl estradiol, fosfestrol, medroxyprogesterone, estradiol cypionates, estradiol benzoates, tranilast, kamebaukarin and other terpenoids applied in the therapy of cancer, verapamil, tyrosine kinase inhibitors (tyrphostines), cyclosporine A, paclitaxel and derivatives thereof such as 6-.alpha.-hydroxy-paclitaxel, baccatine, taxotere, macrocyclic oligomers of carbon suboxide (MCS) obtained synthetically and from native sources and derivatives thereof, mofebutazone, acemetacin, diclofenac, lonazolac, dapsone, o-carbamoyl-phenoxyacetic acid, lidocaine, ketoprofen, mefenamic acid, piroxicam, meloxicam, chloroquine phosphate, penicillamine, tumstatin, avastin, D-24851, SC-58125, hydroxychloroquine, auranofin, sodium aurothiomalate, oxaceprol, celecoxib, .beta.-sitosterin, ademetionine, myrtecaine, polidocanol, nonivamide, levomenthol, benzocaine, aescin, ellipticine, D-24851 (Calbiochem), colcemid, cytochalasin A-E, indanocine, nocadazole, protein S 100, bacitracin, vitronectin receptor antagonists, azelastine, guanidyl cyclase stimulator, tissue inhibitor of metal proteinase 1 and 2, free nucleic acids, nucleic acids incorporated into virus transmitters, DNA and RNA fragments, plasminogen activator inhibitor 1, plasminogen activator inhibitor 2, antisense oligonucleotides, VEGF inhibitors, IGF-1, active agents from the group of antibiotics such as cefadroxil, cefazolin, cefaclor, cefoxitin, tobramycin, gentamycin, penicillins such as dicloxacillin, oxacillin, sulfonamides, metronidazole, antithrombotics such as argatroban, aspirin, Abciximab, synthetic antithrombin, bivalirudin, coumadin, enoxoparin, desulphated and N-reacetylated heparin, tissue plasminogen activator, GpIIb/IIIa platelet membrane receptor, factor X.sub.a inhibitor antibody, heparin, hirudin, r-hirudin, PPACK, protamine, sodium salt of 2-methylthiazolidine-2,4-dicarboxylic acid, prourokinase, streptokinase, warfarin, urokinase, vasodilators such as dipyramidole, Trapidil.RTM., nitroprussides, PDGF antagonists such as triazolopyrimidine and seramin, ACE inhibitors such as captopril, cilazapril, lisinopril, enalapril, losartan, thioprotease inhibitors, prostacyclin, vapiprost, interferon .alpha., .beta. and .gamma., histamine antagonists, serotonin blockers, apoptosis inhibitors, apoptosis regulators such as p65, NF-kB or Bcl-xL antisense oligonucleotides, halofuginone, nifedipine, Tocopherol, vitamin B1, B2, B6 and B12, folic acid, molsidomine, tea polyphenols, epicatechin gallate, epigallocatechin gallate, Boswellic acids and derivatives thereof, leflunomide, anakinra, etanercept, sulfasalazine, etoposide, dicloxacillin, tetracycline, triamcinolone, mutamycin, procainimide, D24851, SC-58125, retinoic acid, quinidine, disopyrimide, flecamide, propafenone, sotolol, amidorone, natural and synthetically obtained steroids such as bryophyllin A, inotodiol, maquiroside A, ghalakinoside, mansonine, strebloside, hydrocortisone, betamethasone, dexamethasone, non-steroidal substances (NSAIDS) such as fenoprofen, ibuprofen, indomethacin, naproxen, phenylbutazone and other antiviral agents such as acyclovir, ganciclovir and zidovudine, antimycotics such as clotrimazole, flucytosine, griseofulvin, ketoconazole, miconazole, nystatin, terbinafine, antiprotozoal agents such as chloroquine, mefloquine, quinine, moreover natural terpenoids such as hippocaesculin, barringtogenol-C21-angelate, 14-Dehydroagrostistachin, agroskerin, agroskerin, agrostistachin, 17-Hydroxyagrostistachin, ovatodiolids, 4,7-oxycycloanisomelic acid, baccharinoids B1, B2, B3 and B7, tubeimoside, bruceanoles A, B and C, bruceantinoside C, yadanziosides N and P, isodeoxyelephantopin, tomenphantopin A and B, coronarin A, B, C and D, ursolic acid, hyptatic acid A, zeorin, iso-iridogermanal, maytenfoliol, effusantin A, excisanin A and B, longikaurin B, sculponeatin C, kamebaunin, leukamenin A and B, 13,18-dehydro-6-alpha-senecioyloxychaparrin, taxamairin A and B, regenilol, triptolide, moreover cymarin, apocymarin, aristolochic acid, aminopterin, hydroxyanopterin, anemonin, protoanemonin, berberine, cheliburin chloride, cicutoxin, sinococuline combrestatin A and B, cudraisoflavone A, curcumin, dihydronitidine, nitidine chloride, 12-.beta.-hydroxypregnadien-3,20-dione, bilobol, ginkgol, ginkgolic acid, helenalin, indicine, indicine-N-oxide, lasiocarpine, glycoside 1.alpha., justicidin A and B, larreatin, malloterin, mallotochromanol, isobutyrylmallotochromanol, maquiroside A, marchantin A, maytansin, lycoridicin, margetine, pancratistatin, liriodenine, oxoushinsunine, aristolactam-AII, bisparthenolidine, periplocoside A, ursolic acid, deoxypsorospermin, psycorubin, ricin A, sanguinarine, manwu wheat acid, methylsorbifolin, chromones from spathelia, stizophyllin, mansonine, akagerine, dihydrousambaraensine, hydroxyusambarine, strychnopentamine, strychnophylline, usambarine, usambarensine, daphnoretin, lariciresinol, methoxylariciresinol, syringaresinol, umbelliferone, afromoson, acetylvismione B, desacetylvismione A, vismione A and B and sulphurous amino acids such as cystine as well as salts, hydrates, solvates, enantiomers, racemates, enantiomer mixtures, diastereomeric mixtures and mixtures of the above active agents mentioned above. 13. Method according to claim 1, wherein the endoprosthesis to be coated has a tubular, helical and/or braided structure. 14. Method according to claim 1, wherein the endoprosthesis to be coated is a stent, coronary stent, vascular stent, tracheal stent, bronchial stent, urethral stent, esophageal stent, biliary stent, renal stent, stent for use in the small intestine, stent for use in the large intestine, laryngeal implant, bypass, catheter or ileostomy. 15. Endoprosthesis which can be obtained according to claim 1. 16. Endoprosthesis according to claim 15 suited for the prevention, reduction or treatment of stenosis, restenosis, arteriosclerosis, atherosclerosis, vessel occlusions, vessel constrictions, aneurysms, and for artificial openings and accesses. 17. Method according to claim 3, wherein the coating step b) is performed by spray coating or electrospinning. 18. Method according to claim 3, wherein the interstices between the struts are not being covered with a polymer layer in the coating step b). 19. Method according to claim 3, wherein the wetting according to step c) is performed by dip coating or spray coating. 20. Method according to claim 3, wherein the organic solvent used for the wetting according to step c) contains the polymer B in a concentration lower than that of the polymer B in a solution used for coating according to step d). 21. Method according to claim 3, wherein the polymer A and/or the polymer B are/is selected from the group comprising: polyacrylic acid and polyacrylates such as polymethylmethacrylate, polybutylmethacrylate, polyacrylamide, polyacrylonitriles, polyamides, polyetheramides, polyethylene amine, polyimides, polycarbonates, polycarbourethanes, polyvinyl ketones, polyvinyl halides, polyvinylidene halides, polyvinyl ethers, polyvinylarenes, polyvinyl esters, polyvinyl pyrrollidones, polyoxymethylenes, polyethylene, polypropylene, polytetrafluoro-ethylene, polyurethanes, polyolefine elastomers, polyisobutylenes, EPDM gums, fluorosilicones, carboxymethyl chitosans, polyethylene terephthalate, polyvalerates, carboxymethylcellulose, cellulose, rayon, rayon triacetates, cellulose nitrates, cellulose acetates, hydroxyethyl cellulose, cellulose butyrates, cellulose acetate butyrates, ethyl vinyl acetate copolymers, polysulphones, polyethersulphones, epoxy resins, ABS resins, silicones such as polysiloxanes, polyvinyl halogens and copolymers, cellulose ethers, cellulose triacetates, chitosan, chitosan derivatives, polymerizable oils such as linseed oil and copolymers and/or mixtures thereof. 22. Method according to claim 3, wherein the polymer A and/or the polymer B are/is selected from the group comprising: polyvalerolactones, poly-.epsilon.-decalactones, polylactides, polyglycolides, copolymers of the polylactides and polyglycolides, poly-.epsilon.-caprolactone, polyhydroxybutyric acid, polyhydroxybutyrates, polyhydroxyvalerates, polyhydroxybutyrate-co-valerates, poly(1,4-dioxane-2,3-diones), poly(1,3-dioxane-2-one), poly-para-dioxanones, polyanhydrides such as polymaleic acid anhydrides, polyhydroxymethacrylates, fibrin, polycyanoacrylates, polycaprolactone-dimethylacrylates, poly-.beta.-maleic acid, polycaprolactonebutyl-acrylates, multiblock polymers such as from oligocaprolactonedioles and oligodioxanonedioles, polyetherester multiblock polymers such as PEG and poly(butyleneterephthalate), polypivotolactones, polyglycolic acid trimethyl-carbonates, polycaprolactone-glycolides, poly(.gamma.-ethylglutamate), poly(DTH-iminocarbonate), poly(DTE-co-DT-carbonate), poly(bisphenol-A-iminocarbonate), polyorthoesters, polyglycolic acid trimethyl-carbonates, polytrimethylcarbonates, polyiminocarbonates, poly(N-vinyl)-pyrrolidone, polyvinylalcohols, polyesteramides, glycolated polyesters, polyphosphoesters, polyphosphazenes, poly[p-carboxyphenoxy)propane], polyhydroxypentanoic acid, polyanhydrides, polyethylene oxide-propylene oxide, soft polyurethanes, polyurethanes with amino acid residues in the backbone, polyetheresters such as polyethylene oxide, polyalkeneoxalates, polyorthoesters as well as copolymers thereof, carrageenanes, fibrinogen, starch, collagen, protein based polymers, polyamino acids, synthetic polyamino acids, zein, modified zein, polyhydroxyalkanoates, pectic acid, actinic acid, modified and unmodified fibrin and casein, carboxymethyl sulphate, albumin, furthermore hyaluronic acid, heparan sulphate, heparin, chondroitine sulphate, dextran, .beta.-cyclodextrins, and copolymers with PEG and polypropylene glycol, gummi arabicum, guar, gelatine, collagen, collagen-N-Hydroxysuccinimide, modifications and copolymers and/or mixtures of the substances mentioned above. 23. Method according to claim 2, wherein the surface of the endoprosthesis is completely covered with a polymer coating by means of dip coating, electrospinning and/or micropippetting. 24. Method according to claim 3, wherein the surface of the endoprosthesis is completely covered with a polymer coating by means of dip coating, electrospinning and/or micropippetting. 25. Method according to claim 3, wherein at least one antiproliferative, anti-migration, antiangiogenic, anti-inflammatory, antiphlogistic, cytostatic, cytotoxic and/or antithrombotic active agent is applied and/or incorporated beneath, in and/or on the layer of polymer A and/or beneath, in and/or on the layer of polymer B or portions of said layers. 26. Method according to claim 25, wherein the antiproliferative, anti-migration, anti-angiogenic, anti-inflammatory, antiphlogistic, cytostatic, cytotoxic and/or antithrombotic active agent is selected from the group comprising: sirolimus (rapamycin), everolimus, pimecrolimus, somatostatin, tacrolimus, roxithromycin, daunaimycin, ascomycin, bafilomycin, erythromycin, midecamycin, josamycin, concanamycin, clarithromycin, troleandomycin, folimycin, cerivastatin, simvastatin, lovastatin, fluvastatin, rosuvastatin, atorvastatin, pravastatin, pitavastatin, vinblastine, vincristine, vindesine, vinorelbine, etoposide, teniposide, nimustine, carmustine, lomustine, cyclophosphamide, 4-Hydroxyoxycyclophosphamide, estramustine, melphalan, ifosfamide, trofosfamide, chlorambucil, bendamustine, dacarbazine, busulfan, procarbazin, treosulfan, temozolomide, thiotepa, Doxorubicin, aclarubicin, epirubicin, mitoxantrone, idarubicin, bleomycin, mitomycin, dactinomycin, methotrexate, fludarabine, fludarabine-5'-dihydrogenphosphate, cladribine, mercaptopurine, thioguanine, cytarabine, fluorouracil, gemcitabine, capecitabine, Docetaxel, carboplatin, cisplatin, oxaliplatin, amsacrine, irinotecan, topotecan, hydroxycarbamide, miltefosine, pentostatin, aldesleukin, tretinoin, asparaginase, pegaspargase, anastrozole, exemestane, letrozole, formestane, aminoglutethimide, adriamycin, azithromycin, spiramycin, cepharanthin, 8-.alpha.-ergolines, dimethyl ergoline, agroclavin, 1-allyl lisuride, 1-allyl terguride, bromerguride, bromocriptine, elymoclavine, ergocristine, ergocristinine, ergocornine, ergocorninine, ergocryptine, ergocryptinine, ergometrine, ergonovine, ergosine, ergosinine, ergometrinine, ergotamine, ergotaminine, ergovaline, lergotrile, lisuride, lysergol, lysergic acid, lysergic acid amide, lysergic acid diethylamide, isolysergic acid, isolysergic acid amide, isolysergic acid diethylamide, mesulergine, metergoline, methergine, methylergometrine, methysergide, pergolide, proterguride and terguride, celecoxib, thalidomide, Fasudil.RTM., cyclosporine, inhibitor-2.omega. of SMC proliferation, epothilones A and B, mitoxanthrone, azathioprine, mycophenolate mofetil, c-myc antisense, b-myc antisense, betulinic acid, camptothecin, PI-88 (sulphated oligosaccharide), melanocyte stimulating hormone (.alpha.-MSH), activated protein C, IL1-.beta.-Inhibitor, Thymosin .alpha.-1, fumaric acid and esters thereof, calcipotriol, tacalcitol, lapachol, .beta.-lapachone, podophyllotoxin, betulin, 2-ethylhydrazide of podophyllic acid, molgramostim (rhuGM-CSF), peginterferon .alpha.-2b, lanograstim (r-HuG-CSF), filgrastim, macrogol, dacarbazine, basiliximab, daclizumab, selectin (cytokine antagonist), CETP inhibitor, cadherins, cytokine inhibitors, COX-2-Inhibitor, NFkB, angiopeptin, ciprofloxacin, fluoroblastin, monoclonal antibodies inhibiting the muscle cell proliferation, bFGF antagonists, probucol, prostaglandins, 1,11-dimethoxycanthin-6-one, 1-hydroxy-11-methoxycanthin-6-one, scopoletin, colchicine, NO donors such as pentaerythritol tetranitrate and sydnonimines, S-nitroso derivatives, tamoxifen, staurosporine, .beta.-estradiol, .alpha.-estradiol, estriol, estrone, ethinyl estradiol, fosfestrol, medroxyprogesterone, estradiol cypionates, estradiol benzoates, tranilast, kamebaukarin and other terpenoids applied in the therapy of cancer, verapamil, tyrosine kinase inhibitors (tyrphostines), cyclosporine A, paclitaxel and derivatives thereof such as 6-.alpha.-hydroxy-paclitaxel, baccatine, taxotere, macrocyclic oligomers of carbon suboxide (MCS) obtained synthetically and from native sources and derivatives thereof, mofebutazone, acemetacin, diclofenac, lonazolac, dapsone, o-carbamoyl-phenoxyacetic acid, lidocaine, ketoprofen, mefenamic acid, piroxicam, meloxicam, chloroquine phosphate, penicillamine, tumstatin, avastin, D-24851, SC-58125, hydroxychloroquine, auranofin, sodium aurothiomalate, oxaceprol, celecoxib, .beta.-sitosterin, ademetionine, myrtecaine, polidocanol, nonivamide, levomenthol, benzocaine, aescin, ellipticine, D-24851 (Calbiochem), colcemid, cytochalasin A-E, indanocine, nocadazole, protein S 100, bacitracin, vitronectin receptor antagonists, azelastine, guanidyl cyclase stimulator, tissue inhibitor of metal proteinase 1 and 2, free nucleic acids, nucleic acids incorporated into virus transmitters, DNA and RNA fragments, plasminogen activator inhibitor 1, plasminogen activator inhibitor 2, antisense oligonucleotides, VEGF inhibitors, IGF-1, active agents from the group of antibiotics such as cefadroxil, cefazolin, cefaclor, cefoxitin, tobramycin, gentamycin, penicillins such as dicloxacillin, oxacillin, sulfonamides, metronidazole, antithrombotics such as argatroban, aspirin, Abciximab, synthetic antithrombin, bivalirudin, coumadin, enoxoparin, desulphated and N-reacetylated heparin, tissue plasminogen activator, GpIIb/IIIa platelet membrane receptor, factor X.sub.a inhibitor antibody, heparin, hirudin, r-hirudin, PPACK, protamine, sodium salt of 2-methylthiazolidine-2,4-dicarboxylic acid, prourokinase, streptokinase, warfarin, urokinase, vasodilators such as dipyramidole, Trapidil.RTM., nitroprussides, PDGF antagonists such as triazolopyrimidine and seramin, ACE inhibitors such as captopril, cilazapril, lisinopril, enalapril, losartan, thioprotease inhibitors, prostacyclin, vapiprost, interferon .alpha., .beta. and .gamma., histamine antagonists, serotonin blockers, apoptosis inhibitors, apoptosis regulators such as p65, NF-kB or Bcl-xL antisense oligonucleotides, halofuginone, nifedipine, Tocopherol, vitamin B1, B2, B6 and B12, folic acid, molsidomine, tea polyphenols, epicatechin gallate, epigallocatechin gallate, Boswellic acids and derivatives thereof, leflunomide, anakinra, etanercept, sulfasalazine, etoposide, dicloxacillin, tetracycline, triamcinolone, mutamycin, procainimide, D24851, SC-58125, retinoic acid, quinidine, disopyrimide, flecamide, propafenone, sotolol, amidorone, natural and synthetically obtained steroids such as bryophyllin A, inotodiol, maquiroside A, ghalakinoside, mansonine, strebloside, hydrocortisone, betamethasone, dexamethasone, non-steroidal substances (NSAIDS) such as fenoprofen, ibuprofen, indomethacin, naproxen, phenylbutazone and other antiviral agents such as acyclovir, ganciclovir and zidovudine, antimycotics such as clotrimazole, flucytosine, griseofulvin, ketoconazole, miconazole, nystatin, terbinafine, antiprotozoal agents such as chloroquine, mefloquine, quinine, moreover natural terpenoids such as hippocaesculin, barringtogenol-C21-angelate, 14-Dehydroagrostistachin, agroskerin, agroskerin, agrostistachin, 17-Hydroxyagrostistachin, ovatodiolids, 4,7-oxycycloanisomelic acid, baccharinoids B1, B2, B3 and B7, tubeimoside, bruceanoles A, B and C, bruceantinoside C, yadanziosides N and P, isodeoxyelephantopin, tomenphantopin A and B, coronarin A, B, C and D, ursolic acid, hyptatic acid A, zeorin, iso-iridogermanal, maytenfoliol, effusantin A, excisanin A and B, longikaurin B, sculponeatin C, kamebaunin, leukamenin A and B, 13,18-dehydro-6-alpha-senecioyloxychaparrin, taxamairin A and B, regenilol, triptolide, moreover cymarin, apocymarin, aristolochic acid, aminopterin, hydroxyanopterin, anemonin, protoanemonin, berberine, cheliburin chloride, cicutoxin, sinococuline combrestatin A and B, cudraisoflavone A, curcumin, dihydronitidine, nitidine chloride, 12-.beta.-hydroxypregnadien-3,20-dione, bilobol, ginkgol, ginkgolic acid, helenalin, indicine, indicine-N-oxide, lasiocarpine, glycoside 1.alpha., justicidin A and B, larreatin, malloterin, mallotochromanol, isobutyrylmallotochromanol, maquiroside A, marchantin A, maytansin, lycoridicin, margetine, pancratistatin, liriodenine, oxoushinsunine, aristolactam-AII, bisparthenolidine, periplocoside A, ursolic acid, deoxypsorospermin, psycorubin, ricin A, sanguinarine, manwu wheat acid, methylsorbifolin, chromones from spathelia, stizophyllin, mansonine, akagerine, dihydrousambaraensine, hydroxyusambarine, strychnopentamine, strychnophylline, usambarine, usambarensine, daphnoretin, lariciresinol, methoxylariciresinol, syringaresinol, umbelliferone, afromoson, acetylvismione B, desacetylvismione A, vismione A and B and sulphurous amino acids such as cystine as well as salts, hydrates, solvates, enantiomers, racemates, enantiomer mixtures, diastereomeric mixtures and mixtures of the above active agents mentioned above. 27. Method according to claim 2, wherein the endoprosthesis to be coated has a tubular, helical and/or braided structure. 28. Method according to claim 3, wherein the endoprosthesis to be coated has a tubular, helical and/or braided structure. 29. Method according to claim 2, wherein the endoprosthesis to be coated is a stent, coronary stent, vascular stent, tracheal stent, bronchial stent, urethral stent, esophageal stent, biliary stent, renal stent, stent for use in the small intestine, stent for use in the large intestine, laryngeal implant, bypass, catheter or ileostomy. 30. Method according to claim 3, wherein the endoprosthesis to be coated is a stent, coronary stent, vascular stent, tracheal stent, bronchial stent, urethral stent, esophageal stent, biliary stent, renal stent, stent for use in the small intestine, stent for use in the large intestine, laryngeal implant, bypass, catheter or ileostomy. 31. Endoprosthesis which can be obtained according to claim 2. 32. Endoprosthesis which can be obtained according to claim 3. 33. Endoprosthesis according to claim 31 suited for the prevention, reduction or treatment of stenosis, restenosis, arteriosclerosis, atherosclerosis, vessel occlusions, vessel constrictions, aneurysms, and for artificial openings and accesses. 34. Endoprosthesis according to claim 32 suited for the prevention, reduction or treatment of stenosis, restenosis, arteriosclerosis, atherosclerosis, vessel occlusions, vessel constrictions, aneurysms, and for artificial openings and accesses.

Details for Patent 8,916,227

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Microbix Biosystems Inc.	KINLYTIC	urokinase	For Injection	021846	01/16/1978		2025-05-05
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2025-05-05
Clinigen, Inc.	PROLEUKIN	aldesleukin	For Injection	103293	05/05/1992		2025-05-05