# US 9,999,595 B2 · Eye device > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,999,595 B2 - Document ID: US9999595B2 - Status: Granted - Kind: B2 - Application number: 15/034,869 - Filed: 2014-11-14 - Published: 2016-10-06 - Granted: 2018-06-19 - Earliest claimed: 2013-11-14 - Assignees: Eyed Pharma - Applicants: Eyed Pharma - Inventors: Jean-Marie Rakic; Jean-Michel Foidart - Web page: https://patentgrep.com/patent/US9999595B2 ## CPC - A61K 9/0051: {Ocular inserts or implants} - A61F 9/0017: {implantable in, or in contact with, the eye, e.g. ocular inserts} - A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol - A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} - A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) - A61P 9/00: Drugs for disorders of the cardiovascular system - A61P 27/02: Ophthalmic agents - A61P 27/06: Antiglaucoma agents or miotics - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61F 2240/005: Templates - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The invention provides a sustained release intraocular drug delivery device comprising: (a) a polymeric matrix core into which at least one therapeutic agent is mixed, and; (b) a polymeric coating completely surrounding said polymeric matrix material; wherein said polymeric matrix core and polymeric coating are insoluble and inert in ocular fluids, and wherein said sustained release intraocular drug delivery device has a compliant annular segment shape and is to be inserted into the sulcus of the intact and/or pseudophakic eye. ## Claims ### Claim 1 A sustained release intraocular drug delivery device having the shape of a compliant annular segment configured for a sulcus of a human eye, comprising: (a) an annular rod shaped solid polymeric matrix core into which at least one therapeutic agent is mixed, and; (b) a solid polymeric coating completely surrounding said polymeric matrix material; wherein said polymeric matrix core and polymeric coating are insoluble and inert in ocular fluids, and wherein said sustained release intraocular drug delivery device has a cross sectional diameter ranging from 0.10 to 0.80 mm, wherein the annular segment ranges from 90 to 360 degrees of the ring; and wherein the polymeric coating regulates the release of the therapeutic agent contained in the polymeric matrix material. ### Claim 2 (depends on 1) The device according to claim 1, wherein said polymeric matrix core has a cross-sectional diameter of 0.1 mm to 0.48 mm. ### Claim 3 (depends on 1) The device according to claim 1, wherein said polymeric coating is a polymeric membrane with a thickness ranging from 0.05 to 0.32 mm. ### Claim 4 (depends on 1) The device according to claim 1, wherein said annular segment has length configured to extend along from 180 to 360° of the sulcus. ### Claim 5 (depends on 1) The device according to claim 1, wherein said polymeric matrix core comprises a polymer selected from the group consisting of ethylene-co-vinylacetate, poly(dimethylsiloxane), polypropylene, high density polyethylene, plasticized polyethylene terephthalate, poly(methyl methacrylate), polyvinyl acetate, cross-linked polyvinyl alcohol, cross-linked polyvinyl butyrate, ethylene ethylacrylate copolymer, polyethyl hexylacrylate, polyvinyl chloride, polyvinyl acetals, polyvinyl alcohol, polyvinyl acetate, ethylene vinylchloride copolymer, polyvinyl esters, polyvinylbutyrate, polyvinylformal, polyamides, polymethylmethacrylate, polybutylmethacrylate, plasticized polyvinyl chloride, plasticized nylon, plasticized soft nylon, natural rubber, polyisoprene, polyisobutylene, polybutadiene, polyethylene, polytetrafluoroethylene, polyvinylidene chloride, polyacrylonitrile, cross-linked polyvinylpyrrolidone, polytrifluorochloroethylene, chlorinated polyethylene, poly(1,4-isopropylidene diphenylene carbonate), vinylidene chloride, acrylonitrile copolymer, vinyl chloride-diethyl fumerale copolymer, silicone rubbers, ethylene-propylene rubber, silicone-carbonate copolymers, vinylidene chloride-vinyl chloride copolymer, vinyl chloride-acrylonitrile copolymer and vinylidene chloride-acrylonitride copolymer, polycarbonate, polyurethane, thermoplastic elastomers (TPE), SEBS (styrene-ethylene-butylene-styrene), SBS (styrene-butadiene-styrene), MBM (methylmethacrylate-butadiene-methylmethacrylate)), and combinations thereof. ### Claim 6 (depends on 5) The device according to claim 5, wherein said polymeric matrix core comprises a polymer selected from the group consisting of high density polyethylene, poly(methyl methacrylate), and combinations thereof. ### Claim 7 (depends on 5) The device according to claim 5, wherein said polymeric matrix core comprises from 1.0 to 50% by weight of said at least one therapeutic agent. ### Claim 8 (depends on 5) The device according to claim 5, wherein said polymeric coating comprises a polymer selected from the group consisting of ethylene-co-vinylacetate, poly(dimethylsiloxane), polypropylene, polyethylene, plasticized polyethylene terephthalate, poly(methyl methacrylate), crosslinked polyvinyl alcohol, polyolefins or polyvinyl chlorides or cross-linked gelatins; regenerated, insoluble, nonerodible cellulose, acylated cellulose, esterified celluloses, cellulose acetate propionate, cellulose acetate butyrate, cellulose acetate phthalate, cellulose acetate diethyl-aminoacetate; polyurethanes, polycarbonates, and microporous polymers formed by co-precipitation of a polycation and a polyanion modified insoluble collagen, and combinations thereof. ### Claim 9 (depends on 8) The device according to claim 8, wherein said polymeric coating comprises a polymer selected from the group consisting of polyethylene, high density polyethylene, poly(methyl methacrylate), and combinations thereof. ### Claim 10 (depends on 1) The device according to claim 1, wherein said polymeric matrix core comprises a polymer selected from the group consisting of high density polyethylene, poly(methyl methacrylate), and combinations thereof; wherein said polymeric coating comprises a polymer selected from the group consisting of high density polyethylene, poly(methyl methacrylate), and combinations thereof; wherein said at least one therapeutic agent is selected from the group consisting of antibiotic agents, antibacterial agents, antiviral agents, prostaglandin analogues, anti-glaucoma agents, antiallergenic agents, anti-inflammatory agents, anti-angiogenesis agents, immune system modifying agents, anti-cancer agents, antisense agents, antifungal agents, myotic and anticholinesterase agents, mydriatic agents, differentiation modulator agents, sympathomimetic agents, anaesthetic agents, vasoconstrictive agents, vasodillatory agents, decongestants, cell transport/mobility impending agents, polypeptides and protein agents, steroidal agents, carbonic anhydrase inhibitor agents, polycations, polyanions, and lubricating agents. ### Claim 11 (depends on 10) The device according to claim 10, wherein said at least one therapeutic agent is selected from the group consisting of prostaglandin analogues, anti-glaucoma agents, anti-inflammatory agents, anti-angiogenesis compounds, and immune system modifying agents. ### Claim 12 (depends on 10) The device according to claim 10, wherein said at least one therapeutic agent is selected from the group consisting of bevacizumab, ranibizumab, aflibercept, timolol, latanoprost, dorzolamide, triamcinolone, dexamethasone, and cyclosporin. ### Claim 13 (depends on 4) The device according to claim 4, wherein said polymeric matrix core comprises polyethylene, and wherein said polymeric coating comprises polyethylene, high density polyethylene, or poly(methyl methacrylate). ### Claim 14 (depends on 4) The device according to claim 4, wherein said polymeric matrix core comprises poly(methyl methacrylate), and wherein said polymeric coating comprises polyethylene, high density polyethylene, or poly(methyl methacrylate). ### Claim 15 (depends on 13) The device according to claim 13, wherein said at least one therapeutic agent comprises timolol. ### Claim 16 (depends on 1) A method of treatment of ocular diseases comprising administering a therapeutic agent incorporated within a sustained release intraocular drug delivery device according to claim 1, and wherein said sustained release intraocular drug delivery device is inserted into the sulcus of the human eye. ### Claim 17 (depends on 16) The method of treatment according to claim 16, wherein the therapeutic agent is selected from the group consisting of: bevacizumab, ranibizumab, aflibercept, timolol, latanoprost, dorzolamide, triamcinolone, dexamethasone, and cyclosporine. ### Claim 18 (depends on 17) The method according to claim 17, wherein said therapeutic agent is selected from the group consisting of: timolol, triamcinolone, dexamethasone, and cyclosporine. ### Claim 19 A process for preparing a sustained release intraocular drug delivery device, comprising: mixing the at least one therapeutic agent with an insoluble and inert polymer; molding and/or extruding said mixture to form a solid polymeric matrix core; and, providing the resulting polymeric matrix core with a polymeric coating, wherein the polymeric coating is a solid and completely surrounding said polymeric matrix material; wherein said polymeric matrix core and polymeric coating are insoluble and inert in ocular fluids, and wherein said sustained release intraocular drug delivery device forms a compliant annular segment having a cross sectional diameter ranging from 0.10 to 0.80 mm and length sufficient to extend along 90 to 360 degrees of the sulcus of the human eye. ### Claim 20 (depends on 19) The process of claim 19, wherein the step of providing the resulting polymer matrix core with a polymeric coating is performed by covering said resulting polymeric matrix core with a polymeric membrane in a mold, and heating said mold. ### Claim 21 (depends on 20) The process according to claim 20, for use in manufacturing an intraocular device for the treatment of ocular diseases by inserting said device in the sulcus of the eye. ### Claim 22 (depends on 1) A surgical method for inserting or implanting the device according to claim 1, comprising the steps of partially straightening the device by applying force, inserting the device in the sulcus of the human eye, and releasing said device. ### Claim 23 (depends on 1) The device according to claim 1, wherein the said polymeric matrix core comprises a polymer selected from the group of ethylene-co-vinylacetate, a polyurethane, a polyolefin, and combinations thereof; wherein said polymeric coating comprises a polymer selected from the group of ethylene-co-vinylacetate, a polyurethane, a polyolefin, and combinations thereof; and wherein said at least one therapeutic agent is selected from the group consisting of antibiotic agents, antibacterial agents, antiviral agents, prostaglandin analogues, anti-glaucoma agents, antiallergenic agents, anti-inflammatory agents, anti-angiogenesis agents, immune system modifying agents, anti-cancer agents, antisense agents, antifungal agents, myotic and anticholinesterase agents, mydriatic agents, differentiation modulator agents, sympathomimetic agents, anaesthetic agents, vasoconstrictive agents, vasodillatory agents, decongestants, cell transport/mobility impending agents, polypeptides and protein agents, steroidal agents, carbonic anhydrase inhibitor agents, polycations, polyanions, and lubricating agents. ### Claim 24 (depends on 23) The device according to claim 23, wherein said at least one therapeutic agent is selected from the group consisting of prostaglandin analogues, anti-glaucoma agents, anti-inflammatory agents, anti-angiogenesis compounds, and immune system modifying agents. ### Claim 25 (depends on 23) The device according to claim 23, wherein said at least one therapeutic agent is selected from the group consisting of bevacizumab, ranibizumab, aflibercept, timolol, latanoprost, dorzolamide, triamcinolone, dexamethasone, and cyclosporin. ### Claim 26 (depends on 1) The device according to claim 1, wherein said polymeric matrix core comprises polyethylene, ethylene-co-vinylacetate, a polyurethane, or a polyolefin, and wherein said polymeric coating comprises polyethylene, high density polyethylene, poly(methyl methacrylate), ethylene-co-vinylacetate, a polyurethane, or a polyolefin. ### Claim 27 (depends on 1) The device according to claim 1, wherein said polymeric matrix core comprises poly(methyl methacrylate), ethylene-co-vinylacetate, a polyurethane, or a polyolefin, and wherein said polymeric coating comprises polyethylene, high density polyethylene, poly(methyl methacrylate), ethylene-co-vinylacetate, a polyurethane, or a polyolefin. ### Claim 28 (depends on 26) The device according to claim 26, wherein said at least one therapeutic agent comprises timolol. ### Claim 29 (depends on 23) A method of treatment of ocular diseases comprising administering a therapeutic agent incorporated within a sustained release intraocular drug delivery device according to claim 23, and wherein said sustained release intraocular drug delivery device is inserted into the sulcus of the human eye. ### Claim 30 (depends on 29) The method of treatment according to claim 29, wherein the therapeutic agent is selected from the group consisting of: bevacizumab, ranibizumab, aflibercept, timolol, latanoprost, dorzolamide, triamcinolone, dexamethasone, and cyclosporine.