(19) TZZ __T

(11) EP 2 654 715 B1

(12) EUROPEAN PATENT SPECIFICATION

(45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 9/20 (2006.01) A61F 9/007 (2006.01) 25.01.2017 Bulletin 2017/04 A61K 9/00 (2006.01) A61F 9/00 (2006.01)

(21) Application number: 11808403.7 (86) International application number: PCT/US2011/061967 (22) Date of filing: 22.11.2011 (87) International publication number: WO 2012/071476 (31.05.2012 Gazette 2012/22)

(54) DRUG ELUTING OCULAR IMPLANT ARZNEIMITTELFREISETZENDES AUGENIMPLANTAT IMPLANT OCULAIRE À ÉLUTION DE MÉDICAMENT

(84) Designated Contracting States: • HEITZMANN, Harold AL AT BE BG CH CY CZ DE DK EE ES FI FR GB Irvine, CA 92606 (US) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO • APPLEGATE, David PL PT RO RS SE SI SK SM TR Laguna Hills, CA 92653 (US)

(30) Priority: 24.11.2010 US 417154 P (74) Representative: Hoffmann Eitle Patent- und Rechtsanwälte PartmbB (43) Date of publication of application: Arabellastraße 30 30.10.2013 Bulletin 2013/44 81925 München (DE)

(73) Proprietor: Dose Medical Corporation (56) References cited: Laguna Hills, CA 92653 (US) WO-A1-2010/135369 WO-A2-2009/063222 WO-A2-2011/127064 US-A1- 2004 115 268 (72) Inventors: US-A1- 2004 127 843 US-A1- 2004 176 341 • HAFFNER, David US-A1- 2004 180 075 US-A1- 2005 244 467 Mission Viejo, CA 92692 (US) US-A1- 2007 298 073 US-A1- 2008 107 694 • CURRY, Ken US-A1- 2008 292 679 US-A1- 2009 220 572 Oceanside, CA 92056 (US) US-A1- 2011 098 640

Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 2 654 715 B1

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Description The "uveoscleral outflow pathway" is the space or pas- sageway whereby aqueous exits the eye by passing BACKGROUND through the ciliary muscle bundles located in the angle of the anterior chamber and into the tissue planes be- Field of the Invention 5 tween the choroid and the sclera, which extend posteri- orly to the optic nerve. About two percent of people in [0001] This disclosure relates to implantable intraocu- the United States have , which is a group of lar drug delivery devices structured to provide targeted eye diseases encompassing a broad spectrum of clinical and/orcontrolled release of a drugto a desired intraocular presentations and etiologies but unified by increased in- target tissue and methods of using such devices for the 10 traocular pressure. Glaucoma causes pathological treatment of ocular diseases and disorders. In certain changes in the optic nerve, visible on the optic disk, and embodiments, this disclosure relates to a treatment of it causes corresponding visual field loss, which can result increased intraocular pressure wherein aqueous humor in blindness if untreated. Increased intraocular pressure is permitted to flow out of an anterior chamber of the eye is the only risk factor associated with glaucoma that can through a surgically implanted pathway. In certain em- 15 be treated,thus lowering intraocular pressure is themajor bodiments, this disclosure also relates particularly to a treatment goal in all , and can be achieved by treatment of ocular diseases with drug delivery devices drug therapy, surgical therapy, or combinations thereof. affixed to the eye, such as to fibrous tissue within the eye. [0005] Many pathologies of the eye progress due to the difficulty in administering therapeutic agents to the Description of the Related Art 20 eye in sufficient quantities and/or duration necessary to ameliorate symptoms ofthe pathology. Often, uptakeand [0002] The mammalian eye is a specialized sensory processing of the active drug component of the thera- organ capable of light reception and is able to receive peutic agent occurs prior to the drug reaching an ocular visual images. The retina of the eye consists of photore- target site. Due to this metabolism, systemic administra- ceptors that are sensitive to various levels of light, in- 25 tion may require undesirably high concentrations of the terneurons that relay signals from the photoreceptors to drug to reach therapeutic levels at an ocular target site. the retinal ganglion cells, which transmit the light-induced This can not only be impractical or expensive, but may signals to the brain. The iris is an intraocular membrane also result in a higher incidence of side effects. Topical that is involved in controlling the amount of light reaching administration is potentially limited by limited diffusion the retina. The iris consists of two layers (arranged from 30 across the cornea, or dilution of a topically applied drug anterior to posterior), the pigmented fibrovascular tissue by tear-action. Even those drugs that cross the cornea known as a stroma and pigmented epithelial cells. The may be unacceptably depleted from the eye by the flow stroma connects a sphincter muscle (sphincter pupillae), of ocular fluids and transfer into the general circulation. which contracts the pupil, and a set of dilator muscles Thus, a means for ocular administration of a therapeutic (dilator pupillae) which open it. The pigmented epithelial 35 agent in a controlled and targeted fashion would address cells block light from passing through the iris and thereby the limitations of other delivery routes. restrict light passage to the pupil. [0006] US 2007/298073 A1 discloses a biocompatible [0003] Numerous pathologies can compromise or en- intraocular implant system for discontinuous or intermit- tirely eliminate an individual’s ability to perceive visual tent release of therapeutic levels of a therapeutic agent images, including trauma to the eye, infection, degener- 40 such as a steroid. ation, vascular irregularities, and inflammatory problems. [0007] WO 2009/063222 A2 discloses a solid, implant- The central portion of the retina is known as the macula. able dosage form comprising a theraoeutically active The macula, which is responsible for central vision, fine agent in solid form, optionally with one or more pharma- visualization and color differentiation, may be affected ceutically acceptable excipients. by age related macular degeneration (wet or dry), dia- 45 [0008] US 2008/107694 A1 discloses a biocompatible betic macular edema, idiopathic choroidal neovascular- sustained release intraocular drug delivery system com- ization, or high myopia macular degeneration, among prising a protein or polynucleotide therapeutic agent, a other pathologies. polymeric carrier for the therapeutic agent and a long [0004] Other pathologies, such as abnormalities in in- chain fatty alcohol release modifier. traocular pressure, can affect vision as well. Aqueous 50 [0009] US 2009/220572 A1 provides composition, humor is a transparent liquid that fills at least the region methods and articles of manufacture for treating an eye between the cornea, at the front of the eye, and the lens disorder. One method of the disclosure comprises the and is responsible for producing a pressure within the step of administering first and second therapeutic agents ocular cavity. Normal intraocular pressure is maintained to the subject’s eye in a single procedure, wherein the by drainage of aqueous humor from the anterior chamber 55 first therapeutic agent provides rapid improvement in the by way of a trabecular meshwork which is located in an condition of the subject’s eye and the second therapeutic anterior chamber angle, lying between the iris and the agent is administered as a sustained release formulation cornea or by way of the "uveoscleral outflow pathway." of the second therapeutic agent.

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[0010] US 2005/244467 A1 discloses biodegradable gions of drug