Posterior Segment Drug Delivery

• US 20100255061A1
• Filed: 01/29/2010
• Published: 10/07/2010
• Est. Priority Date: 01/29/2009
• Status: Active Grant

• Current Assignee: Forsight Vision4, Inc. (Roche Holding AG)
• Original Assignee: Forsight Labs, LLC
• Inventors: Barrett, Michael, Campbell, Randolph E., MacFarlane, K. Angela, Alster, Yair, Gifford, Hanson S. III, Reich, Cary J., George, Robert, de Juan, Eugene JR., Farinas, Kathleen Cogan, Chamow, Steven M., Sutton, Douglas
• Granted Patent: US 8,399,006 B2
• Time in Patent Office: Days
• US Class Current: 424/427
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 38/385 Serum albumin
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: 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
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: Y10T 29/49826 Assembling or joining

Abstract

A therapeutic device to release a therapeutic agent comprises a porous structure coupled to a container comprising a reservoir. The reservoir comprises a volume sized to release therapeutic amounts of the therapeutic agent for an extended time when coupled to the porous structure and implanted in the patient. The porous structure may comprise a first side coupled to the reservoir and a second side to couple to the patient to release the therapeutic agent. A plurality of interconnecting channels can extend from the first side to the second side so as to connect a first a plurality of openings on the first side with a second plurality of openings on the second side. Each of the openings on the first side can be connected to each of the openings on the second side with the plurality of interconnecting channels, such that the rate of release of the therapeutic agent can be substantially maintained when one or more of the openings is blocked, for example with particles, cells, bacteria or tissue when the device is implanted for an extended time. The length of the channels extending from the first side to the second side may comprise an effective length greater than a distance across the porous structure from the first side to the second side. The therapeutic device many comprise an expandable retention structure and an expandable reservoir, such that the device can be delivered from a lumen of a delivery device and expand when positioned in the patient. The therapeutic device may comprises a penetrable barrier to inject therapeutic agent into the device when implanted in the patient.

Claims

1. A therapeutic device to deliver a therapeutic agent to an eye having a sclera and a vitreous humor, the device comprising:

a container configured to hold the therapeutic agent, the container configured to release the therapeutic agent into the vitreous humor at therapeutic amounts for an extended time.

2. The therapeutic device of claim 1 wherein the therapeutic agent comprises molecules having a molecular weight from about 100 Daltons to about 1,000,000 Daltons.

4. The therapeutic device of claim 1 wherein the therapeutic agent comprises a corticosteroid or an analogue thereof and wherein the corticosteroid or the analogue thereof comprises one or more of trimacinalone, trimacinalone acetonide, dexamethasone, dexamethasone acetate, fluocinolone, fluocinolone acetate, or analogues thereof.

6. The therapeutic device of claim 1 wherein the therapeutic agent comprise a VEGF inhibitor.

7. The therapeutic device of claim 1 wherein the therapeutic agent comprises a macromolecule having a molecular weight from about 10 k Daltons to about 400 k Daltons.

8. The therapeutic device of claim 7 wherein the macromolecule comprise a VEGF inhibitor.

9. The therapeutic device of claim 7 wherein the macromolecule comprise one or more of antibodies or antibody fragments.

10. The therapeutic device of claim 9 wherein the one or more of the antibodies or the antibody fragments comprise a VEGF inhibitor.

16. The therapeutic device of claim 1 wherein the container comprises a reservoir volume sized to contain a liquid formulation of the therapeutic agent.

17. The therapeutic device of claim 1 wherein the volume to contain the liquid formulation is within a range from 10 uL to about 100 uL.

18. The therapeutic device of claim 1 wherein the container is sized to contain from about 0.001 mg to about 50 mg of therapeutic agent.

22. The therapeutic device of claim 1 wherein the container and the therapeutic agent are configured to release the therapeutic agent to sustain from about 0.1 ug/mL to about 10 ug/mL of therapeutic agent in the vitreous humor for the extended time.

25. The therapeutic device of claim 1 wherein the extended time comprises at least about 1 month.

31. The therapeutic device of claim 1 further comprising a binding agent to couple to the therapeutic agent such that the therapeutic agent is released from the container for the extended time.

37. The therapeutic device of claim 1 further comprising a stabilizer to extend release of the therapeutic agent.

42. The therapeutic device of claim 1, wherein the container comprises a reservoir having a capacity from about 0.005 cc to about 2 cc to deliver therapeutic amounts of the therapeutic agent for the extended time and wherein the device comprises a volume of no more than about 0.25 cc to minimize distension of the eye when the device is inserted.

44. The therapeutic device of claim 1, wherein the therapeutic device comprising a length extending through the sclera and into the vitreous humor and wherein the length is within a range from about 2 to 12 mm.

46. The therapeutic device of claim 1, further comprising:

a retention structure coupled to the container and configured to couple to the sclera to retain the container at least partially within the eye.

47. The therapeutic device of claim 46 wherein the retention structure comprises an extension coupled to the container and extending outward from the container to extend between the sclera and the conjunctiva to retain the container.

50. The therapeutic device of claim 1 further comprising an injection port extending to the container and having a channel extending through sclera to receive an injection of therapeutic agent to refill the container when the container is implanted at least partially within the vitreous humor.

54. The therapeutic device of claim 1 further comprising a bactericidal agent around at least a portion of an outer surface of the device to inhibit bacterial growth along the outer surface.

55. The therapeutic device of claim 1 further comprising a sponge to encourage tissue ingrowth.

60. The therapeutic device of claim 1 wherein the container comprises a plurality of chambers connected with a plurality of channels to linearize a rate of release of the therapeutic agent.

3. (canceled)

5. (canceled)

11-15. -15. (canceled)

19-21. -21. (canceled)

23-24. -24. (canceled)

26-30. -30. (canceled)

32-36. -36. (canceled)

38-41. -41. (canceled)

43. (canceled)

45. (canceled)

48-49. -49. (canceled)

51-53. -53. (canceled)

56-59. -59. (canceled)

61. A therapeutic device to treat an eye comprising a vitreous humor, the device comprising:

a therapeutic agent;

a binding agent, wherein the therapeutic agent is reversibly coupled to the binding agent such that the binding agent releases therapeutic amounts of the therapeutic agent into the vitreous humor of the eye for an extended time.

62. The therapeutic device of claim 61 wherein the binding agent and the therapeutic agent are sized for injection into a vitreous humor of the eye when the therapeutic agent is reversibly coupled to the binding agent and wherein the binding agent is configured to release therapeutic amounts of the therapeutic agent for at least about 3 months.

63-64. -64. (canceled)

65. A therapeutic device to deliver a therapeutic agent to an eye having a sclera and a vitreous humor, the device comprising:

a retention structure configured to couple to the sclera;

a container coupled to the retention structure and configured to hold the therapeutic agent, the container comprising,

a chamber to hold the therapeutic agent,

a barrier to inhibit flow of the therapeutic agent from the container, the barrier comprising at least one opening to release the therapeutic agent to the vitreous humor,

a porous structure disposed between the barrier and the chamber to release the therapeutic agent into the vitreous humor through the at least one opening at therapeutic amounts for an extended time.

66. The therapeutic device of claim 65 wherein the porous structure comprises a glass frit.

67. The therapeutic device of claim 65 wherein porous structure comprises a porous annular portion and a porous circular end.

68. The therapeutic device of claim 65 wherein the barrier comprises a material to inhibit substantially the release of the therapeutic agent from the container and wherein the material is shaped so as to define the at least one opening to release the therapeutic agent.

69-71. -71. (canceled)

72. A therapeutic device to deliver a therapeutic agent to an eye having a sclera and a vitreous humor, the device comprising:

a retention structure configured to couple to the sclera;

a container coupled to the retention structure and configured to hold the therapeutic agent and a binding agent; and

a porous barrier coupled to the retention structure and the rigid container, the porous barrier extending substantially around the container.

73. The therapeutic device of claim 72 wherein therapeutic agent and the binding agent are configured to release the therapeutic agent at therapeutic amounts for a sustained time.

76. The therapeutic device of claim 72 wherein the porous barrier comprises pores sized to pass the therapeutic agent from the container to the vitreous humor.

77. The therapeutic device of claim 72 wherein the porous barrier comprises a pore size of at least about 10 nm to release the therapeutic agent and no more than about 200 nm to inhibit at least one of bacterial migration out of the container, macrophage migration or antibody migration into the container.

79. The therapeutic device of claim 72 wherein the porous barrier comprises an inflatable balloon configured to inflate when the therapeutic agent is injected into the container.

80. The therapeutic device of claim 72 wherein the container comprises a rigid material to retain the therapeutic agent and the binding agent.

82. The therapeutic device of claim 72 further comprising an injection port sized to receive a needle.

74-75. -75. (canceled)

78. (canceled)

81. (canceled)

83. A therapeutic device to deliver a therapeutic agent to an eye having a sclera and a vitreous humor, the device comprising:

a retention structure configured to couple to the sclera;

a container coupled to the retention structure and configured to hold a therapeutic quantity of the therapeutic agent, the container comprising,

a first chamber to hold the therapeutic agent,

a barrier to inhibit flow of the therapeutic agent from the container, the barrier comprising at least one opening sized to release the therapeutic agent,

a second chamber coupled to the container through the at least one opening, the second chamber configured to couple to the vitreous humor through a second at least one opening, the first at least one opening and the second at least one opening sized to release the therapeutic agent into the vitreous humor through the second at least one opening at therapeutic amounts for an extended time.

84. (canceled)

85. A method of sustained drug deliver to a posterior segment of an eye having a sclera and a vitreous humor, the method comprising:

inserting a container at least partially into the vitreous humor of the eye such that the container is retained with the sclera, the container comprising a first portion of therapeutic agent reversibly coupled to a first binding medium, wherein the first portion of therapeutic agent released from the first binding medium and through container to the vitreous at therapeutic amounts for an extended time;

removing the binding medium from the container; and

replacing the binding medium with a second binding medium and a second portion of the therapeutic agent, wherein second portion of the therapeutic agent is released from the container for a second extended time.

86. The method of claim 85 wherein a protective barrier is inserted with the container and wherein the protective barrier is disposed substantially around the container to inhibit at least one of a bacterial migration, a macrophage migration or an antibody migration into the container.

87-92. -92. (canceled)

93. A device to deliver a therapeutic agent to a container implanted at least partially in the eye, the device comprising;

a first chamber configured to store the therapeutic agent;

a second chamber configured to receive a liquid from the container; and

an elongate structure extending distally and comprising at least one channel coupled to the first chamber and the second chamber.

94-96. -96. (canceled)

97. A therapeutic device to deliver a therapeutic agent to an eye having a sclera and a vitreous humor, the device comprising:

a retention structure configured to couple to the sclera;

a container coupled to the retention structure and configured to hold the therapeutic agent; and

a stop disposed inside the container.

98. The therapeutic device of claim 97 wherein the retention structure is configured to receive a needle and wherein the stop comprises a concave surface directed toward the retention structure such that fluid is mixed within the container when a substance is injected with the needle.

99. (canceled)

100. A therapeutic device to release at least one therapeutic agent into a patient, the therapeutic device comprising:

a container to contain a therapeutic amount of the at least one therapeutic agent, the container comprising a reservoir with a volume sized to contain a therapeutic quantity of the at least one therapeutic agent for release over the extended time, the container comprising,

a rigid porous structure comprising a thickness and a surface area coupled to the reservoir and configured to release therapeutic amounts of the at least one therapeutic agent for the extended time.

101. The therapeutic device of claim 100 wherein the container comprises a penetrable barrier configured to receive an injection of a therapeutic quantity of the at least one therapeutic agent and wherein the container comprises a barrier coupled to the penetrable barrier and the rigid porous structure to contain the at least one therapeutic agent.

105. The therapeutic device of claim 100 wherein the channels of the rigid porous structure comprise interconnected substantially fixed channels.

106. The therapeutic device of claim 105 wherein the rigid porous structure remains rigid and the channels remain substantially fixed when the therapeutic agent is injected into the reservoir with at least some pressure.

112. The therapeutic device of claim 100 wherein the rigid porous structure comprises a low resistance to flow.

153. The therapeutic device of claim 100 wherein the interconnecting channels of the rigid porous structure are sized to limit a size of molecules passed through the channels of the rigid porous structure.

162. The therapeutic device of claim 100 wherein the porous structure comprises a porosity, a thickness, a channel parameter and a surface area configured to release therapeutic amounts for the extended period.

191. The therapeutic device of claim 100 wherein the porous structure comprises a sintered material.

200. The therapeutic device of claim 191 wherein the channels are sized to pass therapeutic quantities of the at least one therapeutic agent through the sintered material for the extended time.

212. The therapeutic device of claim 100 wherein the at least one therapeutic agent stored in the reservoir of the container comprises at least one of a solid comprising the at least one therapeutic agent, a solution comprising the at least one therapeutic agent, a suspension comprising the at least one therapeutic agent, particles comprising the at least one therapeutic agent adsorbed thereon, or particles reversibly bound to the at least one therapeutic agent.

102-104. -104. (canceled)

107-111. -111. (canceled)

113-130. -130. (canceled)

132-152. -152. (canceled)

154-161. -161. (canceled)

163-169. -169. (canceled)

171-190. -190. (canceled)

192-199. -199. (canceled)

201-211. -211. (canceled)

213. (canceled)

214. A therapeutic device to release at least one therapeutic agent into a patient having a retina, the therapeutic device comprising:

a container to contain a therapeutic amount of the at least one therapeutic agent, the container comprising a reservoir with a volume sized to contain a therapeutic quantity of the at least one therapeutic agent for release over the extended time, the container comprising,

a porous structure comprising a thickness and a surface area coupled to the reservoir and configured to release therapeutic amounts of the at least one therapeutic agent for the extended time, the porous structure disposed on a distal portion of the container;

a retention structure coupled to the container to couple to a sclera of the eye and position the porous structure at a location of the eye to deliver the therapeutic agent toward a target region of the retina with convective flow of the vitreous humor.

215. The therapeutic device of claim 214 wherein the target location of the retina corresponds to neovascularization of a lesion coupled to the target region of the retina.

219. The therapeutic device of claim 214 wherein the therapeutic agent comprises a prostaglandin or a prostaglandin analog.

216-217. -217. (canceled)

218. A therapeutic device to release at least one therapeutic agent into a patient having a retina, the therapeutic device comprising:

a container to contain a therapeutic amount of the at least one therapeutic agent, the container comprising a reservoir with a volume sized to contain a therapeutic quantity of the at least one therapeutic agent for release over the extended time, the container comprising,

a porous structure comprising a thickness and a surface area coupled to the reservoir and configured to release therapeutic amounts of the at least one therapeutic agent for the extended time, the porous structure disposed on a proximal portion of the container;

a retention structure coupled to the container to couple to a sclera of the eye and position the porous structure at a location of the eye to deliver the therapeutic agent to one or more of the ciliary body or a trabecular meshwork of the eye to treat glaucoma.

220. A method of treating an eye of a having a vitreous humor and a retina, the method comprising:

identifying a target location of the retina for treatment; and

positioning a container having a therapeutic amount of a therapeutic agent, the container comprising a porous structure to release therapeutic amounts of the at least one therapeutic agent for the extended time, wherein the porous structure is positioned in the vitreous humor at a location away from the retina to deliver the therapeutic agent to the target location with convective flow of the vitreous humor.

221-222. -222. (canceled)

223. A therapeutic device to release at least one therapeutic agent into an eye of a patient, the therapeutic device comprising:

a container to contain a therapeutic amount of the at least one therapeutic agent, the container comprising a reservoir with a volume sized to contain a therapeutic quantity of the at least one therapeutic agent for release over the extended time, the container comprising,

a rigid porous structure comprising a thickness, a surface area and interconnecting channels coupled to the reservoir and configured to release therapeutic amounts of the at least one therapeutic agent for the extended time, the rigid porous structure disposed on a distal portion of the container to release the at least one therapeutic agent into the eye, and

a penetrable barrier coupled to the reservoir and disposed on a proximal portion of the container to receive an injection of the at least one therapeutic agent; and

a retention structure affixed to the container and configured to couple to a tissue of the eye of the patient for the extended period.

224. A method of treating an eye, the method comprising:

placing a container comprising a reservoir and a penetrable barrier at least partially through a sclera of the eye, wherein the reservoir comprises a fluid; and

passing at least one needle through the penetrable barrier and the conjunctiva disposed over the penetrable barrier; and

injecting a therapeutic amount of at least one therapeutic agent into the container, wherein the fluid in the reservoir is substantially removed from the container when the therapeutic amount is injected.

225-231. -231. (canceled)

232. A device to inject at least one therapeutic agent into a container positioned at least partially within the eye, the device comprising:

a chamber to hold a therapeutic quantity of at least one therapeutic agent;

at least one needle coupled to the chamber and comprising a first lumen sized to inject the at least one therapeutic agent into the container and a second lumen sized to receive liquid from the container when a quantity of at least one therapeutic agent is injected.

233. The device of claim 232 wherein at least one needle comprises a first needle coupled to the chamber and a second needle coupled to a receptacle to receive the liquid ejected from the container when the at least one therapeutic agent is injected.

234-235. -235. (canceled)

236. A therapeutic device to release at least one therapeutic agent into a vitreous humor of an eye of a patient, the therapeutic device comprising:

a container to contain a therapeutic amount of the at least one therapeutic agent, the container comprising a reservoir with a volume sized to contain a therapeutic quantity of at least one therapeutic agent for release over an extended time of at least one year, reservoir comprising a volume of at least about 10 uL, the container comprising,

a barrier coupled to the reservoir and disposed along at least a portion of the reservoir container to contain therapeutic agent within the reservoir, and

a porous structure comprising a thickness, a surface area and channels coupled to the reservoir and configured to release therapeutic amounts of the at least one therapeutic agent for the extended time of at least one year, the porous structure coupled to the container to release the at least one therapeutic agent into the eye; and

a retention structure affixed to the container and configured to couple to a sclera of the eye of the patient for the extended period.

237-243. -243. (canceled)

244. A therapeutic device to release at least one therapeutic agent into a vitreous humor of an eye of a patient, the therapeutic device comprising:

a container to contain a therapeutic amount of the at least one therapeutic agent, the container comprising a reservoir with a volume sized to contain a therapeutic quantity of at least one therapeutic agent for release over an extended time, the container comprising,

a barrier coupled to the reservoir and disposed along at least a portion of the reservoir container to contain therapeutic agent within the reservoir, and

a porous structure comprising a first side having comprising a first plurality of openings coupled to the reservoir and a second side comprising a second plurality of openings to couple to the vitreous humor, wherein interconnecting channels extend between each of the first plurality of openings of the first side and each of the second plurality of openings of the second side to maintain release of the therapeutic agent through the porous structure when partially blocked,

a retention structure affixed to the container to couple to a sclera of the eye of the patient for the extended period.

245. The therapeutic device of claim 244, wherein the release of the therapeutic agent through the porous structure is maintained when partially blocked with particles.

250. The therapeutic device of claim 244, wherein the release of the therapeutic agent through the porous structure is maintained when a portion of the first side or the second side is blocked with a covering material.

246-249. -249. (canceled)

251. A therapeutic device to release at least one therapeutic agent into a vitreous humor of an eye of a patient, the therapeutic device comprising:

a container to contain a therapeutic amount of the at least one therapeutic agent, the container comprising a reservoir with a volume sized to contain a therapeutic quantity of at least one therapeutic agent for release over an extended time, the container comprising,

a barrier coupled to the reservoir and disposed along at least a portion of the reservoir container to contain therapeutic agent within the reservoir, and

a porous structure comprising a first side having comprising a first area coupled to the reservoir and a second side having a second area to couple to the vitreous humor, wherein a flow rate of the therapeutic agent through the porous structure decreases less than a per cent amount when the first area or the second area are decreased by the per cent amount; and

a retention structure affixed to the container to couple to a sclera of the eye of the patient for the extended period.

252. The therapeutic device of claim 251 wherein the flow rate of the therapeutic agent through the porous structure decreases less than the per cent amount when the first area and the second area are decreased by the per cent amount.

253. (canceled)

254. A therapeutic device to release at least one therapeutic agent into a vitreous humor of an eye of a patient, the therapeutic device comprising:

a container to contain a therapeutic amount of the at least one therapeutic agent, the container comprising a reservoir with a volume sized to contain a therapeutic quantity of at least one therapeutic agent for release over an extended time, the container comprising,

a barrier coupled to the reservoir and disposed along at least a portion of the reservoir container to contain therapeutic agent within the reservoir, and

a porous structure comprising a first side having a first plurality of openings coupled to the reservoir and a second side having a second plurality of openings to couple to the vitreous humor, wherein interconnecting channels extend from the first plurality of openings on the first side to the second plurality of openings on the second side to connect each of the plurality of openings on the first side with each of the plurality of openings on the second side; and

a retention structure affixed to the container and configured to couple to a sclera of the eye of the patient for the extended period.

255. The therapeutic device of claim 254 wherein the first plurality comprises at least about 10 openings on the first side and the second plurality comprises at least about 10 openings on the second side and wherein each of the at least about 10 openings of the first side is connected to each of the at least about 10 openings on the second side with the interconnecting channels.

256-257. -257. (canceled)

258. A therapeutic device to release at least one therapeutic agent into a vitreous humor of an eye of a patient, the therapeutic device comprising:

a container to contain a therapeutic amount of the at least one therapeutic agent, the container comprising a reservoir with a volume sized to contain a therapeutic quantity of at least one therapeutic agent for release over an extended time, the container comprising,

a barrier coupled to the reservoir and disposed along at least a portion of the reservoir container to contain therapeutic agent within the reservoir, and

a porous structure comprising a first side having comprising a first plurality of openings coupled to the reservoir and a second side comprising a second plurality of openings to couple to the vitreous humor, wherein the porous material comprises particles sintered to form interconnecting channels extending between each of the first plurality of openings of the first side and each of the second plurality of openings of the second side, and wherein release of the therapeutic agent through the porous structure corresponds substantially to a distribution of sizes of the sintered material and a porosity of the sintered material above a percolation threshold; and

a retention structure affixed to the container to couple to a sclera of the eye of the patient for the extended period.

259. (canceled)

260. A therapeutic device to release at least one therapeutic agent into a vitreous humor of an eye of a patient, the therapeutic device comprising:

a container to contain a therapeutic amount of the at least one therapeutic agent, the container comprising a reservoir with a volume sized to contain a therapeutic quantity of at least one therapeutic agent for release over an extended time, the volume corresponding to a cross-sectional dimension of the container and a height of the container, the container comprising,

a barrier coupled to the reservoir and disposed along at least a portion of the reservoir to contain therapeutic agent within the reservoir, and

a porous structure comprising a first side coupled to the reservoir and a second side to couple to the vitreous humor, the porous structure comprising a thickness extending between the first side and the second side and a cross-sectional dimension corresponding to an area of the first side and an area of the second side, wherein cross-sectional dimension of the porous structure comprises at least about ten percent of the cross-sectional dimension of the container to release the therapeutic agent for the extended time; and

a retention structure affixed to the container to couple to a sclera of the eye of the patient for the extended time.

261. The therapeutic device of claim 260 wherein cross-sectional dimension of the porous structure comprises at least about twenty percent of the cross-sectional dimension of the container to release the therapeutic agent for the extended time.

262. (canceled)

263. A therapeutic device to release at least one therapeutic agent into a vitreous humor of an eye of a patient, the therapeutic device comprising:

an expandable container to contain a therapeutic amount of the at least one therapeutic agent, the expandable container comprising a first narrow profile configuration for insertion into the eye and a second expanded profile configuration having a reservoir sized to contain a therapeutic amount of the at least one therapeutic agent, the expandable container comprising a porous structure coupled to the reservoir to release the at least one therapeutic agent; and

an expandable retention structure comprising a first narrow profile configuration for insertion at least partially into a sclera of the eye and a second expanded profile configuration to couple to the sclera of the eye, the expandable retention structure affixed to the expandable container to couple the expandable container to the vitreous humor for the extended time.

264-267. -267. (canceled)

268. A therapeutic device to release at least one therapeutic agent into a vitreous humor of an eye of a patient, the therapeutic device comprising:

an expandable container comprising a first narrow profile configuration for insertion into the eye and a second expanded configuration comprising a reservoir to contain a therapeutic amount of the at least one therapeutic agent, the expandable container comprising,

a rigid porous structure to release the at least one therapeutic agent,

an expandable barrier to inhibit release of the at least one therapeutic agent,

an expandable support affixed to the porous structure and the expandable barrier to couple the porous structure to the reservoir when the container comprise the expanded configuration; and

an expandable retention structure comprising a first narrow profile configuration for insertion at least partially into a sclera of the eye and a second expanded profile configuration to couple to the sclera of the eye, the expandable retention structure affixed to the expandable container to couple the expandable container to the vitreous humor for the extended time.

269-273. -273. (canceled)

274. A therapeutic device to release at least one therapeutic agent into a vitreous humor of an eye of a patient, the therapeutic device comprising:

a container to contain a therapeutic amount of the at least one therapeutic agent, the container comprising a reservoir with a volume sized to contain a therapeutic quantity of at least one therapeutic agent for release over an extended time; and

a retention structure affixed to the container to couple to a sclera of the eye of the patient for the extended time, the retention structure comprising an extension to couple to an upper side of the sclera, the retention structure comprising a portion to receive the sclera under the extension, the portion comprising a first width extending in a first direction and a second width extending in a second direction, the first width greater than the second width.

275. The therapeutic device of claim 274 wherein the portion comprises an elongate cross-sectional profile having the first width extending along a first axis and the second width extending along a second axis.

277. The therapeutic device of claim 274 wherein the portion comprises a narrow portion having the first width sized larger than a cross-sectional dimension of the container and having the second width sized smaller than a cross-sectional dimension of the container to seal an incision of the sclera with the cross-sectional profile.

282. The therapeutic device of claim 274 wherein the container comprises a cross-sectional profile having a first distance across and a second distance across greater than the first distance across and wherein the first distance is aligned substantially with the first width and the second dimension across is aligned substantially with the second width to decrease visual interference.

276. (canceled)

278-281. -281. (canceled)

283. (canceled)

284. A method of treating an eye having a vitreous humor and a sclera, the method comprising:

providing a therapeutic device to release at least one therapeutic agent into the vitreous humor of an eye of a patient, the therapeutic device comprising a container and a retention structure affixed to the container, the retention structure comprising a narrow portion having a first longer distance across extending in a first direction and a second shorter distance across extending in a second direction, the first longer distance greater than the second shorter distance;

forming an elongate incision in the sclera, the incision comprising a length extending along a pars plana of the eye and a width, the length greater than the width; and

positioning the container in the eye to release the therapeutic agent, wherein the narrow portion of the retention structure is aligned with the elongate incision such that the first longer distance across extends substantially along the elongate incision and the second shorter distance across extends substantially across the width of the incision.

285-286. -286. (canceled)

287. A method of treating an eye of a patient, the method comprising:

providing a therapeutic device comprising a reservoir and a therapeutic agent disposed therein;

positioning the container in the eye to release the therapeutic agent, wherein the narrow portion of the retention structure is aligned with the elongate incision such that the first longer distance across extends substantially along the elongate incision and the second shorter distance across extends substantially across the width of the incision.

288. A method of treating an eye of a patient, the method comprising:

providing a therapeutic device comprising a container and a therapeutic agent disposed within the container, the therapeutic agent comprising a half-life within the container of at least about 20 days when implanted; and

positioning the container in the eye to release the therapeutic agent, wherein the eye is treated with the therapeutic agent for at least about 90 days.

289. A method of treating an eye of a patient, the method comprising:

providing a therapeutic device comprising a reservoir and a therapeutic agent disposed within the reservoir, the therapeutic agent comprising a half-life within the reservoir of no more than about 30 days when implanted; and

positioning the container in the eye to release the therapeutic agent, wherein the eye is treated with the therapeutic agent for at least about 180 days.

290. A method of treating an eye of a patient, the method comprising:

providing a therapeutic device comprising a reservoir and a therapeutic agent disposed within the reservoir, the therapeutic agent comprising a half-life within the reservoir when implanted, the half life within the reservoir substantially greater than a corresponding half-life of the therapeutic agent when injected directly into the vitreous; and

positioning the container in the eye to release the therapeutic agent, wherein the eye is treated with the therapeutic agent for at least about 180 days.

291. (canceled)

292. A method of manufacturing a therapeutic device to release a therapeutic agent, the method comprising:

measuring a gas coupled to a porous structure;

providing a container to contain the therapeutic agent; and

coupling the porous structure to the container.

293. The method of claim 292 wherein the gas is measured to determine a release rate of the therapeutic agent through the porous structure.

294-300. -300. (canceled)

301. A method of treating an eye having a vitreous humor, the method comprising:

injecting a quantity of a formulation of therapeutic agent into a therapeutic device, wherein the therapeutic device is tuned to receive the quantity.

302. A method of treating an eye having a vitreous humor, the method comprising:

providing a formulation of a therapeutic agent, the therapeutic agent capable of treating the eye with bolus injections, the formulation having a corresponding period between each of the bolus injections to treat the eye, each of the bolus injections comprising a volume of the formulation, wherein each of the bolus injections corresponds to a range of therapeutic concentrations of the therapeutic agent in the vitreous humor to treat the eye; and

providing a therapeutic device to treat the eye with an injection of the volume of the formulation into the device, wherein the device comprises a container having a chamber to contain a volume of the therapeutic agent and a mechanism to release the therapeutic agent from the chamber to the vitreous humor and wherein the volume of the container and the release mechanism are tuned to treat the eye with therapeutic concentrations of the therapeutic agent within the range for an extended time with each injection of the quantity, the extended time comprising at least about twice the period.

303. The method of claim 302 wherein the chamber comprises a substantially fixed volume and the release rate mechanism comprises a substantially rigid structure to maintain release of the therapeutic agent above the minimum inhibitory concentration for the extended time with each injection of a plurality of injections.

311. The method of claim 302 wherein the volume and the mechanism are tuned to release the therapeutic concentration within the range for the extended time based on a half life of the therapeutic agent in the vitreous humor of the eye.

312. The method of claim 311 wherein the eye comprises a human eye and the half life is determined based on the half life of the therapeutic agent in the human eye.

304-310. -310. (canceled)

313-314. -314. (canceled)

315. A method of treating an eye having a vitreous humor, the method comprising:

providing a therapeutic device having a chamber sized to contain a volume of a therapeutic agent and a porous structure coupled to the chamber;

providing an injector comprising at least one lumen to inject a formulation of a therapeutic agent, the injector comprising a valve coupled to the at least one lumen;

coupling the therapeutic device to the injector with the at least one lumen extending at least partially into the therapeutic device;

injecting a first portion of the formulation into the chamber when the valve is open to exchange material disposed within the chamber with the first portion formulation; and

injecting a second portion of the formulation when the valve is closed to pass formulation through the porous structure.

316-317. -317. (canceled)

318. A therapeutic device for treating an eye having a vitreous humor, the therapeutic device comprising a reservoir volume and porous structure tuned to receive a volume of a formulation and to release for an extended time therapeutic amounts of a therapeutic agent injected into the reservoir.

319. The therapeutic device of claim 318 wherein the porous structure comprises a release mechanism and wherein the reservoir volume and the release mechanism are tuned to release the therapeutic amounts of the therapeutic agent for the extended time based on a half life of the therapeutic agent in the vitreous humor of the eye.

320-321. -321. (canceled)

322. A method of treating an eye an eye having a vitreous humor, the method comprising:

providing the therapeutic device comprising a reservoir and porous structure tuned to release therapeutic amounts of a therapeutic agent for an extended time; and

injecting a quantity of therapeutic agent into the reservoir, wherein the therapeutic agent is released from the tuned reservoir and porous structure for the extended time.

323. An apparatus to treat an eye having a vitreous humor, the apparatus comprising:

a therapeutic device comprising reservoir to contain a therapeutic agent and a porous structure; and

an injector having a first chamber and a second chamber and at least one needle comprising a first lumen and a second lumen, the first chamber coupled to the first lumen to inject the therapeutic agent from the first chamber into the reservoir, the second chamber coupled to the second lumen with a valve disposed therebetween to receive material from the reservoir when the valve is open and pass therapeutic agent through the porous structure when the valve is closed.

324. A method of treating an eye having a vitreous humor, the method comprising:

injecting into a therapeutic device a volume of a formulation of Ranibizumab, the volume within a range from about 40 to 60 uL, the concentration of Ranibizumab of the formulation within a range from about 8 to 12 mg/mL, such that the injection comprises a weight Ranibizumab within a range from about 0.4 to about 0.6 mg of Ranibizumab, and wherein the Ranibizumab is released in therapeutic amounts for an extended time at least about 4 months.

325. The method of claim 324 wherein the formulation comprises a commercially available formulation of Lucentis™

and wherein the volume corresponds to a monthly bolus injection of about 50 uL of Lucentis™ and

wherein a concentration of the Ranibizumab in the vitreous humor comprises at least about 4 ug/mL for the extended time.

326. A method of treating an eye, the method comprising:

placing a container comprising a reservoir and a penetrable barrier at least partially through a sclera of the eye, wherein the reservoir comprises a fluid; and

injecting a therapeutic amount of at least one therapeutic agent into the container, wherein the therapeutic amount corresponds to a bolus injection to treat the eye for about one month and wherein therapeutic quantities of the therapeutic agent are released from the container for at least about two months to treat the eye.

327. A method of treating an eye, the eye having a sclera and a pars plana, the method comprising:

providing a therapeutic device comprising a drug reservoir, a porous structure and a retention structure, the retention structure comprising an elongate cross-sectional profile;

forming an incision through the sclera and extending along the pars plana region;

advancing the therapeutic device into the sclera with the elongate cross-sectional profile aligned with the incision along the pars plana, and wherein the elongate cross-sectional profile seals the incision when the elongate cross-sectional profile contacts the sclera.

328. The method of claim 327 wherein the retention structure comprises a conformable flange disposed over the elongate cross-sectional profile and wherein the conformable flange contacts and upper surface of the sclera when the elongate cross-sectional profile contacts the sclera.

329. (canceled)

330. An apparatus, the apparatus comprising:

a therapeutic device comprising a shape changing drug reservoir, a porous structure and a retention structure; and

a cannula, wherein the therapeutic device is positioned within the cannula.

331. The apparatus of claim 330 wherein the therapeutic device comprises an elongate narrow shape for insertion into the sclera and wherein the device is configured to expand to a second elongate wide shape for retention in the sclera

332. (canceled)

333. A therapeutic device to treat a patient, the device comprising:

means for releasing therapeutic amounts of a therapeutic agent for an extended period.