Posterior segment drug delivery

• US 8,298,578 B2
• Filed: 10/04/2011
• Issued: 10/30/2012
• Est. Priority Date: 01/29/2009
• Status: Active Grant

• Current Assignee: Forsight Vision4, Inc. (Roche Holding AG)
• Original Assignee: Forsight Vision4, Inc. (Roche Holding AG)
• Inventors: de Juan, Eugene Jr., Alster, Yair, Farinas, Kathleen Cogan, Gifford, Hanson S. III, MacFarlane, K. Angela, Reich, Cary J., Barrett, Michael, Campbell, Randolph E., Sutton, Douglas
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): EBRAHIM, NABILA G
• Application Number:
  US13/252,942
• Publication Number:
  US 20120029470A1
• Time in Patent Office: 392 Days
• Field of Search: None
• US Class Current: 424/464
• 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: G01N 33/558 using diffusion or migration of antigen or antibody immunochromatographic test strips G01N33/54387
• 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.

Claims

1. A method of treating an eye of a patient having a posterior chamber, the method comprising:

implanting a therapeutic device into the eye, said device comprising;

a rigid, hollow, refillable body for implantation within the posterior chamber of the eye through a penetration in the sclera, the body formed of a substantially rigid, impermeable wall of biocompatible material, the body having a proximal cap portion adapted to be positioned outside the sclera, an intermediate neck portion, and a distal reservoir portion adapted to reside in the posterior chamber such that the sclera is positioned about the neck portion when the device is positioned in the eye, wherein the neck portion has a smaller transverse outer dimension than at least one transverse outer dimension of the cap portion and at least one transverse outer dimension of the reservoir portion;

the cap portion adapted to receive an injection of a therapeutic agent into the reservoir and to remain external to the posterior chamber;

a rigid porous structure having a plurality of interconnecting, irregularly shaped channels, said rigid porous structure coupled to a discrete, distal portion of the reservoir and tuned to release therapeutic amounts of a therapeutic agent from the reservoir through said plurality of channels and into said posterior chamber for an extended time, wherein the therapeutic device has a substantially fixed volume during implantation and use; and

injecting a therapeutic agent into the reservoir portion.

2. The method of claim 1, wherein the channels of the rigid porous structure comprise interconnected substantially fixed channels.

3. The method of claim 2, wherein the rigid porous structure remains rigid and the channels remain substantially fixed when the therapeutic agent is injected into the reservoir.

4. The method of claim 1, wherein said injecting is performed before implanting the device in the eye.

5. The method of claim 1, wherein the device reservoir of the therapeutic device is refilled with an injection through the conjunctiva and a penetrable barrier of the therapeutic device, such that the therapeutic device is refilled trans-sclerally without penetration of the sclera or choroid.

6. The method of claim 1, wherein at least some of the plurality of interconnecting channels intersect at a plurality of locations.

7. The method of claim 1, wherein the rigid porous structure comprises a sintered material.

8. The method of claim 1, wherein the rigid porous structure comprises a sintered metallic disc.

9. The method of claim 1, wherein the rigid porous structure comprises one or more of a metal, a ceramic, or a glass.

10. The method of claim 1, wherein the rigid, porous structure comprises a thickness and a surface area corresponding to a rate of release of the therapeutic agent over the extended time.

11. The method of claim 10, wherein the thickness extends between a first side and a second side of the structure, and wherein the plurality of interconnecting channels extends between the first side and the second side and wherein the plurality of interconnecting channels of the rigid porous structure comprise interconnected substantially fixed tortuous channels having an effective length extending from the first side of the porous structure to the second side of the porous structure, the effective length greater than the thickness of said structure.

12. The method of claim 1, wherein the interconnecting channels of the rigid porous structure are configured to pass the at least one therapeutic agent among the interconnecting channels.

13. The method of claim 1, wherein the rigid porous structure comprises rigid grains of material and wherein the interconnecting channels extend at least partially around the grains of rigid material to pass the at least one therapeutic agent through the porous material.

14. The method of claim 1, wherein the therapeutic device comprises a retention structure and a penetrable barrier, the retention structure comprising an extension coupled to the reservoir and extending outward from the reservoir between the sclera and the conjunctiva to retain the therapeutic device and wherein injecting comprises injecting the therapeutic agent through the conjunctiva and the penetrable barrier with a needle when the retention structure extends between the sclera and the conjunctiva without sutures.

15. The method of claim 1, wherein the therapeutic agent comprises a half-life within the reservoir of at least about 20 days when implanted and wherein the eye is treated with the therapeutic agent for at least about 90 days.

16. The method of claim 1, wherein the therapeutic agent comprises a half-life within the reservoir of at least about 30 days when implanted and wherein the eye is treated with the therapeutic agent for at least about 120 days.

17. The method of claim 1, wherein the therapeutic agent comprises 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 wherein the eye is treated with the therapeutic agent for at least about 120 days.

18. The method of claim 1, 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.

19. The method of claim 18, wherein the channel parameter comprises a fit parameter corresponding to an effective length of interconnecting channels extending from a first side of the porous structure to a second side of the porous structure.

20. The method of claim 19, wherein the rate of release of the at least one therapeutic agent corresponds to a ratio of the porosity to the channel parameter and wherein the ratio of the porosity to the channel parameter is less than about 0.5 such that the porous structure releases the at least one therapeutic agent for the extended period.

21. The method of claim 1, wherein the porous structure comprises a release rate index of no more than about 5.0 mm.

22. The method of claim 1, wherein the reservoir comprises a volume sized to contain the quantity of the therapeutic agent for release over a predetermined extended time and wherein the rigid porous structure comprises a thickness and a surface area corresponding to a rate of release of the therapeutic agent and wherein the volume and the rate of release provide a half life of the therapeutic agent in the reservoir corresponding to an optimal half-life of the therapeutic agent in the reservoir chamber such that the volume and the release rate are tuned to release therapeutic amounts of the therapeutic agent for the predetermined extended time.

23. The method of claim 22, wherein the volume and the release rate correspond to an optimal volume and an optimal release rate providing the optimal half life, wherein the optimal half life corresponds to therapeutic concentrations of the therapeutic agent above a minimum inhibitory concentration for the predetermined extended time and wherein the release rate is within about within about +/−

50% of the optimal release rate and the volume is +/−

50% of the optimal volume to provide the therapeutic concentrations for the predetermined extended time.

24. A method of treating a patient, comprising:

implanting a medical device into an eye, said device comprising;

a rigid, hollow, refillable body for implantation within the posterior chamber of the eye through a penetration in the sclera, the body formed of a substantially rigid, impermeable wall of biocompatible material, the body having a proximal cap portion adapted to be positioned outside the sclera, an intermediate neck portion, and a distal reservoir portion adapted to reside in the posterior chamber such that the sclera is positioned about the neck portion when the device is positioned in the eye, wherein the neck portion has a smaller transverse outer dimension than at least one transverse outer dimension of the cap portion and at least one transverse outer dimension of the reservoir portion;

the cap portion adapted to receive an injection of a therapeutic agent into the reservoir and to remain external to the posterior chamber; and

a rigid porous structure having a plurality of interconnecting, irregularly shaped channels, said rigid porous structure coupled to a discrete, distal portion of the reservoir and tuned to release therapeutic amounts of a therapeutic agent from the reservoir through said plurality of channels and into said posterior chamber for an extended time, wherein the therapeutic device has a substantially fixed volume during implantation and use;

injecting the therapeutic agent into the medical device; and

permitting the therapeutic agent to release through the rigid porous structure and into the eye for the extended period of time.

25. The method of claim 24, further comprising:

determining whether to introduce an additional quantity of therapeutic agent into the reservoir after the extended period of time based on the patient'"'"'s treatment needs.

26. A method of delivering a therapeutic agent into an eye of a patient, comprising:

providing a therapeutic device comprising;

a rigid, hollow, refillable body for implantation within the posterior chamber of the eye through a penetration in the sclera, the body formed of a substantially rigid, impermeable wall of biocompatible material, the body having a proximal cap portion adapted to be positioned outside the sclera, an intermediate neck portion, and a distal reservoir portion adapted to reside in the posterior chamber such that the sclera is positioned about the neck portion when the device is positioned in the eye, wherein the neck portion has a smaller transverse outer dimension than at least one transverse outer dimension of the cap portion and at least one transverse outer dimension of the reservoir portion;

the cap portion adapted to receive an injection of a therapeutic agent into the reservoir and to remain external to the posterior chamber; and

a rigid porous structure having a plurality of interconnecting, irregularly shaped channels, said rigid porous structure coupled to a discrete, distal portion of the reservoir and tuned to release therapeutic amounts of a therapeutic agent from the reservoir through said plurality of channels and into said posterior chamber for an extended time, wherein the therapeutic device has a substantially fixed volume during implantation and use;

implanting the device into the eye such that at least the rigid, porous structure is placed in fluid communication with an interior portion of the eye, wherein the therapeutic agent is capable of releasing into the interior of the eye;

monitoring the patient'"'"'s response to the release of therapeutic agent into the eye;

determining whether to introduce additional of therapeutic agent into the reservoir portion based on the patient'"'"'s response to the release of therapeutic agent; and

injecting additional therapeutic agent into the reservoir portion, such that the additional therapeutic agent is capable of releasing into the interior of the eye for an additional extended period of time.