Implantable therapeutic device

• US 8,623,395 B2
• Filed: 08/05/2011
• Issued: 01/07/2014
• Est. Priority Date: 01/29/2010
• 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, MacFarlane, K. Angela, Reich, Cary J., Campbell, Randolph E.
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): EBRAHIM, NABILA G
• Application Number:
  US13/204,638
• Publication Number:
  US 20120095439A1
• Time in Patent Office: 886 Days
• Field of Search: None
• US Class Current: 424/422
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/179 for growth factors; for growth regulators
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 2317/94 Stability, e.g. half-life, pH, temperature or enzyme-resistance

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. 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 may comprise a penetrable barrier to inject therapeutic agent into the device when implanted in the patient.

Claims

1. An ophthalmic drug delivery system comprising:

an extended release device configured to be implanted in an eye, the device comprising;

a reservoir having a reservoir volume; and

a rigid porous structure coupled to the reservoir and having a release rate index (RRI)=PA/FL, where P is porosity corresponding to the percentage of void space of channels extending within the rigid porous structure, A is area, F is channel parameter, and L is thickness, the rigid porous structure having a plurality of irregularly shaped channels, the porous structure located at the outlet of the reservoir and tuned to release a predetermined rate profile of a drug formulation from the reservoir through the plurality of channels and into the eye to treat the eye for an extended period of time; and

a drug formulation contained in and delivered by the extended release device, wherein the drug formulation comprises a drug having a concentration in a solution volume and a given half-life upon bolus injection of the solution volume into an eye,

wherein the extended release device is tuned to the drug formulation by selecting a value for at least one of the group consisting of;

the concentration, the reservoir volume, and the RRI, to achieve an effective half-life in the eye when the drug formulation is delivered by the implantable extended release device,

wherein the effective half-life is longer than the given half-life; and

wherein the porosity P is between about 3% to about 70%, area A is between about 0.37 mm2 to about 16 mm2, channel parameter F is within a range of about 1.2 to 5.0 times the thickness of the porous structure, and thickness L is between about 0.029″

to about 0.049″

.

2. The system of claim 1, wherein the drug is an anti-VEGF therapeutic agent.

3. The system of claim 1, wherein the drug is ranibizumab, bevacizumab, pegaptanib, aflibercept, lapatinib, sunitinib, sorafenib, axitinib, or pazopanib.

4. The system of claim 1, wherein the drug is a commercially-available formulation selected from the group consisting of ranibizumab, bevacizumab, pegaptanib, and aflibercept.

5. The system of claim 1, wherein the concentration is between 10 mg/mL and 200 mg/mL.

6. The system of claim 1, wherein the given half-life is within a range from about 1 hour to about 9 days.

7. The system of claim 1, wherein the effective half-life is within a range from about 18 days to about 250 days.

8. The system of claim 1, wherein the reservoir volume is within a range from about 10 uL to about 50 uL.

9. The system of claim 1, wherein the reservoir is refillable.

10. The system of claim 1, wherein the reservoir is flushable.

11. The system of claim 1, wherein the drug formulation is delivered from the reservoir into the vitreous for at least 30 days, 60 days, 90 days, 120 days, 5 months, 6 months, 1 year, 2 years, or 3 years after the device is implanted into the eye without removing the device.

12. The system of claim 11, wherein the drug formulation is a commercially-available formulation of ranibizumab, wherein the concentration is between 10 mg/mL and 200 mg/mL, the solution volume is between 10 uL and 50 uL, and the given half-life in the vitreous is between 2 days and 9 days.

13. The system of claim 12, wherein the system is configured to have a reservoir volume of between 10 uL and 100 uL and a release rate index of between 0.01 and 0.09 to achieve the effective half-life that is between 30 days and 12 months.

14. The system of claim 1, wherein the effective half-life in the eye maintains a concentration of the drug in the eye that is above a therapeutic target concentration for a longer period of time than the given half-life maintains the concentration of the drug in the eye that is above the therapeutic target concentration.

15. The system of claim 14, wherein the therapeutic target concentration is between about 0.1 ug/mL to about 5 ug/mL.

16. The system of claim 1, wherein the drug is released as a release rate of about 2 ug/day to about 8 ug/day from the device.

17. The system of claim 1, wherein the release rate index (RRI)=PA/FL, where P is porosity, A is area, F is channel parameter, and L is thickness.

18. The system of claim 17, wherein the RRI is within a range from about 0.01 and 0.09.

19. The system of claim 17, wherein the RRI is within a range from about 0.001 to about 5.

20. The system of claim 17, wherein the RRI is within a range from about 0.002 to about 5.

21. The system of claim 17, wherein the RRI is from about 0.01 to about 5.