Combined drug delivery methods and apparatus

• US 10,617,557 B2
• Filed: 08/05/2011
• Issued: 04/14/2020
• Est. Priority Date: 08/05/2010
• Status: Active Grant

• Current Assignee: Forsight Vision4, Inc. (Roche Holding AG)
• Original Assignee: Forsight Vision4, Inc. (Roche Holding AG)
• Inventors: de Juan, Eugene, Alster, Yair, Farinas, Kathleen Cogan, Reich, Cary J., Campbell, Randolph E., MacFarlane, K. Angela, Erickson, Signe
• Primary Examiner(s): Mehta, Bhisma
• Assistant Examiner(s): Darb, Hamza A
• Application Number:
  US13/814,466
• Publication Number:
  US 20130274691A1
• Time in Patent Office: 3,175 Days
• Field of Search: 604246, 6048901, 6048911, 6048921, 60428801, 604297-300, 604175, 604500, 604506
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• 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 31/74 Synthetic polymeric materials
• 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: A61P 27/02 Ophthalmic agents

Abstract

Methods and apparatus provide treatment with a first therapeutic agent and a second therapeutic agent for an extended time. The first therapeutic agent may comprise a VEGF inhibitor and the second therapeutic agent may comprise an antiinflammatory, such as a non-steroidal anti-inflammatory, for example a cyclooxygenase inhibitor. One or more of the first therapeutic agent or the second therapeutic agent can be injected into the eye, for example injected into a therapeutic device implanted into the eye to release the injected therapeutic agent for an extended time.

Claims

1. A therapeutic device to treat an eye, the device comprising:

a non-permeable housing having a substantially fixed reservoir volume during implantation and use, wherein the reservoir volume is sized to extend through a sclera into a vitreous humor when the device is implanted in the eye;

a proximal cap portion coupled near a proximal end region of the housing and adapted to be positioned outside the sclera when the device is implanted in the eye, the cap portion comprising a retention structure and a penetrable, non-permeable barrier;

a narrow portion adjacent the proximal cap portion, the narrow portion having a cross-sectional shape defined along a plane perpendicular to a longitudinal axis of the device, wherein the cross-sectional shape of the narrow portion is defined at a widest location of the narrow portion by a first long width and a cross-sectional shape of the non-permeable housing is defined at a widest location of the non-permeable housing by a second long width such that the second long width of the non-permeable housing is greater than the first long width of the narrow portion;

a first chamber located within the reservoir volume and configured to hold a first therapeutic agent, the first chamber defining an opening at a distal end region of the first chamber, a first rigid, porous structure positioned within the opening at the distal end region of the first chamber, the first porous structure configured to be positioned in direct communication with the vitreous humor and comprised of sintered material; and

a second chamber located within the reservoir volume and configured to hold a second therapeutic agent, the second chamber defining an opening at a distal end region of the second chamber, a second rigid, porous structure positioned within the opening at the distal end region of the second chamber, the second porous structure configured to be positioned in direct communication with the vitreous humor and comprised of sintered material;

wherein the housing comprises a barrier extending through the reservoir volume from the proximal end region of the housing to a distal end region of the housing thereby forming the first chamber and the second chamber, and wherein at least one of the first and second chambers is refillable.

2. The device of claim 1, wherein the first chamber has a first volume and the first rigid, porous structure has a first release rate index and a first porosity so as to release the first therapeutic agent in therapeutic amounts into the vitreous humor from the device for a first extended period of time when the device is implanted in the eye.

3. The device of claim 2, wherein the non-permeable housing is formed of a tubular sidewall that extends approximately perpendicular to a plane of the sclera upon implantation and use, the first and second chambers are arranged in parallel relative to the longitudinal axis of the device, the longitudinal axis extending from the proximal end region of the housing to the distal end region of the housing, such that the distal end region of the first chamber is adjacent the distal end region of the second chamber near the distal end region of the housing, and wherein both the first and second chambers are accessible by an injector to refill the first and second chambers with the first and second therapeutic agents, respectively.

4. The device of claim 3, further comprising a first injector configured to be coupled to the first chamber to deliver the first therapeutic agent into the first chamber.

5. The device of claim 4, further comprising a second injector configured to be coupled to the second chamber to deliver the second therapeutic agent into the second chamber.

6. The device of claim 5, wherein the second chamber has a second volume and the second rigid, porous structure has a second release rate index so as to release the second therapeutic agent in therapeutic amounts into the vitreous humor from the device for a second extended period of time when the device is implanted in the eye.

7. The device of claim 1, wherein the first therapeutic agent comprises an antineoplastic agent and the second therapeutic agent comprises an anti-inflammatory agent.

8. The device of claim 7, wherein the antineoplastic agent comprises a VEGF inhibitor and the anti-inflammatory agent comprises a non-steroidal anti-inflammatory agent.

9. The device of claim 8, wherein the VEGF inhibitor is LUCENTIS.

10. The device of claim 8, wherein the non-steroidal anti-inflammatory agent is a COX inhibitor.

11. The device of claim 10, wherein the COX inhibitor is a water insoluble COX inhibitor.

12. The device of claim 1, wherein the cap portion is adapted to receive an injection of at least the first therapeutic agent into the first chamber.

13. The device of claim 12, wherein the penetrable, non-permeable barrier is configured to allow introduction of at least the first therapeutic agent into the first chamber when the device is implanted in the eye.

14. The device of claim 1, wherein the cross-sectional shape of the narrow portion comprises a first cross-sectional dimension and a second cross-sectional dimension, such that the first cross-sectional dimension is greater than the second cross-sectional dimension so as to form an elongated profile.

15. The device of claim 14, wherein the elongated profile is a lentoid, oval, or ellipse.

16. The device of claim 1, wherein the cross-sectional shape of the narrow portion comprises a first curve along a first axis and a second curve along a second axis different than the first curve.

17. A therapeutic device to treat an eye, the device comprising:

a non-permeable housing having a substantially fixed reservoir volume during implantation and use, wherein the reservoir volume is sized to extend through a sclera into a vitreous humor when the device is implanted in the eye;

a proximal cap portion coupled near the proximal end region of the housing and adapted to be positioned outside the sclera when the device is implanted in the eye;

a narrow portion adjacent the proximal cap portion, the narrow portion having a cross-sectional shape defined along a plane perpendicular to a longitudinal axis of the device;

a first chamber located within the reservoir volume and configured to hold a first therapeutic agent, the first chamber defining an opening at a distal end region of the first chamber, a first rigid, porous structure positioned within the opening at the distal end region of the first chamber, the first porous structure configured to be positioned in direct communication with the vitreous humor and comprised of sintered material; and

a second chamber located within the reservoir volume and configured to hold a second therapeutic agent, the second chamber defining an opening at a distal end region of the second chamber, a second rigid, porous structure positioned within the opening at the distal end region of the second chamber, the second porous structure configured to be positioned in direct communication with the vitreous humor and comprised of sintered material;

wherein the housing comprises a barrier extending through the reservoir volume from the proximal end region of the housing to a distal end region of the housing thereby forming the first chamber and the second chamber, and wherein at least one of the first and second chambers is refillable.

18. The device of claim 17, wherein the first chamber has a first volume and the first rigid, porous structure has a first release rate index and a first porosity so as to release the first therapeutic agent in therapeutic amounts into the vitreous humor from the device for a first extended period of time when the device is implanted in the eye.

19. The device of claim 18, wherein the non-permeable housing is-formed of a tubular sidewall that extends approximately perpendicular to a plane of the sclera upon implantation and use, the first and second chambers are arranged in parallel relative to the longitudinal axis of the device, the longitudinal axis extending from the proximal end region of the housing to the distal end region of the housing, such that the distal end region of the first chamber is adjacent the distal end region of the second chamber near the distal end region of the housing, and wherein both the first and second chambers are accessible by an injector to refill the first and second chambers with the first and second therapeutic agents, respectively.

20. The device of claim 19, wherein the second chamber has a second volume and the second rigid, porous structure has a second release rate index so as to release the second therapeutic agent in therapeutic amounts into the vitreous humor from the device for a second extended period of time when the device is implanted in the eye.