Biodegradable intravitreal tyrosine kinase implants

• US 20050244475A1
• Filed: 04/29/2005
• Published: 11/03/2005
• Est. Priority Date: 04/30/2004
• Status: Active Grant

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Inventors: Malone, Thomas C., Edelman, Jeffrey L., Hughes, Patrick M., Spada, Lon T., Chang-Lin, Joan-En, Nivaggioli, Thierry, Blanda, Wendy M., DeVries, Gerald W., Shiah, Jane Guo
• Granted Patent: US 8,512,738 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 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• 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 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/204 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 27/02 Ophthalmic agents

Abstract

Biocompatible intraocular implants include a tyrosine kinase inhibitor and a biodegradable polymer that is effective to facilitate release of the tyrosine kinase inhibitor into the vitreous of an eye for an extended period of time. The therapeutic agents of the implants may be associated with a biodegradable polymer matrix, such as a matrix that is substantially free of a polyvinyl alcohol. The implants can be placed in an eye to treat or reduce the occurrence of one or more ocular conditions, such as posterior ocular conditions.

Claims

1. A biodegradable intravitreal implant comprising:

a tyrosine kinase inhibitor (TKI) and a biodegradable polymer, the implant releasing the TKI at a rate effective to sustain release of the TKI from the implant for at least about one week after the implant is placed in the vitreous of an eye.

2. The implant of claim 1, wherein the polymer is selected from the group consisting of polylactides, poly(lactide-co-glycolides), polycaprolactones, derivatives thereof, and mixtures thereof.

3. The implant of claim 1, wherein the matrix releases the TKI at a rate effective to sustain release of an amount of the TKI from the implant for more than one month from the time the implant is placed in the vitreous of the eye.

4. The implant of claim 1, wherein the tyrosine kinase inhibitor is provided in an amount from about 30% by weight to about 70% by weight of the implant, and the biodegradable polymer matrix comprises a poly(lactide-co-glycolide) in an amount from about 30% by weight to about 70% by weight of the implant.

5. The implant of claim 1, wherein the implant is made by an extrusion process.

6. A method of making a biodegradable intravitreal implant, comprising the step of:

extruding a mixture of a TKI and a biodegradable polymer to form a biodegradable implant that degrades at a rate effective to sustain release of an amount of the TKI from the implant for at least about one week after the implant is placed in the vitreous of an eye.

7. The method of claim 6, wherein mixture consists essentially of the TKI and the biodegradable polymer.

8. The method of claim 6, wherein the polymer comprises a polymer selected from the group consisting of polylactides, poly(lactide-co-glycolides), polycaprolactones, and combinations thereof.

9. A method of treating an ocular condition of an eye of a patient, comprising the step of placing a biodegradable intraocular implant into the vitreous of an eye of the patient, the implant comprising a TKI and a biodegradable polymer, wherein the implant degrades at a rate effective to sustain release of an amount of the TKI from the implant effective to treat the ocular condition.

10. The method of claim 9, wherein the method is effective to treat a retinal ocular condition.

11. The method of claim 9, wherein the ocular condition is glaucoma.

12. The method of claim 9, wherein the ocular condition is proliferative vitreoretinopathy.

13. The implant of claim 9, wherein the TKI is a compound selected from the group of compounds consisting of compounds having the formulas: