Device and method for treating ophthalmic diseases

• US 6,299,895 B1
• Filed: 04/27/1999
• Issued: 10/09/2001
• Est. Priority Date: 03/24/1997
• Status: Expired due to Term

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System), Neurotech USA, Inc. (Woodbrook Group Holdings, Inc.)
• Original Assignee: Neurotech S.A. (LivaNova Plc)
• Inventors: Baetge, E. Edward, Hammang, Joseph P., Spear, Peter D., Tsiarias, William G.
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US09/155,066
• Time in Patent Office: 896 Days
• Field of Search: 424/427, 435/177, 435/178, 435/182
• 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 9/0051 Ocular inserts, ocular implants

Abstract

A method and device for delivering a biologically active molecule to the eye, either intraocularly or periocularly, and method and device for treating ophthalmic disorders in a patient suffering therefrom.

Claims

1. A method for delivering a biologically active molecule to the eye comprising:

implanting a capsule periocularly in the sub-Tenon'"'"'s space, the capsule comprising a core containing a cellular source of the biologically active molecule and a surrounding biocompatible jacket, the jacket permitting diffusion of the biologically active molecule into the eye wherein the dosage of the biologically active molecule delivered is between 50 pg and 1000 ng per eye per patient per day.

2. The method of claim 1 wherein the jacket comprises a permselective, immunoisolatory membrane.

3. The method of claim 1 wherein the capsule is configured as a hollow fiber or a flat sheet.

4. The method of claim 1 wherein the biologically active molecule is selected from the group consisting of anti-angiogenic factors, neurotrophic factors, growth factors, antibodies and antibody fragments, neurotransmitters, hormones, enzymes, cytokines, and lymphokines.

5. The method of claim 1 wherein the biologically active molecule is selected from the group consisting of anti-angiogenic factors, anti-inflammatory factors, neurotrophic factors, and combinations thereof.

6. The method of claim 1 wherein the number of capsules implanted is between 1 and 5 capsules per eye.

7. The method of claim 1 wherein a second biologically active molecule or peptide is co-delivered from the capsule to the eye.

8. A method for delivering a biologically active molecule to the eye comprising:

implanting a capsule intraocularly, the capsule comprising a core containing a cellular source of the biologically active molecule and a surrounding biocompatible jacket, the jacket permitting diffusion of the biologically active molecule into the eye wherein the dosage of the biologically active molecule delivered is between 50 pg to 500 ng per eye per patient per day.

9. The method of claim 8 wherein the jacket comprises a permselective, immunoisolatory membrane.

10. The method of claim 8 wherein the jacket comprises a microporous membrane.

11. The method of claim 8 wherein the capsule is configured as a hollow fiber or a flat sheet.

12. The method of claim 8 wherein the biologically active molecule is selected from the group consisting of anti-angiogenic factors, neurotrophic factors, growth factors, antibodies and antibody fragments, neurotransmitters, hormones, enzymes, cytokines, and lymphokines.

13. The method of claim 8 wherein the biologically active molecule is selected from the group consisting of anti-angiogenic factors, anti-inflammatory factors, neurotrophic factors, and combinations thereof.

14. The method of claim 8 wherein the number of capsules implanted is between 1 and 5 capsules per eye.

15. A method for delivering a biologically active molecule to the eye comprising implanting a capsule intraocularly, the capsule comprising a core containing a cellular source of the biologically active molecule and a surrounding biocompatible jacket, the jacket permitting diffusion of the biologically active molecule into the eye wherein a second biologically active molecule or peptide is co-delivered from the capsule to the eye.

16. A method for delivery of biologically active molecules to an eye comprising:

implanting a first capsule intraocularly, the first capsule comprising a core containing a cellular source of a first biologically active molecule and a surrounding biocompatible jacket, the jacket permitting difffusion of the first biologically active molecule into the eye;

implanting a second capsule periocularly, the second capsule comprising a core containing a cellular source of a second biologically active molecule and a surrounding biocompatible, immunoisolatory jacket, the jacket permitting diffusion of the second biologically active molecule into the eye.

17. The method of claim 16 wherein the first capsule is implanted in the vitreous and the second capsule is implanted in the sub-Tenon'"'"'s space.

18. A method for treating ophthalmic disorders in a patient suffering therefrom, comprising:

implanting into an eye of the patient a biocompatible capsule, the capsule comprising

(a) a core comprising a cellular source of a biologically active molecule, and

(b) a jacket surrounding said core, the jacket comprising a biocompatible material that permits diffusion of the biologically active molecule to the eye in a therapeutically effective amount,

wherein the dosage of the biologically active molecule that diffuses into the eye is between 50 pg and 1000 ng per eye per patient per day.

19. The method of claim 18 wherein the biologically active molecule is selected from the group consisting of anti-angiogenic factors, neurotrophic factors, growth factors, antibodies and antibody fragments, neurotransmitters, hormones, enzymes, cytokines, and lymphokines.

20. The method of claim 18 wherein the biologically active molecule is selected from the group consisting of anti-angiogenic factors, anti-inflammatory factors, neurotrophic factors, and combinations thereof.

21. The method of claim 18 wherein the ophthalmic disorder is selected from the group consisting of angiogenic disorders, inflammatory disorders, degenerative disorders, and combinations thereof.

22. The method of claim 18 wherein the ophthalmic disorder is selected from the group consisting of uveitis, retinitis pigmentosa, age-related macular degeneration, and diabetic retinopathy.

23. The method of claim 18 wherein the biologically active molecule is selected from the group consisting of BDNF, TGF-β

, GDNF, NGF, CNTF, bFGF, aFGF, IL-1β

, IL-10, IFN-β

, IFN-α and

VEGF inhibitors.

24. The method of claim 18 wherein the capsule is immunoisolatory.

25. A method for treating ophthalmic disorders in a patient suffering therefrom, comprising:

implanting into an eye a biocompatible capsule, the capsule comprising;

(a) a core comprising a cellular source of a biologically active molecule, and

(b) a jacket surrounding said core, the jacket comprising a biocompatible material that permits diffusion of the biologically active molecule to the eye in a therapeutically effective amount, wherein a second biologically active molecule is co-delivered to the eye.

26. A device for delivery of a biologically active molecule to the eye comprising a capsule, the capsule comprising:

a core comprising encapsulated cells that produce a biologically active molecule,

a biocompatible jacket surrounding said core, the jacket permitting diffusion of the biologically active molecule into the eye,

the capsule configured as a hollow fiber, with an outer diameter of less than or equal to 1 mm, and a length between 0.4 and 1.5 cm, wherein the dosage of the biologically active molecule that diffuses into the eye is between 50 pg and 1000 ng per eye per patient per day.

28. The device of claims 26 or 27 wherein the capsule further comprises a tether adapted for securing the capsule to an ocular structure.

27. A device for delivery of a biologically active molecule to the eye comprising a capsule, the capsule comprising:

a core comprising encapsulated cells that produce a biologically active molecule,

a biocompatible jacket surrounding said core, the jacket permitting diffusion of the biologically active molecule into the eye,

the capsule configured as a flat sheet having a surface area less than or equal to 25 mm², wherein the dosage of the biologically active molecule that diffuses into the eye is between 50 pg and 1000 ng per eye per patient per day.

29. An encapsulated cell system for periocular delivery of a biologically active molecule to the eye comprising:

at least one capsule, each capsule comprising a core containing a cellular source of a biologically active molecule and a surrounding biocompatible jacket, the jacket permitting diffusion of the biologically active molecule into the eye, the encapsulated cell system delivering 50 pg to 1000 ng periocularly per eye per patient per day of the biologically active molecule.

30. The system of claim 29 wherein the jacket comprises a permselective, immunoisolatory membrane.

31. The system of claim 29 wherein the jacket comprises a microporous membrane.

32. The system of claim 29 wherein the capsule is implanted in the sub-Tenon'"'"'s space.

33. The system of claim 29 wherein the capsule is configured as a hollow fiber or a flat sheet.

34. The system of claim 29 wherein the biologically active molecule is selected from the group consisting of anti-angiogenic factors, neurotrophic factors, growth factors, antibodies and antibody fragments, neurotransmitters, hormones, enzymes, cytokines, and lymphokines.

36. The system of claim 29 wherein the number of capsules implanted is between 1 and 5 capsules per eye.

35. The system of claim w wherein the biologically active molecule is selected from the group consisting of anti-angiogenic factors, anti-inflammatory factors, neurotrophic factors, and combinations thereof.

37. An encapsulated cell system for periocular delivery of a biologically active molecule to the eye comprising:

at least one capsule, each capsule comprising a core containing a cellular source of a biologically active molecule and a surrounding biocompatible jacket, the jacket permitting diffusion of the biologically active molecule into the eye, the encapsulated cell system delivering 50 pg to 1000 ng periocularly per eye per patient per day of the biologically active molecule, wherein a second biologically active molecule or peptide is co-delivered from the capsule to the eye.

38. The system of claim 37 wherein the dosage of the second biologically active molecule or peptide delivered is between 50 pg to 1000 ng per eye per patient per day.

39. An encapsulated cell system for intraocular delivery of a biologically active molecule to the eye comprising:

at least one capsule, each capsule comprising a core containing a cellular source of a biologically active molecule and a surrounding biocompatible jacket, the jacket permitting diffusion of the biologically active molecule into the eye, the encapsulated cell system delivering 50 pg to 500 ng intraocularly per eye per patient per day of the biologically active molecule.

40. The system of claim 39 wherein the jacket comprises a permselective, immunoisolatory membrane.

41. The system of claim 39 wherein the jacket comprises a microporous membrane.

42. The system of claim 39 wherein the capsule is implanted in the vitreous.

43. The system of claim 39 wherein the capsule is implanted in the anterior chamber.

44. The system of claim 39 wherein the capsule is implanted in the posterior chamber.

45. The system of claim 39 wherein the capsule is configured as a hollow fiber or a flat sheet.

46. The system of claim 39 wherein the biologically active molecule is selected from the group consisting of anti-angiogenic factors, neurotrophic factors, growth factors, antibodies and antibody fragments, neurotransmitters, hormones, enzymes, cytokines, and lymphokines.

47. The system of claim 39 wherein the biologically active molecule is selected from the group consisting of anti-angiogenic factors, anti-inflammatory factors, neurotrophic factors, and combinations thereof.

48. The system of claim 39 wherein the number of capsules implanted is between 1 to 5 capsules per eye.

49. The system of claim 39 wherein a second biologically active molecule or peptide is co-delivered from the capsule to the eye.

50. The system of claim 49 wherein the dosage of the second biologically active molecule or peptide delivered is between 50 pg to 500 ng per eye per patient per day.