INJECTABLE SUSTAINED RELEASE INTRAOCULAR DEVICE

1 . A method for treating an eye disease in a subject, comprising administering to the subject a sustained-release drug delivery device comprising:

a shell; and

a kinase inhibitor disposed in the shell,

wherein the device is shaped and sized for injection through a needle or cannula having a size from about 30 gauge to about 22 gauge.

2 . (canceled)

3 . The method of claim 1 , wherein the kinase inhibitor is a VEGF receptor kinase inhibitor, PDGF receptor kinase inhibitor, or inflammasome inhibitor.

4 . The method of claim 1 , wherein the kinase inhibitor is apatinib, axitinib, cabozantinib, cediranib, crenolanib, foretinib, lenvatinib, linifanib, masitinib, motesanib, nintedanib, pazopanib, pegaptanib, regorafenib, semaxanib, sorafenib, sunitinib, tivozanib, toceranib, vandetanib, or vatalanib.

5 . The method of claim 4 , wherein the kinase inhibitor is sorafenib or pazopanib.

6 . The method of claim 1 , wherein the kinase inhibitor is bafetinib, bosutinib, dasatinib, imatinib, nilotinib, ponatinib, radotinib, or SU6656.

7 . The method of claim 6 , wherein the kinase inhibitor is dasatinib.

8 . The method of claim 1 , wherein the kinase inhibitor is admixed with a polymeric matrix.

9 . The method of claim 8 , wherein the polymeric matrix comprises one or more polymers selected from poly(vinyl acetate), poly(caprolactone), polyethylene glycol, poly(dl-lactide-co-glycolide), ethylene vinyl acetate polymer, polyvinyl alcohol, poly(lactic acid), poly(glycolic acid), polyalkyl cyanoacrylate, polyurethane, and nylon, and a copolymer thereof.

10 . The method of claim 9 , wherein the polymeric matrix comprises polyvinyl alcohol (PVA).

11 . The method of claim 1 , wherein the shell comprises a tube having first and second ends, and the kinase inhibitor is disposed in the tube.

12 . The method of claim 11 , wherein the tube comprises one or more polymers selected from polyimide, poly(vinyl acetate), poly(caprolactone), polyethylene glycol, poly(dl-lactide-co-glycolide), ethylene vinyl acetate polymer, polyvinyl alcohol, poly(lactic acid), poly(glycolic acid), polyalkyl cyanoacrylate, polyurethane, polyimide, and nylon, and a copolymer thereof.

13 - 15 . (canceled)

16 . The method of claim 11 , wherein the tube is impermeable to the kinase inhibitor.

17 . The method of claim 11 , wherein:

the shell further comprises a first member positioned at the first end of the tube and a second member positioned at the second end of the tube; and

the first member is permeable to the passage of the kinase inhibitor.

18 - 19 . (canceled)

20 . The method of claim 17 , wherein the first member or the second member comprises one or more polymers selected from poly(vinyl acetate), poly(caprolactone), polyethylene glycol, poly(dl-lactide-co-glycolide), ethylene vinyl acetate polymer, polyvinyl alcohol, poly(lactic acid), poly(glycolic acid), polyalkyl cyanoacrylate, polyurethane, and nylon, and a copolymer thereof.

21 . The method of claim 20 , wherein the first member or the second member comprises polyvinyl alcohol (PVA).

22 . The method of claim 17 , wherein the second member is permeable to the passage of the kinase inhibitor.

23 - 24 . (canceled)

25 . The method of claim 17 , wherein the second member is impermeable to the passage of the kinase inhibitor.

26 . The method of claim 25 , wherein the second member comprises silicone.

27 . The method of claim 11 , wherein the tube has a length of between 1 mm and 4 mm.

28 . The method of claim 11 , wherein the tube has a diameter of between 0.2 mm and 0.5 mm.

29 . The method of claim 1 , wherein the device is bioerodible.

30 - 31 . (canceled)

32 . The method of claim 1 , wherein administering the device comprises inserting the device into an eye of the subject.

33 . (canceled)

34 . The method of claim 32 , wherein administering the device comprises injecting the device into the vitreous of the eye.

35 . (canceled)

36 . The method of claim 1 , wherein the device is configured to maintain a therapeutically effective concentration of the kinase inhibitor in the eye for at least 1 week, at least 1 month, or at least 6 months.

37 - 38 . (canceled)

39 . The method of claim 36 , wherein the device is configured to maintain a therapeutically effective concentration of the kinase inhibitor in the eye for a period of time between 2 weeks and 4 years, between 2 months and 3 years, between 6 months and 30 months, between 1 month and 12 months, or between 4 months and 12 months.

40 - 43 . (canceled)

44 . The method of claim 1 , wherein the device is configured to release the kinase inhibitor at a rate of less than 10 μg per day.

45 . The method of claim 44 , wherein the device is configured to release the kinase inhibitor at a rate of about 0.1 μg per day to about 10 μg per day or a rate of about 0.4 μg per day to about 4 μs per day.

46 . (canceled)

47 . The method of claim 1 , wherein the subject is selected from rodents, lagomorphs, ovines, porcines, canines, felines, equines, bovines, and primates.

48 . The method of claim 47 , wherein the subject is a human.

49 . The method of claim 1 , wherein the subject has age-related macular degeneration, dry macular degeneration, or wet macular degeneration.

50 - 54 . (canceled)

55 . The method of claim 1 , wherein the subject has geographic atrophy, the subject is at risk of developing geographic atrophy, the subject has vision loss; the subject is at risk of developing vision loss, or the subject has ischemic or non-ischemic retinal vein occlusion.

56 - 59 . (canceled)

60 . A sustained-release drug delivery device for insertion into the vitreous of an eye, comprising:

a shell; and

a kinase inhibitor disposed in the shell;

wherein:

the device is shaped and sized for injection through a needle or cannula having a size from about 30 gauge to about 22 gauge;

the device is configured to release the kinase inhibitor at a rate of less than 10 μg per day; and

the device is configured to maintain a therapeutically effective concentration of the kinase inhibitor in the eye for a period of time between 2 weeks and 4 years.

61 . The device of claim 60 , wherein the kinase inhibitor is apatinib, axitinib, cabozantinib, cediranib, crenolanib, foretinib, lenvatinib, linifanib, masitinib, motesanib, nintedanib, pazopanib, pegaptanib, regorafenib, semaxanib, sorafenib, sunitinib, tivozanib, toceranib, vandetanib, or vatalanib.

62 . The device of claim 61 , wherein the kinase inhibitor is sorafenib.

63 . The device of claim 61 , wherein the kinase inhibitor is pazopanib.

64 . The device of claim 60 , wherein the kinase inhibitor is bafetinib, bosutinib, dasatinib, imatinib, nilotinib, ponatinib, radotinib, or SU6656.

65 . The device of claim 64 , wherein the kinase inhibitor is dasatinib.

66 . A method for treating an eye disease in a human subject, comprising administering to the subject a sustained-release drug delivery device comprising:

a shell; and

a kinase inhibitor disposed in the shell;

wherein:

the device is shaped and sized for injection through a needle or cannula having a size from about 30 gauge to about 22 gauge;

the device is configured to release the kinase inhibitor at a rate of less than 10 μg per day; and

the device is configured to maintain a therapeutically effective concentration of the kinase inhibitor in the eye for a period of time between 2 weeks and 4 years.

67 . The method of claim 66 , wherein the kinase inhibitor is apatinib, axitinib, cabozantinib, cediranib, crenolanib, foretinib, lenvatinib, linifanib, masitinib, motesanib, nintedanib, pazopanib, pegaptanib, regorafenib, semaxanib, sorafenib, sunitinib, tivozanib, toceranib, vandetanib, or vatalanib.

68 . The method of claim 67 , wherein the kinase inhibitor is sorafenib.

69 . The method of claim 67 , wherein the kinase inhibitor is pazopanib.

70 . The method of claim 66 , wherein the kinase inhibitor is bafetinib, bosutinib, dasatinib, imatinib, nilotinib, ponatinib, radotinib, or SU6656.

71 . The method of claim 70 , wherein the kinase inhibitor is dasatinib.