METHODS AND DEVICES FOR TREATING POSTERIOR OCULAR DISORDERS

• US 20180042765A1
• Filed: 06/17/2015
• Published: 02/15/2018
• Est. Priority Date: 06/17/2014
• Status: Abandoned Application

• Current Assignee: Clearside Biomedical, Inc.
• Original Assignee: Clearside Biomedical, Inc.
• Inventors: NORONHA, Glenn, BROOKS, Christopher John, ANDINO, Rafael Victor, PATEL, Samirkumar, WHITE, Daniel
• Application Number:
  US15/319,045
• Publication Number:
  US 20180042765A1
• Time in Patent Office: Days
• CPC Class Codes: A61F 9/0008 Introducing ophthalmic products into the ocular cavity or retaining products therein putting in contact lenses A61F9/0061; introducing or retaining media in cavities of the body in general A61M31/00
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention relates to a methods and devices for treating uveitis, macular edema associated with uveitis and macular edema associated with retinal vein occlusion in a human subject in need thereof. In certain aspects, devices provided herein include a medicament container defining a lumen configured to contain a medicament, a distal end portion of the medicament container including a coupling portion configured to be removably coupled to a needle assembly, a proximal end portion of the medicament container including a flange and a longitudinal shoulder; a piston assembly including a distal end portion movably disposed within the lumen of the medicament container; and a handle coupled to a proximal end portion of the piston assembly.

Claims

1. A method of treating macular edema associated with uveitis or macular edema associated with retinal vein occlusion (RVO) in a human subject in need thereof, the method comprising,

in a dosing session, non-surgically administering an effective amount of a drug formulation comprising a first drug to the suprachoroidal space (SCS) of the eye of the human subject in need of treatment of the macular edema associated with uveitis.

2. The method of claim 1, wherein the uveitis is selected from the group consisting of infectious uveitis, noninfectious uveitis, acute uveitis, chronic uveitis, intermediate uveitis, posterior uveitis, and pan uveitis.

10. The method of claim 1, wherein the RVO is selected from the group consisting of branch retinal vein occlusion (BRVO), hemiretinal vein occlusion (HRVO), and central retinal vein occlusion (CRVO).

13. The method of claim 1, wherein the effective amount of the drug formulation is present in a volume of from about 10 μ

L to about 200 μ

L.

15. The method of claim 1, wherein the first drug comprises an anti-inflammatory drug, a non-steroid anti-inflammatory drug (NSAID), or a steroid.

16. The method of claim 15, wherein the anti-inflammatory drug is selected from mycophenolate, infliximab, nepafenac, azathioprine, cyclosphosphamide, dexamethasone, difluprednate, fluocinolone, fluorometholone, leteprednol, prednisolone acetate, prednisolone sodium phosphate, rimexolone, triamcinolone, bromfenac, diclofenac, fluibiprofen, ketorolac, adalimumab, etanercept, certolizumab, gotimumab, daclizumab, rituximab, abatacept, basiliximab, belimumab, anakinra, efalizuma, alefacept, and natalizumab.

18. The method of claim 15, wherein the anti-inflammatory drug is triamcinolone acetonide.

21. The method of claim 1, wherein the intraocular pressure of the eye of the human subject remains substantially constant about 10 minutes, about 20 minutes, about 30 minutes or about 1 hr. after a dosing session of the drug formulation has been completed.

22. The method of claim 21, wherein the intraocular pressure of the eye of the human subject varies by no more than about 10% about 10 minutes, about 20 minutes, about 30 minutes or about 1 hr. after a dosing session of the drug formulation has been completed.

23. The method of claim 1, wherein administration of the first drug to the SCS of the eye provides a decreased number of side effects, or a reduced severity of one or more side effects, as compared to the identical dosage of the first drug administered intravitreally, intracamerally, sub-tenonally, topically, parenterally or orally.

24. The method of claim 1, wherein the dosage of the first drug sufficient to elicit a therapeutic response when administered to the SCS is less than the dosage of the drug sufficient to elicit a therapeutic response when administered intravitreally, intracamerally, sub-tenonally, topically, parenterally or orally.

37. The method of claim 1, further comprising non-surgically administering a second drug to the eye of the patient.

38. The method of claim 37, wherein the second drug is present in the drug formulation.

39. The method of claim 37, wherein the second drug is present in a second drug formulation.

40. The method of claim 37, wherein the second drug is a VEGF modulator.

42. The method of claim 37, wherein the second drug is a VEGF antagonist selected from a VEGF-receptor kinase antagonist, an anti-VEGF antibody or fragment thereof, an anti-VEGF receptor antibody, an anti-VEGF aptamer, a small molecule VEGF antagonist, a thiazolidinedione, a quinoline or a designed ankyrin repeat protein (DARPin).

43. The method of claim 42, wherein the VEGF antagonist is aflibercept, ziv-aflibercept, bevacizumab, sonepcizumab, VEGF sticky trap, cabozantinib, foretinib, vandetanib, nintedanib, regorafenib, cediranib, ranibizumab, lapatinib, sunitinib, sorafenib, plitidepsin, regorafenib, verteporfin, bucillamine, axitinib, pazopanib, fluocinolone acetonide, nintedanib, AL8326, 2C3 antibody, AT001 antibody, XtendVEGF antibody, HuMax-VEGF antibody, R3 antibody, AT001/r84 antibody, HyBEV, ANG3070, APX003 antibody, APX004 antibody, ponatinib, BDM-E, VGX100 antibody, VGX200, VGX300, COSMIX, DLX903/1008 antibody, ENMD2076, INDUS815C, R84 antibody, KD019, NM3, MGCD265, MG516, MP0260, NT503, anti-DLL4/VEGF bispecific antibody, PAN90806, Palomid 529, BD0801 antibody, XV615, lucitanib, motesanib diphosphate, AAV2-sFLT01, soluble Flt1 receptor, AV-951, Volasertib, CEP11981, KH903, lenvatinib, lenvatinib mesylate, terameprocol, PF00337210, PRS050, SP01, carboxyamidotriazole orotate, hydroxychloroquine, linifanib, ALG1001, AGN150998, MP0112, AMG386, ponatinib, PD173074, AVA101, BMS690514, KH902, golvatinib (E7050), dovitinib, dovitinib lactate (TKI258, CHIR258), ORA101, ORA102, Axitinib (Inlyta, AG013736), PTC299, pegaptanib sodium, troponin, EG3306, vatalanib, Bmab100, GSK2136773, Anti-VEGFR Alterase, Avila, CEP7055, CLT009, ESBA903, GW654652, HMPL010, GEM220, HYB676, JNJ17029259, TAK593, Nova21012, Nova21013, CP564959, smart Anti-VEGF antibody, AG028262, AG13958, CVX241, SU14813, PRS055, PG501, PG545, PTI101, TG100948, ICS283, XL647, enzastaurin hydrochloride, BC194, COT601M06.1, COT604M06.2, MabionVEGF, Apatinib, RAF265 (CHIR-265), Motesanib Diphosphate (AMG-706), Lenvatinib (E7080), TSU-68 (SU6668, Orantinib), Brivanib (BMS-540215), MGCD-265, AEE788 (NVP-AEE788), ENMD-2076, OSI-930, CYC116, Ki8751, Telatinib, KRN 633, SAR131675, Dovitinib (TKI-258) Dilactic Acid, Apatinib, BMS-794833, Brivanib Alaninate (BMS-582664), Golvatinib (E7050), Semaxanib (SU5416), ZM 323881 HC1, Cabozantinib malate (XL184), ZM 306416, AL3818, AL8326, 2C3 antibody, AT001 antibody, HyBEV, bevacizumab (Avastin®

), ANG3070, APX003 antibody, APX004 antibody, ponatinib (AP24534), BDM-E, VGX100 antibody (VGX100 CIRCADIAN), VGX200 (c-fos induced growth factor monoclonal antibody), VGX300, COSMIX, DLX903/1008 antibody, ENMD2076, sunitinib malate (Sutent®

), INDUS815C, R84 antibody, KDO19, NM3, allogenic mesenchymal precursor cells combined with an anti-VEGF antagonist (e.g., anti-VEGF antibody), MGCD265, MG516, VEGF-Receptor kinase inhibitor, MP0260, NT503, anti-DLL4/VEGF bispecific antibody, PAN90806, Palomid 529, BD0801 antibody, XV615, lucitanib (AL3810, E3810), AMG706 (motesanib diphosphate), AAV2-sFLT01, soluble Flt1 receptor, cediranib (Recentin™

), AV-951, tivozanib (KRN-951), regorafenib (Stivarga®

), volasertib (BI6727), CEP11981, KH903, lenvatinib (E7080), lenvatinib mesylate, terameprocol (EM1421), ranibizumab (Lucentis®

), pazopanib hydrochloride (Votrient™

), PF00337210, PRS050, SP01 (curcumin), carboxyamidotriazole orotate, hydroxychloroquine, linifanib (ABT869, RG3635), fluocinolone acetonide (Iluvien®

), ALG1001, AGN150998, DARPin MP0112, AMG386, ponatinib (AP24534), AVA101, nintedanib (VargatefrM), BMS690514, KH902, golvatinib (E7050), everolimus (Afinitor®

), dovitinib lactate (TKI258, CHIR258), ORA101, ORA102, axitinib (Inlyta®

, AG013736), plitidepsin (Aplidin®

), PTC299, aflibercept (Zaltrap®

, Eylea®

), pegaptanib sodium (Macugen™

, LI900015), verteporfin (Visudyne®

), bucillamine (Rimatil, Lamin, Brimani, Lamit, Boomiq), R3 antibody, AT001/r84 antibody, troponin (BLS0597), EG3306, vatalanib (PTK787), Bmab100, GSK2136773, Anti-VEGFR Alterase, Avila, CEP7055, CLT009, ESBA903, HuMax-VEGF antibody, GW654652, HMPL010, GEM220, HYB676, JNJ17029259, TAK593, XtendVEGF antibody, Nova21012, Nova21013, CP564959, Smart Anti-VEGF antibody, AG028262, AG13958, CVX241, SU14813, PRS055, PG501, PG545, PTI101, TG100948, ICS283, XL647, enzastaurin hydrochloride (LY317615), BC194, quinolines, COT601M06.1, COT604M06.2, MabionVEGF, SIR-Spheres coupled to anti-VEGF or VEGF-R antibody, Apatinib (YN968D1), or AL3818.

47. The method of claim 37, wherein the second drug is administered to the suprachoroidal space (SCS) of the eye of the subject.

48. The method of claim 37, wherein the second drug is administered intravitreally in a second drug formulation.

54. The method of claim 1, wherein subsequent to a dosing session, the patient substantially maintains his or her vision, as measured by losing fewer than 15 letters in a best-corrected visual acuity (BCVA) measurement, compared to the patient'"'"'s BCVA measurement prior to the dosing session, and the loss of fewer than 15 letters is measured at least about 1 week, at least about 2 weeks, at least about 1 month, at least about 2 months, at least about 3 months or at least about 4 months after the at least one dosing session.

55. The method of claim 1, wherein the patient experiences an improvement in vision subsequent to a dosing session, as measured by gaining ≧

5 letters, ≧

10 letters or ≧

15 letters in a best-corrected visual acuity (BCVA) measurement, compared to the patient'"'"'s BCVA prior to the dosing session, and the gain of letters in the BCVA is measured at least about 1 week, at least about 2 weeks, at least about 1 month, at least about 2 months, at least about 3 months or at least about 4 months subsequent to the at least one dosing session.

57. The method of claim lany onc of claims 1, wherein subsequent to the at least one dosing session in the eye in need of treatment, the patient experiences a decrease in retinal thickness in the treated eye, as measured by optical coherence tomography (OCT) compared to the patient'"'"'s retinal thickness in the eye in need of treatment prior to the at least one dosing session, and the decrease in retinal thickness is measured at least about 1 week, at least about 2 weeks, at least about 1 month, at least about 2 months, at least about 3 months or at least about 4 months after the at least one dosing session.

58. The method of claim 57, wherein the retinal thickness is central subfield thickness (CST).

59. The method of claim 57, wherein the decrease in retinal thickness is ≧

25 μ

m, ≧

50 μ

m, ≧

75 μ

m or ≧

100.

60. The method of claim 57, wherein the decrease in retinal thickness is ≧

5%, ≧

10% or ≧

25%.

103. The method of claim 1, wherein upon administration, the drug formulation flows away from the insertion site and is substantially localized to the posterior segment of the eye.

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