Methods and devices for the treatment of ocular diseases in human subjects

• US 9,572,800 B2
• Filed: 03/31/2016
• Issued: 02/21/2017
• Est. Priority Date: 11/08/2012
• Status: Active Grant

• Current Assignee: Clearside Biomedical, Inc.
• Original Assignee: Clearside Biomedical, Inc.
• Inventors: Kissner, Jennifer, Zarnitsyn, Vladimir, Patel, Samirkumar, White, Daniel, Noronha, Glenn, Burke, Brian
• Primary Examiner(s): Sasan, Aradhana
• Application Number:
  US15/086,485
• Publication Number:
  US 20160213662A1
• Time in Patent Office: 327 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• 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 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• 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: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/16 Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/10 for accommodation disorders, e.g. myopia
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/20 : for DNA viruses
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/22 : against growth factors ; against growth regulators

Abstract

Methods and devices are provided for targeted non-surgical administration of a drug formulation to the suprachoroidal space (SCS) of the eye of a human subject for the treatment of a posterior ocular disorder or a choroidal malady. In one embodiment, the method comprises inserting a hollow microneedle into the eye at an insertion site and infusing a drug formulation through the inserted microneedle and into the suprachoroidal space of the eye, wherein the infused drug formulation flows within the suprachoroidal space away from the insertion site during the infusion. In one embodiment, the fluid drug formulation comprises drug nanoparticles or microparticles.

Claims

1. A method of treating a posterior ocular disorder in a human subject in need thereof, the method comprising,

non-surgically administering an effective amount of a drug formulation comprising axitinib to the suprachoroidal space (SCS) of the eye of the human subject in need of treatment of the posterior ocular disorder,

wherein upon administration, the drug formulation is substantially localized to the posterior segment of the eye.

2. The method of claim 1, wherein the posterior ocular disorder is a choroidal malady, macular degeneration, macular edema, branch retinal vein occlusion, central retinal vein occlusion, retinopathy, diabetic retinopathy, retinal detachment, ocular neovascularization, eye cancer, or glaucoma.

3. The method of claim 2, wherein the choroidal malady is choroidal neovascularization, subfoveal choroidal neovascularization, polypoidal choroidal vasculopathy, choroidal sclerosis, central sirrus choroidopathy, or multi-focal choroidopathy.

4. The method of claim 2, wherein the macular degeneration is age-related macular degeneration, neovascular age-related macular degeneration, or subfoveal neovascular age related macular degeneration.

5. The method of claim 1, wherein an effective amount of axitinib sufficient to elicit a therapeutic response when administered to the SCS is less than an effective amount of axitinib sufficient to elicit a therapeutic response when administered intravitreally, intracamerally, topically, parenterally or orally.

6. The method of claim 5, wherein a dosage of axitinib sufficient to elicit a therapeutic response when administered to the SCS is 50% or less of a dosage of axitinib sufficient to elicit a therapeutic response when administered intravitreally, intracamerally, topically, parenterally or orally.

7. The method of claim 1, wherein the retention of axitinib in the posterior segment of the eye is greater than the retention of axitinib in the posterior segment of the eye when axitinib is administered intravitreally, intracamerally, topically, parenterally or orally.

8. The method of claim 1, wherein an intraocular C_max of axitinib is greater than an intraocular C_max of axitinib when axitinib is administered intravitreally, intracamerally, topically, parenterally or orally.

9. The method of claim 1, wherein the systemic exposure of axitinib is less than the systemic exposure of axitinib when axitinib is administered intravitreally, intracamerally, topically, parenterally or orally.

10. The method of claim 1, wherein the non-surgically administering includes conveying the effective amount of the drug formulation to the SCS via a microneedle having a length of from about 500 μ

m to about 1500 μ

m.

11. The method of claim 1, wherein the drug formulation comprises a suspension of microparticles or nanoparticles.

12. The method of claim 11, wherein the microparticles have a D₅₀ of 2 μ

m or less.

13. The method of claim 1, wherein the intraocular pressure of the eye of the subject varies by no more than about 10% during the administration of the drug formulation.