# US 12,599,609 B2 · Methods of treating fuchs endothelial corneal dystrophy after descemetorhexis

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- Number: US 12,599,609 B2
- Document ID: US12599609B2
- Status: Granted
- Kind: B2
- Application number: 18/270,728
- Filed: 2022-01-20
- Published: 2024-03-14
- Granted: 2026-04-14
- Earliest claimed: 2021-01-21
- Assignees: Kowa Company, Ltd.
- Applicants: Kowa Company, Ltd.
- Inventors: Gary Gordon; Kazuhito Suehira
- Web page: https://patentgrep.com/patent/US12599609B2

## CPC

- A61K 9/0048: {Eye, e.g. artificial tears}
- A61K 31/551: having two nitrogen atoms, e.g. dilazep
- A61K 31/4709: Non-condensed quinolines and containing further heterocyclic rings
- A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
- A61K 47/02: Inorganic compounds
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61P 27/02: Ophthalmic agents
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Methods for treating Fuchs endothelial corneal dystrophy (“FECD”), and medications that promote healing in FECD patients following descemetorhexis.

## Claims

### Claim 1

A method of treating Fuchs Endothelial Corneal Dystrophy (“FECD”) affecting the Descemet membrane of a patient's cornea, in a patient in need thereof, comprising:
a) removing a central portion of the Descemet membrane from the patient's eye;
b) topically administering to the patient's eye a therapeutically effective amount of ripasudil or a pharmaceutically acceptable salt thereof, from 2 to 4 times per day, for from 8-12 weeks; and
c) tapering the therapeutically effective amount to zero over approximately two weeks.

### Claim 2

A method of treating Fuchs Endothelial Corneal Dystrophy (“FECD”) affecting the Descemet membrane of a patient's cornea, comprising:
a) removing a central portion of the Descemet membrane from the patient's eye; and
b) topically administering to the patient's eye a therapeutically effective amount of ripasudil or a pharmaceutically acceptable salt thereof for from 8 to 12 weeks;
c) tapering the therapeutically effective amount to zero over approximately two weeks.

### Claim 3 (depends on 1)

The method of claim 1, wherein the patient has a central corneal thickness less than 670 μm.

### Claim 4 (depends on 1)

The method of claim 1, wherein the patient has a peripheral endothelial cell density less than 1000 cells per mm2.

### Claim 5 (depends on 1)

The method of claim 1, wherein the ripasudil or pharmaceutically acceptable salt thereof is administered in a preservative-free liquid formulation.

### Claim 6 (depends on 1)

The method of claim 1, wherein the ripasudil or a pharmaceutically acceptable salt thereof is administered 4 times per day.

### Claim 7 (depends on 1)

The method of claim 1, wherein the ripasudil or pharmaceutically acceptable salt thereof is administered for approximately 12 weeks.

### Claim 8 (depends on 1)

The method of claim 1, wherein the ripasudil or pharmaceutically acceptable salt thereof is administered as a formulation comprising about 4 mg/mL ripasudil hydrochloride based on the weight of the free base and excluding any hydration.

### Claim 9 (depends on 1)

The method of claim 1, wherein the ripasudil or pharmaceutically acceptable salt thereof is administered as a formulation comprising glycerin, sodium dihydrogen phosphate and sodium hydroxide at a pH of from about 5 to about 7.

### Claim 10 (depends on 1)

The method of claim 1, wherein the ripasudil or pharmaceutically acceptable salt thereof is first administered after step (a), and no later than 24 hours after step (a).

### Claim 11 (depends on 1)

The method of claim 1, wherein step (a) comprises removing from 4.5 to 5.5 mm of the central portion of the Descemet membrane from the patient's eye.

### Claim 12 (depends on 1)

The method of claim 1, wherein the treatment comprises increasing visual acuity in the treated eye.

### Claim 13 (depends on 1)

The method of claim 1, wherein the therapeutically effective amount of ripasudil or a pharmaceutically acceptable salt thereof is administered as a preservative-free liquid solution of ripasudil hydrochloride comprising:
a) from 0.3% (w/v) to 0.5% (w/v) ripasudil hydrochloride, based on the weight of the free base of ripasudil excluding any waters of hydration;
b) an optional pH buffer;
c) from 1.5% (w/v) to 2.0% (w/v) glycerol;
d) sodium hydroxide q.s. to a pH of from 4 to 7.5; and
e) purified water q.s. to 100%.

### Claim 14 (depends on 13)

The method of claim 13 wherein the solution comprises from 0.35% (w/v) to 0.45% (w/v) sodium dihydrogen phosphate, excluding any waters of hydration.

### Claim 15 (depends on 13)

The method of claim 13 wherein the solution comprises:
a) approximately 0.4% (w/v) ripasudil hydrochloride, based on the weight of the free base of ripasudil excluding any waters of hydration;
b) approximately 0.4% (w/v) sodium dihydrogen phosphate, excluding any waters of hydration;
c) approximately 1.77% (w/v) glycerol;
d) sodium hydroxide q.s. to a pH of from 5 to 7; and
e) purified water q.s. to 100%.

### Claim 16 (depends on 13)

The method of claim 13, wherein the solution comprises:
a) approximately 0.49 g/100 mL ripasudil hydrochloride dihydrate; and/or
b) approximately 0.52 g/100 mL sodium dihydrogen phosphate dihydrate.

### Claim 17 (depends on 13)

The method of claim 13, wherein the solution lacks any preservatives, anti-oxidants, or chelating agents.

### Claim 18 (depends on 13)

The method of claim 13, wherein the solution lacks benzalkonium chloride.

### Claim 19 (depends on 1)

The method of claim 1, wherein the ripasudil or a pharmaceutically acceptable salt thereof is administered 4 times per day for approximately 12 weeks.

### Claim 20 (depends on 1)

The method of claim 1, wherein the ripasudil or a pharmaceutically acceptable salt thereof is administered 4 times per day for approximately 12 weeks in a formulation comprising about 4 mg/mL ripasudil hydrochloride based on the weight of the free base and excluding any hydration.

### Claim 21

A method of treating Fuchs Endothelial Corneal Dystrophy (“FECD”) affecting the Descemet membrane of a patient's cornea, comprising:
a) removing a central portion of the Descemet membrane from the patient's eye; and
b) topically administering to the patient's eye a therapeutically effective amount of ripasudil hydrochloride, in a concentration of about 0.4 mg/mL based on the weight of the free base excluding any hydration, in the absence of any preservatives, four times per day, for from 8 to 12 weeks;
c) tapering the therapeutically effective amount to zero over approximately two weeks.

### Claim 22 (depends on 21)

The method of claim 21, comprising administering the therapeutically effective amount of ripasudil hydrochloride for 12 weeks.

### Claim 23 (depends on 21)

The method of claim 21, wherein the patient has a central corneal thickness less than 670 μm.

### Claim 24 (depends on 21)

The method of claim 21, wherein the patient has a peripheral endothelial cell density less than 1000 cells per mm2.

### Claim 25 (depends on 22)

The method of claim 22, wherein the patient has a central corneal thickness less than 670 μm.

### Claim 26 (depends on 22)

The method of claim 22, wherein the patient has a peripheral endothelial cell density less than 1000 cells per mm2.