# US 11,896,710 B2 · Methods of treating eosinophilic esophagitis

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- Number: US 11,896,710 B2
- Document ID: US11896710B2
- Status: Granted
- Kind: B2
- Application number: 17/376,996
- Filed: 2021-07-15
- Published: 2021-11-11
- Granted: 2024-02-13
- Earliest claimed: 2016-08-18
- Assignees: Ellodi Pharmaceuticals, L.P.
- Applicants: Ellodi Pharmaceuticals, L.P.
- Inventors: Brian A. Meltzer; Gail M. Comer
- Web page: https://patentgrep.com/patent/US11896710B2

## CPC

- A61K 9/006: {Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays}
- A61K 31/56: Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K 31/565: not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K 31/58: containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin (digitoxin {A61K31/7048})
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- 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

The present disclosure provides methods of treating inflammation of the upper gastrointestinal tract, especially the esophagus, by administering an oral corticosteroid. In some cases, the methods include treating eosinophilic esophagitis (EoE) by administering an oral corticosteroid in an induction phase and a maintenance phase to improve peak eosinophilic counts and symptoms. In embodiments, the methods include treating EoE by administering the oral corticosteroid at nighttime and/or while the patient is lying down.

## Claims

### Claim 1

A method of topically treating an esophageal stricture in a patient in need thereof with an oral corticosteroid, comprising:
administering the oral corticosteroid while the patient is lying down or immediately prior to the patient lying down,
wherein a therapeutically effective amount of the oral corticosteroid contacts the esophageal stricture, thereby reducing the severity of the esophageal stricture.

### Claim 2 (depends on 1)

The method of claim 1, wherein the patient also has a ring.

### Claim 3 (depends on 2)

The method of claim 2, wherein the ring is a grade 2 or grade 3 ring.

### Claim 4 (depends on 3)

The method of claim 3, wherein administrating the oral corticosteroid reduces the grade of the ring by at least 1 grade.

### Claim 5 (depends on 1)

The method of claim 1, wherein the lying down is in a supine position.

### Claim 6 (depends on 1)

The method of claim 1, wherein the oral corticosteroid is administered about 30 minutes or less before target sleep time.

### Claim 7 (depends on 1)

The method of claim 1, wherein the oral corticosteroid is administered within about 5 minutes prior to the patient lying down.

### Claim 8 (depends on 1)

The method of claim 1, wherein the oral corticosteroid has a systemic bioavailability of less than or equal to about 20% of its dose.

### Claim 9 (depends on 1)

The method of claim 1, wherein the oral corticosteroid is budesonide, fluticasone, flunisolide, ciclesonide, mometasone or beclomethasone, or a pharmaceutically acceptable salt, solvent, ester, polymorph or prodrug thereof.

### Claim 10 (depends on 1)

The method of claim 1, wherein the oral corticosteroid is budesonide, fluticasone, or a pharmaceutically acceptable ester thereof.

### Claim 11 (depends on 1)

The method of claim 1, wherein the oral corticosteroid is fluticasone propionate.

### Claim 12 (depends on 1)

The method of claim 1, wherein the oral corticosteroid is formulated as a solid composition.

### Claim 13 (depends on 1)

The method of claim 1, wherein the oral corticosteroid is formulated to form a solution, suspension or gel after oral administration.

### Claim 14 (depends on 12)

The method of claim 12, wherein the solid composition is in the form of a gel, lozenge, lollipop, effervescent tablet, powder, granules or an orally disintegrating composition.

### Claim 15 (depends on 14)

The method of claim 14, wherein the orally disintegrating composition is a tablet, wafer, film, or lyophilized matrix.

### Claim 16 (depends on 13)

The method of claim 13, wherein the orally disintegrating composition is a tablet.

### Claim 17 (depends on 16)

The method of claim 16, wherein the tablet comprises:
a. the oral corticosteroid in an amount of from about 1.5 mg to about 7.5 mg;
b. a pharmaceutically acceptable carrier combined with the corticosteroid; and
c. rapidly dispersing microgranules,
wherein the orally disintegrating tablet disintegrates within 60 seconds when tested using the USP <701> method for disintegration time.

### Claim 18 (depends on 1)

The method of claim 1, wherein the oral corticosteroid provides an average maximum blood plasma concentration (Cmax) of less than or equal to about 500 pg/mL after oral administration of about 0.01 mg to about 20 mg of the oral corticosteroid.

### Claim 19 (depends on 1)

The method of claim 1, wherein the oral corticosteroid provides an average AUC0-24 of less than or equal to about 3,000 pg*h/mL after oral administration of about 0.01 mg to about 20 mg of the oral corticosteroid.

### Claim 20 (depends on 1)

The method of claim 1, wherein the patient has a Cmax of the oral corticosteroid of less than or equal to about 200 pg/mL following oral administration of about 1.5 mg to about 7.5 mg of the oral corticosteroid.

### Claim 21 (depends on 1)

The method of claim 1, wherein the oral corticosteroid is fluticasone propionate, and the patient has a Cmax within the range of about 80% to about 125% of about 15 pg/mL to about 45 pg/mL following oral administration of 6 mg fluticasone propionate or 3 mg of fluticasone propionate.

### Claim 22 (depends on 1)

The method of claim 1, wherein after 12 weeks of daily administration of the oral corticosteroid, esophageal inflammation is reduced as measured by a reduction in eosinophil count, an increase in dysphagia-free days, a reduction in episodes of dysphagia, improvement in EREFS score, EndoFLIP documentation of improved esophageal compliance, evaluation of biomarkers, a decrease in episodes of food impaction, an improvement in EEsAI scores (patient, physician, endoscopy, pathology scores), EoE-QOL-A, Visual Dysphagia Questionnaire (VDQ), Avoidance Modification and Slow Eating (AMS) scores, or histology.

### Claim 23 (depends on 1)

The method of claim 1, wherein the patient has eosinophilic esophagitis (EoE), gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD), erosive esophagitis, Barrett's esophagus, eosinophilic gastroenteritis, hypereosinophilic syndrome, corrosive chemical esophagi tis, radiation-induced esophagitis, chemotherapy-induced esophagitis, transient drug-induced esophagitis, persistent drug-induced esophagitis, Crohn's disease of the esophagus, or pseudomembranous esophagitis.

### Claim 24 (depends on 1)

The method of claim 1, wherein the patient has EoE.

### Claim 25 (depends on 2)

The method of claim 2, wherein the patient has EoE.

### Claim 26 (depends on 3)

The method of claim 3, wherein the patient has EoE.

### Claim 27 (depends on 4)

The method of claim 4, wherein the patient has EoE.

### Claim 28 (depends on 24)

The method of claim 24, wherein the corticosteroid is fluticasone propionate, and it is formulated in an orally disintegrant tablet comprising
a. from about 1.5 mg to about 7.5 mg of fluticasone propionate; and
b. a pharmaceutically acceptable carrier combined with fluticasone propionate;
wherein the orally disintegrating tablet disintegrates within 60 seconds when tested using the USP <701> method for disintegration time.

### Claim 29 (depends on 27)

The method of claim 27, wherein the corticosteroid is fluticasone propionate, and it is formulated in an orally disintegrant tablet comprising
a. from about 1.5 mg to about 7.5 mg of fluticasone propionate; and
b. a pharmaceutically acceptable carrier combined with fluticasone propionate;
wherein the orally disintegrating tablet disintegrates within 60 seconds when tested using the USP <701> method for disintegration time.