# US 10,307,386 B2 · Methods of treating non-alcoholic steatohepatitis (NASH) using cysteamine products

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- Number: US 10,307,386 B2
- Document ID: US10307386B2
- Status: Granted
- Kind: B2
- Application number: 15/362,782
- Filed: 2016-11-28
- Published: 2017-10-26
- Granted: 2019-06-04
- Earliest claimed: 2007-11-30
- Assignees: The Regents of the University of California
- Applicants: The Regents of the University of California
- Inventors: Ranjan Dohil; Jerry Schneider
- Web page: https://patentgrep.com/patent/US10307386B2

## CPC

- A61K 31/145: having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2) (isothiourea A61K31/155)
- A61K 9/4891: {Coated capsules; Multilayered drug free capsule shells (with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004)}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/06: Antihyperlipidemics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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 disclosure relates, in general, to treatment of fatty liver disorders comprising administering compositions comprising cysteamine products. The disclosure provides administration of enterically coated cysteamine compositions to treat fatty liver disorders, such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

## Claims

### Claim 1

A method of treating a patient suffering from fatty liver disease comprising administering a therapeutically effective amount of a composition comprising cysteamine or a pharmaceutically acceptable salt thereof, or cystamine or a pharmaceutically acceptable salt thereof, wherein the composition is administered at a total daily dose of 10-40 mg/kg.

### Claim 2 (depends on 1)

The method of claim 1, wherein the fatty liver disease is selected from the group consisting of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), fatty liver disease resulting from hepatitis, fatty liver disease resulting from obesity, fatty liver disease resulting from diabetes, fatty liver disease resulting from insulin resistance, fatty liver disease resulting from hypertriglyceridemia, Abetalipoproteinemia, glycogen storage diseases, Weber-Christian disease, Wolmans disease, acute fatty liver of pregnancy, and lipodystrophy.

### Claim 3 (depends on 1)

The method of claim 1, wherein the composition is administered at a frequency of 4 or less times per day.

### Claim 4 (depends on 3)

The method of claim 3, wherein the composition is administered two times per day.

### Claim 5 (depends on 1)

The method of claim 1, wherein the composition is a delayed or controlled release dosage form that provides increased delivery of the cysteamine or a pharmaceutically acceptable salt thereof, or cystamine or a pharmaceutically acceptable salt thereof to the small intestine.

### Claim 6 (depends on 5)

The method of claim 5, wherein the delayed or controlled release dosage form comprises an enteric coating that releases the cysteamine product when the composition reaches the small intestine or a region of the gastrointestinal tract of a subject in which the pH is greater than about pH 4.5.

### Claim 7 (depends on 6)

The method of claim 6, wherein the composition comprises a coating selected from the group consisting of polymerized gelatin, shellac, methacrylic acid copolymer type C NF, cellulose butyrate phthalate, cellulose hydrogen phthalate, cellulose proprionate phthalate, polyvinyl acetate phthalate (PVAP), cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT), hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate, dioxypropyl methylcellulose succinate, carboxymethyl ethylcellulose (CMEC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), and acrylic acid polymers and copolymers, typically formed from methyl acrylate, ethyl acrylate, methyl methacrylate and/or ethyl methacrylate with copolymers of acrylic and methacrylic acid esters.

### Claim 8 (depends on 1)

The method of claim 1, wherein the composition is administered orally.

### Claim 9 (depends on 1)

The method of claim 1, wherein the composition is administered parenterally.

### Claim 10 (depends on 1)

The method of claim 1, wherein the administering results in improvement in liver fibrosis compared to levels before administration of the cysteamine product.

### Claim 11 (depends on 1)

The method of claim 1, wherein the administering results in a reduction in fat content of liver.

### Claim 12 (depends on 1)

The method of claim 1, wherein the administering results in a reduction in the incidence of or progression of cirrhosis.

### Claim 13 (depends on 1)

The method of claim 1, wherein the administering results in a reduction in the incidence of hepatocellular carcinoma.

### Claim 14 (depends on 1)

The method of claim 1, wherein the administering results in a decrease in hepatic aminotransferase levels compared to levels before administration.

### Claim 15 (depends on 1)

The method of claim 1, wherein the administering results in a reduction in hepatic transaminase of between approximately 10% to 40% compared to levels before treatment.

### Claim 16 (depends on 1)

The method of claim 1, wherein the administering results in a reduction in alanine aminotransferase levels in a treated patient to approximately 30%, 20% or 10% above normal ALT levels, or at normal ALT levels (≥40 iu/L).

### Claim 17 (depends on 1)

The method of claim 1, wherein the administering results in a reduction in aspartate aminotransferase levels in a treated patient to approximately 30%, 20% or 10% above normal AST levels or to normal AST levels.

### Claim 18 (depends on 1)

The method of claim 1, wherein the administering results in a reduction in serum ferritin levels compared to levels before treatment.

### Claim 19 (depends on 1)

The method of claim 1, wherein the composition is administered with a second agent useful to treat fatty liver disease.

### Claim 20 (depends on 1)

The method of claim 1, wherein the patient is a child or adolescent.