# US 9,750,708 B2 · Enterically coated cysteamine, cystamine and derivatives thereof

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- Number: US 9,750,708 B2
- Document ID: US9750708B2
- Status: Granted
- Kind: B2
- Application number: 15/220,693
- Filed: 2016-07-27
- Published: 2016-11-17
- Granted: 2017-09-05
- Earliest claimed: 2006-01-27
- 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/US9750708B2

## CPC

- A61K 31/194: having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/1605: {Excipients; Inactive ingredients}
- A61K 9/1635: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/284: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone}
- A61K 9/2846: {Poly(meth)acrylates}
- A61K 9/2866: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/2873: {Proteins, e.g. gelatin}
- A61K 9/288: {Compounds of unknown constitution, e.g. material from plants or animals (oils, fats, waxes, shellac A61K9/282)}
- A61K 9/4808: {characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release (capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084)}
- A61K 9/5005: {Wall or coating material}
- A61K 9/5026: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/5042: {Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose}
- A61K 9/5047: {Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose}
- A61K 9/5057: {Gelatin}
- A61K 9/5063: {Compounds of unknown constitution, e.g. material from plants or animals (oils, fats, waxes, shellac A61K9/5015)}
- A61K 31/13: Amines {(A61K31/04 takes precedence)}
- 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)
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 39/06: Free radical scavengers or antioxidants
- 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 provides oral cysteamine and cystamine formulations useful for treating cystinosis and neurodegenerative diseases and disorders. The formulations provide controlled release compositions that improve quality of life and reduced side-effects.

## Claims

### Claim 1

A composition comprising:
a delayed and extended release enterically coated cystamine formulation, the formulation comprising:
a core comprising cystamine and a binder; and
an enteric coating surrounding the core,
wherein the enteric coating releases the cystamine at a pH of 4.5 or greater and provides a time to Cmax of between 2-4 hours after administration.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the enteric coating is 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 3 (depends on 1)

The composition of claim 1, wherein the composition is formulated for oral administration.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the core comprises a granule.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the core comprises a tablet.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the composition comprises a dose of cystamine of about 0.5-1.0 g/m2 body surface area.

### Claim 7 (depends on 1)

The composition of claim 1, wherein the composition comprises a dose of cystamine of about 0.7-0.8 g/m2 body surface area.

### Claim 8 (depends on 1)

The composition of claim 1, wherein the cystamine is delivered to the small intestine.

### Claim 9 (depends on 1)

The composition of claim 1, wherein the cystamine is released during transit in the small intestine.

### Claim 10 (depends on 1)

The composition of claim 1, wherein the composition further comprises a stabilizer.

### Claim 11 (depends on 1)

A method of treating a subject with cystinosis comprising administering a composition of claim 1 less than 4 times per day, wherein the total daily dose of cystamine is about 1.35 g/m2 body surface area or less.

### Claim 12 (depends on 1)

A method of treating a subject with cystinosis comprising administering a composition of claim 1 at a dose of cystamine of about 0.5-1.0 g/m2 body surface area.

### Claim 13 (depends on 1)

A method of treating a subject with cystinosis comprising administering a composition of claim 1 less than 4 times per day in an amount to provide white blood cell cystine suppression with a 12 hour level below 1 nmol/½ cystine/mg protein.

### Claim 14 (depends on 1)

A method of treating a subject with cystinosis comprising administering a composition of claim 1 twice per day in an amount to provide white blood cell cystine suppression with a 12 hour level below 1 nmol/½ cystine/mg protein.

### Claim 15 (depends on 1)

A method of treating a subject with Huntington's Disease comprising administering the composition of claim 1 at a dose of about 100 mg to 1000 mg of cystamine.