# US 2024/0189271 A1 · Pharmaceutical compositions of dimethyl fumarate

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- Number: US 2024/0189271 A1
- Document ID: US20240189271A1
- Status: Published application
- Kind: A1
- Application number: 18/582,320
- Filed: 2024-02-20
- Published: 2024-06-13
- Earliest claimed: 2013-03-24
- Assignees: Arbor Pharmaceuticals, LLC
- Applicants: Arbor Pharmaceuticals, LLC
- Inventors: Sami KARABORNI; Wei CHEN; Suresh Kumar MANTHATI
- Web page: https://patentgrep.com/patent/US20240189271A1

## CPC

- A61K 31/336: having three-membered rings, e.g. oxirane, fumagillin
- A61J 1/035: {Blister-type containers (blisters in general B65D75/36)}
- A61K 31/194: having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
- A61K 31/215: of carboxylic acids
- A61K 31/225: Polycarboxylic acids
- A61K 31/343: condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
- A61K 31/381: having five-membered rings
- A61K 31/403: condensed with carbocyclic rings, e.g. carbazole
- A61K 9/4825: {Proteins, e.g. gelatin (gelatin capsule shells with substantial amounts of other macromolecular substances A61K9/4816)}
- 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)
- A61J: CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE

## Abstract

Pharmaceutical compositions and dosage forms of dimethyl fumarate containing low levels of certain impurities are disclosed.

## Claims

### Claim 1

A dosage form for treating multiple sclerosis, comprising:
(a) a therapeutically effective amount of dimethyl fumarate in solid form;
(b) one or more compounds of Formula (V):
isomers thereof and salts of any of the foregoing, wherein:
each of R13 and R14 is independent chosen from hydrogen and methyl; and wherein the one or more compounds of Formula (V) are present in a combined total amount of less than 2% by weight based on total weight of the dimethyl fumarate; and
(c) a pharmaceutically acceptable vehicle.

### Claim 2 (depends on 1)

The dosage form of claim 1, wherein the one or more compounds of Formula (V) are present in a combined total amount of about 0.001% to 2% by weight based on total weight of the dimethyl fumarate.

### Claim 3 (depends on 1)

The dosage form of claim 1, wherein the one or more compounds of Formula (V) are present in a combined total amount of about 0.001% to 1% by weight based on total weight of the dimethyl fumarate.

### Claim 4 (depends on 1)

The dosage form of claim 1, wherein each of the one or more compounds of Formula (V) is present in an amount of about 0.001% to 0.3% by weight based on total weight of the dimethyl fumarate.

### Claim 5 (depends on 1)

The dosage form of claim 1, wherein each of the one or more compounds of Formula (V) is present in an amount of about 0.001% to 0.2% weight based on total weight of the dimethyl fumarate.

### Claim 6 (depends on 1)

The dosage form of claim 1, wherein the one or more compounds of Formula (V) are selected from: 2,3-dihydroxysuccinic acid dimethyl ester, 2,3-dihydroxysuccinic acid monomethyl ester, 2,3-dihydroxysuccinic acid, isomers thereof and salts of any of the foregoing.

### Claim 7 (depends on 6)

The dosage form of claim 6, wherein the one or more compounds of Formula (V) is 2,3-dihydroxysuccinic acid dimethyl ester, isomers thereof, or salts thereof.

### Claim 8 (depends on 6)

The dosage form of claim 6, wherein the one or more compounds of Formula (V) is 2,3-dihydroxysuccinic acid monomethyl ester, isomers thereof, or salts thereof.

### Claim 9 (depends on 6)

The dosage form of claim 6, wherein the one or more compounds of Formula (V) is 2,3-dihydroxysuccinic acid, isomers thereof, or salts thereof.

### Claim 10 (depends on 1)

The dosage form of claim 1, in the form of a tablet or capsule.

### Claim 11 (depends on 1)

The dosage form of claim 1, wherein the pharmaceutically acceptable vehicle is selected from a carrier, a diluent, an excipient, a wetting agent, an emulsifier, a buffer, a stabilizer, a thickener, a lubricant, a coloring agent and combinations thereof.

### Claim 12 (depends on 1)

The dosage form of claim 1, wherein the dosage form is substantially free of PVP, PEG and polysorbate surfactant.

### Claim 13 (depends on 1)

The dosage form of claim 1, further comprising a free radical scavenger.

### Claim 14

A dosage form for treating multiple sclerosis, comprising:
(a) a therapeutically effective amount of dimethyl fumarate in solid form;
(b) one or more compounds of Formula (VI):
isomers thereof and salts of any of the foregoing, wherein:
Q is —O—, —S—, —NH—, N(R17)— or C(R18)2—;
each of R15 and R16 is independently chosen from hydrogen and methyl;
R17 is alkyl;
each R18 is independently hydrogen or alkyl; and
wherein the one or more compounds of Formula (VI) are impurities and are present in a combined total amount of less than 2% by weight based on total weight of the dimethyl fumarate; and
(c) a pharmaceutically acceptable vehicle.

### Claim 15 (depends on 14)

The dosage form of claim 14, wherein the one or more compounds of Formula (VI) are present in a combined total amount of about 0.001% to 2% by weight based on total weight of the dimethyl fumarate.

### Claim 16 (depends on 14)

The dosage form of claim 14, wherein the one or more compounds of Formula (VI) are present in a combined total amount of about 0.001% to 1% by weight based on total weight of the dimethyl fumarate.

### Claim 17 (depends on 14)

The dosage form of claim 14, wherein each of the one or more compounds of Formula (VI) is present in an amount of about 0.001% to 0.3% by weight based on total weight of the dimethyl fumarate.

### Claim 18 (depends on 14)

The dosage form of claim 14, wherein the one or more compounds of Formula (VI) are selected from the compounds wherein:
Q is —O—, and each R15 and R16 is methyl;
Q is —O—, and each R15 and R16 is H;
Q is —O—, R15 is H, and R16 is methyl;
Q is —S—, and each R15 and R16 is methyl;
Q is —S—, and each R15 and R16 is H;
Q is —S—, R15 is H, and R16 is methyl;
Q is —NH—, and each R15 and R16 is methyl;
Q is —NH—, and each R15 and R16 is H;
Q is —NH—, R15 is H, and R16 is methyl;
Q is —NMe—, and each R15 and R16 is methyl;
Q is —NMe—, and each R15 and R16 is H;
Q is —NMe—, R15 is H, and R16 is methyl;
Q is —CH2—, and each R15 and R16 is methyl;
Q is —CH2—, and each R15 and R16 is H;
Q is —CH2—, R15 is H, and R16 is methyl;
isomers thereof; and salts of any of the foregoing.

### Claim 19 (depends on 14)

The dosage form of claim 14, wherein the dosage form is substantially free of materials that are capable of reacting with DMF to form Diels-Alder products.

### Claim 20 (depends on 14)

The dosage form of claim 14, wherein the dosage form is substantially free of compounds containing cyclopentadiene, furan, thiophene, and pyrrole moieties.