# US 11,439,617 B2 · Polymeric compositions of monomethyl fumarate and their use in treating relapsing remitting multiple sclerosis and psoriasis

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- Number: US 11,439,617 B2
- Document ID: US11439617B2
- Status: Granted
- Kind: B2
- Application number: 16/756,842
- Filed: 2018-10-16
- Published: 2020-07-30
- Granted: 2022-09-13
- Earliest claimed: 2017-10-16
- Applicants: Dynamic Biologics Inc.
- Inventors: Deven Patel; H. Rajan Sharma; Manoj Mishra
- Web page: https://patentgrep.com/patent/US11439617B2

## CPC

- A61K 31/225: Polycarboxylic acids
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 31/21: Esters, e.g. nitroglycerine, selenocyanates
- A61K 31/215: of carboxylic acids
- A61K 31/25: with polyoxyalkylated alcohols, e.g. esters of polyethylene glycol
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61P 17/06: Antipsoriatics
- A61P 25/00: Drugs for disorders of the nervous system
- 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
- C07C 69/60: Maleic acid esters; Fumaric acid esters
- 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
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

The present invention comprises compounds of formula (I): where R1 may be PEG or other polymeric moieties. For example, R1 may be repeating PEG units —(CH2—CH2—O)n—, wherein n=1-455. R1 may also be other polymeric moieties of varying sizes and structures, for example, R1 may be poly(glycolide), poly(lactic acid), poly(lactide), poly(caprolactone), poly(lactide-co-caprolactone), poly(lactide-co-glycolide), or poly(lactic acid)-butanol. One or more embodiments of the invention may also relate to injectable pharmaceutical compositions comprising polymer conjugated monomethyl fumarate, and methods for treating relapsing-remitting multiple sclerosis and psoriasis.

## Claims

### Claim 1

An injectable dosage form comprising an injectable pharmaceutical composition comprising a compound of formula (I):
wherein R1 represents a polymeric moiety selected from the group consisting of polyethylene glycol (PEG), poly(glycolide), poly(lactic acid), poly(lactide), poly(caprolactone), poly(lactide-co-caprolactone), poly(lactide-co-glycolide), and poly(lactic acid)-butanol, wherein the composition is adapted for administration to a patient parenterally.

### Claim 2 (depends on 1)

The composition of claim 1 wherein R1 represents PEG having repeating units —(CH2-CH2-O)n-, wherein n=1-455.

### Claim 3 (depends on 2)

The composition of claim 2 wherein the PEG moiety is PEG-400 having n=8-10.

### Claim 4 (depends on 2)

The composition of claim 2 wherein the PEG moiety is PEG-1000 having n=21-25.

### Claim 5 (depends on 2)

The composition of claim 2 wherein the PEG moiety is PEG-2000 having n=43-48.

### Claim 6

The composition of claim of 2 wherein the PEG moiety is PEG-3000 having n=65-71.

### Claim 7 (depends on 2)

The composition of claim 2 wherein the PEG moiety is PEG-5000, having n=112-117.

### Claim 8 (depends on 2)

The composition of claim 2 wherein the PEG moiety has a molecular weight of approximately between 950 and 1050.

### Claim 9 (depends on 2)

The composition of claim 2 wherein the compound of formula (I) has the 400 MHz proton NMR spectrum of FIG. 2A.

### Claim 10 (depends on 2)

The composition of claim 2 wherein the compound of formula (I) has the 400 MHz proton NMR spectrum of FIG. 2B.

### Claim 11 (depends on 2)

The composition of claim 2 wherein the compound of formula (I) has the following 400 MHz proton NMR spectrum in deuterated chloroform (CDCl3):
δ 3.33 (s, 3H, OCH3 of mPEG), 3.44-3.75 (m, backbone OCH2CH2O of mPEG), 3.79 (s, 3H, OCH3 of MMF), 4.35 (m, 2H, OCH2 of mPEG adjacent to MMF), 6.87 (m, 2H, —CH═CH— of MMF).

### Claim 12 (depends on 2)

The composition of claim 2 wherein the compound of formula (I) has the following 400 MHz proton NMR spectrum in deuterated chloroform (CDCl3):
δ 6.87 (s, 2H, —CH═CH— of MMF), 4.35 (m, 2H, OCH2 of mPEG adjacent to MMF), 3.81 (s, 3H, OCH3 of MMF) 3.43-3.76 (m, backbone OCH2CH2O of mPEG), 3.36 (s, 3H, OCH3 of PEG).

### Claim 13 (depends on 2)

The composition of claim 2 wherein the compound of formula (I) has a molecular weight of 2192.8 g/mol.

### Claim 14 (depends on 1)

The composition of claim 1 wherein the polymeric moiety comprises a straight chain.

### Claim 15 (depends on 1)

The composition of claim 1 wherein the polymeric moiety comprises a branched chain.

### Claim 16 (depends on 1)

The composition of claim 1 wherein the polymeric moiety comprises a substituted chain.

### Claim 17 (depends on 1)

The composition of claim 1 wherein the polymeric moiety comprises an unsubstituted chain.

### Claim 18 (depends on 1)

The composition of claim 1 wherein the polymeric moiety is globular.

### Claim 19

A method for treating relapsing-remitting multiple sclerosis or psoriasis comprising administering to a patient parenterally an injectable pharmaceutical composition comprising a compound of formula (I)
wherein R1 represents a polymeric moiety selected from the group consisting of polyethylene glycol (PEG), poly(glycolide), poly(lactic acid), poly(lactide), poly(caprolactone), poly(lactide-co-caprolactone), poly(lactide-co-glycolide), and poly(lactic acid)-butanol.

### Claim 20 (depends on 19)

The method of claim 19, wherein the polymeric moiety is polyethylene glycol (PEG).