# US 2022/0031679 A1 · Pharmaceutical compositions of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl) benzoic acid and administration thereof

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- Number: US 2022/0031679 A1
- Document ID: US20220031679A1
- Status: Published application
- Kind: A1
- Application number: 17/333,478
- Filed: 2021-05-28
- Published: 2022-02-03
- Earliest claimed: 2010-04-07
- Assignees: Vertex Pharmaceuticals Incorporated
- Applicants: Vertex Pharmaceuticals Incorporated
- Inventors: Marinus Jacobus VERWIJS; Rossitza Gueorguieva ALARGOVA; Ritu Rohit KAUSHIK; Irina Nikolaevna KADIYALA; Christopher YOUNG
- Web page: https://patentgrep.com/patent/US20220031679A1

## CPC

- A61K 31/443: containing a five-membered ring with oxygen as a ring hetero atom
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/141: {Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers ((co) spray-dried products A61K9/16, (co) lyophilised products A61K9/19; the carrier being chemically bound to the active ingredient A61K47/50)}
- A61K 9/1623: {Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules}
- A61K 9/1652: {Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623)}
- A61K 9/1682: {Processes}
- A61K 9/2009: {Inorganic compounds}
- A61K 9/2013: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/2027: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/2077: {Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets}
- A61K 9/2095: {Tabletting processes}
- A61K 9/28: Dragees; Coated pills or tablets {, e.g. with film or compression coating (A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209)}
- A61K 9/2866: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 31/47: Quinolines; Isoquinolines
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/10: Laxatives
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 3/06: Antihyperlipidemics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/14: of the thyroid hormones, e.g. T3, T4
- A61P 5/18: of the parathyroid hormones
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A61P 7/12: Antidiuretics, e.g. drugs for diabetes insipidus (ADH A61P5/10)
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/02: Nasal agents, e.g. decongestants
- A61P 11/06: Antiasthmatics
- A61P 13/02: of urine or of the urinary tract, e.g. urine acidifiers
- A61P 13/12: of the kidneys
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 15/10: for impotence
- A61P 19/00: Drugs for skeletal disorders
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 19/10: for osteoporosis
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 21/02: Muscle relaxants, e.g. for tetanus or cramps
- A61P 21/04: for myasthenia gravis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/02: for peripheral neuropathies
- A61P 25/08: Antiepileptics; Anticonvulsants
- 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 27/02: Ophthalmic agents
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 405/14: containing three or more hetero rings
- C07D 451/02: containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- 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
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

A pharmaceutical composition comprising Compound 1, (3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid), and at least one excipient selected from: a filler, a diluent, a disintegrant, a surfactant, a binder, a glidant and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Methods for treating a patient in need thereof include administering an oral pharmaceutical formulation of Compound 1 to the patient.

## Claims

### Claim at position 1

1-55. (canceled)

### Claim 56

A tablet for oral administration comprising:
a. 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid (Compound 1) Form I, wherein the Compound 1 Form I is present in an amount ranging from 25 mg to 250 mg;
b. a filler;
c. a disintegrant which is croscarmellose sodium and is present in an amount of about 6 wt % to about 10 wt % by weight of the tablet;
d. a surfactant;
e. a lubricant; and
f. a binder.

### Claim 57 (depends on 56)

The tablet of claim 56, wherein the filler is selected from cellulose, modified cellulose, sodium carboxymethyl cellulose, ethyl cellulose hydroxymethyl cellulose, hydroxypropylcellulose, cellulose acetate, microcrystalline cellulose, dibasic calcium phosphate, sucrose, lactose, corn starch, potato starch, and any combination thereof.

### Claim 58 (depends on 56)

The tablet of claim 56, wherein the filler is microcrystalline cellulose (MCC) and is present in the tablet in an amount ranging from 20 wt % to 55 wt % by weight of the tablet.

### Claim 59 (depends on 56)

The tablet of claim 56, wherein the surfactant is selected from sodium lauryl sulfate, sodium stearyl fumarate, polyoxyethylene 20 sorbitan mono-oleate, and any combination thereof.

### Claim 60 (depends on 56)

The tablet of claim 56, wherein the surfactant is sodium lauryl sulfate and is present in an amount of 0.3 wt % to 2 wt % by weight of the tablet.

### Claim 61 (depends on 56)

The tablet of claim 56, wherein the lubricant is selected from magnesium stearate, calcium stearate, zinc stearate, sodium stearate, stearic acid, aluminum stearate, leucine, glyceryl behenate, hydrogenated vegetable oil, and any combination thereof.

### Claim 62 (depends on 56)

The tablet of claim 56, wherein the lubricant is magnesium stearate and is present at a concentration of 0.15 wt % to 4.5 wt % by weight of the tablet.

### Claim 63 (depends on 56)

The tablet of claim 56, wherein the binder is selected from polyvinylpyrrolidone, dibasic calcium phosphate, sucrose, corn starch, modified cellulose, and any combination thereof.

### Claim 64 (depends on 56)

The tablet of claim 56, wherein the polyvinylpyrrolidone is present at a concentration of 1 wt % to 8 wt % by weight of the tablet.

### Claim 65 (depends on 56)

The tablet of claim 56, wherein Compound 1 Form I is present in an amount of 30 wt % to 70 wt % by weight of the tablet.

### Claim 66 (depends on 56)

The tablet of claim 56, wherein the Compound 1 Form I is present in the tablet in an amount of 200 mg.

### Claim 67 (depends on 56)

The tablet of claim 56, wherein the Compound 1 Form I is present in the tablet in an amount of 100 mg.

### Claim 68 (depends on 56)

A method of treating cystic fibrosis in a subject, comprising administering to the subject a tablet of claim 56.

### Claim 69 (depends on 68)

The method of claim 68, wherein the subject is homozygous for the ΔF508 mutation in cystic fibrosis transmembrane conductance regulator (CFTR).

### Claim 70

A method of treating cystic fibrosis in a subject, comprising administering a tablet for oral administration comprising:
a. 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid (Compound 1) Form I wherein the Compound 1 Form I is present in an amount ranging from 25 mg to 250 mg;
b. a filler;
c. a disintegrant;
d. a surfactant which is sodium lauryl sulfate and is present in an amount of 0.3 wt % to 2 wt % by weight of the tablet;
e. a lubricant; and
f. a binder.

### Claim 71 (depends on 70)

The method of claim 70, wherein the subject is homozygous for the ΔF508 mutation in cystic fibrosis transmembrane conductance regulator (CFTR).

### Claim 72

A method of treating cystic fibrosis in a subject, comprising administering a tablet for oral administration comprising:
a. 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid (Compound 1) Form I wherein the Compound 1 Form I is present in an amount ranging from 25 mg to 250 mg;
b. a filler;
c. a disintegrant;
d. a surfactant;
e. a lubricant; and
f. a binder;
wherein Compound 1 Form I is present in an amount of 30 wt % to 70 wt % by weight of the tablet.

### Claim 73 (depends on 72)

The method of claim 72, wherein the subject is homozygous for the ΔF508 mutation in cystic fibrosis transmembrane conductance regulator (CFTR).