# US 11,026,918 B2 · Method of preventing or treating a pulmonary disease or condition

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- Number: US 11,026,918 B2
- Document ID: US11026918B2
- Status: Granted
- Kind: B2
- Application number: 15/527,103
- Filed: 2015-11-24
- Published: 2017-12-21
- Granted: 2021-06-08
- Earliest claimed: 2014-11-24
- Assignees: The Board of Trustees of the University of Illinois
- Applicants: The Board of Trustees of the University of Illinois
- Inventors: Anantha Harijith; Viswanathan Natarajan; Roberto F. Machado; Jeffrey Jacobson
- Web page: https://patentgrep.com/patent/US11026918B2

## CPC

- A61K 31/40: having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K 9/008: {comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]}
- A61K 31/402: 1-aryl substituted, e.g. piretanide
- A61M 15/009: {using medicine packages with incorporated spraying means, e.g. aerosol cans (pocket atomiser of the injector type A61M11/08)}
- A61P 11/00: Drugs for disorders of the respiratory system
- 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)
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A pharmaceutical composition for aerosol administration and method of preventing or treating a pulmonary disease or condition in a subject with a SphK1 inhibitor are provided.

## Claims

### Claim 1

A method of treating a pulmonary disease or condition in a subject comprising administering to a subject in need of treatment an effective amount of a SphK1 inhibitor to treat the subject's pulmonary disease or condition, wherein the SphK1 inhibitor
(a) exhibits at least a 20-fold greater selectivity for SphK1than SphK2; and
(b) is cell permeable, has an IC50 value of less than 10 μM, or has a Ki of less than 10 μM, or a combination thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the pulmonary disease or condition comprises pulmonary hypertension, adult respiratory distress syndrome, restrictive lung disease, chronic obstructive pulmonary disease, bronchiectasis, bronchiolectasis, bronchiolitis, bronchitis, emphysema, a diffuse interstitial or infiltrative lung disease, serofibrinous pleuritis, suppurative pleuritis, hemorrhagic pleuritis, a pleural effusion, idiopathic pulmonary fibrosis, bronchopulmonary dysplasia, hyperoxia or oxygen-induced lung injury, injury due to drug or chemotherapeutic toxicity, radiation-induced injury, or chemical injury.

### Claim 3 (depends on 1)

The method of claim 1, wherein the SphK1 inhibitor comprises [(2R)-1-[[4-[[3-(benzenesulfonyl methyl)-5-methylphenoxy]methyl]phenyl] methyl] pyrrolidin-2-yl] methanol (PF-543) or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 3)

The method of claim 3, wherein the pharmaceutically acceptable salt is a citric acid salt.

### Claim 5 (depends on 1)

The method of claim 1, wherein said SphK1 inhibitor is administered to the lungs of the subject.

### Claim 6

A method of treating a pulmonary disease or condition in a subject comprising administering to a subject in need of treatment an effective amount of [(2R)-1-[[4-[[3-(benzenesulfonyl methyl)-5-methylphenoxy]methyl]phenyl]methyl] pyrrolidin-2-yl] methanol (PF-543), or a pharmaceutically acceptable salt thereof, to treat the subject's pulmonary disease or condition, wherein the pulmonary disease or condition comprises restrictive lung disease, bronchiectasis, bronchiolectasis, bronchitis, emphysema, a diffuse interstitial lung disease, a diffuse infiltrative lung disease, serofibrinous pleuritis, suppurative pleuritis, hemorrhagic pleuritis, idiopathic pulmonary fibrosis, bronchopulmonary dysplasia, hyperoxia or oxygen-induced lung injury, injury due to drug or chemotherapeutic toxicity, radiation-induced injury, or chemical injury.

### Claim 7 (depends on 6)

The method of claim 6, wherein the pharmaceutically acceptable salt is a citric acid salt.

### Claim 8 (depends on 6)

The method of claim 6, wherein said SphK1 inhibitor is administered to the lungs of the subject.