# US 2014/0155361 A1 · Method for treating lung disease

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- Number: US 2014/0155361 A1
- Document ID: US20140155361A1
- Status: Published application
- Kind: A1
- Application number: 14/175,155
- Filed: 2014-02-07
- Published: 2014-06-05
- Earliest claimed: 2010-12-07
- Applicants: Duke University
- Inventors: John W. Hollingsworth; William Michael Foster; Erin Potts-Kant; Zhuowei Li
- Web page: https://patentgrep.com/patent/US20140155361A1

## CPC

- A61K 31/122: having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
- A61K 31/343: condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 11/08: Bronchodilators
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- G01N 2333/90209: acting on NADH or NADPH (1.6), e.g. those with a heme protein as acceptor (1.6.2) (general), Cytochrome-b5 reductase (1.6.2.2) or NADPH-cytochrome P450 reductase (1.6.2.4)
- G01N 2800/122: Chronic or obstructive airway disorders, e.g. asthma COPD
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Methods of treating lung diseases comprising administering inducers of NAD(P)H:quinone oxidoreductase 1 (NQO1) are disclosed. Inducers of NQO1 include naphthoquinones such as β-lapachone. Methods of predicting whether a subject with a lung disease will respond to treatment with a naphthoquinone are also described herein.

## Claims

### Claim 1

A method of treating a lung disease in a subject, comprising administering to the subject an effective amount of a naphthoquinone and a bronchodilator, wherein the naphthoquinone and the bronchodilator are administered via inhalation.

### Claim 2 (depends on 1)

The method of claim 1, wherein the lung disease is selected from chronic obstructive pulmonary disease (COPD), emphysema, chronic bronchitis, asthma, reactive airway disease and pulmonary fibrosis.

### Claim 3 (depends on 2)

The method of claim 2, wherein the lung disease is COPD.

### Claim 4 (depends on 1)

The method of claim 1, wherein the naphthoquinone is a 1,2-naphthoquinone.

### Claim 5 (depends on 4)

The method of claim 4, wherein the 1,2-naphthoquinone is selected from the group consisting of β-lapachone, tanshinone and cryptotanshinone.

### Claim 6 (depends on 1)

The method of claim 1, wherein the naphthoquinone and bronchodilator are administered with at least one additional therapeutic agent.

### Claim 7 (depends on 6)

The method of claim 6, wherein the additional therapeutic agent is a corticosteroid.

### Claim 8 (depends on 1)

The method of claim 1, wherein the bronchodilator is selected from an anti-cholinergic and a beta-agonist.

### Claim at position 9

-19. (canceled)

### Claim 20

A method of predicting responsiveness of a subject with a lung disease to treatment with a naphthoquinone, comprising:
a) detecting the level or activity of NQO1 in a sample obtained from the subject; and
b) comparing the level or activity of NQO1 in the sample to a standard level, wherein an altered level or activity of NQO1 indicates that the subject is responsive to treatment with a naphthoquinone.

### Claim 21

A method of identifying a subject with a lung disease as a candidate for treatment with a naphthoquinone, comprising:
a) detecting the level or activity of NQO1 in a sample obtained from the subject; and
b) comparing the level or activity of NQO1 in the sample to a standard level, wherein a difference in the level or activity of NQO1 indicates that the subject is a candidate for treatment with a naphthoquinone.

### Claim 22

A method for identifying a subject as having an increased risk of developing lung disease, comprising:
a) providing a sample from a subject;
b) determining the presence or absence of a functional variant of NQO1 in the sample; and
c) identifying the patient as having an increased risk of developing lung disease when a functional variant of NQO1 is present in the sample.

### Claim 23 (depends on 22)

The method of claim 22, wherein the functional variant of NQO1 is Pro187Ser.