# US 9,006,203 B2 · Method of reducing inflammatory infiltration in subjects with inflammatory lung disease

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- Number: US 9,006,203 B2
- Document ID: US9006203B2
- Status: Granted
- Kind: B2
- Application number: 13/932,906
- Filed: 2013-07-01
- Published: 2013-10-24
- Granted: 2015-04-14
- Earliest claimed: 2002-10-08
- Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services
- Applicants: The United States of America as Represented by the Secretary of the Department of Health and Human Services
- Inventors: Dennis M. Klinman; Hiroshi Yamada
- Web page: https://patentgrep.com/patent/US9006203B2

## CPC

- C12N 15/117: Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/08: Bronchodilators
- A61P 11/10: Expectorants
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- C12N 2310/151: more than 3 strands, e.g. tetrads, H-DNA
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure relates to oligodeoxynucleotides that suppress an immune response. Methods are disclosed for reducing neutrophil infiltration in subjects with inflammatory lung disease-by administering a therapeutically effective amount of a suppressive oligodeoxynucleotide.

## Claims

### Claim 1

A method of reducing infiltration of neutrophils into a lung of a subject with an inflammatory lung disease, comprising
administering to the subject with the inflammatory lung disease a therapeutically effective amount of a suppressive oligodeoxynucleotide, wherein the suppressive oligodeoxynucleotide comprises from 2 to 4 guanosine-rich sequences, forms a G-tetrad, is at most 100 nucleotides in length, and has a CD value of greater than about 2.9 wherein the oligodeoxynucleotide comprises the nucleic acid sequence set forth as SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, or SEQ ID NO: 21,
thereby reducing the infiltration of neutrophils into the lung of the subject with the inflammatory lung disease.

### Claim 2 (depends on 1)

The method of claim 1, wherein the inflammatory lung disease is acute respiratory distress syndrome, pneumonia, respiratory distress of prematurity, chronic bronchitis, chronic obstructive pulmonary disease, cystic fibrosis, pulmonary fibrosis, or pulmonary sarcoidosis.

### Claim 3 (depends on 1)

The method of claim 1, wherein the inflammatory lung disease is acute respiratory distress syndrome.

### Claim 4 (depends on 1)

The method of claim 1, wherein the suppressive oligodeoxynucleotide is administered parenterally, orally, intravenously, intramuscularly, subcutaneously, intranasally, intratracheally or by inhalation.

### Claim 5 (depends on 1)

The method of claim 1, wherein the suppressive oligodeoxynucleotide is administered by inhalation.

### Claim 6 (depends on 1)

The method of claim 1, wherein the suppressive oligodeoxynucleotide has a CD value of greater than about 3.2.

### Claim 7 (depends on 1)

The method of claim 1, wherein the suppressive oligodeoxynucleotide is from about 10 to about 30 nucleotides in length.

### Claim 8 (depends on 1)

The method of claim 1, wherein the suppressive oligodeoxynucleotide comprises multiple guanosine-rich sequences.

### Claim 9 (depends on 1)

The method of claim 1, wherein the suppressive oligodeoxynucleotide comprises from about 2 to about 20 TTAGGG motifs.

### Claim 10 (depends on 1)

The method of claim 1, wherein the suppressive oligodeoxynucleotide comprises the nucleic acid sequence set forth as one of SEQ ID NO: 1.

### Claim 11 (depends on 1)

The method of claim 1, further comprising administering an additional anti-infective agent, anti-inflammatory agent, bronchodilator, enzyme, expectorant, leukotriene antagonist, leukotriene formation inhibitor, or mast cell stabilizer.

### Claim 12 (depends on 1)

The method of claim 1, wherein the subject is human.

### Claim 13 (depends on 1)

The method of claim 1, comprising administering the suppressive oligodeoxynucleotide locally.

### Claim 14 (depends on 1)

The method of claim 1, further comprising
measuring the infiltration of neutrophils into the lung of the subject with the inflammatory lung disease.

### Claim 15 (depends on 1)

The method of claim 1, wherein the suppressive oligodeoxynucleotide comprises the nucleic acid sequence set forth as SEQ ID NO: 4.

### Claim 16 (depends on 15)

The method of claim 15, wherein the suppressive oligodeoxynucleotide comprises the nucleic acid sequence set forth as SEQ ID NO: 2 or SEQ ID NO: 3.

### Claim 17 (depends on 16)

The method of claim 16, wherein the suppressive oligodeoxynucleotide comprises the nucleic acid sequence set forth as SEQ ID NO: 2.

### Claim 18 (depends on 15)

The method of claim 15, wherein the suppressive oligodeoxynucleotide is at most 30 nucleotides in length.

### Claim 19 (depends on 1)

The method of claim 1, wherein the oligodoexynucleotide is modified to prevent degradation.

### Claim 20 (depends on 19)

The method of claim 19, wherein the oligodoexynucleotide comprises phosphorothioate nucleotides.

### Claim 21 (depends on 1)

The method of claim 1, wherein the suppressive oligodeoxynucleotide comprises the nucleic acid sequence set forth as one of SEQ ID NO: 1, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ED NO: 19, SEQ ID NO: 21 and wherein the oligodeoxynucleotide is at most 30 nucleotides in length.
