# US 9,872,839 B2 · Compositions and methods for diagnosing or treating neutrophil-mediated inflammatory disease

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- Number: US 9,872,839 B2
- Document ID: US9872839B2
- Status: Granted
- Kind: B2
- Application number: 15/425,528
- Filed: 2017-02-06
- Published: 2017-05-25
- Granted: 2018-01-23
- Earliest claimed: 2013-06-28
- Assignees: The Board of Trustees of the University of Illinois
- Applicants: The Board of Trustees of the University of Illinois
- Inventors: Zhenjia Wang; Jaehyung Cho; Asrar Malik
- Web page: https://patentgrep.com/patent/US9872839B2

## CPC

- A61K 31/05: Phenols {(cannabinoids A61K31/658)}
- 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 9/1658: {Proteins, e.g. albumin, gelatin}
- A61K 9/5169: {Proteins, e.g. albumin, gelatin}
- A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
- G01N 33/5005: {involving human or animal cells (immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025)}
- G01N 2800/22: Haematology
- 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)
- 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

Disclosed are nanoparticle compositions comprising nanoparticles prepared from denatured, cross-linked albumin and a therapeutic agent for treating a neutrophil-mediated inflammation, and methods of treating neutrophil-mediated inflammation using the compositions.

## Claims

### Claim 1

A method of treating a neutrophil-mediated inflammatory disease in a subject in need of treatment comprising:
administering to the subject a therapeutically effective amount of a composition comprising nanoparticles, each nanoparticle consisting of denatured, cross-linked albumin and a therapeutic agent, the nanoparticles selectively binding to and internalized by activated neutrophils.

### Claim 2 (depends on 1)

The method of claim 1, wherein the therapeutic agent is one or more selected from the group consisting of anti-inflammatory glucocorticoids, NF-kB inhibitors, p38MAP kinase inhibitors, Syk/Zap kinase inhibitors and siRNA oligonucleotides.

### Claim 3 (depends on 1)

The method of claim 1, wherein the therapeutic agent is dexamethasone or piceatannol.

### Claim 4 (depends on 1)

The method of claim 1, wherein the neutrophil-mediated inflammatory disease is selected from the group consisting of sepsis, myocardial infarction, acute lung injury, stroke and ischemia-reperfusion injury.

### Claim 5 (depends on 1)

The method of claim 1, wherein the therapeutic agent is loaded within the nanoparticles or covalently conjugated to the albumin.

### Claim 6 (depends on 1)

The method of claim 1, wherein each of the nanoparticles has a mean particle diameter of about 90 nm to about 110 nm.

### Claim 7 (depends on 1)

The method of claim 1, wherein the nanoparticles are administered intravenously.

### Claim 8 (depends on 1)

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

### Claim 9 (depends on 1)

The method of claim 1 wherein the denatured albumin is denatured by desolvation.

### Claim 10 (depends on 9)

The method of claim 9 wherein the albumin is desolvated by treatment with ethanol.

### Claim 11 (depends on 1)

The method of claim 1 wherein the albumin is bovine serum albumin.

### Claim 12 (depends on 1)

The method of claim 1 wherein the albumin is cross-linked with glutaraldehyde.

### Claim 13

A composition comprising nanoparticles, each nanoparticle consisting of denatured, cross-linked albumin and a therapeutic agent, the nanoparticles selectively binding to and internalized by activated neutrophils.