# US 10,245,319 B2 · Lymph node-targeting nanoparticles

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- Number: US 10,245,319 B2
- Document ID: US10245319B2
- Status: Granted
- Kind: B2
- Application number: 15/698,500
- Filed: 2017-09-07
- Published: 2018-04-12
- Granted: 2019-04-02
- Earliest claimed: 2010-10-04
- Assignees: Duke University
- Applicants: Duke University
- Inventors: Soman Abraham; Kam Leong; Herman Staats; Ashley St. John
- Web page: https://patentgrep.com/patent/US10245319B2

## CPC

- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 9/5123: {Organic compounds, e.g. fats, sugars}
- A61K 9/513: {Organic macromolecular compounds; Dendrimers}
- A61K 38/191: {Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta}
- A61K 38/20: Interleukins [IL]
- A61K 38/2006: {IL-1}
- A61K 38/2013: {IL-2}
- A61K 38/2066: {IL-10}
- A61K 38/208: {IL-12}
- A61K 38/21: Interferons {[IFN]}
- A61K 39/0008: {Antigens related to auto-immune diseases; Preparations to induce self-tolerance}
- A61K 39/085: Staphylococcus
- A61K 39/12: Viral antigens
- A61K 39/145: Orthomyxoviridae, e.g. influenza virus
- A61P 31/12: Antivirals
- A61P 37/04: Immunostimulants
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- A61K 2039/5252: {inactivated (killed)}
- A61K 2039/55505: {Inorganic adjuvants}
- A61K 2039/55527: {Interleukins}
- A61K 2039/55555: {Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers}
- C12N 2760/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- Y10S 977/773: Nanoparticle, i.e. structure having three dimensions of 100 nm or less
- Y10S 977/906: Drug delivery
- 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
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

Provided are nanoparticles comprising heparin, chitosan, and at least one immunomodulatory agent, e.g. a cytokine. The cytokine can be selected from the group consisting of TNF, IL-12, IL-2, IL-23, IL-1α, IL-10, IL-18, and combinations thereof. Further provided are methods of making a nanoparticle comprising mixing a first composition comprising heparin with a second composition comprising chitosan in the presence of at least one cytokine to form a third composition. Further provided are methods of modulating an immune response comprising co-administering to a subject an antigen or vaccine with nanoparticles comprising heparin, chitosan, and at least one cytokine.

## Claims

### Claim 1

A method of treating asthma comprising administering to a subject a nanoparticle comprising:
heparin; and
chitosan,
wherein the heparin and the chitosan nanoparticle encapsulates IL-12, and
wherein the nanoparticle is administered by a route selected from the group consisting of oral, sublingual, intramuscular, subcutaneous, intravenous, transdermal, topical, parenteral, buccal, rectal, mucosal, intranasal, injection, inhalation, implant, and a combination thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the nanoparticle further comprises an antigen, wherein the antigen comprises at least one selected from the group consisting of a protein, peptide, polysaccharide, lipid, glycoprotein, glycolipid, glycoprotein, lipoprotein, lipopolysaccharide, or a combination thereof.

### Claim 3 (depends on 1)

The method of claim 1, wherein the nanoparticle further comprises at least one immunomodulatory agent selected from the group consisting of TNF, IL-1α, IL-2, IL-23, IL-18, IL-10, and IFN.

### Claim 4 (depends on 2)

The method of claim 2, wherein the antigen provoked the asthma.