# US 9,439,958 B2 · Stabilized virus like particles having enhanced mucosal immunogenicity

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- Number: US 9,439,958 B2
- Document ID: US9439958B2
- Status: Granted
- Kind: B2
- Application number: 13/518,504
- Filed: 2010-12-23
- Published: 2013-04-18
- Granted: 2016-09-13
- Earliest claimed: 2009-12-23
- Assignees: Arizona Board of Regents, acting for and on behalf of Arizona State University
- Applicants: Charles J. Arntzen; Melissa Herbst-Kralovetz
- Inventors: Charles J. Arntzen; Melissa Herbst-Kralovetz
- Web page: https://patentgrep.com/patent/US9439958B2

## CPC

- A61K 39/12: Viral antigens
- A61K 9/0043: {Nose}
- A61K 9/1652: {Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623)}
- A61K 9/1694: {resulting in granules or microspheres of the matrix type containing more than 5% of excipient}
- A61K 39/125: Picornaviridae, e.g. calicivirus
- A61P 31/12: Antivirals
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- A61K 2039/5258: {Virus-like particles}
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/542: {oral/gastrointestinal}
- A61K 2039/543: {intranasal}
- C12N 2770/16023: Virus like particles [VLP]
- C12N 2770/16034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2770/16051: Methods of production or purification of viral material
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

A method of producing an immune response in a subject including the step of administering to the subject a dry powder vaccine composition having a dry powder containing a subunit antigen with virus-like particles, where the subunit antigen is stabilized by a polysaccharide-containing plant extract, and where mucosal vaccination results in an immune response which is not further enhanced by co-inclusion of adjuvants.

## Claims

### Claim 1

A method of producing an immune response in a subject, comprising the steps of:
(i) preparing a dry powder immunogenic composition, wherein said composition consists of:
a) viral protein subunits which can assemble into virus-like particles consisting of a norovirus capsid protein (NoVCP); and
b) an anionic polysaccharide extracted from an aloe vera plant, wherein said VLPs are stabilized by the anionic polysaccharide at a pH over 6.5, and wherein the anionic polysaccharide has characteristics including a degree of methylation of 10% or less, a molecular weight >1×106 Daltons, an intrinsic viscosity from about 550 ml/g to about 978 ml/g, when dissolved in 0.1 M NaCl at a concentration of 0.0005-0.2% (w/v), a galacturonic acid content of at least 70%, a rhamnose content from about 2 to about 15% by mole, and capable of calcium gel formation when present at a concentration of 0.2% (w/v) in an aqueous solution comprising 2 mM calcium chloride; and
(ii) intranasally inoculating the subject with the dry powder immunogenic composition to elicit an immune response, where said dry powder immunogenic composition does not include an adjuvant in addition to the anionic polysaccharide.

### Claim 2 (depends on 1)

The method of claim 1, wherein the norovirus is selected from the group consisting of norovirus genogroup I, norovirus genogroup II, norovirus genogroup III or norovirus genogroup IV.

### Claim 3 (depends on 1)

The method of claim 1, wherein said dry powder immunogenic composition does not include TLR agonists.

### Claim 4 (depends on 1)

The method of claim 1, wherein the polysaccharide may comprise low methoxy-pectin, Xanthan, carboxymethylcellulose, or a combination thereof.

### Claim 5 (depends on 1)

The method of claim 1, wherein said dry powder formulation forms a gel upon delivery to the nasal passage, wherein said polysaccharide in said formulation is sodium polygalacturonate having a galacturonic acid (Gal UA) content of >90%, a degree of methylation of <10%, and a molecular weight of >400 kDa weight average.

### Claim 6 (depends on 1)

The method of claim 1, wherein said polysaccharide is sodium polygalacturonate.