# US 9,518,096 B2 · Virus-like particles comprising composite capsid amino acid sequences for enhanced cross reactivity

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- Number: US 9,518,096 B2
- Document ID: US9518096B2
- Status: Granted
- Kind: B2
- Application number: 14/341,375
- Filed: 2014-07-25
- Published: 2015-01-22
- Granted: 2016-12-13
- Earliest claimed: 2008-08-08
- Assignees: Takeda Vaccines, Inc.
- Applicants: Takeda Vaccines, Inc.
- Inventors: Charles Richardson; Robert F. Bargatze; Joel Haynes; Bryan Steadman
- Web page: https://patentgrep.com/patent/US9518096B2

## CPC

- C07K 14/005: from viruses
- A61K 39/12: Viral antigens
- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 31/20: for DNA viruses
- A61P 37/04: Immunostimulants
- 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 2039/5258: {Virus-like particles}
- A61K 2039/543: {intranasal}
- A61K 2039/55505: {Inorganic adjuvants}
- A61K 2039/55572: {Lipopolysaccharides; Lipid A; Monophosphoryl lipid A}
- A61K 2039/55583: {Polysaccharides}
- A61K 2039/70: {Multivalent vaccine}
- C12N 2770/16022: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- 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
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention provides polypeptides having a composite amino acid sequence derived from a consensus sequence representing the capsid proteins of two or more circulating strains of a non-enveloped virus. In particular, the invention provides virus-like particles comprising at least one composite polypeptide. Such virus-like particles have antigenic epitopes of two or more circulating strains of a non-enveloped virus and produce an increase in antisera cross-reactivity to one or more circulating strains of the non-enveloped virus. Methods of making composite virus-like particles and vaccine formulations comprising composite virus-like particles are also disclosed.

## Claims

### Claim 1

An isolated polypeptide or fragment thereof having a composite amino acid sequence, wherein said composite amino acid sequence comprises SEQ ID NO: 1 or SEQ ID NO: 22.

### Claim 2 (depends on 1)

A vaccine formulation comprising the polypeptide of claim 1.

### Claim 3 (depends on 2)

The vaccine formulation of claim 2, further comprising a second polypeptide, wherein said second polypeptide comprises a capsid protein from a Norovirus.

### Claim 4 (depends on 3)

The vaccine formulation of claim 3, wherein said Norovirus is a genogroup I or genogroup II Norovirus.

### Claim 5 (depends on 2)

The vaccine formulation of claim 2 further comprising an adjuvant.

### Claim 6 (depends on 5)

The vaccine formulation of claim 5, wherein the adjuvant is selected from the group consisting of toll-like receptor (TLR) agonists, monophosphoryl lipid A (MPL), synthetic lipid A, lipid A mimetics or analogs, aluminum salts, cytokines, saponins, muramyl dipeptide (MDP) derivatives, CpG oligos, lipopolysaccharide (LPS) of gram-negative bacteria, polyphosphazenes, emulsions, virosomes, cochleates, poly(lactide-co-glycolides) (PLG) microparticles, poloxamer particles, microparticles, liposomes, oil-in-water emulsion, MF59, and squalene.

### Claim 7 (depends on 5)

The vaccine formulation of claim 5, further comprising a delivery agent.

### Claim 8 (depends on 7)

The vaccine formulation of claim 7, wherein the delivery agent is a mucoadhesive.

### Claim 9 (depends on 8)

The vaccine formulation of claim 8, wherein the mucoadhesive is selected from the group consisting of glycosaminoglycans, carbohydrate polymers, polyvinyl alcohol, polyvinyl pyrollidone, polysaccharides, polyions, cellulose derivatives, proteins, and deoxyribonucleic acid.

### Claim 10 (depends on 9)

The vaccine formulation of claim 9, wherein the mucoadhesive is a polysaccharide.

### Claim 11 (depends on 10)

The vaccine formulation of claim 10, wherein said polysaccharide is chitosan, chitosan salt, or chitosan base.

### Claim 12 (depends on 5)

The vaccine formulation of claim 5, wherein the vaccine formulation is a liquid formulation.

### Claim 13 (depends on 5)

The vaccine formulation of claim 5, wherein the vaccine formulation is a dry powder formulation.

### Claim 14 (depends on 13)

The dry powder formulation of claim 13 in combination with one or more devices for administering one or more doses of said formulation.

### Claim 15 (depends on 14)

The dry powder formulation of claim 14, wherein said one or more doses are unit doses.

### Claim 16 (depends on 14)

The dry powder formulation of claim 14, wherein the device is a single-use nasal administration device.

### Claim 17 (depends on 2)

The vaccine formulation of claim 2, wherein said formulation is administered to a subject by a route selected from the group consisting of mucosal, intramuscular, intravenous, subcutaneous, intradermal, subdermal, and transdermal routes of administration.

### Claim 18 (depends on 17)

The vaccine formulation of claim 17, wherein said mucosal administration is intranasal, oral, or vaginal.

### Claim 19 (depends on 18)

The vaccine formulation of claim 18, wherein the formulation is in the form of a nasal spray, nasal drops or dry powder.

### Claim 20 (depends on 2)

A method of inducing a protective immunity to a norovirus viral infection in a subject comprising administering to the subject the vaccine formulation of claim 2.

### Claim 21 (depends on 20)

The method of claim 20, wherein said vaccine formulation confers protection from one or more symptoms of Norovirus infection.

### Claim 22 (depends on 1)

A method of making a norovirus virus-like particle comprising expressing the polypeptide of claim 1 in a host cell; growing the cell in conditions in which the virus like particle is formed; and isolating the virus-like particle.