# US 8,883,171 B2 · Computationally optimized broadly reactive antigens for influenza

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- Number: US 8,883,171 B2
- Document ID: US8883171B2
- Status: Granted
- Kind: B2
- Application number: 13/822,844
- Filed: 2011-09-09
- Published: 2013-07-18
- Granted: 2014-11-11
- Earliest claimed: 2010-09-14
- Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Applicants: Ted M. Ross; Brendan M. Giles
- Inventors: Ted M. Ross; Brendan M. Giles
- Web page: https://patentgrep.com/patent/US8883171B2

## CPC

- A61K 39/145: Orthomyxoviridae, e.g. influenza virus
- A61K 39/12: Viral antigens
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- C07K 14/005: from viruses
- C07K 14/11: Orthomyxoviridae, e.g. influenza virus
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 9/2402: {hydrolysing O- and S- glycosyl compounds (3.2.1)}
- C12N 15/86: Viral vectors
- C12Y 302/01018: Exo-alpha-sialidase (3.2.1.18), i.e. trans-sialidase
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- A61K 2039/5258: {Virus-like particles}
- A61K 2039/54: {characterised by the route of administration}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- A61K 2039/552: {Veterinary vaccine}
- A61K 2039/55505: {Inorganic adjuvants}
- A61K 2039/575: {humoral response}
- C07K 2319/00: Fusion polypeptide
- C12N 2760/16122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2760/16123: Virus like particles [VLP]
- C12N 2760/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2760/16143: viral genome or elements thereof as genetic vector
- C12N 2760/16171: Demonstrated in vivo effect
- C12N 2760/16223: Virus like particles [VLP]
- C12N 2760/16234: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2760/16323: Virus like particles [VLP]
- C12N 2760/16334: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2800/22: Vectors comprising a coding region that has been codon optimised for expression in a respective host
- 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)
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Y: ENZYMES

## Abstract

Described herein is the development of a computationally optimized influenza HA protein that elicits broadly reactive immune response to all H5N1 influenza virus isolates. The optimized HA protein was developed through a series of HA protein alignments, and subsequent generation of consensus sequences, for clade 2 H5N1 influenza virus isolates. The final consensus HA amino acid sequence was reverse translated and optimized for expression in mammalian cells. Influenza virus-like particles containing the optimized HA protein are an effective vaccine against H5N1 influenza virus infection in animals.

## Claims

### Claim 1

An isolated nucleic acid molecule comprising a nucleotide sequence encoding an influenza hemagglutinin (HA) polypeptide, wherein the nucleotide sequence encoding the HA polypeptide is at least 96% identical to SEQ ID NO: 1.

### Claim 2 (depends on 1)

The isolated nucleic acid molecule of claim 1, wherein the nucleotide sequence encoding the HA polypeptide comprises SEQ ID NO: 1.

### Claim 3 (depends on 1)

A vector comprising the isolated nucleic acid molecule of claim 1.

### Claim 4 (depends on 3)

The vector of claim 3, wherein the nucleotide sequence of the vector comprises SEQ ID NO: 7.

### Claim 5 (depends on 3)

An isolated cell comprising the vector of claim 3.

### Claim 6

An isolated influenza HA polypeptide, wherein the amino acid sequence of the polypeptide is at least 99% identical to SEQ ID NO: 2.

### Claim 7 (depends on 6)

The influenza HA polypeptide of claim 6, wherein the amino acid sequence of the polypeptide comprises SEQ ID NO: 2.

### Claim 8 (depends on 6)

A fusion protein comprising the polypeptide of claim 6 and a heterologous protein.

### Claim 9 (depends on 6)

A composition comprising the influenza HA protein of claim 6 and a pharmaceutically acceptable carrier.

### Claim 10 (depends on 9)

A method of eliciting an immune response to an H5 influenza virus in a subject, comprising administering the composition of claim 9.

### Claim 11 (depends on 10)

The method of claim 10, further comprising administering an adjuvant.

### Claim 12 (depends on 3)

The vector of claim 3, wherein the vector comprises a promoter operably linked to the nucleic acid sequence that is at least 96% identical to SEQ ID NO: 1.

### Claim 13 (depends on 12)

The vector of claim 12, wherein the promoter is a cytomegalovirus (CMV) promoter.