# US 10,865,228 B2 · Computationally optimized broadly reactive antigens for human and avian H5N1 influenza

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- Number: US 10,865,228 B2
- Document ID: US10865228B2
- Status: Granted
- Kind: B2
- Application number: 16/211,720
- Filed: 2018-12-06
- Published: 2019-03-28
- Granted: 2020-12-15
- Earliest claimed: 2012-02-13
- Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Applicants: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Inventors: Ted M. Ross; Corey J. Crevar; Brendan M. Giles
- Web page: https://patentgrep.com/patent/US10865228B2

## CPC

- C07K 14/005: from viruses
- A61K 39/12: Viral antigens
- A61K 39/145: Orthomyxoviridae, e.g. influenza virus
- A61P 31/16: for influenza or rhinoviruses
- C12N 5/0686: {Kidney cells}
- 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 2039/55505: {Inorganic adjuvants}
- A61K 2039/55561: {CpG containing adjuvants; Oligonucleotide containing adjuvants}
- A61K 2039/575: {humoral response}
- C07K 2319/00: Fusion polypeptide
- C12N 2760/16034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- 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 2760/16171: Demonstrated in vivo effect
- C12N 2760/16222: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2760/16234: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- 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)

## Abstract

Described herein is the generation of optimized H5N1 influenza HA polypeptides for eliciting a broadly reactive immune response to H5N1 influenza virus isolates. The optimized HA polypeptides were developed through a series of HA protein alignments, and subsequent generation of consensus sequences, based on human and avian H5N1 isolates. Provided herein are optimized H5N1 HA polypeptides, and compositions, fusion proteins and VLPs comprising the HA polypeptides. Further provided are codon-optimized nucleic acid sequences encoding the HA polypeptides. Methods of eliciting an immune response against influenza virus in a subject are also provided by the present disclosure.

## Claims

### Claim 1

A recombinant influenza hemagglutinin (HA) polypeptide, comprising an amino acid sequence at least 99.8% identical to SEQ ID NO: 1, or at least 99.8% identical to residues 2-566 of SEQ ID NO: 1.

### Claim 2 (depends on 1)

The influenza HA polypeptide of claim 1, wherein the amino acid sequence of the polypeptide comprises no more than 1 amino acid substitution relative to SEQ ID NO: 1.

### Claim 3 (depends on 1)

The influenza HA polypeptide of claim 1, comprising the amino acid sequence of SEQ ID NO: 1 or residues 2-566 of SEQ ID NO: 1.

### Claim 4 (depends on 1)

A fusion protein comprising the influenza HA polypeptide of claim 1.

### Claim 5 (depends on 1)

A composition comprising the influenza HA polypeptide of claim 1 and a pharmaceutically acceptable carrier.

### Claim 6 (depends on 5)

A method of eliciting an immune response to influenza virus in a subject, comprising administering the composition of claim 5.

### Claim 7 (depends on 6)

The method of claim 6, wherein the composition further comprises an adjuvant.

### Claim 8 (depends on 6)

The method of claim 6, wherein the composition is administered intramuscularly.