# US 10,870,682 B2 · Methods and compositions for dengue virus vaccines

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- Number: US 10,870,682 B2
- Document ID: US10870682B2
- Status: Granted
- Kind: B2
- Application number: 16/105,346
- Filed: 2018-08-20
- Published: 2019-07-25
- Granted: 2020-12-22
- Earliest claimed: 2013-06-26
- Assignees: The University of North Carolina at Chapel Hill
- Applicants: The University of North Carolina at Chapel Hill
- Inventors: William Messer; Ralph Baric; Aravinda de Silva; Boyd Yount
- Web page: https://patentgrep.com/patent/US10870682B2

## CPC

- C07K 14/005: from viruses
- A61P 31/04: Antibacterial agents
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 37/02: Immunomodulators
- C07K 14/1825: {Flaviviruses or Group B arboviruses, e.g. yellow fever virus, japanese encephalitis, tick-borne encephalitis, dengue}
- C07K 16/116: Togaviridae (F); Matonaviridae (F); Flaviviridae (F)
- 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 39/12: Viral antigens
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2319/00: Fusion polypeptide
- C12N 2770/24121: Viruses as such, e.g. new isolates, mutants or their genomic sequences
- C12N 2770/24122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2770/24134: 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)
- 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)
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention provides compositions and methods of use comprising a chimeric dengue virus E glycoprotein comprising a dengue virus E glycoprotein backbone, which comprises amino acid substitutions that introduce an epitope that is recognized by an antibody from a dengue virus serotype that is different from the dengue virus serotype of the dengue virus E glycoprotein backbone.

## Claims

### Claim 1

A chimeric dengue virus E glycoprotein comprising a dengue virus E glycoprotein backbone that comprises the following amino acid substitutions that introduce an epitope that is recognized by an antibody that is reactive with a dengue virus serotype that is different from the dengue virus serotype of the dengue virus E glycoprotein backbone; wherein the amino acid residue numbering is based on the reference amino acid sequence of an E glycoprotein of dengue virus serotype 3 (DENV3) identified as SEQ ID NO:1: T138S, Q158H, V160T, S169P, A173I, I174Q, P176T, E177D, N272T, G275T, and S277T, and wherein said dengue virus E glycoprotein further comprises an insertion of the amino acid residues T and E between amino acid residues 155 and 156.

### Claim 2 (depends on 1)

A flavivirus particle or virus like particle (VLP) comprising the chimeric dengue virus E glycoprotein of claim 1.

### Claim 3 (depends on 1)

A composition comprising the chimeric dengue virus E glycoprotein of claim 1 in a pharmaceutically acceptable carrier.

### Claim 4 (depends on 2)

A composition comprising the flavivirus particle or VLP of claim 2 in a pharmaceutically acceptable carrier.

### Claim 5 (depends on 1)

A method of producing an immune response to a dengue virus in a subject, comprising administering to the subject an effective amount of the chimeric dengue virus E glycoprotein of claim 1.

### Claim 6 (depends on 2)

A method of producing an immune response to a dengue virus in a subject, comprising administering to the subject an effective amount of the flavivirus particle or VLP of claim 2.