# US 10,308,689 B2 · Dengue virus (DV) polypeptide sequences, T cell epitopes and methods and uses thereof

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- Number: US 10,308,689 B2
- Document ID: US10308689B2
- Status: Granted
- Kind: B2
- Application number: 14/800,468
- Filed: 2015-07-15
- Published: 2016-05-12
- Granted: 2019-06-04
- Earliest claimed: 2010-06-24
- Assignees: La Jolla Institute for Allergy and Immunology
- Applicants: La Jolla Institute for Allergy and Immunology
- Inventors: Sujan Shresta; Lauren Yauch; Alessandro Sette; Daniela Weiskopf
- Web page: https://patentgrep.com/patent/US10308689B2

## CPC

- C07K 14/005: from viruses
- A61K 39/12: Viral antigens
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- G01N 33/56983: {Viruses}
- A61K 2039/55566: {Emulsions, e.g. Freund's adjuvant, MF59}
- C07K 2319/00: Fusion polypeptide
- C07K 2319/21: containing a His-tag
- 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)
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Dengue virus (DV) peptides, including T cell epitopes, structural and non-structural (NS) polypeptide sequences, subsequences and modifications thereof, nucleotide sequences encoding such peptides, and compositions including such peptides and encoding nucleotide sequences, and cells expressing such peptides, are provided. Such DV peptides, nucleotide sequences and compositions, can be used to elicit, stimulate, induce, promote, increase, enhance or activate an anti-DV CD8+ T cell response or an anti-DV CD4+ T cell response. Such peptides, nucleotide sequences and compositions can also be used for and in methods of vaccination/immunization of a subject against Dengue virus (DV) (e.g., to provide protection against DV infection and/or pathology), and for treatment of a subject in need thereof, for example, treatment of the subject for a Dengue virus (DV) infection or pathology.

## Claims

### Claim 1

A pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient, an adjuvant and a peptide consisting of a sequence 9-25 amino acids in length wherein 9 contiguous amino acids are identical to VATTFVTPM (SEQ ID NO:134), wherein the peptide elicits, stimulates, induces, promotes, increases, or enhances an anti-DV CD8+ T cell response or an anti-DV CD4+ T cell response, wherein the adjuvant is present in an amount that increases immunogenicity of the peptide.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein the peptide is isolated or purified.

### Claim 3 (depends on 1)

The pharmaceutical composition of claim 1, wherein said anti-DV CD8+ T cell response comprises increased IFN-gamma, TNF-alpha, IL-1alpha, IL-6 or IL-8 production by CD8+ T cells in the presence of the peptide.

### Claim 4 (depends on 1)

The pharmaceutical composition of claim 1, wherein the CD4+ T cells produce IFN-gamma, TNF, IL-2, or CD40L in the presence of the peptide, or kill peptide-pulsed target cells.

### Claim 5 (depends on 1)

The pharmaceutical composition of claim 1, wherein the adjuvant comprises Freund's complete adjuvant (CFA), Freund's incomplete adjuvant (IFA), metal or metallic salts, aluminum or aluminum salts, aluminum phosphate, aluminum hydroxide, alum, hydrated potassium aluminum sulfate, bacterially derived compounds, Monophosphoryllipid A and derivatives thereof, enterobacteriallipopolysaccharides (LPS), plant derived saponins and derivatives thereof, Quil A and fragments thereof, soya lecithin or oleic acid surfactants, sorbitan trioleate, polyvinylpyrrolidone, CpG oligonucleotides, polyriboA and polyriboU, block copolymers, GM-CSF, IL-1, or Muramyl tripeptide (MTP).

### Claim 6 (depends on 1)

A method of stimulating, inducing, promoting, increasing, or enhancing an immune response against Dengue virus serotype 2 (DENV-2) in a subject, comprising administering to a subject an amount of the pharmaceutical composition of claim 1 sufficient to stimulate, induce, promote, increase, or enhance an immune response against DENV-2 in the subject.

### Claim 7 (depends on 6)

The method of claim 6, wherein the Dengue virus (DV) infection is acute.

### Claim 8 (depends on 1)

The pharmaceutical composition of claim 1, wherein the composition is sterile.