# US 12,178,867 B2 · MHC class i associated peptides for prevention and treatment of multiple flavi virus

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- Number: US 12,178,867 B2
- Document ID: US12178867B2
- Status: Granted
- Kind: B2
- Application number: 18/332,022
- Filed: 2023-06-09
- Published: 2023-11-02
- Granted: 2024-12-31
- Earliest claimed: 2018-01-06
- Assignees: Emergex Vaccines Holding Ltd.
- Applicants: Emergex Vaccines Holding Limited
- Inventors: Ramila Philip
- Web page: https://patentgrep.com/patent/US12178867B2

## CPC

- A61K 39/12: Viral antigens
- A61K 47/6929: {the form being a nanoparticle, e.g. an immuno-nanoparticle}
- C07K 14/1816: {Flaviviridae, e.g. pestivirus, mucosal disease virus, bovine viral diarrhoea virus, classical swine fever virus (hog cholera virus), border disease virus}
- A61K 2039/60: {characteristics by the carrier linked to the antigen}
- 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
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The invention provides a vaccine composition comprising a flavi peptide comprising one or more CD8+ T cell epitopes.

## Claims

### Claim 1

A vaccine composition comprising a conjugate, the conjugate comprising a flavivirus peptide attached to a gold nanoparticle, wherein:
(i) the flavivirus peptide is 8 to 30 amino acids in length, and comprises a CD8+ T cell epitope comprising the amino acid sequence set forth in SEQ ID NO: 15 or SEQ ID NO: 18, or a variant thereof which differs from SEQ ID NO: 15 or SEQ ID NO: 18 by one amino acid substitution, deletion or insertion; and
(ii) the gold nanoparticle is coated with galactose and/or GlcNAc.

### Claim 2 (depends on 1)

The vaccine composition of claim 1, wherein the gold nanoparticle is coated with alpha-galactose and/or beta-GlcNAc.

### Claim 3 (depends on 1)

The vaccine composition of claim 1, wherein the gold nanoparticle is coated with galactose and GlcNAc.

### Claim 4 (depends on 1)

The vaccine composition of claim 1, wherein the flavivirus peptide is attached to the nanoparticle by a linker.

### Claim 5 (depends on 4)

The vaccine composition of claim 4, wherein the linker has the structure:
—S—(CH2)2—CONH-AAY-
wherein the S is attached to the nanoparticle and AAY is a peptide joined to the N-terminus of the flavivirus peptide.

### Claim 6 (depends on 1)

The vaccine composition of claim 1, wherein the variant differs from SEQ ID NO: 15 or SEQ ID NO: 18 by one conservative amino acid substitution.

### Claim 7 (depends on 1)

The vaccine composition of claim 1, wherein the flavivirus peptide comprises the T cell epitope set forth in SEQ ID NO: 15.

### Claim 8 (depends on 1)

The vaccine composition of claim 1, wherein the flavivirus peptide comprises the T cell epitope set forth in SEQ ID NO: 18.

### Claim 9 (depends on 1)

The vaccine composition of claim 1, comprising a first conjugate and a second conjugate, each comprising a flavivirus peptide attached to a gold nanoparticle, wherein each flavivirus peptide is 8 to 30 amino acids in length, the gold nanoparticle is coated with galactose and GlcNAc and:
(i) the first conjugate comprises a flavivirus peptide comprising a first CD8+ T cell epitope comprising the amino acid sequence set forth in SEQ ID NO: 15 or SEQ ID NO: 18, or a variant thereof which differs from SEQ ID NO: 15 or SEQ ID NO: 18 by one amino acid substitution, deletion or insertion; and
(ii) the second conjugate comprises a flavivirus peptide comprising a second CD8+ T cell epitope comprising the amino acid sequence set forth in any one of SEQ ID NOs: 1 to 23, or a variant thereof which differs from any one of SEQ ID NOs: 1 to 23 by one amino acid substitution, deletion or insertion;
wherein the first and second CD8+ T cell epitopes are different.

### Claim 10 (depends on 9)

The vaccine composition of claim 9, comprising:
(i) a conjugate comprising SEQ ID NO: 15 or a variant thereof;
(ii) a conjugate comprising SEQ ID NO: 16 or a variant thereof;
(iii) a conjugate comprising SEQ ID NO: 17 or a variant thereof;
(iv) a conjugate comprising SEQ ID NO: 18 or a variant thereof;
(v) a conjugate comprising SEQ ID NO: 19 or a variant thereof;
(vi) a conjugate comprising SEQ ID NO: 20 or a variant thereof;
(vii) a conjugate comprising SEQ ID NO: 21 or a variant thereof;
(viii) a conjugate comprising SEQ ID NO: 22 or a variant thereof; and
(ix) a conjugate comprising SEQ ID NO: 23 or a variant thereof;
wherein said variants differ from each of SEQ ID NOs: 15 to 23 by one amino acid substitution, deletion or insertion.

### Claim 11 (depends on 10)

The vaccine composition of claim 10, comprising:
(i) a conjugate comprising SEQ ID NO: 15;
(ii) a conjugate comprising SEQ ID NO: 16;
(iii) a conjugate comprising SEQ ID NO: 17;
(iv) a conjugate comprising SEQ ID NO: 18;
(v) a conjugate comprising SEQ ID NO: 19;
(vi) a conjugate comprising SEQ ID NO: 20;
(vii) a conjugate comprising SEQ ID NO: 21;
(viii) a conjugate comprising SEQ ID NO: 22; and
(ix) a conjugate comprising SEQ ID NO: 23.

### Claim 12 (depends on 1)

The vaccine composition of claim 1, further comprising a pharmaceutically acceptable diluent, carrier or excipient.

### Claim 13 (depends on 1)

A method of treating or preventing a flavivirus infection in a subject, comprising administering the vaccine composition of claim 1 to an individual infected with, or at risk of being infected with, a flavivirus.

### Claim 14 (depends on 13)

The method of claim 13, wherein the method is for preventing a flavivirus infection in a subject, and the individual is at risk of being infected with a flavivirus.

### Claim 15 (depends on 13)

The method of claim 13, wherein the flavivirus infection is a Zika virus infection, West Nile virus infection, dengue virus infection, yellow fever virus infection, and/or Japanese encephalitis virus infection.

### Claim 16 (depends on 15)

The method of claim 15, wherein the flavivirus infection is a dengue virus infection.

### Claim 17 (depends on 13)

The method of claim 13, wherein the method comprises intradermal or transdermal administration of the vaccine composition to the individual.

### Claim 18 (depends on 2)

The vaccine composition of claim 2, wherein the gold nanoparticle is coated with alpha-galactose and beta-GlcNAc.

### Claim 19 (depends on 1)

A method of stimulating an immune response in an individual, comprising administering to the individual the vaccine composition of claim 1.

### Claim 20 (depends on 19)

The method of claim 19, wherein the method comprises intradermal or transdermal administration of the vaccine composition to the individual.
