# US 10,946,087 B2 · Vaccine compositions against dengue virus diseases

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- Number: US 10,946,087 B2
- Document ID: US10946087B2
- Status: Granted
- Kind: B2
- Application number: 15/507,952
- Filed: 2015-09-02
- Published: 2017-10-26
- Granted: 2021-03-16
- Earliest claimed: 2014-09-02
- Assignees: Sanofi Pasteur Limited
- Applicants: Sanofi Pasteur
- Inventors: Nadia Tornieporth; Alain Bouckenooghe; Fernando Noriega; Melanie Saville; Nicholas Jackson; Yves Girerd-Chambaz
- Web page: https://patentgrep.com/patent/US10946087B2

## CPC

- A61K 39/12: Viral antigens
- A61K 39/295: Polyvalent viral antigens (vaccinia virus or variola virus A61K39/285); Mixtures of viral and bacterial antigens
- A61P 31/14: for RNA viruses
- A61P 37/04: Immunostimulants
- 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 2039/5252: {inactivated (killed)}
- A61K 2039/5254: {avirulent or attenuated}
- A61K 2039/5256: {expressing foreign proteins}
- A61K 2039/5258: {Virus-like particles}
- C12N 2770/24123: Virus like particles [VLP]
- C12N 2770/24134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2770/24144: Chimeric viral vector comprising heterologous viral elements for production of another viral vector
- 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)
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention relates to vaccine compositions that are useful in a method of protecting a human subject against dengue disease.

## Claims

### Claim 1

A method of protecting a dengue immune human subject against dengue disease caused by a dengue virus of serotype 2, comprising
A) administering only 2 doses of an effective amount of a vaccine composition to the dengue immune human subject, wherein the doses are 6 months apart, and wherein said composition comprises:
a dengue antigen of each of serotypes 1 to 4, wherein said dengue antigens of serotypes 1 to 4 are each a live attenuated chimeric dengue virus comprising a yellow fever virus genome whose prM-E sequence has been substituted with the prM-E sequence of a dengue virus;
wherein the prM-E sequence of the dengue antigen of serotype 1 comprises SEQ ID NO: 1, the prM-E sequence of the dengue antigen of serotype 2 comprises SEQ ID NO: 2, the prM-E sequence of the dengue antigen of serotype 3 comprises SEQ ID NO: 3 and the prM-E sequence of the dengue antigen of serotype 4 comprises SEQ ID NO: 4:
wherein each dose of tetravalent vaccine comprises 5±1 log10 CCID50 of each live attenuated chimeric dengue virus;
wherein the route of administration is subcutaneous; and
wherein said dengue immune human subject is aged between 2 and 60 years old; and
B) protecting the dengue immune human subject against dengue disease caused by a dengue virus of serotype 2.

### Claim 2 (depends on 1)

The method of claim 1, wherein said dengue disease is severe dengue disease.

### Claim 3 (depends on 1)

The method of claim 1, wherein said method results in a reduction in the incidence or likelihood of hospitalization due to said dengue disease.

### Claim 4 (depends on 1)

The method of claim 1, wherein said method also protects said human subject against dengue disease caused by a dengue virus of serotype 1, dengue disease caused by a dengue virus of serotype 3 and dengue disease caused by a dengue virus of serotype 4.

### Claim 5 (depends on 4)

The method of claim 4, wherein said dengue disease caused by a dengue virus of serotype 1 is severe dengue disease, said dengue disease caused by a dengue virus of serotype 2 is severe dengue disease, said dengue disease caused by a dengue virus of serotype 3 is severe dengue disease and said dengue disease caused by a dengue virus of serotype 4 is severe dengue disease.

### Claim 6 (depends on 1)

The method of claim 1, wherein said subject is aged between 6 and 60 years old, between 9 and 60 years old, or between 12 and 60 years old.

### Claim 7 (depends on 1)

The method of claim 1, wherein said subject is at least 9 years of age.

### Claim 8 (depends on 6)

The method of claim 6, wherein said subject is aged between 2 and 16 years old, between 6 and 16 years old, or between 9 and 16 years old.

### Claim 9 (depends on 1)

The method of claim 1, wherein said subject is yellow fever immune.

### Claim 10 (depends on 1)

The method of claim 1, wherein said subject resides in a dengue endemic area.

### Claim 11 (depends on 1)

The method of claim 1, wherein said dengue disease caused by a dengue virus of serotype 2 is dengue disease caused by a dengue virus of serotype 2 having an American, Asian/American, or a Cosmopolitan genotype.

### Claim 12 (depends on 1)

The method of claim 1, wherein said composition further comprises a pharmaceutically acceptable carrier or excipient.

### Claim 13 (depends on 1)

The method of claim 1, wherein said method of protecting results in a statistically significant reduction in the incidence or likelihood of repeated symptomatic virologically-confirmed dengue cases.

### Claim 14 (depends on 1)

The method of claim 1, wherein the human subject is protected against dengue disease caused by a dengue virus of serotype 2 after a first dose of the vaccine composition.

### Claim 15 (depends on 1)

The method of claim 1, wherein the human subject is monotypic dengue immune.

### Claim 16 (depends on 1)

The method of claim 1, wherein the human subject is multitypic dengue immune.

### Claim 17 (depends on 12)

The method of claim 12, wherein the pharmaceutically acceptable carrier is 0.4% NaCl buffer containing excipients consisting of essential amino acids, non-essential amino acids, L-arginine chlorhydrate, saccharose, D-trehalose, dehydrate, sorbitol, tris (hydroxymethyl) aminoethane and urea.

### Claim 18 (depends on 1)

The method of claim 1, wherein the vaccine composition is administered in a volume between 0.1 and 1.0 ml.

### Claim 19 (depends on 1)

The method of claim 1, wherein the vaccine composition is administered in a volume of 0.5 ml.

### Claim 20 (depends on 1)

The method of claim 1, wherein the dengue immune human subject is in good health based on medical history and physical examination.

### Claim 21

A method of protecting a dengue immune human subject against dengue disease caused by a dengue virus of serotype 2, comprising
A) administering only 2 doses of an effective amount of a vaccine composition to the dengue immune human subject, wherein the doses are 6 months apart, and wherein said composition comprises:
a dengue antigen of each of serotypes 1 to 4, wherein said dengue antigens of serotypes 1 to 4 are each a live attenuated chimeric dengue virus comprising a yellow fever virus genome whose prM-E sequence has been substituted with the prM-E sequence of a dengue virus;
wherein the prM-E sequence of the dengue antigen of serotype 1 comprises SEQ ID NO: 1, the prM-E sequence of the dengue antigen of serotype 2 comprises SEQ ID NO: 2, the prM-E sequence of the dengue antigen of serotype 3 comprises SEQ ID NO: 3 and the prM-E sequence of the dengue antigen of serotype 4 comprises SEQ ID NO: 4;
wherein each dose of tetravalent vaccine comprises 5±1 log10 CCID50 of each live attenuated chimeric dengue virus;
wherein the route of administration is subcutaneous;
wherein the vaccine composition further comprises a pharmaceutically acceptable carrier which is 0.4% NaCl buffer containing excipients consisting of essential amino acids, non-essential amino acids, L-arginine chlorhydrate, saccharose, D-trehalose, dehydrate, sorbitol, tris (hydroxymethyl) aminoethane and urea;
wherein the vaccine composition is administered in a volume between 0.1 and 1.0 ml;
wherein said subject is aged between 2 and 60 years old;
wherein the dengue immune human subject is in good health based on medical history and physical examination; and
wherein said subject resides in a dengue endemic area; and
B) protecting the dengue immune human subject against dengue disease caused by a dengue virus of serotype 2.

### Claim 22 (depends on 21)

The method of claim 21, wherein the human subject is monotypic dengue immune.

### Claim 23 (depends on 21)

The method of claim 21, wherein the human subject is multitypic dengue immune.

### Claim 24 (depends on 21)

The method of claim 21, wherein the human subject is aged between 6 and 60 years old.

### Claim 25 (depends on 21)

The method of claim 21, wherein the human subject is aged between 9 and 16 years old.

### Claim 26 (depends on 21)

The method of claim 21, wherein the prM-E sequence of the dengue antigen of serotype 2 comprises SEQ ID NO: 2.

### Claim 27 (depends on 21)

The method of claim 21, wherein the prM-E sequence of the dengue antigen of serotype 2 comprises SEQ ID NO: 2.