# US 12,005,114 B2 · Coronavirus vaccine comprising a mosaic protein

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- Number: US 12,005,114 B2
- Document ID: US12005114B2
- Status: Granted
- Kind: B2
- Application number: 18/156,982
- Filed: 2023-01-19
- Published: 2023-08-17
- Granted: 2024-06-11
- Earliest claimed: 2021-04-08
- Assignees: Vaxthera SAS
- Applicants: Vaxthera SAS
- Inventors: Jorge E. Osorio
- Web page: https://patentgrep.com/patent/US12005114B2

## CPC

- A61K 39/12: Viral antigens
- A61K 39/215: Coronaviridae, e.g. avian infectious bronchitis virus
- A61P 31/14: for RNA viruses
- C07K 14/005: from viruses
- A61K 2039/5256: {expressing foreign proteins}
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/575: {humoral response}
- C07K 2319/00: Fusion polypeptide
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- C12N 2770/20034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- 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
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Disclosed herein are mosaic coronavirus (MoCoV) spike (S) proteins or antigenic fragments thereof. Also disclosed herein are nucleic acid constructs comprising one or more nucleic acid sequences encoding a MoCoV S protein or antigenic fragment thereof. Also disclosed herein are coronavirus vaccine vectors comprising one or more polynucleotides encoding a MoCoV S protein or antigenic fragment thereof. Also disclosed herein are coronavirus vaccines comprising one or more MoCoV S proteins or antigenic fragments thereof and one or more carriers. Also disclosed herein are pharmaceutical compositions, host cells, and kits comprising one or more of the MoCoV S proteins or antigenic fragments thereof, nucleic acid constructs, coronavirus vaccine vectors, and/or coronavirus vaccines. Also disclosed herein are methods of eliciting an immune response in a subject against one or more coronavirus antigens and methods of preventing, reducing the incidence of, attenuating, or treating coronavirus infection in a subject in need thereof.

## Claims

### Claim 1

A nucleic acid construct comprising one or more nucleic acid sequences selected from the group consisting of:
a first nucleic acid sequence encoding a first mosaic coronavirus (MoCoV) spike (S) protein or an antigenic fragment thereof, wherein the first MoCoV S protein or antigenic fragment thereof is optimized for maximum T cell epitope coverage of at least two human coronaviruses;
(ii) a first nucleic acid sequence encoding a first MoCoV S protein or an antigenic fragment thereof and a second nucleic acid sequence encoding a second MoCoV S protein or an antigenic fragment thereof, wherein the first and second MoCoV S proteins or antigenic fragments thereof are optimized for maximum T cell epitope coverage of at least two human coronaviruses;
(iii) a first nucleic acid sequence encoding a first MoCoV S protein or an antigenic fragment thereof, a second nucleic acid sequence encoding a second MoCoV S protein or an antigenic fragment thereof, and a third nucleic acid sequence encoding a third MoCoV S protein or an antigenic fragment thereof, wherein the first, second, and third MoCoV S proteins or antigenic fragments thereof are optimized for maximum T cell epitope coverage of at least two human coronaviruses; and
(iv) combinations thereof,
wherein:
(a) the first nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 4, and the second nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 6;
(b) the first nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 10, and the second nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 12;
(c) the first nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 10, the second nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 4, and the third nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 6; or
(d) the first nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 12, the second nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 4, and the third nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 6.

### Claim 2

A nucleic acid construct comprising a first nucleic acid sequence operatively linked to a first promoter, a second nucleic acid sequence operatively linked to a second promoter, and a third nucleic acid sequence operatively linked to a third promoter, wherein:
(i) the first nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 10, wherein the second nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 4, and wherein the third nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 2, SEQ ID NO: 6, or SEQ ID NO: 14;
(ii) the first nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 12, wherein the second nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 4, and wherein the third nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 2, SEQ ID NO: 6, or SEQ ID NO: 14; or
(iii) wherein the first nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 10, wherein the second nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 12, and wherein the third nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, or SEQ ID NO: 14.

### Claim 3 (depends on 2)

The nucleic acid construct of claim 2, wherein the first, second, and third promoters are selected from the group consisting of: a S E/L promoter, a LEO promoter, and any combination thereof.

### Claim 4 (depends on 3)

The nucleic acid construct of claim 3, wherein the first promoter is a S E/L promoter, the second promoter is a S E/L promoter, and the third promoter is a LEO promoter.

### Claim 5

A nucleic acid construct comprising a first nucleic acid sequence encoding a first MoCoV S protein, a second nucleic acid sequence encoding a second MoCoV S protein, and a third nucleic acid sequence encoding a third MoCoV S protein, wherein:
(i) the first MoCoV S protein comprises the amino acid sequence of SEQ ID NO: 9, wherein the second MoCoV S protein comprises the amino acid sequence of SEQ ID NO: 3, and wherein the third MoCoV S protein comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 16, or SEQ ID NO: 17;
(ii) the first MoCoV S protein comprises the amino acid sequence of SEQ ID NO: 11, wherein the second MoCoV S protein comprises the amino acid sequence of SEQ ID NO: 3, and wherein the third MoCoV S protein comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 16, or SEQ ID NO: 17; or
(iii) the first MoCoV S protein comprises the amino acid sequence of SEQ ID NO: 9, wherein the second MoCoV S protein comprises the amino acid sequence of SEQ ID NO: 11, and wherein the third MoCoV S protein comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 16, or SEQ ID NO: 17.

### Claim 6 (depends on 5)

The nucleic acid construct of claim 5, wherein the nucleic acid construct further comprises a first promoter capable of controlling the expression of the first MoCoV S protein, a second promoter capable of controlling the expression of the second MoCoV S protein, and a third promoter capable of controlling the expression of the third MoCoV S protein.

### Claim 7 (depends on 6)

The nucleic acid construct of claim 6, wherein the first, second, and third promoters are selected from the group consisting of: a S E/L promoter, a LEO promoter, and any combination thereof.

### Claim 8 (depends on 7)

The nucleic acid construct of claim 7, wherein the first promoter is a S E/L promoter, the second promoter is a S E/L promoter, and the third promoter is a LEO promoter.

### Claim 9 (depends on 1)

A pharmaceutical composition comprising the nucleic acid construct of claim 1 and one or more carriers that render the composition suitable for pharmaceutical use.

### Claim 10 (depends on 1)

A host cell comprising the nucleic acid construct of claim 1, wherein the host cell is a cell line.

### Claim 11 (depends on 10)

The host cell of claim 10, wherein the host cell is a human host cell.

### Claim 12 (depends on 10)

The host cell of claim 10, wherein the host cell is a yeast host cell.

### Claim 13 (depends on 1)

A coronavirus vaccine vector comprising the nucleic acid construct of claim 1.

### Claim 14

A coronavirus vaccine comprising a first MoCoV S protein or an antigenic fragment thereof and one or more carriers, wherein the first MoCoV S protein or antigenic fragment thereof is optimized for maximum T cell epitope coverage of at least two human coronaviruses, wherein the first MoCoV S protein or antigenic fragment thereof comprises the amino acid sequence of SEQ ID NO: 9.

### Claim 15 (depends on 14)

The coronavirus vaccine of claim 14, wherein the coronavirus vaccine further comprises a second MoCoV S protein or an antigenic fragment thereof, wherein the second MoCoV S protein or an antigenic fragment thereof comprises the amino acid sequence of SEQ ID NO: 3.

### Claim 16 (depends on 15)

The coronavirus vaccine of claim 15, wherein the coronavirus vaccine further comprises a third MoCoV S protein or an antigenic fragment thereof, wherein the third MoCoV S protein or an antigenic fragment thereof comprises an amino acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 16, or SEQ ID NO: 17.

### Claim 17 (depends on 16)

The coronavirus vaccine of claim 16, wherein the third MoCoV S protein comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 5, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 16, or SEQ ID NO: 17.

### Claim 18 (depends on 14)

The coronavirus vaccine of claim 14, wherein the carrier is a MVA virus, a vaccinia virus, or a poxvirus.

### Claim 19 (depends on 1)

A kit comprising the nucleic acid construct of claim 1.

### Claim 20 (depends on 14)

A method of eliciting an immune response in a subject against one or more coronavirus antigens, the method comprising administering the coronavirus vaccine of claim 14 to the subject.

### Claim 21 (depends on 20)

The method of claim 20, wherein the coronavirus vaccine is effective to elicit an immune response in the subject to the one or more coronavirus antigens.

### Claim 22 (depends on 21)

The method of claim 21, wherein the coronavirus vaccine is effective to elicit an immune response in the subject to coronavirus antigens from at least two different coronavirus strains, wherein the coronavirus strains are selected from the group consisting of: HCoV-OC43, SARS-CoV, MERS-CoV, SARS-CoV-2, HCoV-229E, HCoV-NL63, BtCoV-HKU4, BtCoV-HKU5, BtCoV-HKU9, BtCoV-273, BtCoV-HKU3, and BtCoV-279.

### Claim 23 (depends on 14)

A method of preventing, reducing the incidence of, attenuating, or treating coronavirus infection in a subject in need thereof, the method comprising administering the coronavirus vaccine of claim 14 to the subject.

### Claim 24 (depends on 23)

The method of claim 23, wherein the coronavirus vaccine prevents, reduces the incidence of, attenuates or treats infection with a coronavirus strain selected from the group consisting of: HCoV-OC43, SARS-CoV, MERS-CoV, SARS-CoV-2, HCoV-229E, and HCoV-NL63.

### Claim 25 (depends on 23)

The method of claim 23, wherein the coronavirus vaccine is administered to the subject by a buccal, epidermal, epidural, intraarterial, intraarticular, intracapsular, intracardiac, intracoronary, intradermal, intralesional, intralymphatic, intramuscular, intranasal, intraorbital, intraperitoneal, intraspinal, intrasterna, intrathecal, intravenous, mucosal, oral, rectal, subarachnoid, subcapsular, subcutaneous, subcuticular, sublingual, topical, transtracheal, or vaginal route of administration or any combination thereof.

### Claim 26 (depends on 14)

The coronavirus vaccine of claim 14, wherein the coronavirus vaccine is a mRNA vaccine and wherein the coronavirus vaccine is administered in the form of a lipid nanoparticle.

### Claim 27 (depends on 26)

The coronavirus vaccine of claim 26, wherein the lipid nanoparticle comprises a PEG-modified lipid, a non-cationic lipid, a sterol, an ionizable cationic lipid, or any combination thereof.

### Claim 28 (depends on 26)

The coronavirus vaccine of claim 26, wherein the mRNA vaccine comprises a mRNA comprising a 5′ untranslated region (UTR) and a 3′ UTR.

### Claim 29 (depends on 28)

The coronavirus vaccine of claim 28, wherein the mRNA comprises a chemical modification.