# US 11,298,417 B2 · Measles virus vaccine expressing SARS-CoV-2 protein(s)

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- Number: US 11,298,417 B2
- Document ID: US11298417B2
- Status: Granted
- Kind: B2
- Application number: 17/143,740
- Filed: 2021-01-07
- Published: 2021-12-16
- Granted: 2022-04-12
- Earliest claimed: 2020-06-15
- Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Applicants: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Inventors: William Paul Duprex; Natasha Louise Tilston-Lunel; Shamkumar Nambulli
- Web page: https://patentgrep.com/patent/US11298417B2

## CPC

- A61K 39/12: Viral antigens
- A61K 39/215: Coronaviridae, e.g. avian infectious bronchitis virus
- A61K 39/165: Mumps or measles virus
- A61P 31/14: for RNA viruses
- C07K 14/005: from viruses
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 15/86: Viral vectors
- A61K 2039/5256: {expressing foreign proteins}
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/572: {cytotoxic response}
- A61K 2039/575: {humoral response}
- C12N 2760/18434: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2760/18443: viral genome or elements thereof as genetic vector
- C12N 2770/20022: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- 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

A recombinant measles viral vector comprising a nucleic acid sequence encoding a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike glycoprotein is provided. Polypeptides comprising the SARS-CoV-2 spike glycoprotein also are provided, as well as related nucleic acids, vectors, and compositions. The polypeptides, nucleic acids, vectors, and compositions can be used in methods of preventing, inhibiting, reducing, eliminating, protecting, or delaying the onset of an infection or an infectious clinical condition caused by coronavirus and methods for inducing an immune response against a coronavirus.

## Claims

### Claim 1

A method for preventing, inhibiting, reducing, eliminating, protecting, or delaying the onset of an infection or an infectious clinical condition caused by coronavirus in a subject comprising administering a recombinant measles viral vector comprising a nucleic acid sequence encoding a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike glycoprotein to the subject, wherein the nucleic acid sequence contains at least one modification that disrupts the endoplasmic reticulum (ER) retention sequence of the SARS-CoV-2 spike glycoprotein.

### Claim 2 (depends on 1)

The method of claim 1, wherein the recombinant measles viral vector is a recombinant Edmonston-Zagreb (EZ) measles viral vector.

### Claim 3 (depends on 1)

The method of claim 1, wherein the nucleic acid sequence has been codon optimized.

### Claim 4 (depends on 1)

The method of claim 1, wherein the ER retention sequence of the SARS-CoV-2 spike glycoprotein contains AxAxx rather than KxHxx in the cytoplasmic tail.

### Claim 5 (depends on 1)

The method of claim 1, wherein the nucleic acid sequence encoding the SARS-CoV-2 spike glycoprotein is SEQ ID NO: 3 (S-CO-AA).

### Claim 6 (depends on 1)

The method of claim 1, wherein the SARS-CoV-2 spike glycoprotein comprises the amino acid sequence of SEQ ID NO: 10 (S-CO-AA).

### Claim 7 (depends on 1)

The method of claim 1, wherein the recombinant measles viral vector comprises the nucleic acid sequence of SEQ ID NO: 17 (SARS-CoV-2-S-CO-AA).

### Claim 8

A method for inducing an immune response against a coronavirus in a subject comprising administering a recombinant measles viral vector comprising a nucleic acid sequence encoding a SARS-CoV-2 spike glycoprotein to the subject, wherein the nucleic acid sequence contains at least one modification that disrupts the endoplasmic reticulum (ER) retention sequence of the SARS-CoV-2 spike glycoprotein.

### Claim 9 (depends on 1)

The method of claim 1, wherein the subject is a human subject.

### Claim 10 (depends on 1)

The method of claim 1, wherein the recombinant measles viral vector is administered by oral, sublingual, buccal, intradermal, parenteral, subcutaneous, intravenous, intramuscular, intraarterial, intrathecal, or interperitoneal administration.

### Claim 11

A polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 10 (S-CO-AA).

### Claim 12 (depends on 11)

A pharmaceutical composition comprising (i) the polypeptide of claim 11, a nucleic acid encoding the polypeptide, or a recombinant vector comprising the nucleic acid and (ii) a pharmaceutically acceptable carrier.

### Claim 13 (depends on 11)

A method for preventing, inhibiting, reducing, eliminating, protecting, or delaying the onset of an infection or an infectious clinical condition caused by coronavirus in a subject comprising administering the polypeptide of claim 11, a nucleic acid encoding the polypeptide, a recombinant vector comprising the nucleic acid, or a pharmaceutical composition thereof to the subject.

### Claim 14 (depends on 11)

A method for inducing an immune response against a coronavirus in a subject comprising administering the polypeptide of claim 11, a nucleic acid encoding the polypeptide, a recombinant vector comprising the nucleic acid, or a pharmaceutical composition thereof to the subject.

### Claim 15 (depends on 8)

The method of claim 8, wherein the recombinant measles viral vector is a recombinant Edmonston-Zagreb (EZ) measles viral vector.

### Claim 16 (depends on 8)

The method of claim 8, wherein the nucleic acid sequence has been codon optimized.

### Claim 17 (depends on 8)

The method of claim 8, wherein the ER retention sequence of the SARS-CoV-2 spike glycoprotein contains AxAxx rather than KxHxx in the cytoplasmic tail.

### Claim 18 (depends on 8)

The method of claim 8, wherein the nucleic acid sequence encoding the SARS-CoV-2 spike glycoprotein is SEQ ID NO: 3 (S-CO-AA).

### Claim 19 (depends on 8)

The method of claim 8, wherein the SARS-CoV-2 spike glycoprotein comprises the amino acid sequence of SEQ ID NO: 10 (S-CO-AA).

### Claim 20 (depends on 8)

The method of claim 8, wherein the recombinant measles viral vector comprises the nucleic acid sequence of SEQ ID NO: 17 (SARS-CoV-2-S-CO-AA).