# US 11,896,664 B2 · Corona virus vaccine formulations

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,896,664 B2
- Document ID: US11896664B2
- Status: Granted
- Kind: B2
- Application number: 17/572,182
- Filed: 2022-01-10
- Published: 2022-04-28
- Granted: 2024-02-13
- Earliest claimed: 2020-01-27
- Assignees: Novavax, Inc.
- Applicants: Novavax, Inc.
- Inventors: Gale Smith; Michael J. Massare; Jing-Hui Tian
- Web page: https://patentgrep.com/patent/US11896664B2

## CPC

- A61K 39/215: Coronaviridae, e.g. avian infectious bronchitis virus
- A61K 39/12: Viral antigens
- A61P 31/14: for RNA viruses
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- A61K 2039/55555: {Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers}
- A61K 2039/55577: {Saponins; Quil A; QS21; ISCOMS}
- 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
- 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 coronavirus Spike (S) proteins and nanoparticles comprising the same, which are suitable for use in vaccines. The nanoparticles present antigens from pathogens surrounded to and associated with a detergent core resulting in enhanced stability and good immunogenicity. Dosages, formulations, and methods for preparing the vaccines and nanoparticles are also disclosed.

## Claims

### Claim 1

A non-naturally occurring sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (CoV S) glycoprotein, wherein the CoV S glycoprotein comprises two modifications compared to a native S glycoprotein wherein
(i) the first modification is an inactivated furin cleavage site having the amino acid sequence of QQAQ (SEQ ID NO: 7); and
(ii) the second modification is mutation of amino acids 973 and 974 to proline;
wherein the amino acids are numbered according to SEQ ID NO: 2.

### Claim 2 (depends on 1)

An isolated host cell comprising the CoV S glycoprotein of claim 1.

### Claim 3 (depends on 2)

The isolated host cell of claim 2, wherein the cell is an insect cell.

### Claim 4 (depends on 3)

The isolated host cell of claim 3, wherein the insect cell is selected from the group consisting of a Spodoptera frugiperda 9 (Sf9) cell, a Spodoptera frugiperda 21 (Sf21) cell, a Trichoplusia ni cell, and a Drosophila S2 cell.

### Claim 5 (depends on 3)

The isolated host cell of claim 3, wherein the insect cell is a Sf9 cell.

### Claim 6 (depends on 1)

An isolated nucleic acid encoding the CoV S glycoprotein of claim 1.

### Claim 7 (depends on 6)

An isolated host cell expressing the isolated nucleic acid of claim 6.

### Claim 8 (depends on 1)

An immunogenic composition comprising the CoV S glycoprotein of claim 1 and a pharmaceutically acceptable buffer.

### Claim 9 (depends on 8)

The immunogenic composition of claim 8, comprising about 5 μg of the CoV S glycoprotein.

### Claim 10 (depends on 8)

The immunogenic composition of claim 8, comprising about 3 μg of the CoV S glycoprotein.

### Claim 11 (depends on 8)

The immunogenic composition of claim 8, comprising a saponin adjuvant.

### Claim 12 (depends on 11)

The immunogenic composition of claim 11, wherein the saponin adjuvant comprises:
(i) a first iscom particle comprising fraction A of Quillaja saponaria Molina and not fraction C of Quillaja saponaria Molina; and
(ii) a second iscom particle comprising fraction C of Quillaja saponaria Molina and not fraction A of Quillaja saponaria Molina.

### Claim 13 (depends on 12)

The immunogenic composition of claim 12, wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for about 85% by weight and about 15% by weight; respectively, of the sum of the weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the saponin adjuvant.

### Claim 14 (depends on 11)

The immunogenic composition of claim 11, comprising about 50 μg of the saponin adjuvant.

### Claim 15 (depends on 8)

The immunogenic composition of claim 8, comprising a nanoparticle comprising the CoV S glycoprotein and a non-ionic detergent core, wherein the CoV S glycoprotein is anchored to the detergent core via the transmembrane domain of the CoV S glycoprotein.

### Claim 16 (depends on 15)

The immunogenic composition of claim 15, wherein the non-ionic detergent is selected from the group consisting of polysorbate-20 (PS20), polysorbate-40 (PS40), polysorbate-60 (PS60), polysorbate-65 (PS65), and polysorbate-80 (PS80).

### Claim 17 (depends on 16)

The immunogenic composition of claim 16, wherein the non-ionic detergent is PS80.

### Claim 18 (depends on 8)

A method of stimulating an immune response against SARS-CoV-2 in a subject comprising administering the immunogenic composition of claim 8.

### Claim 19 (depends on 18)

The method of claim 18, wherein the immunogenic composition comprises about 5 μg of CoV S glycoprotein.

### Claim 20 (depends on 18)

The method of claim 18, wherein the immunogenic composition comprises about 3 μg of CoV S glycoprotein.

### Claim 21 (depends on 18)

The method of claim 18, wherein the immunogenic composition comprises a nanoparticle comprising the CoV S glycoprotein and a non-ionic detergent core, wherein the CoV S glycoprotein is anchored to the detergent core via the transmembrane domain of the CoV S glycoprotein.

### Claim 22 (depends on 21)

The method of claim 21, wherein the non-ionic detergent is selected from the group consisting of polysorbate-20 (P520), polysorbate-40 (PS40), polysorbate-60 (PS60), polysorbate-65 (PS65), and polysorbate-80 (PS80).

### Claim 23 (depends on 22)

The method of claim 22, wherein the non-ionic detergent is PS80.

### Claim 24 (depends on 18)

The method of claim 18, wherein the subject is administered a first dose at day 0 and a boost dose at day 21.

### Claim 25 (depends on 18)

The method of claim 18, wherein a single dose of the immunogenic composition is administered.

### Claim 26 (depends on 8, 18)

The method of claim 18, comprising administering a second immunogenic composition before or after the immunogenic composition of claim 8 is administered.

### Claim 27 (depends on 8, 26)

The method of claim 26, wherein the second immunogenic composition is the immunogenic composition of claim 8.

### Claim 28 (depends on 8, 26)

The method of claim 26, wherein the second immunogenic composition is a different immunogenic composition than the immunogenic composition of claim 8.

### Claim 29 (depends on 28)

The method of claim 28, wherein the second immunogenic composition is selected from the group consisting of an mRNA encoding a SARS-CoV-2 Spike glycoprotein, a plasmid DNA encoding a SARS-CoV-2 Spike glycoprotein, a viral vector encoding a SARS-CoV-2 Spike glycoprotein, and an inactivated SARS-CoV-2 virus.

### Claim 30 (depends on 18)

The method of claim 18, wherein the immunogenic composition comprises a saponin adjuvant.

### Claim 31 (depends on 30)

The method of claim 30, wherein the saponin adjuvant comprises:
(i) a first iscom particle comprising fraction A of Quillaja saponaria Molina and not fraction C of Quillaja saponaria Molina; and
(ii) a second iscom particle comprising fraction C of Quillaja saponaria Molina and not fraction A of Quillaja saponaria Molina.

### Claim 32 (depends on 31)

The method of claim 31, wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for about 85% by weight and about 15% by weight, respectively, of the sum of the weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the saponin adjuvant.

### Claim 33 (depends on 30)

The method of claim 30, wherein the immunogenic composition comprises about 50 μg of saponin adjuvant.

### Claim 34 (depends on 8)

The immunogenic composition of claim 8, comprising from about 3 μg to 25 μg of the CoV S glycoprotein.