# US 11,896,662 B2 · Multivalent influenza nanoparticle vaccines

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- Number: US 11,896,662 B2
- Document ID: US11896662B2
- Status: Granted
- Kind: B2
- Application number: 17/534,659
- Filed: 2021-11-24
- Published: 2022-03-17
- Granted: 2024-02-13
- Earliest claimed: 2018-03-19
- Assignees: Novavax, Inc.
- Applicants: Novavax, Inc.
- Inventors: Sarathi Boddapati; Anushree Herwadkar; Jason Wong; Yen-Huei Lin; Gale Smith; Jing-Hui Tian
- Web page: https://patentgrep.com/patent/US11896662B2

## CPC

- A61K 39/145: Orthomyxoviridae, e.g. influenza virus
- A61K 9/0051: {Ocular inserts or implants}
- A61K 9/51: Nanocapsules; {Nanoparticles; (nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00)}
- A61K 39/12: Viral antigens
- A61P 31/16: for influenza or rhinoviruses
- A61K 2039/55555: {Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers}
- A61K 2039/55577: {Saponins; Quil A; QS21; ISCOMS}
- A61K 2039/70: {Multivalent vaccine}
- C12N 2760/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2760/16171: Demonstrated in vivo effect
- C12N 2760/16234: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2760/16271: Demonstrated in vivo effect
- 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 multivalent nanoparticle vaccine compositions suitable for use in influenza vaccines. The nanoparticles include effective amounts of influenza glycoproteins that provide increased immune responses compared to a commercially available influenza vaccine composition. The present disclosure also provides vaccine formulation strategies that are cost effective and are convenient for clinical use. Methods of administering the nanoparticle vaccine compositions to a subject are also disclosed.

## Claims

### Claim 1

A composition comprising:
(i) a first HaSMaN (Hemagglutinin Saponin Matrix Nanoparticle) comprising:
(a) a first ISCOM matrix particle comprising Fraction A of Quillaja Saponaria Molina and not Fraction C of Quillaja Saponaria Molina, and
(b) a first recombinant influenza hemagglutinin (HA) glycoprotein trimer, wherein the HA glycoprotein tail is associated with the first ISCOM matrix particle and wherein the HA glycoprotein head extends distally from the first ISCOM matrix particle;
(ii) a second HaSMaN comprising:
(a) a second ISCOM matrix particle comprising Fraction C of Quillaja Saponaria Molina and not Fraction A of Quillaja Saponaria Molina, and
(b) a second recombinant influenza HA glycoprotein trimer, wherein the HA glycoprotein tail is associated with the second ISCOM matrix particle and wherein the HA glycoprotein head extends distally from the second ISCOM matrix particle; and
(iii) a pharmaceutically acceptable buffer or carrier;
wherein each of the first and the second HA glycoprotein is from a Type A influenza strain, and
wherein each of the first and the second HA glycoprotein contains a transmembrane domain.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the Type A influenza strain is of a subtype selected from the group consisting of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, and H18.

### Claim 3

A method of preparing a HaSMaN comprising combining a detergent core nanoparticle containing hemagglutinin (HA) with an ISCOM matrix particle for at least about four hours,
wherein the ISCOM matrix particle comprises Fraction A of Quillaja Saponaria Molina and not Fraction C of Quillaja Saponaria Molina;
wherein the HA contains a transmembrane domain, and
wherein the HA is from a Type A influenza strain.

### Claim 4 (depends on 3)

The method of claim 3, wherein the detergent is PS80.

### Claim 5 (depends on 3)

The method of claim 3, comprising combining the detergent core nanoparticle with the ISCOM matrix particle at a temperature of about 25° C. for at least about 24 hours.

### Claim 6 (depends on 3)

The method of claim 3, wherein the Type A influenza strain is selected from the group consisting of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, and H18.

### Claim 7 (depends on 1)

A method of stimulating an immune response against influenza comprising administering the composition of claim 1.

### Claim 8 (depends on 7)

The method of claim 7, wherein the composition is administered intramuscularly.

### Claim 9

A method of preparing a HaSMaN comprising combining a detergent core nanoparticle containing hemagglutinin (HA) with an ISCOM matrix particle for at least about four hours,
wherein the ISCOM matrix particle comprises Fraction C of Quillaja Saponaria Molina and not Fraction A of Quillaja Saponaria Molina;
wherein the HA contains a transmembrane domain, and
wherein the HA is from a Type A influenza strain.

### Claim 10 (depends on 9)

The method of claim 9, wherein the detergent is PS80.

### Claim 11 (depends on 9)

The method of claim 9, comprising combining the detergent core nanoparticle with the ISCOM matrix particle at a temperature of about 25° C. for at least about 24 hours.

### Claim 12 (depends on 9)

The method of claim 9, wherein the Type A influenza strain is selected from the group consisting of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, and H18.