Prefusion coronavirus spike proteins and their use

Patent metadata

Field	Value
Publication number	US-11964010-B2
Application number	US-202117194834-A
Country	US
Kind code	B2
Filing date	Mar 8, 2021
Priority date	Oct 25, 2016
Publication date	Apr 23, 2024
Grant date	Apr 23, 2024

Abstract

Coronavirus S ectodomain trimers stabilized in a prefusion conformation, nucleic acid molecules and vectors encoding these proteins, and methods of their use and production are disclosed. In several embodiments, the coronavirus S ectodomain trimers and/or nucleic acid molecules can be used to generate an immune response to coronavirus in a subject. In additional embodiments, the therapeutically effective amount of the coronavirus S ectodomain trimers and/or nucleic acid molecules can be administered to a subject in a method of treating or preventing coronavirus infection.

First claim

It is claimed:

1. A nucleic acid molecule encoding a recombinant coronavirus S protein comprising two proline substitutions between the heptad repeat 1 (HR1) and the central helix of the S protein.

2. The nucleic acid molecule of claim 1 , wherein the coronavirus is a betacoronavirus.

3. The nucleic acid molecule of claim 1 , wherein the coronavirus is one of MERS-CoV, SARS-CoV, NL63-CoV, 229E-CoV, 0C43-CoV, HKU1-CoV, WIV1-CoV, MHV, HKU9-CoV, PEDV-CoV, or SDCV.

4. The nucleic acid molecule of claim 1 , wherein the recombinant coronavirus S protein further comprises a mutation to inhibit cleavage of a S1/S2 protease cleavage site.

5. The nucleic acid molecule of claim 1 , operably linked to a promoter.

6. An immunogenic composition comprising the nucleic acid molecule of claim 1 , and a pharmaceutically acceptable carrier.

7. A method for generating an immune response to a coronavirus S protein in a subject, comprising administering to the subject an effective amount of the nucleic acid molecule of claim 1 to generate the immune response.

8. The method of claim 7 , wherein the immune response inhibits infection with the coronavirus.

9. The nucleic acid molecule of claim 1 , wherein the nucleic acid molecule is an mRNA molecule.

10. The nucleic acid molecule of claim 9 , wherein the coronavirus is a betacoronavirus.

11. The nucleic acid molecule of claim 9 , wherein the coronavirus is one of MERS-CoV, SARS-CoV, NL63-CoV, 229E-CoV, OC43-CoV, HKU1-CoV, WIV1-CoV, MHV, HKU9-CoV, PEDV-CoV, or SDCV.

12. The nucleic acid molecule of claim 9 , wherein the recombinant coronavirus S protein further comprises a mutation to inhibit cleavage of a S1/S2 protease cleavage site.

13. An immunogenic composition comprising the nucleic acid molecule of claim 9 , and a pharmaceutically acceptable carrier.

14. A method for generating an immune response to a coronavirus S protein in a subject, comprising administering to the subject an effective amount of the nucleic acid molecule of claim 9 to generate the immune response.

15. The method of claim 14 , wherein the immune response inhibits infection with the coronavirus.

Assignees

• Us Health
• Scripps Research Inst
• Dartmouth College

Inventors

• Graham Barney
• Mclellan Jason
• Ward Andrew
• Kirchdoerfer Robert
• Cottrell Christopher
• Joyce Michael Gordon
• Kanekiyo Masaru
• Wang Nianshuang
• Pallesen Jesper
• Yassine Hadi
• Turner Hannah
• Corbett Kizzmekia

Classifications

• A61K39/215 Primary

  Coronaviridae, e.g. avian infectious bronchitis virus · CPC title

• A61P31/14

  for RNA viruses · CPC title

• C07K14/005

  from viruses · CPC title

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• C12N2770/20022

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title