# US 2021/0275664 A1 · Prefusion coronavirus spike proteins and their use > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0275664 A1 - Document ID: US20210275664A1 - Status: Published application - Kind: A1 - Application number: 17/194,834 - Filed: 2021-03-08 - Published: 2021-09-09 - Earliest claimed: 2016-10-25 - Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Servic; The Scripps Research Institute; Trustees of Dartmouth College - Applicants: The United States of America, as represented by the Secretary, Department of Health and Human Servic; The Scripps Research Institute; Trustees of Dartmouth College - Inventors: Barney Graham; Jason McLellan; Andrew Ward; Robert Kirchdoerfer; Christopher Cottrell; Michael Gordon Joyce; Masaru Kanekiyo; Nianshuang Wang; Jesper Pallesen; Hadi Yassine; Hannah Turner; Kizzmekia Corbett - Web page: https://patentgrep.com/patent/US20210275664A1 ## 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 - 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 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 - C12N 2770/20071: 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 - 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 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. ## Claims ### Claim 1 (canceled) ### Claim 2 An immunogen, comprising: a recombinant coronavirus S ectodomain trimer comprising protomers comprising two proline substitutions between a heptad repeat 1 (HR1) and a central helix that stabilize the S ectodomain trimer in a prefusion conformation. ### Claim 3 A nucleic acid molecule encoding a recombinant coronavirus S protein comprising two proline substitutions between a heptad repeat 1 (HR1) and a central helix of the S protein. ### Claim 4 (depends on 3) The nucleic acid molecule of claim 3, wherein the coronavirus is a betacoronavirus. ### Claim 5 (depends on 3) The nucleic acid molecule of claim 3, 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. ### Claim 6 (depends on 3) The nucleic acid molecule of claim 3, wherein the recombinant coronavirus S protein further comprises a mutation to inhibit cleavage of a S1/S2 protease cleavage site. ### Claim 7 (depends on 3) The nucleic acid molecule of claim 3, operably linked to a promoter. ### Claim 8 (depends on 3) An immunogenic composition comprising the nucleic acid molecule of claim 3, and a pharmaceutically acceptable carrier. ### Claim 9 (depends on 3) 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 3 to generate the immune response. ### Claim 10 (depends on 9) The method of claim 9, wherein the immune response inhibits infection with the coronavirus. ### Claim 11 (depends on 3) The nucleic acid molecule of claim 3, wherein the nucleic acid molecule is an mRNA molecule. ### Claim 12 (depends on 11) The nucleic acid molecule of claim 11, wherein the coronavirus is a betacoronavirus. ### Claim 13 (depends on 11) The nucleic acid molecule of claim 11, 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. ### Claim 14 (depends on 11) The nucleic acid molecule of claim 11, wherein the recombinant coronavirus S protein further comprises a mutation to inhibit cleavage of a S 1/S2 protease cleavage site. ### Claim 15 (depends on 11) The nucleic acid molecule of claim 11, operably linked to a promoter. ### Claim 16 (depends on 11) An immunogenic composition comprising the nucleic acid molecule of claim 11, and a pharmaceutically acceptable carrier. ### Claim 17 (depends on 11) 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 11 to generate the immune response. ### Claim 18 (depends on 17) The method of claim 17, wherein the immune response inhibits infection with the coronavirus.