# US 11,993,633 B2 · Conformationally stabilized RSV pre-fusion F proteins > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,993,633 B2 - Document ID: US11993633B2 - Status: Granted - Kind: B2 - Application number: 17/332,901 - Filed: 2021-05-27 - Published: 2022-04-21 - Granted: 2024-05-28 - Earliest claimed: 2013-07-25 - Applicants: Calder Biosciences Inc.; The United States of America, AS Represented By the Secretary, Department of Health and Human Services - Inventors: Christopher Patrick Marshall; Jason Scott McLellan; Peter Joseph Alff; Claudio Bertuccioli; Roberto Mariani - Web page: https://patentgrep.com/patent/US11993633B2 ## CPC - C07K 14/005: from viruses - A61K 39/12: Viral antigens - A61K 39/155: Paramyxoviridae, e.g. parainfluenza virus - A61P 31/12: Antivirals - A61K 2039/525: {Virus} - C12N 2760/18534: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - 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) - 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 In some embodiments, the present invention provides respiratory syncytial virus (RSV) F proteins, polypeptides and protein complexes that comprise one or more cross-links to stabilize the protein, polypeptide or protein complex in its pre-fusion conformation. In some embodiments the present invention provides RSV F proteins, polypeptides and protein complexes comprising one or more mutations to facilitate such cross-linking. In some embodiments the present invention provides compositions comprising such proteins, polypeptides or protein complexes, including vaccine compositions, and methods of making and using the same. ## Claims ### Claim 1 An RSV F polypeptide, protein or protein complex comprising: (a) a point mutation to tyrosine at amino acid position 226, or an amino acid position corresponding to position 226 as determined by alignment to, and using the amino acid numbering of, SEQ ID NO. 1, (b) one or more cavity-filling hydrophobic amino acid substitutions, and (c) a trimerization domain. ### Claim 2 (depends on 1) The RSV F polypeptide, protein or protein complex according to claim 1, wherein the trimerization domain is a foldon domain. ### Claim 3 (depends on 1) The RSV F polypeptide, protein or protein complex according to claim 1, further comprising a di-tyrosine cross-link between the tyrosine at amino acid position 226 and a tyrosine at amino acid position 198, or an amino acid position corresponding to position 198 as determined by alignment to, and using the amino acid numbering of, SEQ ID NO.1. ### Claim 4 (depends on 2) The RSV F polypeptide, protein or protein complex according to claim 2, further comprising a di-tyrosine cross-link between the tyrosine at amino acid position 226 and a tyrosine at amino acid position 198, or an amino acid position corresponding to position 198 as determined by alignment to, and using the amino acid numbering of, SEQ ID NO.1. ### Claim 5 (depends on 1) A nucleic acid molecule encoding an RSV F polypeptide, protein or protein complex according to claim 1. ### Claim 6 (depends on 2) A nucleic acid molecule encoding an RSV F polypeptide, protein or protein complex according to claim 2. ### Claim 7 (depends on 3) A nucleic acid molecule encoding an RSV F polypeptide, protein or protein complex according to claim 3. ### Claim 8 (depends on 4) A nucleic acid molecule encoding an RSV F polypeptide, protein or protein complex according to claim 4. ### Claim 9 (depends on 1) A composition comprising an RSV F polypeptide, protein or protein complex according to claim 1. ### Claim 10 (depends on 9) The composition of claim 9, further comprising an adjuvant. ### Claim 11 (depends on 2) A composition comprising an RSV F polypeptide, protein or protein complex according to claim 2. ### Claim 12 (depends on 11) The composition of claim 11, further comprising an adjuvant. ### Claim 13 (depends on 3) A composition comprising an RSV F polypeptide, protein or protein complex according to claim 3. ### Claim 14 (depends on 13) The composition of claim 13, further comprising an adjuvant. ### Claim 15 (depends on 4) A composition comprising an RSV F polypeptide, protein or protein complex according to claim 4. ### Claim 16 (depends on 15) The composition of claim 15, further comprising an adjuvant.