# US 2021/0277069 A1 · Modified meningococcal fhbp polypeptides > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0277069 A1 - Document ID: US20210277069A1 - Status: Published application - Kind: A1 - Application number: 17/265,610 - Filed: 2019-08-09 - Published: 2021-09-09 - Earliest claimed: 2018-08-09 - Assignees: Glaxosmithkline Biologicals SA - Applicants: Glaxosmithkline Biologicals SA - Inventors: Maria SCARSELLI; Daniele VEGGI - Web page: https://patentgrep.com/patent/US20210277069A1 ## CPC - C07K 14/22: from Neisseriaceae (F) - A61K 39/095: Neisseria - A61P 31/04: Antibacterial agents - C12N 15/62: DNA sequences coding for fusion proteins - C07K 2319/00: Fusion polypeptide - 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 The present invention provides mutated fHbp polypeptides and fusion proteins comprising said mutated fHbp polypeptides that are useful as components of immunogenic compositions for immunizing against Neisseria meningitidis infection. ## Claims ### Claim 1 A mutant v1.13 meningococcal fHbp polypeptide comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 2, wherein the amino acid sequence of said mutant v1.13 meningococcal fHbp polypeptide includes a substitution mutation at one or more of residues E211, S216 and E232 of SEQ ID NO: 2. ### Claim 2 (depends on 1) The polypeptide of claim 1, wherein the amino acid sequence differs from SEQ ID NO: 2 by at least one or more of the substitutions E211A, S216R and E232A. ### Claim 3 (depends on 2) The polypeptide of claim 2, wherein the amino acid sequence comprises substitutions at multiple residues selected from the following: (i) E211A and S216R, and (ii) E211A and E232A. ### Claim 4 (depends on 3) The polypeptide of claim 3, wherein the amino acid sequence comprises substitutions at residues E211A and S216R. ### Claim 5 (depends on 4) The polypeptide of claim 4, comprising or consisting of the amino acid sequence of SEQ ID NO: 4. ### Claim 6 (depends on 3) The polypeptide of claim 3, wherein the amino acid sequence comprises substitutions at residues E211A and E232A. ### Claim 7 (depends on 6) The polypeptide of claim 6, comprising or consisting of the amino acid sequence of SEQ ID NO: 3. ### Claim at position 8 8-11. (canceled) ### Claim 12 (depends on 1) A fusion polypeptide comprising v1, v2 and v3 meningococcal fHbp polypeptides, wherein the variant fHbp sequences are in the order v2-v3-v1 from N- to C-terminus, and wherein the v1 fHbp polypeptide is a mutant v1.13 fHbp polypeptide according to claim 1. ### Claim 13 (canceled) ### Claim 14 (depends on 12) The fusion polypeptide of claim 12, wherein: (a) the v2 fHbp polypeptide is a mutant v2 fHbp polypeptide comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 12, wherein the v2 fHbp amino acid sequence includes a substitution mutation at residues S32 and L123 of SEQ ID NO:12, and wherein the substitutions are S32V and L123R; and (b) the v3 fHbp polypeptide is a mutant v3 fHbp polypeptide comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 15 wherein the v3 fHbp amino acid sequence includes a substitution mutation at residues S32 and L126 of SEQ ID NO: 15, and wherein the substitutions are S32V and L126R. ### Claim 15 (depends on 14) The fusion polypeptide of claim 14, wherein: (a) the v2 fHbp polypeptide comprises or consists of the amino acid sequence of SEQ ID NO: 16; and/or (b) the v3 fHbp polypeptide comprises or consists of the amino acid sequence of SEQ ID NO: 17. ### Claim 16 (depends on 12) The fusion polypeptide of claim 12, wherein the v2 and v3 sequences and the v3 and v1 sequences are connected by a glycine-serine linker. ### Claim 17 (canceled) ### Claim 18 (depends on 12) The fusion polypeptide of claim 12, comprising the amino acid sequence of any of SEQ ID NOS: 18-22. ### Claim 19 (depends on 12) The fusion polypeptide of claim 12, further comprising the N-terminal amino acid sequence of SEQ ID NO. 34. ### Claim 20 (depends on 1) An isolated nucleic acid molecule, optionally a plasmid, comprising a nucleotide sequence encoding the mutant v1.13 fHbp polypeptide of claim 1. ### Claim 21 (depends on 20) A recombinant host cell transformed with the nucleic acid molecule of claim 20. ### Claim 22 (depends on 1) An immunogenic composition comprising the mutant v1.13 fHbp polypeptide of claim 1. ### Claim 23 (depends on 22) The immunogenic composition of claim 22, further comprising one or more of: a meningococcal NHBA antigen, a meningococcal NadA antigen, a meningococcal fHbp antigen, and meningococcal outer membrane vesicles (OMVs). ### Claim 24 (depends on 23) The immunogenic composition of claim 23, comprising the 4CMenB composition. ### Claim 25 (depends on 22) The immunogenic composition of claim 22, further comprising a conjugated capsular saccharide from N. meningitidis serogroup A, C, W135 and/or Y. ### Claim 26 (depends on 25) The immunogenic composition of claim 25, further comprising conjugated capsular saccharides from each of N. meningitidis serogroups A, C, W135 and Y. ### Claim 27 (depends on 22) A method for raising an immune response in a mammal, comprising administering the immunogenic composition of claim 22 to the mammal. ### Claim at position 25 28-30. (canceled) ### Claim 31 (depends on 22) A method of immunizing a mammal against N. meningitidis infection, comprising administering the immunogenic composition of claim 22 to the mammal. ### Claim 32 (depends on 27) The method of claim 27, wherein the mammal is a human. ### Claim 33 (depends on 31) The method of claim 31, wherein the mammal is a human.