Modified meningococcal fhbp polypeptides

Patent metadata

Field	Value
Publication number	US-2019315812-A1
Application number	US-201916458365-A
Country	US
Kind code	A1
Filing date	Jul 1, 2019
Priority date	Feb 28, 2014
Publication date	Oct 17, 2019
Grant date	—

Abstract

Modified meningococcal fHbp polypeptides with increased stability.

First claim

1 - 15 . (canceled)

16 . A mutant v3 fHbp polypeptide comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 17 and containing an amino acid residue corresponding to residue S32 of SEQ ID NO: 17 that has been substituted with any other amino acid, and further comprising a substitution at a position corresponding to L126 of SEQ ID NO: 17.

17 . The polypeptide of claim 16 , comprising:
(a) a sequence that differs from SEQ ID NO: 17 only by substitution at the position corresponding to S32 and at a position corresponding to L126; or (b) a sequence that differs from SEQ ID NO: 17 only by substitutions of S32V and L126R.

18 . The polypeptide of claim 16 , having a sequence comprising: substitutions S32V and L126R.

19 . A polypeptide comprising a sequence selected from:
(a) SEQ ID NO: 44, (b) SEQ ID NO: 44 with 1, 2, 3, 4, or 5 single amino acid substitutions, deletions and/or insertions at positions other than residue V32 and R126, wherein the polypeptide can elicit antibodies which bind to a meningococcal fHbp polypeptide consisting of the amino acid sequence of SEQ ID NO: 40; and (c) a fHbp v3 amino acid sequence, wherein the v3 amino acid sequence is identical to a v3 wild-type amino acid sequence except for a mutation at the amino acid position corresponding to Leu-126 of SEQ ID NO: 17, provided that the mutation is not a substitution to alanine.

20 . An immunogenic composition comprising a polypeptide of claim 16 .

21 . The composition of claim 20 , further comprising a second polypeptide that, when administered to a mammal, elicits an antibody response that is bactericidal against meningococcus.

22 . The composition of claim 20 , further comprising a conjugated capsular saccharide selected from (i) a conjugated capsular saccharide from N. meningitidis serogroup A, C, W135 or Y, and (ii) a conjugated capsular saccharide from S. pneumoniae

23 . A method for raising an antibody response in a mammal, comprising administering an immunogenic composition of claim 20 to said mammal.

24 . The polypeptide of claim 17 , comprising a sequence that differs from SEQ ID NO: 17 only by substitutions of S32V and L126R.

25 . An immunogenic composition comprising a polypeptide of claim 19 .

Assignees

• Glaxosmithkline Biologicals Sa

Inventors

• Bottomley Matthew
• Malito Enrico
• Martinelli Manuele

Classifications

• C12N15/74

  Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora · CPC title

• A61K2039/55511

  Organic adjuvants · CPC title

• A61K2039/70

  Multivalent vaccine · CPC title

• C07K14/22 Primary

  from Neisseriaceae (F) · CPC title

• A61P31/04

  Antibacterial agents · CPC title