Modified meningococcal fHbp polypeptides

Patent metadata

Field	Value
Publication number	US-11932671-B2
Application number	US-202117245681-A
Country	US
Kind code	B2
Filing date	Apr 30, 2021
Priority date	Feb 28, 2014
Publication date	Mar 19, 2024
Grant date	Mar 19, 2024

Abstract

Modified meningococcal fHbp polypeptides with increased stability.

First claim

The invention claimed is:

1. A fusion polypeptide comprising a mutant v2 fHbp polypeptide and/or a mutant v3 fHbp polypeptide and at least one other fHbp, wherein:
i. the mutant v2 fHbp polypeptide comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 5 and includes a residue corresponding to residue 32 from SEQ ID NO: 5, wherein the amino acid sequence of the mutant v2 fHbp polypeptide differs from SEQ ID NO: 5 at residue 32 by the substitution S32V; and/or
ii. the mutant v3 fHbp polypeptide comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 17 and includes a residue corresponding to residue 32 from SEQ ID NO: 17, wherein the amino acid sequence of the mutant v3 fHbp polypeptide differs from SEQ ID NO: 17 at residue 32 by the substitution S32V.

2. The polypeptide of claim 1 , wherein:
i. the amino acid sequence of the mutant v2 fHbp polypeptide further differs from SEQ ID NO: 5 by substitution at one or more of L123, V124, 5125, G126, L127 and/or G128; where the substitution(s) are selected from the group consisting of: L123R; V124I; S125G or S125T; G126D; L127I; G128A; and/or
ii. the amino acid sequence of the mutant v3 fHbp polypeptide further differs from SEQ ID NO: 17 by substitution at L126, where the substitution is L126R.

3. The polypeptide of claim 1 , comprising:
i. A polypeptide having the amino acid sequence of SEQ ID NO: 45;
ii. SEQ ID NO: 45 modified by up to 5 single amino acid substitutions, deletions and/or insertions; and/or
iii. A polypeptide having the amino acid sequence SEQ ID NO: 44;
iv. SEQ ID NO: 44 modified by up to 5 single amino acid substitutions, deletions and/or insertions,
wherein the 5 single amino acid substitutions, deletions and/or insertions do not include amino acid positions V32, R123 and R126.

4. The polypeptide of claim 1 , wherein the other fHbp is a v1 fHbp polypeptide.

5. The polypeptide of claim 4 , wherein the v1 fHbp polypeptide comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 16 and/or comprises a fragment of SEQ ID NO: 16.

6. The polypeptide of claim 1 , wherein the polypeptide comprises:
i. a v1 fHbp polypeptide;
ii. a mutant v2 fHbp polypeptide; and
iii. a mutant v3 fHbp polypeptide,
wherein the polypeptides are arranged in the order v2 fHbp polypeptide, v3 fHbp polypeptide and v1 fHbp polypeptide from N- to C-terminus.

7. The polypeptide of claim 4 , wherein the mutant v2 fHbp, mutant v3 fHbp and a mutant v1 fHbp are connected by a linker having the amino acid sequence of SEQ ID NO: 50 between each sequence.

8. An immunogenic composition comprising the polypeptide of claim 1 .

9. The fusion polypeptide of claim 1 , wherein the mutant v2 fHbp polypeptide further comprises a L123 mutation.

10. The fusion polypeptide of claim 9 , wherein the L123 mutation is a L123R mutation.

11. The fusion polypeptide of claim 1 , wherein the mutant v3 fHbp polypeptide further comprises a L126 mutation.

Assignees

• Glaxosmithkline Biologicals Sa

Inventors

• Bottomley Matthew
• Malito Enrico
• Martinelli Manuele
• Scarselli Maria

Classifications

• C07K14/22 Primary

  from Neisseriaceae (F) · CPC title

• A61K39/095 Primary

  Neisseria · CPC title

• A61K2039/523

  expressing foreign proteins · CPC title

• A61K2039/55511

  Organic adjuvants · CPC title

• A61K2039/70

  Multivalent vaccine · CPC title