FimH mutant, compositions therewith and use thereof

Patent metadata

Field	Value
Publication number	US-2021221856-A1
Application number	US-202117150025-A
Country	US
Kind code	A1
Filing date	Jan 15, 2021
Priority date	Jan 16, 2020
Publication date	Jul 22, 2021
Grant date	—

Abstract

Polypeptides comprising a FimH lectin domain comprising an amino acid mutation that causes the FimH lectin domain to be in the low affinity conformation for mannose are described. Pharmaceutical compositions which comprise such polypeptides and methods of stimulating an immune response in a subject in need thereof by administration of the polypeptide are further described.

First claim

1 . A polypeptide comprising a FimH lectin domain, wherein the FimH lectin domain comprises an amino acid selected from the group consisting of valine (V), isoleucine (I), leucine (L), glycine (G), methionine (M), and alanine (A) at the position that corresponds to position 144 in SEQ ID NO: 1.

2 . The polypeptide according to claim 1 , wherein the polypeptide comprises a mutation and wherein the mutation is a F144V substitution.

3 . The polypeptide according to claim 1 , wherein the FimH lectin domain has an amino acid sequence having at least 90% sequence identity with SEQ ID NO: 1.

4 . The polypeptide according to claim 1 , further comprising a FimH pilin domain.

5 . The polypeptide according to claim 1 , wherein the polypeptide is a full length FimH having at least 90% sequence identity with SEQ ID NO: 2.

6 . A complex comprising the polypeptide according to claim 4 and FimC (FimCH).

7 . A polynucleotide encoding the polypeptide of claim 1 .

8 . A pharmaceutical composition comprising the polypeptide according to claim 1 .

9 . The pharmaceutical composition according to claim 8 , further comprising an adjuvant.

10 . (canceled)

11 . A method of inducing an immune response against a bacterium of the family of Enterobacteriaceae in a subject, comprising administering to the subject an effective amount of the pharmaceutical composition according to claim 8 .

12 . The method according to claim 11 , wherein the bacterium is E. coli or Klebsiella.

13 . A method of preventing or treating a urinary tract infection caused by E. coli in a subject in need thereof, comprising administering to the subject an effective amount of the pharmaceutical composition according to claim 8 .

14 . A method for treating or preventing an enterobacillus-related condition a subject in need thereof comprising administering to the subject an effective amount of the pharmaceutical composition according to claim 8 .

15 . A vector comprising a polynucleotide according to claim 7 .

16 . A method for producing a polypeptide comprising a FimH lectin domain, comprising expressing the polypeptide from a recombinant cell containing the polynucleotide of claim 7 .

17 . The method of claim 16 , further comprising recovering and purifying the polypeptide.

18 . The polypeptide according to claim 3 , wherein the FimH lectin domain comprises SEQ ID NO: 1 wherein the phenylalanine residue at position 144 is substituted by valine.

19 . The polypeptide according to claim 5 , wherein the FimH comprises SEQ ID NO: 2 wherein the phenylalanine residue at position 144 is substituted by valine.

20 . A polynucleotide encoding the polypeptide of claim 2 .

21 . A method for producing a polypeptide comprising a FimH lectin domain, comprising expressing the polypeptide from a recombinant cell containing the vector of claim 15 .

Assignees

• Janssen Pharmaceuticals Inc

Inventors

• Grijpstra Jan
• Weerdenburg Marleen Eveline
• Geurtsen Jeroen
• Fae Cristhina Kellen
• Feitsma Jakob Louris

Classifications

• C07K14/245 Primary

  Escherichia (G) · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61K39/0258

  Escherichia · CPC title

• C07K16/1232 Primary

  Escherichia (G) · CPC title

• A61K2039/55566

  Emulsions, e.g. Freund's adjuvant, MF59 · CPC title