US 11,446,370 B2 · Bioconjugates of E. coli o-antigen polysaccharides, methods of production thereof, and methods of use thereof

Bioconjugates of E. coli o-antigen polysaccharides, methods of production thereof, and methods of use thereof

AssigneesJanssen Pharmaceuticals, Inc., Glaxosmithkline Biologicals SA

InventorsJeroen Geurtsen, Jan Theunis Poolman, Kellen Cristhina Fae, Pieter Jan Burghout, Eveline Marleen Weerdenburg, Patricia Ibarra Yon, Darren Robert Abbanat, Stefan Jochen Kemmler, Michael Thomas Kowarik, Manuela Mally, Veronica Gambillara Fonck, Martin Edward Braun, Maria Paula Carranza Sandmeier

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Abstract

A bioconjugate of an E. coli glucosylated O4 antigen polysaccharide covalently linked to a carrier protein and compositions thereof are provided. Also provided are recombinant host cells for producing the bioconjugate, and methods of producing the bioconjugate using the recombinant host cells. The recombinant host cells contain a nucleic acid encoding a glucosyl transferase capable of modifying the E. coli O4 antigen with glucose branching to produce the glucosylated O4 antigen polysaccharide. Bioconjugates of an E. coli glucosylated O4 antigen polysaccharide described herein can be used alone or in combination with one or more additional E. coli O-antigen polysaccharides to induce antibodies against an E. coli glucosylated antigen, and to vaccinate a subject against extra-intestinal pathogenic E. coli (ExPEC).

Claims42

Dependent claims

A bioconjugate of an E. coli glucosylated O4 antigen polysaccharide covalently linked to a carrier protein, wherein the E. coli glucosylated O4 antigen polysaccharide comprises the structure of Formula (O4-Glc+):

wherein n is an integer of 1 to 100.

A composition comprising:

(i) a bioconjugate of an E. coli glucosylated O4 antigen polysaccharide covalently linked to a detoxified Exotoxin A of P. aeruginosa (EPA carrier protein) comprising SEQ ID NO:
3, wherein the E. coli glucosylated O4 antigen polysaccharide comprises the structure of Formula (O4-Glc+);
(ii) a bioconjugate of an E. coli O1A antigen polysaccharide covalently linked to an EPA carrier protein comprising SEQ ID NO:
3, wherein the E. coli O1A antigen polysaccharide comprises the structure of Formula (O1A);
(iii) a bioconjugate of an E. coli O2 antigen polysaccharide covalently linked to an EPA carrier protein comprising SEQ ID NO:
3, wherein the E. coli O2 antigen polysaccharide comprises the structure of Formula (O2);
(iv) a bioconjugate of an E. coli O6A antigen polysaccharide covalently linked to an EPA carrier protein comprising SEQ ID NO:
3, wherein the E. coli O6A antigen polysaccharide comprises the structure of Formula (O6A);
(v) a bioconjugate of an E. coli O8 antigen polysaccharide covalently linked to an EPA carrier protein comprising SEQ ID NO:
3, wherein the E. coli O8 antigen polysaccharide comprises the structure of Formula (O8);
α-D-Manp3Me-(1→[3)-β-D-Manp-(1→2)-α-D-Manp-(1→2)-α-D-Manp-(1→]n;
(vi) a bioconjugate of an E. coli O15 antigen polysaccharide covalently linked to an EPA carrier protein comprising SEQ ID NO:
3, wherein the E. coli O15 antigen polysaccharide comprises the structure of Formula (O15);
[→2)-β-D-Galp-(1→3)-α-L-FucpNAc-(1→3)-β-D-GlcpNAc-(1→]n;
(vii) a bioconjugate of an E. coli O16 antigen polysaccharide covalently linked to an EPA carrier protein comprising SEQ ID NO:
3, wherein the E. coli O16 antigen polysaccharide comprises the structure of Formula (O16);
(viii) a bioconjugate of an E. coli O25B antigen polysaccharide covalently linked to an EPA carrier protein comprising SEQ ID NO:
3, wherein the E. coli O25B antigen polysaccharide comprises the structure of Formula (O25B);
(ix) a bioconjugate of an E. coli O75 antigen polysaccharide covalently linked to an EPA carrier protein comprising SEQ ID NO:
3, wherein the E. coli O75 antigen polysaccharide comprises the structure of Formula (O75);
and
(x) a bioconjugate of an E. coli O18A antigen polysaccharide covalently linked to an EPA carrier protein comprising SEQ ID NO:
3, wherein the E. coli O18A antigen polysaccharide comprises the structure of Formula (O18A);
wherein each n is independently an integer of 1 to 100.

21 more elements

Dependencies are inferred from the claim text.

Facts

Application

16/822,340Filed 18 Mar 2020 · us provisional application

Priority

18 Mar 2019

Published

US 2020/0316184 A18 Oct 2020

Granted

20 Sep 2022

Term ends

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Classification17 codes

A61K 39/0258
Enterobacteriales, e.g. Enterobacter: escherichia
A61P 13/02
Drugs for disorders of the urinary system: of urine or of the urinary tract, e.g. urine acidifiers
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents
A61P 37/04
Immunomodulators: immunostimulants