Granted Patent B2

US 12,233,118 · App. 17/478,584 · Granted Feb 25, 2025

Inventors: Jan Theunis Poolman (Vogelenzang, NL); Kellen Cristhina Fae (Oegstgeest, NL); Michal Sarnecki (Basel, CH); Jeroen Geurtsen (Vleuten, NL); Darren Robert Abbanat (Cornwall, NY); Bart Gustaaf M. Spiessens (Bierbeek, BE); Frank Germaine F. Struyf (Bierbeek, BE)

Assignee: Janssen Pharmaceuticals, Inc.

A61K39/0258A61K31/739A61K47/6415A61K47/646A61K2039/55583A61K2039/70

Abstract

Claims (38)

1. A composition comprising an E. coli O1 antigen polysaccharide covalently linked to a carrier protein, an E. coli O2 antigen polysaccharide covalently linked to a carrier protein, an E. coli O4 antigen polysaccharide covalently linked to a carrier protein, an E. coli O15 antigen polysaccharide covalently linked to a carrier protein, an E. coli O16 antigen polysaccharide covalently linked to a carrier protein, an E. coli O18 antigen polysaccharide covalently linked to a carrier protein, an E. coli O25 antigen polysaccharide covalently linked to a carrier protein, an E. coli O75 antigen polysaccharide covalently linked to a carrier protein and an E. coli O6 antigen polysaccharide covalently linked to a carrier protein, wherein:

(i) the E. coli O1 antigen polysaccharide is O1A antigen polysaccharide comprising the structure of Formula (O1A):

(ii) the E. coli O2 antigen polysaccharide comprises the structure of Formula (O2):

(iii) the E. coli O4 antigen polysaccharide is O4-Glc+ antigen polysaccharide comprising the structure of Formula (O4-Glc+):

(iv) the E. coli O6 antigen polysaccharide is O6A antigen polysaccharide comprising the structure of Formula (O6A):

(v) 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 ,

(vi) the E. coli O16 antigen polysaccharide comprises the structure of Formula (O16):

(vii) the E. coli O18 antigen polysaccharide is O18A antigen polysaccharide comprising the structure of Formula (O18A):

(viii) the E. coli O25 antigen polysaccharide is O25B antigen polysaccharide comprising the structure of Formula (O25B):

 and

(ix) the E. coli O75 antigen polysaccharide comprises the structure of Formula (O75):

wherein the weight ratio of the E. coli antigen polysaccharides

O1:O2:O4:O6:O15:O16:O18:O25:O75 is about 1:1:1:1:1:1:1:2:2 and wherein each n is independently an integer of 1 to 100.

2. The composition of claim 1 , wherein the weight ratio of the E. coli antigen polysaccharides O1:O2:O4:O6:O15:O16:O18:O25:O75 is 1:1:1:1:1:1:1:2:2.

3. The composition of claim 1 , wherein the concentration of the E. coli O75 antigen polysaccharide is from about 8 to about 64 μg/mL.

4. The composition of claim 1 , wherein the E. coli O antigen polysaccharides present in the composition consist of the E. coli O1, O2, O4, O6, O15, O16, O18, O25, and O75 antigen polysaccharides, wherein each of the polysaccharides is covalently linked to its carrier protein.

5. The composition of claim 1 , further comprising at least one additional E. coli O antigen polysaccharide covalently linked to a carrier protein.

6. The composition of claim 1 , wherein each of the carrier proteins is a detoxified exotoxin A of Pseudomonas aeruginosa (EPA) or CRM 197 .

7. The composition of claim 1 , wherein each of the E. coli antigen polysaccharides O1, O2, O4, O6, O15, O16, O18, O25, and O75 is covalently linked to its carrier protein by bioconjugation or by chemical conjugation.

8. A method of inducing an immune response to E. coli in a mammalian subject, the method comprising administering to the subject an effective amount of the composition of claim 1 .

9. The method of claim 8 , wherein the E. coli O antigen polysaccharides administered to the subject consist of the E. coli O1, O2, O4, O6, O15, O16, O18, O25, and O75 antigen polysaccharides, wherein each of the polysaccharides is covalently linked to its carrier protein.

10. The method of claim 8 , wherein the subject is a human having or at risk of having an E. coli infection.

11. The method of claim 8 , wherein 16 μg of the E. coli O75 antigen polysaccharide is administered per administration.

12. The composition of claim 1 , wherein each n is independently an integer of 5 to 30.

13. The composition of claim 3 , wherein the concentration of the E. coli O75 antigen polysaccharide is from about 28 to about 36 μg/mL.

14. The composition of claim 2 , wherein the concentration of the E. coli O75 antigen polysaccharide is about 32 μg/mL.

15. The composition of claim 6 , wherein each of the carrier proteins is EPA comprising 1 to 20 glycosylation sequences having the amino acid sequence of SEQ ID NO: 1.

16. The composition of claim 1 , wherein each of the carrier proteins comprises the amino acid sequence of SEQ ID NO: 3.

17. The composition of claim 2 , wherein each of the carrier proteins comprises the amino acid sequence of SEQ ID NO: 3.

18. The composition of claim 7 , wherein each of the E. coli O antigen polysaccharides is covalently linked by bioconjugation to an Asn residue in a glycosylation site in its carrier protein.

19. The composition of claim 2 , wherein each of the E. coli O antigen polysaccharides is covalently linked to its carrier protein by bioconjugation.

20. A method of inducing an immune response to E. coli in a mammalian subject, the method comprising administering to the subject an effective amount of the composition of claim 2 .

21. The method of claim 20 , wherein the E. coli is extra-intestinal pathogenic E. coli (ExPEC).

22. The composition of claim 2 , wherein each n is independently an integer of 5 to 30, wherein each of the carrier proteins comprises the amino acid sequence of SEQ ID NO: 3, and wherein the concentration of the E. coli O75 antigen polysaccharide is about 32 μg/mL.

23. The method of claim 9 , wherein the composition administered to the subject further comprises from 1 to 15 additional E. coli O antigen polysaccharides, each independently covalently linked to a carrier protein.

24. The composition of claim 18 , wherein the polysaccharide to the carrier protein ratio by weight/weight (w/w) of each of the E. coli O antigen polysaccharides covalently linked to its carrier protein is about 0.1 to 0.5.

25. The composition of claim 22 , wherein the polysaccharide to the carrier protein ratio by weight/weight (w/w) of each of the E. coli O antigen polysaccharides covalently linked to its carrier protein is about 0.1 to 0.5.

Assignments (9)

Priority Claims (1)

Continuity (3)

References Cited (218)