ExPEC glycoconjugate vaccine formulations

Patent metadata

Field	Value
Publication number	US-10159751-B2
Application number	US-201715792242-A
Country	US
Kind code	B2
Filing date	Oct 24, 2017
Priority date	Oct 24, 2016
Publication date	Dec 25, 2018
Grant date	Dec 25, 2018

Abstract

Compositions and methods for inducing an immune response against extra-intestinal pathogenic Escherichia coli (ExPEC) are described. In particular, multivalent vaccines containing E. coli antigen polysaccharide covalently bound to a exotoxin A of Pseudomonas aeruginosa (EPA) carrier protein that can withstand multiple environmental stresses are described.

First claim

What is claimed is:

1. An immunogenic composition comprising:
a. an E. coli 025B antigen polysaccharide, an E. coli O1A antigen polysaccharide, an E. coli 02 antigen polysaccharide, and an E. coli O6A antigen polysaccharide, wherein each antigen polysaccharide is independently covalently bound to an exotoxin A of Pseudomonas aeruginosa (EPA) carrier protein;
b. 3% to 8% (w/v) sorbitol;
c. 5 to 15 mM methionine;
d. 5 to 20 mM phosphate buffer comprising potassium phosphate and sodium phosphate at a pH of 6.5 to 7.5; and
e. 0.01% to 0.2% (w/v) surfactant.

2. The immunogenic composition of claim 1 , wherein the concentration of sorbitol is 5% (w/v).

3. The immunogenic composition of claim 1 , wherein the concentration of methionine is 10 mM.

4. The immunogenic composition of claim 1 , wherein the concentration of the phosphate buffer is 10 mM, and the pH of the phosphate buffer is 7.0.

5. The immunogenic composition of claim 1 , wherein the surfactant is a non-ionic surfactant.

6. The immunogenic composition of claim 5 , wherein the surfactant is polysorbate 80 (PS80).

7. An immunogenic composition consisting of:
a. an E. coli 025B antigen polysaccharide, an E. coli O1A antigen polysaccharide, an E. coli 02 antigen polysaccharide, and an E. coli O6A antigen polysaccharide, wherein each antigen polysaccharide is independently covalently bound to an exotoxin A of Pseudomonas aeruginosa (EPA) carrier protein;
b. 5% (w/v) sorbitol;
c. 10 mM methionine;
d. 10 mM phosphate buffer comprising KH 2 PO 4 and Na 2 HPO 4 at a pH of 7.0;
e. 0.02% (w/v) polysorbate 80 (PS80); and
f. water.

8. The immunogenic composition of claim 1 , which is stable for at least 6 months when stored at a temperature of 2-8° C.

9. The immunogenic composition of claim 1 , wherein the concentration for each 0-antigen polysaccharide is about 1 to 200 μg/mL.

10. A method for stably maintaining a liquid immunogenic composition comprising an E. coli O-antigen covalently coupled to an EPA carrier protein, the method comprising storing a composition according to claim 1 at a temperature of 2-8° C. for at least 6 months.

11. The immunogenic composition of claim 7 , wherein the concentration for each 0-antigen polysaccharide is about 1 to 200 μg/mL, and the immunogenic composition is stable for at least 6 months when stored at a temperature of 2-8° C.

12. The immunogenic composition of claim 1 , wherein the surfactant is selected from the group consisting of poloxamer 188, polysorbate 20 (PS20), and polysorbate 80 (PS801.

13. The immunogenic composition of claim 6 , wherein the concentration of PS80 is 0.02% (w/v).

14. A method for stably maintaining a liquid immunogenic composition comprising an E. coli O-antigen covalently coupled to an EPA carrier protein, the method comprising storing a composition according to claim 7 at a temperature of 2-8° C. for at least 6 months.

15. An immunogenic composition comprising:
a. an E. coli 025B antigen polysaccharide, wherein the antigen polysaccharide is covalently bound to an exotoxin A of Pseudomonas aeruginosa (EPA) carrier protein;
b. 3% to 8% (w/v) sorbitol;
c. 5 to 15 mM methionine;
d. 5 to 20 mM phosphate buffer comprising potassium phosphate and sodium phosphate at a pH of 6.5 to 7.5; and
e. 0.01% to 0.2% (w/v) surfactant,
wherein the immunogenic composition is stable for at least 6 months when stored at a temperature of 2-8° C.

16. The immunogenic composition of claim 15 , wherein the concentration of sorbitol is 5% (w/v).

17. The immunogenic composition of claim 15 , wherein the concentration of methionine is 10 mM.

18. The immunogenic composition of claim 15 , wherein the concentration of the phosphate buffer is 10 mM, and the pH of the phosphate buffer is 7.0.

19. The immunogenic composition of claim 15 , wherein the surfactant is a non-ionic surfactant selected from the group consisting of poloxamer 188, polysorbate 20 (PS20), and polysorbate 80 (PS80).

20. The immunogenic composition of claim 15 , wherein the surfactant is polysorbate 80 (PS80) and the concentration of PS80 is 0.02% (w/v).

Assignees

• Janssen Pharmaceuticals Inc

Inventors

• Labovitiadi Olga
• Tonnis Wouter Frank
• Doro Francesco
• Adriaansen Janik

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61K47/20

  containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids · CPC title

• A61K2039/6037

  Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT] · CPC title

• A61K2039/55583

  Polysaccharides · CPC title

• A61K47/65

  Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers · CPC title