Glycoconjugation processes and compositions

Patent metadata

Field	Value
Publication number	US-11110160-B2
Application number	US-202016774309-A
Country	US
Kind code	B2
Filing date	Jan 28, 2020
Priority date	Aug 16, 2012
Publication date	Sep 7, 2021
Grant date	Sep 7, 2021

Abstract

The invention provides eTEC linked glycoconjugates comprising a saccharide covalently conjugated to a carrier protein through a (2-((2-oxoethyl)thio)ethyl)carbamate (eTEC) spacer, immunogenic compositions comprising such glycoconjugates, and methods for the preparation and use of such glycoconjugates and immunogenic compositions.

First claim

The invention claimed is:

1. A glycoconjugate comprising a Streptococcus pneumoniae -derived capsular polysaccharide conjugated to a carrier protein through a (2-((2-oxoethyl)thio)ethyl)carbamate (eTEC) spacer, wherein the polysaccharide is covalently linked to the eTEC spacer through a carbamate linkage, and wherein the carrier protein is covalently linked to the eTEC spacer through an amide linkage, as shown by formula (I):

wherein the glycoconjugate comprises at least one covalent linkage between the carrier protein and the polysaccharide for every 4, 10, 15 or 25 saccharide repeat units of the polysaccharide.

2. The glycoconjugate of claim 1 , wherein said glycoconjugate comprises at least one covalent linkage between the carrier protein and the polysaccharide for every 4 saccharide repeat units of the polysaccharide.

3. The glycoconjugate of claim 1 , wherein said glycoconjugate comprises at least one covalent linkage between the carrier protein and the polysaccharide for every 10 saccharide repeat units of the polysaccharide.

4. The glycoconjugate of claim 1 , wherein said glycoconjugate comprises at least one covalent linkage between the carrier protein and the polysaccharide for every 15 saccharide repeat units of the polysaccharide.

5. The glycoconjugate of claim 1 , wherein said glycoconjugate comprises at least one covalent linkage between the carrier protein and the polysaccharide for every 25 saccharide repeat units of the polysaccharide.

6. The glycoconjugate of claim 1 , wherein said Streptococcus pneumoniae -derived capsular polysaccharide is selected from the group consisting of Pn-serotype 10A, 11A, 22F, and 33F capsular polysaccharide.

7. The glycoconjugate of claim 1 , wherein said Streptococcus pneumoniae -derived capsular polysaccharide is a Pn-serotype 10A capsular polysaccharide.

8. The glycoconjugate of claim 1 , wherein said Streptococcus pneumoniae -derived capsular polysaccharide is a Pn-serotype 11A capsular polysaccharide.

9. The glycoconjugate of claim 1 , wherein said Streptococcus pneumoniae -derived capsular polysaccharide is a Pn-serotype 22F capsular polysaccharide.

10. The glycoconjugate of claim 1 , wherein said Streptococcus pneumoniae -derived capsular polysaccharide is a Pn-serotype 33F capsular polysaccharide.

11. The glycoconjugate of claim 1 , wherein said carrier protein is CRM 197 .

12. An immunogenic composition comprising a glycoconjugate according to claim 1 and a pharmaceutically acceptable excipient, carrier, or diluent.

13. An immunogenic composition according to claim 12 further comprising an additional antigen.

14. An immunogenic composition according to claim 13 , wherein the additional antigen comprises a glycoconjugate of a Streptococcus pneumoniae -derived capsular polysaccharide selected from the group consisting of Pn-serotype 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F and 33F capsular polysaccharides.

15. An immunogenic composition according to claim 14 further comprising at least one adjuvant.

16. A glycoconjugate comprising a Streptococcus pneumoniae -derived capsular polysaccharide conjugated to a carrier protein through a (2-((2-oxoethyl)thio)ethyl)carbamate (eTEC) spacer, wherein the polysaccharide is covalently linked to the eTEC spacer through a carbamate linkage, and wherein the carrier protein is covalently linked to the eTEC spacer through an amide linkage, as shown by formula (I):

wherein the glycoconjugate comprises at least one covalent linkage between the carrier protein and the polysaccharide for every 4, 10, 15 or 25 saccharide repeat units of the polysaccharide, and
wherein the Streptococcus pneumoniae -derived capsular polysaccharide is selected from the group consisting of Pn-serotype 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F and 33F capsular polysaccharides.

17. A glycoconjugate comprising a Streptococcus pneumoniae -derived capsular polysaccharide conjugated to a carrier protein through a (2-((2-oxoethyl)thio)ethyl)carbamate (eTEC) spacer, wherein the polysaccharide is covalently linked to the eTEC spacer through a carbamate linkage, and wherein the carrier protein is covalently linked to the eTEC spacer through an amide linkage, as shown by formula (I):

wherein the glycoconjugate comprises at least one covalent linkage between the carrier protein and the polysaccharide for every 4, 10, 15 or 25 saccharide repeat units of the polysaccharide, and
wherein the Streptococcus pneumoniae -derived capsular polysaccharide is a Pn-serotype 33F capsular polysaccharide.

18. An immunogenic composition comprising a glycoconjugate according to claim 17 and a pharmaceutically acceptable excipient, carrier, or diluent.

19. An immunogenic composition according to claim 18 further comprising an additional antigen.

20. An immunogenic composition according to claim 19 , wherein the additional antigen comprises a glycoconjugate of a Streptococcus pneumoniae -derived capsular polysaccharide selected from the group consisting of Pn-serotype 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, and 23F capsular polysaccharides.

Assignees

• Pfizer

Inventors

• Gu Jianxin
• Kim Jin-Hwan
• Prasad Avvari Krishna
• Yang Yu-Ying

Classifications

• A61K39/092

  Streptococcus · CPC title

• A61K2039/627

  characterised by the linker · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61K39/095 Primary

  Neisseria · CPC title

• A61K47/646

  the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines · CPC title