Glycoconjugation processes and compositions

Patent metadata

Field	Value
Publication number	US-11723965-B2
Application number	US-202117395108-A
Country	US
Kind code	B2
Filing date	Aug 5, 2021
Priority date	Aug 16, 2012
Publication date	Aug 15, 2023
Grant date	Aug 15, 2023

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 said glycoconjugate has a molecular size distribution (K d ) of ≥35%, at ≤0.3.

2. The glycoconjugate of claim 1 , wherein said glycoconjugate has a molecular size distribution (K d ) of ≥67%, at ≤0.3.

3. The glycoconjugate of claim 1 , wherein said Streptococcus pneumoniae -derived capsular polysaccharide is covalently linked to the eTEC spacer through a carbamate linkage, and wherein said carrier protein is covalently linked to the eTEC spacer through an amide linkage.

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

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

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

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

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

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

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

11. An immunogenic composition according to claim 10 , further comprising an additional antigen.

12. An immunogenic composition according to claim 11 , wherein the additional antigen comprises a glycoconjugate of a Streptococcus pneumoniae -derived capsular polysaccharide selected from 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.

13. An immunogenic composition according to claim 12 , further comprising at least one adjuvant.

14. 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 said glycoconjugate has a molecular size distribution (K d ) of ≥35%, at ≤0.3, and
wherein said Streptococcus pneumoniae -derived capsular polysaccharide is selected from 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. 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 said glycoconjugate has a molecular size distribution (K d ) of ≥67%, at ≤0.3, and
wherein said Streptococcus pneumoniae -derived capsular polysaccharide is a Pn-serotype 33F capsular polysaccharide.

16. An immunogenic composition comprising a glycoconjugate according to claim 15 and a pharmaceutically acceptable excipient, carrier, or diluent.

17. An immunogenic composition according to claim 16 , further comprising an additional antigen.

18. An immunogenic composition according to claim 17 , 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

• A61K39/095 Primary

  Neisseria · CPC title

• A61K39/092

  Streptococcus · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K47/64 Primary

  Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) · CPC title

• A61K47/646

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