Capsular polysaccharide solubilisation and combination vaccines

Patent metadata

Field	Value
Publication number	US-9358278-B2
Application number	US-32146409-A
Country	US
Kind code	B2
Filing date	Jan 20, 2009
Priority date	Jun 20, 2001
Publication date	Jun 7, 2016
Grant date	Jun 7, 2016

Abstract

Precipitated bacterial capsular polysaccharides can be efficiently re-solubilised using alcohols as solvents. The invention provides a process for purifying a bacterial capsular polysaccharide, comprising the steps of (a) precipitation of said polysaccharide, followed by (b) solubilisation of the precipitated polysaccharide using ethanol. CTAB can be used for step (a). The material obtained, preferably following hydrolysis and sizing, can be conjugated to a carrier protein and formulated as a vaccine. Also, in vaccines comprising saccharides from both serogroups A and C, the invention provides that the ratio (w/w) of MenA saccharide:MenC saccharide is >1.

First claim

The invention claimed is:

1. A process for purifying a bacterial capsular polysaccharide, comprising the steps of (a) precipitating the polysaccharide using one or more cationic detergents without an inert porous support, followed by (b) solubilising the precipitated polysaccharide using an alcohol, wherein the bacterial capsular polysaccharide is from Neisseria meningitidis, Haemophilus influenzae or Streptococcus pneumoniae , wherein the process does not comprise precipitating the polysaccharide using one or more cationic detergents on an inert porous support.

2. A process for purifying a bacterial capsular polysaccharide, comprising the steps of (a) precipitating the polysaccharide using one or more cationic detergents, followed by (b) solubilising the precipitated polysaccharide using an alcohol, wherein the alcohol comprises ethanol and the ethanol has a final concentration of between 65% and 95%.

3. A process for purifying a bacterial capsular polysaccharide, comprising the steps of (a) precipitating the polysaccharide using one or more cationic detergents, followed by (b) solubilising the precipitated polysaccharide using pure ethanol or an ethanol:water mixture, wherein the ethanol:water mixture does not comprise a salt.

4. The process of any one of claims 1 to 2 , wherein the cationic detergent(s) comprise a cetyltrimethylammonium salt, a tetrabutylammonium salt, a myristyltrimethylammonium salt and/or hexadimethrine bromide.

5. The process of any one of claims 1 to 3 , wherein the polysaccharide obtained in step (b) is then precipitated.

6. The process of claim 5 , wherein precipitation is by addition of calcium or sodium salts.

7. The process of any one of claim 1 , 2 , or 3 , further comprising the step of conjugation to a carrier protein.

8. The process of claim 7 , wherein the carrier protein is a diphtheria toxoid or tetanus toxoid.

9. The process of claim 7 , wherein the saccharide is activated prior to conjugation.

10. The process of claim 9 , wherein activation involves a cyanylating reagent.

11. The process of claim 9 , wherein conjugation is with a linker.

12. The process of claim 7 , wherein, after conjugation, free and conjugated saccharides are separated.

13. The process of claim 12 , wherein separation uses hydrophobic chromatography, tangential ultrafiltration, or diafiltration.

Assignees

• Costantino Paolo
• Novartis Ag

Inventors

• Costantino Paolo

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K2039/545

  characterised by the dose, timing or administration schedule · CPC title