Modified saccharides

Patent metadata

Field	Value
Publication number	US-9803030-B2
Application number	US-44870908-A
Country	US
Kind code	B2
Filing date	Jan 11, 2008
Priority date	Jan 11, 2007
Publication date	Oct 31, 2017
Grant date	Oct 31, 2017

Abstract

Modified capsular saccharides comprising a blocking group at a hydroxyl group position on at least one of the monosaccharide units of the corresponding native capsular saccharide, wherein the blocking group is of the formula (Ia) or (Ib): —OX—Y (Ia) or —O—R 1 (Ib) wherein X is C(O), S(O) or SO 2 ; Y is NR 1 R 2 or R 3 ; R 1 is C 1-6 alkyl substituted with 1, 2 or 3 groups independently selected from hydroxyl, sulphydryl and amine; R 2 is H or C 1-6 alkyl; and R 3 is C 1-6 alkyl; processes for modifying a capsular saccharide with the blocking groups; saccharide-protein conjugates comprising the modified capsular saccharide; processes for making the saccharide-protein conjugates, pharmaceutical compositions comprising the modified capsular saccharides and/or saccharide-protein conjugates; and methods and uses of the same.

First claim

The invention claimed is:

1. A saccharide-protein conjugate, wherein the saccharide is a modified Neisseria meningitidis serogroup A capsular saccharide wherein at least 90% of the hydroxyl groups at position 3 and at least 90% of the hydroxyl groups at position 4 of the monosaccharide units of the saccharide comprise a blocking group of the formula (Ia):
—O—X—Y  (Ia)

wherein
X is C(O);
Y is R 3 ; and
R 3 is CH 3 ,

wherein
the capsular saccharide comprises four or more monosaccharide units,
and
an effective amount of the modified capsular saccharide is able to induce a protective immune response in mammals.

2. The conjugate according to claim 1 , wherein all the monosaccharide units of the saccharide have blocking groups, at both the position 3 hydroxyl groups and the position 4 hydroxyl groups.

3. The conjugate according to claim 1 , wherein the modified capsular saccharide is an oligosaccharide.

4. The conjugate according to claim 1 , wherein there is at least one monosaccharide unit of the modified capsular saccharide where two vicinal hydroxyl groups of the saccharide do not comprise blocking groups.

5. The conjugate of claim 1 , wherein the protein is a bacterial toxin or toxoid.

6. The conjugate of claim 5 , wherein the bacterial toxin or toxoid is diphtheria toxin or toxoid.

7. The conjugate of claim 5 , wherein the bacterial toxin or toxoid is CRM197.

8. A pharmaceutical composition comprising (a) the conjugate according to claim 1 , and (b) a pharmaceutically acceptable carrier.

9. The composition according to claim 8 , further comprising a saccharide antigen from one or more of semigroups C, W135 and Y of N. meningitidis.

10. The composition according to claim 8 or claim 9 , further comprising a vaccine adjuvant.

11. The composition according to claim 10 , wherein the adjuvant is an aluminium phosphate.

12. The composition according to claim 8 , which is a vaccine against a disease caused by N. meningitidis.

13. A method for raising an antibody response in a mammal, comprising administering the pharmaceutical composition according to claim 8 to the mammal.

14. The composition according to claim 9 , wherein the saccharide, in the conjugate, is an oligosaccharide.

15. A molecule comprising a saccharide moiety of formula:

wherein
T is of the formula (A) or (B):

n is an integer from 2 to 100;
each Z group is independently selected from OH or a blocking group of the formula (1a):
—O—X—Y  (Ia);

each Q group is independently selected from OH or a blocking group of the formula (1a):
—O—X—Y  (Ia);

W is selected from OH or a blocking group of the formula (Ia):
—O—X—Y  (Ia):

L is O, NH, NE, S or Se, wherein the free covalent bond of L is joined to a protein carrier; and wherein the protein carrier is a bacterial toxin or toxoid;
wherein at least 90% of the Z groups and at least 90% of the Q groups comprise a blocking group of formula (1a);
wherein in formula (Ia);
X is C(O);
Y is R 3 ; and R 3 is CH 3 .

16. A pharmaceutical composition comprising (a) a molecule according to claim 15 , and (b) a pharmaceutically acceptable carrier.

17. The composition according to claim 16 , further comprising a saccharide antigen from one or more of semigroups C, W135 and Y of N. meningitidis.

18. The composition according to claim 17 , wherein the saccharide, in the molecule, is an oligosaccharide.

19. The composition according to claim 16 or claim 17 , further comprising a vaccine adjuvant.

Assignees

• Berti Francesco
• Costantino Paolo
• Pianigiani Alessandro
• Glaxosmithkline Biologicals Sa

Inventors

• Bardotti Angela
• Berti Francesco
• Costantino Paolo

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61K39/095

  Neisseria · CPC title

• C08B37/006

  Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof · CPC title

• A61K2039/55505

  Inorganic adjuvants · CPC title