Conjugated beta-1,3-linked glucans

Patent metadata

Field	Value
Publication number	US-9439954-B2
Application number	US-73479508-A
Country	US
Kind code	B2
Filing date	Nov 26, 2008
Priority date	Nov 26, 2007
Publication date	Sep 13, 2016
Grant date	Sep 13, 2016

Abstract

Glucans having exclusively or mainly β-1,3 linkages are used as immunogens. These comprise β-1,3-linked glucose residues. Optionally, they may include β-1,6-linked glucose residues, provided that the ratio of β-1,3-linked residues to β-1,6-linked residues is at least 8:1 and/or there are one or more sequences of at least five adjacent non-terminal residues linked to other residues only by β-1,3 linkages. The glucans will usually be used in conjugated form. A preferred glucan source is curdlan, which may be hydrolyzed to a suitable form prior to conjugation.

First claim

What is claimed is:

1. A conjugate comprising a glucan covalently linked to a carrier molecule directly or via a linker, wherein the glucan has exclusively linear β-1,3-linked glucose residues and has from 6-50 glucose monosaccharide units, wherein the glucan comprises one or more sequences of at least five adjacent non-terminal glucose residues linked to other glucose residues only by β-1,3-linkages, and wherein the carrier molecule is a bacterial toxin, a toxoid of diphtheria toxin, a toxoid of tetanus toxin or CRM197, wherein the conjugate is capable of generating a protective antibody response specific for the glucan in a mammal, wherein the protective antibody response is capable of protecting against infections of Candida species in the mammal.

2. The conjugate of claim 1 , wherein the glucan is linear β-D-glucopyranose with exclusively 1,3 linkages.

3. The conjugate of claim 1 , wherein the glucan is a curdlan, a paramylon, or a fragment thereof.

4. The conjugate of claim 2 , wherein the glucan is a hydrolysis fragment of the curdlan.

5. The conjugate of claim 1 , wherein the glucan has the following structure:

wherein n+2 is in the range of 11-19.

6. The conjugate of claim 5 , wherein the n+2 is 15.

7. The conjugate of claim 1 , wherein the carrier molecule is diphtheria toxin or tetanus toxin, or a toxoid thereof or CRM197.

8. The conjugate of claim 7 , wherein the carrier molecule is CRM197.

9. A pharmaceutical composition comprising the conjugate of claim 1 , in combination with a pharmaceutically acceptable carrier.

10. The composition of claim 9 , wherein the composition is an immunogenic composition.

11. The composition of claim 10 , wherein the composition includes an adjuvant.

12. A pharmaceutical composition comprising the conjugate of claim 5 in combination with a pharmaceutically acceptable carrier.

13. The composition of claim 12 , wherein the composition is an immunogenic composition.

14. The composition of claim 13 , wherein the composition comprises an adjuvant.

Assignees

• Berti Francesco
• Costantino Paolo
• Romano Maria Rosaria
• Glaxosmithkline Biologicals Sa

Inventors

• Berti Francesco
• Costantino Paolo
• Romano Maria Rosaria

Classifications

• A61K9/02

  Suppositories; Bougies; Bases therefor; {Ovules}(apparatus for making A61J3/08; devices for introducing into the body A61M31/00) · CPC title

• A61K2039/55566

  Emulsions, e.g. Freund's adjuvant, MF59 · CPC title

• A61K47/6415

  Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins · CPC title

• A61K2039/55561

  CpG containing adjuvants; Oligonucleotide containing adjuvants · CPC title

• A61P37/02

  Immunomodulators · CPC title