H. pylori lipopolysaccharide outer core epitope

Patent metadata

Field	Value
Publication number	US-9475863-B2
Application number	US-201514739013-A
Country	US
Kind code	B2
Filing date	Jun 15, 2015
Priority date	Jul 31, 2009
Publication date	Oct 25, 2016
Grant date	Oct 25, 2016

Abstract

Helicobacter pylori , one of the most common human pathogens, is associated with the development of human chronic gastritis, peptic ulcers and gastric cancer. The invention relates to a α1,6-glucan-containing Helicobacter pylori compound comprising the structure of Formula I:

wherein R is a α-DDHep-3-α-L-Fuc-3-β-GlcNAc trisaccharide substituted with an α1,6-glucan linked to an α1,3-DD-heptan, and wherein the last DD-Hep residue of α1,3-DD-heptan is capped with β-GlcNAc residue. Compositions comprising the compound, uses of the compound, and antibodies raised against the compound are also described.

First claim

The invention claimed is:

1. A monoclonal antibody that specifically binds to an α1,6-glucan-containing Helicobacter pylori compound comprising the structure of Formula I:

wherein the R is a α-DDHep-3-α-L-Fuc-3-β-GlcNAc trisaccharide substituted with an α1,6-glucan comprising from 4 to 12 α1,6-linked glucose residues linked to an α1,3-DD-heptan, wherein the last DD-Hep residue of the α1,3-DD-heptan is capped with β-GlcNAc residue.

2. The monoclonal antibody of claim 1 , wherein in the structure of Formula I, the heptan moiety comprises from 2 to 6 α1,3-linked DD-heptose residues.

3. The monoclonal antibody of claim 1 , wherein in the structure of Formula I, the R comprises

wherein the β-GlcNAc residue L is linked to O-2 of the Hep G, n=1 to 11, and m=0 to 4.

4. The monoclonal antibody of claim 3 , wherein in the structure of Formula I, n=9.

5. The monoclonal antibody of claim 3 , wherein in the structure of Formula I, m=2.

6. The monoclonal antibody of claim 1 , wherein the structure of Formula I further comprises a lipid A moiety covalently attached to the Kdo residue C.

7. The monoclonal antibody of claim 6 , wherein in the structure of Formula I, the lipid A molecule is O-deacylated or is cleaved through hydrolysis of the ketosidic linkage of the Kdo residue.

8. The monoclonal antibody of claim 1 , wherein the compound is isolated or purified from H. pylori strain HP0826::Kan.

9. Monoclonal antibody 1C4F9, produced by a cell line deposited with the International Depositary Authority of Canada, National Microbiology Laboratory, Public Health Agency of Canada under the accession number 300709-01.

Assignees

• Nat Res Council Canada

Inventors

• Altman Eleonora
• Harrison Blair A
• Chandan Vandana

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P35/00

  Antineoplastic agents · 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