Methods and compositions relating to synthetic beta-1,6 glucosamine oligosaccharides

Patent metadata

Field	Value
Publication number	US-10034927-B2
Application number	US-201615258417-A
Country	US
Kind code	B2
Filing date	Sep 7, 2016
Priority date	Jul 21, 2008
Publication date	Jul 31, 2018
Grant date	Jul 31, 2018

Abstract

The invention relates to the compositions of synthetic oligo-β-(1→6)-2-amino-2-deoxy-D-glu-copyranosides conjugated to carriers, and methods for making and use same.

First claim

What is claimed is:

1. A method for stimulating an immune response in a subject comprising
administering to a subject in need thereof an oligosaccharide-carrier conjugate comprising an oligosaccharide conjugated to a carrier through a linker that is

wherein the linker is O-linked to the oligosaccharide and N-linked to the carrier, wherein n is greater than 1, m is a number selected from 1 to 10, p is a number selected from 1 to 20, and R is H or an alkyl group, wherein the oligosaccharide comprises a beta-1,6-glucosamine polymer, having a length of at least two monomeric units, wherein the oligosaccharide is 0-40% acetylated,
in an amount effective to stimulate an immune response in the subject.

2. The method of claim 1 , wherein the subject is a human.

3. The method of claim 1 , wherein the subject is non-human.

4. The method of claim 1 , further comprising isolating antibodies or antibody-forming cells from the subject.

5. The method of claim 1 , wherein the oligosaccharide is 5-11 monomers in length.

6. The method of claim 5 , wherein the carrier is tetanus toxoid.

7. The method of claim 6 , wherein the conjugate has an oligosaccharide to carrier ratio in the range of 10:1 to 50:1.

8. A method for preventing an infection in a subject comprising administering to a subject having or at risk of developing an infection of a bacterial species that produces poly-N-acetyl glucosamine (PNAG) an effective amount for inducing an immune response of an oligosaccharide-carrier conjugate comprising an oligosaccharide conjugated to a carrier through a linker that is

wherein the linker is O-linked to the oligosaccharide and N-linked to the carrier, n is greater than 1, m is a number selected from 1 to 10, p is a number selected from 1 to 20, and R is H or an alkyl group, wherein the oligosaccharide comprises a beta-1,6-glycosamine polymer, having a length of at least two monomeric units and 0-40% N-acetylation.

9. The method of claim 8 , wherein the oligosaccharide is 5-11 monomers in length.

10. The method of claim 9 , wherein the carrier is tetanus toxoid.

11. The method of claim 10 , wherein the conjugate has an oligosaccharide to carrier ratio of 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 20:1, 30:1, 40:1, 50:1, 60:1, 70:1, 80:1, 90: 1 or 100:1.

12. The method of claim 10 , wherein the conjugate has an oligosaccharide to carrier ratio in the range of 10:1 to 50:1.

13. The method of claim 8 , wherein the carrier is tetanus toxoid.

14. The method of claim 8 , wherein the conjugate has an oligosaccharide to carrier ratio of 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 20:1, 30:1, 40:1, 50:1, 60:1, 70:1, 80:1, 90: 1 or 100:1.

15. The method of claim 8 , wherein the conjugate has an oligosaccharide to carrier ratio in the range of 10:1 to 50:1.

16. The method of claim 1 , wherein the carrier is tetanus toxoid.

17. The method of claim 1 , wherein the conjugate has an oligosaccharide to carrier ratio in the range of 10:1 to 50:1.

Assignees

• Brigham & Womens Hospital Inc

Inventors

• Pier Gerald B
• Nifantiev Nikolay
• Tsvetkov Yury
• Gening Marina

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61K2039/6037

  Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT] · CPC title