Oligosaccharide-protein conjugates

Patent metadata

Field	Value
Publication number	US-11279725-B2
Application number	US-201916581148-A
Country	US
Kind code	B2
Filing date	Sep 24, 2019
Priority date	Dec 16, 2008
Publication date	Mar 22, 2022
Grant date	Mar 22, 2022

Abstract

Provided herein are conjugates comprising a protein and an oligosaccharide of one of Formulae I-VI. Also provided herein are pharmaceutical compositions comprising such conjugates. Further provided herein are methods of treating a lysosomal storage disorder in a mammal by administration of an oligosaccharide-glycoprotein conjugate.

First claim

The invention claimed is:

1. An oligosaccharide-protein conjugate, comprising (1) a protein and (2) an oligosaccharide of Formula 2:

wherein k is selected from α, β, and a mixture of α and β.

2. An oligosaccharide-protein conjugate, comprising (1) a protein and (2) an oligosaccharide of Formula 3:

wherein k is selected from α, β, and a mixture of α and β.

3. The oligosaccharide-protein conjugate of claim 1 , wherein the protein is a glycoprotein.

4. The oligosaccharide-protein conjugate of claim 3 , wherein the glycoprotein is a lysosomal enzyme.

5. The oligosaccharide-protein conjugate of claim 4 , wherein the lysosomal enzyme is acid α-glucosidase, α-galactosidase A, acid sphingomyelinase, α-L-iduronidase, iduronate-2-sulfatase, or N-acetylgalactosamine-4-sulfatase.

6. The oligosaccharide-protein conjugate of claim 4 , wherein the lysosomal enzyme is acid α-glucosidase.

7. A pharmaceutical composition comprising the oligosaccharide-protein conjugate of claim 1 and an excipient.

8. A method of treating a lysosomal storage disorder, comprising administering to a mammal an oligosaccharide-glycoprotein conjugate comprising (1) a lysosomal enzyme and (2) an oligosaccharide of any one of Formulae 1-3:

wherein:
k is selected from α, β, and a mixture of α and β.

9. The method of claim 8 , wherein the lysosomal storage disorder is chosen from Fabry disease, Pompe disease, Niemann-Pick A disease, Niemann-Pick B disease, mucopolysaccharidosis I, mucopolysaccharidosis II, and mucopolysaccharidosis VI.

10. The method of claim 9 , wherein the lysosomal storage disorder is Pompe disease.

11. The method of claim 8 , further comprising administering methotrexate to the mammal before, after, or during treatment with the oligosaccharide-glycoprotein conjugate.

12. The method of claim 8 , wherein the oligosaccharide is an oligosaccharide of Formula 1, wherein k is selected from α, β, and a mixture of α and β.

13. The method of claim 8 , wherein the oligosaccharide is an oligosaccharide of Formula 2, wherein k is selected from α, β, and a mixture of α and β.

14. The method of claim 8 , wherein the oligosaccharide is an oligosaccharide of Formula 3, wherein k is selected from α, β, and a mixture of α and β.

15. The oligosaccharide-protein conjugate of claim 2 , wherein the protein is a glycoprotein.

16. The oligosaccharide-protein conjugate of claim 15 , wherein the glycoprotein is a lysosomal enzyme.

17. The oligosaccharide-protein conjugate of claim 16 , wherein the lysosomal enzyme is acid α-glucosidase, α-galactosidase A, acid sphingomyelinase, α-L-iduronidase, iduronate-2-sulfatase, or N-acetylgalactosamine-4-sulfatase.

18. The oligosaccharide-protein conjugate of claim 16 , wherein the lysosomal enzyme is acid α-glucosidase.

19. A pharmaceutical composition comprising the oligosaccharide-protein conjugate of claim 2 and an excipient.

Assignees

• Genzyme Corp

Inventors

• Avila Luis Z
• Pan Clark Q
• Finn Patrick
• Harrahy John
• Zhou Qun
• Zhu Yunxiang
• Konowicz Paul A
• Paterson Duncan E
• Peer Andreas
• Kutzko Joseph P
• Reardon Michael R
• Stefano James E
• Zheng Xiaoyang
• Miller Robert J
• Young Lauren

Classifications

• C07H15/04 Primary

  attached to an oxygen atom of the saccharide radical · CPC title

• A61K47/61

  the organic macromolecular compound being a polysaccharide or a derivative thereof · CPC title

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title

• A61K38/46 Primary

  Hydrolases (3) · CPC title

• A61P43/00

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