IP Library › Granted Patent US 8,063,015
Granted Patent B2
US 8,063,015 · App. 12/496,595 · Granted Nov 22, 2011

Glycopegylation methods and proteins/peptides produced by the methods

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Quick Facts
Patent No.
US 8,063,015
App. No.
12/496,595
Granted
Nov 22, 2011
Kind
B2
Abstract

The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.

Claims (20)

1. A covalent conjugate between a peptide and a water-soluble polymer, wherein said water-soluble polymer is not a naturally occurring sugar and is covalently attached to said peptide through an intact glycosyl linking group, and wherein said covalent conjugate is formed via reaction with Campylobacter sialyltransferase I (CST-I).

2. The covalent conjugate according to claim 1 , wherein said water-soluble polymer is a poly(ether).

3. The covalent conjugate according to claim 2 , wherein said poly(ether) is a poly(alkylene oxide).

4. The covalent conjugate according to claim 3 , wherein said poly(alkylene oxide) is a poly(ethylene glycol).

5. The covalent conjugate according to claim 4 , wherein said poly(ethylene glycol) is a member selected from linear poly(ethylene glycol) and branched poly(ethylene glycol).

6. The covalent conjugate according to claim 4 , wherein said poly(ethylene glycol) has a degree of polymerisation of from about 1 to about 5,000.

7. The covalent conjugate according to claim 6 , wherein said poly(ethylene glycol) has a degree of polymerisation of from about 1 to about 1,000.

8. The covalent conjugate according to claim 1 , wherein said intact glycosyl linking group is attached to a member selected from a carbohydrate moiety, an amino acid moiety and combinations thereof.

9. The covalent conjugate according to claim 8 , wherein said intact glycosyl linking group is attached to said carbohydrate moiety which is a member selected from an O- or N-linked glycan and combinations thereof.

10. The covalent conjugate according to claim 8 , wherein said intact glycosyl linking group is attached to hydroxyl or amino groups or combinations thereof of said amino acid moiety.

11. The covalent conjugate according to claim 8 , wherein said intact glycosyl linking group comprises sialic acid, galactose, N-acetylglucosamine or N-acetylgalactosamine residue.

12. The covalent conjugate according to claim 1 , wherein said water-soluble polymer is attached to a sialic acid residue at a position which is a member selected from the 5-, and the 9-position of said sialic acid.

13. The covalent conjugate according to claim 1 , wherein said peptide is a therapeutic agent.

14. The covalent conjugate according to claim 1 , wherein said peptide is selected from the group consisting of granulocyte colony stimulating factor, interferon-alpha, interferon-beta, Factor VIIa, Factor VIII, Factor IX, follicle stimulating hormone, erythropoietin, granulocyte macrophage colony stimulating factor, interferon-gamma, alpha-1-protease inhibitor, beta-glucosidase, tissue plasminogen activator protein, interleukin-2, chimeric tumor necrosis factor receptor, urokinase, chimeric anti-glycoprotein IIb/IIIa antibody, chimeric anti-HER2 antibody, chimeric anti-respiratory syncytial virus antibody, chimeric anti-CD20 antibody, DNase, chimeric anti-tumor necrosis factor antibody, human insulin, hepatitis B sAg, and human growth hormone.

15. A pharmaceutical composition comprising the covalent conjugate according to claim 1 and a pharmaceutically acceptable diluent.

16. A cell-free, in vitro method of forming a covalent conjugate between a peptide and a water-soluble polymer, wherein said water-soluble polymer is covalently attached to said peptide through an intact glycosyl linking group, said method comprising:

contacting said peptide with a mixture comprising at least one nucleotide sugar covalently linked to said water soluble polymer and at least one glycosyltransferase for which said nucleotide sugar is a substrate, wherein said glycosyltransferase is Campylobacter sialyltransferase I (CST-I), thereby forming said covalent conjugate of said peptide.

17. The method according to claim 16 , wherein said water-soluble polymer is a poly(ether).

18. The method according to claim 17 , wherein said poly(ether) is a poly(ethylene glycol).

19. The method of claim 16 , wherein said peptide is selected from the group consisting of granulocyte colony stimulating factor, interferon-alpha, interferon-beta, Factor VIIa, Factor VIII, Factor IX, follicle stimulating hormone, erythropoietin, granulocyte macrophage colony stimulating factor, interferon-gamma, alpha-1-protease inhibitor, beta-glucosidase, tissue plasminogen activator protein, interleukin-2, chimeric tumor necrosis factor receptor, urokinase, chimeric anti-glycoprotein IIb/IIIa antibody, chimeric anti-HER2 antibody, chimeric anti-respiratory syncytial virus antibody, chimeric anti-CD20 antibody, DNase, chimeric anti-tumor necrosis factor antibody, human insulin, hepatitis B sAg, and human growth hormone.