Glycopegylated granulocyte colony stimulating factor

• US 7,956,032 B2
• Filed: 06/23/2005
• Issued: 06/07/2011
• Est. Priority Date: 12/03/2003
• Status: Active Grant

• Current Assignee: Novo Nordisk A/S
• Original Assignee: Novo Nordisk A/S
• Inventors: Bowe, Caryn, DeFrees, Shawn, Wang, Zhi-Guang, Zopf, David A.
• Primary Examiner(s): Tsang; Cecilia
• Assistant Examiner(s): HEARD, THOMAS SWEENEY
• Application Number:
  US11/166,404
• Publication Number:
  US 20070014759A1
• Time in Patent Office: 2,175 Days
• Field of Search: None
• US Class Current: 514/7.7
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]

Abstract

The present invention provides conjugates between Granulocyte Colony Stimulating Factor and PEG moieties. The conjugates are linked via an intact glycosyl linking group that is interposed between and covalently attached to the peptide and the modifying group. The conjugates are formed from both glycosylated and unglycosylated peptides by the action of a glycosyltransferase. The glycosyltransferase ligates a modified sugar moiety onto either an amino acid or glycosyl residue on the peptide. Also provided are pharmaceutical formulations including the conjugates. Methods for preparing the conjugates are also within the scope of the invention.

Claims

1. A Granulocyte Colony Stimulating Factor peptide conjugate comprising a glycosyl linking group attached to an amino acid residue of said peptide, said glycosyl linking group comprising a modified sialyl residue having the formula:

2. The peptide conjugate according to claim 1, wherein said modified sialyl residue has the formula:

3. The peptide conjugate according to claim 1, wherein Q is selected from H and CH₃.

4. The peptide conjugate according to claim 1, wherein said glycosyl linking group comprises the formula:

5. The peptide conjugate according to claim 4, wherein s is 1;

b is 0and f is an integer from about 200 to about 500.

6. The peptide conjugate according to claim 5, wherein s is 1;

b is 0and f is an integer from about 400 to about 500.

7. The peptide conjugate according to claim 1, wherein said amino acid residue is a member selected from serine or threonine.

8. The peptide conjugate according to claim 1, wherein said peptide has the amino acid sequence of SEQ ID NO:

1.

9. The peptide conjugate according to claim 8, wherein said amino acid residue is a threonine at position 134 of SEQ ID NO:

1.

10. A pharmaceutical formulation comprising the Granulocyte Colony Stimulating Factor peptide conjugate according to claim 1, and a pharmaceutically acceptable carrier.