Protein-polymer conjugates

• US 8,143,214 B2
• Filed: 08/15/2008
• Issued: 03/27/2012
• Est. Priority Date: 08/16/2007
• Status: Active Grant

• Current Assignee: PharmaEssentia Corporation
• Original Assignee: PharmaEssentia Corporation
• Inventors: Lin, Ko-Chung
• Primary Examiner(s): Ha, Julie
• Application Number:
  US12/192,485
• Publication Number:
  US 20090053177A1
• Time in Patent Office: 1,320 Days
• Field of Search: None
• US Class Current: 514/4.3
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/20 for DNA viruses

Abstract

Protein-polymer conjugates are described. Also described are a method for preparing a protein-polymer conjugate and its use in treating hepatitis B virus or hepatitis C virus infection.

Claims

1. A protein-polymer conjugate of formula I:

2. The conjugate of claim 1, wherein G₃ is a bond and P is a protein in which the amino group at the N-terminus is bonded to G₃.

3. The conjugate of claim 2, wherein each of A₁ and A₂ is mPEG having a molecular weight of 10-30 kD.

4. The conjugate of claim 3, wherein each of G₁ and G₂ is

5. The conjugate of claim 4, wherein P is modified interferon containing 1-4 additional amino acid residues at the N-terminus.

6. The conjugate of claim 5, wherein n is 2.

7. The conjugate of claim 6, wherein the conjugate is

9. The conjugate of claim 1, wherein P is interferon-a having 1-4 additional amino acid residues at the N-terminus.

10. The conjugate of claim 1, wherein P is SEQ ID NO:

1, 2, 3, 4, or 5.

11. The conjugate of claim 1, wherein P is SEQ ID NO:

6 or 7.

12. The conjugate of claim 1, wherein P is SEQ ID NO:

8 or 9.

8. A method of treating hepatitis C virus infection or hepatitis B virus infection comprising administering to a subject in need thereof an effective amount of a

protein-polymer conjugate of formula I: