Therapeutic peptides

• US 8,143,380 B2
• Filed: 07/08/2005
• Issued: 03/27/2012
• Est. Priority Date: 07/08/2004
• Status: Active Grant

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Walker, Kenneth W., Kinstler, Olaf B., Sitney, Karen C.
• Primary Examiner(s): Huff, Sheela J
• Application Number:
  US11/631,461
• Publication Number:
  US 20080254020A1
• Time in Patent Office: 2,454 Days
• Field of Search: None
• US Class Current: 530/391.7
• 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: A61K 47/6811 the drug being a protein or peptide, e.g. transferrin or bleomycin
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents

Abstract

The invention relates to compounds that exhibit improved bioefficacy in multidose administration. More specifically, the invention relates to polypeptides or peptides modified to include an antibody Fc region and one or more water soluble polymers.

Claims

1. A compound comprising a structure set out in Formula V

[F¹-(L²)_e-P¹-(L³)_f-P²]-(L¹)_c-PEG_d 

 

Formula V

wherein;

F¹ is an Fc domain;

wherein P¹ and P² are each independently sequences of pharmacologically active peptides;

L¹, L² and L³ are each independently linkers;

c, e and f are each independently 0 or 1;

d is at least 1; and

wherein the Fc domain is attached at the N-terminus of -L²-P¹-L³-P² and one or more PEG is attached to any reactive moiety in the Fc domain, optionally through linker L¹;

said compound having a property of improved bioefficacy when administered in a multidose regimen.

2. The compound of claim 1 which is a multimer.

3. The compound of claim 2 which is a dimer.

4. The compound of claim 1 wherein P¹ and/or P² are independently selected from a peptide set out in any one of Tables 4 through 20.

5. The compound of claim 1 wherein P¹ and P² have the same amino acid sequence as SEQ ID NO:

459.

6. The compound of claim 1 wherein PEG has a molecular weight of between about 2 kDa and 100 kDa.

7. The compound of claim 6 wherein said PEG has a molecular weight of between about 6 kDa and 25 kDa.

8. A composition comprising the compound of claim 1, wherein said composition comprises the PEGylated compound in an amount selected from the group consisting of:

at least 50% PEGylated compound, at least 75% PEGylated compound, at least 85% PEGylated compound, at least 90% PEGylated compound, at least 95% PEGylated compound.

9. A method of treating a disease or disorder comprising administering a composition comprising the compound of claim 1 in an amount effective to treat the disease or disorder.

10. The method of claim 9, wherein said amount is from 0.1-1000 μ

g/kg—

of body weight or from 0.1-150 μ

g/kg body weight.

11. A pharmaceutical composition comprising the compound of claim 1 in admixture with a pharmaceutically acceptable carrier thereof.