Antibodies and other selective IL-1 binding agents that allow binding to IL-1 receptor but not activation thereof

• US 20030026806A1
• Filed: 10/29/2001
• Published: 02/06/2003
• Est. Priority Date: 10/27/2000
• Status: Abandoned Application

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Witte, Alison, Qian, Xueming, Vezina, Chris, Varnum, Brian C.
• Application Number:
  US10/011,931
• Publication Number:
  US 20030026806A1
• Time in Patent Office: Days
• US Class Current: 424/145.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: C07K 16/245 IL-1
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered

Abstract

The invention concerns methods of treating IL-1-mediated disease by administering a selective IL-1 binding agents that form an antagonist complex with the IL-1 ligand. The antagonist complex can bind to the IL-1 receptor without activating the receptor. The selective binding agents contemplated by this invention thus have the properties of free ligand absorption (through binding of the selective binding agent to free IL-1α or β) and receptor activation inhibition (through binding of the antagonist complex to the receptor and preventing its activation).

Claims

1. A method of treating IL-1-mediated disease, which comprises administering an IL-1 selective binding agent that is capable of binding to IL-1β

, wherein the selective binding agent-IL-1 complex is capable of binding to IL-1 receptor without activating said receptor.

2. The method of claim 1, wherein the selective binding agent-IL-1 complex is capable of blocking association of the IL-1 receptor with IL-1 receptor accessory protein.

3. The method of claim 1, wherein the IL-1 selective binding agent is an antibody.

4. The method of claim 3, wherein the antibody is a chimeric antibody.

5. The method of claim 3, wherein the antibody is a humanized antibody.

6. The method of claim 3, wherein the antibody is a fully human antibody.

7. The method of claim 3, wherein the antibody is generated by phage display.

8. The method of claim 3, wherein the antibody comprises SEQ ID NO:

2.

9. A method of blocking IL-1α

and IL-1β

from binding to the IL-1 receptor, which comprises administering an IL-1 selective binding agent that is capable of binding to IL-1β

, wherein the selective binding agent-IL-1 complex is capable of binding to IL-1 receptor without activating said receptor.

10. A method of treating IL-1-mediated disease, which comprises administering an IL-1 selective binding agent that is capable of binding to IL-1α

, wherein the selective binding agent-IL-1α

complex is capable of binding to IL-1 receptor without activating said receptor.

11. The method of claim 10, wherein the selective binding agent-IL-1α

complex is capable of blocking association of the IL-1 receptor with IL-1 receptor accessory protein.

12. The method of claim 10, wherein the IL-1 selective binding agent is an antibody.

13. The method of claim 12, wherein the antibody is a chimeric antibody.

14. The method of claim 12, wherein the antibody is a humanized antibody.

15. The method of claim 12, wherein the antibody is a fully human antibody.

16. The method of claim 12, wherein the antibody is generated by phage display.

17. A method of blocking IL-1α

and IL-1β

from binding to the IL-1 receptor, which comprises administering an IL-1 selective binding agent that is capable of binding to IL-1α

, wherein the selective binding agent-IL-1α

complex is capable of binding to IL-1 receptor without activating said receptor.