Composition and method for treating inflammatory diseases

• US 6,294,170 B1
• Filed: 08/07/1998
• Issued: 09/25/2001
• Est. Priority Date: 08/08/1997
• Status: Expired due to Term

• Current Assignee: Swedish Orphan Biovitrum AB (publ)
• Original Assignee: Amgen Inc.
• Inventors: Collins, David S., Boone, Thomas C., Bevilacqua, Michael P., Hershenson, Susan
• Primary Examiner(s): BORIN, MICHAEL L
• Application Number:
  US09/131,247
• Time in Patent Office: 1,145 Days
• Field of Search: 424/134.1, 514/12, 530/324
• US Class Current: 424/134.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 47/6813 the drug being a peptidic cytokine, e.g. an interleukin or interferon
• CPC Class Codes: A61K 47/6835 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
• CPC Class Codes: C07K 14/54 Interleukins [IL]
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

A protein which exhibits a therapeutic effect on inflammation and is useful for treating IL-1-mediated inflammatory diseases, particularly diseases of the joint.

Claims

1. A fusion protein comprising an interleukin-1 receptor antagonist (IL-1ra) which comprises:

(a) the amino acid sequence of SEQ ID NO;

2, or

(b) an IL-1 inhibitory fragment of the amino acid sequence of SEQ ID NO;

2 in which 1 to 30 amino acids are deleted from the N-terminus or C-terminus, or

(c) an IL-1 inhibitory sequence which is at least 70% homologous to the amino acid sequence of SEQ ID NO;

2;

with a constant domain of a heavy or light chain of human immunoglobulin at the amino-terminus of said IL-1ra.

2. The fusion protein according to claim 1, wherein said IL-1ra is non-glycosylated.

3. The fusion protein according to claim 2, wherein said IL-1ra is methionyl IL-1ra.

4. The fusion protein according to claim 1, wherein said IL-1ra is glycosylated.

5. The fusion protein according to claim 1, wherein said human immunoglobulin is the constant domain of a heavy chain.

6. The fusion protein according to claim 5, wherein said heavy chain is IgG1.

7. The fusion protein according to claim 1, wherein said constant domain comprises all domains except the first domain of the constant region of such heavy chain of human immunoglobulin.

8. The fusion protein according to claim 7, wherein said heavy chain is selected from the group consisting of IgG, IgA, IgM or IgE.

9. The fusion protein according to claim 8, wherein said IgG is IgG1 or IgG3.

10. The fusion protein according to claim 1, wherein said human immunoglobulin is the constant domain of a heavy chain.

11. The fusion protein according to claim 10, wherein said heavy chain is IgG1.

12. The fusion protein according to claim 1, wherein said constant domain comprises all domains except the first domain of the constant region of such heavy chain of human immunoglobulin.

13. The fusion protein according to claim 12, wherein said heavy chain is selected from the group consisting of IgG, IgA, IgM or IgE.

14. The fusion protein according to claim 13, wherein said IgG is IgG1 or IgG3.

15. A pharmaceutical composition comprising an effective amount of a fusion protein according to any one of claims 1 and 2-14 and a pharmaceutically acceptable carrier.