IL-1 binding proteins

• US 9,670,276 B2
• Filed: 07/12/2013
• Issued: 06/06/2017
• Est. Priority Date: 07/12/2012
• Status: Active Grant

• Current Assignee: Abbvie Incorporated
• Original Assignee: Abbvie Incorporated
• Inventors: Chhaya, Meha, Miller, Renee, Chari, Ravi, Heighton, Sarah J., Bixby, Jacqueline G., Lacy, Susan E., Benatuil, Lorenzo, Fung, Emma
• Primary Examiner(s): Saoud, Christine J
• Assistant Examiner(s): Seharaseyon, Jegatheesan
• Application Number:
  US13/940,506
• Publication Number:
  US 20140178389A1
• Time in Patent Office: 1,425 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• 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
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/60 characterized by non-natural combinations of immunoglobulin fragments
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The disclosure provides binding proteins that specifically bind to IL-1α and IL-1β. These binding proteins can be organized into DVD-Igs. These proteins can be used to modulate the activity of IL-1α and/or IL-1β and can be used for the treatment immunological diseases such as rheumatoid arthritis, osteoarthritis, psoriasis, multiple sclerosis, and other autoimmune diseases. In addition, their uses in the amelioration and/or treatment of pain in an individual suffering from a disease or disorder associated with IL-1 accumulation.

Claims

1. A binding protein that specifically binds to both IL-1α

and IL-1β

, said binding protein comprising an IL-1β

antigen binding domain comprising six CDRs, wherein the six CDRs are CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3, as defined below;

the CDR-H1 comprises the amino acid sequence of residues 31-35 of SEQ ID NO;

34;

the CDR-H2 comprises the amino acid sequence of residues 50-65 of SEQ ID NO;

34;

the CDR-H3 comprises the amino acid sequence of residues 98-111 of SEQ ID NO;

34;

the CDR-L1 comprises the amino acid sequence of residues 24-34 of SEQ ID NO;

348;

the CDR-L2 comprises the amino acid sequence of residues 50-56 of SEQ ID NO;

348; and

the CDR-L3 comprises the amino acid sequence of residues 89-97 of SEQ ID NO;

348,

wherein the binding protein comprises a heavy chain variable domain and a light chain variable domain that binds IL-1α and

a heavy chain variable domain and a light chain variable domain that binds IL-1β

.

2. The binding protein according to claim 1, wherein the heavy chain variable domain that binds IL-1β

comprises the amino acid sequence of SEQ ID NO;

34.

3. The binding protein according to claim 1, wherein the light chain variable domain that binds IL-1β

comprises the amino acid sequence of SEQ ID NO;

348.

4. The binding protein according to claim 1, wherein the heavy chain variable domain that binds IL-1β

comprises the amino acid sequence of SEQ ID NO;

34; and

wherein the light chain variable domain that binds IL-1β

comprises the amino acid sequence of SEQ ID NO;

348.

5. The binding protein according to claim 4, wherein the heavy chain variable domain that binds IL-1α

comprises the amino acid sequence of SEQ ID NO;

128, and wherein the light chain variable domain that binds IL-1α

comprises the amino acid sequence of SEQ ID NO;

129.

6. The binding protein according to claim 4, wherein the binding protein further comprises an IgG1 Fc region comprising the amino acid sequence of SEQ ID NO:

73 and an Ig kappa constant region comprising the amino acid sequence of SEQ ID NO;

74.

7. The binding protein according to claim 5, wherein the binding protein further comprises an IgG1 Fc region comprising the amino acid sequence of SEQ ID NO:

73 and an Ig kappa constant region comprising the amino acid sequence of SEQ ID NO;

74.

8. A composition comprising a binding protein as described in claim 5 and a pharmaceutically acceptable carrier.

9. A composition comprising a binding protein as described in claim 4 and a pharmaceutically acceptable carrier.

10. The binding protein according claim 1, further comprising an IL-1α

antigen binding domain comprising a CDR-H1 comprising an amino acid sequence of SEQ ID NO;

132, a CDR-H2 comprising an amino acid sequence of SEQ ID NO;

133, and a CDR-H3 comprising an amino acid sequence of SEQ ID NO;

134, a CDR-L1 comprising an amino acid sequence of SEQ ID NO;

135, a CDR-L2 comprising an amino acid sequence of SEQ ID NO;

136, and a CDR-L3 comprising an amino acid sequence of SEQ ID NO;

137.

11. The binding protein according to claim 10, wherein the binding protein further comprises an IgG1 Fc region comprising the amino acid sequence of SEQ ID NO:

73 and an Ig kappa constant region comprising the amino acid sequence of SEQ ID NO;

74.

12. A composition comprising a binding protein as described in claim 10 and a pharmaceutically acceptable carrier.

13. The binding protein according to claim 1, wherein the binding protein further comprises a Fc region selected from the group consisting of an Fc region from an IgG1, an IgG1 LL to AA 234, 235 mutant, IgG2, IgG3, IgG4, IgA, IgM, IgE, and IgD.

14. A binding protein conjugate comprising a binding protein as described in claim 1, said binding protein conjugate further comprising an agent selected from the group consisting of:

an immunoadhesion molecule, an imaging agent, a therapeutic agent, and a cytotoxic agent.

15. A composition comprising a binding protein as described in claim 1 and a pharmaceutically acceptable carrier.

16. The binding protein according to claim 1, wherein the heavy chain variable domain that binds IL-1α

comprises the amino acid sequence of SEQ ID NO;

128.

17. The binding protein according to claim 1, wherein the light chain variable domain that binds IL-1α

comprises the amino acid sequence of SEQ ID NO;

129.

18. The binding protein according to claim 1, wherein the heavy chain variable domain that binds IL-1α

comprises the amino acid sequence of SEQ ID NO;

128, and wherein the light chain variable domain that binds IL-1α

comprises the amino acid sequence of SEQ ID NO;

129.

19. The binding protein according to claim 1, wherein the binding protein further comprises an IgG1 Fc region comprising the amino acid sequence of SEQ ID NO:

73 and an Ig kappa constant region comprising the amino acid sequence of SEQ ID NO;

74.

20. A binding protein that specifically binds to both IL-1α

and IL-1β

, comprising first and second polypeptide chains, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO;

52, and wherein the second polypeptide chain comprises the amino acid sequence of SEQ ID NO;

53.

21. A binding protein conjugate comprising a binding protein as described in claim 20, said binding protein conjugate further comprising an agent selected from the group consisting of an immunoadhesion molecule, an imaging agent, a therapeutic agent, and a cytotoxic agent.

22. A composition comprising a binding protein as described in claim 20, and a pharmaceutically acceptable carrier.

23. A binding protein that specifically binds to both IL-1α

and IL-1β

, comprising first and second polypeptide chains, wherein the first polypeptide chain comprises from N terminus to C terminus the amino acid sequences of SEQ ID NOs;

52 and 73, and wherein the second polypeptide chain comprises from N terminus to C terminus the amino acid sequences of SEQ ID NOs;

53 and 74.

24. A composition comprising a binding protein as described in claim 23 and a pharmaceutically acceptable carrier.