Antibodies directed against interleukin-33 (IL-33) and methods of making and using
The invention relates to an isolated immunoglobulin heavy chain polypeptide and an isolated immunoglobulin light chain polypeptide that bind to interleukin-33 (IL-33). The invention provides an IL-33-binding agent that comprises the aforementioned immunoglobulin heavy chain polypeptide and immunoglobulin light chain polypeptide. The invention also provides related vectors, compositions, and methods of using the IL-33-binding agent to treat a disorder in a mammal that is responsive to IL-33 inhibition.
1. An interleukin-33 (IL-33)-binding protein comprising an immunoglobulin heavy chain comprising the CDR1, CDR2, and CDR3 of SEQ ID NO: 136, and an immunoglobulin light chain comprising the CDR1, CDR2, and CDR3 of SEQ ID NO: 171.
2. The IL-33 binding protein of claim 1 comprising the immunoglobulin heavy chain variable region of SEQ ID NO: 136, and the immunoglobulin light chain variable region of SEQ ID NO: 171.
3. The IL-33-binding protein of claim 1 , wherein the IL-33 binding protein is an antibody, an antibody conjugate, or an antigen-binding fragment thereof.
4. The IL-33-binding protein of claim 2 , wherein the IL-33 binding protein is an antibody, an antibody conjugate, or an antigen-binding fragment thereof.
5. The IL-33-binding protein of claim 1 , wherein the IL-33 binding protein is a F(ab′)2, Fab′, Fab, Fv, scFv, dsFv, dAb, or a single chain binding polypeptide.
6. The IL-33-binding protein of claim 2 , wherein the IL-33 binding protein is a F(ab′)2, Fab′, Fab, Fv, scFv, dsFv, dAb, or a single chain binding polypeptide.
7. The IL-33-binding protein of claim 1 , wherein the IL-33 binding protein is an IgG1 antibody.
8. The IL-33-binding protein of claim 2 , wherein the IL-33 binding protein is an IgG1 antibody.
9. A pharmaceutical composition comprising (a) the IL-33-binding protein of claim 1 , and (b) a pharmaceutically acceptable carrier.
10. A pharmaceutical composition comprising (a) the IL-33-binding protein of claim 2 , and (b) a pharmaceutically acceptable carrier.
11. A method of treating atopic dermatitis in a mammal, which method comprises administering an effective amount of the IL-33 binding protein of claim 1 to the mammal.
12. The method of claim 11 , wherein the IL-33 binding protein is an antibody, an antibody conjugate, or an antigen-binding fragment thereof.
13. The method of claim 11 , wherein the IL-33 binding protein is a F(ab′)2, Fab′, Fab, Fv, scFv, dsFv, dAb, or a single chain binding polypeptide.
14. The method of claim 11 , wherein the half-life of the IL-33-binding protein in the mammal is between 30 minutes and 45 days.
15. The method of claim 11 , wherein the IL-33-binding protein binds to IL-33 with a K D less than or equal to 1 nanomolar.
16. The method of claim 11 , wherein the IL-33 binding protein is an IgG1 antibody.
17. A method of treating atopic dermatitis in a mammal, which method comprises administering an effective amount of the IL-33 binding protein of claim 2 to the mammal.
18. The method of claim 17 , wherein the IL-33 binding protein is an antibody, an antibody conjugate, or an antigen-binding fragment thereof.
19. The method of claim 17 , wherein the IL-33 binding protein is a F(ab′)2, Fab′, Fab, Fv, scFv, dsFv, dAb, or a single chain binding polypeptide.
20. The method of claim 17 , wherein the half-life of the IL-33-binding protein in the mammal is between 30 minutes and 45 days.
21. The method of claim 17 , wherein the IL-33-binding protein binds to IL-33 with a K D less than or equal to 1 nanomolar.
22. The method of claim 17 , wherein the IL-33 binding protein is an IgG1 antibody.
23. A nucleic acid encoding the immunoglobulin heavy chain and/or immunoglobulin light chain of claim 1 , optionally in a vector.
24. A An isolated cell comprising the nucleic acid of claim 23 .
25. A nucleic acid encoding the immunoglobulin heavy chain and/or immunoglobulin light chain of claim 2 , optionally in a vector.
26. A An isolated cell comprising the nucleic acid of claim 25 .
27. A method of preparing the IL-33 binding protein of claim 1 , the method comprising expressing in a cell a nucleic acid encoding an immunoglobulin heavy chain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 136, and a nucleic acid encoding an immunoglobulin light chain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 171, thereby preparing the IL-33 binding protein.
28. A method of preparing the IL-33 binding protein of claim 2 , the method comprising expressing in a cell a nucleic acid encoding the immunoglobulin heavy chain variable region of SEQ ID NO: 136, and the immunoglobulin light chain variable region of SEQ ID NO: 171, thereby preparing the IL-33 binding protein.