Antibodies against interleukin-22

Abstract

To provide a new treatment for atopic dermatitis. [Solution] The present invention relates to an isolated antibody that binds to human IL22, defined by a set of specific CDR sequences and / or variable region sequences, and provides an antibody that inhibits its interaction with one or more of its natural ligands. The therapeutic use of the antibody for psoriasis, psoriatic arthritis, contact dermatitis, chronic hand eczema, or atopic dermatitis, and methods for producing such antibodies are also provided.

Claims

1. An isolated antibody that binds to interleukin 22 (IL22) and inhibits or attenuates the binding of IL22 to IL22 receptor 1 (IL22R1).

2. The antibody according to claim 1, wherein the antibody binds to a region on IL22 such that it sterically blocks the interaction between IL22 and IL22R1.

3. The antibody according to claim 1 or 2, which inhibits or attenuates IL22 binding to IL22-binding protein (IL22RA2).

4. An antibody according to any one of claims 1 to 3, which binds to human IL22 and / or cynomolgus monkey IL22.

5. The antibody according to any one of claims 1 to 4, wherein the antibody has a dissociation equilibrium constant (KD) of less than 100 pM for human IL-22.

6. An antibody according to any one of claims 1 to 5, which specifically binds to the polypeptide VRLIGEKLFHGVSM (SEQ ID NO: 96), which corresponds to residues 72 to 85 of the amino acid sequence of IL22 as defined by SEQ ID NO:

1.

7. The antibody according to any one of claims 1 to 6, wherein the antibody binds to an epitope of human IL22, and the epitope is determined by a contact distance of less than 5 Å between the antibody and IL22, and comprises five or more residues selected from Lys44, Phe47, Gln48, Ile75, Gly76, Glu77, Phe80, His81, Gly82, Val83, Ser84, Met85, Ser86, Arg88, Leu169, Met172, Ser173, Arg175, Asn176 and Ile179 of human IL22 (SEQ ID NO: 1).

8. The antibody according to claim 7, wherein the binding is determined using X-ray crystallography.

9. CDR-L1 containing Sequence ID No. 5, CDR-L2 containing Sequence ID 6, and CDR-L3 containing Sequence ID 7 A light chain variable region including, CDR-H1 containing Sequence ID 8, CDR-H2 containing Sequence ID 9, and CDR-H3 containing Sequence ID 10 A heavy chain variable region including, The antibody according to any one of claims 1 to 8, comprising:

10. The antibody according to any one of claims 1 to 9, wherein the light chain variable region includes the sequence shown in SEQ ID NO:

22.

11. The antibody according to any one of claims 1 to 9, wherein the heavy chain variable region includes the sequence shown in SEQ ID NO:

24.

12. The antibody according to any one of claims 1 to 9, wherein the light chain variable region includes the sequence shown in SEQ ID NO: 22, or a sequence that is at least 90% identical thereto, and the heavy chain variable region includes the sequence shown in SEQ ID NO: 24, or a sequence that is at least 90% identical thereto.

13. The antibody comprises a light chain variable region and a heavy chain variable region, The light chain variable region includes the sequence shown in Sequence ID No. 22, wherein one or more residues at positions 91, 95 and / or 96 are substituted with another amino acid. The heavy chain variable region includes the sequence shown in Sequence ID No. 24, wherein one or more residues at positions 54, 55 and / or 107 are substituted with another amino acid. The antibody according to any one of claims 1 to 9.

14. The antibody according to claim 9, wherein each CDR contains up to three amino acid substitutions, and such amino acid substitutions are conserved.

15. The antibody according to claim 9, wherein the light chain variable region and the remaining portion of the heavy chain variable region have at least 90% identity with SEQ ID NOs: 22 and 24, respectively.

16. The antibody according to any one of claims 1 to 15, which is a full-length antibody.

17. An antibody fragment, the antibody according to any one of claims 1 to 15.

18. The antibody fragments are Fab, Fab', F(ab') ２ The antibody according to claim 17, which is Fv, dsFv, scFv, or dsscFv.

19. The antibody according to claim 18, comprising a Fab containing a light chain containing the sequence shown in SEQ ID NO: 26 and a heavy chain containing the sequence shown in SEQ ID NO:

28.

20. The antibody according to claim 18, comprising CDR-L1 / CDR-L2 / CDR-L3 / CDR-H1 / CDR-H2 / CDR-H3, each containing the sequences shown in SEQ ID NOs. 5 / 6 / 7 / 8 / 9 / 10, respectively, wherein the remaining portions of the light chain and heavy chain have at least 90% identity or similarity to SEQ ID NOs. 26 and 28, respectively.

21. The antibody according to claim 16, comprising an IgG1 having a light chain containing the sequence shown in SEQ ID NO: 26 and a heavy chain containing the sequence shown in SEQ ID NO:

30.

22. The antibody according to claim 16, wherein the antibody is an IgG1 comprising CDR-L1 / CDR-L2 / CDR-L3 / CDR-H1 / CDR-H2 / CDR-H3 containing the sequences shown in SEQ ID NOs. 5 / 6 / 7 / 8 / 9 / 10, and the remaining portions of the light chain and heavy chain have at least 90% identity or similarity with SEQ ID NOs. 26 and 30, respectively.

23. The antibody according to claim 16, comprising an IgG4P having a light chain containing the sequence shown in SEQ ID NO: 26 and a heavy chain containing the sequence shown in SEQ ID NO:

32.

24. The antibody according to claim 16, wherein the antibody is an IgG4P comprising CDR-L1 / CDR-L2 / CDR-L3 / CDR-H1 / CDR-H2 / CDR-H3 containing the sequences shown in SEQ ID NOs. 5 / 6 / 7 / 8 / 9 / 10, and the remaining portions of the light chain and heavy chain have at least 90% identity or similarity with SEQ ID NOs. 26 and 32, respectively.

25. An isolated polynucleotide encoding an antibody according to any one of claims 1 to 24.

26. An expression vector supporting a polynucleotide as described in claim 25.

27. A host cell comprising the vector according to claim 26.

28. A method for producing an antibody according to any one of claims 1 to 24, comprising culturing the host cells described in claim 27 under conditions that enable the production of the antibody, and recovering the produced antibody.

29. A pharmaceutical composition comprising an antibody according to any one of claims 1 to 24 and a pharmaceutically acceptable adjuvant or carrier.

30. An antibody according to any one of claims 1 to 24, or a pharmaceutical composition according to claim 29, for use in a method of treating the body of a human or animal by therapy.

31. An antibody according to any one of claims 1 to 24, or a pharmaceutical composition according to claim 29, for use as a pharmaceutical.

32. Use of an antibody according to any one of claims 1 to 24 or a pharmaceutical composition according to claim 29 for the manufacture of a pharmaceutical product.

33. An antibody according to any one of claims 1 to 24 or a pharmaceutical composition according to claim 29, for use in the treatment of an inflammatory skin condition.

34. A method for treating or preventing an inflammatory skin condition, comprising administering a therapeutically effective amount of an antibody according to any one of claims 1 to 24 or a pharmaceutical composition according to claim 29 to a patient in need thereof.

35. Use of an antibody according to any one of claims 1 to 24 or a pharmaceutical composition according to claim 29 for manufacturing a pharmaceutical for treating an inflammatory skin condition.

36. The antibody or pharmaceutical composition according to claim 33, the method according to claim 34, or the use according to claim 35, wherein the inflammatory skin condition is psoriasis, psoriatic arthritis, contact dermatitis, chronic hand eczema, or atopic dermatitis.

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