Antibodies to canine interleukin-4 alpha receptor

Claims

1. An isolated nucleic acid encoding the light chain of an antibody or antigen-binding fragment thereof that binds to canine interleukin-4 receptor α (IL-4Rα); wherein the nucleic acid comprises a nucleotide sequence encoding a light chain containing three light chain CDRs: CDR 1 (LCDR1), CDR 2 (LCDR2), and CDR 3 (HCDR3), and wherein (a) LCDR1 comprises the amino acid sequence of SEQ ID NO: 30; (b) LCDR2 comprises the amino acid sequence of SEQ ID NO: 32; and (c) LCDR3 comprises the amino acid sequence of SEQ ID NO:

34.

2. The isolated nucleic acid of claim 1, wherein the light chain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 35 or SEQ ID NO:

43.

3. The isolated nucleic acid of claim 1, wherein the light chain comprises the amino acid sequence of SEQ ID NO: 35 or SEQ ID NO:

43.

4. The isolated nucleic acid of claim 1, wherein LCDR1 is encoded by the nucleotide sequence SEQ ID NO:

29.

5. The isolated nucleic acid of claim 1, wherein LCDR2 is encoded by the nucleotide sequence SEQ ID NO:

31.

6. The isolated nucleic acid of claim 1, wherein LCDR3 is encoded by the nucleotide sequence SEQ ID NO:

33.

7. An isolated nucleic acid encoding one or more CDRs of a light chain of an antibody or antigen-binding fragment thereof that binds to canine interleukin-4 receptor α (IL-4Rα), wherein the nucleic acid comprises one or more nucleotide sequences selected from SEQ ID NO: 29, SEQ ID NO: 31, and SEQ ID NO:

33.

8. An isolated nucleic acid encoding a light chain of an antibody or antigen-binding fragment thereof that binds to canine interleukin-4 receptor α (IL-4Rα), wherein the nucleic acid comprises the nucleotide sequences of SEQ ID NO: 29, SEQ ID NO: 31, and SEQ ID NO:

33.

9. An expression vector containing the isolated nucleic acid according to claim 7 or 8.

10. A host cell for producing a light chain of an antibody or an antigen-binding fragment thereof that binds to the canine interleukin-4 receptor α (IL-4Rα), wherein the cell contains the expression vector of claim 9.

11. An isolated nucleic acid encoding the heavy chain of an antibody or antigen-binding fragment thereof that binds to canine IL-4Rα; wherein the nucleic acid comprises a nucleotide sequence encoding a heavy chain containing three heavy chain CDRs: HCDR1, HCDR2, and HCDR3, and wherein (a) HCDR1 comprises the amino acid sequence of SEQ ID NO: 24; (b) HCDR2 comprises the amino acid sequence of SEQ ID NO: 26; and (c) HCDR3 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 16 and SEQ ID NO:

49.

12. The isolated nucleic acid of claim 11, wherein the heavy chain comprises an amino acid sequence that is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 36, SEQ ID NO: 37, or SEQ ID NO:

38.

13. The isolated nucleic acid of claim 11, wherein the heavy chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 36, SEQ ID NO: 37, or SEQ ID NO:

38.

14. The isolated nucleic acid of claim 11, wherein HCDR1 is encoded by the nucleotide sequence of SEQ ID NO:

23.

15. The isolated nucleic acid of claim 11, wherein HCDR2 is encoded by the nucleotide sequence of SEQ ID NO:

25.

16. The isolated nucleic acid of claim 11, wherein HCDR3 is encoded by the nucleotide sequence of SEQ ID NO: 15 or SEQ ID NO:

48.

17. An isolated nucleic acid encoding one or more CDRs of the heavy chain of an antibody or antigen-binding fragment thereof that binds to the canine interleukin-4 receptor α (IL-4Rα), wherein the nucleic acid comprises one or more nucleotide sequences selected from SEQ ID NO: 23, SEQ ID NO: 25, and SEQ ID NO:

27.

18. An isolated nucleic acid encoding one or more CDRs of the heavy chain of an antibody or antigen-binding fragment thereof that binds to the canine interleukin-4 receptor α (IL-4Rα), wherein the nucleic acid comprises one or more nucleotide sequences selected from SEQ ID NO: 23, SEQ ID NO: 25, and SEQ ID NO:

48.

19. An isolated nucleic acid encoding a heavy chain of an antibody or antigen-binding fragment thereof that binds to canine IL-4Rα, wherein the nucleic acid comprises the nucleotide sequences of SEQ ID NO: 23, SEQ ID NO: 25, and SEQ ID NO:

27.

20. An isolated nucleic acid encoding the heavy chain of an antibody or antigen-binding fragment thereof that binds to canine IL-4Rα, wherein the nucleic acid comprises the nucleotide sequences of SEQ ID NO: 23, SEQ ID NO: 25, and SEQ ID NO:

48.

21. An expression vector containing the isolated nucleic acid of any one of claims 17-20.

22. A host cell for producing an antibody heavy chain or antigen-binding fragment thereof that binds to canine IL-4Rα, wherein the host cell comprises the expression vector of claim 21.

23. A nucleic acid encoding an antibody or antigen-binding fragment thereof that binds to canine IL-4Rα, where the nucleic acid contains a first nucleotide sequence encoding the heavy chain of an antibody or antigen-binding fragment thereof; wherein the heavy chain comprises three heavy chain CDRs: HCDR1, HCDR2, and HCDR3, and wherein (a) HCDR1 comprises the amino acid sequence of SEQ ID NO: 24; (b) HCDR2 comprises the amino acid sequence of SEQ ID NO: 26; and (c) HCDR3 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 28 and SEQ ID NO: 49; and a second nucleotide sequence encoding a light chain of the antibody or antigen-binding fragment thereof; wherein the light chain comprises three light chain CDRs: LCDR1, LCDR2, and LCDR3, and wherein (a) LCDR1 comprises the amino acid sequence of SEQ ID NO: 30; (b) LCDR2 comprises the amino acid sequence of SEQ ID NO: 32; and (c) LCDR3 comprises the amino acid sequence of SEQ ID NO: 34; wherein the antibody or antigen-binding fragment thereof binds to canine IL-4Rα.

24. The nucleic acid of claim 23, wherein the first nucleotide sequence further encodes a hinge region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO:

9.

25. The nucleic acid of claim 23, wherein the first nucleotide sequence encodes a heavy chain comprising a modified canine IgG-B (IgG-Bm) comprising the amino acid sequence of SEQ ID NO:

10.

26. The nucleic acid of claim 23, wherein the first nucleotide sequence encodes a heavy chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 36, SEQ ID NO: 37 and SEQ ID NO:

38.

27. The nucleic acid of any one of claims 23-26, wherein the second nucleotide sequence encodes a light chain comprising the amino acid sequence of SEQ ID NO: 35 or SEQ ID NO:

43.

28. The nucleic acid of any one of claims 23-27, wherein the first nucleotide sequence comprises the nucleotide sequences of SEQ ID NO: 23, SEQ ID NO: 25 and SEQ ID NO: 27; and the second nucleotide sequence comprises the nucleotide sequences of SEQ ID NO: 29, SEQ ID NO: 31 and SEQ ID NO:

33.

29. The nucleic acid of any one of claims 23-27, wherein the first nucleotide sequence comprises the nucleotide sequences of SEQ ID NO: 23, SEQ ID NO: 25 and SEQ ID NO: 48; and wherein the second nucleotide sequence comprises the nucleotide sequences of SEQ ID NO: 29, SEQ ID NO: 31 and SEQ ID NO:

33.

30. The nucleic acid of any one of claims 23 to 29, wherein the first nucleotide sequence and the second nucleotide sequence are in a single nucleic acid molecule.

31. The nucleic acid of claim 30, wherein the nucleic acid molecule is an expression vector.

32. The nucleic acid of any one of claims 23 to 29, wherein the first nucleotide sequence and the second nucleotide sequence are in separate nucleic acid molecules.

33. The nucleic acid of claim 32, wherein each of the individual nucleic acid molecules is an expression vector.

34. An expression vector system comprising an expression vector according to claim 9 and an expression vector according to claim 21.

35. An expression vector system comprising a first expression vector comprising the nucleotide sequences of SEQ ID NO: 23, SEQ ID NO: 25 and SEQ ID NO: 27, and a second expression vector comprising the nucleotide sequences of SEQ ID NO: 29, SEQ ID NO: 31 and SEQ ID NO:

33.

36. An expression vector system comprising a first expression vector comprising the nucleotide sequences of SEQ ID NO: 23, SEQ ID NO: 25 and SEQ ID NO: 48, and a second expression vector comprising the nucleotide sequences of SEQ ID NO: 29, SEQ ID NO: 31 and SEQ ID NO:

33.

37. A pharmaceutical composition for reducing inflammation associated with atopic dermatitis, wherein the composition comprises a nucleic acid according to any one of claims 23-33, an expression vector system according to any one of claims 34-36, or any combination thereof, and a pharmaceutically acceptable carrier or diluent.

38. A host cell for producing an antibody or antigen-binding fragment thereof that binds to canine IL-4Rα, wherein the cell contains the expression vector system according to claims 34, 35 or 36.

39. A method for producing an antibody or antigen-binding fragment thereof that binds to canine IL-4Rα, wherein the method comprises culturing the host cell according to any one of claims 10, 22 or 38 in a culture medium and isolating the antibody or antigen-binding fragment thereof from the host cell or the culture medium.