Antibodies to canine interleukin-4 receptor alpha
The present invention discloses antibodies and blocking antibodies to canine IL-4 receptor alpha that have specific sequences and a high binding affinity for canine IL-4 receptor α. The present invention also discloses the use of the antibodies of the present invention in the treatment of atopic dermatitis in dogs. The present invention further discloses unique epitopes that bind to the antibodies to canine IL-4 receptor alpha.
1. An antibody or antigen binding fragment thereof that binds to canine interleukin-4 receptor α (IL-4R α ), wherein the antibody or antigen binding fragment thereof comprises:
(i) a light chain variable region (VL) comprising a VL complementarity determining region (CDR) 1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO:120; and
(ii) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO:118.
2. The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or the antigen-binding fragment thereof comprises:
(a) a VL comprising: a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 129, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:134, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:137; and
(b) a VH comprising: a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 140, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:146, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:151.
3. The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or the antigen-binding fragment thereof comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 120.
4. The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or the antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO:120.
5. The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or the antigen-binding fragment thereof comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 118.
6. The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or the antigen-binding fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO:118.
7. The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or the antigen-binding fragment thereof comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 120; and a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:118.
8. The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or the antigen-binding fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO:120; and a VH comprising the amino acid sequence of SEQ ID NO: 118.
9. The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment is a caninized antibody or a caninized antigen binding fragment.
10. The antibody or antigen binding fragment thereof of claim 9 , wherein the antibody or antigen binding fragment thereof comprises a hinge region selected from a canine IgGA hinge region, a canine IgGB hinge region, a canine IgGC hinge region, and a canine IgGD hinge region.
11. The antibody or antigen binding fragment thereof of claim 9 , wherein the antibody or antigen binding fragment thereof comprises a hinge region comprising the amino acid sequence of SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, and SEQ ID NO: 104.
12. The antibody or antigen binding fragment thereof of claim 9 , wherein the antibody or antigen binding fragment thereof comprises a canine fragment crystallizable (cFc) region selected from a canine IgGA Fc region, a canine IgGB Fc region, a canine IgGC Fc region, and a canine IgGD Fc region.
13. The antibody or antigen binding fragment thereof of claim 12 , wherein the cFc region is selected from a genetically modified canine IgGA Fc region, a genetically modified canine IgGB Fc region, a genetically modified canine IgGC Fc region, and a genetically modified canine IgGD Fc region.
14. The antibody or antigen binding fragment thereof of claim 13 , wherein the cFc region is a genetically modified canine IgGB Fc region comprising one or more of the amino acid substitution selected from P4A, D31A, N63A, G64P, T65A, A93G, and P95A in the native canine IgGB Fc region.
15. The antibody or antigen binding fragment thereof of claim 1 , wherein when bound to canine IL-4R α , binds to at least one amino acid residue within the amino acid sequence of SEQ ID NO:125, or at least one amino acid residue within the amino acid sequence of SEQ ID NO:126, or any combination thereof.
16. The antibody or antigen binding fragment thereof of claim 1 , wherein when bound to canine IL-4R α , blocks the binding of canine IL-4R α to one or more of canine interleukin-4 and canine interleukin-13.
17. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier or diluent.