Antibody for binding to interleukin 4 receptor
Disclosed is an antibody capable of binding to the interleukin 4 (IL-4) receptor (IL-4). Also disclosed are a nucleic acid sequence encoding the antibody, a vector including the nucleic acid sequence, and a host cell transformed or transfected with the vector. Provided are a method for producing the antibody, a medical use of the antibody, and a kit including the antibody.
1. A method of treating or ameliorating inflammation or allergic disease in a subject in need thereof, comprising administering to the subject an isolated anti-interleukin 4 receptor (IL-4R) antibody comprising a heavy chain variable domain (VH) comprising three heavy chain complementarity determining regions (CDRs) (CDR-H1, CDR-H2, and CDR-H3), and a light chain variable domain (VL) comprising three light chain CDRs (CDR-L1, CDR-L2, and CDR-L3) wherein:
a. the CDR-L1 comprises the amino acid sequence set forth in SEQ ID NO: 2, the CDR-L2 comprises the amino acid sequence set forth in SEQ ID NO: 3, the CDR-L3 comprises the amino acid sequence set forth in SEQ ID NO: 8, the CDR-H1 comprises the amino acid sequence set forth in SEQ ID NO: 14, the CDR-H2 comprises the amino acid sequence set forth in SEQ ID NO: 18, and the CDR-H3 comprises the amino acid sequence set forth in SEQ ID NO: 19;
b. the CDR-L1 comprises the amino acid sequence set forth in SEQ ID NO: 2, the CDR-L2 comprises the amino acid sequence set forth in SEQ ID NO: 4, the CDR-L3 comprises the amino acid sequence set forth in SEQ ID NO: 8, the CDR-H1 comprises the amino acid sequence set forth in SEQ ID NO: 14, the CDR-H2 comprises the amino acid sequence set forth in SEQ ID NO: 18, and the CDR-H3 comprises the amino acid sequence set forth in SEQ ID NO: 19; or
c. the CDR-L1 comprises the amino acid sequence set forth in SEQ ID NO: 2, the CDR-L2 comprises the amino acid sequence set forth in SEQ ID NO: 4, the CDR-L3 comprises the amino acid sequence set forth in SEQ ID NO: 5, the CDR-H1 comprises the amino acid sequence set forth in SEQ ID NO: 14, the CDR-H2 comprises the amino acid sequence set forth in SEQ ID NO: 18, and the CDR-H3 comprises the amino acid sequence set forth in SEQ ID NO: 19.
2. The method of claim 1 , wherein:
a. the VL comprises the amino acid sequence set forth in SEQ ID NO: 55 and the VH comprises the amino acid sequence set forth in SEQ ID NO: 91;
b. the VL comprises the amino acid sequence set forth in SEQ ID NO: 54 and the VH comprises the amino acid sequence set forth in SEQ ID NO: 91; or
c. the VL comprises the amino acid sequence set forth in SEQ ID NO: 44 and the VH chain scqucncc comprises the amino acid sequence set forth in SEQ ID NO: 91.
3. The method of claim 1 , wherein the isolated antibody binds to human IL-4Rα.
4. The method of claim 1 , wherein the isolated antibody binds to soluble human IL-4Rα.
5. The method of claim 1 , wherein the isolated antibody is a monoclonal antibody.
6. The method of claim 1 , wherein the isolated antibody is an immunoglobulin having a human isotype of IgA, IgD, IgE, IgG or IgM.
7. The method of claim 1 , wherein the isolated antibody is a human IgG1, IgG2, IgG3, or IgG4 subtype.
8. The method of claim 1 , wherein the isolated antibody is a human IgG4 subtype.
9. The method of claim 1 , wherein the inflammation or allergic disease comprises atopic dermatitis.
10. The method of claim 1 , wherein the inflammation or allergic disease comprises asthma.
11. The method of claim 1 , wherein the CDR-L1 comprises the amino acid sequence set forth in SEQ ID NO: 2, the CDR-L2 comprises the amino acid sequence set forth in SEQ ID NO: 3, the CDR-L3 comprises the amino acid sequence set forth in SEQ ID NO: 8, the CDR-H1 comprises the amino acid sequence set forth in SEQ ID NO: 14, the CDR-H2 comprises the amino acid sequence set forth in SEQ ID NO: 18, and the CDR-H3 comprises the amino acid sequence set forth in SEQ ID NO: 19.
12. The method of claim 11 , wherein the isolated antibody is a monoclonal antibody.
13. The method of claim 11 , wherein the inflammation or allergic disease is selected from the group consisting of allergic dermatitis, asthma, eosinophilic esophagitis, eczema, allergic rhinitis, nasal polyp, and rheumatoid arthritis.
14. The method of claim 11 , wherein the inflammation or allergic disease is an autoimmune disease.
15. The method of claim 11 , wherein the inflammation or allergic disease is atopic dermatitis.
16. The method of claim 11 , wherein the inflammation or allergic disease is asthma.
17. The method of claim 11 , wherein the isolated antibody is a human IgG4 subtype.
18. The method of claim 1 , wherein the CDR-L1 comprises the amino acid sequence set forth in SEQ ID NO: 2, the CDR-L2 comprises the amino acid sequence set forth in SEQ ID NO: 4, the CDR-L3 comprises the amino acid sequence set forth in SEQ ID NO: 8, the CDR-H1 comprises the amino acid sequence set forth in SEQ ID NO: 14, the CDR-H2 comprises the amino acid sequence set forth in SEQ ID NO: 18, and the CDR-H3 comprises the amino acid sequence set forth in SEQ ID NO: 19.
19. The method of claim 1 , wherein the CDR-L1 comprises the amino acid sequence set forth in SEQ ID NO: 2, the CDR-L2 comprises the amino acid sequence set forth in SEQ ID NO: 4, the CDR-L3 comprises the amino acid sequence set forth in SEQ ID NO: 5, the CDR-H1 comprises the amino acid sequence set forth in SEQ ID NO: 14, the CDR-H2 comprises the amino acid sequence set forth in SEQ ID NO: 18, and the CDR-H3 comprises the amino acid sequence set forth in SEQ ID NO: 19.
20. The method of claim 1 , wherein the VL comprises the amino acid sequence set forth in SEQ ID NO: 55 and the VH comprises the amino acid sequence set forth in SEQ ID NO: 91.
21. The method of claim 20 , wherein the isolated antibody is a monoclonal antibody.
22. The method of claim 20 , wherein the inflammation or allergic disease is an autoimmune disease.
23. The method of claim 20 , wherein the inflammation or allergic disease is selected from the group consisting of allergic dermatitis, asthma, eosinophilic esophagitis, eczema, allergic rhinitis, nasal polyp, and rheumatoid arthritis.
24. The method of claim 20 , wherein the inflammation or allergic disease is atopic dermatitis.
25. The method of claim 20 , wherein the inflammation or allergic disease is asthma.
26. The method of claim 20 , wherein the isolated antibody is a human IgG4 subtype.
27. The method of claim 1 , wherein the VL comprises the amino acid sequence set forth in SEQ ID NO: 54 and the VH comprises the amino acid sequence set forth in SEQ ID NO: 91.
28. The method of claim 1 , wherein the VL comprises the amino acid sequence set forth in SEQ ID NO: 44 and the VH comprises the amino acid sequence set forth in SEQ ID NO: 91.
29. The method of claim 1 , wherein the inflammation or allergic disease is an autoimmune disease.
30. The method of claim 1 , wherein the inflammation or allergic disease is selected from the group consisting of allergic dermatitis, asthma, eosinophilic esophagitis, eczema, allergic rhinitis, nasal polyp, and rheumatoid arthritis.
31. The method of claim 1 , wherein the inflammation or allergic disease is atopic dermatitis.
32. The method of claim 1 , wherein the inflammation or allergic disease is asthma.