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. An isolated anti-interleukin 4 receptor (IL-4R) antibody comprising a variable heavy (VH) chain sequence comprising three heavy chain CDR sequences, CDR-H1, CDR-H2, and CDR-H3, and a variable light (VL) chain sequence comprising three light chain CDR sequences, CDR-L1, CDR-L2, and CDR-L3, wherein:
a. the CDR-L1 comprises the sequence set forth in SEQ ID NO: 2, the CDR-L2 comprises the sequence set forth in SEQ ID NO: 3, the CDR-L3 comprises the sequence set forth in SEQ ID NO: 8, the CDR-H1 comprises the sequence set forth in SEQ ID NO: 14, the CDR-H2 comprises the sequence set forth in SEQ ID NO: 18, and the CDR-H3 comprises the sequence set forth in SEQ ID NO: 19;
b. the CDR-L1 comprises the sequence set forth in SEQ ID NO: 2, the CDR-L2 comprises the sequence set forth in SEQ ID NO: 4, the CDR-L3 comprises the sequence set forth in SEQ ID NO: 8, the CDR-H1 comprises the sequence set forth in SEQ ID NO: 14, the CDR-H2 comprises the sequence set forth in SEQ ID NO: 18, and the CDR-H3 comprises the sequence set forth in SEQ ID NO: 19; or
c. the CDR-L1 comprises the sequence set forth in SEQ ID NO: 2, the CDR-L2 comprises the sequence set forth in SEQ ID NO: 4, the CDR-L3 comprises the sequence set forth in SEQ ID NO: 5, the CDR-H1 comprises the sequence set forth in SEQ ID NO: 14, the CDR-H2 comprises the sequence set forth in SEQ ID NO: 18, and the CDR-H3 comprises the sequence set forth in SEQ ID NO: 19.
2. The isolated antibody of claim 1 , wherein:
a. the VL chain sequence comprises the sequence set forth in SEQ ID NO: 55 and the VH chain sequence comprises the sequence set forth in SEQ ID NO: 91;
b. the VL chain sequence comprises the sequence set forth in SEQ ID NO: 54 and the VH chain sequence comprises the sequence set forth in SEQ ID NO: 91; or
c. the VL chain sequence comprises the sequence set forth in SEQ ID NO: 44 and the VH chain sequence comprises the sequence set forth in SEQ ID NO: 91.
3. The isolated antibody of claim 1 , wherein the isolated antibody binds to human IL-4Ra.
4. The isolated antibody of claim 1 , wherein the isolated antibody binds to soluble human IL-4Ra.
5. The isolated antibody of claim 1 , wherein the isolated antibody is a monoclonal antibody.
6. The isolated antibody of claim 1 , wherein the isolated antibody is an immunoglobulin having a human isotype of IgA, IgD, IgE, IgG, or IgM.
7. The isolated antibody of claim 1 , wherein the isolated antibody is a human IgG1, IgG2, IgG3, or IgG4 subtype.
8. The isolated antibody of claim 7 , wherein the isolated antibody is a human IgG4 subtype.
9. A pharmaceutical composition comprising the isolated antibody of claim 1 and a pharmaceutically acceptable excipient.
10. The isolated antibody of claim 1 , wherein the CDR-L1 comprises the sequence set forth in SEQ ID NO: 2, the CDR-L2 comprises the sequence set forth in SEQ ID NO: 3, the CDR-L3 comprises the sequence set forth in SEQ ID NO: 8, the CDR-H1 comprises the sequence set forth in SEQ ID NO: 14, the CDR-H2 comprises the sequence set forth in SEQ ID NO: 18, and the CDR-H3 comprises the sequence set forth in SEQ ID NO: 19.
11. The isolated antibody of claim 10 , wherein the isolated antibody is a human IgG4 subtype.
12. A pharmaceutical composition comprising the isolated antibody of claim 11 and a pharmaceutically acceptable excipient.
13. A pharmaceutical composition comprising the isolated antibody of claim 10 and a pharmaceutically acceptable excipient.
14. The isolated antibody of claim 1 , wherein the VL chain sequence comprises the sequence set forth in SEQ ID NO: 55 and the VH chain sequence comprises the sequence set forth in SEQ ID NO: 91.
15. The isolated antibody of claim 14 , wherein the isolated antibody is a human IgG4 subtype.
16. A pharmaceutical composition comprising the isolated antibody of claim 15 and a pharmaceutically acceptable excipient.
17. A pharmaceutical composition comprising the isolated antibody of claim 14 and a pharmaceutically acceptable excipient.
18. The isolated antibody of claim 1 , wherein the CDR-L1 comprises the sequence set forth in SEQ ID NO: 2, the CDR-L2 comprises the sequence set forth in SEQ ID NO: 4, the CDR-L3 comprises the sequence set forth in SEQ ID NO: 8, the CDR-H1 comprises the sequence set forth in SEQ ID NO: 14, the CDR-H2 comprises the sequence set forth in SEQ ID NO: 18, and the CDR-H3 comprises the sequence set forth in SEQ ID NO: 19.
19. The isolated antibody of claim 18 , wherein the isolated antibody is a human IgG4 subtype.
20. The isolated antibody of claim 1 , wherein the VL chain sequence comprises the sequence set forth in SEQ ID NO: 54 and the VH chain sequence comprises the sequence set forth in SEQ ID NO: 91.
21. The isolated antibody of claim 20 , wherein the isolated antibody is a human IgG4 subtype.
22. The isolated antibody of claim 1 , wherein the CDR-L1 comprises the sequence set forth in SEQ ID NO: 2, the CDR-L2 comprises the sequence set forth in SEQ ID NO: 4, the CDR-L3 comprises the sequence set forth in SEQ ID NO: 5, the CDR-H1 comprises the sequence set forth in SEQ ID NO: 14, the CDR-H2 comprises the sequence set forth in SEQ ID NO: 18, and the CDR-H3 comprises the sequence set forth in SEQ ID NO: 19.
23. The isolated antibody of claim 22 , wherein the isolated antibody is a human IgG4 subtype.
24. The isolated antibody of claim 1 , wherein the VL chain sequence comprises the sequence set forth in SEQ ID NO: 44 and the VH chain sequence comprises the sequence set forth in SEQ ID NO: 91.
25. The isolated antibody of claim 24 , wherein the isolated antibody is a human IgG4 subtype.