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 nucleic acid or set of nucleic acids encoding 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 isolated nucleic acid or set of nucleic acids 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.
3 . The isolated nucleic acid or set of nucleic acids 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.
4 . The isolated nucleic acid or set of nucleic acids 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.
5 . The isolated nucleic acid or set of nucleic acids 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 comprises the amino acid sequence set forth in SEQ ID NO: 91.
6 . A vector comprising the isolated nucleic acid or set of nucleic acids of claim 5 .
7 . A host comprising the isolated nucleic acid or set of nucleic acids of claim 5 .
8 . A method of producing an isolated anti-IL-4R antibody, comprising expressing the isolated antibody with the host cell of claim 7 and isolating the expressed antibody.
9 . The isolated nucleic acid or set of nucleic acids 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.
10 . The isolated nucleic acid or set of nucleic acids of claim 9 , wherein the isolated antibody is a human IgG4 subtype.
11 . A vector comprising the isolated nucleic acid or set of nucleic acids of claim 10 .
12 . A host comprising the isolated nucleic acid or set of nucleic acids of claim 10 .
13 . A method of producing an isolated anti-IL-4R antibody, comprising expressing the isolated antibody with the host cell of claim 12 and isolating the expressed antibody.
14 . A vector comprising the isolated nucleic acid or set of nucleic acids of claim 9 .
15 . A host comprising the isolated nucleic acid or set of nucleic acids of claim 9 .
16 . A method of producing an isolated anti-IL-4R antibody, comprising expressing the isolated antibody with the host cell of claim 15 and isolating the expressed antibody.
17 . The isolated nucleic acid or set of nucleic acids 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.
18 . The isolated nucleic acid or set of nucleic acids 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.
19 . The isolated nucleic acid or set of nucleic acids of claim 1 , wherein the isolated antibody binds to human IL-4Rα.
20 . The isolated nucleic acid or set of nucleic acids of claim 1 , wherein the isolated antibody binds to soluble human IL-4Rα.
21 . The isolated nucleic acid or set of nucleic acids of claim 1 , wherein the isolated antibody is a monoclonal antibody.
22 . The isolated nucleic acid or set of nucleic acids of claim 1 , wherein the isolated antibody is an immunoglobulin having a human isotype of IgA, IgD, IgE, IgG or IgM.
23 . The isolated nucleic acid or set of nucleic acids of claim 1 , wherein the isolated antibody is a human IgG1, IgG2, IgG3, or IgG4 subtype.
24 . The isolated nucleic acid or set of nucleic acids of claim 1 , wherein the isolated antibody is a human IgG4 subtype.
25 . A vector comprising the isolated nucleic acid or set of nucleic acids of claim 24 .
26 . A host comprising the isolated nucleic acid or set of nucleic acids of claim 24 .
27 . A method of producing an isolated anti-IL-4R antibody, comprising expressing the isolated antibody with the host cell of claim 26 and isolating the expressed antibody.
28 . A vector comprising the isolated nucleic acid or set of nucleic acids of claim 1 .
29 . A host comprising the isolated nucleic acid or set of nucleic acids of claim 1 .
30 . A method of producing an isolated antibody which binds to IL-4R, comprising expressing the isolated antibody with the host cell of claim 29 and isolating the expressed antibody.