Antibodies against human IL33R and uses thereof
An antibody binding to IL33R characterized in that the heavy chain variable domain comprises a CDR3 region of SEQ ID NO:1, a CDR2 region of SEQ ID NO:2 and a CDR1 region of SEQ ID NO:3 and in that the light chain variable domain comprises a CDR3 region of SEQ ID NO:4, a CDR2 region of SEQ ID NO:5 and a CDR1 region of SEQ ID NO:6 or a chimeric, humanized or T cell epitope depleted antibody variant thereof has advantageous properties for the treatment of inflammatory diseases.
1. An anti-human IL33R antibody, wherein said antibody has a heavy chain variable domain comprising a CDR3 region of SEQ ID NO:24, a CDR2 region of SEQ ID NO:23 and a CDR1 region of SEQ ID NO:22 and a light chain variable domain comprising a CDR3 region of SEQ ID NO:33, a CDR2 region of SEQ ID NO:32 and a CDR1 region of SEQ ID NO:31.
2. The antibody according to claim 1 , wherein the heavy chain variable domain comprises SEQ ID NO:21.
3. The antibody according to claim 2 , wherein the heavy chain variable domain comprises SEQ ID NO:21 and the light chain variable domain comprises SEQ ID NO:30.
4. The antibody according to claim 1 , which is a chimeric antibody, a humanized antibody or a T cell epitope-depleted antibody.
5. An anti-human IL33R antibody having a human IgG1 or IgG4 isotype but modified in the hinge region at one or more amino acid position between 216-240, and/or in the second inter-domain region at one or more amino acid position between 327-331 between C H 2 and C H 3, wherein said antibody is selected from:
a) An anti-human IL33R antibody comprising a heavy chain variable domain comprising a CDR3 region of SEQ ID NO:24, a CDR2 region of SEQ ID NO:23 and a CDR1 region of SEQ ID NO:22 and a light chain variable domain comprising a CDR3 region of SEQ ID NO:33, a CDR2 region of SEQ ID NO:32 and a CDR1 region of SEQ ID NO:31;
b) An anti-human IL33R antibody, wherein the heavy chain variable domain comprises SEQ ID NO:21 and the light chain variable domain comprises SEQ ID NO:30; or
c) An anti-human IL33R antibody according to a) or b), which is a chimeric antibody, a humanized antibody or a T cell epitope-depleted antibody.
6. An anti-human IL33R antibody according to claim 5 , wherein said hinge region is modified by replacing the amino acid at position 234 and the amino acid at position 235 with alanine.
7. An anti-human IL33R antibody according to claim 5 , wherein said hinge region is modified by replacing the amino acid at position 235 and the amino acid at position 228 with glutamic acid and proline, respectively.
8. A pharmaceutical composition comprising an anti-human IL33R antibody, wherein said antibody is selected from:
a) An anti-human IL33R antibody comprising a heavy chain variable domain comprising a CDR3 region of SEQ ID NO:24, a CDR2 region of SEQ ID NO:23 and a CDR1 region of SEQ ID NO:22 and a light chain variable domain comprising a CDR3 region of SEQ ID NO:33, a CDR2 region of SEQ ID NO:32 and a CDR1 region of SEQ ID NO:31;
b) An anti-human IL33R antibody, wherein the heavy chain variable domain comprises SEQ ID NO:21 and the light chain variable domain comprises SEQ ID NO:30; or
c) An anti-human IL33R antibody according to a) or b) having a human IgG1 or IgG4 isotype but modified in the hinge region at one or more amino acid position between 216-240, and/or in the second inter-domain region at one or more amino acid position between 327-331 between C H 2 and C H 3;
d) An anti-human IL33R antibody according to c), wherein said hinge region is modified by replacing the amino acid at position 234 and the amino acid at position 235 with alanine; or
e) An anti-human IL33R antibody according to c), wherein said hinge region is modified by replacing the amino acid at position 235 and the amino acid at position 228 with glutamic acid and proline, respectively;
and a pharmaceutically acceptable carrier.
9. A pharmaceutical composition according to claim 8 , wherein the antibody binds to the same IL33R epitope to which the antibody according to claim 3 binds.
10. A nucleic acid encoding a heavy chain of an antibody binding to IL33R, wherein said antibody comprises a CDR3 region of SEQ ID NO:24, a CDR2 region of SEQ ID NO:23 and a CDR1 region of SEQ ID NO:22 and a light chain variable domain comprises a CDR3 region of SEQ ID NO:33, a CDR2 region of SEQ ID NO:32 and a CDR1 region of SEQ ID NO:31.
11. An expression vector comprising a nucleic acid encoding an anti-human IL33R antibody or antigen binding fragment thereof selected from:
a) An anti-human IL33R antibody comprising a heavy chain variable domain comprising a CDR3 region of SEQ ID NO:24, a CDR2 region of SEQ ID NO:23 and a CDR1 region of SEQ ID NO:22 and a light chain variable domain comprising a CDR3 region of SEQ ID NO:33, a CDR2 region of SEQ ID NO:32 and a CDR1 region of SEQ ID NO:31;
b) An anti-human IL33R antibody, wherein the heavy chain variable domain comprises SEQ ID NO:21 and the light chain variable domain comprises SEQ ID NO:30;
c) An anti-human IL33R antibody according to a) or b) having a human IgG1 or IgG4 isotype but modified in the hinge region at one or more amino acid position between 216-240, and/or in the second inter-domain region at one or more amino acid position between 327-331 between CH2 and CH3;
d) An anti-human IL33R antibody according to c), wherein said hinge region is modified by replacing the amino acid at position 234 and the amino acid at position 235 with alanine; or
e) An anti-human IL33R antibody according to c), wherein said hinge region is modified by replacing the amino acid at position 235 and the amino acid at position 228 with glutamic acid and proline, respectively.
12. The vector according to claim 11 , wherein the vector is capable of expressing the anti-human IL33R antibody or antigen binding fragment thereof in a host cell.
13. A host cell comprising a vector according to claim 11 .
14. The host cell of claim 13 wherein the host cell is a prokaryotic cell.
15. The host cell of claim 13 wherein the host cell is a eukaryotic cell.
16. A method for producing a recombinant anti-human IL33R antibody or antigen binding fragment thereof comprising a heavy chain variable domain comprising a CDR3 region of SEQ ID NO:24, a CDR2 region of SEQ ID NO:23 and a CDR1 region of SEQ ID NO:22 and a light chain variable domain comprising a CDR3 region of SEQ ID NO:33, a CDR2 region of SEQ ID NO:32 and a CDR1 region of SEQ ID NO:31, said method comprising culturing a host cell according to claim 13 and recovering said antibody from said cell or the cell culture supernatant.