Antibodies against interleukin-22
The present invention relates to antibodies binding to IL22 and inhibiting its interaction with one or more of its natural ligands. Specific examples of such antibodies are provided. The therapeutic uses of the antibodies and methods of generating such are also provided.
1 . An isolated antibody that binds to interleukin 22 (IL22) and inhibits or attenuates IL22 binding to IL22 receptor 1 (IL22R1), the isolated antibody comprising:
a light chain variable region comprising:
a CDR-L1 comprising SEQ ID NO:5,
a CDR-L2 comprising SEQ ID NO:6, and
a CDR-L3 comprising SEQ ID NO:7;
and a heavy chain variable region comprising:
a CDR-H1 comprising SEQ ID NO:8,
a CDR-H2 comprising SEQ ID NO:9, and
a CDR-H3 comprising SEQ ID NO: 10.
2 . The antibody according to claim 1 , wherein said antibody:
(a) binds to a region on IL22, wherein the binding sterically blocks the interaction between IL22 and IL22R1;
(b) inhibits or attenuates IL22 binding to IL22 binding protein (IL22RA2); and
(c) binds to human and cynomolgus monkey IL22.
3 . The antibody according to claim 1 , wherein said antibody has dissociation equilibrium constant (KD) of less than 100 pM for human IL22.
4 . The antibody according to claim 1 , wherein the antibody specifically binds to the polypeptide VRLIGEKLFHGVSM (SEQ ID NO: 96) corresponding to residues 72-85 of the amino-acid sequence of IL22 defined by SEQ ID NO:1.
5 . The antibody according to claim 1 , wherein the antibody binds to an epitope of human IL22, the epitope comprising five or more residues selected from Lys44, Phe47, Gln48, Ile75, Gly76, Glu77, Phe80, His81, Gly82, Val83, Ser84, Met85, Ser86, Arg88, Leu169, Met172, Ser173, Arg175, Asn176 and Ile179 of human IL22 (SEQ ID NO: 1) as determined at the distance of less than 5 Å contact distance between the antibody and IL22.
6 . The antibody according to claim 5 , wherein said binding is determined by X-ray crystallography.
7 . The antibody according to claim 1 , wherein the light chain variable region comprises the sequence set forth in SEQ ID NO:22.
8 . The antibody according to claim 1 , wherein the heavy chain variable region comprises the sequence set forth in SEQ ID NO:24.
9 . The antibody according to claim 1 , wherein the light chain variable region comprises the sequence set forth in SEQ ID NO: 22, or a sequence which is at least 90% identical thereto; and the heavy chain variable region comprises the sequence set forth in SEQ ID NO: 24, or a sequence which is at least 90% identical thereto.
10 . The antibody according to claim 1 , wherein said antibody is a full length antibody.
11 . The antibody according to claim 1 , wherein said antibody is an antibody fragment.
12 . The antibody according to claim 11 , wherein said antibody fragment is Fab, Fab′, F(ab′) 2 , Fv, dsFv, scFv, or dsscFv.
13 . The antibody according to claim 12 , wherein the antibody is a Fab comprising a light chain comprising the sequence set forth SEQ ID NO: 26 and a heavy chain comprising the sequence set forth in SEQ ID NO: 28.
14 . The antibody according to claim 12 , wherein the antibody is a Fab.
15 . The antibody according to claim 10 , wherein the antibody is an IgG1 comprising a light chain comprising the sequence set forth in SEQ ID NO: 26 and a heavy chain comprising the sequence set forth in SEQ ID NO: 30.
16 . The antibody according to claim 10 , wherein the antibody is an IgG1.
17 . The antibody according to claim 10 , wherein the antibody is an IgG4P comprising a light chain comprising the sequence set forth SEQ ID NO: 26 and a heavy chain comprising the sequence set forth in SEQ ID NO: 32.
18 . The antibody according to claim 10 , wherein the antibody is an IgG4P.
19 . A pharmaceutical composition comprising the antibody of claim 1 , and a pharmaceutically acceptable adjuvant or carrier.