Anti-IL-18 antibodies and their uses
The present invention provides human, humanized and/or chimeric antibodies as well as fragments, derivatives/conjugates and compositions thereof with a specific binding affinity for interleukin-18. The invention includes the use of these antibodies for diagnosing and treating diseases associated with increased IL-18 activity, the latter in the form of a pharmaceutical composition.
1. An isolated antibody molecule for human Interleukin-18(IL-18) which specifically binds to an epitope of human IL-18 which wholly or partially overlaps with the IL-18BP binding site on human IL-18, wherein the antibody molecule comprises:
(a) a HCDR1 having an amino acid sequence identical to or comprising 3 or fewer amino acid residue substitutions relative to SEQ ID NO: 153;
(b) a HCDR2 having an amino acid sequence identical to or comprising 4 or fewer amino acid residue substitutions relative to SEQ ID NO: 154;
(c) a HCDR3 having an amino acid sequence identical to or comprising 5 or fewer amino acid residue substitutions relative to SEQ ID NO: 155;
(d) a LCDR1 having an amino acid sequence identical to or comprising 4 or fewer amino acid residue substitutions relative to SEQ ID NO: 158;
(e) a LCDR2 having an amino acid sequence identical to or comprising 4 or fewer amino acid residue substitutions relative to SEQ ID NO: 159; and
(f) a LCDR3 having an amino acid sequence identical to or comprising 9 or fewer amino acid residue substitutions relative to SEQ ID NO: 160.
2. The antibody molecule according to claim 1 , wherein the antibody molecule comprises an antibody VH domain and an antibody VL domain,
wherein the VH domain comprises HCDR1, HCDR2, HCDR3 having the amino acid sequences of SEQ ID NOS: 153, 154 and 155, respectively; and,
the VL domain comprises LCDR1, LCDR2, LCDR3 having the amino acid sequences of SEQ ID NOS: 158, 159 and 160, respectively.
3. The antibody molecule according to claim 1 , wherein the heavy and/or light chain framework regions are germlined to human germline gene segment sequences.
4. The antibody molecule according to claim 2 , wherein the amino acid sequence of the antibody VH domain is at least 90% identical with SEQ ID NO: 152 and wherein the amino acid sequence of the antibody VL domain is at least 90% identical with SEQ ID NO: 157.
5. The antibody molecule according to claim 4 , wherein the amino acid sequence of the antibody VH domain is SEQ ID NO: 152 and the amino acid sequence of the antibody VL domain sequence is SEQ ID NO: 157.
6. The antibody molecule according to claim 1 , wherein the antibody molecule is an IgG1 with YTE and TM mutations in the Fc region.
7. A composition comprising an isolated antibody molecule according to claim 1 and a pharmaceutically acceptable excipient.
8. The antibody molecule according to claim 2 , wherein the antibody molecule is an IgG1 with YTE and TM mutations in the Fc region.
9. The antibody molecule according to claim 4 , wherein the antibody molecule is an IgG1 with YTE and TM mutations in the Fc region.
10. The antibody molecule according to claim 5 , wherein the antibody molecule is an IgG1 with YTE and TM mutations in the Fc region.
11. A composition comprising an isolated antibody molecule according to claim 2 and a pharmaceutically acceptable excipient.
12. A composition comprising an isolated antibody molecule according to claim 4 and a pharmaceutically acceptable excipient.
13. A composition comprising an isolated antibody molecule according to claim 5 and a pharmaceutically acceptable excipient.