IL-1β neutralizing human monoclonal antibodies
The present invention is directed to antigen binding proteins and in particular to IL-1β antigen binding proteins. The present invention further provides compositions comprising the antigen binding proteins, use of the antigen binding proteins and methods for production.
1. An isolated IL-1β specific antigen binding protein comprising one or more binding units selected from the group consisting of the following binding units:
(i) a binding unit LI comprising Kabat residues 24-33 of SEQ ID NO: 17;
(ii) a binding unit L2 comprising Kabat residues 49-55 of SEQ ID NO: 17;
(iii) a binding unit L3 comprising Kabat residues 88-96 of SEQ ID NO: 17, or a variant thereof which contains up to five conservative amino acid substitutions in the binding unit L3;
(iv) a binding unit HI comprising Kabat residues 31-35 of SEQ ID NO: 14;
(v) a binding unit H2 comprising Kabat residues 50-65 of SEQ ID NO: 14; and
(vi) a binding unit H3 comprising Kabat residues 98-108 of SEQ ID NO: 14.
2. The isolated antigen binding protein of claim 1 , wherein said isolated antigen binding protein is capable of specifically binding to IL-1β.
3. The isolated antigen binding protein as claimed in claim 2 , wherein the IL-1β is human, murine or simian IL-1β.
4. The isolated antigen binding protein of claim 1 , wherein said protein is an antibody.
5. The isolated antigen binding protein of claim 4 , wherein said antibody is monoclonal, polyclonal, bispecific, multispecific or heteroconjugate.
6. The isolated antigen binding protein of claim 4 , wherein said antibody is fully human.
7. The isolated antigen binding protein of claim 4 , wherein said antibody is of the subtype IgG1, of the subtype IgG2, of the subtype IgG4, or of the subtype IgG3.
8. The isolated antigen binding protein of claim 1 , wherein said protein is a single variable domain, a domain antibody, an antigen binding fragment, an immunologically effective fragment, a single chain Fv, a diabody or a tetravalent bispecific antibody (Tandab).
9. The isolated antigen binding protein of claim 1 , wherein the protein is recombinant.
10. The isolated antigen binding protein of claim 1 , wherein said binding protein further comprises an agent selected from the group consisting of an immunoadhesion molecule, an imaging agent, a therapeutic agent, and a cytotoxic agent.
11. The binding protein of claim 10 , wherein said agent is an imaging agent selected from the group consisting of a radiolabel, an enzyme, a fluorescent label, a luminescent label, a bioluminescent label, a magnetic label, and biotin.
12. The binding protein of claim 10 , wherein said agent is a therapeutic or cytotoxic agent selected from the group consisting of an anti-metabolite, an alkylating agent, an antibiotic, a growth factor, a cytokine, an anti-angiogenic agent, an anti-mitotic agent, an anthracycline, toxin and an apoptotic agent.
13. A composition comprising the antigen binding protein of claim 1 and a pharmaceutically acceptable carrier.
14. The composition of claim 13 , further comprising one or more therapeutic agents.
15. An isolated cell line that is capable of producing the antigen binding protein of claim 1 .
16. An isolated IL-1β specific antigen binding protein according to claim 1 , consisting of:
(i) a light chain sequence set forth in SEQ ID NO: 17; and
(ii) a heavy chain sequence set forth in SEQ ID NO: 14.
17. An isolated IL-1β specific antigen binding protein consisting of the following binding units:
(i) a binding unit L1 comprising Kabat residues 24-33 of SEQ ID NO: 17;
(ii) a binding unit L2 comprising Kabat residues 49-55 of SEQ ID NO: 17;
(iii) a binding unit L3 comprising any one of the sequences as defined in SEQ ID NOs: 9, 10, 11, 12, 13, and 19;
(iv) a binding unit H1 comprising Kabat residues 31-35 of SEQ ID NO: 14;
(v) a binding unit H2 comprising Kabat residues 50-65 of SEQ ID NO: 14; and
(vi) a binding unit H3 comprising Kabat residues 98-108 of SEQ ID NO: 14.