Anti-IL-12/IL-23 antibodies
The present invention provides an antibody comprising an antigen binding domain which binds to human IL-12 and human IL-23. The antibody binds human IL-12p40 existing as a monomer (human IL-12p40) and as a homodimer (human IL-12p80) and the antibody inhibits the binding of human IL-12 to human IL-12R β2 and human IL-23 to human IL-23R but does not inhibit the binding of human IL-12 or human IL-23 or human IL-12p40 or human IL-12p80 to human IL-12Rβ1.
1. An isolated antibody which binds human IL-12p40, said antibody comprising an immunoglobulin heavy chain variable region selected from the group consisting of SEQ ID NO: 6, SEQ ID NO: 115, SEQ ID NO: 119, SEQ ID NO: 158, SEQ ID NO: 159, SEQ ID NO: 162, and SEQ ID NO: 112.
2. The antibody as claimed in claim 1 in which the antibody comprises a human or non-human primate heavy chain immunoglobulin constant region selected from a group consisting of IgG1, IgG2, IgG3, IgG4, IgM, IgE and IgA.
3. An isolated antibody which binds human IL-12p40, said antibody comprising an immunoglobulin light chain variable region selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 169, SEQ ID NO: 189, and SEQ ID NO: 179.
4. The antibody as claimed in claim 3 in which the antibody comprises a human or non-human primate light chain immunoglobulin constant region selected from a group consisting of kappa or lambda.
5. An isolated antibody which binds human IL-12p40, said antibody comprising two immunoglobulin variable regions, wherein said two immunoglobulin variable regions are selected from a group consisting of:
SEQ ID NO:6 and SEQ ID NO:7;
SEQ ID NO:119 and SEQ ID NO:179;
SEQ ID NO:112 and SEQ ID NO:169;
SEQ ID NO:158 and SEQ ID NO:189;
SEQ ID NO:159 and SEQ ID NO:189;
SEQ ID NO:162 and SEQ ID NO:189; and
SEQ ID NO:115 and SEQ ID NO:189.
6. The antibody as claimed in claim 5 in which the antibody comprises a human or non-human primate heavy chain immunoglobulin constant region selected from a group consisting of IgG1, IgG2, IgG3, IgG4, IgM, IgE and IgA.
7. The antibody as claimed in claim 5 in which the antibody comprises a human or non-human primate light chain immunoglobulin constant region selected from a group consisting of kappa or lambda.
8. The antibody as claimed in claim 5 in which the antibody is modified by the covalent attachment of an organic moiety.
9. The antibody as claimed in claim 8 in which the organic moiety is a linear or branched hydrophilic polymeric group, fatty acid group, or fatty acid ester group.
10. The antibody as claimed in claim 5 in which the antibody is modified to modulate a functional characteristic selected from the group consisting of antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, serum half-life, biodistribution and binding to Fc receptors.
11. The antibody as claimed in claim 10 in which the modification is by protein engineering, glycoengineering or chemical methods.