Anti-IL12Rbeta1 antibodies and their use in treating autoimmune and inflammatory disorders
The present invention relates to antibodies that specifically bind to IL12Rβ1, the non-signal transducing chain of both the heterodimeric IL12 and IL23 receptors. The invention more specifically relates to specific antibodies that are IL12 and IL23 receptor antagonists capable of inhibiting IL12/1L18 induced IFNγ production of blood cells and compositions and methods of use for said antibodies to treat pathological disorders that can be treated by inhibiting IFNγ production, IL12 and/IL23 signaling, such as rheumatoid arthritis, psoriasis or inflammatory bowel diseases or other autoimmune and inflammatory disorders.
1. An isolated antibody or a protein with an antigen-binding portion of an antibody, comprising a variable heavy chain amino acid sequence comprising HCDR1 sequence of SEQ ID NO:1, HCDR2 sequence of SEQ ID NO:2, HCDR3 sequence of SEQ ID NO:3 and a variable light chain amino acid sequence comprising LCDR1 sequence of SEQ ID NO:4, LCDR2 sequence of SEQ ID NO:5 and LCDR3 sequence of SEQ ID NO:6, wherein said antibody or protein binds to the IL12Rβ1 polypeptide of SEQ ID NO:89.
2. The isolated antibody or protein of claim 1 , wherein said antibody or protein cross-reacts with cynomolgous IL12Rβ1 polypeptide of SEQ ID NO:98.
3. The isolated antibody or protein of claim 1 wherein said antibody or protein inhibits IL12 dependent IFN-γproduction in human blood cells with an IC 50 of 1nM or less.
4. The isolated antibody or protein according to claim 1 , which is fully human.
5. The isolated antibody or protein according to claim 1 , which comprises a mutant or chemically modified amino acid Fc region, wherein said mutated or chemically modified Fc region confers no or decreased ADCC activity to said antibody when compared to a corresponding antibody with wild type Fc region.
6. The isolated antibody or protein according to claim 1 , comprising a V H polypeptide sequence having at least 95 percent sequence identity to SEQ ID NO:49 and a V L polypeptide sequence having at least 95 percent sequence identity to SEQ ID NO:50.
7. An isolated antibody or protein that binds to the IL12Rβ1 polypeptide of SEQ ID NO:89, comprising a V H polypeptide sequence of SEQ ID NO:49 and a V L polypeptide sequence of SEQ ID NO:50.
8. The isolated antibody or protein according to claim 7 , comprising
(a) heavy chain amino acid sequence of SEQ ID NO:57 and light chain amino acid sequence of SEQ ID NO:69;
(b) heavy chain amino acid sequence of SEQ ID NO:61 and light chain amino acid sequence of SEQ ID NO:69;
(c) heavy chain amino acid sequence of SEQ ID NO:65 and light chain amino acid sequence of SEQ ID NO:69; or
(d) heavy chain amino acid sequence of SEQ ID NO:90 and light chain amino acid sequence of SEQ ID NO:69.
9. A composition comprising an antibody or protein according to claim 1 or 7 , in combination with one or more of a pharmaceutically acceptable excipient, diluent or carrier.