Anti-IL12Rβ1 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/IL18 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 nucleic acid encoding at least the heavy and/or light variable region(s) of the antibody or protein with an antigen-binding portion of an antibody, comprising a variable heavy chain amino acid sequence comprising an HCDR1 sequence of SEQ ID NO:1, an HCDR2 sequence of SEQ ID NO:2, an HCDR3 sequence of SEQ ID NO:3 and a variable light chain amino acid sequence comprising an LCDR1 sequence of SEQ ID NO:4, an LCDR2 sequence of SEQ ID NO:5 and an LCDR3 sequence of SEQ ID NO: 6, wherein said antibody or protein binds to the IL12Rβ1 polypeptide of SEQ ID NO:89.
2. A cloning or expression vector comprising one or more nucleic acids according to claim 1 .
3. A host cell comprising one or more cloning or expression vectors of claim 2 .
4. A cloning or expression vector, suitable for the recombinant production of an antibody according to claim 1 in a host cell, said host cell or expression vector comprising at least one nucleic acid selected from the group consisting of SEQ ID NOs: 73, 77, 81, 85, and 94.
5. A cloning or expression vector according to claim 4 , comprising the coding sequences selected from the group consisting of: (a) SEQ ID NO:73 and SEQ ID NO:85; (b) SEQ ID NO:77 and SEQ ID NO:85; (c) SEQ ID NO:81 and SEQ ID NO:85; and (d) SEQ ID NO:94 and SEQ ID NO:85; wherein said coding sequences are operatively linked to a promoter sequence.
6. A host cell comprising one or more cloning or expression vectors of claim 5 .
7. A host cell comprising one or more cloning or expression vectors of claim 4 .
8. An isolated nucleic acid encoding at least the heavy and/or light variable region(s) of the antibody or protein with an antigen-binding portion of an antibody, 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, wherein the antibody binds to the IL12Rβ1 polypeptide of SEQ ID NO: 89.
9. A cloning or expression vector comprising one or more nucleic acids according to claim 8 .
10. A host cell comprising one or more cloning or expression vectors of claim 9 .
11. An isolated nucleic acid encoding at least the heavy and/or light variable region(s) of the antibody or protein with an antigen-binding portion of an antibody, comprising a V H polypeptide sequence of SEQ ID NO: 49 and a V L polypeptide sequence of SEQ ID NO: 50.
12. A cloning or expression vector comprising one or more nucleic acids according to claim 11 .
13. A host cell comprising one or more cloning or expression vectors of claim 12 .
14. An isolated nucleic acid encoding the antibody or protein with an antigen-binding portion of an antibody, 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.
15. A cloning or expression vector comprising one or more nucleic acids according to claim 14 .
16. A host cell comprising one or more cloning or expression vectors of claim 15 .