Human CGRP receptor binding proteins
Antigen binding proteins that bind to human CGRP receptor (CGRP R) are provided. Nucleic acids encoding the antigen binding protein, vectors, and cells encoding the same are also provided. The antigen binding proteins can inhibit binding of CGRP R to CGRP, and are useful in a number of CGRP R related disorders, including the treatment and/or prevention of migraine headaches.
1. An isolated antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof specifically binds the human CGRP receptor and comprises a CDRH1 having the sequence of SEQ ID NO:73, a CDRH2 having the sequence of SEQ ID NO:74, a CDRH3 having the sequence of SEQ ID NO:75, a CDRL1 having the sequence of SEQ ID NO:42, a CDRL2 having the sequence of SEQ ID NO:43, and a CDRL3 having the sequence of SEQ ID NO:44.
2. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the isolated antibody is a monoclonal antibody selected from the group consisting of a fully human antibody and a chimeric antibody.
3. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody is a monoclonal IgG1 or monoclonal IgG2 antibody.
4. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the isolated antibody or antigen-binding fragment thereof specifically binds to human CGRP receptor with a K D ≦100 nM.
5. The isolated antibody or antigen-binding fragment thereof of claim 4 , wherein the isolated antibody or antigen-binding fragment thereof specifically binds to human CGRP receptor with a K D ≦10 nM as determined using a FACS binding assay.
6. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody or antigen-binding fragment thereof comprises (i) a heavy chain variable region (V H ) sequence that has at least 95% sequence identity with SEQ ID NO:158, and (ii) a light chain variable region (V L ) sequence that has at least 95% sequence identity with SEQ ID NO:142.
7. The isolated antibody or antigen-binding fragment thereof of claim 1 wherein the isolated antibody or antigen-binding fragment thereof is selected from the group consisting of a monoclonal antibody, a Fab fragment, an Fab′ fragment, an F(ab′) 2 fragment, an Fv fragment, a diabody, and a single chain antibody.
8. The isolated antibody or antigen-binding fragment thereof of claim 7 , wherein the isolated antibody or antigen-binding fragment thereof is a monoclonal antibody selected from the group consisting of a fully human antibody and a chimeric antibody.
9. The isolated antibody or antigen-binding fragment thereof of claim 8 , wherein the monoclonal antibody is an IgG1-, IgG2-, IgG3-, or IgG4-type antibody.
10. The isolated antibody or antigen-binding fragment thereof of claim 9 , wherein the monoclonal antibody is an IgG1 or IgG2 antibody.
11. The isolated antibody or antigen-binding fragment thereof of claim 6 , wherein the isolated antibody is a monoclonal antibody selected from the group consisting of a fully human antibody and a chimeric antibody.
12. The isolated antibody or antigen-binding fragment thereof of claim 6 , wherein the antibody is a monoclonal IgG1 or monoclonal IgG2 antibody.
13. An isolated antibody that specifically binds the human CGRP receptor and comprises a heavy chain variable region (V H ) comprising the sequence of SEQ ID NO:158, and a light chain variable region (V L ) comprising the sequence of SEQ ID NO:142.
14. An isolated antibody that specifically binds the human CGRP receptor and comprises a heavy chain comprising the sequence of SEQ ID NO:29, and a light chain comprising the sequence of SEQ ID NO:17.
15. A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable excipient.