Cadherin-11 EC1 domain antagonists for treating inflammatory joint disorders
The present invention relates to Cadherin-11 antagonists and compositions comprising Cadherin-11 antagonists. The invention also relates to methods for treating inflammatory joint disorders, such as rheumaotid arthritis, in a mammalian subject by administering a therapeutically effective amount of a Cadherin-11 antagonist.
1. An isolated antibody that specifically binds an EC1 domain of a mammalian Cadherin-11 protein, wherein the antibody binds an epitope comprising SEQ ID NO:11, or an epitope that is present in SEQ ID NO:12, in the EC1 domain of the mammalian Cadherin-11 protein.
2. The isolated antibody of claim 1 , wherein the antibody binds an epitope that is present in SEQ ID NO:3.
3. The isolated antibody of claim 2 , wherein the epitope does not include the amino acid sequence EEY.
4. The isolated antibody of claim 1 , wherein the antibody is selected from the group consisting of a monoclonal antibody, a polyclonal antibody, a humanized antibody, a chimeric antibody, a single chain antibody, and an antibody fragment.
5. The isolated antibody of claim 4 , wherein the antibody is an antibody fragment.
6. The isolated antibody of claim 5 , wherein the antibody fragment is selected from the group consisting of an Fab, an Fab′, an F(ab′) 2 and an scFv.
7. A pharmaceutical composition comprising an antibody that specifically binds an EC1 domain of a mammalian Cadherin-11 protein, wherein the antibody binds an epitope comprising SEQ ID NO:11, or an epitope that is present in SEQ ID NO:12, in the EC1 domain of the mammalian Cadherin-11 protein.
8. The pharmaceutical composition of claim 7 , wherein the antibody binds SEQ ID NO:3.
9. The pharmaceutical composition of claim 7 , further comprising a disease-modifying anti-rheumatic drug.
10. The pharmaceutical composition of claim 9 , wherein the disease-modifying anti-rheumatic drug is methotrexate.
11. The pharmaceutical composition of claim 7 , further comprising an anti-inflammatory agent.
12. The pharmaceutical composition of claim 11 , wherein the anti-inflammatory agent is an NSAID or a steroid.
13. The pharmaceutical composition of claim 11 , wherein the anti-inflammatory agent is a disease modifying antirheumatic drug.
14. The isolated antibody of claim 1 , wherein the antibody binds an epitope that comprises SEQ ID NO:11.
15. The isolated antibody of claim 1 , wherein the antibody binds an epitope that is present in SEQ ID NO:12.
16. The pharmaceutical composition of claim 7 , wherein the antibody binds an epitope that comprises SEQ ID NO:11.
17. The pharmaceutical composition of claim 7 , wherein the antibody binds an epitope that is present in SEQ ID NO:12.