High-affinity human antibodies to human protease-activated receptor-2
The present invention provides antibodies that bind to protease-activated receptor-2 (PAR-2) and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human PAR-2. The antibodies of the invention are useful for the treatment of diseases and disorders associated with one or more PAR-2 biological activities, including the treatment of pain conditions, inflammatory conditions and gastrointestinal conditions.
1. An isolated human antibody or antigen-binding fragment thereof that specifically binds to human PAR-2 (SEQ ID NO:851), wherein the antibody or antigen-binding fragment thereof:
(a) interacts with Ser-37, Leu-38, Ile-39, Gly-40, Val-42 and Asp-43 of human PAR-2;
(b) does not interact with Lys-41 of human PAR-2;
(c) blocks trypsin cleavage of human PAR-2 at the activating cleavage site located at the junction of residues Arg-36 and Ser-37 of human PAR-2;
(d) does not block trypsin cleavage of human PAR-2 at the non-activating cleavage site located at the junction of residues Arg-31 and Ser-32; and
(e) competes for binding to human PAR-2 with a reference antibody comprising heavy chain complimentary determining regions (HCDR1-HCDR2-HCDR3) having the amino acid sequences of SEQ ID NOs:700-702-704; and the light chain CDRs (LCDR1-LCDR2-LCDR3) having the amino acid sequences of SEQ ID NOs:708-710-712.
2. The isolated human antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein the HCVR comprises the heavy chain CDRs (HCDR1-HCDR2-HCDR3) having the amino acid sequences of SEQ ID NOs:700-702-704, and wherein the LCVR comprises the light chain CDRs (LCDR1-LCDR2-LCDR3) having the amino acid sequences of SEQ ID NOs:708-710-712.
3. The isolated human antibody or antigen-binding fragment of claim 2 , wherein the antibody or antigen-binding fragment comprises a HCVR having the amino acid sequence of SEQ ID NO:714 and a LCVR having the amino acid sequence of SEQ ID NO:692.
4. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 1 and a pharmaceutically-acceptable carrier.
5. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 2 and a pharmaceutically-acceptable carrier.
6. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 3 and a pharmaceutically-acceptable carrier.