Antagonists of protease activated receptor-1 (PAR1)
The present invention provides antibodies or antigen-binding molecules that specifically recognize and antagonize human PAR1 receptor. Also provided in the invention are polynucleotides and vectors that encode such molecules and host cells that harbor the polynucleotides or vectors.
1. An antibody or antigen binding molecule that specifically binds to an epitope of human PAR1 which antibody or antigen binding molecule comprises heavy chain complementarity determining region (CDR) sequences CDR1, CDR2, and CDR3 of SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23, respectively; and light chain CDR sequences CDR1, CDR2, and CDR3 of SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26, respectively, and wherein the antibody or antigen binding molecule is a PAR1 antagonist.
2. An antibody or antigen binding molecule that specifically binds to an epitope of human PAR1, which antibody or antigen binding molecule comprises a heavy chain complementarity determining region (CDR) sequences CDR1, CDR2, and CDR3 of SEQ ID NO:27, SEQ ID NO:28 and SEQ ID NO:29, respectively; and light chain CDR sequences CDR1, CDR2, and CDR3 of SEQ ID NO:30, SEQ ID NO:31, and SEQ ID NO:32, respectively, and wherein the antibody or antigen binding molecule is a PAR1 antagonist.
3. The antibody or antigen-binding molecule of claim 1 which comprises a heavy chain variable region amino acid sequence of SEQ ID NO:5 and a light chain variable region amino acid sequence of SEQ ID NO:6.
4. The antibody or antigen-binding molecule of claim 1 which is a mouse antibody.
5. The antibody or antigen-binding molecule of claim 1 which is a monoclonal antibody.
6. The antibody or antigen-binding molecule of claim 1 which is a chimeric antibody.
7. The antibody or antigen-binding molecule of claim 6 which comprises a human heavy chain constant region and a human light chain constant region.
8. The antibody or antigen-binding molecule of claim 1 which is a humanized antibody.
9. The antibody or antigen-binding molecule of claim 1 which is a single chain antibody.
10. The antibody or antigen-binding molecule of claim 1 which is a Fab fragment.
11. The antibody or antigen-binding molecule of claim 1 which is a monobody with a scaffold derived from a human fibronectin type III domain.
12. A pharmaceutical composition comprising an antibody or antigen binding molecule that specifically binds to an epitope of human PAR1, wherein the antibody or antigen binding molecule comprises heavy chain CDR1, CDR2, and CDR3 sequences, SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23, respectively; and light chain CDR1, CDR2, and CDR3 sequences, SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26, respectively, and wherein the antibody or antigen binding molecule is a PAR1 antagonist.
13. A pharmaceutical composition comprising an antibody or antigen binding molecule that specifically binds to an epitope of human PAR1, wherein the antibody or antigen binding molecule comprises heavy chain CDR1, CDR2, and CDR3 sequences, SEQ ID NO:27, SEQ ID NO:28 and SEQ ID NO:29, respectively; and light chain CDR1, CDR2, and CDR3 sequences, SEQ ID NO:30, SEQ ID NO:31, and SEQ ID NO:32, respectively, and wherein the antibody or antigen binding molecule is a PAR1 antagonist.
14. The antibody or antigen-binding molecule of claim 2 which comprises a heavy chain variable region amino acid sequence of SEQ ID NO:7 and a light chain variable region amino acid sequence of SEQ ID NO:8.
15. The antibody or antigen-binding molecule of claim 2 which is a mouse antibody.
16. The antibody or antigen-binding molecule of claim 2 which is a monoclonal antibody.
17. The antibody or antigen-binding molecule of claim 2 which is a chimeric antibody.
18. The antibody or antigen-binding molecule of claim 17 which comprises a human heavy chain constant region and a human light chain constant region.
19. The antibody or antigen-binding molecule of claim 2 which is a humanized antibody.
20. The antibody or antigen-binding molecule of claim 2 which is a single chain antibody.
21. The antibody or antigen-binding molecule of claim 2 which is a Fab fragment.
22. The antibody or antigen-binding molecule of claim 2 which is a monobody with a scaffold derived from a human fibronectin type III domain.