Plasma kallikrein binding proteins

1. An isolated monoclonal antibody that binds to the active form of human plasma kallikrein and does not bind human prekallikrein.

2. The isolated monoclonal antibody of claim 1 , wherein the antibody binds and inhibits the active form of human plasma kallikrein.

3. The isolated monoclonal antibody of claim 1 , wherein the antibody has an on rate of greater than 10 5 or 10 6 .

4. An isolated monoclonal antibody that binds the same epitope in plasma kallikrein as or competes for binding to plasma kallikrein with an antibody comprising the same heavy chain and light chain variable regions of an antibody selected from the group consisting of: M162-A04, M160-G12, M142-H08, X63-G06, X101-A01, X81-B01, X67-D03, X67-G04, X115-B07, X115-D05, X115-E09, X115-H06, X115-A03, X115-D01, X115-G04, M29-D09, M145-D11, M06-D09 and M35-G04.

5. The isolated monoclonal antibody of claim 4 , wherein the antibody competes with or binds the same epitope in plasma kallikrein as an antibody comprising the same heavy chain and light chain variable regions as X81-B01.

6. The isolated monoclonal antibody claim 4 , wherein the antibody competes with or binds the same epitope in plasma kallikrein as an antibody comprising the same heavy chain and light chain variable regions as X67-D03.

7. The isolated monoclonal antibody of claim 4 , wherein the antibody competes with or binds the same epitope in plasma kallikrein as an antibody comprising the same heavy chain and light chain variable regions as X101-A01.

8. The isolated monoclonal antibody of claim 4 , wherein the antibody competes with or binds the same epitope in plasma kallikrein as A04 an antibody comprising the same heavy chain and light chain variable regions as M162-A04.

9. The isolated monoclonal antibody of claim 4 , wherein the antibody competes with or binds the same epitope in plasma kallikrein as an antibody comprising the same heavy chain and light chain variable regions as X63-G06.

10. The isolated monoclonal antibody of claim 4 , wherein the antibody binds human plasma kallikrein and murine plasma kallikrein but does not bind human prekallikrein.

11. The isolated monoclonal antibody of claim 10 , wherein the antibody does not bind murine prekallikrein.

12. The isolated monoclonal antibody of claim 1 , wherein the antibody binds one or more of amino acids of: Arg551, Gln553, Tyr555, Thr558, and Arg560 of human plasma kallikrein.

13. The isolated monoclonal antibody of claim 1 , wherein the antibody binds one or more of amino acids of: 5478, N481, 5525, and K526 of human plasma kallikrein.

14. The isolated monoclonal antibody of claim 1 , wherein the antibody binds one or more of amino acids of: Ser479, Tyr563, and Asp585 of human plasma kallikrein.

15. The isolated monoclonal antibody of claim 1 , wherein the antibody has an apparent inhibition constant (K i,app ) of plasma kallikrein of less than 100 nM.

16. The isolated monoclonal antibody of claim 15 , wherein the antibody has an apparent inhibition constant (K i,app ) of plasma kallikrein of less than 10 nM.

17. The isolated monoclonal antibody of claim 16 , wherein the antibody has an apparent inhibition constant (K i,app ) of plasma kallikrein of less than 1 nM.

18. The isolated monoclonal antibody of claim 1 , wherein the antibody is an IgG or a soluble Fab (sFab).

19. The isolated monoclonal antibody of claim 4 , wherein the antibody comprises a heavy chain immunoglobulin variable domain sequence comprising three CDRs from the heavy chain variable domain of an antibody selected from the group consisting of: M162-A04, M160-G12, M142-H08, X63-G06, X101-A01, X81-B01, X67-D03, X67-G04, X115-B07, X115-D05, X115-E09, X115-H06, X115-A03, X115-D01, X115-G04, M29-D09, M145-D11, M06-D09 and M35-G04, and a light chain immunoglobulin variable domain sequence comprising three CDRs from the light chain variable domain of the selected antibody.

20. The isolated monoclonal antibody of claim 19 , wherein the antibody comprises three CDRs from the heavy chain variable domain of X81-B01 and three CDRs from the light chain variable domain of X81-B01.

21. The isolated monoclonal antibody of claim 19 , wherein the antibody comprises three CDRs from the heavy chain variable domain of X67-D03 and three CDRs from the light chain variable domain of X67-D03.

22. The isolated monoclonal antibody of claim 19 , wherein the antibody comprises three CDRs from the heavy chain variable domain of X101-A01 and three CDRs from the light chain variable domain of X101-A01.

23. The isolated monoclonal antibody of claim 19 , wherein the antibody comprises three CDRs from the heavy chain variable domain of X63-G06 and three CDRs from the light chain variable domain of X63-G06.

24. The isolated monoclonal antibody of claim 19 , wherein the antibody comprises three CDRs from the heavy chain variable domain of M162-A04 and three CDRs from the light chain variable domain of M162-A04.

25. The isolated monoclonal antibody of claim 19 , wherein the heavy chain variable domain sequence comprises a heavy chain variable domain sequence of an antibody selected from the group consisting of X81-B01, X63-G06, X101-A01, M162-A04, M160-G12, M142-H08, X67-D03, X67-G04, X115-B07, X115-D05, X115-E09, X115-H06, X115-A03, X115-D01, X115-G04, M29-D09, M145-D11, M06-D09 and M35-G04, and the light chain variable domain sequence comprises a light chain variable domain of the selected antibody.

26. The isolated monoclonal antibody of claim 1 , wherein the antibody competes for binding to active plasma kallikrein with epi-Kal2.

27. The isolated monoclonal antibody of claim 1 , wherein the antibody competes for binding to active plasma kallikrein with AEBSF.

28. The isolated monoclonal antibody of claim 1 , wherein the antibody binds and inhibits plasma kallikrein.

29. A pharmaceutical composition comprising the isolated monoclonal antibody of claim 1 and a pharmaceutically acceptable carrier.

30. The isolated monoclonal antibody of claim 1 , wherein the antibody is a full-length antibody or an antigen-binding fragment thereof.

31. The isolated monoclonal antibody of claim 4 , wherein the isolated antibody is a full-length antibody or an antigen-binding fragment thereof.

32. The pharmaceutical composition of claim 29 , wherein the isolated monoclonal antibody is a full-length antibody or an antigen-binding fragment thereof.