Antibodies specifically binding to MASP-3 for the treatment of various diseases and disorders
The present invention relates to MASP-3 inhibitory antibodies and compositions comprising such antibodies for use in inhibiting the adverse effects of MASP-3 dependent complement activation.
1. An isolated antibody, or antigen-binding fragment thereof, that binds to human MASP-3 comprising:
a heavy chain variable region comprising a HC-CDR1 set forth as SEQ ID NO:72 (SYGMS) a HC-CDR2 set forth as SEQ ID NO:74 (WINTYSGVPTYADDFKG); and a HC-CDR3 set forth as SEQ ID NO:76 (GGEAMDY); and a light chain variable region comprising a LC-CDR1 selected from the group consisting of SEQ ID NO:153 (KSSQSLLDSDGKTYLN), SEQ ID NO:261 (KSSQSLLDSEGKTYLN), SEQ ID NO:262 (KSSQSLLDSAGKTYLN) and SEQ ID NO:263 (KSSQSLLDSDAKTYLN); a LC-CDR2 set forth as SEQ ID NO:155 (LVSKLDS); and a LC-CDR3 set forth as SEQ ID NO:157 (WQGTHFPWT).
2. The isolated antibody, or antigen-binding fragment thereof of claim 1 , wherein the LC-CDR1 comprises SEQ ID NO:261 (KSSQSLLDSEGKTYLN).
3. The isolated antibody, or antigen-binding fragment thereof of claim 1 , wherein the LC-CDR1 comprises SEQ ID NO:262 (KSSQSLLDSAGKTYLN).
4. The isolated antibody, or antigen-binding fragment thereof of claim 1 , wherein the LC-CDR1 comprises SEQ ID NO:263 (KSSQSLLDSDAKTYLN).
5. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the HC-CDR1 comprises SEQ ID NO:72, the HC-CDR2 comprises SEQ ID NO:74, the HC-CDR3 comprises SEQ ID NO:76, the LC-CDR1 comprises SEQ ID NO:153, the LC-CDR2 comprises SEQ ID NO:155 and the LC-CDR3 comprises SEQ ID NO:157.
6. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the HC-CDR1 comprises SEQ ID NO:72, the HC-CDR2 comprises SEQ ID NO:74, the HC-CDR3 comprises SEQ ID NO:76, the LC-CDR1 comprises SEQ ID NO:263, the LC-CDR2 comprises SEQ ID NO:155 and the LC-CDR3 comprises SEQ ID NO:157.
7. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NO:28, SEQ ID NO:251 and SEQ ID NO:252.
8. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the light chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NO:43, SEQ ID NO:253 and SEQ ID NO:279.
9. The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment is selected from the group consisting of a humanized antibody, a chimeric antibody, a murine antibody, and an antigen-binding fragment of any of the foregoing.
10. The antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody or antigen binding fragment thereof is selected from the group consisting of a single chain antibody, an ScFv, a Fab fragment, an Fab′ fragment, an F(ab′)2 fragment, a univalent antibody lacking a hinge region and a whole antibody.
11. The antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody inhibits alternative pathway activation in mammalian blood.
12. A composition comprising the antibody or antigen-binding fragment of claim 1 and a pharmaceutically acceptable excipient.
13. An isolated antibody or antigen-binding fragment thereof that binds to human MASP-3, comprising a heavy chain variable region selected from the group consisting of SEQ ID NO:28, SEQ ID NO:251 and SEQ ID NO:252 and a light chain variable region selected from the group consisting of SEQ ID NO:43, SEQ ID NO:253 and SEQ ID NO:279.
14. The isolated antibody or antigen-binding fragment thereof of claim 13 , wherein the heavy chain variable region comprises SEQ ID NO:28 and the light chain variable region comprises SEQ ID NO:43.
15. The isolated antibody or antigen-binding fragment thereof of claim 13 , wherein the heavy chain variable region comprises SEQ ID NO:251 or SEQ ID NO:252 and the light chain variable region comprises SEQ ID NO:253.
16. The isolated antibody or antigen-binding fragment thereof of claim 13 , wherein the heavy chain variable region comprises SEQ ID NO:251 or SEQ ID NO:252 and the light chain variable region comprises SEQ ID NO:279.
17. The isolated antibody of claim 13 , wherein the antibody is selected from the group consisting of a single chain antibody, an ScFv, a Fab fragment, an Fab′ fragment, an F(ab′)2 fragment, a univalent antibody lacking a hinge region and a whole antibody.
18. The isolated antibody or antigen-binding fragment thereof of claim 13 , wherein said antibody inhibits alternative pathway activation in mammalian blood.
19. A composition comprising the antibody or antigen-binding fragment of claim 13 and a pharmaceutically acceptable excipient.