Methods for treating conditions associated with MASP-2 dependent complement activation
View Patent ↗In one aspect, the invention provides methods of inhibiting the effects of MASP-2-dependent complement activation in a living subject. The methods comprise the step of administering, to a subject in need thereof, an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation. In some embodiments, the MASP-2 inhibitory agent inhibits cellular injury associated with MASP-2-mediated alternative complement pathway activation, while leaving the classical (C1q-dependent) pathway component of the immune system intact. In another aspect, the invention provides compositions for inhibiting the effects of lectin-dependent complement activation, comprising a therapeutically effective amount of a MASP-2 inhibitory agent and a pharmaceutically acceptable carrier.
1. A method of inhibiting MASP-2-dependent complement activation in a subject suffering from or age-related macular degeneration, comprising administering to the subject an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation, wherein the MASP-2 inhibitory agent comprises an anti-MASP-2 antibody or fragment thereof that specifically binds to a portion of SEQ ID NO:6.
2. The method of claim 1 , wherein the MASP-2 inhibitory agent specifically binds to a polypeptide comprising SEQ ID NO:6.
3. The method of claim 1 , wherein the MASP-2 inhibitory agent specifically binds to a polypeptide comprising SEQ ID NO: 6 with an affinity of at least 10 times greater than it binds to a different antigen in the complement system.
4. The method of claim 1 , wherein the antibody or fragment thereof is monoclonal.
5. The method of claim 1 , wherein the antibody or fragment thereof is polyclonal.
6. The method of claim 1 , wherein the antibody or fragment thereof is a recombinant antibody.
7. The method of claim 1 , wherein the antibody has reduced effector function.
8. The method of claim 1 , wherein the antibody is a chimeric, humanized or human antibody.
9. The method of claim 1 , wherein the antibody is produced in a MASP-2 deficient transgenic animal.
10. The method of claim 1 , wherein the MASP-2 inhibitory agent effective to selectively inhibit inhibits MASP-2-dependent complement activation without substantially inhibiting C1q-dependent complement activation.
11. A method of treating a subject suffering from or age-related macular degeneration comprising administering a composition comprising an amount of an anti-MASP-2 antibody or fragment thereof that specifically binds to a portion of SEQ ID NO:6 effective to inhibit MASP-2-dependent complement activation.
12. The method of claim 11 , wherein the composition comprises an amount of an anti-MASP-2 antibody or fragment thereof effective to selectively inhibit MASP-2 dependent complement activation without substantially inhibiting C1q-dependent complement activation.
13. The method of claim 11 , wherein the anti-MASP-2 antibody or fragment thereof specifically binds to a polypeptide comprising SEQ ID NO:6.
14. The method of claim 13 , wherein the anti-MASP-2 antibody or fragment thereof specifically binds to a polypeptide comprising SEQ ID NO:6 with an affinity of at least 10 times greater than it binds to a different antigen in the complement system.
15. The method of claim 11 , wherein the anti-MASP-2 antibody or fragment thereof is monoclonal.
16. The method of claim 11 , wherein the anti-MASP-2 antibody or fragment thereof is recombinant.
17. The method of claim 11 , wherein the anti-MASP-2 antibody or fragment thereof has reduced effector function.
18. The method of claim 11 , wherein the anti-MASP-2 antibody or fragment thereof is chimeric, humanized or human.
19. The method of claim 11 , wherein the composition further comprises a pharmaceutical carrier.
20. The method of claim 11 , wherein the composition is administered to the eye.
21. The method of claim 11 , wherein the composition is administered systemically.