Methods for Treating Conditions Associated with MASP-2 Dependent Complement Activation
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 treating a subject suffering from refractory thrombotic thrombocytopenic purpura (TTP) comprising administering to the subject a composition comprising an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2 dependent complement activation.
2 . The method of claim 1 , wherein the composition is administered subcutaneously.
3 . The method of claim 1 , further comprising periodically determining the level of at least one complement factor, wherein the determination of a reduced level of the at least one complement factor in comparison to a standard value or a healthy subject is indicative of the need for continued treatment with the composition.
4 . The method of claim 1 , wherein the MASP-2 inhibitory agent is an anti-MASP-2 antibody, or antigen-binding fragment thereof.
5 . The method of claim 4 , wherein the MASP-2 inhibitory agent is an anti-MASP-2 monoclonal antibody, or antigen-binding fragment thereof that specifically binds to a portion of SEQ ID NO:6.
6 . The method of claim 5 , wherein the MASP-2 inhibitory antibody selectively inhibits MASP-2-dependent complement activation without substantially inhibiting the C1q-dependent complement pathway.
7 . The method of claim 5 , wherein the monoclonal antibody or antigen-binding fragment thereof is human or humanized.
8 . The method of claim 5 , wherein the monoclonal antibody or antigen-binding fragment thereof is a recombinant antibody.
9 . The method of claim 1 , wherein the composition is administered systemically.
10 . The method of claim 9 , wherein the composition is administered subcutaneously.