Compositions and Methods of Inhibiting MASP-1 and/or MASP-2 and/or MASP-3 for the Treatment of Various Diseases and Disorders
In one aspect, the invention provides methods and compositions for inhibiting MASP-3-dependent complement activation in a subject suffering from or at risk for developing, a disease or disorder selected from the group consisting of paroxysmal nocturnal hemoglobinuria, age-related macular degeneration, arthritis, disseminated intravascular coagulation, thrombotic microangiopathy, asthma, dense deposit disease, pauci-immune necrotizing crescentic glomerulonephritis, traumatic brain injury, aspiration pneumonia, endophthalmitis, neuromyelitis optica and Behcet's disease by administering to the subject a composition comprising an amount of a MASP-3 inhibitory agent in an amount effective to inhibit MASP-3-dependent complement activation. In some embodiments, the subject is administered a MASP-2 inhibitory agent and a MASP-1 inhibitory agent, a MASP-2 inhibitory agent and a MASP-3 inhibitory agent administered, a MASP-3 inhibitory agent and a MASP-1 inhibitory agent, or a MASP-1 inhibitory agent, a MASP-2 inhibitory agent and a MASP-3 inhibitory agent.
1 - 47 . (canceled)
48 . A method of inhibiting MASP-2-dependent complement activation in a subject suffering from, or at risk for developing a disease or disorder selected from the group consisting of dense deposit disease, pauci-immune necrotizing crescentic glomerulonephritis, traumatic brain injury, aspiration pneumonia, endophthalmitis, neuromyelitis optica and Behcet's disease, comprising administering to the subject a composition comprising an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2 dependent complement activation.
49 . The method of claim 48 , wherein the MASP-2 inhibitory agent is a MASP-2 antibody or fragment thereof.
50 . The method of claim 48 , wherein the MASP-2 inhibitory agent is a MASP-2 monoclonal antibody, or fragment thereof that specifically binds to a portion of SEQ ID NO:5.
51 . The method of claim 50 , wherein the MASP-2 antibody is a chimeric, humanized or human antibody.
52 .- 55 . (canceled)
56 . The method of claim 48 , wherein the composition is administered systemically.
57 . The method of claim 56 , wherein the composition is administered subcutaneously, intra-muscularly, intravenously, intra-arterially or as an inhalant.
58 . The method of claim 48 , wherein the subject is suffering from, or at risk for developing dense deposit disease.
59 . The method of claim 48 , wherein the subject is suffering from, or at risk for developing pauci-immune necrotizing crescentic glomerulonephritis.
60 . The method of claim 48 , wherein the subject is suffering from, or at risk for developing traumatic brain injury.
61 . The method of claim 48 , wherein the subject is suffering from, or at risk for developing aspiration pneumonia.
62 . The method of claim 48 , wherein the subject is suffering from, or at risk for developing endophthalmitis.
63 . The method of claim 48 , wherein the subject is suffering from, or at risk for developing neuromyelitis optica.
64 . The method of claim 48 , wherein the subject is suffering from, or at risk for developing Behcet's disease.