Methods for Treating Disseminated Intravascular Coagulation by Inhibiting 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. In one embodiment, the invention provides methods of treating a subject suffering from a complement mediated coagulation disorder, such as disseminated intravascular coagulation. 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 systemic coagulation in a subject suffering from a complement-mediated coagulation disorder, comprising administering to the subject an amount of a MASP 2 inhibitory agent effective to selectively inhibit MASP 2 dependent complement activation.
2 . The method of claim 1 , wherein the MASP-2 inhibitory agent is a MASP-2 antibody or fragment thereof.
3 . The method of claim 2 , wherein the MASP-2 antibody or fragment thereof specifically binds to a portion of SEQ ID NO:6.
4 . The method of claim 2 , wherein the MASP-2 antibody or fragment thereof is monoclonal.
5 . The method of claim 2 , wherein the MASP-2 antibody or fragment thereof is a recombinant antibody.
6 . The method of claim 2 , wherein the antibody is a chimeric, humanized or human antibody.
7 . The method of claim 2 , wherein the antibody has reduced effector function.
8 . The method of claim 1 , wherein the MASP-2 inhibitory agent selectively inhibits MASP-2-dependent complement activation without substantially inhibiting C1q-dependent complement activation.
9 . 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.
10 . The method of claim 1 , wherein the MASP-2 inhibitory agent is administered systemically to the subject.
11 . The method of claim 1 , wherein the complement-mediated coagulation disorder is secondary to a malignancy.
12 . The method of claim 1 , wherein the complement-mediated coagulation disorder is secondary to a transplant rejection.
13 . The method of claim 1 , wherein the complement-mediated coagulation disorder is secondary to a transfusion reaction,.
14 . The method of claim 1 , wherein the complement-mediated coagulation disorder is secondary to an obstetric complication.
15 . The method of claim 1 , wherein the complement-mediated coagulation disorder is secondary to a vascular aneurysm.
16 . The method of claim 1 , wherein the complement-mediated coagulation disorder is secondary to hepatic failure.
17 . The method of claim 1 , wherein the complement-mediated coagulation disorder is secondary to heat stroke.
18 . The method of claim 1 , wherein the complement-mediated coagulation disorder is secondary to a burn.
19 . The method of claim 1 , wherein the complement-mediated coagulation disorder is secondary to radiation exposure.
20 . The method of claim 1 , wherein the complement-mediated coagulation disorder is secondary to a severe toxic reaction.
21 . The method of claim 1 , wherein the complement-mediated coagulation disorder is secondary to sepsis.
22 . The method of claim 1 , wherein the complement-mediated coagulation disorder is secondary to an infection.
23 . The method of claim 1 , wherein the complement-mediated coagulation disorder is secondary to trauma.
24 . The method of claim 1 , wherein the complement-mediated coagulation disorder is secondary to surgery.