Methods for Treating Disseminated Intravascular Coagulation by Inhibiting MASP-2 Dependent Complement Activation

Abstract

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.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows: 
     
         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.