Methods for treating conditions associated with 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. 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 adverse effects of transplantation in a subject that has undergone, is undergoing, or will undergo an organ or tissue transplant procedure comprising administering to the subject, or pretreating the organ or tissue to be transplanted with, a composition comprising a monoclonal MASP-2 inhibitory antibody, or antigen-binding fragment thereof, that specifically binds to a portion of SEQ ID NO:6 and inhibits MASP 2 dependent complement activation. 
     
     
         2 . The method of Claim I, wherein the monoclonal MASP-2 inhibitory antibody, or antigen-binding 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. 
     
     
         3 . The method of  claim 1 , wherein the monoclonal MASP-2 inhibitory antibody, or antigen-binding fragment thereof, selectively inhibits MASP-2 dependent complement activation while leaving C1q-dependent classical complement pathway activation functionally intact. 
     
     
         4 . The method of  claim 1 , wherein the monoclonal MASP-2 inhibitory antibody has reduced effector function. 
     
     
         5 . The method of  claim 1 , wherein the monoclonal MASP-2 inhibitory antibody or antigen-binding fragment thereof is recombinant, chimeric, humanized or human. 
     
     
         6 . The method of  claim 1 , wherein the organ or tissue transplant procedure is selected from the group consisting of organ allotransplantation, organ xenotransplantation and tissue graft. 
     
     
         7 . The method of  claim 6 , wherein the subject has undergone, is undergoing, or will undergo a tissue graft. 
     
     
         8 . The method of  claim 7 , wherein the tissue graft is selected from the group consisting of bone marrow, valve(s) and tendon(s). 
     
     
         9 . The method of  claim 1 , wherein the subject has undergone, is undergoing, or will undergo an organ transplant. 
     
     
         10 . The method of  claim 9 , wherein the organ transplant procedure is organ xenotransplantation. 
     
     
         11 . The method of  claim 10 , wherein the method further comprises administering to the subject an additional agent to prevent hyperacute xenograft rejection. 
     
     
         12 . The method of  claim 9 , wherein the subject has undergone, is undergoing, or will undergo a lung transplant procedure. 
     
     
         13 . The method of  claim 9 , wherein the subject has undergone, is undergoing, or will undergo a heart transplant. 
     
     
         14 . The method of  claim 9 , wherein the subject has undergone, is undergoing, or will undergo a liver transplant. 
     
     
         15 . The method of  claim 9 , wherein the subject has undergone, is undergoing, or will undergo a pancreas transplant. 
     
     
         16 . The method of  claim 9 , wherein the subject has undergone, is undergoing, or will undergo a cornea transplant. 
     
     
         17 . The method of  claim 10  wherein the subject has undergone, is undergoing, or will undergo a kidney transplant. 
     
     
         18 . The method of  claim 1 , wherein the method prevents or reduces an inflammatory reaction resulting from said tissue or organ transplantation. 
     
     
         19 . The method of  claim 1 , wherein the composition is administered to the subject by at least one of intra-arterial, intravenous, intramuscular, or subcutaneous administration. 
     
     
         20 . The method of claim I, wherein the method comprises pretreating the organ or tissue to be transplanted with the composition comprising the monoclonal MASP-2 inhibitory antibody, or antigen-binding fragment thereof, that specifically binds to a portion of SEQ ID NO:6 and selectively inhibits MASP 2 dependent complement activation without substantially inhibiting C1q-dependent complement activation. 
     
     
         21 . The method of  claim 1 , wherein the method comprises administering the composition to the subject prior to the transplant procedure. 
     
     
         22 . The method of  claim 1 , wherein the method comprises administering the composition to the subject during the transplant procedure. 
     
     
         23 . The method of  claim 1 , wherein the method comprises administering the composition to the subject during the acute period following the transplant procedure. 
     
     
         24 . The method of  claim 1 , wherein the method comprises administering the composition to the subject as a long term post-transplantation therapy. 
     
     
         25 . The method of  claim 11  wherein the subject has undergone, is undergoing, or will undergo a kidney transplant.