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 inhibiting adverse effects of transplantation in a subject that has undergone, is undergoing, or will undergo a lung transplant procedure comprising administering to the subject, or pretreating the lung 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 1 , 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 transplant procedure is selected from the group consisting of organ allotransplantation or a tissue graft.
7 . The method of claim 1 , wherein the subject has undergone, is undergoing, or will undergo a lung transplant.
8 . The method of claim 1 , wherein the method prevents or reduces an inflammatory reaction resulting from said lung transplantation.
9 . 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.
10 . The method of claim 1 , wherein the method comprises pretreating the lung 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.
11 . The method of claim 1 , wherein the method comprises administering the composition to the subject prior to the transplant procedure.
12 . The method of claim 1 , wherein the method comprises administering the composition to the subject during the transplant procedure.
13 . The method of claim 1 , wherein the method comprises administering the composition to the subject during the acute period following the transplant procedure.
14 . The method of claim 1 , wherein the method comprises administering the composition to the subject as a long term post-transplantation therapy.