Methods of treating antibody-mediated rejection in organ transplant patients with c1-esterase inhibitor

Abstract

A method and composition for treating or preventing antibody-mediated rejection (AMR) of a transplanted organ are provided.

1 . A C1 esterase inhibitor (C1 -INH) for use in a method of treating antibody-mediated rejection (AMR) of an organ allograft in a patient in need thereof. 
     
     
         2 . A C1-INH for use according to  claim 1 , wherein the method comprises early and/or short term duration administration of the inhibitor. 
     
     
         3 . A C1-INH for use according to  claim 1  or  2  wherein the method comprises administration of the inhibitor in an amount sufficient to provide long-lasting therapeutic effect. 
     
     
         4 . A C1-INH for use according to any preceding claim, wherein the patient has been subjected to plasmapheresis or is currently subject to plasmapheresis. 
     
     
         5 . A C1-INH for use according to any preceding claim wherein the method further comprises subjecting the patient to plasmapheresis. 
     
     
         6 . A C1-INH for use according to any preceding claim, wherein the method further comprises administering fresh frozen plasma. 
     
     
         7 . A C1-INH for use according to any preceding claim, wherein the method further comprises administering intravenous immunoglobulin. 
     
     
         8 . A C1-INH for use according to any preceding claim, wherein the method further comprises administering an anti-lymphocyte preparation, rituximab, bortezomib, eculizumab, or a combination thereof. 
     
     
         9 . A C1-INH for use according to any preceding claim, wherein the organ is a solid organ. 
     
     
         10 . A C1-INH for use according to  claim 9 , wherein the solid organ is selected from the group consisting of kidney, pancreas, intestine, heart, lung, liver, and a combination thereof 
     
     
         11 . A C1-INH for use according to any one of the preceding claims, wherein the organ is a kidney. 
     
     
         12 . A C1-INH for use according to  claim 11 , wherein the method further comprises administering intravenous immunoglobulin and said patient has been subjected to plasmapheresis or is currently subject to plasmapheresis. 
     
     
         13 . A C1-INH and an additional biologically active agent selected from the group consisting of an anti-lymphocyte preparation, rituximab, bortezomib, eculizumab, immunoglobulin (Ig), and a combination thereof as a combined preparation for concurrent or sequential use in a method of treatment of antibody-mediated rejection (AMR) of an organ allograft in a patient in need thereof 
     
     
         14 . The C1-INH and an additional biologically active agent for use according to  claim 13 , wherein the additional biologically active agent is immunoglobulin, preferably intravenous immunoglobulin. 
     
     
         15 . The C1-INH and an additional biologically active agent for use according to  claim 13  or  14  wherein the organ is as defined in any one of  claims 9  to  11 , preferably a kidney. 
     
     
         16 . The C1-INH and an additional biologically active agent for use according to any one of  claims 13  to  15 , wherein said patient has been subjected to plasmapheresis or is currently subject to plasmapheresis. 
     
     
         17 . The C1-INH and an additional biologically active agent for use according to any one of  claims 13  to  16  said method further comprising subjecting the patient to plasmapheresis. 
     
     
         18 . The C1-INH and an additional biologically active agent for use according to any one of  claims 13  to  15 , wherein the wherein the organ is a kidney, the additional biologically active agent is intravenous immunoglobulin and said patient has been subjected to plasmapheresis or is currently subject to plasmapheresis. 
     
     
         19 . A kit comprising:
 (i) C1-INH; and   (ii) an additional biologically active agent selected from the group consisting of an anti-lymphocyte preparation, rituximab, bortezomib, eculizumab, immunoglobulin (Ig), and a combination thereof,   wherein said components (i) and (ii) are packaged for concurrent or sequential administration to a patient, optionally for use in a method of treatment of antibody-mediated rejection (AMR) of an organ allograft in the patient.   
     
     
         20 . The kit of  claim 19 , wherein the method further comprises subjecting the patient to plasmapheresis. 
     
     
         21 . A method of treating antibody-mediated rejection (AMR) of an organ allograft in a patient in need thereof, the method comprising early and/or short term duration administration of a therapeutically effective amount of a C1 esterase inhibitor (C1-INH), wherein the therapeutically effective amount of the C1-INH is sufficient to provide long-lasting therapeutic effect. 
     
     
         22 . The method of  claim 21 , further comprising subjecting the patient to plasmapheresis. 
     
     
         23 . The method according to  claim 21  or  22 , further comprising administering fresh frozen plasma. 
     
     
         24 . The method according to any one of  claims 21  to  23 , further comprising administering intravenous immunoglobulin. 
     
     
         25 . The method according to any one of  claims 21  to  24 , further comprising administering an anti-lymphocyte preparation, rituximab, bortezomib, eculizumab, or a combination thereof. 
     
     
         26 . The method according to any one of  claims 21  to  25 , wherein the organ is a solid organ. 
     
     
         27 . The method according to  claim 26 , wherein the solid organ is selected from the group consisting of kidney, pancreas, intestine, heart, lung, liver, and a combination thereof. 
     
     
         28 . The method according to any one of  claims 21  to  27 , wherein the organ is a kidney. 
     
     
         29 . A pharmaceutical composition comprising a C1-esterase inhibitor (C1-INH); an additional biologically active agent; and a pharmaceutically acceptable carrier medium. 
     
     
         30 . The pharmaceutical composition of  claim 29 , wherein the biologically active agent is selected from the group consisting of an anti-lymphocyte preparation, rituximab, bortezomib, eculizumab, immunoglobulin (Ig), and a combination thereof. 
     
     
         31 . A method of treating antibody-mediated rejection (AMR) in a patient receiving or who has received a kidney transplant, the method comprising administering sufficient therapeutic amounts of intravenous immunoglobulin and a C1-INH inhibitor to a patient who has or is currently subject to plasmapheresis