Inhibiting activation with human anti-factor c3 antibodies and use thereof

Abstract

A method of inhibiting complement activation mediated by C3b inhibitors in a subject includes administering a C3B inhibitor to the subject to inhibit at least one of C3b binding to factors B and properdin, inhibit C3 cleavage, inhibit the activation of neutrophils, monocytes, platelets, and endothelium; or inhibit the formation of C3a, C5a, and MAC.

1 - 36 . (canceled) 
   
   
       37 . A method of treating tissue damage in a subject associated with complement activation, comprising:
 administering to the subject an amount of an anti-C3b antibody or fragment thereof effective to inhibit at least one of C3 dependent complement activation, complement dependent cellular activation, or complement mediated production of inflammatory mediators, the anti-C3b antibody or fragment thereof inhibiting alternative complement pathway activation without inhibiting classical complement pathway activation.   
   
   
       38 . The method of  claim 37  wherein the anti-C3b antibody or fragment thereof specifically binds to C3b protein sequences involved in C3b binding to properdin or factor B or C3b cleavage from C3. 
   
   
       39 . The method of  claim 37  wherein the antibody or fragment thereof is monoclonal. 
   
   
       40 . The method of  claim 37  wherein the antibody or fragment thereof is a recombinant antibody. 
   
   
       41 . The method of  claim 37  wherein the antibody is a chimeric, humanized or human antibody. 
   
   
       42 . The method of  claim 37  wherein the antibody or fragment thereof inhibits properdin binding to C3b or factor B binding to C3b. 
   
   
       43 . The method of  claim 37  wherein the tissue damage results from or is associated with at least one of a vascular condition, an ischemia-reperfusion injury, atherosclerosis, an inflammatory gastrointestinal disorder, a pulmonary condition, an extracorporeal reperfusion procedure, a musculoskeletal condition, a renal condition, a skin condition, an organ or tissue transplant procedure, a nervous system disorder, a blood disorder, a urogenital condition, diabetes, malignancy, endocrine disorder, or an opthalmologic condition. 
   
   
       44 . The method of  claim 43  wherein the vascular condition comprises at least one of a cardiovascular condition, a cerebrovascular condition, a peripheral vascular condition, a renovascular condition, a mesenteric/enteric vascular condition, revascularization to transplants and/or replants, vasculitis, Henoch-Schonlein purpura nephritis, systemic lupus erythematosus-associated vasculitis, vasculitis associated with rheumatoid arthritis, immune complex vasculitis, Takayasu's disease, dilated cardiomyopathy, diabetic angiopathy, Kawasaki's disease, venous gas embolus (VGE), and restenosis following stent placement, rotational atherectomy or percutaneous transluminal coronary angioplasty (PTCA). 
   
   
       45 . The method of  claim 43 , wherein the ischemia-reperfusion injury is associated with at least one of aortic aneurysm repair, cardiopulmonary bypass, vascular reanastomosis in connection with organ transplants and/or extremity/digit replantation, stroke, myocardial infarction, hemodynamic resuscitation following shock and/or surgical procedures, or an extracorporeal reperfusion procedure. 
   
   
       46 . The method of  claim 43  wherein the extracorporeal reperfusion procedure is selected from the group consisting of hemodialysis, plasmapheresis, leukopheresis, extracorporeal membrane oxygenator (ECMO), heparin-induced extracorporeal membrane oxygenation LDL precipitation (HELP) and cardiopulmonary bypass (CPB). 
   
   
       47 . The method of  claim 37  wherein the musculoskeletal condition is selected from the group consisting of osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, gout, neuropathic arthropathy, psoriatic arthritis, spondyloarthropathy, crystalline arthropathy and systemic lupus erythematosus (SLE). 
   
   
       48 . The method of  claim 43  wherein the opthalmologic condition is age-related macular degeneration. 
   
   
       49 . A method of treating tissue damage in a subject associated with complement activation, comprising:
 administering to the subject an amount of an anti-C3b antibody or fragment thereof effective to inhibit at least one of C3 dependent complement activation, complement dependent cellular activation, or complement mediated production of inflammatory mediators, the anti-C3b antibody or fragment thereof inhibiting alternative complement pathway activation without inhibiting classical complement pathway activation, wherein the anti-C3b antibody or fragment thereof specifically binding to C3b protein sequences involved in C3b binding to properdin or factor B or C3b cleavage from C3 and wherein the anti-C3b antibody or fragment thereof inhibits alternative complement pathway activation without inhibiting classical complement pathway activation.   
   
   
       50 . The method of  claim 49  wherein the antibody or fragment thereof is monoclonal. 
   
   
       51 . The method of  claim 49  wherein the antibody is a chimeric, humanized or human antibody. 
   
   
       52 . The method of  claim 49  wherein the antibody or fragment thereof inhibits properdin binding to C3b or factor B binding to C3b. 
   
   
       53 . The method of  claim 49  wherein the tissue damage results from or is associated with at least one of a vascular condition, an ischemia-reperfusion injury, atherosclerosis, an inflammatory gastrointestinal disorder, a pulmonary condition, an extracorporeal reperfusion procedure, a musculoskeletal condition, a renal condition, a skin condition, an organ or tissue transplant procedure, a nervous system disorder, a blood disorder, a urogenital condition, diabetes, malignancy, endocrine disorder, or an opthalmologic condition. 
   
   
       54 . A method of treating a complement mediated disorder in a subject, comprising:
 administering to the subject an amount of an anti-C3b antibody or fragment thereof effective to inhibit at least one of C3 dependent complement activation, complement dependent cellular activation, or complement mediated production of inflammatory mediators, the anti-C3b antibody or fragment thereof inhibiting alternative complement pathway activation without inhibiting classical complement pathway activation, wherein the anti-C3b antibody or fragment thereof specifically binding to C3b protein sequences involved in C3b binding to properdin or factor B or C3b cleavage from C3 and wherein the anti-C3b antibody or fragment thereof inhibits alternative complement pathway activation without inhibiting classical complement pathway activation.   
   
   
       55 . The method of  claim 54  wherein the antibody or fragment thereof inhibits properdin binding to C3b or factor B binding to C3b. 
   
   
       56 . The method of  claim 55  wherein the disorder results from or is associated with at least one of a vascular condition, an ischemia-reperfusion injury, atherosclerosis, an inflammatory gastrointestinal disorder, a pulmonary condition, an extracorporeal reperfusion procedure, a musculoskeletal condition, a renal condition, a skin condition, an organ or tissue transplant procedure, a nervous system disorder, a blood disorder, a urogenital condition, diabetes, malignancy, endocrine disorder, or an opthalmologic condition.