Factor H for the Treatment of Chronic Nephropathies and Production thereof

Abstract

The invention is directed to novel uses of Factor H, in particular in antibody-independent chronic nephropathies, e.g. in tubulointerstitial fibrosis (TIF). The invention is further directed to novel large scale manufacturing processes for Factor H.

1 .- 13 . (canceled) 
   
   
       14 . A method of treating antibody-independent chronic nephropathy not causally associated with proteinuria in a patient in need thereof, the method comprising administering an effective amount of Factor H to the patient. 
   
   
       15 . The method of  claim 14 , wherein treatment results in supraphysiological levels of Factor H in the patient's plasma. 
   
   
       16 . The method of  claim 14 , wherein the patient has a Factor H defect. 
   
   
       17 . The method of  claim 16 , wherein plasma levels of Factor H at least 10% above the level of the patient's endogenous defective Factor H are achieved. 
   
   
       18 . The method of  claim 16 , wherein the Factor H defect is a mutation resulting in the absence of Factor H from the patient's plasma. 
   
   
       19 . The method of  claim 16 , wherein the Factor H defect is a mutation in the regulatory domain of Factor H. 
   
   
       20 . The method of  claim 19 , wherein the Factor H is capable of binding to membranes. 
   
   
       21 . The method of  claim 16 , wherein the Factor H defect is a mutation in the recognition domain of Factor H. 
   
   
       22 . The method of  claim 14 , wherein the patient is a human and has a normal human Factor H concentration. 
   
   
       23 . The method of  claim 22 , wherein plasma levels of Factor H at least 10% above the level of the patient's endogenous defective Factor H are achieved. 
   
   
       24 . The method of  claim 14 , wherein the patient suffers from atypical hemolytic uremic syndrome (aHUS) and/or membranoproliferative glomerulonephritis type II (MPGN II). 
   
   
       25 . The method of  claim 24 , wherein the patient suffers from tubulointerstitial fibrosis (TIF) and/or progressive renal failure. 
   
   
       26 . The method of  claim 14 , wherein the Factor H is a recombinant Factor H. 
   
   
       27 . A process for purifying Factor H comprising:
 obtaining a sample of human plasma,   contacting the human plasma sample with ethanol, cooling the sample, and fractionally precipitating the sample,   adsorbing the supernatant of the fractional precipitation on a heparin affinity chromatography column, and   eluting Factor H from the column separately from antithrombin adsorbed on the column.   
   
   
       28 . The process of  claim 27  wherein the sample of human plasma is at least 200 liters. 
   
   
       29 . The process of  claim 28 , wherein the sample of human plasma is at least 500 liters. 
   
   
       30 . The process of  claim 29 , wherein the sample of human plasma is at least 2000 liters. 
   
   
       31 . The process of  claim 26 , wherein the Factor H product is at least 60% pure with respect to contaminating proteins and nucleic acid molecules. 
   
   
       32 . The process of  claim 26 , wherein the Factor H product is free from infectious agents.