Method for preparing a concentrate of factor xi

Abstract

The invention concerns a concentrate of human Factor XI having high specific activity prepared using a method comprising a filtration-adsorption step and a chromatography step on cation exchange resin. The concentrate obtained is fully adapted for therapeutic use as substitution therapy in cases of Factor XI deficiency.

1 .- 10 . (canceled) 
     
     
         11 . A Factor XI (FXI) composition obtainable by a method comprising,
 a) filtration-adsorption of a supernatant of human plasma cryoprecipitate using a filter comprising cellulose and perlites and a charged resin, wherein the filter has a grade ranging from 0.1 to 0.4 μm, wherein the filtration-adsorption step comprises passing the supernatant of plasma cryoprecipitate through the filter to adsorb FXI on the filter, and desorbing or eluting the adsorbed FXI; and   b) chromatography of the product of step a) on a cation exchange resin to obtain a solution of FXI.   
     
     
         12 . The composition according to  claim 11  wherein the FXI adsorbed on the filter is desorbed or eluted using a solution adjusted to a pH of 5.5 to 6.5 comprising sodium citrate, disodium phosphate, potassium phosphate, disodium EDTA and sodium chloride, the concentration of said sodium chloride being higher than 0.5 M. 
     
     
         13 . The composition according to  claim 12  wherein step a) comprises washing of the filter prior to eluting the adsorbed FXI, using a buffer adjusted to a pH of 5.5 to 6.5 comprising sodium citrate, disodium phosphate, potassium phosphate and sodium chloride, the concentration of said sodium chloride being equal to lower than 0.5 M. 
     
     
         14 . The composition according to  claim 11  comprising an additional step for viral inactivation between step a) and step b), and/or a virus removal step after step b). 
     
     
         15 . The composition according to  claim 11  wherein the cation exchange resin of step b) is equilibrated with a buffer adjusted to a pH of 5.5 to 6.5 comprising sodium citrate, sodium chloride, lysine and arginine. 
     
     
         16 . The composition according to  claim 11  wherein the cation exchange resin of step b) is loaded with the FXI resulting from step a), then washed with a buffer adjusted to a pH of 6.1 to 6.9 comprising sodium citrate, disodium phosphate, potassium phosphate, sodium chloride, lysine and arginine. 
     
     
         17 . The composition according to  claim 11  wherein the solution of FXI obtained from step b) is stabilised through the addition of 0.5 to 3 IU Antithrombin III, 0.5 to 4 IU of heparin and 0.5 to 2 IU of C1-inhibitor per 100 IU of FXI. 
     
     
         18 . The composition according to  claim 11  further comprising packaging the stabilised solution of FXI as pharmaceutical product. 
     
     
         19 . The composition according to  claim 11  further comprising lyophilisation of the solution of FXI obtained from step b).