Recombinant co-expression of vitamin k epoxide reductase subunit 1 to improve vitamin k dependent protein expression

Abstract

The present invention relates to a host organism containing recombinant nucleic acids coding for the vitamin K reductase complex subunit 1 (VKORC1) and recombinant nucleic acids coding for a vitamin K dependent (VKD) protein, wherein both the recombinant VKORC1 and the recombinant VKD protein are expressed in said host organism. Further, the present invention relates to a cell culture system comprising cells which contain said recombinant nucleic acids and to methods for improving the productivity of recombinant VKD protein expression in a host organism being cultured in suitable systems.

1 . A host organism containing a recombinant nucleic acid coding for a vitamin K reductase complex subunit 1 (VKORC1) or a functionally active derivative thereof, and a recombinant nucleic acid coding for a vitamin K dependent (VKD) protein or a functionally active derivative thereof, wherein both the recombinant VKORC1 and the recombinant VKD protein are expressed in said host organism. 
     
     
         2 . The host organism of  claim 1 , wherein either the nucleic acid coding for recombinant VKORC1 or the nucleic acid coding for the recombinant VKD protein or both are expressed via an expression mode selected from the group consisting of induced, transient, and permanent expression. 
     
     
         3 . The host organism of  claim 1 , wherein the host organism is a mammalian cell. 
     
     
         4 . The host organism of  claim 3 , wherein the mammalian cell is a cell derived from a mammalian cell line selected from the group consisting of CHO cells and HEK293 cells. 
     
     
         5 . The host organism of  claim 1 , wherein the recombinant VKD protein is a procoagulant blood factor or a functionally active derivative thereof. 
     
     
         6 . The host organism of  claim 5 , wherein the procoagulant blood factor is selected from the group consisting of factor II, factor VII, factor IX and factor X. 
     
     
         7 . The host organism of  claim 6 , wherein the procoagulant blood factor is human factor IX. 
     
     
         8 . The host organism of  claim 1 , wherein either the nucleic acid coding for VKORC1 or the nucleic acid coding for the VKD protein or both are expressed via an expression mode selected from the group consisting of induced, transient, and permanent expression. 
     
     
         9 .- 20 . (canceled)