Ultrapure transferrin for pharmaceutical compositions

Abstract

The present invention relates to an ultrapure human transferrin, and to methods for manufacturing the ultrapure transferrin. The transferrin may be holo-, apo- or at any desired degree of iron saturation. The invention further relates to the use of ultrapure transferrin as the protein moiety of conjugates, and to pharmaceutical compositions comprising ultra transferrin alone as well as in the form of a conjugate.

1 . A transferrin product obtained by a method which comprises: 
 pre-treating virus-free Cohn's fraction IV.4 for subsequent application on anion exchange chromatography;    subjecting the pre-treated Cohn's fraction IV.4 to a first anion exchange chromatography, under conditions at which the transferrin is adsorbed;    eluting the adsorbed transferrin from the ion-exchange column, followed by concentration and filter sterilizing;    saturating the eluted transferrin with iron to provide iron-containing transferrin;    subjecting the iron-containing transferrin to a second anion exchange chromatography, under conditions at which the transferrin is adsorbed;    eluting the iron-containing transferrin from the ion-exchange column;    concentrating the eluted iron-containing transferrin;    sterilizing the concentrated iron-containing transferrin by filter-sterilization; and    inactivating remaining viruses in the concentrated and sterilized iron-containing transferrin to obtain ultrapure, sterile, non-pyrogenic, virus-free transferrin.    
     
     
         2 . A covalent conjugate between a bioactive moiety and the transferrin product of  claim 1 , wherein the bioactive moiety is selected from the group consisting of a cytotoxic compound, a cytostatic compound, an antisense compound, an anti-viral agent, a specific antibody, an imaging agent and a biodegradable carrier.