Factor VII composition having a substantially homogenous isoelectric point

A method of making a composition comprising factor VII molecules having a substantially homogeneous isoelectric point, said method comprising:

• (a) inserting a DNA sequence comprising a gene encoding for factor VII in an embryonic non-human mammal, said gene being under the transcriptional control of a beta-casein promoter,
• (b) transferring the embryos obtained in step a) into an oviduct of a female non-human mammal so that it develops into an adult mammal,
• (c) inducing lactation in the adult non-human mammal obtained in step b) of the female type or in a female descendant of the non-human mammal wherein the gene and the promoter are present in its genome,
• (d) collecting milk of the lactating non-human mammal, and
• wherein the female non-human mammal is a rabbit,
• wherein among all N-glycan forms of the factor VII molecules, between 70% and 80% of the N-glycan forms are monocharged and between 15% and 25% of the N-glycan forms are bicharged,
• wherein at least 80% of the factor VII molecules have γcarboxylation on 9 residues of glutamic acid, and
• wherein the factor VII originated from transgenic rabbits produced by microinjection of an expression vector comprising a beta-globin insulating sequence from chicken, a control region of goat beta-casein at 5′, an optimized cDNA sequence for expression in mammal cells coding for human FVII, a non-translated region of beta-casein at 3′
• (e) purifying factor VII present in the collected milk.