Factor VII Composition Having a Substantially Homogeneous Isoelectric Point

1 . A factor VII composition wherein the factor VII molecules have a substantially homogeneous isoelectric point.

2 . A factor VII composition wherein, among all the N-glycan forms of the factor VII of the composition, at least 60% of said N-glycan forms are monocharged, and at least 80% of said molecules have γ-carboxylation on 9 residues of glutamic acid.

3 . The composition according to claim 2 , wherein, at least 65%, preferably at least 70%, preferably at least 80% of the N-glycan forms of the factor VII of the composition are monocharged.

4 . The composition according to one of claims 2 to 3 , wherein among all the factor VII molecules of the composition, at least 85%, preferably 85% to 100%, preferably 90% to 100%, preferably from 95% to 100% of said molecules have γ-carboxylation on 9 residues of glutamic acid.

5 . The composition according to claim 4 , wherein the γ-carboxylation level present on the residue of glutamic acid 35 (Glu 35 ) is less than 20%, preferably less than 15%, preferably less than 10%.

6 . The factor VII composition according to one of claims 1 to 5 , wherein at least 60% of the N-glycan forms of the factor VII of the composition are monosialylated complexes.

7 . The factor VII composition according to one of claims 1 to 5 , wherein at least 10%, preferably at least 15%, preferably at least 20%, preferably at least 25% of the N-glycan forms of the factor VII of the composition are high Mannose/hybrid.

8 . The composition according to one of claims 1 to 7 , wherein at least 90%, preferably at least 95% of the factor VII molecules of the composition have an isoelectric point comprised in a pH unit interval of less than 1.2.

9 . The composition according to one of claims 1 to 8 , wherein at least 50%, preferably at least 55%, preferably 60% of the factor VII molecules of the composition have an isoelectric point comprised in a pH unit interval of less than 1; preferably less than 0.5, preferably less than 0.4.

10 . The composition according to one of claims 1 to 9 , wherein the factor VII is recombinant or transgenic.

11 . The composition according to one of claims 1 to 10 , wherein the factor VII of the composition is produced by transgenic rabbits.

12 . The composition according to one of claims 1 to 11 , wherein the factor VII is an activated factor VII.

13 . The factor VII composition according to any of claims 1 to 12 , for use in the treatment of bleeding episodes.

14 . The factor VII composition according to any of claims 1 to 12 , for use in preventing hemorrhages occurring during surgical operations or invasive procedures.

15 . The factor VII composition according to any one of claims 1 to 14 obtainable by a method comprising the steps of:

(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 the beta-casein promoter,

(b) transferring the embryos obtained in step a) into the 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 said non-human mammal, and

(e) purifying the factor VII present in the milk collected.

16 . A method for formulating an activated factor VII composition according to any of claims 1 to 15 , said method comprising the mixing of the composition of activated factor VII with a buffer solution, the adjustment of the pH if required, filtration and then drying if necessary for obtaining the solid form.

17 . The formulation method according to claim 16 , wherein the steps for mixing the composition of the activated factor VII with a buffer solution is applied in chromatography of the gel filtration type.

18 . The formulation method according to one of claims 16 to 17 , wherein the buffer solution comprises one or several of the constituents selected from:

a salt, preferably a citrate salt, preferably trisodium citrate;

an amino acid or a hydrophilic amino acid salt, preferably a hydrophilic amino acid salt, preferably arginine hydrochloride and/or lysine hydrochloride;

an amino acid or a hydrophobic amino acid salt, preferably a hydrophobic amino acid, preferably isoleucine and/or glycine.

19 . The formulation method according to any of claims 16 to 18 , said method further comprising a step for filtering the formulated factor VII composition.

20 . The formulation method according to one of claims 16 to 18 , said method further comprising a step for freeze drying the formulated factor VII composition.