Proteolytically cleavable fusion protein comprising a blood...

Details Proteolytically cleavable fusion protein comprising a blood... Proteolytically cleavable fusion protein comprising a blood...

C - Chemistry, Metallurgy

07

K

C07K 19/00 (2006.01) C12N 15/62 (2006.01)

Patent

CA 2655248

The invention relates to therapeutic fusion proteins in which a coagulation factor is fused to a half-life enhancing polypeptide, and both are connected by a linker peptide that is proteolytically cleavable. The cleavage of such linkers liberates the coagulation factor from any activity-compromising steric hindrance caused by the half-life enhancing polypeptide and, thereby, allows the generation of fusion proteins with high molar specific activity when tested in coagulation-related assays. Furthermore, the fact that the linker is cleavable can enhance the rates of inactivation and/or elimination after proteolytic cleavage of the peptide linker compared to the corresponding therapeutic fusion protein linked by the non- cleavable linker having the amino acid sequence GGGGGGV.

L'invention concerne des protéines de fusion thérapeutiques qui contiennent un facteur de coagulation fusionné à un polypeptide prolongateur de demi-vie, les deux entités étant réunies par un peptide lieur susceptible de subir un clivage protéolytique. Le clivage de tels lieurs libère le facteur de coagulation de toute entrave stérique compromettant l'activité due au polypeptide prolongateur de demi-vie et il permet ainsi la génération de protéines de fusion dotées d'une activité molaire spécifique élevée, comme l'indiquent des essais relatifs à la coagulation. Le fait, en outre, que le lieur puisse être clivé peut augmenter les vitesses d'inactivation et/ou d'élimination du peptide lieur après le clivage protéolytique par rapport à la protéine de fusion thérapeutique correspondante liée par le lieur non clivable, dont la séquence d'acides aminés est GGGGGGV.

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