Variants of human recombinant interferon-.gamma....

C - Chemistry – Metallurgy – 07 – K

Patent

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C07K 14/57 (2006.01) A61K 38/21 (2006.01) C12N 1/21 (2006.01) C12N 7/00 (2006.01) C12N 15/23 (2006.01) C12N 15/63 (2006.01) G01N 33/68 (2006.01) C07K 1/16 (2006.01)

Patent

CA 2232264

The invention concerns variants of recombinant human interferon-.gamma. (rhu-IFN-.gamma.) having increased heat-stability. Proceeding from rhu-IFN- .gamma., at least one of the following amino acid pairs is changed into cysteine in the amino acid sequence of the polypeptide monomer. Glu8 and Ser7O, Ala18 and His112, Lys81 and Leu121, and Gln49 and Leu96. Additionally, the C-terminal end of the polypeptide can be shortened by between 1 and 10 amino acids. The novel proteins according to the invention have greater heat-stability than the unchanged rhu-IFN-.gamma. without any loss in biological activity. The invention further concerns the preparation of the oligonucleotides, vectors and micro-organisms necessary for producing the proteins according to the invention. Finally, the invention concerns a process for the preparation of the proteins and uses thereof.

L'invention concerne des variantes de l'interféron-.gamma. (rhu-IFN-.gamma.) humain recombiné, à stabilité thermique renforcée. A partir de rhu-IFN-.gamma., au moins une des paires suivantes d'aminoacides a été convertie en cystéine dans la séquence d'aminoacide du monomère polypeptidique: Glu8 et Ser70, Ala18 et His112, Lys81 et Leu121, ou Gln49 et Leu96. L'extrémité C-terminale du polypeptide peut également être raccourcie d'1 à 10 aminoacides. Ces nouvelles protéines obtenues selon l'invention sont thermiquement plus stables que le rhu-IFN-.gamma. non modifié, sans diminution de l'activité biologique. L'invention concerne en outre la préparation d'oligonucléides, de vecteurs et de micro-organismes nécessaires pour obtenir lesdites protéines. L'invention concerne par ailleurs un procédé de préparation desdites protéines et leurs utilisations.

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