C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/24 (2006.01) A01K 67/027 (2006.01) A61K 38/20 (2006.01) C07K 1/22 (2006.01) C07K 14/54 (2006.01) C07K 14/715 (2006.01) G01N 33/68 (2006.01) A61K 38/00 (2006.01)
Patent
CA 2372566
The invention relates to methods for the stabilisation of cytokines and to cytokines generated by such methods. The methods of the invention involve mutating the amino acid sequence of a cytokine so as to remove solvent-exposed hydrophobic residues, and/or mutating the amino acid sequence of the cytokine so as to stabilise one or more secondary structure elements in the molecule. These steps have the effect of destabilising intermediates that are formed during the folding process, relative to the stability of the cytokine in its naturally folded state, so increasing the yield of the cytokine as produced in vitro.
La présente invention concerne des procédés de stabilisation de cytokines et des cytokines produites grâce à ces procédés. Les procédés de l'invention font intervenir la mutation de la séquence d'acides aminés d'une cytokine de manière à éliminer les résidus hydrophobes exposés aux solvants et/ou la mutation de la séquence d'acides aminés de la cytokine de manière à stabiliser un ou plusieurs éléments structurels secondaires dans la molécule. Ces étapes ont pour effet de déstabiliser les intermédiaires qui sont produits durant le processus de repliement, par rapport à la stabilité de la cytokine dans son état naturellement replié, de sorte que la quantité de cytokine produite in vitro se trouve augmentée.
Domingues Helena
Oschkinat Hartmut
Peters Joerg
Serrano Luis
Bayer Ag
Bayer Schering Pharma Aktiengesellschaft
European Molecular Biology Laboratory
Kirby Eades Gale Baker
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