Chromatographic method for high yield purification and viral...

C - Chemistry – Metallurgy – 07 – K

Patent

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C07K 16/00 (2006.01) A61K 39/395 (2006.01) A61L 2/00 (2006.01) C07K 1/36 (2006.01) C07K 16/06 (2006.01) C12N 7/06 (2006.01)

Patent

CA 2239237

An improved process for the purification of antibodies from human plasma or other sources is disclosed. The process involves suspension of the antibodies at pH 3.8 to 4.5 followed by addition of caprylic acid and a pH shift to pH 5.0 to 5.2. A precipitate of contaminating proteins, lipids and caprylate forms and is removed, while the majority of the antibodies remain in solution. Sodium caprylate is again added to a final concentration of not less than about 15 mM. This solution is incubated for 1 hour at 25°C to effect viral inactivation. A precipitate (mainly caprylate) is removed and the clear solution is diluted with purified water to reduce ionic strength. Anion exchange chromatography using two different resins is utilized to obtain an exceptionally pure IgG with subclass distribution similar to the starting distribution. The method maximizes yield and produces a gamma globulin with greater than 99% purity.

On décrit un procédé amélioré de purification d'anticorps à partir de plasma humain ou d'autres sources. Le procédé comprend la suspension de l'anticorps à un pH compris entre 3,8 et 4,5, suivie de l'addition d'acide caprylique et d'un passage du pH à 5,0 à 5,2. Il se forme alors un précipité de protéines contaminantes, de lipides et de formes de caprylate que l'on retire, tandis que la plus grande partie de l'anticorps reste dans la solution. On ajoute une fois de plus du caprylate de sodium à une concentration finale d'au moins environ 15 mM. Cette solution est incubée pendant 1 heure à 25°C pour assurer l'inactivation virale. Un précipité (principalement caprylate) est éliminé et la solution claire est diluée avec de l'eau purifiée afin de réduire la force ionique. On utilise la chromatographie par échange d'anions à l'aide de deux résines différentes pour obtenir IgG exceptionnellement pur dont la distribution de la sous-classe est particulièrement similaire à la distribution de départ. Le procédé permet de maximiser le rendement et de produire une gamma-globuline ayant une pureté supérieure à 99 %.

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