Reversed-phase hplc assay for plasminogen activators

C - Chemistry – Metallurgy – 12 – Q

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Details

C12Q 1/56 (2006.01) C12N 9/72 (2006.01) C12Q 1/37 (2006.01) G01N 30/02 (2006.01)

Patent

CA 2384756

A process is described for monitoring the effectiveness of a purification process in removing plasminogen activator (PA) endogenous to Chinese hamster ovary (CHO) cells from a sample containing human tPA or variants thereof. This process comprises incubating the sample with a protease capable of specifically cleaving the Arg275 - IIe276 bond of human wild-type tPA and then with denaturing/reducing agents in respective amounts effective to reduce the disulfide bonds of human wild-type tPA; subjecting the sample to a reversed-phase high-performance liquid chromatography step, and analyzing the elution profile from the chromatography step for the amount of PA endogenous to the CHO cells present therein.

L'invention concerne un procédé servant à surveiller l'efficacité d'un procédé de purification lors du retrait d'un activateur de plasminogène endogène dans les cellules d'ovaire de hamster chinois (cellule CHO) à partir d'un échantillon contenant des activateurs tissulaires du plasminogène humains ou des variantes de ceux-ci. Ce procédé consiste à incuber l'échantillon au moyen d'une protéase capable de cliver de manière spécifique la liaison Arg¿275? - Ile¿276? d'activateurs tissulaires du plasminogène humains de type sauvage, puis par dénaturation/réduction des agents en quantités efficaces respectives à réduire les liaisons disulfures des activateurs tissulaires du plasminogène humains de type sauvage; à soumettre l'échantillon à un étage de chromatographie liquide haute performance en phase inverse, et à analyser le profil d'élution à partir de l'étage de chromatographie pour la quantité d'activateurs de plasminogène endogènes présents dans les cellules CHO.

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