Production and purification of recombinant arylsulfatase a

C - Chemistry – Metallurgy – 12 – N

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C12N 9/16 (2006.01) A61K 38/46 (2006.01)

Patent

CA 2554883

The present invention pertains to a process for production of recombinant arylsulfatase A in a cell culture system, the process comprising culturing a mammalian cell capable of producing rASA in liquid medium in a system comprising one or more bio-reactors; and concentrating, purifying and formulating the rASA by a purification process comprising one or more steps of chromatography. Other aspects of the invention provides a pharmaceutical composition comprising rASA, which is efficiently endocytosed via the mannose- 6-phosphate receptor pathway in vivo as well as a rhASA a medicament and use of a rhASA for the manufacture of a medicament for reducing the galactosyl sulphatide levels within target cells in the peripheral nervous system and/or within the central nervous system in a subject. A final aspect of the invention provides a method of treating a subject in need thereof, said method comprising administering to said subject a pharmaceutical composition comprising a rhASA and thereby obtaining a reduction in the galactosyl sulphatide levels in target cells within said subject.

La présente invention a trait à un procédé pour la production d'arylsulfatase A recombinante dans un système de culture cellulaire, le procédé comprenant la culture d'une cellule mammalienne capable de production d'arylsulfatase A recombinante dans un milieu liquide dans un système comportant un ou des bioréacteurs ; et la concentration, la purification et la formulation de l'arylsulfatase A recombinante par un procédé de purification comprenant une ou plusieurs étapes de chromatographie. D'autres modes de réalisation de l'invention ont trait à une composition pharmaceutique comportant de l'arylsulfatase A recombinante, qui est soumise à une endocytose efficace via la voie de récepteur du mannose-6-phosphate in vivo ainsi qu'à un médicament à base d'arylsulfatase A humaine recombinante et l'utilisation d'arylsulfatase A humaine recombinante pour la fabrication d'un médicament permettant la réduction de niveaux de galactosyle sulfatide dans des cellules cibles dans le système nerveux périphérique et/ou dans le système nerveux central chez un sujet. Enfin, l'invention a trait à un procédé de traitement d'un sujet qui en a besoin, ledit procédé comprenant l'administration au dit sujet d'une composition pharmaceutique comportant une arylsulfatase A humaine recombinante permettant ainsi la réduction des niveaux de galactosyle sulfatide dans des cellules cibles chez ledit sujet.

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