Shortened purification process for the production of...

C - Chemistry – Metallurgy – 08 – B

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C08B 37/00 (2006.01) A61K 39/09 (2006.01) A61K 47/48 (2006.01)

Patent

CA 2681570

A shortened process for producing a solution containing substantially purified capsular polysaccharides from a cellular Streptococcus pneumoniae lysate broth is described. Ultrafiltering and diafiltering a clarified S. pneumoniae lysate followed by pH adjustment to less than 4.5, preferably about 3.5, precipitated at least 98% of the protein in the solution without seriously affecting polysaccharide yield. Furthermore, following ultrafiltration and diafiltration and acidification to a pH of less than 4.5, filtration using activated carbon precipitated at least 90% of remaining protein without seriously affecting polysaccharide yield. Exemplary, non-limiting S. pneumoniae serotypes that can be purified using the shortened process of the invention are 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. In one embodiment, the Streptococcus pneumoniae cells are lysed using deoxycholate sodium (DOC), while in another embodiment the lytic agent is a non-animal derived lytic agent such as N-lauryl sarcosine sodium (NLS).

Cette invention a trait à un procédé rapide permettant de produire une solution contenant des polysaccharides capsulaires sensiblement purifiés à partir d'un bouillon de lysat cellulaire de Streptococcus pneumoniae. L'ultrafiltration et la diafiltration d'un lysat de S. pneumoniae clarifié, puis l'ajustement du pH à une valeur inférieure à 4,5, de préférence environ 3,5, permet de précipiter au moins 98 % de la protéine en solution sans affecter sérieusement le rendement des polysaccharides. Par ailleurs, après l'ultrafiltration, la diafiltration et l'acidification à un pH inférieur à 4,5, la filtration utilisant du charbon actif permet de précipiter au moins 90 % des protéines restantes sans affecter sérieusement le rendement des polysaccharides. A titre d'exemple, les sérotypes de S. pneumoniae pouvant faire l'objet d'une purification par le procédé rapide de l'invention sont, notamment, les sérotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F et 23F. Dans un mode de réalisation, les cellules de Streptococcus pneumoniae sont lysées avec du désoxycholate de sodium, tandis que dans un autre mode de réalisation, l'agent lytique est un agent lytique d'origine non animale comme le N-lauryl sarcosine sodique.

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