Glycosylation technologies for biosimilars and ‘biobetters’

Biosimilars/Research | Posted 10/03/2010 post-comment

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According to Mr Hans Baumeister and Mr Steffen Goletz of Glycotope, human cell lines providing a human glycosylation pattern – such as those of Crucell (PER.C6), Cevec (CAP) and Glycotope (GlycoExpress) – have attracted increasing amounts of attention over the past years. In the case of biosimilars, regulatory approval now requires an extensive programme of bioequivalence studies to be undertaken to characterise the product in terms of its biochemical properties, safety and activity. As a consequence, glycosylated biosimilars need to be equipped with a similar pattern of glycosylation. For example, the degree of sialylation should not deviate by more than 20% from that of the original product. Hence, the chosen cell clone with high productivity has to be able to provide post-translational modifications as closely related to the originator’s cell line as possible. However, since glycosylation differs within clones, during the bioequivalence study it is often realised that the product carries different carbohydrates, usually resulting in a hyposialylation; this requires the screening process to be repeated in order to identify a new cell clone that is able to provide the equivalent glycosylation. Several glycosylation analysis technologies are available for the development and production of glycosylated biotherapeutics, applicable to both biosimilars and second-generation ‘biobetters’ (see Table 1).

Table 1: Glycosylation analysis technologies for biosimilars and ‘biobetters’

GlycoProfiling	Characterisation of the cellular glycosylation machinery (mRNA, enzymatic) and analysis of key structures on cell colonies, cell lines and recombinant products
GlycoAnalytics	Analysing the structure of N- and O-glycans attached to recombinant proteins in detail
GlycoAccess	The preclinical development of glycosylated biotherapeutics including in vitro and in vivo bioassays
GlycoEngineering of cells	Engineering of cell lines with a novel and stable glycosylation profile without necessarily generating a genetically modified organism for biopharmaceutical production
GlycoProtein engineering	Recombinant protein and antibody engineering and optimisation, such as addition/omission of glycosylation sites, humanisation and chimaerisation
Glyco-Optimisation	Optimisation of biotherapeutics to achieve a favourable glycosylation pattern by targeting the fucosylation, sialylation, galactosylation, antenarity and bisecting N- acetylglucosamine to get an optimal bioactivity, bioavailability and stability
GlycoBodies	Generation of monoclonal antibodies specifically recognising carbohydrates and carbohydrate-protein mixed epitopes

Reference:

Hans Baumeister and Steffen Goletz. Novel Glycosylation Technologies for the Development of Biosimilars and Biobetters. Innovations in Pharmaceutical Technology. pp 52-58. December 2009.

Source: Innovations in Pharmaceutical Technology