Module 9 2024

03/09/2024

Impact of Glycosylation Heterogeneity

Neu5Gc and α gal Non human or non

G0F

G2F Terminal galactose key in complement dependent cytotoxicity (CDC). CDC increases proportionally to galactose content

G0 Afucosyl glycans show

Man-5 High mannose species demonstrate faster clearance via

G2-NeuAc Sialic acids linked to increased circulating lifespan by covering galactose and preventing clearance via the hepatocyte asialo glycoprotein

increased affinity to FcyRIII

mammalian glycans, can cause immune reactions,

and be targets for antidrug antibodies (ADAs)

which is the key receptor for NK mediated ADCC

mannose receptors

expressed by macrophages

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needs for its characterisation and the determination of its quality a combination of physico-chemical biological testing…

Key learnings

• Biologics are complex, multicomponent, often large, labile

• Cannot be characterised by a single method

• Product of a biological system: heterogeneity

• We hope to show batch to batch consistency in the pattern of heterogeneity.

• Reading ICH Q6B,

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