Stability of IgG isotypes in serum

Figures & data

Figure 1 Schematic of the human IgG isotypes and their disulfide linkages.

Figure 2 Deamidation of asparagine residue.

Figure 5 The different Fc glycans present on antibodies.

Figure 4 Exchange of Fab arms between endogenous IgG4 molecules and a therapeutic IgG4 molecule.

Figure 5 Formation of functional covalent dimers between identical as well as different IgG2 molecules.

Figure 6 Shuffling of inter-chain disulfide bonds of IgG2 in serum.

Figure 7 Analysis on LabChip GXII showing recovery of mAbs from blood-precision data (n = 3) after 4 and 24 hours.

Figure 8 (See opposite page). Monitoring aggregate and fragment formation of a mAb in whole blood using the LabChip GXII (T = 0, 4 and 24 hrs).

Table 1 Amino acid sequence of hinge region for different IgG isotypes

IgG isotype	Core hinge region sequence (from refs. 96, 97)
IgG1	EPKSCDKTHTCPPCP
IgG2	ERKCCVECPPCP
IgG3	ELKTPLGDTTHTCPRCP ...... (EPKSCDTPPPCPRCP) × 3
IgG4	ESKYGPPCPSCP

Table 2 Summary of studies to evaluate influence of the Fc glycan structure on serum clearance

Author(s)	Antibody	Fc glycan studied	Host	Effect on clearance
Wright and Morrison77	Chimeric mouse/human	Oligomannoses	Mice	Oligomannoses rapidly cleared
Kanda et al.81	Chimeric mouse/human	Fucosylated vs. non-fucosylated and oligomannoses	Mice	Oligomannoses rapidly cleared. No difference between fucosylation
Zhou et al.76	Human	Non-fucosylated oligomannoses	Mice	No impact on clearance
Millward et al.79	Human	Complex type or high mannose enrichment	Mice	No impact on clearance
Newkirk et al.78	Mouse (IgG1 and IgG2a)	G0 (NGA2F) versus NA2F	Mice	G0 has longer half-life for IgG2a
Chen et al.75	Human	All glycans	Human	No impact on clearance
Jones et al.106	Fusion Fc with TNF receptor	Terminal N-acetyl-glucosamine	Human/cyno monkey	Terminal N-acetyl glucosamine is rapidly cleared
Keck et al.80	Fusion Fc with TNF receptor	Terminal N-acetyl glucosamine	Human	Terminal N-acetyl glucosamine is rapidly cleared
Wawrzynczak et al.l07	Mouse (IgG2b)	Aglycosylated vs. glycosylated	Rat	Aglycosylated is rapidly cleared

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