Biosimilar, biobetter and next generation therapeutic antibodies

Figures & data

Table 1 Selected examples of first generation, Biosimilars, Biobetter, second and third generation monoclonal antibodies and alternatives formats

1^st generation mAbs	Biosimilars	Biobetters	2^nd generation	3^nd generation	Alternative formats
CD20
Rituximab (1997) chIgG1 (CHO) (Rituxan/Mabthera)	Reditux (2007, Dr. Reddy) chIgG1 (CHO)	“Rituximab” GS4:0 aFuc hzIgG1 (Pichia pastoris) Same epitope	Ofatumumab (2009) hIgG1 (CHO) Different epitope and mechanism of action (MOA) (Arzerra)	Obinutuzumab (PhIII) aFuc hIgG1 (CHO) Different epitope and MOA	TRU-015 (PhIIb) SMIP
	TL011 (PhI, Teva/Lonza) chIgG1 (CHO)		Ocrelizumab (PhIII) hzIgG1 (CHO) Same epitope
TNFα
Infliximab (1998) chIgG1 (SP2/0) (Remicade)	TNFmab (Pre-clin, LGLS)		Adalimumab (2002) huIgG1 (CHO) (Humira)		Certolizumab (2008) Fab-PEG (E-coli) (Cimzia)
	CT-P13 « infliximab » (PhIII, Celltrion)		Golimumab (2009) huIgG1 (CHO) s.c. every 4 wk (Simponi)
Etanercept (1998) TNFR-Fc (CHO) (Enbrel)	TNFcept (PhI, LGLS)
HER2
Trastuzumab (1998) chIgG1 (CHO) (Herceptin)	CT-P6 « trastuzumab » (PhIII, Celltrion)	Trastuzumab s.c. formulation every 4 wk (PhIII)	Pertuzumab (PhIII) huIgG1 (CHO) Different epitope (targets HER2 and HER3)		Trastuzumab emtansine (PhIII) Antibody Drug Conjugate (targets HER2 and tubulin)
		“Trastuzumab” GFI5:0 aFuc hzIgG1 (Pichia pastoris) Same epitope			2 in 1, bispecific (targets HER2 and VEGFA)
EGFR
Cetuximab (2004) chIgG1 (SP2/0) (Erbitux)		CMAB009 (PhI) chIgG1 (CHO)	Necitumumab (PhIII) huIgG1 (CHO) Same epitope
		Xtend EGFR, M428L/N434S hzIgG1 (CHO) Fc-engineered (longer half life) Same epitope
VEGF-A
Bevacizumab (2004) hzIgG1 (CHO) (Avastin)		Xtend VEGF, M428L/N434S hzlgG1 (CHO) Fc-engineered (longer half life) Same epitope			Ranibizumab Fab, affinity maturated (E. coli) (Lucentis)
					2 in 1, bispecific (targets HER2 and VEGFA)
RSV—Prot F
Palivizumab (1998) hzIgG1 (NS0) (Synagis)			Motavizumab (PhIII, stopped) hzIgG1 affinity maturated (NS0) (Numax)	Motavizumab-YTE, long-lasting Fc-engineered version (PhI)

Note: Adapted from reference 4 and updated from reference 22 (6^th European Antibody Congress 2010).

Beck A, Wurch T, Bailly C, Corvaia N. Strategies and challenges for the next generation of therapeutic antibodies. Nat Rev Immunol 2010; 10:345 - 352

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Beck A, Wurch T, Reichert JM. 6th European Antibody Congress 2010: November 29–December 1, 2010. mAbs 2011; 3:111 - 134

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