Immunoglobulin Gamma-Like Therapeutic Bispecific Antibody Formats for Tumor Therapy

Table 1

Immunoglobulin gamma-like bispecific antibody formats.

Format	Company	Publication date		Molecule	Targets	Function	Indication	Clinical trials	Company	Publication number
(A) Immunoglobulin gamma-like asymmetric bispecific antibodies
Knobs-into-holes (KiH)	Genentech	06 September 1996		(Including in the CrossMAb)
CrossMAb	Roche	02 July 2009		RG-6026	CD3×CD20	T cell recruitment	Relapsed or refractory non-Hodgkin’s lymphoma	I	Roche	WO2016020309 A1
				RG-7221	Angiopoietin 2×VEGF	2-ligand inactivation	Colorectal cancer	II	Roche	WO2011117329 A1
							Solid tumors	I
				RG-7386	FAP×DR5	Tumor site-specific cell apoptosis	Solid tumors	I	Roche	WO2014161845 A1
				RG-7716	Angiopoietin-2×VEGF	2-ligand inactivation	Diabetic macular edema, wet age-related macular degeneration	II	Roche	US20170260265 A1
				RG-7802	CEA×CD3	T cell recruitment	Solid tumors	I	Roche	WO2013026833 A1
				RG-7828	CD3×CD20	T cell recruitment	Chronic lymphocytic leukemia, non-Hodgkin’s lymphoma	I	Genentech	WO2016204966 A1
Triomab quadroma	Fresenius Biotech, TriOn Pharma	14 December 1995	Catumaxomab	EpCAM×CD3	T cell recruitment, Fc-mediated effector function	Malignant ascites, EpCAM-positive gastric and ovarian tumors	Marketed, approved in 2009 by the European Medicines Agency	Neovii Biotech/TriOn Pharma	WO2002020039 A3
			Ertumaxomab	HER2×CD3	T cell recruitment, Fc-mediated effector function	Her2-positive breast cancer	II	Fresenius/TriOn Pharma	US20170210819 A1
			FBTA05	CD3×CD20	T cell recruitment	Lymphoma	I/II	Fresenius/TriOn Pharma	WO20080220568 A1
FcΔAdp	Regeneron	29 December 2010	REGN-1979	CD3×CD20	T cell recruitment	Non-Hodgkin’s lymphoma, B cell lymphoma, acute lymphoblastic leukemia, and chronic lymphocytic leukemia	I	Regeneron	WO2014047231 A1
Asymmetric reengineering technology-immunoglobulin (ART-Ig)	Chugai	12 October 2006	Emicizumab	FIXa×FX	2-factor dimerization	Hemophilia A	Marketed, approved in 2017 by the United States Food and Drug Administration	Roche, Chugai (Tokyo)	WO2006109592 A1
			ERY-974	CD3×GPC3	T cell recruitment	Solid tumors	I	Chugai	WO2011078332 A1
BiMAb	OncoMed	24 February 2011	OMP-305B83	DLL4×VEGF	2-ligand inactivation	Solid tumors	I	OncoMed	WO2013044215 A9
Biclonics	Merus	24 October 2013	MCLA-117	CLEC12A×CD3	T cell recruitment	Acute myeloid leukemia	I	Merus	WO2014051433 A1
			MCLA-128	HER2×HER3	2-receptor tyrosine kinase inactivation	Solid tumors	I/II	Merus	WO2015130173 A1
			MCLA-158	Lgr5×EGFR	2-receptor tyrosine kinase inactivation	Solid tumors	I	Merus	WO2016093023 A1
Bispecific Engagement by Antibodies based on the T cell receptor (BEAT)	Glenmark	27 December 2012	GBR-1302	HER2×CD3	T cell recruitment	HER2 positive cancers	I	Glenmark	WO2015063339A1
DuoBody	Genmab	29 December 2011	JNJ-61186372	EGFR×cMET	2-receptor tyrosine kinase inactivation	Non-small-cell lung cancer	I	Janssen, Genmab	WO2014081954 A1
			JNJ-63709178	CD3×CD123	T cell recruitment	Acute myeloid leukemia	I	Janssen, Genmab	WO2016036937 A1
			JNJ-61178104	Undisclosed	Undisclosed	Autoimmune disorders	I	Janssen, Genmab	WO2016052071 A1
Azymetric	Zymeworks	28 June 2012	ZW-25	Two nonoverlapping epitopes of HER2	Receptor tyrosine kinase inactivation	HER2-expressing cancers	I	Zymeworks	WO2015077891 A1
XmAb	Xencor	10 March 2011	XmAb-13676	CD3×CD20	T cell recruitment	B cell malignancies	I	Novartis, Xencor	US20170174781 A1
			XmAb-14045	CD3×CD123	T cell recruitment	Hematological malignancies	I	Novartis, Xencor	WO2016086189 A3
(B) Immunoglobulin gamma-like symmetric bispecific antibodies
Dual variable domain-immunoglobulin (DVD-Ig)	Abbott	18 August 2006	ABT-122	TNFα×IL-17A	2-ligand inactivation	Psoriatic arthritis, rheumatoid arthritis	II	AbbVie (Abbott)	WO2014144280 A3
			ABT-165	DLL4 × VEGF	2-ligand inactivation	Phase I in solid tumors/phase II in colorectal cancer	I/II	AbbVie (Abbott)	WO2014071074 A3
			ABT-981	IL-1α×IL-1β	2-ligand inactivation	Osteoarthritis	II	AbbVie (Abbott)	WO2008082651 A3
			SAR156597	IL4 + IL13	2-ligand inactivation	Idiopathic pulmonary fibrosis	II	Sanofi	US20170145089 A1
			GSK2434735	IL4 + IL13	2-ligand inactivation	Asthma	I	GlaxoSmithKline	US20170136581 A1
FynomAb	Covagen	23 October 2014	COVA-322	TNFα×IL-17A	2-ligand inactivation	Plaque psoriasis	I/II	Covagen	WO2011023685 A1
Two-in-one/dual action Fab (DAF)	Genentech	18 December 2008	RG-7597	EGFR×HER3	2-receptor tyrosine kinase inactivation	Head and neck, colorectal cancers	II	Genentech, Roche	WO2010108127 A1