Format of bispecific antibodies (BsAbs)-C-terminal linker of Fc

SOCAIL MEDIA

ADAPTIR-FLEX platform technologies can be used to produce monospecific, bispecific, and multispecific immunotherapeutic proteins. These protein candidates bind to one or more targets found on tumor cells, immune cells, or other cells in the body or circulation to either amplify, suppress, or regulate the body’s defense mechanisms to treat cancer and autoimmune diseases. ADAPTIR-FLEX molecules are composed of two different polypeptides that form a dimer through modifying specific sequences in the Fc region of each polypeptide. Each end of the polypeptide may contain one or two different binding domains, enabling the ADAPTIR-FLEX molecules to bind up to four targets. In addition, the ADAPTIR-FLEX platform can be used to modify the valency of binding to each target, which means it can bind a target, through one binding domain or through multiple binding domains, to a specific target to enable modifying the strength of binding to a specific target.

Formats of bispecific antibodies (BsAbs)

Many formats have been developed for BsAb generation as listed in the following table.

Format	Description	Example BsAb	Trademark	Company
tandem VHH	Tandem VHH fragment-based BsAb	N/A
tandem scFv	Tandem ScFv fragment-based BsAb	AMG330	BiTE^TM	Amgen
Dual-affinity re-targeting antibody	Tandem domain-exchanged Fv (can also be used to fuse with Fc domain to create whole Abs)	Flotetuzumab	DART^TM	Macrogenics
Diabody	dimer of single-chain Fv (scFv) fragment	vixtimotamab	ReSTORE^TM	Amphivena Therapeutics
(scFv)2-Fab	a Fab domain and two scFv domains bind	A-337	ITab^TM	Generon/EVIVE Biotech
Rat–mouse hybrid IgG	Full-size IgG-like half antibodies from two different species	Catumaxomab	Triomab^TM	Trion Pharma
Hetero heavy chain, Common light chain	Hetero heavy chain, Common light chain	Emicizumab	ART-Ig^TM	Genentech/ Chugai/Roche
Controlled Fab arm exchange	Recombin the parental half antibodies	JNJ-64007957	Duobody^TM	Genmab/ Janssen
Hetero H, forced HL IgG1	KIH technology for heterodimerization of 2 distinct H chains, replacing the native disulfide bond in one of the CH1-CL interfaces with an engineered disulfide bond to enhance the cognate of H and L paring	MEDI5752	DuetMab^TM	MedImmune/ AstraZeneca
cH IgG1	Identical heavy chains; 2 different light chains: one kappa (κ) and one lambda (λ)	NI-1701	κλ body^TM	Novimmune SA
Hetero H, CrossMab	KIH technology; domain crossover of immunoglobulin domains in the Fab region	Vanucizumab	CrossMab^TM	Roche
scFv-Fab IgG	Fab-Fc; ScFv-Fc	Vibecotamab; M802	Xmab^TM (the engineered Fc to enhance the generation of heterodimeric Fc); YBODY^TM	Xencor/Amgen; YZYBio
VH1-VH2-CH1-Fc1(G1) x VL2-VL1-CL-Fc2(G1)	2 binding motif in one half antibody	SAR440234	CODV-Ig^TM	Sanofi
VL1-CL1-VH2-CH2-Fc x VH1-CH1 x VL2-CL2	2 binding motif in one half antibody	EMB-01	FIT-Ig^TM	EPIMAB BIOTHERAPEUTICS
VH-1-TCR Cα x VL-1-TCR Cβ; VH-2-CH-2-Fc x VL-2-CL-2	KIH technology; TCR Cα/Cβ is used to substitute the CH1 and CL domain in one arm		WuXibody^TM	WuXi Biologics
C-terminal linker of Fc	Link the other molecules at the C-terminal of Fc	APVO442	ADAPTIR-FLEX^TM	Aptevo Therapeutics
Fc antigen binding site	2 natural binding sites; 2 additional binding sites in the Fc loop	FS118	mAb²	F-star Therapeutics