scFv Fragment

Modality

Antibody fragments are used as substitutes to conventional monoclonal antibodies (mAbs) in diagnostic and therapeutic applications, among which scFvs are one of the most popular types. scFvs can be produced in various expression systems and modified into plenty of different Ab formats. As they can be expressed in bacteria (e.g., Escherichia coli), scFvs are smaller and therefore easier and less expensive to manufacture, whereas mAbs typically need a mammalian expression system. Moreover, the size of scFvs still offers benefits in clinical research, including reduced immunogenicity when administered in vivo for the absence of an Fc region; better tissue penetration, which is useful for therapeutic and imaging applications; and rapid blood clearance, which is useful for imaging applications.

Complete antigen binding sites are included in scFvs, such as the variable heavy (VH) and variable light (VL) domains, of an Ab. Through the introduction of a flexible peptide linker (e.g., (GGGGS)3), the VH structural domain is linked to the VL structural domain. Alternative monovalent fragments to scFv include dsFv that constitutes VH and VL chains connected by disulfide bonds inserted into the frame region. dsFvs have a higher degree of stability and do not aggregate in comparison to scFvs.

Fig 1 . Structure of scFv and derivatives

scFv Fragment for Therapeutic Use

After years of discovery and engineering, scFv and scFv-based fragments have emerged as viable therapeutic and diagnostic alternatives to mAbs for cancer, autoimmune diseases, inflammation, chronic viral diseases, etc. Several scFv fragments have been approved for therapeutic use, such as Blinatumomab (Blincyto), Moxetumomab pasudotox (Lumoxiti), Brolucizumab (Beovu), and Tebentafusp (Kimmtrak).

Moxetumomab pasudotox

Moxetumomab pasudotox (Lumoxiti) is a CD22-targeting cytotoxin. It comprised of a recombinant, murine immunoglobulin variable domain fused to a truncated Pseudomonas exotoxin, PE38, that inhibits protein synthesis. Moxetumomab pasudotox has a molecular weight of approximately 63 kDa and is produced by recombinant DNA technology in E. coli. It was developed by Medimmune (R&D arm of AstraZeneca) and approved for treating adult patients with relapsed or refractory hairy cell leukemia (HCL).

Brolucizumab

Brolucizumab was developed by Novartis to treat patients with exudative (wet) age-related macular degeneration (AMD), diabetic macular oedema, and macular oedema secondary to retinal vein occlusion. Brolucizumab is an E. coli-produced humanized scFv antibody fragment that targets human vascular endothelial growth factor (VEGF) with a molecular weight of around 26 kDa.

Tebentafusp (Kimmtrak)

As a bispecific gp100 peptide-HLA-directed T cell receptor CD3 T cell engager, Tebentafusp (Kimmtrak) is indicated for treating HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma. Tebentafusp was developed by Immunocore and produced in E. coli cells with 77 kDa molecular weight.

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scFv Fragment Pipelines

Generic Name	Brand Name/ Alternative Name	Target	Expression System	Indications	Manufacturer	R&D Stage
Blinatumomab	BiTE-MT-103, bscCD19xCD3, AMG-103, MEDI-538, ビーリンサイト, Blincyto, 倍利妥	CD19, CD3	CHO cell	Acute lymphoblastic leukemia (ALL), lymphoma	Amgen, BeiGene	Approval
Brolucizumab-dbll	AL-86810, XSZ53G39H5 (UNII code), RTH-258, ESBA-1008, DLX-1008, Beovu, ベオビュ	VEGF-A	Escherichia coli (E. coli)	Macular degeneration	Novartis	Approval
Moxetumomab pasudotox	Lumoxiti, scFv-PE38	CD22	E. coli	Hairy cell leukemia	AstraZeneca,Innate	Approval
Tebentafusp	Kimmtrak, CD3, gp100	CD3, gp100	E. coli	Unresectable or metastatic uveal melanoma	Immunocore	Approval
Licaminlimab	ESBA-1622, LME-636, OCS 02, ESBA 1622	TNF-α	Pending update	xerophthalmiaAnterior uveitis	Novartis Pharma AG、Oculis SA、Alcon AG	Phase II
SAR-443726	anti-IL13/OX40L nanobody (Sanofi)	IL13R, OX40L	Pending update	Genetic diseases and malformationsSkin and musculoskeletal disorders	Sanofi	Phase I
Deoxymab	3E10, PAT-DX1	DNA	Pending update	Pancreatic cancer,Systemic lupus erythematosus	Patrys Ltd.	Phase I
VTx 002	Pending update	TDP43	Pending update	Amyotrophic lateral sclerosis	VectorY BV	Pre-clinical
VH-7Vk9	TDP-43 targeting single chain antibody, VH-7Vk9	TDP43	Pending update	Frontotemporal dementia	ImStar Therapeutics, Inc.	Pre-clinical
scFv-h3D6	bapineuzumab derivative, scFv-h3D6	APP	Pending update	Alzheimer's Disease	Universitat Autonoma de Barcelona	Pre-clinical
Fv-Hsp70	RBB-001, Fv-Hsp72	DNA, HSP70	Pending update	Ischemic stroke	Rubicon	Pre-clinical
SMET-D1	Pending update	Pending update	Pending update	Arthritis, eczema, psoriasis	CentryMed	Pre-clinical
PMC-401s	Anti-ANG2 antagonistic fully human ScFv, PMC-401s	Ang2	Pending update	Diabetic retinopathy, Macular degeneration	PharmAbcine Inc.	Pre-clinical
T-1649	Pending update	TNF-α	Pending update	Psoriasis	Teraclon	Pre-clinical
IMX-120	GLUT-1 antibody scFv-containing nanoparticles	GLUT1	Pending update	Ulcerative colitis, Crohn's disease, osteoarthritis	Immix Biopharma, Inc.	Pre-clinical
CGX-208	anti-misfolded alpha-synuclein scFv	α-synuclein	Pending update	Parkinson's disease	Cognyxx Pharmaceuticals	Pre-clinical
GTB-5550	GTB-5550 TriKE, GTB-5550	CD276	Pending update	Squamous cell carcinoma of head and neck, Multiple myeloma	GT Biopharma	Pre-clinical
scFv-235	single chain variable antibody fragment, scFv-235	TAU	Pending update	Alzheimer's Disease	Lundbeck Foundation	Pre-clinical
TA-101	recombinant single domain antibody fragment, TA-101	TNF-α	Pending update	Rheumatoid arthritis	TechnoPhage	Pre-clinical
DNX-214	Pending update	Pending update	Pending update	Wet age-related macular degeneration	DNX	Pre-clinical
NI-205	Pending update	TDP43	Pending update	Frontotemporal dementia	Biogen, Neurimmune	Pre-clinical
ARA-8	Pending update	Pending update	Pending update	Inflammation		Pre-clinical
P-1000	Pending update	Pending update	Pending update	Cancer	German Cancer Research Center	Pre-clinical
MRT-201	granzyme B synthetic antibody, GranzymeB-Fc-scFv4D5, MRT-201	HER2	Pending update	Cancer	Clayton、Mirata	Pre-clinical
MRT-101	Granzyme B/antibody fusion protein, GrB-Fc-IT4	TWEAK	Pending update	Cancer	Clayton、Mirata	Pre-clinical

Reference:

[1] Weisser NE, Hall JC. Applications of single-chain variable fragment antibodies in therapeutics and diagnostics. Biotechnol Adv. 2009 Jul-Aug;27(4):502-20. doi: 10.1016/j.biotechadv.2009.04.004.

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scFv Fragment

Modality

scFv Fragment

scFv Fragment for Therapeutic Use

Moxetumomab pasudotox

Brolucizumab

Tebentafusp (Kimmtrak)

Yaohai Bio-Pharma Offers One-Stop CDMO Solution for Antibody Fragments

scFv Fragment Pipelines

Reference:

MICROBIAL CDMO

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