Advantages
- Simply replace the conventional linker that connects VH and VL with this linker.
- Universal platform technology applicable to all scFvs
- Can also be applied to cyclic scFv, tandem scFv, Fc fusion, albumin fusion, CAR-T, etc.
Background and Technology
A single-chain Fv (scFv) is a low-molecular-weight antibody (25 kDa) in which the Fv domains derived from the heavy chain of an antibody (VH) and from the light chain (VL) are connected by a peptide linker. Most peptide linkers are composed of repeating modules of one or more of the glycine and serine, and a 15 amino acids (GGGGS)×3 peptide linker has been most frequently used. The scFv proteins exist as a closed state in which the VH and the VH domains interact intramolecularly, and an open state in which the VH and VL are dissociated. The open state scFv causes intermolecular VH-VL interactions, which causes aggregation.
We developed a unique peptide linker that binds to a highly conserved region at the VH-VL interface within the scFv molecule. The linker enhanced the intramolecular interaction between VH and VL in multiple types of scFv, forming a stable antigen-binding site. This suppressed intermolecular association and aggregation of scFv.
 |
Reference
- Patent Pending (unpublished yet)
Principal Investigator
Hiroshi MORIOKA, Prof. (Faculty of Life Sciences, Kumamoto University)
Yoshihiro KOBASHIGAWA, Associate Prof. (Faculty of Life Sciences, Kumamoto University)
Current Stage and Next Step
- For multiple types of existing antibodies, including those for pharmaceutical use, we have created multiple types of scFv in Escherichia coli by linking each VH and VL with our peptide linker. We have confirmed the association between molecules and antigen-binding activity.
- An in-silico method for designing the mutant scFv antibodies that improve the thermal stability has also been established.
- We are looking for collaborative partner companies to develop pharmaceuticals that apply scFv using our unique peptide linker.
Project No. BK-04657