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IgG-scFv BsAb Generation Service

Creative Biolabs provides a first-class construction service for different types of IgG-scFv bispecific antibodies (BsAbs). Our strong expertise in constructing BsAbs allows us to generate complex IgG-scFv BsAbs. The antibody types that we can offer include IgG(H)-scFv or scFv-(H) IgG; IgG(L)-scFv or scFv-(L)IgG; and 2scFv-IgG or IgG-2scFv.

As monoclonal antibodies have exhibited success in the clinic for many diseases, multi-specific antibodies, with an ability to bind to more than one target, may further enhance clinical efficacy by novel mechanisms. Multi-specific antibodies have been designed for various applications comprising improved antibody-dependent cell-mediated cytotoxicity (ADCC), tumor surface-receptor blocking and down regulation, binding to two soluble effector molecules simultaneously, as well as pretargeting tumor cells for the subsequent capture of radionuclides, drugs and prodrugs. Early efforts to generate BsAbs mainly contained chemical conjugation of two antibodies or fragments thereof or co-expression of two antibodies with different specificities via the hybrid hybridoma technique. However, the conditions needed for chemical conjugation may inactivate, unfold or aggregate the BsAb. Moreover, the hybrid hybridoma technique not only forms the desired BsAb but also undesired products.

Bispecific formats for scFv fusion molecules.

Figure 1. Bispecific formats for scFv fusion molecules. (A) TascFv-Fc fusion, (B) scFv-Fc-scFv fusion and (MicroCal) (C) IgG-scFv fusion proteins served as construct formats for assembly of bsAbs. (Mabry, R., 2010)

IgG-scFv BsAb

Creative Biolabs offers novel IgG-scFv BsAb generation services. This technique is based on the C-terminal fusion of a disulfide-stabilized scFv to the light chain of an IgG. It enables to be expressed in mammalian cell culture and purified to homogeneity by protein A chromatography. IgG-scFv BsAb is a kind of BsAbs which is engineered for bispecificity by fusing two scFvs respectively to a monospecific IgG. The specificity of each scFv can be same or different. Furthermore, either the amino or the carboxy terminus of each light or heavy chain can be appended with paired antibody variable domains, which leads to the production of diverse types of IgG-scFv BsAbs:

  • IgG(H)-scFv or scFv-(H)IgG: IgG(H)-scFv, two scFvs with same specificity linked to the C terminus of the full-length IgG HC; scFv-(H)IgG, which is same like IgG(H)-scFv, except that the scFvs are linked to the HC N terminus.
  • IgG(L)-scFv or scFv-(L)IgG: the two same scFvs connected to the C or N terminus of the IgG light chain, which forms the IgG(L)-scFv or scFv-(L)IgG, respectively.
  • 2scFv-IgG or IgG-2scFv: generated by fusing two paired scFvs with different specificity to either the N terminus (2scFv-IgG) or the C terminus (IgG-2scFv).

With our well-established IgG-scFv BsAb technology platform, the experienced scientists here at Creative Biolabs are dedicated to help you develop therapeutic BsAbs. We also provide other various services regarding BsAbs development. Please feel free to contact us for more information and a detailed quote.

References

1. Mabry, R.; et al. Engineering of stable bispecific antibodies targeting IL-17A and IL-23. Protein Engineering Design and Selection. 2010, 23(3): 115-127.
2. Orcutt, K. D.; et al. A modular IgG-scFv bispecific antibody topology. Protein Engineering Design and Selection. 2010, 23(4): 221-228.

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