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Zybody Generation Service

Creative Biolabs is an undisputed global leader in the rapidly emerging market of bispecific antibodies (BsAbs). With our professional scientists hammering at Creative Biolabs and various advanced technology such as Zybody, we offer a full range of BsAbs for both academic and clinical fields. We are confident to deliver you the best procedure to meet your individual requirements.

BsAbs have become more and more of interest for diagnostic and therapeutic applications. Except retargeting of effector molecules, cells and genetic vehicles, dual targeting and pretargeting strategies, half-life extension, and delivery through biological barriers have also been studied. To promote the developablity of BsAbs, a large number of institutes are devoted to establishing novel platforms.

Zybody Technology

Based on years of exploration, Creative Biolabs has developed a novel Zybody technology for BsAbs generation. Zybody is engineered by fusing modular recognition domains (MRDs) to N- and C-termini of both the heavy and the light chains of a full-length monoclonal antibody (mAb). It is a multi-specific, multi-valent antibody format that enhances the activity of conventional mAb without compromising their desirable drug-like properties. The MRDs include small polypeptides sequences (< 60 amino acids), domain-based structures selected for target specificity, such as knottins or Protein A Scaffolds, unstructured (linear) or disulfide-constrained peptides. Zybodies possess up to four distinct specificities, depending on the number of MRDs fused to the mAb scaffold, while retaining the original functionality and specificity of the scaffold antibody.

This figure shows the zybody assembly and nomenclature.

Figure 1. This figure shows the zybody assembly and nomenclature. Part A shows the immunoglobulin heavy (H) and light (L) chain genetic fusions that form a penta-specific zybody with four unique MRDs. Part B shows the mono-specific antibody scaffold along with three exemplary zybodies. (David LaFleur, 2013)

Zybody Production

There are three primal steps to validate the zybody platform, including build the capacity of the mAb scaffold to hold MRD fusions at its each terminus; confirm the number of specificities that could be added without altering scaffold function; study the diversity of MRD structures amenable to the platform. Zybodies and the parent scaffold mAbs enable to be generated in HEK293F suspension cells which are transiently transfected with equimolar ratios of independent heavy and light chain cDNA expression constructs, and usually formed protein levels ranged from 50 to 250 μg/ml.

With our well-established Zybody 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. LaFleur, D. W.; et al. Monoclonal antibody therapeutics with up to five specificities Functional enhancement through fusion of target-specific peptides. MAbs. 2013, 5(2):208-18.
2. Kanakaraj, P.; et al. Simultaneous targeting of TNF and Ang2 with a novel bispecific antibody enhances efficacy in an in vivo model of arthritis. MAbs. 2012, 4(5): 600-613.

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