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Biparatopic Agonistic Antibody Service

Creative Biolabs is a pioneer company in antibody discovery and manufacture. With years of experience and professional scientists, we have established advanced agonistic antibody engineering platform for research, diagnostic and therapeutic use. Importantly, we are capable of offering a full package of biparatopic agonistic antibody engineering services for biological therapeutic development.

Bispecific Antibody

Bispecific antibodies (BsAb) represent new emerging antibody (Ab) -based therapeutics. Different from monoclonal antibody binding a single epitope site, BsAb are generally built with different antigen (Ag)-binding sites (Fab or single-chain Fv), each one used to provide a different target-binding specificity, albeit within the same molecule. They allow for potential synergy by engaging two separate targets or result in superior properties by engaging two epitopes on the same target. In addition, BaAb may enable new functions that are not possible to achieve with monospecific antibodies alone such as tissue-specific delivery or bringing cytotoxic T cells to tumor sites. What’s more, biparatopic agonistic antibody has been developed to simultaneously activate multicomponent receptor complexes.

Model for potential dual activities of some immune agonist antibodies. Fig.1 Model for potential dual activities of some immune agonist antibodies. (Mayes, 2018)

Biparatopic Agonistic Antibody Engineering

Recently, several approaches based on traditional monoclonal antibody design and construction have been developed to generate a bispecific molecule. However, the custom random assembly of light chains and heavy chains may result in unwanted IgG species and thus lead to reduced yield of the correct product. To avoid this problem, the engineering of a single VH and VL pair to bind two different antigens has been developed. This bispecific format is constructed by using the antibody against the first antigen as the base to generate a library of light chain pairings which are then screened for their ability to bind a second antigen.

In addition, a unique approach that takes advantage of the properties of single-domain antibodies in therapeutic drug development has been developed for biparatopic agonistic antibody engineering. Using this method, BsAb is constructed by grafting two different antigen-specific VH domains onto the VH and VL positions of an IgG, yielding a tetravalent binder with two potential geometries, a close and a distant, between the two paratopes. What’s more, engineering biparatopic agonistic antibodies constructed by this approach have been proved have activities that are not observed when either paratope is targeted alone.

With years of experience and advanced technology platforms, Creative Biolabs is able to offer all the available approaches for biparatopic agonistic antibody engineering. With the extensive experience, abundant industry knowledge and advanced technical skills, our scientists are fully confident in accomplishing even the most challenging antibody engineering project to promote the development of your projects. For more detailed information, just feel free to contact us or directly send us a quote.

Reference

  1. Mayes, P.A.; et al. The promise and challenges of immune agonist antibody development in cancer. Nature reviews Drug discovery. 2018, 17(7), p.509.

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