As a pioneer of bispecific antibody development and manufacture, Creative Biolabs has used the advanced technology platform to generate dock and lock (DNL) bispecific antibody (BsAb) products. Our experienced scientists in BsAb development field can provide first class services tailored according to your needs.
Creative Biolabs has developed a useful approach of producing BsAbs by the DNL method, which allows the site-specific self-assembly of two modular components with each other, leading to a covalent structure of defined composition with retained bioactivity. The main point of the DNL approach is the utilization of the specific protein/protein interactions between the anchoring domain (AD) of A-kinase anchoring proteins and the regulatory (R) subunits of protein kinase A (PKA) occurred in nature. Actually, the dimerization and docking domain (DDD) discovered in the regulatory subunit of PKA and the anchoring domain of an interactive A-kinase anchoring protein are each belonged to a biological entity. However, the resulting derivatives of these domains, when combined, produced a stably tethered complex of a defined which entirely maintains the functions of individual constituents.
Our DNL BsAb is designed by utilizing the specific interaction between the regulatory (R) subunits of cAMP-dependent protein kinase (PKA) and the anchoring domains of A kinase anchor proteins (AKAPs), the mechanism of which has been applied in generation of bioactive conjugates of distinct protein and nonprotein molecules. This method allows quantitative and site-specific self-assembly of diverse biological molecules applied for various medical purposes. Generally, our scientists apply DNL method to generate trivalent bispecific antibody which is composed of three Fab fragments. The advantage of this method is that this bispecific antibody form without a Fc region, which has a rather short half-life for pretargeting approaches. This format can be further extended to generate a hexavalent BsAb (HexAb, Hex-IgG) through linking DNL domains to the C-terminus of another antibody.
Figure 1. Schematic of Tri-Fab and Hex-IgG made by DNL conjugation (Edmund A. Ross, et al, 2008)
Each AD- or DDD- comprising entity is a module and any DDD module is able to be paired with any AD module. Such modules enable to be generated alone, stored separately ‘‘on shelf’’, and combined ‘‘on demand,’’ without requiring purification before mixing.
Modules are able to be produced recombinantly or chemically, which may be formed in microbial or mammalian systems, may contain derivatives of antibodies or antibody fragments, enzymes, natural carrier proteins, cytokines, or various natural or artificial non-antibody binding or scaffold proteins.
With the well-established DNL BsAb generation platform, the experienced scientists here at Creative Biolabs are dedicated to help you develop unique DNL BsAbs. We also provide other various services regarding BsAbs development. Please feel free to contact us for more information and a detailed quote.
1. Goldenberg, D. M.; et al. Multifunctional antibodies by the Dock-and-Lock method for improved cancer imaging and therapy by pretargeting. Journal of Nuclear Medicine. 2013, 49(1): 158-163.
2. Chang, C. H.; et al. The dock and lock method: a novel platform technology for building multivalent, multifunctional structures of defined composition with retained bioactivity. Clinical Cancer Research. 2007, 13(18): 5586s-5591s.
3. Rossi, E. A.; et al. Novel Designs of Multivalent Anti-CD20 Humanized Antibodies as Improved Lymphoma Therapeutics. Cancer Research. 2008, 68(20): 8384-92.