Extending Half-life of sdAb for Drug Development
Creative Biolabs is a well-recognized expert in the field of sdAb drug development. With over a decade of extensive experience and advanced platform, Creative Biolabs is professional in supporting a variety of sdAb drug development projects to solve our customers' specific requirement of sdAb half-life extension.
Half-life of sdAb
Molecular in vitro selection technology such as phage display has generated an array of novel therapeutically promising sdAbs with specificity toward signaling molecules as well as tumor surface antigens. sdAbs can display improved tissue penetration due to their smaller size (~15kDa) compared to full antibodies. Short serum half-life values may be desirable for certain applications (e.g., radionuclide-based imaging, clearance of toxic drugs, transient interference with the function of a target protein in vivo).
However, in many cases, a long circulation time in the blood is desirable to ensure long-lasting function in vivo and reduce the number of administrations, especially a concern for therapeutic applications such as cancer and chronic inflammatory diseases. Conventional sdAb candidates usually have short in vivo serum half-lives and are typically cleared very rapidly from the body by renal filtration and excretion after administration. It limits the therapeutic efficiency of sdAb drug candidates in the clinical study. Thus, strategies to tailor their biodistribution and serum half-life are highly needed to prolong the circulation of these sdAbs in the blood and thus to improve administration and pharmacokinetic as well as pharmacodynamic properties.
Fig.1 Extending half-life of sdAb. (Rissiek, et al., 2014)
Extension of sdAb Half-life at Creative Biolabs
With an increasing number of sdAbs developed for clinical applications, strategies to improve pharmacokinetics, especially half-life extension, have become increasingly important, not only concerning therapeutic efficacy but also regarding the costs of therapy as well as convenience and compliance for patients. With our rich experience of sdAb development, Creative Biolabs is now offering extending half-life of sdAb service, which can solve our customers' trouble for drug development.
A variety of new strategies at Creative Biolabs have been considered and developed to extend serum half-lives and improve the pharmacokinetic properties of sdAbs. They can be achieved by several means including but not limited to chemical conjugation (e.g., PEGylation) or genetic modification (e.g., bispecific sdAb, fusion with Fc, albumin, or albumin-binding molecules). A series of sdAb candidates can be rapidly optimized for the increased binding specificity and affinity and desired serum half-lives to meet your particular application requirements. These custom solutions could produce a sdAb drug with a terminal half-life in humans of up to several days, while also have the potential for improving the therapeutic effect via improving the pharmacokinetic and pharmacodynamic properties.
In terms of our advanced technical platforms, scientists at Creative Biolabs are confident in offering custom sdAb half-life extension solutions to assist your valuable projects. Our scientists are pleased to tailor therapeutic sdAbs with long serum half-lives to meet your particular application requirements. If you are interested in the development of specific sdAb as therapeutic drugs, please feel free to contact us for more details.
Reference
- Rissiek, B.; et al. Nanobodies as modulators of inflammation: potential applications for acute brain injury. Frontiers in cellular neuroscience. 2014, 8: 344.
Case Study
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