For Research Use Only. Not for Clinical Use.

It is well-known that immunoglobulin G (IgG) has an unusually long serum half-life in comparison to other natural proteins due to its ability to bind the neonatal Fc receptor (FcRn). Hence, the in vivo pharmacokinetic properties of therapeutic recombinant monoclonal antibody can be inferred by measuring its binding ability to FcRn. As an approach to determine the binding capacity between proteins, biolayer interferometry was widely accepted in protein research area and is regarded as a golden standard due to its high-throughput and high-accuracy. Creative Biolabs is a leading service provider that focuses on therapeutic protein development. With rich experience and an established platform, we are capable of offering a suitable half-life assay service by biolayer interferometry to support your protein drugs development.

Introduction of Half-life Assay by Biolayer Interferometry

Pharmacokinetics properties are often critical to the success of a therapeutic, and recent reports have suggested about 15% of Phase 1 clinical studies fail due to inadequate pharmacokinetics or pharmacodynamics properties. This is especially true for antibodies, where typically a longer half-life is desired for therapeutics to decrease dosing frequency and increase efficacy. The discovery of FcRn mediated cycling explains the reason of the long half-life of IgG as well as provides a creative approach to extending the half-life of therapeutic protein. Therefore, many therapeutic proteins try to attach the Fc region from IgG to take advantage of FcRn dependent recycling, aiming to prolong half-life of protein drugs.

Biolayer interferometry platform is a novel in vitro, high throughput method for predicting antibody half-life based on the binding ability between target protein molecule and FcRn. The key point of this technology is the establishment of the prediction model, which was proven by lots of protein molecules with known half-lives. Nowadays, more recombine monoclonal antibodies have chosen Fc fusion as a method to prolong the half-life, whose effect can be tested by biolayer interferometry model.

Fig.1 Various mAbs with predicted half-life. (Souders, 2015)

Applications of Half-life Assay by Biolayer Interferometry

With the details of FcRn mediated transportation that have been widely investigated, it is now well known that the binding ability between Fc region and FcRn affects the half-life of proteins. However, some studies have determined the potency active region can have a significant effect on the protein-FcRn interaction and in vivo half-life.

Some researchers determined the human FcRn association rate for 5 human IgG monoclonal antibodies using a high-throughput biolayer interferometry platform. Comparing the combined FcRn association and dissociation rates to the clinical study half-lives resulted in a strong correlation, which was also verified in vivo using mice transgenic for human FcRn. This result suggests that this FcRn binding model could precisely predict the half-life of therapeutic proteins and serving as a screening tool for the development of antibodies with desired pharmacokinetic properties.

Biolayer interferometry platform measures the half-life of specific antibodies without the use of live cells. This convenient and rapid method shown great potential in large-scale applications. For more details about our services, please directly contact us.

Reference

1. Souders, C. A.; et al. A novel in vitro assay to predict neonatal Fc receptor-mediated human IgG half-life. Taylor & Francis. 2015, 7(5), 912-921.