Improving stability and secretion of antibodies
Bayerische Patentallianz GmbH
Antibodies represent one of the most important groups of proteins in the field of biotechnology. They are not only used in basic research but are also exploited for diagnostic and therapeutic purposes such as cancer treatment. However, due to their complex folding and assembly, production of antibodies for experimental and medical use is expensive. Hence, improving antibody properties is of high commercial interest. The constant domain of the antibody light chain (CL) is essential for both folding of the heavy chain CH1 domain and consequently also for quality control of correct antibody assembly. Since the CH1 domain can only adopt its native conformation after association with the CL domain, mutations in CL may have an impact on the efficiency of assembly and secretion of antibodies.
Here, we present an invention that improves the biophysical properties of antibodies and therefore results in increased secretion. In line with this technology, the CL domain is modified by introducing two intra-molecular changes
whereby a significant stabilization is achieved.
Compared to the wild type CL, the melting point of the modified CL domain is almost 10°C higher and its stability against urea-induced denaturation is also markedly increased. Notably, when light chains comprising this optimized CL domain were co-expressed with Ig heavy chains, a significant increase in the assembly and subsequent secretion of complete IgG antibody molecules from mammalian cells was observed. Although this technology was established using IgG, it is applicable to all classes of antibodies because of the ubiquitous presence of CL in all immunoglobulin classes. Furthermore, the invention will also be applicable for the optimization of other constant domains besides CL.
- Antibodies have a broad field of application (basic research, diagnostics, therapy) but high costs of production
- USP: antibodies with significantly higher stability and strongly increased secretion
- Target groups for technology: Antibody manufacturer, CMOs
Proof of concept in cell culture