New linker for Protein A boosts binding capacity

Protein A chromatography is an essential step in most commercial antibody/mAb purification processes. It is immobilized on chromatography resins to specifically capture and thus purify antibodies. The actual binding capacity is usually much lower than the theoretical one, due to steric constraints. To remediate this problem, our researchers have developed a new rigid protein linker that ensures ideal accessibility of binding surfaces and thus boosts binding capacity and purification yields. Protein A resins are commonly used commercial antibody purifications. However, this step often becomes a bottleneck for the manufacturing process due to generally low binding capacities. One underestimated factor affecting binding capacity is that many binding sites of the immobilized Protein A ligand are not accessible to the relatively large antibodies. Since Protein A resin is expensive, increasing its binding capacity can directly lower antibody/mAb productions costs.

Our team of inventors from the Technical University of Munich have developed a new, rigid protein linker for Protein A affinity resins. It serves to ideally space out Protein A binding surfaces, which drastically increases antibody capture in antibody downstream processing. So far, a more than 50% increase in antibody capture per molar amount of Protein A could be achieved, as compared to a standard flexible linker. This directly translates into faster and cheaper industrial downstream processing. Our technology can easily be combined with other capacity-optimizing strategies such as domain multiplication or affinity-increasing point mutations.

• Rigid inter-domain linker enhances the accessibility of individual Protein A binding sites
• Simple way to boost binding capacity of a Protein A resin 1.5 to 2-fold
• Can be combined with other capacity-optimizing strategies (e.g. multiple domains, point mutations)
• Potential to reduce costs and increase productivity in downstream platform processes

TRL 3.5