Anticalins are engineered lipocalins, endogenous low-molecular weight human proteins typically found in blood plasma and other body fluids that naturally bind, store and transport a wide spectrum of molecules. The defining attributes of the 12-member human lipocalin class (and, therefore, Anticalins) are a four-loop variable region and a rigidly conserved beta-barrel backbone, which, together, form a pliable cup-like binding pocket.
Anticalins contain rationally diversified amino acids within these four loops and ligand-binding areas of the beta barrel, while maintaining the integrity of the lipocalin structure.
This diversity has yielded a drug class that:
- provides a coveted specificity and affinity against a wide spectrum of targets;
- exhibits the safety of an endogenous protein performing an endogenous function;
- is durable, creating greater flexibility of formulation and delivery; and
- tightly binds a target as a monovalent molecule, overcoming the complications of multivalent binding approaches, when agonist receptor cross-linking is therapeutically counter-productive.
To obtain a specific Anticalin, Pieris applies its significant protein engineering know-how and the breadth of its exclusive Anticalin libraries. The company's suite of proprietary phage display libraries has been created by rationally diversifying the lipocalin regions that are responsible for ligand binding, with different libraries applied to different types of targets. Once defined, a novel Anticalin can be produced in any number of bacterial expression systems, including Wacker Biosolutions’ ESETEC® system, with which Pieris has achieved impressive yields. Using best-in-class bacterial production remains constant from the earliest stages of drug discovery through to and including GMP, ensuring quality as well as cost effective production.