Anticalin® technology

Anticalins® are derived from lipocalins, a family of low molecular weight proteins that are naturally and abundantly expressed in human tissues and body fluids. Lipocalins have evolved to perform a range of functions in vivo associated with the physiological transport and storage of chemically sensitive or insoluble compounds. Lipocalins have a robust intrinsic structure comprising a highly conserved ß-barrel which supports four loops at one terminus of the protein. These loops form the entrance to a binding pocket and conformational differences in this part of the molecule account for the variation in binding specificity between individual lipocalins.

While the overall structure of hypervariable loops supported by a conserved ß-sheet framework is reminiscent of immunoglobulins, lipocalins differ considerably from antibodies in terms of size, being composed of a single polypeptide chain of 160-180 amino acids which is marginally larger than a single immunoglobulin domain.

Lipocalins are cloned and their loops subjected to engineering (using recombinant methods pioneered by Pieris’ founders) in order to create Anticalins®. Libraries of structurally diverse Anticalins® have been generated and developed by the company; Anticalin® display allows the selection and screening of binding function, followed by the expression and production of soluble protein for further analysis in prokaryotic or eukaryotic systems. Pieris has successfully demonstrated that Anticalins® specific for virtually any human target protein can be isolated and binding affinities in the nanomolar or higher range can be obtained - equivalent to the affinities of monoclonal antibodies derived by hyperimmunization. Anticalins® can be readily screened for a range of biological functions in both cell- and non cell-based screens as the basis of both diagnostic and therapeutic discovery programs.