Tailored half-life extension

Immunogenicity shielding

Biodegradable polymer

Enhanced pharmacological activity

Antibody drug conjugate


The genetic fusion with conformationally disordered polypeptide sequences composed of the amino acids Pro, Ala, and/or Ser (‘PASylation’) provides a simple way to attach a solvated random chain with large hydrodynamic volume to the protein of biopharmaceutical interest. This amino acid string adopts a bulky random coil structure, which significantly increases the size of the resulting fusion protein. By this means the typically rapid clearance of the biologically active component via kidney filtration is retarded by 1-2 orders of magnitude. Compared with other strategies to prolong the plasma half-life of biopharmaceuticals the PAS-technology provides several adavantages.

Most of the commercially successful first generation biopharmaceuticals are small proteins that suffer from rapid renal clearance, leading to disappointingly short circulation times. Chemical conjugation of such therapeutic proteins with poly-ethylene glycol (PEG) to extend their effective size beyond the threshold of kidney filtration has emerged as anestablished strategy to prolong their plasma half-lives to a clinically useful range.

However, the chemical coupling of a biologically active protein with synthetic polymers has drawbacks with respect to biopharmaceutical development and production. Suitable PEG derivatives are expensive, especially as high chemical purity is needed, and their conjugation with a recombinant protein requires additional in vitro processing and purification steps, which lower the yield and raise the costs. Furthermore, the pharmaceutical function of a therapeutic protein may be impaired if amino acid side chains in the vicinity of its biochemical active site become chemically modified. Also, PEG is prone to decomposition by oxidation upon storage while, on the other hand, it is not biodegradable, which can cause side effects such as organ accumulation or vacuolation of kidney epithelium upon chronic treatment.

Taken together, PASylation offers a biological alternative to PEGylation with many benefits on the basis of a solid IP position.