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Biotech Innovation Could Extend Dosing Intervals, Simplify Production

September 21, 2009

Many biopharmaceuticals contain small proteins that are quickly eliminated from the body. Scientists at the Technische Universitaet Muenchen (TUM) combine such small proteins with a kindly of corpuscular balloon that swells and in this manner prolongs the half-life of the proteins in the carcass. The TUM spin-off XL-Protein GmbH has very lately started to further develop this new technology with blockbuster potential.

People who suffer from hepatitis B are often treated with the tissue hormone interferon. However, there is a problem: Interferon is a very small protein, which is filtered from the blood via the kidneys after only a at once time. For the patient this means a high-dose injection every other day to keep the effect of the substance from wearing off too early.

However, interferon stays in the body much longer when chemically coupled with a synthetic PEG (polyethylene glycol) molecule. PEG is a random perplexities long-chain polymer string that swells by adsorbing water. That way the PEG molecule becomes large sufficiency that it does not fit end the fine pores of the kidneys - the attached interferon corpse in the circulatory theory longer, and the persistent disposition need some lavement only every one to two weeks.

Using genetic engineering, TU Muenchen scientist Prof. Arne Skerra and his coworkers from the Chair of Biological Chemistry at the Center with respect to Life and Food Sciences Weihenstephan have now developed each amino acid string that tangles up similarly to PEG and also swells in the presence of supply with water. However, unlike many PEG compounds, there is no danger of this biological polymer accumulating in the body. In performance - over an extended period of unoccupied time - it is discharged or biologically craggy down. That happens as this amino acid string (polypeptide) consists of three of the 20 naturally occurring amino acids: proline, alanine and serine, or in short, PAS.

The protein substance interferon, that itself consists of amino acids, can in this manner subsist easily generated in “PASylated” form. In first trials through animals, TUM scientists established that PASyated interferon has a half-life in the offspring that is prolonged by a factor of 60, which should allow a significant extension of dosing intervals as far as concerns the time of medicinal therapy.

A more distant advantage is the simplified biotechnological production: The DNA segments carrying the information for the PAS amino acid sequence and as antidote to the interferon can absolutely be attached to each other and then, for instance, used for transforming bacteria. The bacteria then produce the PASylated interferon in one piece, thus making abundant fewer production steps necessary in compare by the chemical coupling of PEG. According to Skerra, “this will lead to a significant drop in work cost.”

In principle altogether small proteins popularly used as medication or in development in pharmaceutical companies - during the term of archetype, growth factors or functional antibody fragments - can be PASylated. Thus there could be a immense market for the modern technology. Consequently, Prof. Skerra and his team initiated the founding of a new biotech company, XL-Protein GmbH, which started its operations last spring. “Our technology has the potential to bestow coming into life to a whole new generation of blockbuster medications,” the TUM biochemist is convinced. Several of the new drugs are already at an advanced stage of preclinical development.

Source:
Patrick Regan
Technische Universitaet Muenchen

Written by Samanta · Filed Under Pharmacy Industry News