DTU Chemistry - PIPPI

Essential Knowledge of Proteins to Guide Pharmaceutical Industry

Monday 11 Jan 16
|
by Charlotte Malassé

Contact

Pernille Harris
Associate Professor
DTU Chemistry
+45 45 25 20 24

Contact

Günther H.J. Peters
Associate Professor
DTU Chemistry
+45 45 25 24 86

THE PROJECT

PIPPI is short for Protein-excipient Interactions and Protein-Protein Interactions in formulation.

THE PARTNERS

Technical University of Denmark

University of Manchester

Ludwig-Maximilian University of Munich

Lund University

Novozymes A/S

Wyatt Technology Europe GmbH

Medlmmune Ltd

University of Copenhagen

MAXIV Laboratory

NanoTemper Technologies GmbH

Knowledge of the properties of proteins right down to atomic level is essential for making it easier and faster for the pharmaceutical industry to manufacture protein-based drugs in liquid form. Over the next four years, a joint European project, PIPPI, with DTU Chemistry as the overall coordinator, will develop a public database with cutting-edge knowledge about the properties of proteins in pharmaceutical formulations

Although, a variety of new therapeutic proteins has been developed showing benefits in the treatment of ailments like diabetes and cancer, obtaining physical stability in formulations still remains one of the biggest challenges to pharmaceutical scientists. This is mainly due to the limited knowledge of the way these proteins interact in the solutions in which they are marketed.

Towards protein-based drugs
The healthcare sector is challenged as the average age of Europe's population is rising. Greater focus is being devoted to manufacturing safe and risk-free drugs, while the requirements for evaluating new drugs and their possible side effects are becoming stricter. All of this has moved the pharmaceutical industry towards protein-based drugs, which have high specificity and relatively few side effects. But there is very little knowledge of the way these proteins behave in the solutions in which they are sold.

The European Horizon2020 programme has funded € 4 M  to develop a database over a four-year period, which shall ensure more efficient development of the very extensive and protracted screening process that protein drugs, e.g. next generation treatments of cancer, autoimmune- and metabolic diseases, undergo before being put on the market.

The Scientific challenge
"Drugs as we know them from the pharmacy typically consist of an active substance such as paracetamol in painkillers. In addition to the active substance, there are other substances in the finished tablet, for example, excipients facilitating that the tablet is dissolved in the right way and stabilizes the active substances. Similarly, excipients are added to protein solutions to increase the stability of proteins,” explains Pernille Harris, Associate Professor at DTU Chemistry, who is the overall coordinator for the entire project, which has a large number of partners from both the pharmaceutical industry, European universities, and other stakeholders.

Today, the pharmaceutical industry carries out very extensive screening of all these excipients to test their performance with the active substance. It is this screening process that we hope to be able to streamline with this project," she says.

Few universities in Europe have formulation of biologics as a scientific subject. Consequently, the pharmaceutical industry is required to train hired scientists.

“We are proud to be part of a consortium comprising leading researchers in protein and pharmaceutical science in Europe. We have high expectations that PIPPI will help boosting the knowledge in the field. Furthermore, we hope that PIPPI will result in increased focus to the field,” says Jens Bukrinski, senior scientist, Novozymes A/S.

15 new PhD positions from 2016
While e.g. a substance like paracetamol is a small organic molecule, which will be stable for a long time in a tablet, protein-based drugs are very sensitive and the challenge in respect of protein drugs is to eliminate the risk of their degradation in aqueous solution or even of precipitating out from the solution.

"The idea of the project is to establish a comprehensive protein library, representing the different properties that proteins can have, for example in terms of size, charged distribution, hydrophobicity and flexibility,” explains Pernille Harris.

“Subsequently, they will be studied using state-of-the-art techniques from the pharmaceutical industry and finally their abilities to interact with various substances at the atomic level will be characterized. Then everything will be gathered in a database,” she continues.

In the project 15 new PhD positions will be created and the students will work towards this goal with the various partners. Ultimately, knowledge right down to the atomic level about the different types of proteins may make it easier to predict the behaviour of a similar, new protein targeted for use by the pharmaceutical industry. The aim is for the protein to be stable in the solution, and although this result can be achieved today, getting there may be a long and hard process.

"And at the end of the day, you may still not be completely certain why it actually works," says Pernille Harris.

The Consortium PIPPI
Scientists in the field of structural and computational biology, biophysics, protein formulation and stability have formed the consortium ‘Protein-excipient Interactions and Protein-Protein Interactions in formulation’, PIPPI.

PIPPI, funded under the European Horizon2020 programme, is an Innovative Training Network (ITN) concerning the challenges in formulation of protein-based drugs. PIPPI will combine systematic investigations of the physicochemical behavior of a number of proteins with an in-depth understanding of the molecular interactions behind the macroscopic behavior. The overall objective is to develop methodologies, tools and databases to guide the formulation of robust protein-based therapeutics in the future.

The consortium consists of both academic and industrial partners located in Denmark, Sweden, Germany and United Kingdom. Each of the project partners contributes excellent competence in their particular areas. 

PIPPI and DTU Chemistry
The overall project coordinator Associate Professor Pernille Harris as well as Associate Professor Günther Peters from DTU Chemistry contribute to PIPPI. The core research in the group is in the area of Structural and Computational Biology. Our contribution to PIPPI will be studies of the overall atomic structure of the proteins and their intermolecular interactions. Pernille Harris is working with protein crystallography, small-angle X-ray scattering and X-ray absorption spectroscopy. Günther Peters, leader of the Chemistry at the Interface to Biology research group at DTU Chemistry, has extensive expertise in in-silico modelling techniques.


Charlotte Malassé, Special Advisor, Communication, DTU Chemistry, cmal@kemi.dtu.dk

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