PharmaTech: Roche

"New technologies and areas of research are the basis for today’s revolution in medicine,” according to the Roche Breakthrough Technologies research area website (www. roche.com/home/science/sci_res/sci_res_tech.htm). “In combination with information technology, automation and new chemical techniques, biosciences have the tools to develop new and better drugs.” Below, we explore what Roche is doing to provide these tools, through the company’s investment of nearly $3 billion annually in the discovery and development of new products and technologies in both diagnostics and pharmaceuticals (www.roche.us/portal/eipf/us/portal/roche/rd).

Using genomics and bioinformatics, Roche researchers identify genes and gene mutations that play key roles in disease development. Chip technology allows them to examine thousands of genetic sequences simultaneously on a DNA chip the size of a square centimeter and analyze their results in seconds, enabling healthy and diseased tissue to be compared, important disease causes identifi ed, and treatment targets found.

Once targets are found, Roche utilizes laboratory robots to test many substances simultaneously, with the goal of finding “molecules that react with the biological target and therefore have potential as new drugs.” A “huge amount of molecules” can then be stored in Roche’s new large compound depository and smaller substance libraries throughout the company’s research sites.

In the area of Computer-Assisted Drug Design and Combinationatorial Chemistry, Roche identifi es potentially interesting substances, the chemical structures of which are optimized by computer-assisted drug design and combinatorial chemistry (http://en.wikipedia.org/wiki/ Combinatorial_chemistry), permitting production of approximately 50,000 variants of the substance in a year.

Much of the technology used by Roche occurs at the company’s Palo Alto location, where “researchers employ the most advanced tools and technologies available today,” primarily in the areas of biology, chemistry, and informatics. Among the tools and technologies used by Roche biologists (http://paloalto.roche.com/randd/ToolsBiology.html) are the Aff ymetrix Genechip (www.aff ymetrix.com/products/arrays/index. aff x) probe arrays for understanding gene function in the context of human disease and identifying new targets, high-res separation techniques with mass spectrometry and informatics to study genome expression at the functional protein level, integrated robotic systems, automated pipetting stations, and the Flurometric Imaging Plate Reader (FLIPR) workstation for cell-based assays.

Roche chemists (http://paloalto.roche.com/randd/ToolsChemistry. html) use x-ray crystallography for protein production and high-throughput crystallization condition screening, UC Berkeley’s Advanced Light Source (www.als.lbl.gov), and commercial and propriety software for enabling virtual screening, fl exible docking (http://en.wikipedia.org/wiki/ Protein-protein_docking), and bioinformatics. These tools and technologies allow the chemists to increase their “efficiency in the lead identifi - cation and optimization stages of drug discovery.” The chemists also use such state-of-the-art instrumentation as NMR, Fourier transform Raman, and circular dicrosim spectroscopy (http://en.wikipedia.org/wiki/ Spectroscopy); polarimetry (http://en.wikipedia.org/wiki/Polarimetry); gas chromatography (http://orgchem.colorado.edu/hndbksupport/GC/ GC.html); and GC-mass spectrometry (http://en.wikipedia.org/wiki/ Gas_chromatography-mass_spectrometry).

Roche Global Informatics (http://paloalto.roche.com/randd/ToolsInformatics. html) uses in-house-created and vendor-provided tools, such as ActivityBase software (www.idbs.com/activitybase) throughout its “research sites to manage data from functional assays to ultra high-throughput screening;” a self-developed application for scientists to retrieve chemical, biological, and inventory information that uses a “multi-tier architecture with a Web user interface, Java-based components and an Oracle back end;” and licensed applications like Spotfire (www.spotfire.com) to perform “sophisticated analysis of their data in multiple dimensions.”

In the area of diagnostics, Roche “is leading the way in developing ‘actionable health information,’ so that tomorrow, caregivers and their patients will have the right information at the right time in the right place” (www.roche.us/portal/eipf/us/portal/roche/rd). Roche’s recent acquisition of Aff ymetrix, a leading microarray maker, led to generation of the AmpliCHIp CYP450, which allows healthcare professionals to identify certain naturally occurring variation in two important genes in drug metabolism, and therefore obtain information that can help physicians to avoid administering or prescribing drugs that could cause a serious reaction. Roche is also working on a new generation microarray- based diagnostic tool that will allow for better cancer screening and understanding of cancer types.