Medical Device Link.

Originally Published MX January/February 2003

COVER STORY

Building on a Patent

A fundamental building block of research in the field of molecular diagnostics is polymerase chain reaction (PCR), an intellectual property acquired in 1991 by F. Hoffmann-La Roche Ltd. for a mere $300 million. Under licenses issued by Roche Corp., PCR has become the most widely used method for amplifying DNA as part of nucleic acid–based testing. In 2000, Roche revenues from PCR totaled $470 million and were growing at a rate of 26% annually.

PCR allows minute amounts of genetic material to be amplified into billions of copies in a few hours, facilitating the detection of pathogenic organisms even before antibodies to these organisms are formed. The technology is essential to cutting-edge research under way in healthcare and biosciences. PCR’s exquisite sensitivity makes it possible to diagnose infectious agents earlier and to monitor disease progression and response to therapy.

Despite challenges on a number of fronts, Roche has successfully defended its PCR patents, and now holds more than 130 U.S. patents related to the PCR process. The inventions based on these patents have become routine tools in the field of molecular diagnostics.

Nevertheless, developers of molecular diagnostics have long lamented the technological challenges imposed by working with PCR. The method only works for DNA samples (a variant method, reverse transcriptase-PCR, is used to amplify RNA samples), requires carefully controlled thermal cycling, and has traditionally relied on the manual operation of laboratorians with sufficient training in the technique. To eliminate such difficulties (and the licensing fees that go along with the use of PCR), several other IVD manufacturers have developed alternative methods for amplifying nucleic acids. In addition, companies in the field have developed several approaches to automating the sample preparation required before an amplified sample can be analyzed. 

Roche’s Cobas Amplicor analyzer was the first benchtop system to fully automate the amplification and detection steps of the PCR testing process on a single instrument (see Figure 1). It combines a thermal cycler, automatic pipettor, incubator, washer, and reader. Tests available for this platform include assays for the detection and viral-load monitoring of HIV-1, cytomegalovirus, and hepatitis C; and the detection of hepatitis B, Chlamydia trachomatis, Neisseria gonorrhoeae, M. tuberculosis, M. avium, and M. intracellulare. 

The first of Roche’s patents on the PCR process will expire in 2004, and some industry watchers believe that the field of molecular diagnostics will blossom once it has been freed of the restrictions and fees associated with the use of PCR. 

In the meantime, Roche has begun to elaborate a series of assays based on its own platform for advanced PCR handling, called the LightCycler (see Figure 2). Launched in 1998, the LightCycler uses minute quantities of DNA and PCR reagents to achieve rapid, automated amplification and quantitative detection of target DNA. The company promises new molecular-based tests in disease predisposition, cancer screening, cancer therapy selection, and pharmacogenomics.

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