Tokyo

A fierce patent battle over an enzyme widely used by biologists to create gene libraries reached its climax earlier this month.

The case, which was held in Delaware's district court in Wilmington, concluded on 11 October. A ruling that will determine whether cheaper imitations of the popular SuperScript enzyme could become more readily available is expected within the next few months.

At present, biotechnology firm Invitrogen of Carlsbad, California, has four patents associated with SuperScript, and the company dominates distribution of the enzyme in the United States.

SuperScript is a reverse transcriptase used to turn molecules of messenger RNA (mRNA), taken from cells of plants and animals, into complementary DNAs (cDNAs). These cDNAs represent all or part of a gene, and are easier to work with in the lab than mRNA. By assembling the cDNAs into libraries, researchers can study how genes express themselves, for example, during different stages of development or disease (see Nature 419, 3–4; 200210.1038/419003a).

But it is hard to ensure that all of the mRNA is transcribed — especially as reverse transcriptases tend to degrade mRNA while making cDNAs. SuperScript has been refined to minimize this degradation, making it a popular and effective tool.

The Delaware court case saw Invitrogen's patents challenged by BD Biosciences Clontech of Palo Alto, California. During the week-long hearing, Clontech argued that the patents are too narrow to cover SuperScript, that Invitrogen has misrepresented SuperScript features such as the degree to which it can reduce mRNA degradation, and that Invitrogen's protectionist strategy violates anti-trust laws. Clontech wants the judge to hit Invitrogen with massive fines — $500 for each of the thousands of times the enzyme has been used — and to give half to Clontech as compensation.

Invitrogen officials reject all three claims but admit that the company is highly protective of SuperScript. “It is one of our core technologies,” says a spokesman for the firm. Since 1996, Invitrogen has sued at least six companies, including Clontech, for reselling its reverse transcriptase or its products in violation of the purchase agreement. An initial victory in this case by Clontech, which invalidated Invitrogen's patent coverage, was successfully appealed against and the dispute continues in a separate Maryland court case.

An unfavourable ruling for Invitrogen in Delaware could set a precedent for other pending cases, such as that between the company and Stratagene of La Jolla, California. It would also open up the US market to those who have stayed out in deference to Invitrogen's patents, observers of the case say.

In addition, a ruling against Invitrogen might free up the distribution of cDNAs and cDNA-based analytical tools. This could include microarrays made using SuperScript, some of which are only available to academic researchers because of the licensing agreements that Invitrogen demands from commercial collaborators.

Biotechnology firms, such as Tokyo-based Dnaform, which distributes the mouse cDNA libraries for Japan's Institute of Physical and Chemical Research (RIKEN), have complained that the terms of these agreements are too onerous. Toshizo Hayashi, Dnaform's president, claims that Invitrogen refused to grant it a licence to distribute the mouse cDNAs in the United States.

Hayashi says that no agreement has been reached and that the mouse cDNAs cannot be distributed to the United States unless an academic collaboration with RIKEN is established. But Alan Hammond, Invitrogen's patent lawyer, says that the company's protection of its patents is justified by its research efforts. “It's the cost of innovation,” he says.