Nycomed files ultrasound patent claims against MBI, Mallinckrodt, and Sonus

Will patent litigation hold up product commercialization?

The development of ultrasound contrast agent technology is turning into a patent lawyer's paradise. Norwegian contrast developer Nycomed this month became the latest company to resort to the courts as it filed patent infringement claims against Molecular Biosystems and its partner Mallinckrodt. Nycomed also filed a claim against Sonus Pharmaceutical to have one of that company's patents overturned.

Nycomed's claims were brought as part of the company's defense against patent infringement claims filed in August in U.S. District Court for the District of Columbia by MBI of San Diego and Mallinckrodt of St. Louis. In that suit, MBI and Mallinckrodt charged Nycomed, Bracco, ImaRx Pharmaceutical, and Du Pont Merck Pharmaceutical with infringing on MBI's ultrasound contrast patents. The litigation is an outgrowth of a battle over the regulation of ultrasound contrast agents that began last year when several contrast developers successfully petitioned the Food and Drug Administration to regulate MBI's Optison agent as a drug rather than a device (SCAN 8/6/97).

In filing a counterclaim Sept. 2 to the MBI and Mallinckrodt suit, Nycomed charged that Optison infringes Nycomed's patent, U.S. patent no. 5,529,766, which was filed in March 1991 and issued June 25, 1996. The patent covers the development of "microbubbles comprising protein capable of formation of gas-containing microbubbles, said microbubbles containing gas comprising sulfur hexafluoride or a low molecular weight fluorinated hydrocarbon," according to Nycomed. The patent also covers albumin as a protein encapsulation material. Nycomed's contrast agent under development that uses the technology is called NC100100.

Ironically, Nycomed and MBI were once partners in the development of ultrasound contrast technology. The firms signed a licensing and cooperative development agreement in December 1987, but it eventually broke down. Nycomed at one time had European marketing rights to MBI's first agent, Albunex, but returned those rights to MBI in late 1995. Nycomed states in its counterclaim that it was conducting independent research on contrast technology that led to the invention covered by the '766 patent. Nycomed denied MBI's claim that it is entitled to a royalty-free license to the '766 patent.

Regarding Sonus, Nycomed claims that its '766 patent has priority over the Bothell, WA, company's U.S. patent no. 5,573,751, which was filed September 1991 and issued Nov. 12, 1996. Nycomed also charges that certain claims of the Sonus patent are invalid, and the company is asking the court to declare that the Nycomed patent was a prior invention to the Sonus patent.

The litigation points out an interesting anomaly: MBI's Optison, Nycomed's '766 patent, and Sonus' '751 patent all relate to the same invention, namely the use of protein microbubbles or microspheres encapsulating fluorine-containing hydrocarbons. Nycomed appears to be claiming that it was the first to patent this technology, while MBI's position is that enough prior art existed about the technology to render any such patents unenforceable.

As the lawyers wrangle over patents, several ultrasound contrast agents continue to move closer to market. The FDA last month resumed its review of contrast agents, with Optison probably closest to receiving approval and EchoGen from Sonus right behind. It's becoming increasingly possible that the patent battles may impede the market launches of one or more agents.

Some industry observers, however, believe that the stakes involved-the introduction of a new technology that could change the face of ultrasound and lead to increased procedure volume and equipment purchasing-are too great to allow patent battles to get in the way. One industry expert, Harvey Klein of Klein Biomedical Consultants in New York City, believes that lessons can be learned from other contrast markets, where patent infringement battles were settled on the eve of product introductions.

"My suspicion is that (patent battles) have never slowed anything down," Klein said.