V.S.j German astronauts complete spacelab mission U.S. and German astronauts carry out research on effects of microgravity during Spacelab D-2 mission aboard space shuttle Columbia, which landed May 6 after 10 days in Earth orbit. Payload commander Jerry L. Ross (left) changes a sample in materials processing furnace. German payload specialist Ulrich Walter (rear), mission specialist Bernard A. Harris Jr., and German payload specialist Hans W. Schlegel conduct tests on human physiology. Originally slated to fly in late February and delayed three times by technical glitches, Spacelab D-2 was then put on hold while the National Aeronautics & Space Administration launched space shuttle Discovery in April to collect data on, among other things, Earth's ozone layer during the Northern Hemisphere's transition from winter to summer. Columbia finally
Erythropoietin six-year patent dispute settled After almost six years in and out of courts, two biotechnology firms—Amgen and Genetics Institute—last week settled their bitter dispute over patent rights to erythropoietin (EPO). EPO, used to stimulate red blood cell growth in anemic patients, is the biotech industry's leading drug. Amgen's U.S. sales for dialysis patients alone reached $506 million in 1992. Sales are also growing abroad and for other uses. Genetics Institute cannot sell EPO in the U.S., but markets it abroad. Amgen comes out ahead in the settlement. The Thousand Oaks, Calif.-based firm has been in a stronger position since 1991, when a federal appeals court upheld its principal EPO patent and ruled Genetic Institute's patent invalid. After unsuccessful appeals which went as high as the U.S. Supreme Court, the Cambridge, Mass.-based firm has agreed to settle, and will pay Amgen $14 million. Ironically, Genetics Institute might have been able to share in EPO's blockbuster U.S. sales. In early 1990—while both companies7 EPO patents still were considered valid—a federal court ordered the two firms to reach a cross-licensing
blasted off April 26, just nine days after Discovery's April 17 landing. Spacelab D-2's five U.S. and two German astronauts conducted some 90 experiments covering materials sciences, biological sciences, technology (including robotics and automation), Earth observations, at-
agreement. However, no agreement was reached and the fight continued. The settlement clears the way for Amgen to receive additional patents. In late 1991, the Patent & Trademark Office decided a patent interference proceeding in
mospheric physics, and astronomy. The mission was managed by the German Research Establishment for Aerospace (DLR), and scientific operations during flight were run by DLR's center in Oberpfaffenhofen, near Munich (C&EN, March 8, page 6).
Amgen's favor. But Genetics Institute made a last-ditch attempt to challenge the ruling. All lawsuits have now been dropped, and Amgen expects to receive process and product patents for recombinant EPO.
Amgen-Genetics Institute patent dispute has long history 1983 October: Amgen's Fu-Kuen Lin clones gene for human erythropoietin (EPO), a red blood cell stimulant. December: Amgen files patent application for DNA sequence and host cells of recombinant EPO. I f 85 January: Genetics Institute (GI) files patent application for purified EPO. 19®7 June: GI receives patent. October: Amgen receives patent, files suit in district court in Boston against GI, which countersues. 1988 February: Boston court issues summary judgment that Amgen's EPO infringes GI patent. 19H9 June: Amgen receives first FDA marketing approval for recombinant EPO. December: Court finds some Amgen and GI patent claims valid and infringed by each other. 199© January: GI seeks permanent injunction to block Amgen's EPO
sales. March: Court orders Amgen and GI to set up royalty-free cross-licensing agreement, or be barred from the market. Both later appeal court rulings. 1991 March: U.S. Court of Appeals for Federal Circuit upholds Amgen patent but overturns Boston court decision on GI patent, making it invalid and Amgen no longer in infringement. July: GI petitions U.S. Supreme Court after appeals court denies rehearing. Before ever getting U.S. marketing approval, GI is enjoined from EPO sales by Boston court. October: Supreme Court denies GI's appeal. December: Patent & Trademark Office settles patent interference proceeding in Amgen's favor. 1992 January: GI files two lawsuits in district court in Delaware, to set aside patent office decision. 1993 May: Amgen and GI reach settlement, ending U.S. patent disputes.
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The EPO dispute has had repercussions for the entire biotechnology industry. The time, effort, and cost of litigation rank among the largest in the industry. Early on, the International Trade Commission was brought in to rule on EPO importation. The fight even spread to the two firms' licensees in the U.S. and abroad. For example, Amgen's U.S. licensee, Johnson & Johnson, is still battling with Genetics Institute. The dispute's legal implications also shook the industry. Court decisions set new, and sometimes startling, precedents in defining biotechnology intellectual property rights—and then reversed them. Stock prices rose and fell as investor confidence swayed with court decisions. And Genetics Institute challenged Amgen's receipt of orphan drug status for EPO, which gave Amgen seven years of exclusive U.S. marketing rights. Genetic Institute's EPO, through licensees, has been poised for U.S. Food & Drug Administration marketing approval for many years. The firm has received overseas approvals for EPO and other products, but has been slow to market a major U.S. product. In 1990, it lost to Genentech in a patent dispute over another major drug, tissue plasminogen activator. Its factor VIII for hemophilia was approved in late 1992. Ann Thayer
EPA revokes pesticide exemptions Responding to a Supreme Court mandate, the Environmental Protection Agency has canceled five emergency exemptions from federal regulations it had granted to allow use of pesticides on crops. EPA also has denied 16 other requested exemptions. These decisions comply with a Supreme Court ruling in February (C&EN, March 1, page 18). The court said the Delaney amendment to the 1958 Food, Drug & Cosmetic Act gives EPA no discretion to allow pesticide residues in processed foods at levels greater than those allowed in raw food—no matter how small the risk—if a pesticide has been found to induce cancer in animals. The case was brought against EPA in California by a coalition of environmental organizations. The ruling forced a new EPA pesticide policy. EPA will not grant emergency exemptions, will cancel all crisis exemp6
MAY 17,1993 C&EN
tions granted by states or other federal agencies, and will revoke any emergency exemption currently in force, if any data show a pesticide meets the Delaney "induce cancer in animals" test. EPA's current action hits nine pesticides: acephate, bifenthrin, cyromazine, bromoxynil, fosetyl-al, iprodione, pendamethalin, permethrin, and triadimefon. Crops affected include potatoes, tomatoes, hops, apples, rice, mint, and grapes. "We continue to believe that the pesticides affected by the court decision, including those EPA acted on, pose only a negligible risk to public health," stresses EPA Administrator Carol M. Browner. The Delaney amendment needs to be
changed, she adds. 'The Clinton Administration will work with Congress and other interested parties to develop a proposal." Speaking for pesticide makers, National Agricultural Chemicals Association (NACA) president Jay J. Vroom says, "It is critical for consumers to understand that this is a legal issue, not a food safety issue. The food crops protected with these products are safe to eat." NACA contends that, because of the revocations, growers could lose as much as $70 million, especially since, as EPA notes, replacement products in most cases may be less effective. David Hanson
Jaw implant suit targets Du Pont, Dow Corning A potential multi-million-dollar class action suit concerning jaw implant materials has been filed against Du Pont and Dow Corning. The two firms will have a month to respond to the charges once they receive a summons from U.S. District Court in Newark, N.J., which they expect shortly. The suit, which was filed April 14, claims that silicone and fluoropolymer human jaw implant material, and/or devices the two companies manufactured, have caused or have the potential to cause a variety of ills—from facial and neck pain, severe headache, and mental confusion to tumors and "autoimmunetype syndrome"—in 100,000 recipients. The case involves disk jaw implants the size of a quarter used to treat temporomandibular joint dysfunction. The implant replaces the natural disk that connects the lower jaw to the skull after the natural disk has deteriorated and made opening and closing the jaw difficult and painful. The class action suit revives the controversy over implant devices that raged a little more than a year ago when Congress and the Food & Drug Administration dealt with silicone gel breast implants made by Dow Corning and other firms. At the time, silicone gel breast implants were implicated in autoimmune diseases in women, and FDA has since severely limited use of those implants. Dow Corning declines to comment on the suit until it receives the court documents. But Du Pont senior counsel Ross Schmucki says cases such as this class action suit "are overreaching and may deter raw materials companies from do-
ing business with medical device manufacturers." Indeed, Dow Corning discontinued sale of implant-grade silicone last December. Du Pont supplied its Teflon fluoropolymer to the now bankrupt Vitek, Houston, which manufactured the jaw implant. Schmucki notes that many jaw implant suits were previously filed against Du Pont. The company has successfully defended itself in 84 such cases to date, he explains. However, two months ago, an Oregon State circuit court jury in Portland awarded a woman $460,000 in damages for a faulty implant made partly from Du Pont's Teflon fluoropolymer. Du Pont is appealing the case. Schmucki adds that about 500 other lawsuits are pending in various state and federal courts. A Dow Corning spokesman says 30 jaw implant lawsuits are now pending against the company. Dow Corning both manufactured silicone that surgeons fashioned for implants, and made a silicone implant specifically for jaw implants. Christopher Placitella, of Wilentz, Goldman & Spitzer, Woodbridge, N.J., lead lawyer for plaintiffs in the class action suit, says the suit was filed on behalf of eight individuals but seeks certification as a class action suit. This could bring together all jaw implant lawsuits now pending against both Du Pont and Dow Corning, he says. If Judge Nicholas H. Politan certifies the class action complaint, it will be at least two years before the case is heard by a jury, according to Placitella. Marc Reisch
