Cyanamid oncology unit to merge with Immunex - C&EN Global

Following a pattern established by others in the pharmaceutical and biotechnology industries, American Cyanamid will purchase a majority share of Immu...
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Dante prepares for volcano mission foot-high volcano on Ross Island, about 800 miles from the South Pole. On the crater floor, Dante will make measurements that were impossible until now, and gather gas and aerosol samples. Testing this robot under harsh conditions also will help advance robotic technologies for eventual use in exploring other planets. The team includes scientists from Carnegie Mellon University's Robotics Institute, led by William L. Whittaker, and from New Mexico Institute of Mining & Technology, led by volcanologist Philip R. Kyle, a professor of geochemistry. The project is sponsored by the National Aeronautics & Space Administration and the National Science Foundation. In choosing the name Dante, the team alludes to Italian poet Dante Alighieri's descent in his classic "Divine Comedy" into Erebus, a place of darkness in the underworld to which dead souls go. Draped by snow and ice, Erebus is one of a very few volcanoes in the world that have been observed to contain a lava lake over a long period of time. Scientists have long sought to collect data on its rare conditions. Indeed, for the past 20 years, Kyle has spent most Antarctic summers (November to January) on the frozen continent studying Erebus and other volcanoes. Several at-

tempts by researchers to descend into Erebus' crater were stopped by constant small eruptions from the lava lake. Dante weighs 500 kg, and is 2.5 meters high, 3 meters long, and 1.7 meters wide. It will first be deployed at the top of Erebus by a "mother ship" vehicle. The robot then will take 24 to 36 hours to rappel 850 feet down the sheer inside walls to the crater floor, linked to a base station by a fiber optic communications cable. Dante's unique laser range finder, 3-D video cameras, and foot sensors will help scientists guide it. When it reaches the floor, Dante will collect data and samples over eight to 24 hours, and then climb out. But "there are no guarantees it will come back," admits James Osborn, project manager at Carnegie Mellon. Many things could go wrong. "Dante is pushing the robotic technology envelope." The key goal, Osborn tells C&EN, is to sample, for the first time, pristine high-temperature gases directly from vents (fumaroles) near the lava lake, to learn more about processes deep inside the volcano's magma chamber. Dante will stick a titanium tube into the fumaroles, using its gas chromatograph to send back to the team realtime readings of nitrogen, oxygen, carbon monoxide, carbon dioxide, sulfur dioxide, hydrogen sulfide, and hydrogen. This will permit screening for where and when to take samples for later lab analysis. "And it gives us some data even if Dante doesn't get back," Osborn notes. Another goal is to look at Erebus' environmental impact. The team will examine acid vapors from the fumaroles—such as hydrogen fluoride, hydrogen chloride, sulfuric acid, and sulfur dioxide—to study the effects of volcanoes on atmospheric chemistry. The team also will study whether Erebus contributes significantly to global carbon dioxide emissions. In addition, Dante will collect aerosols near fumaroles and elsewhere in the crater for later lab analysis, using its quartz crystal microbalance for screening. Its infrared thermometer will measure temperatures in the lava lake; and its gamma-ray spectrometer will measure potassium, thorium, and uranium in crater soil to collect evidence on the volcano's history. Richard Seltzer

Cyanamid oncology unit to merge with Immunex Following a pattern established by others in the pharmaceutical and biotechnology industries, American Cyanamid will purchase a majority share of Immunex, a leading biotechnology company, and merge its Lederle Laboratories oncology business with Immunex. The resulting new company, to be owned 53.5% by Cyanamid and 46.5% by shareholders of Immunex, will be the second largest oncology firm in North America, Cyanamid notes, with estimated 1993 sales of about $200 million. It will operate independently under the Immunex name at that firm's Seattle headquarters, under the same management. However, Immunex's chief executive officer, Stephan A. Duzan, will step down after the transaction is completed. His successor will be selected by a new board of directors. For each share of existing common stock, Immunex shareholders will receive $21 in cash along with one share of new company stock, costing the company about $380 million. Under the agreement, Cyanamid will pay Immunex $350 million in cash and contribute to the new venture its oncology business, with estimated 1992 sales of $115 million. Cyanamid will have the option to increase its ownership in Immunex to 70% through purchase of stock. However, if product sales from its oncology business do not achieve projected levels in 1993 through 1997, Cyanamid will contribute additional cash or other considerations to the new company. Cyanamid will take a onetime charge against 1993 earnings of $350 million to $400 million. Immunex, with only one biopharmaceutical product on the market, will gain added cash with which to fund what many industry observers consider a promising product development pipeline. Immunex's total revenues for the first nine months of 1992 reached nearly $53 million, but competition, hefty spending on R&D, and litigation costs led to a net loss of $10.4 million. Immunex will use $60 million of the cash to exercise its option to acquire Receptech, an independent product development operation it spun off in 1989. Cyanamid and Immunex will develop therapeutic agents for cancer and immunologic-related diseases through coordinated R&D. Eight oncology products will DECEMBER 21,1992 C&EN

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be marketed and, from a deal made earli­ er this year by Immunex, five BristolMyers Squibb oncology products will be comarketed. Immunex will have exclusive North American rights to new products developed. For these products, Cyanamid will have rights in all other countries. Cyanamid also will have the right of first refusal on new Immunex products—other than anticancer drugs—aimed at markets outside North America. Ann Thayer

Recombinant blood dot factor cleared for sale The Food & Drug Administration and the Canadian Bureau of Biologies have granted the first marketing licenses for a recombinant form of factor VIII. Factor VIII is the blood clotting factor that is deficient in persons with hemo­ philia A, the most common form of the disease. The drug is just the second new genet­ ically engineered product to get FDA clearance in 1992, joining Chiron's interleukin-2. The drug results from a 10-year R&D collaboration between Genetics In­ stitute, a 12-year-old biotechnology firm in Cambridge, Mass., and its marketing licensee worldwide, Baxter Healthcare, Deerfield, ΠΙ. It also is the first product to win FDA approval for Genetics Institute, which wiU manufacture it in bulk and

receive royalties on sales. Recombinant factor VHI differs only in the way it is made—in tissue culture— from factor VHI currently available, which is extracted from large quantities of hu­ man blood. The recombinant protein has pharmacokinetic behavior equivalent to material derived from blood plasma, but eliminates any possibility of transmitting diseases such as AIDS and hepatitis. However, FDA stresses that all antihemo­ philic factors currently licensed in the U.S. are prepared in ways believed to elimi­ nate the risk of transmitting those viruses. Baxter currently produces and markets a form purified from blood plasma. Factor Vin was among the first geneti­ cally engineered proteins to be developed.

genes, had been deleted. All of the ani­ mals have remained healthy for more than three years after innoculation with the mutated virus. Twenty-seven months after the vacci­ nation, four of the six vaccinated animals were challenged with standard doses of wild-type, pathogenic SIV. None devel­ oped evidence of SIV infection. Thirtyseven weeks after the initial challenge, two of the same four animals were chal­ lenged with very high doses of patho­ genic SIV. Again there was no subse­ quent evidence of SIV infection. The researchers say they do not know what mechanisms are responsible for the protective immunity observed in the ex­ periments. They note that most viral vac­ cines currently in use in humans are of the live attenuated variety, because it is "diffi­ cult to match live virus infection for the strength, breadth, nature, and duration of the immune response that is generated." Their current results "suggest that live attenuated HTV-1 may also be the most potent, effective vaccine for the prevention of AIDS," the researchers report. Safety Vaccination with a live, attenuated simi­ concerns are likely to be the key issue for an immunodeficiency virus (SIV) com­ development of this vaccine approach in pletely protects rhesus monkeys from humans, because the approach involves SIV infection, according to researchers at infection with a retrovirus, rather than Harvard Medical School's New England simply exposure to retroviral antigens. Nevertheless, if other vaccine approaches Regional Primate Research Center. The vaccine offered "the most impres­ show little or no efficacy, "limited safety sive protective effects we have seen in any testing of live, multiply deleted HIV-1 in of our vaccine experiments/' the scientists high-risk human volunteers seems war­ reported last week in Science [258, 1941 ranted," the researchers conclude. In another report on AIDS research (1992)]. Indeed, the team, led by Ronald G Desrosiers, suggests that the approach last week in Science [258, 1935 (1992)], may be applicable to developing a vaccine Larry O. Arthur and coworkers at the against human immunodeficiency virus National Cancer Institute's Frederick Cancer Research & Development Center (HIV-1), which causes AIDS. Developing an effective AIDS vaccine demonstrate that human cellular pro­ has proved to be far more difficult than teins associate with the surface of immu­ researchers predicted when HIV-1 was nodeficiency viruses like SIV and HIV-1. identified in 1984. Efforts to develop a The proteins, β2 microglobulin and hu­ protective SIV vaccine—generally ac­ man lymphocyte antigen (HLA) DR α cepted as a model for an HIV-1 vac­ and β chains, are present in appreciable cine—also have largely failed, despite re­ amounts on the viruses. The research searchers' ability to employ riskier strat­ suggests that the proteins play an active egies in developing candidate animal role in the life cycles of these viruses. Researchers reported in 1991 the vaccines than with human vaccines. SIV candidate vaccines tested so far anomolous result that monkeys vacci­ have included SIV subunits, inactivated nated with uninfected human cells whole SIV particles, and vaccinia virus were protected to some degree against subsequent infection with SIV grown recombinants that express SIV genes. Desrosiers and primate research cen­ in human cells. The NCI results sug­ ter collaborators Muthiah D. Daniel, gest that antibodies to proteins found Frank Kirchhoff, Susan C. Czajak, and on human cells may disrupt SIV func­ Prabhat K. Sehgal vaccinated six mon­ tion by binding to the β2 microglobulin keys with SIV from which a portion of or HLA DR molecules on the virus. Rudy Baum the nef gene, one of the SIV regulatory

Genentech licensee Miles also expects ap­ proval soon. Several years ago, Genetics Institute and Genentech cross-licensed— on a worldwide, royalty-free basis—factor VIA patents and its orphan drug designa­ tion, which gives companies a seven-year exclusive market. However, there is an ongoing patent interference proceeding before the U.S. Patent Office involving factor VIII pat­ ents held by Genetics Institute and Chi­ ron, which has licensed its patent to Novo Nordisk. And Scripps Clinic & Re­ search Foundation and drug producer Rorer claim that a patent they hold relat­ ed to factor Vin purification is infringed by recombinant products (C&EN, April 27, page 30). Genetics Institute says a court decision on this suit may come by mid-1993. Ann Thayer

Vaccine shields monkeys against AIDS

However, this factor is relatively large, somewhat fragile, and heavily glycosylat­ cial development. Both Genetics Institute ble drugs, which have been awaiting FDA and Genentech have now developed via­ clearance for over two and a half years. ed, so technical hurdles slowed commer­

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DECEMBER 21,1992 C&EN