WASHINGTON _ Years after the scientists go home from today'sthrombopoietin characterization party, lawyers will still be arguingover patent rights to the discovery. And patent protection will be key toreaping the potentially enormous commercial rewards of the datapublished today in Nature.Just how big will those rewards be? One indication: ZymoGeneticsInc., the wholly owned Seattle-based subsidiary of NovoNordisk A/S,of Denmark, that published data on the sequence and function ofmurine thrombopoietin in Nature, has nicknamed the molecule "TPO."It's a cheery echo of "EPO" (for erythropoietin), Amgen Inc.'s drug tostimulate production of red blood cells that hauled in more than $1billion worldwide in 1993.If safe and effective in humans, TPO could be used by as many as200,000 cancer chemotherapy patients annually, a market size that willinsure a vigorous patent dispute. Analysts said on Wednesday that theprincipal competitors in the TPO patent wars will likely be South SanFrancisco-based Genentech Inc. (which published the sequence andfunction of human TPO in Nature) and ZymoGenetics.One other strong contender may be Amgen Inc., of Thousand Oaks,Calif. Although Amgen did not publish data in Nature today, thecompany announced on Wednesday an agreement to jointly developand market a "novel platelet growth factor" with Kirin, its Japanesepartner for marketing Epogen and Neupogen.It's unclear if Amgen's platelet growth factor is the same molecularentity as the one described in Nature. The company said it will publishits data "very soon" in a scientific journal. Analysts speculated that thetiming of Amgen's announcement, coming one day before the Naturearticles hit, was designed to steal some of the thunder from Genentechand ZymoGenetics _ the first two companies to publish sequence andfunction data for TPO.Amgen would not disclose whether it has filed patent applications forits recently revealed discovery, but Genentech and ZymoGeneticsconfirmed that they have both filed patents. Genentech's press releaseon TPO even included the bold subtitle, "Company is confident ofpatent position."Genentech spokesman Geoff Teeter said that his company believes it isthe first to report the sequence of human TPO but added that the patentsituation is "a very complex and factual and legal question which willbe determined over the next several years."Mark Murray, director of new business development for ZymoGeneticssaid that going from the mouse TPO sequence to the human version is"trivial." And he added, "just because we haven't published the humansequence doesn't mean we don't have it.""If there is only one platelet growth factor, the key will be who firstidentified and cloned it," Amgen spokesman David Kaye toldBioWorld. "Clearly, Amgen has developed an expertise inhematopoietic growth factors and we're confident that we'll continueto be the major player in that field."Credit To Those Who Publish FirstWhile journal publication is only one leg of a scientific race, it'sgenerally the one accompanied by the greatest fanfare. "Credit for thediscovery, in the eye of the casual observer, goes to the party whopublishes first," observed Cowen & Co. analyst David Stone.According to Robertson, Stephens & Co. analyst Mark Simon,Genentech stands to win both the fanfare and patent victories."Based on an extensive due diligence process, we believe thatGenentech will be the big winner in this area," Simon wrote in aninvestment memo dated today. "ZymoGenetics came in second, Amgencame in third and Immunex came in fourth. The key is the patents, andwe are confident that Genentech will win the patent race."Although Immunex Corp., of Seattle, also published an article intoday's Nature, the data concerned basic biology findings in animalsand did not suggest that the company has sequence or function data forTPO (although it doesn't rule out the possibility either). SpokeswomanValerie Dowell said that while the company has been working onidentifying platelet growth factors, its primary focus has been on itsplatelet product PIXYKINE, a fusion protein that combinesinterleukin-3 (IL-3) and granulocyte macrophage-colony stimulatingfactor (GM-CSF). She said she did not know if the company has filedany patents relating to TPO.Dowell pointed out that PIXYKINE was designed to address bothneutropenia (low white blood cell counts) as well as thrombocytopenia(low platelet counts) and thus was "two drugs in one" rather than solelya platelet booster.Numerous biotechnology companies have taken aim at the therapeutictarget of platelet production, proof of its alluring clinical andcommercial potential. An agent that could safely and effectivelyincrease blood platelet levels in patients would likely become ablockbuster drug. Interleukins appear to play a role in plateletstimulation, including IL-3, interleukin-6 (IL-6) and interleukin-11 (IL-11).Cowen and Co. analyst David Stone said that the field for products toboost platelet production is already crowded. Genetics Institute Inc., ofCambridge, Mass., has an IL-11 product in Phase II clinical trials andSandoz Ltd., of Switzerland, has both an IL-6 product and an IL-3/GM-CSF combination product on the verge of Phase III trials.Immunex is ahead of the current pack since PIXYKINE is alreadybeing used in a pivotal Phase III trial."A newly cloned factor will be one more in a long list of factors thataffect platelet lineage," said Stone. "Further, other products are yearsahead in terms of clinical development."But George Demetri, an associate professor at Dana Farber CancerInstitute and Harvard Medical School in Boston, said that the currentcrop of platelet promoters have proven limitations which were revealedin preclinical and early clinical work. Demetri, a self-described"growth factor nut" who has served as a principal investigator inclinical trials of G-CSF, GM-CSF, PIXYKINE, IL-3 and IL-6, said theTPO molecule has all the markings of a winner."The enthusiasm about this discovery is tremendous. The evidencestrongly suggests that this molecule is the pivotal regulator of plateletproduction," he told BioWorld. "All of the other molecules don't havethe right stuff because none of them singularly drive megakaryocyte (alarge cell that is the source of platelets) proliferation. Of course, thatdoesn't mean they won't be useful or important clinically."Demetri said that TPO will be easily translated into clinical use due toits singular and apparently potent effect on megakaryocytes. Hecompared it to G-CSF and EPO, which he called "easy home-run hits."He did offer one note of caution to inject into "the upcoming hysteria"about TPO's enormous market potential: scientists don't know what themolecule's toxicities will be in higher primates and humans. So far, it'sonly been tested in rodents. n

-- Lisa Piercey Washington Editor

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