Amgen Inc.'s ultimate victory in the legal war more than a decade ago against Genetics Institute Inc. (GI) over erythropoietin patents went all the way to the U.S. Supreme Court, but experts last week were split on how far the latest EPO skirmish - pitting Amgen against would-be competitor F. Hoffmann-La Roche Ltd. - might go.

GI ended up pleading its case to the U.S. Supreme Court after an appellate ruling in March 1991 invalidated the firm's EPO patent, which meant a one-time, $11 million charge for GI and turned over the lucrative EPO market to Amgen, which has since developed Aranesp, the second generation of Epogen (epoetin alfa).

In the third quarter of 2006, Aranesp (darbepoetin alfa), for chemotherapy patients with anemia reaped $1.07 billion in sales, a 27 percent increase that helped revenues rise 15 percent to $3.61 billion from $3.15 billion in the third quarter of last year.

Something as lucrative as EPO is bound to attract biotech and pharma players. Another to make news this month was the Chinese firm 3SBIO Inc., which is targeting $124 million in an initial public offering in the U.S. 3SBIO plans to sell about 7.2 million American depositary shares - representing about 50.3 million ordinary shares - priced between $12 and $14 each. The company's ADRs would be listed on Nasdaq under the ticker "SSRX."

Epiao, an injectable EPO, is 3SBIO's top-selling product. Sales of the drug make up nearly 80 percent of revenues, which totaled $11.7 million for the first nine months of 2006. A concentrated high dose of Epiao is undergoing late-stage trials, and the firm hopes to file for approval in China this year. Clinical work on a second-generation Epiao product, NuPiao, is set to begin in 2008.

3SBIO also has Tpaio, a recombinant human thrombopoietin for chemotherapy-induced thrombocytopenia. Cleared about a year ago for marketing in China, Tpiao won five years of marketing exclusivity, threatened only by a firm that gained approval for clinical development of its product ahead of the approval of Tpiao, which Tpiao also is in development for idiopathic thrombocytopenia purpura.

Neose Technologies Inc. is another to grab headlines in the EPO space, with the start this month of a Phase II trial with NE-180, a long-acting glycopegylated EPO for anemia in cancer patients with nonmyeloid malignancies, as well as anemia associated with chronic kidney disease. The Phase II study will test subcutaneous administration of NE-180 in about 45 cancer patients receiving platinum-based chemotherapy for an expected duration of four chemo cycles.

Both of Amgen's EPO products are involved in the company's lawsuit against Roche, which wants to introduce U.S. patients to its red-blood cell booster: continuous erythropoiesis receptor activator (CERA, now branded Mircera), even though six patents held by Amgen have blocked the pharma giant's European EPO product, NeoRecormon (epoetin beta), from sale here.

"Roche is claiming that the longevity of [Mircera] is greatly improved," and the compound is said to function differently in the body from Epogen or Aranesp, noted patent attorney John Iwanicki of Banner & Witcoff Ltd. of Boston, which represented Amgen in the GI battle but is not involved in the current matter.

The case is set for trial in September. "In order for it to terminate early, the judge would have to grant summary judgment," which ordinarily would happen much earlier in the case, Iwanicki said. Since it didn't, there likely are "serious technical issues there that are raising a question of material fact," he told BioWorld Financial Watch.

This didn't stop analysts from offering their opinions. First to gain major notice was Mark Schoenebaum of Bear, Stearns & Co., who said newly filed court documents suggest Mircera is just pegylated EPO, like Amgen's products, and Roche probably can't win the case.

Schoenebaum said Amgen could trade sharply higher if Wall Street "fully digests this development," but investors late last week were still pushing beans around on their plates, with the stock moving little, up or down.

The Roche alarm was sounded as long ago as October 2003, when Sanford C. Bernstein, an investment research and management unit of Alliance Capital Management LP, cited three issues that would determine whether Mircera (then still known as CERA) could reach the U.S. market: the drug's clinical profile; the ability of Roche to break the patent defenses of Amgen and licensee Johnson & Johnson; and CERA's worth against EPO generics. (See BioWorld Financial Watch, Oct. 27, 2003.)

Bernstein's report called CERA's chances "good - a view not fully appreciated by consensus." Full consensus, if it existed in the first place, doesn't anymore, although Christopher Raymond, analyst with Robert Baird & Co., four months ago called Mircera's data set "decidedly less compelling" than Amgen might have feared.

Trials conducted by Roche with Mircera for chronic kidney disease might be even less robust than Amgen's data for the supplemental biologics license application for Aranesp against CKD, which gained an approvable letter in October from the FDA. The agency gave its nod to Aranesp dosed once every two weeks, as well as once-monthly dosing regimens for CKD patients with anemia not on dialysis. But it asked for more data for the once-monthly dosing regimen, including another study.

Eric Schmidt, analyst with Cowen and Co., said at the time of the Bernstein report that the world has "enough experience with the TKT litigation to know [Amgen's] patents are pretty strong, pretty all-encompassing." What's more, the venue in which Amgen will face off with Roche is the same where Amgen triumphed over Cambridge, Mass.-based Transkaryotic Therapies Inc. and Hoechst Marion Roussel Inc. (later to become Aventis Pharma AG) in a disagreement over Dynepo (epoetin delta), a gene-activated EPO that TKT was developing for the U.S. market.

Joel Sendek at Lazard Capital Markets, who favors Amgen, called U.S. District Court Judge William Young "Amgen-friendly." Young already has issued some terse rulings against Roche in pre-trial action, the docket shows. An example is the decision earlier this month on an objection to Amgen's economics experts.

"Roche opposition raises no matters with which this court ought [to] concern itself," the judge said. "Presumably, the purported experts are themselves familiar with their legal duties."

A research report, though, by Michael Aberman, analyst with Credit Suisse, won wide circulation like Schoenebaum's - and Aberman forecasted that Roche would beat Amgen, with a launch of Mircera possible as early as May.