Taking a pre-emptive strike to protect its anemia drug Epogen, Amgen Inc. filed a lawsuit against F. Hoffmann-La Roche Ltd. and its subsidiaries to prevent the pharmaceutical company from selling a pegylated version of recombinant human erythropoietin.

Roche's EPO product, NeoRecormon (epoetin beta), is marketed in Europe but is shut out of the U.S. market because of Amgen's six U.S. patents. That's why Basel, Switzerland-based Roche intends to introduce a different blood disorder product to the U.S., one that it calls Ro50-3821, or CERA (continuous erythropoiesis receptor activator).

But Amgen does not believe that CERA is distinct from NeoRecormon.

"My sense is that they will be trying to show CERA is essentially a pegylated version of NeoRecormon," said Christopher Raymond, an analyst with Chicago-based Robert W. Baird & Co. "And it's my sense that Roche is going to be trying to show that it's not. It's an entirely different compound and stands outside the picket fence that protects Amgen's patents."

According to the complaint filed in the U.S. District Court in Boston, Roche infringes six of Amgen's seven patents that protect the EPO inventions of Amgen scientist Fu-Kuen Lin. It states, based on "information and belief," that Roche's CERA contains glycosylated human EPO and that Roche produces that human EPO by means of one or more processes claimed in Amgen's patents. It also claims that Roche has begun manufacturing operations at a new facility in Penzberg, Germany, is importing the product into the U.S. and plans to soon file a biologics license application with the FDA hoping to gain approval within the next 12 to 14 months.

"When reading the complaint, it looks like there was some sleuthing on the part of Amgen in regard to Roche's activities, and they basically found that it looks like they were hiring managers, and they even tried to recruit some of Amgen's personnel," Raymond told BioWorld Today. "They are even alleging that they are contacting large dialysis clinics about purchasing the drug."

It is the second lawsuit filed in the last month regarding Epogen. A suit was filed in October by New Brunswick, N.J.-based Johnson & Johnson against Amgen for certain contracts with oncology clinics in which Epogen and other drugs are offered at a discount. Licensed from Amgen, J&J markets the recombinant human EPO product Procrit. Amgen has said in a statement that it believes its contracts are "lawful, pro-competitive and in the best interest of customers and their patients."

Thousand Oaks, Calif.-based Amgen has had success in the court system. It defended the validity of an Amgen patent that described isolated purified EPO DNA and cells containing such DNA in a suit against Cambridge, Mass.-based Genetics Institute Inc. and Tokyo-based Chugai Pharmaceutical Co. Ltd., which now is a Roche subsidiary. Roche currently manufactures epoetin beta in Europe under a Genetics Institute license.

Amgen also prevailed more recently in a long battle with Cambridge, Mass.-based Transkaryotic Therapies Inc. and Hoechst Marion Roussel Inc. (now Aventis Pharma AG, of Frankfurt, Germany) concerning Dynepo (epoetin delta), a gene-activated EPO that TKT was developing for the U.S. market. The court's decision enforced and defended the validity of claims in four of Amgen's patents, all of which happen to be at issue again in the suit against Roche. (See BioWorld Today, Oct. 19, 2004.)

Both the suit against Genetics Institute and Chugai, as well as the suit against TKT and Aventis, were presented before a judge in the U.S. District Court in Boston.

"This suit [with Roche] is filed in that very same court," Raymond said. "Looks to me what they're trying to do is get [Judge William G. Young], who heard the last patent suit, since he's done so much work on it."

EPO is a protein naturally produced by humans that stimulates the production of red blood cells. Early attempts to find an EPO product from urine or blood did not work because they yielded only small quantities of unstable or impure proteins. Efforts to purify human EPO from cultured cells also failed because the cells were not available and reports of their ability were overstated. Scientists also found it futile to use conventional scientific techniques to identify the amino acid sequence of human EPO or the DNA that encodes it.

But Lin's inventions found a way to produce therapeutically effective human EPO products. According to Amgen's complaint against Roche, the company's U.S. patents cover ways to "isolate and characterize the DNA that encodes human EPO, the amino acid sequence of human EPO, invented vertebrate and other cells capable of producing human and other EPOs in abundance when grown in culture, invented methods for producing glycosylated EPO polypeptides," and invented EPO products, including Epogen (epoetin alfa).

The patents all have several years of U.S. life left, with certain process patents expiring in 2012, a composition of matter patent expiring in 2013, and others expiring as late as 2015.

Epogen first gained FDA approval in 1989 for anemias associated with kidney failure. Subsequent approvals occurred in 1990 for acute lymphocytic leukemia in HIV-infected patients and in 1993 for anemia caused by chemotherapy in patients with nonmyeloid malignancies.

Third-quarter sales of Epogen fell by 12 percent to $599 million, from $681 million in the third quarter of last year, due to the increased use of Amgen's newer anemia drug, Aranesp (darbepoetin alfa), in the hospital setting.

But some analysts have expected those sales to decline, and do not view Amgen's EPO lawsuits as surprising, let alone a reflection of any nervousness over prospective competition.

"Certainly, they are vigilant about people who they feel infringe," Raymond said, adding that the lawsuit against Roche was "fully expected," although it occurred earlier than anticipated.

Raymond thought Amgen would file later this year, closer to the time that Roche might submit a BLA. But based on what Roche has said at several investor meetings, it was clear that a head-to-head controversy was inevitable.

"There's been a level of belief," Raymond said, "that Roche intends to launch at risk - that is, launching this drug knowing full well that they'll get sued, and believing that they'll win."

Amgen's stock (NASDAQ:AMGN) rose 42 cents Wednesday to close at $80.22.