SMITHKLINE BEECHAM v. GLAXO: ONDANSETRON INFRINGES USE PATENT

SMITHKLINE BEECHAM v. GLAXO: ONDANSETRON INFRINGES USE PATENT issued to SmithKline Beecham on Nov. 8, 1988, the April 26 complaint alleges. Filed in Philadelphia federal court and announced by SB on April 30, the lawsuit charges that Glaxo's I.V. drug Zofran (ondansetron) for the treatment of cytotoxic or radiotherapy-induced nausea and vomiting infringes a SB patent for "the treatment of emesis, nausea and vomiting." The SB patent expires Dec. 12, 2006. The complaint states that its patented method of use "involves administering . . . an effective amount of certain compounds, one of which is ondansetron," the 5HT3-receptor antagonist subsequently covered by a Glaxo product patent. SB's 5HT3 product granisetron currently is in clinicals for an anti-emesis indication. Granisetron was developed in Japan by Beecham Yakuhin. The SB patent itself states that the compounds are of two formulas "or a pharmaceutically acceptable salt thereof: Ar-CO-Y- Z." i.e., "classes of compounds which are aryl amides and esters having an azabicyclic side chain which are 5-HT receptor antagonists." The patent notes that earlier U.K. patent applications described these classes as "useful in the treatment of migraine." Another U.K. patent application "describes a class of tetrahydrocarbazolones which are also 5-HT receptor antagonists. It has now been discovered," the patent states, "that these classes of compounds and related compounds block the emetic response induced by cytotoxic agents such as cisplatin and also by radiation treatment." The complaint charges Glaxo with "willfully and deliberately inducing and/or contributing to the infringement of one or more of claims 5-9" of the patent and seeks a permanent injunction barring Glaxo sales of ondansetron and treble damages, including interest. Glaxo has estimated that there are 1 mil. new cases of cancer diagnosed each year and 500,000 patients who undergo chemotherapy. Based on the repeated courses required for treatment, Zofran could be prescribed for 2.5 mil. annual episodes of chemotherapy and radiotherapy emesis and nausea. The Zofran market easily could surpass $ 100 mil. in annual sales in the U.S. alone ("The Pink Sheet" Dec. 10, p. 11). Glaxo is reviewing the suit. A spokesperson said: "We believe our patent position on ondansetron is strong and does not infringe on any patent of SmithKline Beecham." Glaxo received approval for ondansetron on Jan. 4 and launched the product in February ("The Pink Sheet" Jan. 7, p. 3 and Jan. 14, T&G-2). The company filed its NDA for I.V. ondansetron in October 1989. An NDA for oral ondansetron was filed in August 1990 and Glaxo has said it will file in the fourth quarter of this year for a post-operative nausea and vomiting indication. Granisetron had been in clinical development by SmithKline as a treatment for migraine but was dropped by the company for that indication in the spring of 1990, when long-term dosing studies in rats and mice showed an increased risk of liver tumors ("The Pink Sheet" March 5, 1990, In Brief). Injectable granisetron currently is in Phase III studies for chemo or radiotherapy-induced nausea and vomiting. The company expects to file an NDA this year and recently predicted that it will receive approval for granisetron in 1993 or 1994. Oral granisetron is in Phase II. The product, which will be marketed under the brandname Kytril, has been registered for approval in the U.K. and a number of other European countries. The drug is approved only in South Africa, where it is awaiting introduction. The timing of the SB complaint is curious, coming so long after Glaxo received its ondansetron product patent, filed the NDA, received approval and launched the product. Industry observers note that delays in the filing of litigation can be caused when two parties discuss royalties or cross-licensing arrangements in protracted discussions that ultimately break down. SmithKline's challenge coincided with a Glaxo's hospital sales force annual meeting in California during the week of April 30. If nothing else, the announcement of the suit presumably acted as a distraction to Glaxo's efforts to charge up the sales effort for the product. SB is being represented in the case by Ballard Spahr Andrews & Ingersoll (Philadelphia) and Finnegan, Henderson, Farabow, Garrett & Dunner (Washington, D.C.). Glaxo has not disclosed its attorneys. The case has been assigned to the courtroom of Judge Lewis Bechtle. No court date has been set.