Glaxo/Novopharm Zantac infringement argument questioned by three-judge appeals court.

GLAXO v. NOVOPHARM: ZANTAC INFRINGEMENT QUESTIONED BY FEDERAL APPEALS COURT in a Jan. 7 oral arguments hearing in Washington, D.C. The three-judge D.C. federal appeals court addressed Glaxo Wellcome's argument that Novopharm's ANDA for generic ranitidine Form 1 is an infringement because of the "possibility" that Novopharm's generic Form 1 product also could contain Form 2, which Glaxo says would violate the firm's patent on Zantac (ranitidine Form 2).

Novopharm's ANDA contains a product composition test that theoretically would allow trace amounts of ranitidine Form 2 in its product. The test is the same used by Glaxo in its patent application for Form 1. A Raleigh, N.C. court ruled that Novopharm's use of the test does not support an infringement argument ("The Tan Sheet" July 15, 1996, p. 15). Under the lower court decision, Novopharm is able to launch a generic version of Rx ranitidine (Form 1) in July.

If the circuit court's decision is upheld, private label versions of Zantac 75 could be on OTC shelves in December 1998 -- the expiration date for the H2 antagonist's exclusivity under Waxman/Hatch. If the appellate court reverses the Raleigh court's decision, private label marketers would be unable to introduce generic Zantac 75 until the 2002 patent expiration of Form 2 ranitidine.

D.C. appeals court Judge Alan Lourie declared that "the act of infringement ultimately will be what is sold." If Novopharm were selling ranitidine Form 1 that includes Form 2, then Glaxo would have an obvious infringement case, Lourie pointed out.

"If we affirm the district court's judgment that there was no Form 2 in your product and you go on the market and it turns out that it's 2%-3% Form 2, are you free from infringement," Lourie asked Novopharm. "Absolutely not," Novopharm attorney Robert Green (Leydig, Voit & Mayer, Chicago) replied. "We'd be back in court in the blink of an eye and we know that. There is nothing that comes from this court's decision or the lower court's decision that gives Novopharm any entitlement to make a product that contains a mixture," Green added.

Glaxo attorney Stephen Judlowe, of the New York City firm Hopgood, Calimafde, Kalil & Judlowe, countered that, under the Waxman/Hatch Act, filing for approval of a product that "may be a mix" of infringing material and non-infringing material is in itself an infringement. "The act of infringement is not the [product] sample. It's the scope of the authority that you solicit," he argued. "If the scope of the approval that you seek is broad enough to encompass some Form 2 [ranitidine], you have legal jeopardy."

Glaxo also alleges that Novopharm has not indicated that its ranitidine will contain "pure Form 1 and nothing else," Judlowe said. "The standard that they have achieved...and the one they applied for always had Form 2 in it." Glaxo "had the burden of coming forward to the district court and showing that samples produced by the Novopharm supplier as a raw material infringed the patent at suit and they did not do that," Novopharm attorney Green countered. Novopharm had scientists "analyze samples by X-ray and infrared spectroscopy and testify that...there was no Form 2 in that product."

Novopharm said it is "busy preparing for the launch" of generic Zantac, which received tentative approval from FDA on Nov. 4, 1994. The company has completed construction of its $38 mil. ranitidine production facility in Wilson, N.C. The expiration of the Form 1 patent occurs on July 25.

Glaxo has suits pending against six other potential generic manufacturers of ranitidine, including CibaGeneva/Interchem/Union Quimico, Boehringer Ingelheim, Hoechst Marion Roussel/Chelsea, Torpharm/Apotex, Pharmadyne and Hexal. Glaxo settled with Genpharm.