Judge Rodney Sippel of the U.S. District Court for the eastern district of Missouri, on January 17, 2006, has ruled under summary judgment in favour of the generic challengers, clearing their way to launch generic versions of Toprol-XL in U.S. market. This is, however, a pyrrhic victory for generic manufacturers after successive paragraph IV defeats in Lipitor (Atorvastatin Calcium, Ranbaxy losing to Pfizer), Accupril (Quinapril Hydrochloride, Ranbaxy losing to Pfizer), Norvasc (Amlodipine Besylate, Dr. Reddy's loses to Pfizer) and Zyprexa (Olanzapine, Dr. Reddy's loses Eli Lilly). The court has favoured suits filed by KV Pharmaceutical Co, Andrx Corp. and Eon Labs Inc. (a unit of Novartis AG), challenging the validity and enforceability of Orange Book listed patents. Astra, which earlier contended before the District Court that its patents on Toprol-XL will survive their patent term, has made an appeal against the judgment in the U.S. Court of Appeals maintaining that both U.S. patents (5001161 and 5081154) are valid and enforceable.

Targeting paragraph IV

To recap, in February 2004, AstraZeneca filed a patent infringement lawsuit against Andrx Corp. in the United States District Court for the District of Delaware as a result of a paragraph IV certification letter submitted by Andrx concerning its intent to manufacture and sell generic form of Toprol-XL in the 50 mg dose form in US. Again, in July 2004 AstraZeneca filed a second patent infringement against Andrx Corp. in the same District Court following the Andrx's notification that it had filed ANDA under paragraph IV with US FDA for seeking approval to market generic form of Toprol-XL 50 mg dose form. Astra advocated that Andrx infringes its patents covering Toprol-XL.

In the same year, AstraZeneca also filed a lawsuit in the District Court for the District of Delaware against generic manufacture, Eon Labs, for patent infringement following the Eon's move for market approval of generic form of Toprol-XL for all dose forms under paragraph IV.

Moreover, later in the same year, AstraZeneca filed legal proceedings against KV Pharmaceutical Company in the District Court for the Eastern District of Missouri this time following the KV's notification regarding ANDA submission under paragraph IV for market approval of generic form of Toprol-XL 50 mg dose form. Earlier to this AstraZeneca filed a suit in May 2003 against KV Pharmaceutical Company for patent infringement by the 200 mg dose form of Toprol-XL and again in August 2003 for patent infringement by the 100 mg dose form.

Pre-trial discovery

All of these pending patent litigations later consolidated for pre-trial discovery purposes and motion practice in the U.S. District Court for the Eastern District of Missouri, which do not include a jury. A pre-trial discovery means that a party to a lawsuit should not be surprised by its adversary on the day of trial, and therefore, has the right to full discovery, prior to trial, of all relevant evidence, including documents (broadly defined to include virtually every tangible and intangible form of record keeping) and witness testimony related to the matter at issue in the litigation. In other words, each party to the suit attempts to "discover" relevant or pertinent facts. However, in this trial consideration was of the validity and enforceability of two AstraZeneca patents (US Patent No. 5,081,154 and 5,001,161) relating to active ingredient (metoprolol succinate per se) and composition of Toprol-XL (extended release tablet of metoprolol succinate) and to determine whether the defendants in the case infringe those patents. Both '154 and '161 patent were due to expire in September of 2007.

Back in game!

The judgment day belongs to generics, a much needed victory for all Para IV seekers. Judge Rodney Sippel in his summary judgment found that AstraZeneca's patents (US Patent No. 5,081,154 and 5,001,161) on Toprol-XL were "both invalid due to double patenting and are unenforceable due to inequitable conduct." Astra's both '161 patent and '154 patent are invalidated on the basis of double patenting over the US 4,780,318 patent and are considered unenforceable based on Astra's inequitable conduct in the prosecution of these patents in the United States Patent & Trademark Office concerning inventorship dispute over metoprolol succinate with their competitor named Lejus Medical. However, it was also argued during proceedings that Astra intentionally did not name the correct inventors in Astra's prosecution of patents in suit. Court found that Astra's failure was done with an intent to deceive the patent examiner about the inventorship dispute and to avoid questions concerning Astra's ability to claim priority to the '318 patent application and to avoid potential prior art concerning metoprolol succinate.

This means that now generic challengers can launch their generic copies of Toprol-XL in US. Andrx being the first to file ANDA under Para IV will be, however, entitled to 180 days exclusivity on the 50 mg strength of generic Toprol-XL under Hatch-Waxman Act. But Andrx's approval and launch of generic Toprol-XL will depend on FDA clearance and approval requirements and outcome of subsequent legal proceeding made by AstraZeneca in US Court of Appeals. Even though, Astra has made an appeal against the judgment in the U.S. Court of Appeals, what cannot be denied is that generics challengers are back in game.


(The author is working with a Mumbai-based pharmaceutical company)