US Court of Appeals Decides Enantiomer Patent Term Extension Case

We don't usually report on US issues, but Jeffrey S. Boone, Vice President, Intellectual Property, for Covidien (Hazelwood, Missouri, US) has kindly sent us this update on patent term extensions in the US.

"In the United States, the Court of Appeals for the Federal Circuit (CAFC) today (2010 May 10) issued its decision in the case of Ortho-McNeil Pharmaceutical, Inc. v Lupin Pharmaceutical, Inc. The court decided that the previous approval of a racemic mixture does not prevent a patent term extension for a single isomer of the racemic mixture.

US 4,382,892 claims ofloxacin, an antibiotic which is a racemic mixture of equal amounts of two stereoisomers (enantiomers). The patent was granted in 1983 and the US FDA approved the commercial marketing of ofloxacin (FLOXIN®) in 1990. In 1991 a subsequent patent, US 5,053,407, was granted for levofloxacin, one of the enantiomers in ofloxacin. In 1996 the FDA granted marketing approval for levofloxacin, which has been sold under the proprietary name LEVAQUIN®.

The plaintiff submitted an application for a Hatch-Waxman patent term extension for the ‘407 patent, which claims the single enantiomer. With full knowledge that the racemic mixture had been previously granted marketing approval, the FDA decided that the marketing approval of levofloxacin (the single enantiomer), was the “first” permitted commercial marketing or use of the “product”, as defined under 35 USC 156(f)(1). Thus, the FDA decision, which was consistent with several similar prior cases, was essentially that the racemic mixture and the single enantiomer were not the same “product”, as defined by the statute.

In litigation that resulted from the defendant’s filing of an ANDA (an application for a generic version of LEVAQUIN), the defendant, Lupin, argued that an enantiomer is half of its racemate, and thus the enantiomer was a component of the previously approved drug. However, the district court declared on 2009 April 30 that the patent term extension was valid.

Now, the court of appeals has affirmed the district court. The court quoted one of the witnesses who stated “in each and every instance in which it has considered the question, the FDA has described a racemate as a single active ingredient, distinct from its enantiomers, and each enantiomer as a single active ingredient distinct from the other and from the racemate”."

You can read the case here.

Double-patenting and terminal disclaimer still can't stop generic Mirapex

Following a trial held in March, the US District Court for the District of Delaware held that Boehringer Ingelheim's patent for Mirapex (pramipexole dihydrochloride) was invalid for "obviousness-type double patenting". This product, which is indicated for the treatment of Parkinson's disease and Restless Leg Syndrome, has enjoyed annual sales in the US of approximately $380 million.

Both Barr Labs and, a little later, Mylan filed abbreviated new drug applications (ANDA) to manufacture a generic version of Mirapex in 2005, with paragraph IV certifications against the validity of Boehringer's US patents 4,843,086 and 4,886,812. Boehringer responded by filing suit against Barr and Mylan, and the cases were consolidated for trial.

The district court affirmed the principle that the same invention can't be patented twice. In this case the '086 patent -- which expired during the course of the litigation -- claimed methods of treating certain diseases by administering tetrahydrobenzthiazoles, while the '812 patent claimed the tetrahydrobenzthiazole compounds themselves, including pramipexole dihydrochloride. Said the court:

"Although there are differences between the '812 patent and the '086 patent, . . . those differences are insufficient to support the patentability of the '812 patent in light of the '086 patent".

Double-patenting may be avoided by making a terminal disclaimer. During the trial Boehringer terminally disclaimed

"...only the terminal part of the statutory term of the '812 patent which would extend beyond the 1,564 days after the full statutory term of the '086 patent as that term is defined in 35 U.S.C. § 154, so that by virtue of this disclaimer, the '812 patent will expire on October 8, 2010".

Boehringer received a 1,564 day extension under 35 USC § 156 due to FDA regulatory review of Boehringer's New Drug Application for Mirapex. As a result of this patent term extension, the original expiration date of the '812 patent, 12 December 2006, was extended to 25 March 2011. Thus, by its terminal disclaimer, Boehringer disclaimed five and a half months of patent term (the period of time between the expiration date of the '086 patent and the original expiration date of the '112 patent). According to Boehringer, its terminal disclaimer blocked Barr and Mylan's double-patenting argument. The court disagreed:

"A dual problem is presented in that the terminal disclaimer was not only filed at or near the conclusion of trial in this action, but it was also filed after the expiration of the earlier '086 patent. ...[F]or a terminal disclaimer to be effective, the earlier filed patent must not have expired at the time of the filing of the disclaimer"

Source: iStockAnalyst.