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Lovenox Patent WarMomenta Pharmaceuticals, Inc. v. Amphastar Pharmaceuticals, Inc., Nos. 2012-1062, 1103, 1104 (Aug. 3, 2011) (Chief Judge Rader, Circuit Judges Dyk and Moore)

Litigation surrounding enoxaparin—a pharmaceutical drug used to prevent blood clots—has been raging for nearly a decade. In fact, this Federal Circuit opinion issued one day before the 9th anniversary of the date when the original patent lawsuit was filed.

The first ANDA litigation resulted in the original patent holder, Sanofi-Aventis, losing its case against Amphastar and its patent protection due to a finding of inequitable conduct in prosecuting the patent (under a pre-Therasense inequitable conduct legal standard). Amphastar’s success in that case, though, didn’t guarantee its success in the pharmaceutical marketplace selling generic enoxaparin. This litigation is a little unusual because it’s a battle between generic companies, Momenta and Amphastar.

A little background on the drug will explain why the generics are litigating against each other. Enoxaparin is a low molecular weight version of heparin. Heparin isn’t a single molecule; it’s a complex mix of different protein structures, and doses of enoxaparin contain many molecules with diverse molecular structures. Enoxaparin is created by breaking the heparin polysaccharide into smaller pieces that might have different sizes and disaccharide distributions based on the structure of the original heparin molecules.

Because of the drug’s molecular diversity, it’s difficult to replicate safely and precisely, and it took the FDA several years to determine whether enoxaparin was the type of drug that could even have a generic bioequivalent. Ultimately, the FDA decided that it could and established certain “standards of identity” to define enoxaparin worthy of approval and use by patients.

Although Amphastar was the first company to file an ANDA for enoxaparin (way back in 2003), it didn’t get FDA approval for its generic drug until September 2011. In the meantime, Momenta got FDA approval for its version of generic enoxaparin in June 2010.

Momenta happens to own a patent on its method of analyzing heparin and enoxaparin to characterize the molecular structures found in its generic drug. As soon as Amphastar received FDA approval, Momenta sued Amphastar for patent infringement. It alleged that Amphastar used Momenta’s patented process to test its enoxaparin product to confirm that the product meets the FDA’s bioequivalence standards for generic drugs. Momenta asked the district court for a preliminary injunction against Amphastar, which the court granted. Amphastar appealed that order to the Federal Circuit, which brings us to this opinion.

Smooth Sailing to the Patent Safe Harbor?

To determine whether Momenta is likely to succeed on the merits of its case, the Federal Circuit had to determine whether Amphastar’s process of testing of its generic product falls under the “safe harbor” provision of the Hatch-Waxman Act. This provision explicitly allows pharmaceutical companies that are producing generic drugs to use otherwise patented methods to test drugs and develop information to submit to the FDA—it’s a special exception to the standard patent infringement provisions. This opinion focuses on the scope of that provision, and the scope question incited fierce disagreement among the appellate panel members.

The statutory language in question is:

It shall not be an act of infringement to make, use, offer to sell, or sell within the United States or import into the United States a patented invention … solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs or veterinary biological products.

(See 35 U.S.C. § 271(e)(1) (emphasis added)). Under the majority’s reading, the phrase “reasonably related” is key. The majority interpreted Amphastar’s drug characterization activity as “reasonably related” to developing information for the FDA because it’s using Momenta’s patent method only for quality control testing of its products. The majority also gives “submission” a broad reading—Amphastar doesn’t actually have to give the test results to the FDA; it’s enough that Amphastar is required to conduct that testing and maintain records of it in case the FDA wants to see the results to meet the “submission” limitation.

Finally, the majority concluded that the safe harbor provision doesn’t distinguish between pre- and post-FDA drug approval activity that is “reasonably related” to development and submission of information to the FDA. Both can be covered by this provision since drug manufacturers have post-approval obligations to the FDA that are conditions for maintaining that FDA approval..

Under this broader reading of the safe harbor, the majority rejected the district court’s preliminary injunction order (since Momenta’s likelihood of success on the merits with its infringement case is now very low) and dropped a not-so-subtle hint that this case is primed for summary judgment of noninfringement when remanding it.

… Or Rough Waters?

In dissent, Chief Judge Rader strongly disagreed with the majority’s interpretation of the statute. Relying on piles of Hatch-Waxman legislative history, he concluded that the safe harbor provision applies only to pre-approval testing that’s conducted to get generic drugs on the market more quickly. He focused on the terms “solely” and “submission.” In his view, the word “solely” excludes later routine quality control testing, and “submission” shouldn’t be equated to maintenance of records.

He also expressed concern that the majority’s broad reading will “essentially render manufacturing method patents worthless.” He stated several times that Amphastar’s use is a continued infringement of Momenta’s patent to manufacture and sell its commercial product—it’s not merely experimental activity. He argued that allowing post-approval testing to fall within the safe harbor provision would “repeal[] the incentives of the patent act in this area” because other generic companies would simply copy the testing methods of the earlier-approved generics.

Under the dissent’s interpretation, the correct reading of the safe harbor provision limits the potentially infringing activity to pre-FDA-approval experimentation only.

Balancing Competing Patent and Public Interests

The Hatch-Waxman Act was designed to balance various interests including incentivizing innovation in the pharmaceutical industry and increasing price pressures and competition in the marketplace. This case is a bit unusual, because Momenta is a generic company and a patent holder, battling with Amphastar, another generic manufacturer. But does barring Amphastar from using Momenta’s method only for its quality control testing serve the public interest by incentivizing innovation? Or does it simply further delay competition? And are there other public interests at play, like ensuring safe and efficient regulation of drugs?

These are just a few of the policy questions I see percolating out of this case. And the majority and dissent offered very different readings of Supreme Court and Federal Circuit precedent on the scope of Hatch-Waxman (though I didn’t discuss it in depth here), so this opinion leaves a lot of room for debate about the “correct” reading of this statute. It’s possible the Federal Circuit will want to revisit this case en banc (as Chief Judge Rader suggests in his dissent), given the importance of the issue and the strong dissent by the Chief Judge.

Do you have thoughts on who’s got the better argument? Please weigh in!

(photo credit)