Momenta Pharmaceuticals Inc. et al. v. Amphastar Pharmaceuticals Inc. et al., case numbers 12-1062, 12-1103 and 12-1104 (Aug. 3, 2012).

Momenta and Amphastar are generic drug manufacturers of the generic version of Lovenox (enoxaparin) a low-molecular weight version of heparin for use in preventing blood clots. The composition is produced by enzymatic digestion of heparin to produce a mixture of oligosaccharides. The molecular diversity of the product mixture raised potential problems in light of the FDA’s abbreviated new drug application (ANDA) approval process, which requires an ANDA applicant to submit evidence to establish that its drug is bioequivalent to the reference approved drug.

Momenta and Amphastar both filed ANDAs for marketing approval of enoxaparin. The FDA, exercising its discretion in deciding the type of information required to make a finding of “sameness” of an active ingredient, identified five criteria or “standards for identity,” that together provide sufficient information to conclude that generic enoxaparin has the ‘same’ active ingredient as Lovenox. Further, the FDA required generic manufacturers of enoxaparin to include in their manufacturing process an analysis of each batch of its enoxaparin, to confirm that it includes a defined percentage of non-naturally occurring sugar which includes a 1,6,-anhydro ring structure. Momenta received its FDA market approval in July, 2010, and Amphastar got approval more than a year later.

Two days after Amphastar received its FDA marketing approval, Momenta brought suit for infringement of its U.S. Patent No. 7,575,886. The patent covered methods for analyzing a heterogeneous population of sulfated polysaccharides, e.g., heparin and enoxaparin, and was useful, if not essential, in characterizing the levels of oligosaccharide components in enoxaparin, as required by the FDA in showing drug sameness, in particular, the percentage of sugar which includes a 1,6,-anhydro ring. Momenta alleged that Amphastar infringed its ‘886 patent by manufacturing generic enoxaparin for commercial sale using its claimed method.

The district court granted Momenta’s motion for a preliminary injunction, based on the belief that Amphastar’s quality-control testing infringed the ‘886 patent and that the infringing activity was outside the safe-harbor provision of Hatch-Waxman because “although the safe harbor provision permits otherwise infringing activity that is conducted to obtain regulatory approval of a product, it does not permit a generic manufacturer to continue in that otherwise infringing activity after obtaining such approval.” The safe harbor provision of 35 U.S.C. §271(e)(1) provides that:

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.

In vacating the district court’s grant of a preliminary injunction, a two-judge panel majority reasoned that that Amphastar, as a generic drug manufacturer, “cannot sell a batch of enoxaparin unless it has established that its strength and quality is consistent with the standards set forth in relevant official compendium.” Here FDA regulations require that records associated with batch production of drugs be retained for at least 1 year after expiration of the batch, and these records “shall be readily available for inspection” by the FDA at any time. The panel majority concluded that “the requirement to maintain records for FDA inspection satisfies the requirement that the uses be reasonably related to the development and submission of information to the FDA.”

The panel opinion had to distinguish the facts in the present case from those in Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1070 (Fed. Cir. 2011). At issue in Classen were studies to evaluate the association between the timing of childhood vaccinations and the risk of developing certain immune-mediated disorders. The studies themselves were not mandated by the FDA, but any vaccine license holder was required to report to the FDA “adverse experience information,” such as adverse side effects, it acquired as a result of vaccine studies. The court distinguished the Classen case on the grounds that the information submitted by the generic manufacturer in the present case was necessary both to the continued approval of the ANDA and the ability to market the generic drug.

In short, the safe harbor provision of 35 U.S.C. §271(e)(1) would seem to protect a generic drug manufacturer from infringing a patent being used to generate drug-product information, even after FDA market approval, if the information is mandated by the FDA for continued market approval.