Murky Waters: Post-Approval Regulatory Activities And The § 271(e)(1) Safe Harbor

On January 14, 2013, the U.S. Supreme Court refused to consider the U.S. Court of Appeals for the Federal Circuit's exclusion in Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057 (Fed. Cir. 2011), of post-approval regulatory activity from the safe harbor established by 35 U.S.C. § 271(e)(1). The Supreme Court's denial of the petition for certiorari filed by GlaxoSmithKline (Glaxo) should not be interpreted, however, as approval of the narrow construction adopted below by a divided Federal Circuit panel.

To the contrary, it is likely that the Supreme Court refused to hear this case because the Federal Circuit all but overruled Classen in Momenta Pharmaceuticals, Inc. v. Amphastar Pharmaceuticals, Inc., 686 F.3d 1348 (Fed. Cir. 2012)1.

But given the split in Federal Circuit jurisprudence, the competing public policy considerations, and the need of the pharmaceutical industry for bright-line guidance as to which post-approval regulatory activities fall within the scope of § 271(e)(1) and which fall without, it seems likely that the Supreme Court will soon have another opportunity to construe the scope of the safe harbor - perhaps in the Momenta decision itself.

The § 271(e)(1) Safe Harbor

Generally, a patent is infringed when the patented invention is made, used, offered for sale, or sold in the United States, or imported into the United States, without authority. 35 U.S.C. § 271(a). In 1984, however, Congress exempted from patent infringement certain activities related to satisfying federal regulatory requirements. As amended, this exemption - codified at 35 U.S.C. § 271(e)(1) - applies to otherwise infringing activities that are undertaken "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." Congress created the § 271(e)(1) safe harbor as part of its attempt to balance competing societal interests in promoting innovation through patent protection and hastening the market entry of generic drugs.

The Supreme Court has twice considered the scope of the exemption established by § 271(e)(1), and in both cases adopted a broad, inclusive construction. First, the Court held in Eli Lilly & Co. v. Medtronic, Inc., 496 U.S. 661 (1990), that the § 271(e)(1) safe harbor encompasses not only pharmaceutical products but also medical devices. And in Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S. 193, 208 (2005), the Court concluded that, whether or not ultimately submitted to the FDA, preclinical research is also protected within the § 271(e)(1) safe harbor "as long as there is a reasonable basis for believing that the experiments will produce the types of information that are relevant to an IND or NDA." In so holding, the Supreme Court observed that § 271(e)(1) encompasses "a wide berth," as it "exempt[s] from infringement all uses of patented compounds 'reasonably related' to the process of developing information for submission under any federal law regulating the manufacture, use, or distribution of drugs." The Supreme Court has not, however, considered whether regulatory activities undertaken after a drug's approval by the FDA fall within the confines of the § 271(e)(1) safe harbor.

Post-Approval Regulatory Activities - Take One: Classen

Classen Immunotherapies sued Biogen IDEC, Glaxo, and several additional pharmaceutical companies for infringement of patents relating to methods for improving the safety of vaccine administration schedules. According to these patents, the development of certain chronic disorders can be affected by the timing of infant immunizations. After Dr. Classen published articles suggesting such a relationship, a study sponsored by the Centers for Disease Control and Prevention (CDC) examined the vaccination histories of more than 1000 children and found no association between vaccination schedules and development of diabetes. Classen charged Biogen and Glaxo with infringement based largely on their participation in the CDC-sponsored study. Relying on the Supreme Court's broad language in Merck, the district court granted summary judgment to Biogen and Glaxo on the basis that their activities fell within the § 271(e)(1) safe harbor, reasoning that evaluation of vaccination risks was reasonably related to information required by the FDA, such as annual reports of post-marketing studies as well as reports of adverse reactions. Classen Immunotherapies, Inc. v. Biogen IDEC, 381 F. Supp. 2d 452 (D. Md. 2005).

A divided panel of the Federal Circuit vacated the district court's judgment of non-infringement based on the § 271(e)(1) safe harbor2. In a decision written by Judge Newman and joined by Judge Rader, the panel majority held that "§ 271(e)(1) provides an exception to the law of infringement in order to expedite development of information for regulatory approval . . . [and] does not apply to information that may be routinely reported to the FDA, long after marketing approval has been obtained" (emphasis added). In reaching this conclusion, the majority relied on legislative history, as well as the Supreme Court's decisions in Eli Lilly and Merck, noting that all of these sources discussed § 271(e)(1) solely in the context of pre-approval activity. Accordingly, the majority rejected encompassing post-approval activity within the safe harbor as "a massive enlargement of the statutory exemption."

Judge Moore dissented from the majority's limitation of § 271(e)(1) to pre-approval activities. Judge Moore observed that nothing in the plain language of the statute supported such a limitation in the scope of the safe harbor; that the Supreme Court in Merck, although considering pre-approval activities, "repeatedly underscored the breadth of the statute's text;" and that the legislative history does not speak to whether § 271(e)(1) extends to post-approval activities.

The Federal Circuit refused to rehear the case en banc.

Post-Approval Regulatory Activities - Take Two: Momenta

Less than a year later, however, a divided panel of the Federal Circuit all but overruled Classen. At issue in Momenta was the manufacturing process for a generic version of Lovenox (enoxaparin), a heparin derivative used to prevent blood clots. The FDA required each generic manufacturer to prove on an ongoing basis that its drug contains about 20 percent of a 1,6-anhydro disaccharide derivative. Amphastar chose to satisfy this requirement by implementing during its manufacturing process a batch-testing method that allegedly infringed Momenta's patent. Relying on Classen, the district court concluded that Amphastar's batch-testing method was a post-approval activity that did not fall within the § 271(e)(1) safe harbor, and granted Momenta a preliminary injunction.

A divided panel of the Federal Circuit vacated the district court's decision. The majority, consisting of Judge Moore (the dissenting judge in Classen) and Judge Dyk, acknowledged Classen as holding that § 271(e)(1)...