Source: https://www.orangebookblog.com/fda_exemption_under_271e1/index.html
Timestamp: 2019-04-22 08:29:34+00:00

Document:
Momenta is the assignee of U.S. Patent No. 7,575,886, which generally relates "to methods for analyzing heterogeneous populations of sulfated polysaccharides, e.g. heparin [and] . . . LMWH [low molecular weight heparin--e.g., enoxaparin]." Two days after Amphastar received final FDA approval to market its generic enoxaparin (and more than a year after Momenta received its own approval), Momenta filed suit against Amphastar, accusing Amphastar of "manufacturing generic enoxaparin for commercial sale" and performing "in their process for manufacturing batches of enoxaparin" an analytical method that infringes the '886 patent. According to the majority opinion, Momenta also alleged that this infringing testing was necessary to "satisfy the FDA's requirements."
In a strongly-worded dissent, Chief Judge Rader repeatedly refers to Amphastar as a "trespasser" and "infringer." He traces the legislative history of Section 271(e)(1)--which is curious given that the Supreme Court has twice minimized the legislative history and based its decisions instead on the plain (and broad) language of the statute. And he takes great exception to the majority opinion's basis for distinguishing Classen. Finally, he claims that the majority's "interpretation of 271(e)(1) would essentially render manufacturing method patents worthless." While this is an exaggeration, the Supreme Court might reply: "that is a problem for Congress to fix, if they so choose."
In a 2-1 opinion today, the Federal Circuit held that the Section 271(e)(1) safe harbor "does not apply to information that may be routinely reported to the FDA, long after marketing approval has been obtained."
It shall not be an act of infringement to make, use, offer to sell, or sell within 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 . . . .
The law was passed as part of the Hatch-Waxman Act in 1984, and while the purpose of the law was to shield generic drug makers from claims of patent infringement during the generic drug development process, the Supreme Court has interpreted the law much more broadly.
For instance, in Eli Lilly v. Medtronic, 496 U.S. 661 (1990), the Court held that the safe harbor applies not only to pharmaceutical development, but also to medical device development. More recently, in Merck v. Integra, 545 U.S. 193 (2005), the Court held that the safe harbor applies not only to generic pharmaceutical development, but rather to "all uses of patented inventions that are reasonably related to the development and submission of any information under the FDCA." In addition, the Court stated, "there is simply no room in the statute for excluding certain information from the exemption on the basis of the phase of research in which it is developed or the particular submission in which it could be included." In both Lilly and Merck, the Supreme Court reached its conclusions based on the plain language of the statute, which is intentionally broad.
In this case, Classen accused Biogen IDEC and GlaxoSmithKline of infringing its patents claiming methods of immunization on the ground that both companies participated in post-approval studies "to evaluate suggested associations between childhood vaccinations, particularly against hepatitis B and Haemophilus influenza . . . and risk of developing type 1 diabetes; and to determine whether timing of vaccinations influences risk." The district court granted summary judgment that these activities are within the Section 271(e)(1) safe harbor.
On appeal, Classen argued "that this statute, as enacted and intended, and as judicially interpreted, is limited to activities conducted to obtain pre-marketing approval of generic counterparts of patented inventions, before patent expiration." Biogen and GSK argued, on the other hand, that their participation in studies evaluating risks associated with different vaccination schedules is reasonably related to their requirement under, e.g., 21 C.F.R. § 601.70 and 21 C.F.R. § 600.80, to review and report adverse events to the FDA.
Classen is correct, for § 271(e)(1) provides an exception to the law of infringement in order to expedite development of information for regulatory approval of generic counterparts of patented products. The statute does not apply to information that may be routinely reported to the FDA, long after marketing approval has been obtained.
The majority opinion then proceeds to review the legislative history of the Hatch-Waxman Act, which obviously focused on the then-new abbreviated approval process for generic drugs. While the majority opinion quotes from both Eli Lilly v. Medtronic and Merck v. Integra, it ignores how broadly the Supreme Court interpreted the safe harbor in those cases. Rather, according to the majority opinion, "every decision examining the statute has appreciated that § 271(e)(1) is directed to premarketing approval of generic counterparts before patent expiration."
The majority cites extensively from the legislative history in an attempt to justify its construction. But these citations miss the point entirely. There is no dispute that § 271(e)(1) covers pre-approval studies, as the legislative history indicates. None of the legislative history cited by the majority, nor the cases it references, speak to the question at issue here -- whether the statute as enacted also covers post-approval activities. The question is not whether Congress intended to protect pre-approval activity -- but whether the enacted legislation covers more than just pre-approval activity. The language Congress chose to enact and that was signed by the President is plain on its face. There is no "pre-approval" limitation.
The other main issue addressed in the opinion concerns the patent-eligibility of Classen's claims under 35 U.S.C. § 101. Patently-O has an excellent discussion of that portion of the opinion.
Last Friday, the Court of Appeals for the Federal Circuit decided Integra v. Merck, on remand from the Supreme Court. Click here for the opinion. The case has important implications for owners of "research tools" patents.
In the mid-1990s, Integra sued Merck KGaA (the German company) and Scripps for infringing five patents relating to peptides that contain the RGD sequence of amino acids. This suite of patents included both patents directed to RGD-containing peptide compounds and patents directed to laboratory methods (i.e., research tools) using the RGD-containing peptides.
Merck and Scripps defended their conduct by relying on the FDA safe harbor of 35 USC § 271(e)(1), which precludes liability for activities "reasonably related to the development and submission of information under [the Food, Drug and Cosmetic Act]." The FDA safe-harbor was passed as part of the Hatch-Waxman Act to permit "a limited amount of testing so that generic manufacturers can establish the bioequivalency of a generic substitute." In this sense, the safe harbor encompasses activities that develop information that will normally find its way into an FDA submission.
At the original trial in the district court, Integra argued for a narrow reading of the FDA safe harbor in three respects. First, Integra argued that the safe harbor includes only studies on the safety of administration to humans, and does not include experiments on mode of action (i.e., ADME and PK studies). Second, Integra argued that the safe harbor excludes studies on related compounds that were not the subject of any FDA submission. Third, Integra argued that the safe harbor can only include experiments complying with the FDA’s Good Laboratory Practices (GLP), since only data from GLP-compliant studies qualify for submission to the FDA.
A jury verdict and bench opinion accepted Integra's narrow reading of the safe harbor statute, and found Merck and Scripps liable for infringement. A divided panel of the Federal Circuit affirmed. The Supreme Court granted certiorari on the limited question of "whether uses of patented inventions in preclinical research, the results of which are not ultimately included in a submission to the [FDA], are exempted by [the FDA safe harbor]." The term "patented inventions" presumably included both patented compounds and patented research tools that use those compounds.
The Antitrust & Competition Policy Blog reports on a new paper by Prof. Christopher Leslie of Chicago-Kent College of Law advocating the use of antitrust law to challenge the licensing of invalid patents.
Richard Epstein, my law school Property professor, has a new book out entitled Overdose: How Excessive Government Regulation Stifles Pharmaceutical Innovation. Judy Chevalier has this review at Slate. Prof. Epstein wrote two related Op-Ed pieces for the Boston Globe and L.A. Times.
Via Patent Circle, Abraxis, Orchid, and Sandoz have filed citizen petitions in support of their ANDAs for generic versions of Wyeth's Zosyn. The Economic Times of India published this article about the petitions.
Ed Silverman, veteran reporter for The Star-Ledger of New Jersey, recently started Pharmalot, a new blog covering news and trends in the pharmaceutical industry.
The Voluntary Trade Blog reports that FTC Commissioner William Kovacic, in a recent interview with Dow Jones, harshly critized the Department of Justice for advising the Supreme Court not to take the FTC v. Schering-Plough "reverse payments" case last year.
Peter Zura's Two-Seventy-One Patent Blog reports on a recent district court decision applying the 271(e)(1) "safe harbor" to research tools.
The Economist and The Scientist recently published articles on the current "dismal" state of the pharmaceutical industry.
As reported in a post last week, the Federal Circuit recently heard oral arguments in Merck KGaA v. Integra LifeSciences following remand from the Supreme Court. Since the hearing, both Merck and Integra have submitted letters to the Federal Circuit, urging the court not to decide the issue of whether Merck's use of Integra's patented compounds fell outside the 271(e)(1) FDA exemption as "research tools," in which case Merck would be liable for patent infringement.
Merck asserted in its letter that a Federal Circuit decision based on the research tool issue would be improper because Integra never argued--in the district court, Federal Circuit, or Supreme Court--that the jury verdict for Integra should be sustained on the basis that Merck used Integra's patented compounds as research tools. Integra, in its own letter, agreed with Merck, stating that while the research tool question is extremely important, it should be answered in a case in which the issue has been "squarely raised and thoroughly vetted" in the trial court.
At oral argument, Judge Rader, in particular, seemed gung ho to remand the case to the district court to determine whether Merck used Integra's compounds as research tools and therefore was not entitled to the 271(e)(1) FDA exemption. If the other two members of the panel, Judges Newman and Prost, follow the parties' advice and ignore that issue, then the Federal Circuit will limit its opinion to the narrower technical question of whether Merck's JMOL motion was properly denied by the district court.
NOTE: Thanks to Dennis Crouch for providing the parties' letters!

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