Patent protection is a critical driver of value for the biotech industry. One of the unique aspects of biotech patents, however, is that many otherwise infringing activities are exempt from claims of patent infringement when those activities are “reasonably related to the development and submission of information” to the Food and Drug Administration (FDA).1 The scope of this exemption has been hotly contested since the passage of the Hatch-Waxman Act in 1985 (the Act).2 The Supreme Court has weighed in on this exemption twice, the last time being in Merck KGaA v. Integra LifeSciences I, Ltd.3 In that case, the Supreme Court expressly side-stepped the question of whether research tools are exempt from infringement.4 Since Merck, there have been a number of Federal Circuit and district court decisions that interpret the Act.5 The Supreme Court just recently refused to review another important Federal Circuit decision regarding the question of whether activities engaged in after FDA approval fall within the scope of the Act. Each case is noteworthy for being factually intensive and having difficult to predict outcomes. The following review of the post-Merck decisions is intended to guide patent holders and would be infringers in analyzing whether the use of research tools and other activities are exempt from infringement under the Act.
The exemption under 35 U.S.C. § 271(e)(1) (“safe harbor” or “exemption”) was first codified in the U.S. patent laws with the passage of the Hatch-Waxman Act in 1985:
It shall not be an act of infringement to make, use, offer to sell, or sell... or import... 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...6
The Act is an attempt to balance the demand for low cost generic pharmaceuticals with the rights of patent owners. The Act allows activities that would otherwise infringe a U.S. patent before the expiration of the patent if those activities are “solely for uses reasonably related to the development and submission of information” to the FDA.7 The statute has spurred an abundance of litigation and, over the years, the federal courts have regularly interpreted the language of the statute in broad terms. For example, though the statute explicitly refers to “the use and sale of drugs,” the Supreme Court has interpreted the statute to include medical devices.8 Moreover, the courts have essentially eviscerated the term “solely” from the statute, as there is now no dispute that the infringing activities may be for reasons other than those “solely” related to FDA approval.9
In Merck, the Supreme Court continued the practice of liberally interpreting the safe harbor of § 271(e)(1). This case involved patents on short peptides that Merck supplied to Scripps Research Institute in order for Scripps to test the peptides as potential angiogenesis inhibitors.10 Integra LifeSciences I, Ltd. owned a patent covering the peptides, and sued Merck
and Scripps for patent infringement.11 As a defense, Merck and Scripps asserted that their activities associated with the use of the peptides were exempt from patent infringement under § 271(e)(1) because their testing of the peptides was reasonably related to the development and submission of information about the peptides to the FDA.12
The federal trial court and the appeals court found that the exemption did not apply because the testing of a number of the patented peptide compounds, prior to the selection of any particular compound as a potential drug candidate, was not sufficiently directly related to the submission of information to the FDA.13 The trial and appeal courts found that Scripps was simply conducting biomedical research, which had no relation to FDA approval of any of the peptides.14
The Supreme Court reversed the lower courts and held that the exemption can apply to activities involving a drug compound that infringes a patent even though approval is not sought for that compound as long as the activities are reasonably related to the approval of some other compound.15 The Supreme Court, however, explicitly left open the question of whether a patented research tool can be used without a license.16
Since Merck, a number of courts have reviewed the use of research tools under § 271(e)(1). The Supreme Court’s express intention to avoid addressing the research tool question has left several open questions about the scope of the safe harbor. So far, only one court has found in favor of a research tool exemption.17 In addition, the Federal Circuit has twice reviewed whether post-FDA approval activities are exempt.18
Research Tools Exempt under § 271(e)(1) post-Merck
In Classen Immunotherapies, Inc. v. King Pharms., Inc., Classen owned patents covering methods for identifying and commercializing new uses of existing drugs.19 Elan produced a muscle relaxant drug called Skelaxin.20 Elan conducted studies on the bioavailability of Skelaxin, and found that food significantly impacted absorption rate.21 Elan then submitted a Citizen Petition to the FDA containing the results of the bioavailability study, and requested that the FDA require manufacturers seeking approval for generic Skelaxin to submit fed and fasted studies along with an Abbreviated New Drug Application (ANDA).22 Elan also submitted to the FDA a label supplement that contained the results of its study.23
Classen sued Elan for infringement of its patented process when Elan: 1) conducted the bioavailability of Skelaxin study; 2) identified a new use of the drug; and 3) commercialized the new use.24 Elan claimed that even if its activities were considered infringement, the activities fell under the safe harbor of § 271(e)(1) because the results of the bioavailability study were submitted to the FDA.25
The district court agreed with Elan, and held that Elan’s use of Classen’s patented process was reasonably related to the submission of information to the FDA and was protected under § 271(e)(1).26 In so holding, the district court acknowledged that the Supreme Court in Merck specifically declined to rule on whether the use of “research tools” was protected under § 271(e)(1). Although the Classen process could be considered a “research tool,” the district court found that the extension of the safe harbor to cover the use of these tools was warranted by the language of Merck and a plain reading of the statute.27
Research Tools Not Exempt under § 271(e)(1) post-Merck
In Proveris Scientific Corp. v. InnovaSystems, Inc., the patent at issue covered a system and apparatus for identifying different aerosol sprays that are used in drug delivery devices, such as nasal sprays.28 The patent also disclosed that the characterization of aerosol sprays is a part of the FDA regulatory approval process.29 The defendant, Innova, marketed an Optical Spray Analyzer (OSA) that, although not itself subject to FDA approval, can be used in connection with FDA submissions related to aerosol sprays.30 When Proveris sued Innova for infringement of its patent, Innova claimed that its actions fell within the safe harbor of § 271(e)(1) because the OSA device was used by others for the purpose of generating information to submit to the FDA.31
The Federal Circuit focused its analysis on the terms “patented invention” and “reasonably related” from the statutory language of § 271(e)(1).32 While deciding that the OSA was a medical device that would be covered by § 271(e)(1), the court found that the use of the device was not exempt from infringement because § 271(e)(1) is not designed to protect parties who are not themselves seeking FDA approval of a product.33 As a result, the court concluded that Innova was “not within the category of entities for whom the safe harbor provision was designed to provide relief.”34
In PSN Illinois, LLC v. Abbott Labs., the district court found that Abbot’s use of PSN’s patented invention as a research tool to identify potential drug candidates did not fall under the safe harbor of § 271(e)(1).35 PSN owned patents covering the SIP2 receptor, which is a member of a family of protein receptors involved in vasculature and immune system regulation.36 Abbott’s research focused on identifying drug candidates that might interact with SIP receptors and have therapeutic properties.37 The research revealed three possible drug candidates. Abbott had not offered these candidates for sale, but had submitted information to the FDA.38
In the face of a PSN’s infringement allegation, Abbott argued that the use of the patented SIP2 receptor was included under § 271(e) (1), and turned to Merck for support. The district court disagreed and stated that Merck stands for the proposition that an alleged infringer may still be protected under § 271(e)(1), even if the alleged infringer fails to submit data to the FDA.39 However, the court stated that Merck does not support the broad principle that “any use of a patented invention to gather information to submit to the FDA is protected.”40 The court noted that “Proveris excluded research tools from the purview of the safe harbor exemption.”41 Furthermore, the court looked to the legislative history of the Hatch-Waxman Act, which stated that the “only activity which will be permitted by the bill is a limited amount of testing so that generic manufacturers can establish the bioequivalency of a generic substitute.”42 The court concluded that Abbott was not protected because it was infringing the patented SIP2 receptors to develop its own patented product, as opposed to seeking FDA approval of a generic receptor to enter into the marketplace.43 The court noted that the holding in Proveris forbids this kind of activity from exemption, and that the SIP2 receptors were not considered “patented inventions” under § 271(e)(1) as they did not require regulatory approval.44
Post Approval Activities May be Exempt under § 271(e)(1)
Since Merck, the Federal Circuit has twice considered and reached differing conclusions regarding whether post-FDA approval activities involving patented methods for testing approved compounds are exempt activities under § 271(e)(1). In Classen Immunotherapies, Inc. v. Biogen IDEC, the Federal Circuit held that the § 271(e)(1) safe harbor does not apply to
infringing activities that generate information “routinely reported to the FDA, long after marketing approval has been obtained.”45 Here, Biogen and GlaxoSmithKline utilized Classen’s patented invention to conduct risk assessment studies for childhood vaccines. Classen argued that, by participating in these studies, Biogen and GlaxoSmithKline directly infringed its patent for methods of immunization.46
Biogen argued that reporting vaccine relationships and recommendations are actions in conformity with FDA regulations, and should therefore fall under the safe harbor of § 271(e)(1).47 The Federal Circuit, however, did not agree and found that Biogen’s interpretation was beyond the statutory purpose of § 271(e)(1) because information on vaccine relationships post-approval does not relate to the submission of information for the purpose of obtaining FDA approval of a generic drug.48 The Federal Circuit agreed with Classen, noting that “[e]xtensive precedent recites the purpose of § 271(e)(1) to facilitate market entry upon patent expiration.”49
In Momenta Pharma., Inc. v. Amphastar Pharma., Inc., the Federal Circuit held, contrary to its earlier opinion in Classen, that post-approval studies can fall within the safe harbor of § 271(e)(1).50 Momenta was the licensee of a patent relating to “methods for analyzing heterogeneous populations of sulfated polysaccharides,” such as enoxaparin. Amphastar was the first to submit an ANDA for generic enoxaparin, but Momenta’s ANDA was approved first.51 Once Amphastar was approved, Momenta sued Amphastar for patent infringement when Amphastar tested its commercial batches of generic product using Momenta’s test methods.
In response to Momenta’s allegations, Amphastar argued that its quality control testing of each commercial batch of enoxaparin fell within the scope of § 271(e)(1).52 Momenta, on the other hand, maintained that § 271(e)(1) does not apply to information routinely reported to the FDA during post-market approval, according to the Federal Circuit’s holding in Classen.53
In determining whether Amphastar’s quality control test submissions fell within the safe harbor, the Federal Circuit distinguished this case from the facts of Classen by noting that, in Classen, the studies submitted to the FDA were not required by the FDA for the continued approval of the ANDA.54 Unlike the information submitted in Classen, the data Amphastar submitted to the FDA were not “routine submissions,” rather these submissions were required in order to maintain FDA approval.55 The Federal Circuit also noted that Amphastar was legally required under FDA requirements to submit the quality control data, whereas in Classen, the information submitted was largely for non-FDA purposes.56
Additionally, in response to Momenta’s argument that there were other quality control testing methods available to Amphastar, making Amphastar’s use of the patented method not required by the FDA, the Federal Circuit stated that the Act “does not mandate the use of a noninfringing alternative when one exists.”57
The Supreme Court recently refused to review the Federal Circuit’s opinion in Classen v. Biogen IDEC.58 Therefore, the Federal Circuit’s differentiation of “routine submissions” from those “required” to be submitted to the FDA will be the central tenant for post-approval submissions.
While factually intensive, the foregoing cases offer some guidance about the use of research tools and post-approval submissions to the FDA. Merck suggests that using a patented compound in research that will be submitted to the FDA is exempt activity, even if the compound is not the product for which approval is sought. Caution is advised, however, since the district court in Abbott found that the use of a patent receptor in the search for potential therapeutics that bind the receptor is not a safe harbor activity. The district court in Abbott distinguished Merck and followed the Federal Circuit’s precedent in Proveris that holds that the safe harbor does not cover using a patented device in research, even if the results of the research will be submitted to the FDA. Finally, the Federal Circuit provided guidance through its Classen and Momenta opinions that post-approval activities are protected under the safe harbor as long as those activities are required by the FDA.
1 35 U.S.C. § 271(e)(1) (2006).
2 21 U.S.C. § 355(j) (2006).
3 545 U.S. 193 (2005).
4 Id. at 205 n.7.
5 GlaxoSmithKline v. Classen Immunotherapies, Inc., No. 11-1078, 2013 WL 141405 (U.S. Jan. 14, 2013).
6 35 U.S.C. § 271(e)(1).
8 See Eli Lilly & Co. v. Medtronic, Inc., 496 U.S. 661, 673-74 (1990).
9 See, e.g., Merck, 545 U.S. at 202 n.6 (interpreting the statutory language of § 271(e)(1) broadly without regard to the meaning of the term “solely” in the statute).
10 Id. at 200.
11 Id. at 197, 200.
12 Id. at 200.
13 See Integra LifeSciences I, Ltd. v. Merck KGaA, 331 F.3d 860, 867-68 (Fed. Cir. 2003).
14 See id. at 872.
15 Merck, 545 U.S. at 207-08.
16 Id. at 205 n.7.
17 See Classen Immunotherapies, Inc. v. King Pharms., Inc, 466 F.Supp.2d 621 (N.D.Md. 2006).
18 Proveris Scientific Corp. v. InnovaSystems, Inc., 536 F.3d 1256 (Fed. Cir. 2008); PSN Illinois, LLC v. Abbott Labs, No. 09cv5879, 2011 U.S. Dist. LEXIS 108055 (N.D. Il. Sept. 20, 2011).
19 466 F.Supp.2d at 623.
21 Id. at 624.
25 Id. at 624-25.
26 Id. at 625.
27 Id. at n.2. (internal citations omitted).
28 Proveris, 536 F.3d at 1258.
30 Id. at 1259.
31 Id. at 1260.
32 Id. at 1261.
33 Id. at 1265.
35 PSN Illinois, 2011 U.S. Dist. LEXIS 108055, at *18.
36 Id. at *3.
38 Id. at *6.
39 Id. at *17-18.
40 Id. at *18 (emphasis in original).
41 Id. at *14.
42 Id. at *15 (quoting H.R. Rep. No. 98-857, pt.2, at 8 (1984)).
43 Id. at *18.
45 659 F.3d 1057, 1070 (Fed. Cir. 2011).
49 Id. at 1072.
50 686 F.3d 1348, 1359 (Fed. Cir. 2012).
51 Id. at 1351.
52 Id. at 1353.
54 Id. at 1358.
57 Id. at 1359.
58 GlaxoSmithKline, 2013 WL 141405.