By Vicki G. Norton and Michael A. Swit
FDA-regulated firms — drug, device, biologic or otherwise — on both sides of the patent aisle concerned with the bounds of the “Safe Harbor” exception to patent infringement under 35 U.S.C. § 271(e)(1) can learn several key lessons from the recent decision in Isis Pharmaceuticals, Inc. v Santaris Pharma A/S Corp. (hereafter: “Isis”), particularly how to properly prove the safe harbor defense once the litigation unfolds and also when the harbor provides shelter from post-approval patent storms.
A Lesson on Proper Safe Harbor Pleading
In Isis, the district court for the Southern District of California held that, if a drug developer establishes a reasonable basis for believing that a “patented invention” will have a “particular biological effect” through a “particular biological process,” such a showing would be sufficient, although not the only way, to establish a safe harbor defense to patent infringement under 35 U.S.C. § 271(e)(1) [hereafter: “271(e)(1)”]. The safe harbor provision in § 271(e)(1) exempts otherwise infringing acts from patent liability when those acts are performed “solely for uses reasonably related to the development and submission of information under a Federal law which regulates the . . . use . . . of drugs.”
In reaching its holding, the Isis court relied on the Supreme Court’s observation in Merck v Integra that otherwise infringing experimentation on the road to regulatory approval comes within the safe harbor “[a]t least where a drug maker has a reasonable basis for believing that a patented compound may work, through a particular biological process, to produce a particular biological effect . . . .” Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S. 193, 207 (2005) (emphasis added).
By way of background, Isis sued Santaris (a Danish corporation not to be confused with Isis’s fellow San Diego-based firm Santarus, recently bought by Salix Pharmaceuticals), accusing Santaris of infringing Isis patents to antisense compounds and methods of making the antisense compounds when Santaris contracted to sell antisense drug discovery services and products to four pharmaceutical company customers in the United States. Santaris moved for summary judgment on its affirmative defense that the alleged acts of infringement fell within the safe harbor provision of 35 U.S.C. § 271.
The court denied Santaris’s summary judgment motion, finding that Santaris failed to provide undisputed evidence of the belief that the Merck I Court found was needed to properly claim the 271(e)(1) safe harbor (see above quote). Instead, the Isis court stressed that Santaris’s supporting declaration by one of its officers provided only a general description of the collaborations between Santaris and its customers. This, the court found, did not provide any detailed analysis of Santaris’s uses of the allegedly infringing compounds, methods and processes to establish they rose to the level of a reasonable belief, as contemplated by Merck I, as to a patented compound’s way of achieving a particular biological effect and, thus, failed to show that Santaris fell under the protection of the 271(e)(1) safe harbor.
The court also cited the Santaris officer’s previous statement to the PTO that, “(t)he majority of [Santaris’s] collaborators have taken broad licenses to our proprietary LNA platform in order to discover, develop, and commercialize new LNA-based drugs against RNA targets associated with disease,” observing that the reference to selling “platform” technology so that another company could develop and discover drug candidates, suggested that Santaris was using its technology for “basic research” not covered under the § 271(e)(1) safe harbor.
In determining the legal boundaries of the safe harbor afforded by 271(e)(1), the Isis court considered in detail the Supreme Court’s ruling in Merck v. Integra, and subsequent lower court cases mapping out the contours of the safe harbor. The court noted that the Supreme Court appeared to criticize the Federal Circuit’s suggestion that early stage research to “identif[y] the best drug candidate to subject to future clinical testing under the FDA process” fell outside the safe harbor, by providing guidance on circumstances in which early research would fall within the safe harbor, saying:
Properly construed, § 271(e)(1) leaves adequate space for experimentation and failure on the road to regulatory approval: At least where a drugmaker has a reasonable basis for believing that a patented compound may work, through a particularly biological process, to produce a particular physiological effect, and uses the compound in research that, if successful, would be appropriate to include in a submission to the FDA, that use is “reasonably related” to the “development and submission of information under . . . Federal law.” Id. at 207 (quoting § 271(e)(1); emphasis added).
Accordingly, the district court held that a showing that a drugmaker has a reasonable basis for believing that a patented invention will have a “particular biological effect” through a “particular biological process” would have been sufficient to establish a safe harbor defense if sufficient evidence to support it had been submitted. The district court also agreed with defendant Santaris that the Supreme Court’s use of “at least” in the passage quoted above means that the facts listed are sufficient, though not necessarily the only ones required, to come within the safe harbor.
Nevertheless, although accepting some of Santaris’s legal arguments, the Isis court cited Santaris’s failure to provide undisputed evidence of such knowledge or belief in denying Santaris’s summary judgment motion. The court found instead that fact issues remained as to whether Santaris’s collaboration agreements were “reasonably related” to the type of information submitted to the FDA—that is, whether it was “objectively reasonable for a party in [Santaris’s] . . . situation to believe that there was a decent prospect that the accused activities would contribute, relatively directly, to the generation of the kinds of information that are likely to be relevant in the processes by which the FDA would decide whether to approve the product in question” [citing Merck I, 545 U.S. at 200-01 (district court jury instruction)]. Accordingly, the court found that this fact question regarding what was reasonable, should be left to the trier of fact, as is customary for most questions involving a question of what is reasonable.
Case Also Tackles Safe Harbor’s Application to Allegations of Post-Approval Patent Infringement
Another interesting aspect of the decision is the court’s harmonization of what were viewed by some commentators as split decisions in Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057 (Fed. Cir. 2011) and Momenta Pharmaceuticals, Inc. v. Amphastar Pharmaceuticals, Inc., 686 F.3d 1348 (Fed. Cir. 2012), on the issue of whether 35 U.S.C. § 271(e)(1) can shield post-approval FDA use of a patented technology. See, e.g., Sebor & Norton, Momenta Seeks Supreme Court Review of Whether Safe-Harbor Applies to Post-Approval Uses of a Drug, available at http://aiplabiotech.wordpress.com/page/2/.
In 2011’s Classen, the Federal Circuit panel majority reversed a district court ruling that the defendants’ post approval activities, which included reporting adverse vaccine effects to FDA, fell within the § 271(e)(1) safe harbor provision and held instead that the safe harbor is “limited to activities conducted to obtain pre-marketing approval of generic counterparts of patented inventions” and that the “statute does not apply to information that may be routinely reported to the FDA long after marketing approval has been obtained.” Judge Moore dissented, reasoning that the majority’s analysis and construction of the safe harbor provision were “contrary to the plain language of the statute and clear Supreme Court guidance” (referencing Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S. 193 (2005)), and “[n]owhere does that statute limit the safe harbor to pre-approval uses.”
A year later, in 2012, Judge Moore wrote for the panel majority in Momenta, reaching what was viewed by some as a result conflicting with Classen, by holding that Amphastar’s use of Momenta’s patented process for analyzing drug quality during post-approval manufacture of enoxaparin for commercial sale fell within the safe harbor. The Federal Circuit panel majority sided with Amphastar, concluding that the language of §271(e)(1) is broad and “unambiguously applies to submissions under any federal law, providing that the law ‘regulates the manufacture, use or sale of drugs,’” and is not only directed to activities related to submission for FDA approval, but also to post approval testing.
After reviewing the two decisions, the Isis court found simply that Classen and Momenta “stand for the proposition that, regardless of the stage of the regulatory process in which a patented invention is used to obtain information, the information derived from using the patented invention must be ‘reasonably related’ to the type of information required by FDA at some point during the regulatory process.” Thus, the district court neatly harmonized what at first appeared to be conflicting decisions in Classen and Momenta.
- Where appropriate, draft agreements for drug discovery collaborations in a way that reflects knowledge or a belief of particular biological processes and particular physiological effects for each collaboration compound.
- During litigation, in order to obtain safe harbor protection, drugmakers seeking safe harbor protection should submit evidence sufficient to establish knowledge of the “particular biological process” and “particular physiological effect” for each collaboration compound.
- If using another’s patented invention post-approval, be sure to document, ideally prior to use, the relationship between what you are doing and a corresponding legal duty to submit data to FDA.
- Train key personnel involved in the safe harbor use of patented technology in the proper ways to document such use so that internal records, patent prosecution records, and regulatory filings are consistent with an appropriate Safe Harbor claim.