{"id":51,"date":"2014-03-11T11:54:32","date_gmt":"2014-03-11T15:54:32","guid":{"rendered":"http:\/\/blogs.duanemorris.com\/lifescienceslaw\/?p=51"},"modified":"2015-11-19T17:28:52","modified_gmt":"2015-11-19T21:28:52","slug":"court-offers-insights-on-when-the-271e1-safe-harbor-applies-to-the-use-of-patented-technology-in-early-and-late-drug-development","status":"publish","type":"post","link":"https:\/\/blogs.duanemorris.com\/lifescienceslaw\/2014\/03\/11\/court-offers-insights-on-when-the-271e1-safe-harbor-applies-to-the-use-of-patented-technology-in-early-and-late-drug-development\/","title":{"rendered":"Court Offers Insights On When the 271(e)(1) Safe Harbor Applies to the Use of Patented Technology in Early \u2013 and Late — Drug Development"},"content":{"rendered":"

By Vicki G. Norton and Michael A. Swit<\/strong><\/p>\n

FDA-regulated firms — drug, device, biologic or otherwise — on both sides of the patent aisle concerned with the bounds of the \u201cSafe Harbor\u201d exception to patent infringement under 35 U.S.C. \u00a7 271(e)(1) can learn several key lessons from the recent decision in Isis Pharmaceuticals, Inc. v Santaris Pharma A\/S Corp.<\/em> (hereafter: \u201cIsis\u201d), 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.<\/p>\n

<\/p>\n

A Lesson on Proper Safe Harbor Pleading<\/strong><\/p>\n

In Isis<\/em>, the district court for the Southern District of California held that, if a drug developer establishes a reasonable basis for believing that a \u201cpatented invention\u201d 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. \u00a7 271(e)(1) [hereafter: \u201c271(e)(1)\u201d]. The safe harbor provision in \u00a7 271(e)(1) exempts otherwise infringing acts from patent liability when those acts are performed \u201csolely for uses reasonably related to the development and submission of information under a Federal law which regulates the . . . use . . . of drugs.\u201d<\/p>\n

In reaching its holding, the Isis<\/em> court relied on the Supreme Court\u2019s observation in Merck v Integra<\/em> that otherwise infringing experimentation on the road to regulatory approval comes within the safe harbor \u201c[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<\/strong> . . . .\u201d Merck KGaA v. Integra Lifesciences I, Ltd.<\/em>, 545 U.S. 193, 207 (2005) (emphasis added).<\/p>\n

By way of background, Isis sued Santaris (a Danish corporation not to be confused with Isis\u2019s 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. \u00a7 271.<\/p>\n

The court denied Santaris\u2019s summary judgment motion, finding that Santaris failed to provide undisputed evidence of the belief that the Merck I<\/em> Court found was needed to properly claim the 271(e)(1) safe harbor (see above quote). Instead, the Isis<\/em> court stressed that Santaris\u2019s 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\u2019s 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\u2019s 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.<\/p>\n

The court also cited the Santaris officer\u2019s previous statement to the PTO that, \u201c(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,\u201d observing that the reference to selling \u201cplatform\u201d technology so that another company could develop and discover drug candidates, suggested that Santaris was using its technology for \u201cbasic research\u201d not covered under the \u00a7 271(e)(1) safe harbor.<\/p>\n

In determining the legal boundaries of the safe harbor afforded by 271(e)(1), the Isis<\/em> court considered in detail the Supreme Court\u2019s ruling in Merck v. Integra<\/em>, 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\u2019s suggestion that early stage research to \u201cidentif[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:<\/p>\n

Properly construed, \u00a7 271(e)(1) leaves adequate space for experimentation and failure on the road to regulatory approval: At least<\/strong> 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 \u00a7 271(e)(1); emphasis added).<\/p>\n

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\u2019s use of \u201cat least\u201d 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.<\/p>\n

Nevertheless, although accepting some of Santaris\u2019s legal arguments, the Isis court cited Santaris\u2019s failure to provide undisputed evidence of such knowledge or belief in denying Santaris\u2019s 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\u2014that 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<\/em>, 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.<\/p>\n

Case Also Tackles Safe Harbor\u2019s Application to Allegations of Post-Approval Patent Infringement<\/strong><\/p>\n

Another interesting aspect of the decision is the court\u2019s harmonization of what were viewed by some commentators as split decisions in Classen Immunotherapies, Inc. v. Biogen IDEC<\/em>, 659 F.3d 1057 (Fed. Cir. 2011) and Momenta Pharmaceuticals, Inc. v. Amphastar Pharmaceuticals, Inc.<\/em>, 686 F.3d 1348 (Fed. Cir. 2012), on the issue of whether 35 U.S.C. \u00a7 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<\/em>, available at http:\/\/aiplabiotech.wordpress.com\/page\/2\/<\/a>.<\/p>\n

In 2011\u2019s Classen, the Federal Circuit panel majority reversed a district court ruling that the defendants\u2019 post approval activities, which included reporting adverse vaccine effects to FDA, fell within the \u00a7 271(e)(1) safe harbor provision and held instead that the safe harbor is \u201climited to activities conducted to obtain pre-marketing approval of generic counterparts of patented inventions\u201d and that the \u201cstatute does not apply to information that may be routinely reported to the FDA long after marketing approval has been obtained.\u201d Judge Moore dissented, reasoning that the majority\u2019s analysis and construction of the safe harbor provision were \u201ccontrary to the plain language of the statute and clear Supreme Court guidance\u201d (referencing Merck KGaA v. Integra Lifesciences I, Ltd.<\/em>, 545 U.S. 193 (2005)), and \u201c[n]owhere does that statute limit the safe harbor to pre-approval uses.\u201d<\/p>\n

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<\/em>, by holding that Amphastar\u2019s use of Momenta\u2019s 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 \u00a7271(e)(1) is broad and \u201cunambiguously applies to submissions under any federal law, providing that the law \u2018regulates the manufacture, use or sale of drugs,\u2019” and is not only directed to activities related to submission for FDA approval, but also to post approval testing.<\/p>\n

After reviewing the two decisions, the Isis<\/em> court found simply that Classen<\/em> and Momenta<\/em> \u201cstand[] 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 \u2018reasonably related\u2019 to the type of information required by FDA at some point during the regulatory process.\u201d Thus, the district court neatly harmonized what at first appeared to be conflicting decisions in Classen <\/em>and Momenta<\/em>.<\/p>\n

Key Takeaways<\/strong><\/p>\n