United States: Court Offers Insights On When The 271(E)(1) Safe Harbor Applies To The Use Of Patented Technology In Early – And Late -- Drug Development

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.

Key Takeaways

  • 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.

This article is for general information and does not include full legal analysis of the matters presented. It should not be construed or relied upon as legal advice or legal opinion on any specific facts or circumstances. The description of the results of any specific case or transaction contained herein does not mean or suggest that similar results can or could be obtained in any other matter. Each legal matter should be considered to be unique and subject to varying results. The invitation to contact the authors or attorneys in our firm is not a solicitation to provide professional services and should not be construed as a statement as to any availability to perform legal services in any jurisdiction in which such attorney is not permitted to practice.

Duane Morris LLP, a full-service law firm with more than 700 attorneys in 24 offices in the United States and internationally, offers innovative solutions to the legal and business challenges presented by today's evolving global markets. Duane Morris LLP, a full-service law firm with more than 700 attorneys in 24 offices in the United States and internationally, offers innovative solutions to the legal and business challenges presented by today's evolving global markets. The Duane Morris Institute provides training workshops for HR professionals, in-house counsel, benefits administrators and senior managers.

To print this article, all you need is to be registered on Mondaq.com.

Click to Login as an existing user or Register so you can print this article.

Similar Articles
Relevancy Powered by MondaqAI
In association with
Related Topics
Similar Articles
Relevancy Powered by MondaqAI
Related Articles
Related Video
Up-coming Events Search
Font Size:
Mondaq on Twitter
Register for Access and our Free Biweekly Alert for
This service is completely free. Access 250,000 archived articles from 100+ countries and get a personalised email twice a week covering developments (and yes, our lawyers like to think you’ve read our Disclaimer).
Email Address
Company Name
Confirm Password
Mondaq Topics -- Select your Interests
 Law Performance
 Law Practice
 Media & IT
 Real Estate
 Wealth Mgt
Asia Pacific
European Union
Latin America
Middle East
United States
Worldwide Updates
Registration (you must scroll down to set your data preferences)

Mondaq Ltd requires you to register and provide information that personally identifies you, including your content preferences, for three primary purposes (full details of Mondaq’s use of your personal data can be found in our Privacy and Cookies Notice):

  • To allow you to personalize the Mondaq websites you are visiting to show content ("Content") relevant to your interests.
  • To enable features such as password reminder, news alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our content providers ("Contributors") who contribute Content for free for your use.

Mondaq hopes that our registered users will support us in maintaining our free to view business model by consenting to our use of your personal data as described below.

Mondaq has a "free to view" business model. Our services are paid for by Contributors in exchange for Mondaq providing them with access to information about who accesses their content. Once personal data is transferred to our Contributors they become a data controller of this personal data. They use it to measure the response that their articles are receiving, as a form of market research. They may also use it to provide Mondaq users with information about their products and services.

Details of each Contributor to which your personal data will be transferred is clearly stated within the Content that you access. For full details of how this Contributor will use your personal data, you should review the Contributor’s own Privacy Notice.

Please indicate your preference below:

Yes, I am happy to support Mondaq in maintaining its free to view business model by agreeing to allow Mondaq to share my personal data with Contributors whose Content I access
No, I do not want Mondaq to share my personal data with Contributors

Also please let us know whether you are happy to receive communications promoting products and services offered by Mondaq:

Yes, I am happy to received promotional communications from Mondaq
No, please do not send me promotional communications from Mondaq
Terms & Conditions

Mondaq.com (the Website) is owned and managed by Mondaq Ltd (Mondaq). Mondaq grants you a non-exclusive, revocable licence to access the Website and associated services, such as the Mondaq News Alerts (Services), subject to and in consideration of your compliance with the following terms and conditions of use (Terms). Your use of the Website and/or Services constitutes your agreement to the Terms. Mondaq may terminate your use of the Website and Services if you are in breach of these Terms or if Mondaq decides to terminate the licence granted hereunder for any reason whatsoever.

Use of www.mondaq.com

To Use Mondaq.com you must be: eighteen (18) years old or over; legally capable of entering into binding contracts; and not in any way prohibited by the applicable law to enter into these Terms in the jurisdiction which you are currently located.

You may use the Website as an unregistered user, however, you are required to register as a user if you wish to read the full text of the Content or to receive the Services.

You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these Terms or with the prior written consent of Mondaq. You may not use electronic or other means to extract details or information from the Content. Nor shall you extract information about users or Contributors in order to offer them any services or products.

In your use of the Website and/or Services you shall: comply with all applicable laws, regulations, directives and legislations which apply to your Use of the Website and/or Services in whatever country you are physically located including without limitation any and all consumer law, export control laws and regulations; provide to us true, correct and accurate information and promptly inform us in the event that any information that you have provided to us changes or becomes inaccurate; notify Mondaq immediately of any circumstances where you have reason to believe that any Intellectual Property Rights or any other rights of any third party may have been infringed; co-operate with reasonable security or other checks or requests for information made by Mondaq from time to time; and at all times be fully liable for the breach of any of these Terms by a third party using your login details to access the Website and/or Services

however, you shall not: do anything likely to impair, interfere with or damage or cause harm or distress to any persons, or the network; do anything that will infringe any Intellectual Property Rights or other rights of Mondaq or any third party; or use the Website, Services and/or Content otherwise than in accordance with these Terms; use any trade marks or service marks of Mondaq or the Contributors, or do anything which may be seen to take unfair advantage of the reputation and goodwill of Mondaq or the Contributors, or the Website, Services and/or Content.

Mondaq reserves the right, in its sole discretion, to take any action that it deems necessary and appropriate in the event it considers that there is a breach or threatened breach of the Terms.

Mondaq’s Rights and Obligations

Unless otherwise expressly set out to the contrary, nothing in these Terms shall serve to transfer from Mondaq to you, any Intellectual Property Rights owned by and/or licensed to Mondaq and all rights, title and interest in and to such Intellectual Property Rights will remain exclusively with Mondaq and/or its licensors.

Mondaq shall use its reasonable endeavours to make the Website and Services available to you at all times, but we cannot guarantee an uninterrupted and fault free service.

Mondaq reserves the right to make changes to the services and/or the Website or part thereof, from time to time, and we may add, remove, modify and/or vary any elements of features and functionalities of the Website or the services.

Mondaq also reserves the right from time to time to monitor your Use of the Website and/or services.


The Content is general information only. It is not intended to constitute legal advice or seek to be the complete and comprehensive statement of the law, nor is it intended to address your specific requirements or provide advice on which reliance should be placed. Mondaq and/or its Contributors and other suppliers make no representations about the suitability of the information contained in the Content for any purpose. All Content provided "as is" without warranty of any kind. Mondaq and/or its Contributors and other suppliers hereby exclude and disclaim all representations, warranties or guarantees with regard to the Content, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. To the maximum extent permitted by law, Mondaq expressly excludes all representations, warranties, obligations, and liabilities arising out of or in connection with all Content. In no event shall Mondaq and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use of the Content or performance of Mondaq’s Services.


Mondaq may alter or amend these Terms by amending them on the Website. By continuing to Use the Services and/or the Website after such amendment, you will be deemed to have accepted any amendment to these Terms.

These Terms shall be governed by and construed in accordance with the laws of England and Wales and you irrevocably submit to the exclusive jurisdiction of the courts of England and Wales to settle any dispute which may arise out of or in connection with these Terms. If you live outside the United Kingdom, English law shall apply only to the extent that English law shall not deprive you of any legal protection accorded in accordance with the law of the place where you are habitually resident ("Local Law"). In the event English law deprives you of any legal protection which is accorded to you under Local Law, then these terms shall be governed by Local Law and any dispute or claim arising out of or in connection with these Terms shall be subject to the non-exclusive jurisdiction of the courts where you are habitually resident.

You may print and keep a copy of these Terms, which form the entire agreement between you and Mondaq and supersede any other communications or advertising in respect of the Service and/or the Website.

No delay in exercising or non-exercise by you and/or Mondaq of any of its rights under or in connection with these Terms shall operate as a waiver or release of each of your or Mondaq’s right. Rather, any such waiver or release must be specifically granted in writing signed by the party granting it.

If any part of these Terms is held unenforceable, that part shall be enforced to the maximum extent permissible so as to give effect to the intent of the parties, and the Terms shall continue in full force and effect.

Mondaq shall not incur any liability to you on account of any loss or damage resulting from any delay or failure to perform all or any part of these Terms if such delay or failure is caused, in whole or in part, by events, occurrences, or causes beyond the control of Mondaq. Such events, occurrences or causes will include, without limitation, acts of God, strikes, lockouts, server and network failure, riots, acts of war, earthquakes, fire and explosions.

By clicking Register you state you have read and agree to our Terms and Conditions