This week the Federal Circuit affirmed Amgen’s win against Hospira with respect to Hospira’s erythropoietin (“EPO”) biosimilar—a drug used to increase red blood cell number—in a Delaware trial where Amgen’s U.S. Patent No. 5,856,298 was found to be infringed and not invalid and Amgen was found to be entitled to $70 million for damages associated with its EPO drug Epogen®. Part of the appeal was also dedicated to examining the so-called Safe Harbor provision of 35 U.S.C. § 271(e)(1), where the Federal Circuit agreed with Amgen that Hospira manufactured at least 14 batches of the drug that were not protected by this provision. The Court’s decision provides lessons in how companies should be careful to avoid stretching the bounds of the Safe Harbor provision.


While 35 U.S.C. § 271(a) specifies making, using, selling, or offering to sell a patented invention as infringing activities, these potentially-infringing activities may be exempt from liability in some circumstances. As one example, the so-called Safe Harbor protects research and experimentation on patented inventions that would otherwise be infringing provided that the research is reasonably related to the federal regulatory approval process. This provision, 35 U.S.C. § 271(e)(1), was added by amendment in 1984 and reads as follows:

It shall not be an act of infringement to make, use, offer to sell, or sell within the United States or import into 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 or veterinary biological products.

Courts have interpreted the Safe Harbor provision broadly. For example, although the statute refers specifically only to “drugs or veterinary biological products,” the Supreme Court expanded the scope to include research related to medical devices, holding that “patented invention” as recited in 35 U.S.C. § 271(e)(1) “is defined to include all inventions, not drug-related inventions alone.” Eli Lilly and Co. v. Medtronic, Inc., 496 U.S. 661, 665 (1990).

In relation to the types of research covered by the exemption, the Supreme Court held that the provision “provides a wide berth for the use of patented drugs in activities related to the federal regulatory process.” Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S. 193, 202 (2005) (emphasis added). In Merck the Supreme Court also noted that all uses that are “reasonably related” to the “development and submission of any information” are permitted, specifically stating that preclinical studies are included. Id. (emphasis in original). Furthermore, studies related to mechanism of action, pharmacokinetics, pharmacology, etc. that would not normally be included in a submission to the U.S. Food and Drug Administration (“FDA”) can fall into the exemption. Id. at 203. Additionally, preclinical studies and experimentation on drugs or compounds that fail and are not submitted to the FDA can also fall into the Safe Harbor, provided that the researcher had a reasonable basis for believing that the patented compound may work and would eventually be appropriate as submissions to the FDA. Id. at 206-07.

Furthermore, the Federal Circuit held that activities conducted even after FDA approval has been obtained may still be exempt if related to the development and submission of information to the FDA (i.e., if the activities are required to maintain FDA approval). Momenta Pharms., Inc. v. Amphastar Pharms., Inc., 686 F.3d 1348, 1359-60 (Fed. Cir. 2012).

Finally, although 35 U.S.C. § 271(e)(1) states that the exempt activity must be “solely for uses reasonably related to the development and submission of information” to the FDA, courts have also interpreted this provision liberally. For example, the use of data resulting from exempted research is not limited to submission to the FDA, and using it for other purposes may not affect the exemption. As an example, the Federal Circuit held that derived test data can be used for fund raising and other business purposes such as presenting at conferences, reporting to investors, analysts, or journalists, and describing the data in a fund-raising document and the underlying research would still be considered exempt. Telectronics Pacing Sys., Inc. v. Ventritex, Inc., 982 F.2d 1520, 1524-25 (Fed. Cir. 1992).

In addition, the accused infringer’s intent or potential alternative uses for the infringing activity are irrelevant as long as the activity is reasonably related to obtaining FDA approval. Abtox, Inc. v. Exitron Corp., 122 F.3d 1019, 1030 (Fed. Cir. 1997).

However, research carried out purely for marketing or other commercial purposes (i.e., that does not produce information that would be given to the FDA) will not be considered exempt. Amgen, Inc. v. ITC, 565 F.3d 846, 852-53 (Fed. Cir. 2009).

Amgen v. Hospira

On appeal, Hospira challenged the district court’s jury instructions regarding its Safe Harbor defense, as well as the jury’s conclusion that some, but not all, of Hospira’s erythropoietin drug product were protected under the Safe Harbor.

The jury instructions with respect to the Safe Harbor read:

You must evaluate each of the accused activities separately to determine whether the Safe Harbor applies. If you find that an accused activity was reasonably related to the development and submission of information to the FDA for the purpose of obtaining FDA approval, then Hospira has proved its Safe Harbor defense as to that activity. If Hospira has proved that the manufacture of a particular batch was reasonably related to developing and submitting information to the FDA in order to obtain FDA approval, Hospira’s additional underlying purposes for the manufacture and use of that batch do not remove that batch from the Safe Harbor defense.

While Hospira argued that these instructions improperly focused on intent rather than how each batch was used, the Federal Circuit disagreed, holding that the jury instructions properly articulated the legal principles underlying the Safe Harbor inquiry. According to the Court, “[t]he accused activity is Hospira’s use of Amgen’s claimed methods of manufacture. The relevant inquire, therefore, is not how Hospira used each batch it manufactured, but whether each act of manufacture was for uses reasonably related to submitting information to the FDA.” Slip Op. at 14-15.

Here, 21 batches of EPO were manufactured in 2013, 2014, and 2015. The jury found 7 batches were protected under the Safe Harbor, whereas 14 were not. The protected batches included:

- 2 batches used for qualifying Hospira’s process to make the drug and for qualifying alternative equipment (2013); and

- 5 batches used for a mandatory pre-approval inspection by the FDA (2015).

For the remaining batches, Hospira used the EPO or various types of testing, including biosimilarity, revisions to release specifications, stability testing, and continued process verification. Hospira argued that each type of testing was part of its Biologics License Application or in response to the FDA.

But, the Federal Circuit found that substantial evidence supported the jury’s finding that Hospira was not required to manufacture additional batches after 2012 and that at least some of the testing was not required for the FDA. Perhaps most troublingly, documentary evidence showed that much of the material from 2013-2015 was intended to serve as commercial inventory to support single dose vial launch stock, and after litigation began, Hospira changed the designation of certain batches from “commercial inventory” to “continued process verification.”


Although the Safe Harbor has been broadly applied and can be relied upon to protect a wide variety of otherwise-infringing uses, commingling uses with commercial intent can lead to a finding of infringement.