On December 16, 2019, the Court of Appeals for the Federal Circuit issued an opinion that fully upheld the District of Delaware’s denial of Hospira, Inc.’s motion for judgment as a matter of law (JMOL), or alternative motion for new trial, in Amgen Inc. v. Hospira, Inc., Nos. 2019-1067, 2019-1102.  The ruling maintained the jury’s verdict that: (1) Hospira infringed one of Amgen Inc.’s two asserted patents, (2) fourteen batches of drug substance for Hospira’s biosimilar was not covered by the Safe Harbor provision of 35 U.S.C. § 271(e)(10), and (3) Amgen was entitled to $70 million in damages.

In 2014, Hospira submitted a Biologics License Application (BLA) to the FDA, seeking approval for a biosimilar to Amgen’s Epogen product, a recombinant human erythropoietin (EPO).  EPO is a glycoprotein that regulates red blood cell maturation and production. Amgen sued Hospira for infringement of two patents related to forms of EPO and aspects of their production, U.S. Patent No. 5,856,298 (the ’298 patent) and U.S. Patent No. 5,756,349 (the ’349 patent).  After a trial in 2017, the jury found the asserted claims of the ’298 patent not invalid and infringed, the asserted claims of the ’349 patent not invalid and not infringed, and further concluded that fourteen batches out of twenty-one manufactured by Hospira were not entitled to the Safe Harbor defense.  The jury awarded Amgen $70 million in damages.  Both Hospira and Amgen moved post-trial to vacate the jury’s verdict.  Both motions were denied by the district court.

Hospira and Amgen each appealed the district court’s denial of their respective post-trial motions.  Hospira argued, inter alia, that the district court’s jury instructions on the Safe Harbor defense were improper, and that no reasonable jury could have found that only some, but not all, of its twenty-one drug batches were protected by the Safe Harbor given that all of the batches were used to generate information that was submitted to the FDA.  The Safe Harbor provision, 35 U.S.C. § 271(e)(1), provides a defense for otherwise infringing activities by stating that it is not an act of infringement to make a patented invention which is primarily manufactured “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.”  The jury instructions, in relevant part, stated:

 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. (Emphasis added.).

Hospira argued that the jury instructions improperly focused on reasons why each batch of EPO was manufactured, and not how they were used or whether those uses were reasonably related to the development and submission of information to the FDA.  Hospira further argued that all twenty-one of the EPO batches it manufactured between 2013 and 2015 were used for various types of testing, including biosimilarity, revisions to release specifications, stability testing, and continued process verification.  Hospira contended that because that each type of testing was conducted as part of its BLA submission or its response to the FDA’s Complete Response Letter, all twenty-one batches should have been protected under the Safe Harbor provision.

The Federal Circuit disagreed, reasoning that because the patented inventions are methods of manufacture, the relevant inquiry was not how Hospira used each batch, but whether each act of manufacturing was solely for a use reasonably related to submitting information to the FDA.  The court further emphasized that each accused activity must be evaluated separately.  The Federal Circuit also found that substantial evidence supported the jury’s conclusion that the fourteen batches at issue were not manufactured “solely for uses reasonably related to the development and submission of information” to the FDA.  The jury had limited the protected batches to two that were used for qualifying Hospira’s manufacturing process and equipment, and five that were used for a mandatory pre-approval inspection by the FDA.  Both documentary evidence and expert testimony demonstrated that the manufacturing of the remaining batches was not required for FDA pre-approval, and was instead intended to serve as the commercial inventory of a future launch.  The court focused on the differences between manufacturing required by the FDA for an approval, and drug batches made for commercial use (e.g., continued process verification) or post-approval commitments (e.g., stability testing), where only the former are protected by the Safe Harbor provision.  The court further rejected Hospira’s argument that simply submitting information about a drug substance lot to the FDA brings the manufacture of that lot within the protections of the Safe Harbor, noting that “routine record retention requirements associated with testing and other aspects of the commercial production process” are not protected by the Safe Harbor.  Momenta Pharms., Inc. v. Teva Pharms. USA, Inc., 809 F.3d 610, 620-21 (Fed. Cir. 2015).

This opinion showcases the complex nature of the Safe Harbor provision as applied to biologic medicines.  As the district courts and the Federal Circuit begin to hear more such cases of substance, the meaning of the provision will continue to be shaped and clarified.