Five patent issues that European biosimilar developers should consider before entering the US market

References for ‘Five patent issues that European biosimilar developers should consider before entering the US market’, in European Pharmaceutical Review Issue 3 2020.


  1. See Goodwin, Guide to Biosimilars Litigation and Regulation in the U.S.. 2019-2020 ed. Thompson-Reuters; 2019. (“Biosimilar Guide”).
  2. Since the BPCIA’s enactment in March 2010, FDA has approved 26 applications for biosimilar products, sixteen of which are currently available on the U.S. market. See FDA Approvals [Internet]. Big Molecule Watch Blog. 19 March 2020 [cited 1 April 2020]. Available from: During that period, RPSs and biosmilar applicants have engaged in more than 25 patent litigations under the BPCIA. See BPCIA Litigations [Internet]. Big Molecule Watch Blog. 30 March 2020 [cited 1 April 2020]. Available from
  3. Amgen Inc. v. Sandoz Inc., 794 F.3d 1347, 1351 n.1 (Fed. Cir. 2015) (“Winston Churchill once described Russia as ‘a riddle wrapped in a mystery inside an enigma.’ That is this statute[, the BPCIA]. In these opinions, we do our best to unravel the riddle, solve the mystery, and comprehend the enigma.” (internal citation omitted)).
  4. 35 U.S.C. § 271(e)(2); see Eli Lilly & Co. v. Medtronic, Inc., 496 U.S. 661, 678 (1990).
  5. See Sunovion Pharm., Inc. v. Teva Pharm. USA, Inc., 731 F.3d 1271, 1278 (Fed. Cir. 2013) (“Although no traditional patent infringement has occurred until a patented product is made, used, or sold, under the Hatch-Waxman framework, the filing of an ANDA itself constitutes a technical infringement for jurisdictional purposes.”); see also, e.g., Novartis Pharm. Corp. v. Watson Labs., Inc., 611 F. App’x 988, 997 (Fed. Cir. 2015); Ferring B.V. v. Watson Labs., Inc.-Fla., 764 F.3d 1401, 1408 (Fed. Cir. 2014); Allergan, Inc. v. Alcon Labs., Inc., 324 F.3d 1322, 1331 (Fed. Cir. 2003); Warner-Lambert Co. v. Apotex Corp., 316 F.3d 1348, 1365–66 (Fed. Cir. 2003); Bristol-Myers Squibb v. Royce Labs., 69 F.3d 1130, 1135 (Fed. Cir. 1995).
  6. Sandoz Inc. v. Amgen Inc., 137 S. Ct. 1664, 1675-76 (2017) (holding that an RPS may not compel a biosimilar applicant under federal law to engage in the patent dance), remanded to 877 F.3d 1315, 1326 (Fed. Cir. 2017) (same, but under state law).
  7. Generally, the complete patent dance takes about eight months between FDA acceptance and when litigation in the district court begins. For a summary of different patent dance strategies, see Biosimilar Guide at 45-50.
  8. Some critics have blamed these “patent thickets” – and the corresponding need for extensive patent litigation – for keeping biosimilars in the U.S. from taking off in the way they have in Europe. See, e.g., Price WN, Rai AK. How logically impossible patents block biosimilars. Nature Biotechnology. 2019; 37:862-863.
  9. Biologic drugs are often protected by multiple U.S. patents that may be owned or licensed by numerous entities, and may include patents directed to compositions of matter, formulations, methods of treatment, dosing regimens, manufacturing processes, and cell media, to name a few. Biologics patent portfolios are not required to be listed in a compendium like the Orange Book for small molecule drugs and may include patents that expire many years after expiry of the original compositions of matter patents. Accordingly, without an extensive freedom to operate analysis, a biosimilar applicant may not know all the patents its proposed product could potentially infringe, and when those patents expire. Furthermore, a prospective biosimilar applicant should not necessarily limit its review to the RPS’s patent portfolio. For example, in at least one U.S. case so far, a biosimilar applicant, Coherus, has sued another biosimilar applicant, Amgen, for patent infringement based on Amgen’s biosimilar manufacturing activities in the U.S. Although the case settled after a few months, it is reasonable to assume that the future will bring considerably more of this type of litigation. Indeed, in the generic drug context, there is a long history of generic vs. generic litigation. See Whitehill J, et al. ‘Biosimilar V. Biosimilar’ Patent Case May Be First Of Many [Internet]. 4 May 2019 [cited 1 April 2020]. Available from:
  10. The most commonly applied test for determining equivalency is the “function-way-result” test, which asks whether the “equivalent” feature in the accused product or process performs substantially the same function, in substantially the same way, to obtain substantially the same result as the claimed element. Warner-Jenkinson Co., Inc. v. Hilton Davis Chemical Co., 520 U.S. 17, 39-40 (1997); Graver Tank & Mfg. Co v. Linde Air Products Co., 339 U.S. 605, 608 (1950).
  11. Amgen Inc. v. Sandoz Inc., 295 F. Supp. 3d 1062, 1070 (N.D. Cal. 2017) (granting summary judgment of non-infringement), affirmed by 923 F.3d 1023 (Fed. Cir. 2019), as modified on Sept. 3, 2019.
  12. Amgen Inc. v. Coherus Biosciences Inc., No. 17-cv-546-LPS-CJB, 2018 WL 1517689, *1 (D. Del. Mar. 26, 2018), affirmed, 931 F.3d 1154 (Fed. Cir. 2019) (affirming based only on prosecution history estoppel grounds).
  13. A patentee can surrender subject matter either by making arguments or narrowing the claims to obtain allowance of the claims during prosecution. See Conoco, Inc. v. Energy & Environmental Intern., L.C., 460 F.3d 1349, 1363 (Fed. Cir. 2006).
  14. Based on the Coherus ruling, Amgen ultimately stipulated to non-infringement in a related case against Mylan. See Mylan Prevails in Pegfilgrastim Biosimilar Litigation [Internet]. Big Molecule Watch Blog. 19 September 2019 [cited 1 April 2020]. Available from:
  15. Janssen Biotech, Inc. v. Celltrion Healthcare Co., 210 F. Supp. 3d 278 (D. Mass. 2016), affirmed, No. 18-2321 (Fed. Cir. Mar. 5, 2020).
  16. Courts recognize several other exceptions to the doctrine of equivalence beyond the ones mentioned in these biosimilar cases.
  17. More than half of the patents asserted in BPCIA litigations have been directed to manufacturing processes.
  18. Section 271(g) carves out two exceptions to liability: (1) where the product of the patented process that was made outside the U.S. is “materially changed by subsequent processes”; and (2) where the product “becomes a trivial and nonessential component of another product.” Determining whether either of these exceptions applies requires fact- and context-specific inquiries. A “material change“ requires, at a minimum, that there be a real difference between the product imported, offered for sale, sold, or used in the United States and the products produced by the patented process.” Bio-Tech. Gen. Corp. v. Genentech, Inc., 80 F.3d 1553, 1560 (Fed. Cir. 1996). As an example in the case of biologic process patents, the Federal Circuit has found “a significant change in a protein’s structure and/or properties would constitute a material change.” Amgen Inc. v. F. Hoffman-La Roche Ltd., 580 F.3d 1340, 1379 (Fed. Cir. 2009). Similarly, whether a product of a patented process is a “trivial and nonessential component” is also a “question of degree.” Eli Lilly and Co. v. American Cyanamid Co., 82 F.3d 1568, 1572 (Fed. Cir. 1996).
  19. For example, methods of analysis, even if conducted during the manufacturing process, generally do not implicate § 271(g) because analysis methods merely generate information, as opposed to a product “made by” a patented process, as required by the statute. Rather, “made by” connotes “manufacture,” and extends to “the creation or transformation of a product, such as by synthesizing, combining components, or giving raw materials.” Momenta Pharm., Inc. v. Teva Pharm. USA Inc., 809 F.3d 610, 616 (Fed. Cir. 2015).
  20. This safe harbor “exempt[s] from infringement all uses of patented compounds ‘reasonably related’ to the process of developing information for submission under any federal law regulating the manufacture, use, or distribution of drugs.” Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S. 193, 206 (2005) (emphasis in original).
  21. Merck, 545 U.S. at 208. Section 271 was meant to be “sufficiently broad” to “leave[] adequate space for experimentation and failure on the road to regulatory approval.” Id. at 206-07.
  22. Abtox, Inc. v. Exiron Corp., 122 F.3d 1019, 1027 (Fed. Cir. 1997) (“Once it is determined that the activity is reasonably related to obtaining FDA approval, [] intent or alternative uses are irrelevant to its qualification to invoke the section 271(e) shield.”).
  23. Momenta, 809 F.3d at 613, 619-20 (holding that the safe harbor does protect testing to generate “information that may be routinely reported to the FDA, long after marketing approval has been obtained,” such as “routine quality control testing” or the use of “research tools or devices that are not themselves subject to FDA approval.”).
  24. The jury’s verdict was upheld by the district court and on appeal. Among other things, the Court of Appeals credited the jury for conducting a batch-by-batch analysis and finding that the manufacture of some, but not all, of Hospira’s batches were indeed reasonably related to FDA approval and thus protected by safe harbor. Amgen Inc. v. Hospira, Inc., 944 F.3d 1327 (Fed. Cir. 2019), petition for rehearing denied (Fed. Cir. Mar 16. 2020).
  25. See, e.g., Caraco Pharm. Labs., Ltd. v. Novo Nordisk A/S, 132 S. Ct. 1670, 1676-77 (2012); Takeda Pharm. U.S.A., Inc. v. West-Ward Pharm. Corp., 785 F.3d 625, 630-34 (Fed. Cir. 2015); AstraZeneca LP v. Apotex, Inc., 633 F.3d 1042, 1046 (Fed. Cir. 2010).
  26. See Zheng L. What Is Skinny Labeling — And Will It Work For Biosimilars? [Internet] Biosimilar Development. 5 February 2019 [cited 1 April 2020]. Available from:
  27. 42 U.S.C. § 262(l)(8).
  28. “A plaintiff seeking a preliminary injunction must establish [1] that he is likely to succeed on the merits, [2] that he is likely to suffer irreparable harm in the absence of preliminary relief, [3] that the balance of equities tips in his favor, and [4] that an injunction is in the public interest.” Winter v. Nat. Res. Def Council, Inc., 555 U.S. 7, 20 (2008) (citations omitted); see also Apple, Inc. v. Samsung Elecs. Co., 695 F.3d 1370, 1373-74 (Fed. Cir. 2012).
  29. Genentech, Inc. v. Amgen Inc., No. 18-924-CFC, 2019 WL 3290167, at *2-3 (D. Del. July 18, 2019) (“Thus, the 180-day period is designed to prevent exactly the circumstances that Genentech has engineered in this case—a ‘race to court for immediate relief to avoid irreparable harm from market entry, and … the hurried motion practice that (8)(A) is designed to replace.”), affirmed, No. 19-2156 (Fed. Cir. Mar. 6 2020); Genentech, Inc. v. Immunex Rhode Island Corp., 395 F. Supp. 3d 357 (D. Del. 2019), on appeal, No. 19-2155 (Fed. Cir.).

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