It has been nearly 10 years since the U.S. Biosimilars Pathway (the Biologics Price Competition and Innovation Act) was enacted. The first biosimilar product in U.S. history was approved and launched in 2015. Ten biosimilars were approved in 2019. The Food and Drug Administration (FDA) has now approved 26 biosimilars in total, including biosimilars of nine of the world’s most important biologic medicines: Avastin (2), Epogen (1), Enbrel (2), Herceptin (5), Humira (5), Neupogen (2), Neulasta (3), Remicade (4) and Rituxan (2). The Supreme Court and Federal Circuit have interpreted provisions of the statute. 2019 did not offer any key insights into the statute, but a number of trends emerged and lessons were learned. 

Patent litigations between biosimilar competitors of the same biologic medicine 

• Biosimilar makers are filing for and obtaining manufacturing patents of their own as they do not have to use the manufacturing processes of innovators to obtain approval of their products. 2019 saw the first lawsuit between two biosimilar makers — both with biosimilars of AbbVie’s adalimumab (Humira). In January 2019, Coherus BioSciences, a biosimilar manufacturer, filed a complaint alleging that Amgen’s biosimilar of adalimumab (Amgevita) infringed patents for its own biosimilar version of adalimumab. According to the complaint, Amgen launched Amgevita in Europe but manufactured Amgevita in the United States. Coherus claimed that production of Amgevita in the United States infringed its formulation patents. The parties settled the suit in November 2019. 

• Amgen holds the earliest launch date in the United States of any biosimilar adalimumab and will launch in January 2023. Coherus will launch in December 2023. 

• We are likely to continue to see patent infringement litigation between biosimilar competitors in the years ahead as biosimilar makers continue to procure and enforce patents. 

Expired patents may result in substantial damages awards; the Safe Harbor does not protect all preapproval manufacture 

• Amgen’s lawsuit with Pfizer’s Hospira involving a biosimilar of erythropoietin (EPO) has provided a number of important lessons: patents that are expired at the time of biosimilar approval may still have value to innovators, and the Safe Harbor provision of 35 U.S.C. § 271(e)(1) does not protect all preapproval manufacture. 

• In December 2019, the Federal Circuit upheld a jury verdict that: 1) Amgen’s expired patent was infringed and not invalid; 2) 14 batches of Hospira’s EPO biosimilar were not protected by the Safe Harbor provision; and 3) Amgen was entitled to $70 million in damages. The Federal Circuit made clear that preapproval manufacture of a biosimilar product is not necessarily protected by the Safe Harbor provision unless the biosimilar batches are made solely for regulatory purposes. 

• The case arose over Amgen’s complaint (filed in September 2015) alleging that Hospira infringed U.S. Patent Nos. 5,865,298 and 5,756,349, related to forms of EPO and methods of preparing EPO. At the time the complaint was filed, Hospira’s EPO biosimilar was not approved in the United States. Hospira claimed that its 21 batches of biosimilar EPO, which were prepared between 2013 and 2015, prior to expiration of the patents, fell within the Safe Harbor provision because the batches were related to the development and submission of information to the FDA. 

• At trial, Amgen asserted that the 21 batches of Hospira’s EPO had a commercial value of over $100 million. The jury found that the claims of the ’298 patent were infringed and not invalid, and that 14 of the 21 batches were not covered by the Safe Harbor provision. The jury awarded Amgen $70 million in damages.  

Settlements abound and the USPTO intervenes in biosimilar IPR appeals post-settlement 

• Biosimilar makers continue to make use of inter partes review (IPR) proceedings to challenge patents protecting biologic medicines and to drive settlements. When the settlements occur after a final written decision by the Patent Trial and Appeal Board (PTAB) and the biosimilar maker withdraws from the appeal, the U.S. Patent and Trademark Office (USPTO) has been jumping in to protect the PTAB’s decision. 

• For example, AbbVie appealed the PTAB’s Final Written Decision finding claims of U.S. Patent Nos. 8,889,135; 9,017,680; and 9,073,987, directed to methods of using adalimumab, to be unpatentable. Although Coherus BioSciences and Boehringer Ingelheim settled with AbbVie and withdrew from the appeal, the USPTO intervened to uphold the PTAB’s unpatentability decision.  

• Similarly, Biogen appealed the PTAB’s Final Written Decision finding all claims of U.S. Patent No. 8,821,873, directed to methods of treating diffuse large cell lymphoma with anti-CD20 antibodies, to be unpatentable. After Pfizer settled with Biogen and withdrew from the appeal, the United States intervened in response to Biogen’s constitutional challenge of subjecting its pre-AIA patent to an IPR. The USPTO intervened to uphold the PTAB’s final decision.