By: Suzie Vroman
In March, the Food and Drug Administration (FDA) granted approval for the first biosimilar in U.S. pharmaceutical history under the Biologics Price Competition and Innovation Act (BPCIA). Biosimilars, the generic form of biologics, are not currently on the market in the United States, but this may soon change with the approval of Sandoz’s drug Zarxio. Zarxio is a close copy of Amgen’s drug Neupogen, which is currently on the market and used to prevent infections in cancer patients undergoing chemotherapy. Biosimilars present a great potential to not only lower the costs of some of these expensive biologic drugs, but also grab a share of the pharmaceutical market. Although Sandoz now has the green light from the FDA to launch its product, battles remain on whether Sandoz is infringing on Amgen’s patents and whether or not Sandoz has to follow the BPCIA patent exchange process to resolve any disputes.
Before Zarxio was approved by the FDA, the first round of litigation under the BPCIA had already begun addressing whether the BPCIA’s patent procedures, more commonly known ask the “patent dance,” are mandatory. In December, the United States Court of Appeals for the Federal Circuit affirmed the District Court for the Northern District of California’s decision to dismiss Sandoz’s motion for declaratory judgment that two of Amgen’s patents were invalid, unenforceable, and would not be infringed by the marketing of Sandoz’s biosimilar Enbrel®. At the time of the suit, Sandoz had not filed an abbreviated biologic license application with the FDA and Amgen had not alleged that Sandoz was currently doing anything to infringe its patent rights.
The district court dismissed the complaint on two grounds. First, that its discretion to enter a declaratory judgment is subject to the provisions of the BPCIA, which sets limitations on patent litigation arising from filing an application for market approval of a biosimilar. The court concluded that neither Sandoz nor Amgen may file a lawsuit related to patents until they have “engaged in a series of statutorily-mandated exchanges of information.” Second, the court held that Sandoz did not establish a real and immediate injury or threat caused by Amgen. Amgen never advised Sandoz that it was going to sue and the mere threat that Sandoz was going to file an application with the FDA was not sufficient to establish a case and controversy. On appeal, the Federal Circuit affirmed the district court’s decision on the second ground agreeing that Sandoz did not present a case and controversy when the only activity to create a potential infringement was future activity requiring FDA approval. The Federal Circuit, however, declined to address the district court’s interpretation of the BPCIA.
The Federal Circuit exhibited caution in in interpreting the BPCIA in its decision, but the ruling still casts doubt on the ability of a biosimilar applicant to file a declaratory judgment action prior to filing an abbreviated license application with the FDA. However, with the Federal Circuit’s silence on the BPCIA, it remains unclear whether or not the statutory patent exchange process has to be followed prior to a biosimilar obtaining market approval and entry into the U.S. market.
With the FDA’s approval of Zaxrio in March, the battles over the patent exchange process continue to heat up, this time with Amgen on the offensive. Despite the rulings from the district court and the Federal Circuit saying Sandoz could not bypass the BPCIA through litigation, Sandoz wrote to Amgen stating that it would not be participating in the patent exchange process under §262(l). Sandoz also claimed it had already provided its 180-day notice of commercial marketing to Amgen by notifying its intention to launch its product immediately after FDA approval. This letter triggered Amgen to file a complaint of patent infringement, unfair competition, and theft in which Amgen argued that the patent exchange process is mandatory. The district court however, rejected this argument holding that words such as “shall” make it optional for the biosimilar applicant to take advantage of the opportunities under the BPCIA to restrict the reference product’s ability to initiate patent infringement proceedings. The district court also held that Sandoz could provide its 180-day commercial marketing notice to Amgen prior to FDA approval, because doing so after would extend Amgen’s market exclusivity term past the 12 years and 6 months that Congress had originally indented.
On March 25, 2015 the FDA also weighed in on the patent exchange process in denying Amgen’s citizen petition requesting biosimilar applicants to include certifications that they will comply with 261(1)(2)(A) by providing the reference product a copy of the biosimilar application. The FDA however, declined to endorse Amgen’s interpretation of the BPCIA hoping to avoid a battle that it believes will be fought out in court. The agency was quick to highlight that the BPCIA does not expressly require biologic applicants to identify certain patents for listing by the FDA or for the generic applicants to certify the patents are either invalid, have been designed around, or that they will not launch until the patents have expired. This is in contrast to the BPCIA’s small-molecule generic counterpart, the Hatch-Waxman Act, which does require these steps prior to FDA approval.
The patent disputes before and after FDA approval if Zarxio demonstrate not only how narrowly the current statutory scheme limits the ability of biosimilar applications to resolve lengthy patent issues before FDA approval, but also the uncertainly of when the reference product can rely on the statutory patent exchange process to bring a declaratory judgment action for patent infringement. With little to no interpretation from the Federal Circuit on the BPCIA provisions on either side of the FDA approval fence, both the reference product and the biosimilar applicant are at a disadvantage. Without being able to litigate its complaint for patent invalidity prior to filing an application with the FDA, Sandoz now has to make the decision to delay launching its product onto the market until the litigation has been completed or risk potential damages of patent infringement by launching now without knowing the outcome of the patent dispute. Without clear guidance from the FDA and the courts, Amgen is also left in the dark on when to initiate patent infringement proceedings to keep biosimilars completely off the market while it still may have valid patents to protect.
 Sabrina Tavernise & Andrew Pollack, F.D.A. Approves Zarixo, Its First Biosimilar Drug, NY Times (March 6, 2015) available at https://www.nytimes.com/2015/03/07/health/fda-approves-zarxio-first-biosimilar-drug.html?_r=0.
 See 42 U.S.C. §262(i)(1) (defining biologics as, “a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein (except any chemically synthesized polypeptide), or analogous product, or amphetamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings”).
 New era about to dawn: Novartis, and now Celltrion, present biosimilars to the FDA, FiercePharma, https://www.fiercepharma.com/story/novartis-and-now-celltrion-biosimilars-fda-new-era-about-dawn/2014-08-13 (last visited April 5, 2014).
 See 42 U.S.C. §§262(l)(2)-(6) (outlining the statutorily mandated multi-step patent exchange process known as the “patent dance”).
 Sandoz Inc. v. Amgen Inc., 733 F. 3d 1274 (Fed. Cir. 2014), aff’d, No. CV-13-2904 MMC, 2013 WL 6000069 (N.D. Cal. Nov. 12, 2013).
 See 42 U.S.C. §§262(l)(2)-(6).
 Sandoz, 2013 WL 6000069 at *2.
 Sandoz, 733 F. 3d at 1279.
 Id. at 1275.
 See Kurt R. Karst, Feeling Dissed, Amgen Sues After Sandoz Abandons the BPCIA Patent Dance Procedures for NEUPOGEN Biosimilar; Alleges Unfair Competition, Patent Infringement, and Theft, FDA Law Blog (October 29, 2014) available at https://www.fdalawblog.net/fda_law_blog_hyman_phelps/2014/10/feeling-dissed-amgen-sues-after-sandoz-abandons-the-bpcia-patent-dance-procedures-for-neupogen-biosi.html.
 Complaint at 17, Amgen v. Sandoz, No. 3:14-cv-04741-EDL (N.D. Cal. 2014).
 Amgen v. Sandoz, No. 14-cv-04741-RS, at *13-14 (N.D. Cal. 2015).
 FDA Letter, re: Docket No. 2014-P-1771 (March 25, 2015) at p. 3.
 21 U.S.C. § 355(b)(1)-(2)(A).