This article originally was published at IPWatchdog.com.

Since the Biologics Price Competition and Innovation Act of 2009 (BPCIA) was signed into law in 2010, only a small handful of abbreviated Biologics Licensing Applications (“aBLAs”) have been filed and of those the FDA has approved only two so far: Sandoz’s Zarxio® and Celltrion’s Inflectra™. (Sandoz’s biosimilar to Amgen’s Enbrel® (etanercept) and Amgen’s biosimilar to AbbVie’s Humira® (adalimumab) are well on the path to approval, with both biosimilars awaiting the recommendation of approval from an independent advisory committee following positive FDA reports.) Although Zarxio® (the biosimilar to Amgen’s Neupogen® (filgrastim)) is now available in the U.S., the two pharmaceutical giants remain embroiled in litigation. Likewise, litigation continues over Inflectra™, (Celltrion’s biosimilar to Janssen’s Remicade® (infliximab)). Many of the issues brought to the forefront by these and similar actions are of first impression and highlight the questions and uncertainties surrounding the biosimilar licensing (approval) process envisioned by the BPCIA.

Like the Hatch Waxman Act’s abbreviated approval pathway for generic drugs, the BPCIA also offers an abbreviated process for the licensing of biosimilars (that is, drug products with “no clinically meaningful differences” from the biologic drug serving as the reference product). 42 U.S.C. § 262(i)(2)(B). The BPCIA also provides a framework for dispute resolution to allow for the timely resolution of patent disputes arising from a manufacturer’s efforts to license its biosimilar. § 262(l). Under this dispute resolution protocol (dubbed “the patent dance”), once the FDA accepts an aBLA for review, the patent dance begins with the aBLA filer providing a copy of its application and the biosimilar’s manufacturing information to the reference product sponsor (“RPS”) and continues with the parties exchanging a list of patents that each contends “could reasonably be asserted in an infringement action” by the RPS. § 262(l)(2), (3)(A)(i), and (3)(B)(i).

As part of the exchange, the aBLA filer provides a detailed statement of its positions regarding non-infringement, invalidity, and unenforceability, and the RPS provides a detailed statement of its own in rebuttal. § 262(l)(3)(B) and (3)(C). The parties then negotiate to select one or more patents from the patent lists to be asserted in an infringement action. § 262(l)(4)(A). If an agreement is reached, the RPS sues for infringement of the agreed-to patents. § 262(1)(6)(A). If there is no agreement, the parties again exchange patent lists and the RPS sues on each patent listed by either party. § 262(1)(4)(B), (5)(B), and (6)(B).

Although time consuming in itself, taking the better part of a year or more to complete, the dispute resolution mechanism of the BPCIA promotes information exchange to streamline subsequent patent litigation. But there are obvious drawbacks, with the aBLA filer required to provide confidential and sensitive information upfront and the parties obligated to provide detailed statements of their litigation positions before suit is filed and to engage in, often futile, negotiations. Thus, it is unsurprising that aBLA filers may balk at the constraints of the BPCIA’s dispute resolution framework, and so questions arise as to whether and to what extent a party must engage in the patent dance.

The BPCIA also requires that the aBLA filer provide the RPS with a notice of commercial marketing no later than 180 days before marketing the biosimilar and authorizes the RPS to seek a preliminary injunction upon receiving the notice. § 262(1)(8)(A). The BPCIA prohibits both parties from seeking a declaratory judgment action ahead of the notice of commercial marketing where the aBLA filer has provided its application and manufacturing information to the RPS, but it provides that, should the aBLA filer fail to follow through on any of its remaining obligations, the RPS may seek a declaratory judgment against the aBLA filer. § 262(1)(9)(A) and (9)(B). Where the aBLA filer fails to engage in the dispute resolution provision altogether, the BPCIA authorizes the RPS, but not the aBLA filer, to seek a declaratory judgment. § 262(1)(9)(C). Questions, however, have arisen as to how early the aBLA filer can provide its notice of commercial marketing, what the ramifications of failure to engage in the patent dance are, and what actions are governed by the BPCIA.

In one of the first actions implicating the statute, Celltrion’s suit seeking a declaratory judgment of invalidity against patents covering Remicade® tested the reach of the BPCIA. Celltrion Healthcare Co. v. Kennedy Trust for Rheumatology Research, No. 1:14-cv-2256, 2014 WL 6765996 (S.D.N.Y. Dec. 1, 2014). Although Celltrion had not filed an aBLA for its biosimilar Remsima™, it nevertheless filed suit alleging that it had made substantial preparations to bring Remsima™ to the U.S market and that the defendant had already expressed its intent to sue for infringement. The district court dismissed the suit for lack of jurisdiction, concluding that even if Celltrion had established the existence of an actual case or controversy, Celltrion’s sole avenue for relief was through the BPCIA’s patent dispute resolution process, which would only be triggered once Celltrion filed an aBLA.

In a similar action, the same court also dismissed Hospira’s declaratory judgment action on the patents covering Remicade®. Hospira, the co-exclusive marketer of Celltrion’s Remicade® biosimilar, filed suit after Celltrion filed an aBLA for its Remicade® biosimilar. But Hospira sought to circumvent the patent dance, arguing that because it was not the aBLA filer, the BPCIA provisions did not apply to its suit. Applying Celltrion’s reasoning, the district court concluded that even if Hospira had established the existence of a justiciable case or controversy, “the existence of the BPCIA mechanisms for dispute resolution counsels against the exercise of jurisdiction over this complaint.” Hospira, Inc. v. Janssen Biotech, Inc., No. 1:14-cv-7049, 2014 WL 6766263, at *1 (S.D.N.Y. Dec. 1, 2014).

On the heels of the Celltrion and Hospira decisions, the Federal Circuit addressed the question of a biosimilar manufacturer’s standing to bring a declaratory judgment action in Sandoz Inc. v. Amgen Inc. 773 F.3d 1274 (Fed. Cir. 2014). As in Celltrion and Hospira, Sandoz brought a declaratory judgment action for invalidity of patents covering Amgen’s biologic Enbrel® (etanercept) before it filed an aBLA. The court below had dismissed the action for lack of subject matter jurisdiction and as barred by the BPCIA, reasoning that Sandoz’s intent to file an aBLA at a point in the future did not create a case or controversy to support its declaratory judgment action at the present, that there was no fear of imminent harm as Amgen had not threatened suit, and that the court’s discretion to enter a declaratory judgment in a drug patent case was subject to the BPCIA, which authorizes the FDA to license biosimilars and sets limits on when a suit may be filed related to a drug manufacturer’s efforts to license its biosimilar. Sandoz Inc. v. Amgen Inc., No. 3:13-cv-2904, 2013 WL 6000069 (N.D. Cal. Nov. 12, 2013). While the appellate court agreed that subject matter jurisdiction was lacking, it declined to address whether the BPCIA barred the action outright. Thus, the reach of the BPCIA remains an open question.

In the last of the suits related to Remicade®, Janssen sued Celltrion and Hospira for patent infringement and to enforce the patent dispute resolution provision of the BPCIA. Janssen Biotech Inc. v. Celltrion Healthcare Co., No. 1:15-cv-10698 (D. Mass March 6, 2015). Similarly, Amgen sued Hospira over the filing of Hospira’s aBLA for a biosimlar to Amgen’s Epogen® (epoetin alfa). Amgen Inc. v. Hospira, Inc., No. 1:15-c-v-00839 (D. Del. Sept. 18, 2015). In both cases, the RPS accused the aBLA filer of failing to provide the manufacturing information for its biosimilar, refusing to negotiate over the patent list, and providing a premature notice of commercial marketing. The format in which the aBLA and the manufacturing information was provided to the RPS has also been the subject of a separate litigation, with Immunex alleging that Sandoz failed to abide by the BPCIA by providing only remote access to a Sandoz-hosted database of TIFF images of the required information. See Immunex Corp. v. Sandoz Inc., No. 2:16-cv-01118 (D.N.J. Feb. 26, 2016).

As evidenced by suits involving Sandoz, it appears to currently lead the resistance against compliance with the BPCIA’s patent dispute resolution protocol. In addition to the above-described actions involving Sandoz, in another suit, Amgen’s single count complaint seeks a declaration that Sandoz violated the mandatory procedures of the BPCIA by failing to complete the actions required under § 262(l)(4) and (l)(5), and that this failure to comply with the mandatory exchange procedures prohibits an “immediate patent infringement action” under § 262(l)(6). Amgen Inc. v. Sandoz Inc., No. 2:16-cv-01276 (D.N.J. March 4, 2016). Sandoz has sought to have the complaint dismissed, arguing that non-compliance does not give rise to an action for a violation of the BPCIA and that any controversy between the parties over the exchange procedures is moot because subsequent to the filing of the complaint Sandoz participated in the exchange process

Two recent Federal Circuit opinions provide some answers to the issues presented by complaints alleging non-compliance with the BPCIA. In Amgen Inc. v. Sandoz Inc., the Federal Circuit concluded that an aBLA filer’s participation in the patent dance is not mandatory under the BPCIA. 794 F.3d 1347 (Fed. Cir. 2015). Where an aBLA filer elects to forego the patent dance by failing to provide the aBLA and the biosimilar manufacturing information to the RPS, the only remedy available to the RPS lies in a declaratory judgment action for patent infringement, as expressly contemplated by § 262(1)(9)(C). In addition, the court concluded that an aBLA filer who did not engage in the patent dance was required to provide a notice of commercial marketing and that such notice could be effectively given only after the FDA had approved the aBLA. The court’s ruling left open the question whether an aBLA filer who participated in the patent dance was required to provide a notice of commercial manufacturing. This decision is on appeal to the Supreme Court, which has yet to decide whether it will hear the issue.

The court’s recent decision in Amgen Inc. v. Apotex Inc., however, has answered that question. Amgen Inc. v. Apotex Inc., 2016 WL 3606770, at *1 (Fed. Cir. July 5, 2016). The appeal concerned Amgen’s motion for a preliminary injunction to enjoin Apotex from entering the market with its biosimilar until it provided a 180-day post-licensure notice of commercial marketing. The issues on appeal notwithstanding, July 11, 2106, marked the first day of trial for the underlying patent infringement action.

Aware of the outcome in Amgen, Apotex argued that its situation warranted a different result where the notice of commercial marketing was concerned because, unlike the defendant in Amgen, it had participated in the patent dance after filing an aBLA for a Neulasta® (pegfilgrastim) biosimilar.

Upholding the lower court’s decision, the Federal Circuit concluded that the notice provision is mandatory even for those aBLA filers who engage in the patent dance and is enforceable by a preliminary injunction. Since, under Amgen, an effective notice may be provided only once the biosimilar is licensed and as that license is not expected to be granted before the biologic’s 12-year exclusivity period expires, the practical result is that the notice extends the biologic’s exclusivity period to 12.5 years. However, in addressing this argument, the Federal Circuit noted that it was not aware of a reason that the FDA “may not issue a license before the 11.5-year mark and deem the license to take effect on the 12-year date.” 2016 WL 3606770 at *17. This suggestion is ripe for attention in later-filed actions and may well spin off suits against the FDA.

With biosimilar litigation set to gain momentum, the decisions rendered thus far on the rudimentary, though fundamental, questions over the metes and bounds of the statute are sure to guide the hand of counselors and corporations alike as they decide whether to dance or not to dance.

Ben Bourke is a student at Temple University’s Beasley School of Law and a Womble Carlyle summer associate.