Biosimilar Update – Shall We Dance?

By: Emily A. Curtis  |   April 20, 2016

On April 5, 2016, the U.S. Food and Drug Administration (“FDA”) approved Inflectra, Celltrion Inc.’s biosimilar to Janssen Biotech, Inc.’s Remicade (infliximab). Inflectra was approved as therapy for Crohn’s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and chronic severe plaque psoriasis. This is the second biosimilar approved by the FDA following the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”). Although the FDA just approved Inflectra, Janssen and Celltrion have already begun patent litigation related to the biosimilar. Litigation is related to Janssen’s patents and Celltrion’s statutory requirements under BPCIA.

The BPCIA allows for abbreviated biologics license applications (“aBLA”) to be filed in relation to a reference product. 42 U.S.C. § 262(k). The reference product was originally submitted by a reference product sponsor (“RPS”). Id. at § 262(l)(1)(A). The process includes procedures for addressing patents currently held by the RPS which would be at issue if the proposed biosimilar entered the market. See id. at § 262(l). Under 42 U.S.C. § 262(l)(2)(A), the applicant “shall provide to the reference product sponsor a copy of the application submitted to the Secretary under subsection (k), and such other information that describes the process or processes used to manufacture the biological product that is the subject of such application.” This information exchange is commonly referred to as the “patent dance.” Where the applicant “fails to provide the application and information required under paragraph (2)(A), the reference product sponsor, but not the subsection (k) applicant, may bring an action under section 2201 of Title 28, for a declaration of infringement, validity, or enforceability of any patent that claims the biological product or a use of the biological product.” Id. at § 262(l)(9)(C).

Under 42 U.S.C. § 262(l)(8)(A), the applicant “shall provide notice to the reference product sponsor not later than 180 days before the date of the first commercial marketing of the biological product licensed under subsection (k).” If the applicant does not provide this notice, “the reference product sponsor, but not the subsection (k) applicant, may bring an action under section 2201 of Title 28, for a declaration of infringement, validity, or enforceability of any patent included in the list [created in the information-exchange process].” Id. at § 262(l)(9)(B). Recent litigation relates to the interpretation of this statute and the requirements of aBLA applicants.

In Amgen Inc. v. Sandoz Inc., the Federal Circuit first addressed issues of the BPCIA, including the patent dance and the 180-day exclusionary period. 794 F.3d 1347, 1351-52 (Fed. Cir. 2015). Sandoz filed an aBLA related to Amgen’s Neupogen; however, Sandoz did not provide its aBLA and manufacturing information to Amgen when the FDA accepted the aBLA. Id. at 1352-53. The patent dance, according to Sandoz, was not required of all aBLA filers. Id. The statute states that the applicant “shall provide” information to the RPS, in this case Amgen, to begin the patent dance. Id. at 1354. Sandoz argued that “shall” in this provision did not require the information from all applicants and the Federal Circuit agreed. Id. at 1355. The Court found that the statute provides a specific remedy where an applicant did not share the information. Id. at 1356. Thus, the patent dance of information exchange is not required by the BPCIA. Id. at 1357.

The Court also considered whether a 180-day notice period was required after the FDA approved Sandoz’s biosimilar. Id. at 1358-59. The BPCIA includes consequences where the applicant doesn’t give the RPS 180 days notice before commercially marketing the biosimilar similar to the consequences for avoiding the patent dance. Id. However, the Court determined that such a remedy only applied where the applicant complied with the information-exchange requirements. Id. Since Sandoz did not share the aBLA and manufacturing information to enter the patent dance, the 180-day notice before commercial marketing is required. Id. at 1360.

Unlike Sandoz, Celltrion did provide the Inflectra aBLA to Janssen after the FDA accepted Celltrion’s application, although Janssen disputes the completeness of Celltrion’s manufacturing information. Complaint at 22, Janssen Biotech, Inc. v. Celltrion Healthcare Co., Ltd., No. 15-10698 (D. Mass. March 6, 2015). In Amgen Inc. v. Sandoz Inc., the Court required a 180-day notice because Sandoz did not participate in the patent dance. 794 F.3d at 1360. The question remains whether a 180-day notice is required of applicants who do participate in the “patent dance.” The Federal Circuit will consider this question in Amgen v. Apotex, where Apotex timely provided Amgen with the required aBLA and manufacturing information regarding biosimilar pegfilgrastim. No. 16-1308 (Fed. Cir. 2016). The Court is set to decide whether Apotex must give Amgen 180 days notice before commercially marketing its biosimilar. Id. Given the previous statutory interpretation, it is likely that applicants participating in the patent dance may accept the statutory consequence rather than give 180 day notice. The statute includes a remedy where an applicant does not give notice to the RPS “after the applicant has complied with [the patent dance].” 794 F.3d at 1359. Thus, the remedy should allow the applicant who shares an aBLA and manufacturing information to give 180 days notice before marketing the biosimilar or submit to the statutory consequence. As a consequence, “the reference product sponsor, but not the subsection (k) applicant, may bring an action under section 2201 of Title 28, for a declaration of infringement, validity, or enforceability of any patent included in the list described in paragraph (3)(A).” 42 U.S.C. § 262(l)(9)(B). Otherwise, the applicant would have no reason to participate in the patent dance if the 180-day notice is required with or without the applicant’s participation. This understanding of the BPCIA allows the applicant to participate in the patent dance and/or give 180 days notice before marketing the biosimilar. It has already been determined that the applicant may not avoid both forms of notice. See 794 F.3d 1347. The remedies for failing to fulfill either notice are similar. In either case, the RPS can sue under section 2201 of Title 28 for a declaration of infringement, validity, or enforceability. Where an applicant refuses to enter the patent dance, the applicant must provide 180 day notice before marketing and the reverse should also be true. If, as Amgen and Janssen suggest, every applicant must provide the 180 day notice, there is no incentive for an applicant to enter the patent dance.  Further, there would be no reason to include a statutory consequence of foregoing the 180 day notice.

The Federal Circuit’s opinion in Amgen v. Apotex could affect Janssen and the potential release date of Inflectra. Celltrion has stated that it will not release Inflectra until June 30, 2016, after an asserted patent expires.Even if Celltrion gave notice to Janssen immediately upon FDA approval, the projected biosimilar release date of June 30 is within 180 days of Celltrion’s notice. If the Federal Circuit finds that the 180 day notice is not required where an applicant participated in the patent dance, Celltrion will have to fight Janssen’s motions for injunctions regarding Inflectra in order to release the biosimilar by June 30, 2016. Although the FDA has approved Inflectra, litigation will determine when it may be introduced to the market.