As biosimilar litigation between Amgen, the maker of Enbrel® (etanercept), and Sandoz, the maker of biosimilar ErelziTM (etanercept-szzs) heads toward trial before Judge Claire Cecchi in the District of New Jersey, Sandoz is seeking to stave off Amgen’s infringement claims for three of the patents in suit by pointing to its recent amendment to the Erelzi label, which “carves out” certain treatment indications listed on the Enbrel reference label and, Sandoz argues, moots any claim that Erelzi infringes Amgen’s patents covering the use of etanercept to treat those conditions.

The active ingredient in Enbrel, etanercept, is a fusion protein consisting of a portion of the tumor necrosis factor receptor (TNFR) linked to an Fc (a portion of an antibody) that binds to TNF molecules and inhibits their binding to cell-surface TNF receptors. In doing so, etanercept helps regulate immune responses and inflammation in the body. FDA approved Enbrel for the treatment of five autoimmune and inflammatory disorders: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis.

In September 2015, Sandoz filed an abbreviated Biologics License Application (“aBLA”) seeking authorization from FDA to market Erelzi, an Enbrel biosimilar. At the time, Sandoz sought approval for all of the indications included in the reference product label. In August 2016, FDA approved the biosimilar Erelzi for all five indications. Sandoz has not yet launched Erelzi, however, due to the ongoing patent litigation with Amgen.

In February 2016, while Erelzi’s approval had been pending, Amgen sued Sandoz under the BPCIA, claiming that Sandoz’s aBLA infringed five patents covering Enbrel, its manufacture, and certain therapeutic uses of etanercept. But in the middle of the litigation, Sandoz returned to FDA to seek approval for an amended biosimilar label carving out indications for the treatment of psoriatic conditions—methods covered by three of the patents asserted by Sandoz. FDA approved the request in January 2018.

Meanwhile, in December 2017, Amgen moved for summary judgment on infringement of one of its psoriasis patents on the basis of Sandoz’s original biosimilar label, and Sandoz responded by arguing that the label carve-out mooted Amgen’s infringement claim. In a letter to Judge Cecchi following FDA’s approval of the amended label, Sandoz argued that the amendment “effectively eliminates” Amgen’s psoriasis patents from the case and thus moots Amgen’s pending summary judgment motion. According to Sandoz, Amgen’s summary judgment motion “relies exclusively on allegations of infringement on a Sandoz label—a label Sandoz has not been seeking to use since July 2017 and is indeed no longer able to use for launch as it is not the approved label for Sandoz’s product.” Therefore, Sandoz continued, “there is no longer a live controversy surrounding [Erelzi’s] pre-amendment label.”

In a letter response filed the same day, Amgen referred the court to arguments made in its summary judgment reply brief, which, according to Amgen, “squarely and systematically refute[]” Sandoz’s position that a label carve-out moots Amgen’s claims. Although Amgen’s summary judgment reply brief is heavily redacted, the gist of the argument appears to be that Sandoz has already committed an act of infringement under Section 271(e)(2)(C) by filing its aBLA, which “cannot be retroactively undone” by later carving out indications from the label. Amgen also appears to suggest that Sandoz’s biosimilar may in fact be prescribed as a psoriasis treatment notwithstanding the label carve-out, latching onto FDA’s statement that there was “scientific justification for extrapolating conclusions of biosimilarity to additional indications that had not been studied.” According to Amgen, FDA “published to the physician and patient community” its conclusion that Sandoz’s product was biosimilar to Enbrel and could be used to treat the same indications.

In late-April, Sandoz filed a supplemental brief in opposition to Amgen’s summary judgment motion, in which Sandoz reiterated the argument that its label carve-out “render[s] infringement of the Asserted Claim an impossibility.” Sandoz argues that Amgen is not permitted to sell a product with the pre-amendment label, and thus there is no reasonable expectation that infringement under § 271(a), (b), or (c) will occur. Sandoz further refutes as a hypothetical “what-if” Amgen’s argument that the biosimilar maker could ask FDA to re-approve the old label.

Amgen’s summary judgment motion remains pending as the parties inch closer to trial, now scheduled to begin in September 2018. Although the motion only involves one of the claimed patents, Sandoz has made clear that the reasons supporting denial of the motion also support noninfringement of each of the three psoriasis patents. Judge Cecchi’s decision on the role of label carve-outs would be a first, and may have important implications for innovators and biosimilar makes alike in biosimilar litigation. In particular, the decision will address the role of carve-outs in cases involving alleged infringement of innovators’ method of treatment patents.

The case is captioned Immunex Corp. et al. v. Sandoz Inc. et al., No. 16-cv-1118(CCC)(MF) (D.N.J.).