Under Section 262(l)(8)(A) of the BPCIA, a biosimilar maker must provide notice to the reference product sponsor 180 days before the date of first commercial marketing of the biosimilar.  In Sandoz v. Amgen, 137 S. Ct. 1664, 1678 (2017), the Supreme Court explained that the biosimilar maker does not need to wait until its abbreviated biologics license application (aBLA) is approved by the FDA to give notice; it can provide notice any time.  But, under the statute, a notice of commercial marketing does need to be provided.  The question presented by the appeal decided earlier this week in Genentech, Inc. v. Immunex Rhode Island Corp., No. 2019-2155 (Fed. Cir. July 6, 2020) was whether supplements to a biosimilar’s aBLA—such as to change the drug’s label or add a new manufacturing site—trigger a new Section 262(l)(8)(A) requirement (and with it, a new 180-period following the aBLA supplement prior to marketing).  The Federal Circuit held that a BLA supplement does not require a new notice of commercial marketing. 

The Genentech case involves Genentech’s Avastin® (bevacizumab), a widely used humanized monoclonal antibody approved to treat a variety of cancers, and Amgen’s Mvasi® (bevacizumab-awwb), one of two FDA-approved biosimilars of Avastin.  (FDA approved Mvasi in 2017; Pfizer’s Avastin biosimilar, Zirabev (bevacizumab-bvzr), received approval in 2019.)  Amgen’s aBLA for Mvasi, and the BPCIA information exchange that followed, sparked BPCIA patent litigation that is pending in the District of Delaware (No. 17-cv-1407), set for jury trial before Judge Connolly in November of this year.

Amgen submitted several supplements to its Mvasi aBLA in 2018.  One sought to add Immunex’s Rhode Island facility as a new manufacturing site for the Mvasi antibody.  Another sought to modify Mvasi’s labelling.  Interpreting the supplements as a new aBLA, Genentech proceeded with the so-called patent dance, serving an updated list of patents it could reasonably assert pursuant to 42 U.S.C. § 262(l)(3)(A).  Amgen for its part refused to participate in a patent dance based on its aBLA supplements, prompting Genentech to file a separate BPCIA action in Delaware alleging patent infringement against Amgen and Immunex Rhode Island Corp. (No. 19-cv-906).  During the pendency of that case, Amgen received approval to market Mvasi and informed Genentech on July 8, 2019 that it intended to launch immediately.  Genentech, Inc. v. Immunex Rhode Island Corp., 395 F. Supp. 3d 357, 362 (D. Del. 2019).  Genentech moved for a TRO to prevent that launch, relying on Amgen’s failure to provide a new 180-day notice of commercial marketing following its BLA supplements.  Judge Connolly denied that motion, and Amgen launched Mvasi soon thereafter.  Id. at 366.

On appeal, the Federal Circuit addressed this as a question of pure statutory interpretation:  does the BPCIA’s notice of commercial marketing provision apply to aBLA supplements?  Section 262(l)(8)(A) provides that:

The subsection (k) [i.e. biosimilar] 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) [i.e., the biosimilar product].

Genentech argued that Amgen’s original Section 262(l)(8)(A) notice—provided well before the aBLA supplements—was not applicable to the aBLA as supplemented.  In particular, Genentech argued that the new manufacturing site and label change created a new “biological product licensed under subsection (k).”  With little analysis, the Federal Circuit disagreed. 

Section 262(k), not Section 262(l)(8)(A), details the contents and requirements for biosimilar licensure, including manufacturing and labeling.  Section 262(k) relates to disclosure for licensure.  Section 262(l)(8)(A) expressly requires prior notice regarding commercial marketing of the “biological product,” the definition of which makes no reference to Section 262(k).  Section 262(l)(8)(A) relates to timing.

(Slip op. at 4.)  The panel also relied on the Supreme Court’s Sandoz decision, which it described as holding that the word “licensed” in Section 262(l)(8)(A) “simply means that the product must be licensed on the date of the first commercial marketing, not that each supplemental application results in a new license requiring the biosimilar applicant to provide further notice.”  (Id. at 5.)  The Federal Circuit concluded that a biosimilar maker can amend its aBLA without triggering a new 180-day period under Section 262(l)(8)(A). 

The facts here highlight an important issue in BPCIA litigation:  the process by which a product is made (which, in the world of biologics, dictates the nature of the product) can change prior to approval.  And since manufacturing processes are critical to biotechnology, these process changes can implicate patents that may not have been at issue previously.  Biotechnology innovators must therefore remain vigilant in monitoring the FDA approval process during the pendency of BPCIA litigation because, if this decision stands, they will not be able to rely on a renewed 180-day window to assess the supplement under Section 262(l)(8)(A).