Last year, the Federal Circuit described the Biologics Price Competition and Innovation Act ("BPCIA") as "a riddle wrapped in a mystery inside of an enigma" in the Amgen v. Sandoz case.  Nevertheless, one of the provisions of the BPCIA was still shrouded in mystery after that opinion -- the Notice of Commercial Marketing provision found at 42 U.S.C. § 262(l)(8)(A).  While at the same time describing this Notice provision as both mandatory and a stand-alone provision (independent of the information-disclosure and patent-exchange provisions that comprise the rest of § 262(l)), the Amgen v. Sandoz Court limited the holding to cases in which the biosimilar applicant failed to comply with disclosure provision of § 262(l)(2)(A).  Amgen v. Sandoz, 794 F.3d 1347, 1360 (Fed. Cir. 2015) ("where, as here, a [biosimilar] applicant completely fails to provide its aBLA and the required manufacturing information to the RPS by the statutory deadline, the [notice] requirement of paragraph (l)(8)(A) is mandatory.").

On July 5, 2016, in Amgen v. Apotex, the Court clarified that the commercial-marketing provision is always mandatory–even when the biosimilar applicant engaged in the so-called "patent dance."  Moreover, the Court held that this provision is enforceable by injunction.  Not surprisingly, this decision does not solve the entire riddle that is the BPCIA, and in fact may end up creating more confusion.  One problem is that this opinion suggested that the FDA may begin providing tentative licensure for a biosimilar product, although such action is not specifically provided for in the BPCIA and the FDA has not suggested that it would begin doing so.  Moreover, even though it was not at issue in this case, the opinion would appear to have answered one of the outstanding questions of the BPCIA -- what happens if the RPS does not identify all of the relevant patents during the patent dance?  Even though commentators have been split on the interpretation of 35 U.S.C. § 271(e)(6)(C), and the parties did not even tackle this section of the patent statute (as it was irrelevant to their case), the Federal Circuit in dicta appears to have inadvertently determined that no infringement action will ever be possible for a patent not identified by the RPS during the patent dance.

We previously provided the background of this case.  Briefly, in 2014, Apotex filed an application for an FDA license to market a biosimilar version of Amgen's reference product Neulasta® (pegfilgrastim).  But, unlike Sandoz before it, Apotex participated in the patent dance, beginning with its notice of FDA acceptance and the disclosure of its aBLA.  During the subsequent lawsuit, Apotex notified Amgen that it did not believe it was required to, and indeed did not intend to, provide the Notice of Commercial Marketing specified under § 262(l)(8)(A) of the BPCIA.  Amgen sought a preliminary injunction, which was issued by Judge Cohn of the Southern District of Florida requiring Apotex to "provide Amgen with at least 180 days notice before the date of the first commercial marketing of the biological product approved by the FDA."  Apotex appealed that decision to the Federal Circuit.

The panel of Amgen v. Apotex consisted of Judges Bryson, Wallach, and Taranto, none of whom was on the panel that decided the Amgen v. Sandoz appeal.  The unanimous opinion, authored by Judge Taranto, held that while the (2)(A) notice given by Apotex created a factual distinction from the Amgen v. Sandoz case, it did not create a legally material distinction.  As such, "[t]he (8)(A) requirement of 180 days' post-licensure notice before commercial marketing . . . is a mandatory one enforceable by injunction whether or not a (2)(A) notice was given."  The Court rejected all assertions by Apotex why the two cases were distinct.  First, section (8)(A) "contains no words" that would make the notice requirement turn on whether the earlier (2)(A) notice was given.  Moreover, unlike with the notice and disclosure provision of (2)(A), there is no language in 271(e) that would create a specific remedy for non-compliance.  The Court also explained that the statutory purpose of the Notice of Commercial Marketing provision was to reduce the "reliability-reducing rush that would attend requests for relief against immediate market entry that could cause irreparable injury" -- a purpose that would be frustrated if section (8)(A) notice were not mandatory.

Apotex argued, just as Sandoz did before it, that if the Notice provision of (8)(A) is mandatory, the 12-year exclusivity period of the RPS would be effectively extended six months.  These parties expressed the concern that if a biosimilar applicant cannot give effective notice until after the FDA has licensed its biosimilar product, and the FDA cannot license the product until the 12-year exclusivity period has run, an RPS would always gain an extra six months of exclusivity.  The Court reiterated and expounded on the view expressed by the majority opinion in Amgen v. Sandoz that this would not be an issue for aBLA filings that occur before the expiration of the 12-year period.  This conclusion, however, assumes that the FDA will provide "tentative licensure," although the FDA has provided no guidance on whether it intends to do so.  There is support in the statute to support such an understanding.  § 262(k)(7)(A) does state, in part, that "[a]pproval of an application under this subsection may not be made effective by the Secretary until the date that is 12 years after the date on which the reference product was first licensed . . . ."  As such, the Court pointed out, approval and effectiveness could be two distinct events, with approval serving as a "tentative licensure," potentially before the expiration of the 12-year period.  Of course, now that the Court has made this view explicit, and tacitly approved it, the FDA may face pressure to undertake such a practice.

More problematic, the Court may have inadvertently spoken on an unsettled issue related to the BPCIA, making the pronouncement in dicta.  When the patent infringement statute was amended, 35 U.S.C. § 271(e)(6)(C) was added:

The owner of a patent that should have been included in the list described in section 351(l)(3)(A) of the Public Health Service Act, including as provided under section 351(l)(7) of such Act for a biological product, but was not timely included in such list, may not bring an action under this section for infringement of the patent with respect to the biological product.

Essentially, this section limits the ability of the RPS and/or patent owner to bring an infringement suit if the patent was not identified during the patent dance or was not included in a proper supplement of the list.  Of course, it is not clear what "under this section" means?  Does it mean 271(e), such that an RPS and/or patent holder would be unable to assert that the filing of an aBLA is an act of infringement with regard to such a patent, and instead would be required to wait until actual infringement occurs to allege infringement?  Or does "section" mean the entirety of 35 U.S.C. § 271 -- in which case the failure to properly list a patent would bar any claim of patent infringement related to the biosimilar product at any time.  Such an outcome would be draconian to say the least.

Before the Amgen v. Apotex decision, commentators were fairly split on the subject.  For example, the Treatise "Generic and Innovator Drugs: A Guide to FDA Approval Requirements," eighth edition, authored by Donald O. Beers and Kurt R. Karst, took the former position:

Second, a reference product sponsor's failure to include a relevant patent in its Paragraph 3(A) list, or to timely supplement such list after issuance of a new patent, bars the reference product sponsor from bringing an infringement action under Section 271(e).

Chapter 13, § 13.04[B].  This paragraph was supported by footnote 135, which read:

See id. § 271(e)(6)(C).  The statue does not specifically refer to Section 271(e), but rather states "under this section," presumably referring to Section 271(e).  A reference product sponsor could perhaps later bring an action under 35 U.S.C. §§ 271(a)-(c) once the biosimilar applicant has launched its product after FDA approval.

Kurt Karst is, of course, one of the authors of the FDA Law Blog.  Other commentators have posited the more draconian reading of the statute.  See, e.g., "Shall We Dance? FDA Biosimilar Approval Process Litigation Options."  In fact, in 2013, shortly after the BPCIA was passed, two individuals (one of which was Patent Docs author Kevin Noonan) presented a webinar (the presentations materials of which are archived here), in which they raised the question:

Could [an] RPS file an action under 35 USC § 271(a) after [the] Biosimilar product [is] on market or a DJ action [] launch is imminent?

Slide 51.

The Federal Circuit appears to have answered the question.  Unfortunately, it did so in dicta without any party addressing the question, as it was not at issue in this case.  In describing how patent infringement works in 35 U.S.C. § 271(e) and the BPCIA, the Court stated:

Second: If a patent that the reference product sponsor should have included on its (3)(A) list or its (7) supplement "was not timely included," then the owner of that patent may not sue for infringement under 35 U.S.C. §271 with respect to the biological product product.  35 U.S.C. § 271(e)(6)(C).

Of course, § 271(e)(6)(C) is not so clear.  A patent holder in the future wishing to assert such a patent under 35 U.S.C. § 271(a) will now have an uphill battle in convincing any Court of a reading of the statute that would not bar it from doing so.  The argument can be made that the Court was not speaking on this issue, and that because this section of the opinion is dicta, it should have no controlling authority.  Nevertheless, district courts may be loath to rule contrary to explicit language from the Federal Circuit.  Therefore, we will probably need to wait years for certainty on this issue, until the question is presented to the Federal Circuit.  In the meantime, any RPS and/or patent holder would be well advised to carefully list its patents during the patent dance exchange, and when possible to err on the side of over-inclusion (provided, of course, that the patents can reasonably be asserted).

Amgen Inc. v. Apotex Inc. (Fed. Cir. 2016)
Panel: Circuit Judges Wallach, Bryson, and Taranto
Opinion bu Circuit Judge Taranto