In the third installment of the "Amgen v." trilogy of BPCIA Federal Circuit cases, the Court in Amgen Inc. v. Hospira, Inc. answered a question that had been lingering since the very first case -- can a reference product sponsor use discovery to obtain information from a biosimilar applicant if it does not receive a copy of the aBLA or other information about the manufacturing process as required by the BPCIA?  In Amgen v. Sandoz, the first case in this series, the Federal Circuit found that an aBLA applicant was not required to disclose its application and related information, but noted that such information could be accessed through discovery after an infringement suit is filed.  In the second installment, Amgen v. Apotex, the plot centered on the Notice-of-Commercial-Marketing provision, and did not focus significantly on the provisions of 42 U.S.C. § 262(l)(2)(A).  In this most recent case, the Court appears to have closed the discovery loophole it created, at least with respect to cases in which the requested information is not relevant to the asserted patents.  More importantly, reference product sponsors suffered another blow when the Court suggested that if a patent was not included in its paragraph (l)(3)(A) list, even if there was no reason to suspect that it might be relevant to the present case, the BLA holder could be precluded under 35 U.S.C. § 271(e)(6)(C) from ever asserting that patent (depending on what "under this section" turns out to mean).  Of course, this could lead to the unintended (or maybe intended) consequence of overly long patent lists containing every conceivable patent that could be related to the manufacture of biologics in situations when inadequate information has been provided.

This case stems from Hospira's subsection (k) biosimilar application seeking approval to market a version of Amgen's EPOGEN^® drug product.  BLA 125545 was submitted in December 2014, and shortly thereafter Hospira provided its application to Amgen.  Nevertheless, it did not otherwise provide any additional manufacturing information.  On March 31, 2015, Amgen alerted Hospira that it had failed to comply with paragraph (l)(2)(A) of the BPCIA.  Hospira responded that the application contained sufficient information about both the product and the process of its manufacture.  Notwithstanding, the parties conducted the patent dance.  However, Amgen did not include any cell-culture patents on its paragraph (l)(3)(A) patent list because it alleged it could not "assess the reasonableness of asserting claims for infringement" without the requested information.

Amgen ultimately filed suit on two patents in the U.S. District Court for the District of Delaware, U.S. Patent Nos. 5,756,349 and 5,856,298.  Relying on the Amgen v. Sandoz statement referenced above, Amgen sought discovery of the withheld information, including the composition of Hospira's cell-culture medium.  After Hospira refused to produce the information, the Court denied a motion to compel discovery filed by Amgen because the information sought had "essentially no relevance to the patents that are asserted."  Amgen sought interlocutory appeal and in the alternative mandamus under the All Writs Act.

With regard to whether the Federal Circuit had jurisdiction, the Court looked to the collateral order doctrine to see if the appeal could be heard regardless of the fact that the judgement was not yet final.  The test, established by the Supreme Court, is that "the order must conclusively determine the disputed question, resolve an important issue completely separate from the merits of the action, and be effectively unreviewable on appeal from a final judgment."  Coopers & Lybrand v. Livesay, 437 U.S. 463, 468 (1978).  After acknowledging that the first two conditions were met, the Court concluded that the lower Court's order was not "effectively unreviewable."  In general, discovery rulings fall outside the collateral order doctrine because they are reviewable upon final judgement.  Moreover, this was not a case analogous to an order to unseal confidential information or deny a claim of immunity.  In essence, this was found to be a "run-of-the-mill discovery dispute," and therefore the Court determined it lacked jurisdiction.

With regard to the request for mandamus, the Court noted that such a writ is a "drastic remedy reserved for the most 'extraordinary causes,'" citing Cheney v. U.S. Dist. Court for D.C., 542 U.S. 367, 380 (2004).  Amgen's right to the issuance of a writ, according to Supreme Court precedent, centered on whether there was a "clear and indisputable" right to that relief.  The Court identified five potential avenues based on the BPCIA, but immediately shot down two or three of them.  The first -- an injunction under federal law compelling the disclosures -- was foreclosed in the Supreme Court's Sandoz v. Amgen decision.  The second -- an injunction under state law compelling the disclosures -- was left open by the Supreme Court, but Amgen had not sought a state law remedy in the Hospira case.  Third -- suing the biosimilar applicant under the BPCIA and 35 U.S.C. § 271(e)(2) for failure to comply with the information disclosure provision -- was also foreclosed by the Supreme Court.  The Court had explained in Sandoz that it was the act of submitting the aBLA to the FDA that gave rise to the artificial infringement, not the failure to comply with the provisions of the BPCIA.

The final two potential avenues arise from the ability of the reference product sponsor to bring an infringement suit:  either pursuant to the list of patents created under paragraph (l)(3)(A) (avenue 4), or patents that "could" be identified in the case the aBLA is not disclosed (avenue 5).  The Court did not address avenue 5.  Rather, it noted that Amgen provided a patent list, and sued Hospira on two of the patents on that list.  However, neither of those patents related to cell-culture media.  The Federal Circuit back-peddled from its previous statement in Amgen v. Sandoz (that discovery would always be available) by claiming it had never intended to alter the Federal Rules of Civil Procedure.

Importantly, the Court addressed a question that Practitioners have been wondering ever since the original Amgen v. Sandoz decision:  whether a reference product sponsor could assert a patent in the BPCIA context if it did not receive sufficient information from the biosimilar applicant about that patent.  For example, would Amgen have faced Rule 11 sanctions for asserting the cell-culture patent, considering it did not know if Hospira was indeed practicing the invention claimed therein?  The solution, according the Federal Circuit, is for a patent owner to include every patent that it could conceivably assert on its (l)(3)(A) list.  After all, the statute does not provide for sanctions if a patent is unreasonably listed.  In fact, it is the response from the biosimilar applicant in its "detailed statement" that could give rise to the reasonable basis for asserting the patent in litigation.  Moreover, Rule 11 only requires that a filing be "to the best of the person's knowledge, information, and belief, formed after an inquiry reasonable under the circumstances."  That belief could be based on an inquiry limited to the withholding of information.  As such, the Court concluded, "the reasonableness requirement of paragraph (l)(3)(A) does not preclude a sponsor from listing as patent for which an applicant has not provided information under paragraph (l)(2)(A)."  Ultimately, therefore, the Court concluded that the denial of discovery did not undermine the BPCIA and that denial of the motion to compel was proper.

Of course, this creates a chicken-and-the-egg situation.  If the biosimilar applicant does not disclose its relevant information, the reference product sponsor will not know what patents cover the non-disclosed material.  But if the sponsor will be unable to assert such a non-listed patent, it will be motivated to include every conceivable patent when it does create its list.  This has the potential of escalating the amount of paperwork needed to be exchanged during the patent dance.  Maybe the specter of responding to countless irrelevant patents will ultimately sway some biosimilar applicants to disclosure the information in the first place.  Or maybe the question will be resolved in the next installment of the "Amgen v." series of BPCIA cases.

Before we leave this case, there is an update on the FDA approval process for the aBLA underlying this case.  We had reported in June that the FDA's Oncologic Drug Advisory Committee recommended approval of Hospira's aBLA (see "Biosimilars Update -- Pfizer's Proposed Epogen®/Procrit® Biosimilar Recommended for Approval").  However, on June 22, 2017, Pfizer announced that it had received another Complete Response Letter (CRL) from the FDA.  And even though this CRL did not relate specifically to the manufacture of epoetin alfa, it will likely result in a delay of drug approval.  This is the second CRL that Pfizer received for this drug product application, thereby causing this application to be the longest between submission and approval (if it is, in fact, ultimately approved).  We will continue to monitor the situation and provide updates as warranted.  

Amgen Inc. v. Hospira, Inc. (Fed. Cir, 2017)
Panel:  Circuit Judges Dyk, Bryson, and Chen
Opinion by Circuit Judge Dyk