Biosimilar Litigation Review: BPCIA Federal Circuit Appeals Pending & Recently Decided

By Philip Chen, Felix Eyzaguirre, Tasha Francis, and Jenny Shmuel, Fish & Richardson P.C.

This is the third article in a four-part series on 2019 legal developments related to the biosimilar sector. Part 1 shared statistics regarding Biosimilars Price Competition and Innovation Act (BPCIA) district court litigation and reviewed ongoing BPCIA district court cases. In Part 2, we turned our attention to BPCIA district court cases that were settled in 2019. Here in Part 3, we review BPCIA Federal Circuit appeals that are pending and those that were recently decided.

BPCIA Appeals Pending at the Federal Circuit

The following appeals, discussed below, are currently pending at the Federal Circuit:

• Genentech v. Immunex (CAFC 19-2155); Avastin/Mvasi
• Genentech v. Amgen (CAFC 19-2156); Herceptin/Kanjinti
• Janssen v. Celltrion (CAFC 18-2321; 18-2350); Remicade/Inflectra
• Immunex v. Sandoz (CAFC 20-1037); Enbrel/Erelzi

Genentech v. Immunex (CAFC 19-2155)

This is the appeal from Case No. 19-cv-00602 (D. Del.), discussed in Part 1, which involves Genentech’s Avastin (bevacizumab) and Amgen’s biosimilar Mvasi. The district court denied Genentech’s emergency motions to prevent the launch of Mvasi. The court did not agree that Amgen needed to provide new notice of commercial marketing after filing new supplemental BLAs.

On appeal, Genentech initially sought an emergency motion for an injunction pending appeal (shortly after the district court denied a similar motion) to prevent Amgen from “flood[ing] the market with its biosimilar immediately” (Genentech emergency motion at 4). The Federal Circuit denied the motion, stating that “[w]ithout prejudicing the ultimate disposition of this case, we conclude Genentech has not established that an injunction pending appeal is warranted” (order dated August 16, 2019).

Briefing on the merits is ongoing.

Genentech v. Amgen (CAFC 19-2156)

This is the appeal from Case No. 18-cv-00924 (D. Del.), discussed in Part 1, involving Amgen’s biosimilar ABP 980/Kanjinti, referencing Genentech’s Herceptin (trastuzumab). The district court denied Genentech’s emergency motions to prevent the launch of Kanjinti, finding that Genentech waited too long to file its motion and would not suffer irreparable harm due to its previous licensing activities.

On appeal, Genentech filed a motion for an injunction pending appeal and a request to expedite proceedings. The Federal Circuit denied both, holding that “[w]ithout prejudicing the ultimate disposition of this case, we conclude that Genentech has not established that an injunction pending appeal is warranted …” and “while Genentech has and can continue to self-expedite its own filings, it has not shown that Amgen’s time should be shortened” (order dated August 7, 2019).

On the merits of its interlocutory appeal, Genentech has asked the Federal Circuit to find that the district court erred in two ways: both in “inferring that Genentech will not suffer irreparable harm because it waited to seek preliminary injunctive relief until Amgen affirmatively decided to launch” and in “adopting a categorical rule that licensing of future activity negates irreparable harm from present infringement” (Genentech opening br. at 25-31, 35-38). Genentech further argued that the other factors for a preliminary injunction “overwhelmingly” favor Genentech, including because the merits of Amgen’s validity defense “merely recycled art and arguments already rejected by the Patent Trial and Appeal Board (PTAB) under a lower standard of proof” (Id. at 52).

Briefing is complete. Oral argument has not yet been scheduled.

Janssen v. Celltrion (CAFC 18-2321, 18-2350)

This is an appeal from Case No. 17-cv-11008 (D. Mass.) relating to Celltrion’s infliximab biosimilar Inflectra, referencing Janssen’s Remicade. Only one patent is at issue, U.S. Patent No. 7,598,083, which covers a cell culture medium used to grow antibody-producing cells.

Janssen argued patent infringement under the doctrine of equivalents, since it was undisputed that Celltrion’s media was outside the claimed concentrations of several of the claimed ingredients. In July 2018, Judge Wolf of the District of Massachusetts granted Celltrion’s motion for summary judgment of non-infringement. The court held that the range of equivalents necessary to cover the accused product would impermissibly ensnare the prior art.

In August 2018, Janssen appealed the non-infringement ruling to the Federal Circuit (CAFC 18-2321). Janssen filed its opening brief on December 10, 2018, arguing the district court erred by 1) impermissibly using hindsight to find that a hypothetical claim covering Celltrion’s cell culture medium would have been obvious, 2) failing to find Celltrion’s arguments regarding ensnarement legally baseless where Celltrion failed to offer any motivation to choose and modify the prior art references, and 3) failing to draw reasonable inferences in Janssen’s favor (e.g., teaching away and evidence of copying) in its summary judgment analysis (Janssen opening br.).

Celltrion cross-appealed on an unrelated issue: lack of standing (CAFC-2350). Celltrion argued that Janssen lacked standing because all co-owners of ’083 patent had not been properly joined as plaintiffs (Celltrion opening and response br. at 57-73). Specifically, the patent rights were assigned to “the COMPANY,” a term that, according to Celltrion, was unambiguous and included more companies than just Janssen (Id. at 29-30). Thus, according to defendants, the case should have been dismissed (Id. at 30). Janssen disagreed, stating that “[t]he [assignment] agreements are ambiguous, but their most sensible reading is that they assign the ’083 patent to only one entity: Centocor, Inc., Janssen’s predecessor,” and that “Janssen, as Centocor’s successor, has standing to bring this action” (Janssen response and reply br. at 35).

Briefing is complete. Oral argument has not yet been scheduled.

Note that Janssen v. HyClone Labs (16-cv-00071 D. Utah), which involves the same patent and factual scenario, has been administratively closed pending resolution of this appeal, with no other important updates in 2019.

Immunex v. Sandoz (CAFC 20-1037)

This dispute centers on Erelzi, Sandoz’s biosimilar of Immunex’s Enbrel (etanercept). On August 9, 2019, Judge Cecchi of the District of New Jersey held that U.S. Patent No. 8,063,182, directed to etanercept, the active ingredient in Enbrel, and U.S. Patent No. 8,163,522, directed to Enbrel’s manufacturing process, not invalid (Immunex Corp. v. Sandoz Inc., 395 F. Supp. 3d 366 [D.N.J. 2019]). Sandoz appealed.

The appeal, as framed by appellant Sandoz, concerns three main issues: 1) whether the patents-in-suit are invalid for obviousness-type double patenting 2) whether the asserted claims are invalid for lack of written description, and 3) whether the district court erred in its ruling on obviousness (Sandoz opening br. at 4).

The parties’ briefing is complete. Oral argument has not yet been scheduled.

BPCIA Federal Circuit Appeals Decided in 2019

In 2019, the Federal Circuit issued decisions in Amgen v. Coherus, Amgen v. Sandoz, and Amgen v. Hospira, in addition to ruling on Genentech’s motions for an injunction pending appeal in its cases against Immunex/Amgen (discussed above). We discuss the Coherus, Sandoz, and Hospira decisions below.

Amgen v. Coherus, 931 F.3d 1154 (Fed. Cir. 2019) (CAFC 18-1993)

This decision concerns CHS-170, Coherus’ biosimilar of Amgen’s Neulasta (pegfilgrastim) and follows from the district court’s order dismissing Amgen’s complaint for failure to state a claim (Amgen v. Coherus, No. 17-cv-546, 2018 WL 1517689 [D. Del. Mar. 26, 2018]). In the district court, Amgen alleged infringement of its protein purification patent, U.S. Patent No. 8,273,707, under the doctrine of equivalents based on Coherus’ BLA. The district court found that Coherus’ biosimilar could not infringe in light of Amgen’s “clear and unmistakable surrender” of claim scope during prosecution (Id. at *2). As a separate ground for dismissal, the court further found that by disclosing but not claiming other salt combinations, Amgen had dedicated them to the public under the dedication-disclosure doctrine (Id. at *3).

On appeal, the Federal Circuit affirmed, explaining that “prosecution history estoppel bars Amgen from succeeding on its claim of infringement under the doctrine of equivalents” (Amgen v. Coherus, 931 F.3d 1154, 1156 [Fed. Cir. 2019]). According to the court, Amgen had “clearly and unmistakably surrendered unclaimed salt combinations during prosecution” when it successfully distinguished a prior art reference raised by the examiner by arguing that the reference did not disclose or suggest the “particular combinations” of salts recited in the claims (Id. at 1160). Amgen was therefore estopped from asserting that other salt combinations infringed its patent, including Coherus’ salt combinations. The Federal Circuit did not reach the other independent basis for dismissal under the disclosure-dedication doctrine (Id. at 1161).

Amgen v. Sandoz, 923 F.3d 1023 (Fed. Cir. 2019) (CAFC 18-1551, 18-1552)

This appeal involved Sandoz’s biosimilars of Amgen’s Neupogen (filgrastim) and Neulasta (pegfilgrastim). In 2017, the Northern District of California granted summary judgment of non-infringement as to U.S. Patent No. 8,940,878, which was directed to methods of protein purification (Amgen Inc. v. Sandoz Inc., 295 F. Supp. 3d 1062 [N.D. Cal. 2017]).

On May 8, 2019, the Federal Circuit affirmed the lower court’s ruling (Amgen Inc. v. Sandoz Inc., 923 F.3d 1023 [Fed. Cir. 2019]). The district court had construed claim 7 of the ’878 patent to cover a purification method that required separate steps of washing and eluting, with the eluting step occurring after the washing step (Id. at 1027). Sandoz’s purification process undisputedly involved only a single step, with no separate washing or eluting steps, which defeated Amgen’s literal infringement theory (Id. at 1029).

Turning to Amgen’s doctrine of equivalents argument, the Federal Circuit concluded that the district court correctly held that Sandoz’s one-step, one-solution process did not function in the same way as the claimed process, further stating that “[t]he doctrine of equivalents applies only in exceptional cases and is not ‘simply the second prong of every infringement charge, regularly available to extend protection beyond the scope of the claims’” (Id. at 1029).

Amgen also asserted that the district court improperly denied its Rule 56(d) motion for a continuance in light of Sandoz’s upcoming manufacturing changes (Id.). But the Federal Circuit disagreed, in part because the proposed pegfilgrastim biosimilar would likely follow the same one-step washing and eluting process, and would therefore not infringe under the affirmed claim construction. However, the Federal Circuit clarified that Amgen would not be without a remedy for possible future infringement should Sandoz change its process: Amgen “may in a future action plead infringement of claim 7 by Zarxio or, if approved, Sandoz’s pegfilgrastim biosimilar to the extent permitted by the Patent Act and the principles of res judicata and collateral estoppel” (Id. at 1031).

Amgen petitioned for rehearing en banc on June 7, 2019, to argue that a part of the court’s holding — that the doctrine of equivalents only applies in “exceptional” cases — was contrary to Supreme Court and Federal Circuit precedent, and that under correct standard, the district court’s grant of summary judgment should be reversed. Amgen highlighted the fact that the panel did not define “exceptional.” But on September 3, 2019, the Federal Circuit granted Amgen's petition for rehearing en banc only to remove the statement that the doctrine of equivalents only applies in exceptional cases (Amgen Inc. v. Sandoz Inc., 776 F. App’x 707 [Fed. Cir. 2019]). Amgen’s petition was otherwise denied (Id.).

Amgen v. Hospira, 944 F.3d 1327, 2019 WL 6834390 (CAFC 19-1067, 19-1102)

In September 2017, a jury in the District of Delaware awarded Amgen $70 million in reasonable royalty damages based on Hospira’s infringement of U.S. Patent No. 5,856,298 in relation to a biosimilar of Amgen’s Epogen (epoetin alfa). Although Hospira’s biosimilar had not launched before patent expiration, the jury found that certain of Hospira’s biosimilar batches were not “solely for uses reasonably related” to obtaining biosimilar approval and thus did not qualify for safe harbor protection under 35 U.S.C. § 271(e)(1). The jury also found that Hospira did not infringe U.S. Patent No. 5,756,349. In ruling on post-trial motions, Judge Andrews upheld the jury verdict. The court clarified that evidence of intent can be a relevant factor in determining whether an activity is reasonably related to obtaining FDA approval and therefore subject to the safe harbor. Judge Andrews also upheld the jury’s damages award and additionally awarded Amgen prejudgment interest of about $10 million and post-judgment interest. This case is the first BPCIA case in which damages were awarded.

Hospira appealed the district court’s judgment of infringement and validity of the ’298 patent and the court’s award of approximately $80 million. Amgen cross-appealed the non-infringement finding for the ’349 patent.

On December 16, 2019, the Federal Circuit affirmed the district court’s judgment on each issue (Amgen Inc. v. Hospira, Inc., 944 F.3d 1327, 2019 WL 6834390, at *1 [Fed. Cir. 2019]). In particular, as to the safe harbor defense, the Federal Circuit held that the jury instructions were not legally erroneous and that substantial evidence supported the jury’s finding that certain batches were not protected (Id. at *7-8). The jury instructions stated that “[i]f Hospira has proved that the manufacture of a particular batch was reasonably related to developing and submitting information to FDA in order to obtain FDA approval, Hospira’s additional underlying purposes for the manufacture and use of that batch do not remove that batch from the Safe Harbor defense” (Id. at *6). Hospira claimed this was erroneous for focusing on “why each batch … was manufactured, not how each batch was used or whether that use was reasonably related to the development and submission of information to support Hospira’s BLA” (Id.). The Federal Circuit disagreed because “the patented inventions are Amgen’s claimed methods of manufacture” and the “accused activity is Hospira’s use of Amgen’s claimed methods of manufacture,” so “[t]he relevant inquiry, therefore, is not how Hospira used each batch it manufactured, but whether each act of manufacture was for uses reasonable related to submitting information to FDA” (Id. at *7 [emphasis in original]).

Further, although Hospira argued that each of its accused 21 batches “were used for the development and submission of information” to FDA, the Federal Circuit found that substantial evidence supported the jury’s finding that 14 of those batches were not protected by the safe harbor (Id. at *8). For example, evidence was submitted that Hospira was not required by FDA to manufacture additional batches after 2012 (Id.). Relevant, but not dispositive, was evidence that Hospira planned for some of the batches to “serve as commercial inventory,” even though Hospira later changed the designation of some of its batches after it received a complete response letter from FDA (Id. at *9).

In the fourth and final article in this series, we review 2019 biosimilar litigation related to anticompetitive conduct and post-grant patent challenges at the PTAB, and offer some perspectives on what biosimilar developers can anticipate in the year ahead.

About The Authors:

Philip K. Chen is an associate at Fish & Richardson, where he works on various patent litigation matters including pharmaceutical and biosimilar litigation. He can be reached at pchen@fr.com.

 

Felix A. Eyzaguirre is an associate at Fish & Richardson, where he focuses his practice on patent litigation, including pharmaceutical litigation. He can be reached at eyzaguirre@fr.com.

 

 

Tasha M. Francis, Ph.D., was previously an associate at Fish & Richardson. She is a well-known speaker and writer on topics related to the Biologics Price Competition and Innovation Act and life science post-grant proceedings. Francis has extensive experience in the areas of small molecule and biologic pharmaceuticals (including antibody technologies), drug formulation and drug delivery technologies, diagnostics, protein biochemistry, and chemicals.
 

Jenny Shmuel, Ph.D., is a principal at Fish & Richardson, where she has helped build the firm’s biologics and biosimilar litigation practice. She also represents pharmaceutical clients in competitor litigation and Hatch-Waxman litigation. Dr. Shmuel has extensive experience in all phases of litigation, and, over the last several years, has helped successfully defend a large pharmaceutical franchise and secure a significant damages award for a medical device manufacturer. She can be reached at shmuel@fr.com.

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The opinions expressed are those of the authors on the date noted above and do not necessarily reflect the views of Fish & Richardson P.C., any other of its lawyers, its clients, or any of its or their respective affiliates. This post is for general information purposes only and is not intended to be and should not be taken as legal advice. No attorney-client relationship is formed.