The Doctrine of Equivalents in BPCIA Litigation

As of the end of 2019, reference product sponsors ("RPSs") have filed dozens of patent infringement cases against biosimilar manufacturers under the Biologics Price Competition and Innovation Act ("BPCIA"). The doctrine of equivalents ("DOE") is emerging as a theme in these litigations. Although, as discussed below, RPSs have not yet been successful in their infringement theories under DOE, these cases provide insight into the types of issues of which BPCIA litigants should be aware and add to the general body of DOE case law. Below, we discuss three exemplary cases in which DOE featured in BPCIA litigation.

Janssen v. Celltrion

Janssen, who manufactures the biologic Remicade® (infliximab), alleged that Celltrion's manufacture of its infliximab biosimilar (Inflectra®/Remsima®) infringed Janssen's U.S. Patent No. 7,590,083 (the "'083 Patent") under the doctrine of equivalents. (Janssen v. Celltrion, 1:17-cv-11008 (D. Mass.), dkt. 393, at 2 (Jul. 30, 2018).) The '083 Patent is directed to cell media and claims a series of specific cell culture ingredients in specific concentrations. (Id. at 3.) It was undisputed that Celltrion's media contained all the claimed ingredients, but several of them fell outside the literal concentration ranges recited in the asserted claim. (Id. at 5.) Thus, Celltrion did not literally infringe, and Janssen proceeded under a DOE theory of infringement.

Celltrion invoked an ensnarement defense to support a motion for summary judgment of non-infringement. (Id.) Ensnarement is a patent infringement defense that "prevents the patentee from obtaining under the doctrine of equivalents coverage that could not be lawfully obtained from the PTO by literal claims." (Id.) To evaluate an ensnarement defense, the court can conduct a "hypothetical claim" analysis in which a patentee first "construct[s] a hypothetical claim that literally covers the accused device" (i.e., "expand[s] the claim limitations to encompass the features of the accused product") and then "prior art introduced by the accused infringer is assessed" to determine if the claim is patentable over the prior art. (Id. at 8.) Here, Celltrion argued that hypothetical claims encompassing Celltrion's concentrations were obvious under 35 U.S.C. § 103 in light of two pieces of prior art. (Id. at 8-9.)

The District of Massachusetts agreed and granted Celltrion's motion for summary judgment. The court found that one prior art reference disclosed 50 out of the 52 required ingredients, and the other reference disclosed 47 out of the 52 required ingredients almost all in concentrations that overlapped with the '083 Patent. (Id. at 40.) For each missing ingredient, the district court found that the references disclosed alternative ingredients that contained the same active components as the claimed ingredients in a range that overlapped with the hypothetical claims. (Id. at 46, 52.) On these findings, the district court held that "no reasonable factfinder could conclude that Janssen has satisfied its burden of proving that the hypothetical claims would have been patentable over [the two prior art references]" that is, Janssen failed to show that "the scope of equivalents would not ensnare the prior art." (Id. at 103.)

In August 2018, Janssen appealed the district court's ruling to the Federal Circuit. (Janssen v. Celltrion, Appeal No. 18-2321.) The appeal is fully briefed, but an oral argument date has not yet been set.

Amgen v. Coherus

RPS Amgen's DOE theory was defeated in Amgen v. Coherus, this time due to prosecution history estoppel. Amgen alleged that Coherus's process for manufacturing a biosimilar of Neulasta® (pegfilgrastim) infringed Amgen's U.S. Patent No. 8,273,707 (the "'707 Patent") through the doctrine of equivalents. Amgen Inc. v. Coherus Biosciences Inc., 931 F.3d 1154, 1158 (Fed. Cir. 2019). The '707 Patent claims methods of purifying proteins using a chromatography method containing combinations of salts. Id. at 1156. The '707 Patent expressly claims three salt combinations: sulfate/citrate, sulfate/acetate, and acetate/citrate. Id. at 1157. In its Biologic License Application ("BLA"), Coherus disclosed a chromatography process that "involve[d] a chromatography buffer containing a salt combination, but not one of the specific combinations recited in the ['707 Patent's] claims." Id. at 1158. Because Coherus's salt combination did not align exactly with any of the three expressly claimed combinations, Amgen argued that Coherus's combination was equivalent to the claimed combinations. Id.

The District of Delaware held, and the Federal Circuit affirmed, that Amgen's doctrine of equivalents infringement claim was barred by prosecution history estoppel, and dismissed Amgen's complaint for failure to state a claim. Id. at 1158–59. Amgen, in response to an office action, had distinguished a prior art reference—U.S. Patent No. 5,231,178 ("Holtz")—on the basis that "Holtz did not teach or suggest the particular combinations of salts' recited in Amgen's claims." Id. at 1160. The Federal Circuit determined that this response was a "clear and unmistakabl[e] surrender [of] salt combinations other than the particular combinations recited in the claims." Id. at 1159. Prosecution history estoppel therefore limited Amgen to the three expressly claimed salt combinations and foreclosed Amgen's equivalency argument. See id. at 1160.

In October 2019, Coherus filed a motion seeking to recover its attorneys' fees incurred in litigating Amgen's doctrine of equivalents theory. (Amgen v. Coherus, 1:17-cv-00546-LPS (D. Del.), dkt. 90, 92 (Oct. 18, 2019).) Coherus argued that this case was exceptional for a number of reasons, including the weakness of Amgen's DOE case and Amgen's insistence on litigating all the way through appeal. (dkt. 92, at 6-11; dkt. 97.) In part because of its DOE theory, Coherus has claimed that Amgen engaged in a "fundamentally anti-competitive litigation strategy" to "crippl[e] a nascent competitor like Coherus." (dkt. 97, at 10.) Amgen has opposed. (dkt. 95.) The District of Delaware has not yet ruled on this motion.

Amgen v. Sandoz

Amgen unsuccessfully asserted a DOE infringement theory in another case as well. In Amgen v. Sandoz, Amgen argued that Sandoz's process for manufacturing its biosimilar of Neupogen® (filgrastim) and its proposed biosimilar of Neulasta® (pegfilgrastim) infringed claim 7 of Amgen's U.S. Patent No. 8,940,878 (the "'878 Patent") through the doctrine of equivalents. Amgen Inc. v. Sandoz Inc., 923 F.3d 1023, 1025, 1029 (Fed. Cir. 2019). The '878 Patent "discloses methods of protein purification by adsorbent chromatography." Id. at 1026. Claim 7 "is directed to the use of a non-affinity separation matrix" to purify a protein and contains several limitations relating to the protein purification process. Id. The Northern District of California construed the "washing" and "eluting" steps in claim 7 as two separate steps, where the eluting step must occur after the washing step. Id. at 1027. The Federal Circuit affirmed this claim construction. Id. at 1028.

Since Sandoz's purification process consisted of "applying the refold solution to the matrix, with no separate washing or eluting steps," Amgen argued infringement under DOE. Id. at 1027, 1029. The Northern District of California held, and the Federal Circuit affirmed, that "Sandoz [did] not infringe claim 7 under the doctrine of equivalents because its one-step, one-solution purification process work[ed] in a substantially different way from the claimed three-step, three-solution process." Id. 1029. In declining to find DOE here, the Federal Circuit noted 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. (quoting London v. Carson Pirie Scott & Co., 946 F.2d 1534, 1538 (Fed. Cir. 1991)).

Amgen pushed back against the statement that the doctrine of equivalents applies only in "exceptional cases," petitioning for a rehearing en banc on this issue. Amgen argued that the Federal Circuit established a new bright-line "exceptionality" rule for DOE contrary to Supreme Court and Federal Circuit precedent. (Amgen's Petition for Rehearing En Banc at 2, Appeal. No. 18-1551.) The Federal Circuit issued an opinion granting the petition only to remove the following key words from its opinion: "applies only in exceptional cases and." Amgen Inc. v. Sandoz Inc., 776 F. App'x 707, 707 (Fed. Cir. 2019). The Federal Circuit otherwise denied Amgen's petition. Id.

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These examples highlight how DOE is becoming a common infringement argument in BPCIA litigation, especially when manufacturing patents are at issue. RPSs have patented many different aspects of biologic manufacturing processes—including specific cell culture media, specific cell culture processing parameters, and specific protein purification processes, among other subject matter—and, as we have noted previously and as is illustrated above, RPSs have asserted these manufacturing patents frequently in BPCIA litigation. Because of the many variables in these manufacturing processes, a biosimilar may develop a process that does not literally infringe the specific claims at issue, meaning RPSs may increasingly pursue DOE infringement theories. Although courts to date have been skeptical of finding infringement in BPCIA cases under DOE, the Federal Circuit has confirmed that there is no rule that DOE only applies in "exceptional cases," so RPSs will likely continue advancing DOE arguments. Biosimilar manufacturers should be prepared to address these arguments both on the merits and in light of various defenses such as ensnarement and prosecution history estoppel.

Authors: Jenny Shmuel, Tasha Francis, Kayleigh McGlynn, Tracea Rice