Last week in Actelion Pharmaceuticals Ltd. v. Mylan Pharmaceuticals Inc., the Federal Circuit delivered generic drug maker Mylan Pharmaceuticals Inc. with a notable victory when it affirmed the district court’s judgment that it does not infringe Actelion Pharmaceuticals Ltd.’s patents covering the active ingredient in the pulmonary arterial hypertension drug Veletri^®. In particular, the appellate panel affirmed that the claim term “pH of 13 or higher” refers to a measurement taken at standard temperature (25 ± 2°C), and that prosecution history estoppel and the disclosure-dedication rule independently bar Actelion from pursuing infringement under the doctrine of equivalents.

Background

Actelion owns U.S. Patent Nos. 8,318,802 and 8,598,227 (the ‘802 and ‘227 patents) — both entitled “Epoprostenol Formulation and Method of Making Thereof.” While epoprostenol is a vasodilator and antiplatelet agent used to treat cardiovascular disease, it is notoriously unstable in water, degrading rapidly in acidic conditions. The Actelion patents describe lyophilized (freeze-dried) pharmaceutical compositions of epoprostenol that are purportedly more stable and more convenient than prior hypertension drugs, which require a special basic diluent and refrigeration.

According to the Actelion patents, the key to the invention is manufacturing the epoprostenol composition from a highly basic “bulk solution” — one with a pH of 13 or higher. Once freeze-dried and later reconstituted, the resulting compositions remain stable even with standard intravenous fluids at room temperature. Claim 1 of the ʼ802 patent is representative:

A lyophilized pharmaceutical composition comprising:

(a) a unit dose of 0.5 mg or 1.5 mg of epoprostenol or a salt thereof;

(b) arginine; and

(c) sodium hydroxide,

wherein said lyophilized pharmaceutical composition is (i) formed from a bulk solution having a pH of 13 or higher and (ii) capable of being reconstituted for intravenous administration with an intravenous fluid.

When Mylan filed an Abbreviated New Drug Application (ANDA) seeking FDA approval to market a generic version of Veletri^®, Actelion sued Mylan for patent infringement under 35 U.S.C. § 271(e)(2). Mylan’s position was straightforward: Its generic product was manufactured from a bulk solution with a pH well below the claimed threshold when measured at 25 ± 2°C — the standard temperature used throughout the pharmaceutical industry. Actelion countered that pH should be assessed at the solution’s actual (refrigerated) operating temperature, at which Mylan’s bulk solution would register above pH 13.

The district court had previously construed “pH of 13 or higher” to mean “pH of 12.98 or higher,” following a prior Federal Circuit remand requiring consideration of extrinsic evidence. That construction — unchallenged on this appeal — meant the sole issue at the bench trial was whether Mylan’s bulk solution, as used in manufacturing, had a pH meeting the claims. The district court found no literal infringement and no infringement by equivalents, entering final judgment for Mylan in March 2024.

The Appeal

On appeal, Actelion argued that the district court erred by construing “pH of 13 or higher” as a standard-temperature measurement. Actelion’s theory rested on the argument that “pH” has its ordinary meaning — the hydrogen-ion concentration of a solution as it exists — and that the claim language itself did not specify any temperature for the measurement.

The Federal Circuit disagreed and affirmed, finding the district court made no reversible error. The court’s analysis examined both intrinsic and extrinsic evidence. On the intrinsic side, the specification of the ʼ802 patent never explicitly states the conditions for its pH measurements, but it does define an “alkaline environment” as one with “pH > 7” — a definition that is accurate only at standard temperature. The court found this implicit assumption was consistent in the experimental tables and pH comparisons in the specification. Both parties’ experts agreed that the vast majority of pH measurements described in the specification reflected standard-temperature values.

On the extrinsic side, the court consulted the United States Pharmacopeia (USP) — an influential and widely followed collection of pharmaceutical industry standards — which both parties acknowledged prescribes that, “unless otherwise specified,” pH measurements are taken at 25 ± 2°C. In addition, general chemistry textbooks further supported the understanding that pH values, when generally described, assume standard ambient temperature and pressure. Because there was no evidence that the Actelion patents specified otherwise, the standard-temperature construction was not in error, and Mylan’s ANDA product — with a pH well below the claimed threshold at that temperature — did not literally infringe.

Even setting aside literal infringement, the Federal Circuit independently affirmed two separate bars to Actelion’s doctrine of equivalents (DOE) theory. First, prosecution history estoppel applied here. During prosecution of the ʼ802 patent, Actelion amended the pH limitation from “a pH of greater than 12” to “a pH of 13 or higher” in response to an examiner’s obviousness rejection. The examiner had noted that unexpected results had not been demonstrated for bulk solutions with a pH of 12 or greater, but indicated the claims would be allowable if limited to pH 13 or higher, where such results had been shown. Under Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., this narrowing amendment creates a presumptive surrender of the territory between the original and amended claim scope.

Actelion argued that the tangentiality exception applied — i.e., that the amendment was made for reasons unrelated to the specific equivalents it sought to capture. The Federal Circuit rejected this argument, finding that pH 13 was the precise threshold the examiner identified as demonstrating unexpected results necessary for nonobviousness. The discernible objective reason for the amendment was to narrow the claims to pH 13 or higher, which is directly related to whether a bulk solution with a sub-13 pH (measured at standard temperature) could be equivalent. Actelion was therefore estopped from asserting the doctrine of equivalents to capture pH lower than pH 13.

– The Tangentiality Exception –
when the reason for the original narrowing amendment is only tangentially related to the newly alleged equivalent

Second, the disclosure-dedication rule independently barred Actelion’s equivalents theory. The specification of the ʼ802 patent explicitly disclosed pH ranges for bulk solutions, including values below 13 — specifically pH 12–13, 12.5–13, and greater than 12 — as preferred alternatives, but Actelion did not claim them. The Federal Circuit found these disclosures were sufficiently specific to identify sub-13 pH ranges as alternatives to the “pH of 13 or higher” limitation, and affirmed the bar under the disclosure-dedication rule as well.

– The Disclosure-Dedication Rule –
when a patentee discloses but declines to claim subject matter, that subject matter is dedicated to the public and cannot be recaptured as an equivalent

Takeaways

The Federal Circuit’s decision in Actelion v. Mylan offers some important takeaways about claim construction and the limits of the doctrine of equivalents:

• Industry Standards Shape Claim Meaning – Where a claim term has a well-established meaning within an industry standard (here, the USP’s default standard-temperature pH measurement), courts will apply that meaning unless the patent expressly specifies otherwise. Patentees who rely on non-standard conditions should make those conditions explicit in the claim language and specification.
• Specification Consistency Matters – Even without an explicit definition, consistent use of a term in a particular sense in the specification can establish its meaning. The court’s reliance on the  implicit standard-temperature framework in the specification — embedded in dozens of experimental comparisons — underscores the importance of internal consistency.
• Amendment Scope Carries Real Consequences – Narrowing amendments made to overcome obviousness rejections will be construed broadly in their surrender of equivalent territory. The tangentiality exception is a narrow escape hatch, and patentees should assume it will not be available when the amendment directly targets the alleged equivalents.
• Disclose Only What You Claim – When a specification identifies specific alternatives to a claimed limitation (such as pH ranges below the claimed threshold), those alternatives cannot be recaptured through the doctrine of equivalents, regardless of whether the patentee intended to claim them.

For Actelion, the Federal Circuit’s affirmance means Mylan keeps the door open to bringing a competing generic epoprostenol product to market.