The U.S. Court of Appeals for the Federal Circuit (CAFC) on Wednesday issued a precedential decision, affirming a district court ruling that Mylan Pharmaceuticals Inc. did not infringe two patents owned by Actelion Pharmaceuticals Ltd. covering a lyophilized epoprostenol formulation used to treat pulmonary arterial hypertension. The decision centered on how a single claim term, “a pH of 13 or higher,” should be measured, and whether Actelion could pursue infringement through the doctrine of equivalents.

Actelion owns U.S. Patent Nos. 8,318,802 and 8,598,227, which are both directed to pharmaceutical compositions involving epoprostenol, the active ingredient in its branded hypertension drug Veletri. Epoprostenol is chemically unstable in water and rapidly degrades under acidic conditions. The patents describe a manufacturing process in which a highly alkaline bulk solution adjusted to a pH of 13 or higher is freeze-dried into a stable powder that can later be reconstituted with standard intravenous fluids for administration to patients.

Mylan filed an abbreviated new drug application (ANDA) with the U.S. Food and Drug Administration in February 2020, seeking approval to market a generic version of the drug. Mylan’s bulk solution, when measured at standard temperature (25±2°C), had a pH well below 12.98. Actelion pursued two theories of infringement before the U.S. District Court for the Northern District of West Virginia. First, Actelion argued that pH should be measured at the refrigerated “operating temperature” at which Mylan actually manufactured its product, not at standard temperature, and that Mylan’s cold-temperature pH exceeded 13. Second, Actelion asserted that Mylan’s process infringed under the doctrine of equivalents. The district court rejected both theories, and Actelion appealed.

On the claim construction question, the CAFC agreed with the district court that “a pH of 13 or higher” refers to a measurement taken at standard temperature. The claim language itself did not specify measurement conditions, and the CAFC found that both intrinsic and extrinsic evidence favored a standard-temperature reading. The specification, while silent on the temperature conditions for its reported pH measurements, defined an “alkaline environment” as one with a pH above 7, a definition that is accurate only at standard temperature. The CAFC further noted that the specification’s comparative experimental tables presented straightforward pH comparisons with no indication that measurements were taken at varying temperatures, suggesting a uniform standard-temperature approach.

The CAFC also pointed to evidence in the form of the United States Pharmacopeia (USP), an influential set of pharmaceutical industry standards that both sides’ experts acknowledged. The district court had found that the USP provides a default rule that, “unless otherwise specified,” pH values in the pharmaceutical field refer to measurements at 25±2°C. The CAFC found no clear error in that factual determination, noting that “the ordinary and customary meaning of a claim term is the meaning that the term would have to a person of ordinary skill in the art,” as articulated in Phillips v. AWH Corp. Both experts further agreed that every reference to a pH 13 bulk solution in the specification’s experimental results reflected standard-temperature measurements, reinforcing the default interpretation.

Actelion contended the district court’s analysis was internally inconsistent, pointing to language suggesting a high pH “can be achieved through any technique…including cold temperature.” The CAFC dismissed that argument, reading the district court’s comment as a statement of undisputed scientific fact about temperature's effect on pH, not as a holding that cold-temperature measurements could satisfy the claim. With no evidence that Mylan’s bulk solution reached a pH of 13 or higher at standard temperature, the CAFC affirmed the finding of no literal infringement.

The CAFC then turned to the doctrine of equivalents and found that two independent legal bars prevented Actelion from pursuing that theory. First, prosecution history estoppel applied because Actelion had amended the pH limitation during prosecution, narrowing it from “a pH of greater than 12” to “a pH of 13 or higher” in response to an obviousness rejection. The examiner found that unexpected results had been demonstrated only for pH values of 13 or higher, and that the claims would be allowable on that basis. Under Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., a narrowing amendment made for patentability presumptively surrenders the territory between the original and amended claim scope. Actelion invoked the tangentiality exception, arguing its amendment had nothing to do with surrendering functionally equivalent solutions at lower pH values, but the CAFC was not persuaded. The court concluded that pH 13 was precisely the threshold the examiner identified as the dividing line for unexpected results.

Furthermore, the specification disclosed pH ranges of 12 to 13 and 12.5 to 13 as preferred for the bulk solution, but Actelion chose not to claim them. The CAFC agreed with the district court that “[w]hen a patent drafter discloses but declines to claim subject matter,” the patentee “dedicates that unclaimed subject matter to the public” and cannot recapture it through the doctrine of equivalents, citing Johnson & Johnston Associates Inc. v. R.E. Service Co. Actelion’s argument that the rule should not apply because the disclosed alternatives overlapped with each other was rejected. The CAFC noted that overlapping alternatives can still be clearly disclosed and left partially unclaimed, and ultimately affirmed the district court’s judgment.