ACTELION PHARMACEUTICALS LTD v. MYLAN PHARMACEUTICALS INC.

Authored by: Jeremy J. Gustrowsky

A recent Federal Circuit decision affirmed that a pharmaceutical patent’s reference to “a pH of 13 or higher” refers to a measurement taken at standard laboratory temperature (25±2°C), not at the actual (refrigerated) temperature of the solution during manufacturing. The ruling preserved a finding of no infringement for a generic version of Actelion’s hypertension drug Veletri®.

The case revolves around U.S. Patent Nos. 8,318,802 and 8,598,227, which cover lyophilized (freeze-dried) compositions of epoprostenol, a vasodilator used to treat cardiovascular disease. Because epoprostenol degrades quickly in water when acid is present, the inventor developed compositions made from highly basic “bulk solutions” with a pH of 13 or higher. Mylan Pharmaceuticals submitted an abbreviated new drug application seeking to market a generic version, and Actelion sued for infringement. Mylan’s bulk solution had a pH well below 13 when measured at standard temperature, but Actelion argued the pH should be measured at the colder temperature actually used during Mylan’s manufacturing, where the pH would exceed 13.

The Federal Circuit agreed with the district court that the patent’s claim language refers to a standard-temperature pH measurement. While the claims themselves did not specify measurement conditions, the specification consistently described pH values without temperature qualifications, and the only definition tied to pH (describing “an alkaline environment” as one with “pH greater than 7”) only makes sense at standard temperature. The court also found the United States Pharmacopeia, an influential pharmaceutical industry standard, supports the default rule that pH measurements are taken at 25±2°C unless otherwise specified. Both parties’ experts agreed the specification’s experimental references to pH 13 bulk solutions referred to standard-temperature measurements.

The court also rejected Actelion’s backup theory of infringement under the doctrine of equivalents, applying two separate bars. First, prosecution history estoppel applied because Actelion had narrowed its claims during prosecution from “greater than 12” to “13 or higher” in response to an obviousness rejection, where the examiner specifically noted that unexpected stability results had only been demonstrated at pH 13. The narrowing was not merely tangential to the alleged equivalent, so Actelion was estopped from recapturing pH values below 13.

Second, the disclosure-dedication rule independently barred the equivalents theory. The specification expressly disclosed pH ranges of “about 12.5–13.5” and described pH values “greater than 11, preferably greater than 12, and, most preferably greater than 13” as alternatives. Because these disclosed alternatives were not claimed, the unclaimed subject matter was dedicated to the public. The court rejected Actelion’s argument that the rule should not apply because the disclosed alternatives overlapped rather than being mutually exclusive.

The decision serves as a reminder for patent drafters that technical terms with established industry conventions will be interpreted according to those conventions, even when the patent itself does not spell out measurement standards. It also reinforces that disclosed but unclaimed embodiments, including overlapping ranges, can be dedicated to the public and beyond recapture through equivalents.