CAFC Orders Review of Extrinsic Evidence to Determine Proper Limit of Claimed pH Range

Today, the U.S. Court of Appeals for the Federal Circuit (CAFC) issued a precedential decision in Actelion Pharmaceuticals Ltd. v. Mylan Pharmaceuticals Inc. vacating an infringement judgment against Mylan in the Northern District of West Virginia. The Federal Circuit remanded the case for further consideration of extrinsic evidence from chemistry textbooks to determine the proper meaning of the claim term “a pH of 13 or higher.”

District Court Construes Claims Without Considering Textbook Evidence

Actelion sued Mylan for infringement in district court after Mylan filed a Paragraph IV certification in an Abbreviated New Drug Application filed with the U.S. Food & Drug Administration (FDA) seeking market approval for a generic version of Actelion’s cardiovascular treatment Veletri. The Paragraph IV certification stated Mylan’s belief that Actelion’s Orange Book-listed patents were either invalid or not infringed by the generic. Actelion’s lawsuit asserted claims from U.S. Patent No. 8318802 and U.S. Patent No. 8598227, both titled Epoprostenol Formulation and Method of Making Thereof.

During the district court proceedings, both parties argued the plain and ordinary meaning of the claim term “a pH of 13 or higher,” a limitation on the bulk epoprostenol formulation capable of being reconstituted with a fluid for intravenous administration. The claimed pH level results in a freeze-dried formulation with greater chemical stability than previous cardiovascular treatments using epoprostenol. Actelion argued that, within the context of the claim language, the claim term should be understood as subject to rounding up from a pH level of 12.5. Mylan countered that the proper construction excludes all pH levels under 13.

Actelion cited examples from three textbooks regarding the calculation of pH levels and use of significant figures to identify pH values. According to Actelion, these references indicate that the use of significant digits to the right of a decimal point would indicate a specific pH value rather than an order of magnitude subject to rounding. Although the district court adopted Actelion’s construction of the disputed claim term, it did so without addressing the extrinsic evidence presented by Actelion or Mylan’s argument that the textbook examples cited actually supported a narrow pH range from 12.995 to 13.004.

Inconsistencies in Patent Claims, Specification Require Review of Extrinsic Evidence

While appellate review of extrinsic evidence determinations is conducted under the clear error standard, the Federal Circuit conducted de novo review, as the district court’s ruling based solely on the intrinsic evidence of the patents’ claims and specification amounted to a ruling of law. At the outset of its analysis, the Federal Circuit opined that the intrinsic evidence is “rather equivocal.” The appellate court nixed Mylan’s argument that uncertainty in an open-ended range foreclosed rounding of any specified limit, especially given the factual upper limit on pH ranges, which “as a matter of science” can reach a value of 14 at most.

The Federal Circuit declined to establish a bright-line rule regarding the use of approximation language in claim terms, finding that the absence of approximation language like “about” did not require a precise value while also ruling that claim terms like “precisely” or “exactly” were not necessary to avoid rounding. The court noted that the extrinsic evidence ignored by the district court addresses the issue of whether the claimed pH range carries meaning on the precision of measurement, significant digits and rounding to a person of ordinary skill in the art.

Further complicating the Federal Circuit’s intrinsic evidence review were inconsistent descriptions in the patents’ specification of the level of specificity for the claimed pH range. The ‘802 patent’s specification notes that “[t]he pH of the bulk solution is preferably adjusted to about 12.5-13.5, most preferably 13.” Mylan argued that this language established that “13” could not be understood to encompass “12.5” when the stated range includes 12.5 as a limit. Mylan also pointed to instances within the specification listing pH values of 13.0, but the Federal Circuit found that the values “13.0” and “13” were used interchangeably throughout the specification. “Said otherwise, the specification supplies the same clarity as to the desired level of precision as muddied water,” the Federal Circuit wrote.

The Federal Circuit concluded that proper claim construction in this case required the district court’s review of extrinsic evidence. “We find that this case is one where the proper claim construction cannot be reached without the aid of extrinsic evidence, and that the district court should have considered, at minimum, the textbook excerpts offered and addressed by the parties,” wrote the court.

While the CAFC has previously narrowed claimed ranges based on intrinsic evidence in cases like AstraZeneca v. Mylan Pharmaceuticals (2021), neither the patents’ specification nor prosecution history evaluated the stability of the claimed formulation within the disputed portion of the claimed range. On remand, the district court is directed to answer in the first instance whether a pH value can be measured precisely, to what degree, and how significant figures should be interpreted in this context.

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Author: billperry