Actelion Pharmaceuticals Ltd v. Mylan Pharmaceuticals Inc.

Case: 24-1641   Document: 54     Page: 1   Filed: 05/13/2026




   United States Court of Appeals
       for the Federal Circuit
                 ______________________

       ACTELION PHARMACEUTICALS LTD,
               Plaintiff-Appellant

                            v.

         MYLAN PHARMACEUTICALS INC.,
                Defendant-Appellee
              ______________________

                       2024-1641
                 ______________________

    Appeal from the United States District Court for the
 Northern District of West Virginia in No. 1:20-cv-00110-
 JPB, Judge John Preston Bailey.
                 ______________________

                 Decided: May 13, 2026
                 ______________________

    LISA GLASSER, Irell & Manella LLP, Newport Beach,
 CA, argued for plaintiff-appellant. Also represented by
 JASON SHEASBY, Los Angeles, CA; PHILIP J. WARRICK,
 Washington, DC.

     ERIC THOMAS WERLINGER, Katten Muchin Rosenman
 LLP, Washington, DC, argued for defendant-appellee. Also
 represented by TIMOTHY H. GRAY; JITENDRA MALIK, Char-
 lotte, NC; DEEPRO MUKERJEE, LANCE SODERSTROM, New
 York, NY; JILLIAN SCHURR-HENDRIX, Dallas, TX.
                 ______________________
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 2                          ACTELION PHARMACEUTICALS LTD v.
                                MYLAN PHARMACEUTICALS INC.


     Before REYNA, TARANTO, and STOLL, Circuit Judges.
 TARANTO, Circuit Judge.
     Actelion Pharmaceuticals Ltd owns U.S. Patent
 Nos. 8,318,802 and 8,598,227, which describe certain phar-
 maceutical compositions involving epoprostenol. Epo-
 prostenol is the active ingredient in Actelion’s
 hypertension drug Veletri®. Mylan Pharmaceuticals Inc.
 submitted an abbreviated new drug application (ANDA) to
 the Food and Drug Administration (FDA) seeking approval
 to market a generic epoprostenol drug before the expiration
 of Actelion’s patents. Actelion sued Mylan for patent in-
 fringement in the Northern District of West Virginia under
 

35 U.S.C. § 271

(e)(2) and 

21 U.S.C. § 355

(j), alleging that
 Mylan’s proposed generic drug was covered (literally or un-
 der the doctrine of equivalents) by certain claims of the ’802
 and ’227 patents. The district court found no literal in-
 fringement, concluding, as most relevant here, that the
 claim term “a pH of 13 or higher” refers to a pH measured
 at a temperature standard in the field. The district court
 further ruled that Actelion was barred from asserting, and
 had not proved, infringement by an equivalent. Actelion
 appeals. We now affirm.
                               I
                               A
     The ’802 and ’227 patents are both titled “Epoprostenol
 Formulation and Method of Making Thereof.” The ’227 pa-
 tent issued from a divisional of the application that issued
 as the ’802 patent, and they share a specification, so we cite
 only the ’802 patent’s specification.
     Epoprostenol is a vasodilator and antiplatelet agent
 that can be used to treat cardiovascular disease. It is un-
 stable in water and will react with water molecules to form
 a different compound that lacks epoprostenol’s desirable
 pharmacological properties. ’802 patent, col. 2, lines 41–
 51; col. 2, line 65, through col. 3, line 51.
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 ACTELION PHARMACEUTICALS LTD v.                                 3
 MYLAN PHARMACEUTICALS INC.


     The presence of an acid in an aqueous (water-based)
 solution of epoprostenol rapidly catalyzes this unwanted
 reaction. Acidic molecules in water can dissociate, intro-
 ducing hydrogen ions (H+) into the solution, which are also
 present as a result of water molecules’ own dissociation.
 Such hydrogen ions often interact with water molecules to
 form what is represented as a water molecule with an extra
 hydrogen ion, called hydronium (H3O+). These hydrogen
 ions or hydronium ions facilitate the degradation of epo-
 prostenol in water. As catalysts, they are not consumed by
 the reaction of epoprostenol with water, so even trace
 amounts can cause continuing breakdown of epoprostenol.
 See ’802 patent, col. 2, line 65, through col. 3, line 51; J.A.
 35–36.
     The degree of acidity of a solution is commonly ex-
 pressed using the pH scale. pH is a positive number—the
 negative of the base-ten logarithm of the concentration of
 hydrogen ions, that logarithm being a negative number.
 (For simplicity, we now omit separate mention of hydro-
 nium ions.) The higher the concentration of hydrogen ions,
 the lower the pH. Under standard ambient conditions, in-
 cluding a temperature of 25°C, the pH of pure water is 7,
 sometimes called neutral pH, with values higher than 7
 considered basic and values lower than 7 considered acidic.
 See ’802 patent, col. 4, lines 62–64; J.A. 31–32.
     The concentration of hydrogen ions in a given solution
 can be modified in at least two ways. First, one can add
 acidic or basic compounds to the solution. An acid, as al-
 ready noted, will introduce more hydrogen ions into a solu-
 tion (increasing the concentration, thus lowering the pH),
 and a base will have the opposite effect, reacting with hy-
 drogen ions and neutralizing them (decreasing the hydro-
 gen-ion concentration, thus raising the pH). See ’802
 patent, col. 2, lines 56–57; col. 4, line 62, through col. 5, line
 21. Second, one can change the temperature of the solu-
 tion. Increasing the temperature will cause molecules that
 are susceptible to liberating hydrogen ions (like water) to
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 4                           ACTELION PHARMACEUTICALS LTD v.
                                 MYLAN PHARMACEUTICALS INC.


 dissociate more frequently, while decreasing the tempera-
 ture will do the opposite. See J.A. 35–36.
      Before the priority date of the ’802 patent and
 Actelion’s subsequent introduction of Veletri, the FDA ap-
 proved the marketing of Flolan®, another epoprostenol for-
 mulation for intravenous administration. ’802 patent, col.
 2, lines 41–57. Flolan had three features that mitigated
 the acid-catalyzed degradation of epoprostenol in water.
 First, it was stored as a lyophilized (freeze-dried) powder
 and reconstituted into an aqueous solution (by mixing with
 liquid diluent) just before it was to be administered. Sec-
 ond, Flolan included a special diluent for reconstituting the
 freeze-dried powder that was more basic than typical intra-
 venous fluids. Third, the reconstituted solution was refrig-
 erated. See ’802 patent, col. 3, lines 52–67.
      The ’802 patent states that Flolan’s needs for a special
 diluent and refrigeration were inconvenient, suggesting
 the desirability of providing epoprostenol compositions
 that would be suitably stable even when reconstituted with
 common commercially available intravenous fluids (which
 are more acidic than the Flolan diluent) and kept at room
 temperature (at which hydrogen-ion concentration would
 be greater than during refrigeration). See ’802 patent, col.
 4, lines 1–19. To that end, the inventor designed processes
 for making lyophilized epoprostenol compositions that
 “when reconstituted ha[ve] a pH>11,” a pH higher than
 that of reconstituted Flolan, which is around 10.5. See ’802
 patent, col. 4, lines 20–23; col. 3, lines 52–56; col. 7, line 51,
 through col. 8, line 57. To achieve such a high pH in the
 reconstituted solution without using Flolan’s basic diluent,
 the patent discloses creating a highly basic “bulk solution”
 that includes epoprostenol. The patent discloses adding ar-
 ginine (a mildly basic amino acid) and sodium hydroxide or
 other bases to the bulk solution to increase its pH. ’802
 patent, col. 4, line 62, through col. 5, line 43. The bulk so-
 lution is then freeze-dried to yield a powder containing suf-
 ficient amounts of basic molecules to provide an
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 MYLAN PHARMACEUTICALS INC.


 appropriately basic solution when reconstituted with a cer-
 tain quantity of typical intravenous fluid (e.g., saline). See
 ’802 patent, col. 5, line 22, through col. 7, line 30.
     A number of experimental results are reported in the
 specification, showing the stability of the freeze-dried pow-
 der forms and, separately, of the reconstituted solution
 forms of epoprostenol compositions made from bulk solu-
 tions with varying pH values (among other differences).
 E.g., ’802 patent, col. 10, line 57, through col. 14, line 37.
 The patent states that the freeze-dried powder form of “ep-
 oprostenol is most stable in . . . formulations when the pH
 of the bulk solution [is] adjusted to 13,” comparing formu-
 lations made from bulk solutions with pH 10.5, 11, or 12,
 and also is more stable than the powder form of Flolan. See
 ’802 patent, col. 14, lines 26–37. After reconstitution, as
 well, epoprostenol compositions made from a pH 13 bulk
 solution demonstrated desirable room-temperature stabil-
 ity. See ’802 patent, col. 14, line 39, through col. 18, line
 34. Those compositions degraded at about one tenth the
 degradation rate of reconstituted Flolan kept at a similar
 temperature. See ’802 patent, col. 8, lines 34–57. A further
 benefit of using a pH 13 bulk solution is that the lyophilized
 composition can be manufactured “without cooling the bulk
 solution to 5°C,” something that “would not be possible for
 the currently available [Flolan] product because the pH of
 the [Flolan] bulk solution is 10.5,” so that, if unrefriger-
 ated, it quickly suffers “significant degradation.” ’802 pa-
 tent, col. 10, lines 48–54.
     Despite the ubiquitous references to pH in the specifi-
 cation, and the importance of particular pH thresholds to
 the invention, the term “pH” is not defined, and the condi-
 tions under which pH measurements were taken are not
 directly stated. See ’802 patent, Abstract (“[W]hen recon-
 stituted or in solution, the solution has a pH>11.”); 

id.,

 col.
 11, lines 54–56 (“[T]he stability of epoprostenol is better at
 pH 13 compared to lower pH samples.”).
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 6                           ACTELION PHARMACEUTICALS LTD v.
                                 MYLAN PHARMACEUTICALS INC.


     The claims of Actelion’s patents are product-by-process
 claims to lyophilized pharmaceutical compositions of epo-
 prostenol or method claims for making compositions or ad-
 ministering reconstituted forms of them.               Each
 independent claim of the patents recites a bulk solution pH
 of “13 or higher” or “greater than 13.” Claim 1 of the ’802
 patent is representative:
     1. A lyophilized pharmaceutical composition com-
     prising:
     (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 composi-
     tion is (i) formed from a bulk solution having a
     pH of 13 or higher and (ii) capable of being recon-
     stituted for intravenous administration with an in-
     travenous fluid.
 ’802 patent, col. 18, lines 46–54 (emphasis added).
                               B
     Mylan submitted its ANDA, No. 213913, to the FDA in
 February 2020. See J.A. 29. The following June, Actelion
 sued Mylan for infringement of the ’802 and ’227 patents
 in the Northern District of West Virginia under 

35 U.S.C. § 271

(e)(2)(A), alleging that the ’802 and ’227 patents cover
 the generic drug that Mylan had sought permission to
 manufacture and market. See J.A. 126. Mylan maintained
 that its generic was manufactured from a bulk solution
 with a pH outside the patents’ claims. See J.A. 253.
     The court held a claim-construction hearing and con-
 strued the “pH of 13 or higher” term to be subject to “ordi-
 nary rounding rules,” i.e., to literally encompass pH values
 as low as 12.5. J.A. 2. The parties stipulated to entry of
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 ACTELION PHARMACEUTICALS LTD v.                             7
 MYLAN PHARMACEUTICALS INC.


 final judgment of infringement and a permanent injunction
 following that ruling, and Mylan appealed. 

Id.

 In that ap-
 peal, we vacated the judgment and remanded for further
 consideration, ruling that “the proper claim construction
 cannot be reached without the aid of extrinsic evidence.”
 Actelion Pharmaceuticals Ltd. v. Mylan Pharmaceuticals
 Inc., 

85 F.4th 1167, 1173

 (Fed. Cir. 2023). On remand, the
 district court, after considering both intrinsic and extrinsic
 evidence, construed “a pH of 13 or higher” to mean “a pH
 of 12.98 or higher.” J.A. 25. That ruling is unchallenged
 in the present appeal. Actelion Opening Br. at 11–12 n.6.
      In February 2024, the issue of infringement was tried
 to the bench. J.A. 27–28, 139. The court treated claim 1 of
 the ’802 patent as representative, and the “only dispute at
 trial was whether the pH of the bulk solution used to form
 Mylan’s ANDA product is ‘13 or higher’” within the mean-
 ing of that claim. J.A. 28 (citation omitted), 35. Actelion
 advanced alternative theories of literal infringement and
 infringement by an equivalent.
     First, Actelion argued, Mylan literally infringed even
 though it was undisputed that Mylan’s bulk solution, when
 measured at 25±2°C, has a pH well below 12.98. J.A. 48–
 51. The ANDA indicates that Mylan’s bulk solution is re-
 frigerated when it is manufactured, and, according to
 Actelion, a relevant artisan would understand that pH
 should be measured at the refrigerated “operating temper-
 ature” of the solution, and Mylan’s bulk solution, if meas-
 ured at that cold temperature, has a pH of above 13.
 Second, Actelion contended that Mylan’s generic is an
 equivalent to the invention because Mylan’s manufactur-
 ing process performs the same function (improved manu-
 facturing stability) to achieve the same result (composition
 stability) in the same way (reducing hydrogen ion concen-
 tration) as the claimed invention.
    The district court rejected both arguments, finding that
 Mylan does not infringe literally or by an equivalent.
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 8                         ACTELION PHARMACEUTICALS LTD v.
                               MYLAN PHARMACEUTICALS INC.


 Regarding literal infringement, the court determined that
 a relevant artisan would understand the “bulk solution
 having a pH of 13 or higher” term to refer to a pH meas-
 urement taken at standard temperature, i.e., 25±2°C. J.A.
 34–49, 60–80. The court, looking to the intrinsic record,
 determined that many of the specification’s reported exper-
 imental results would “not make sense” if the measure-
 ments were not taken at 25±2°C. J.A. 66–73. The court
 also considered extrinsic evidence, including the United
 States Pharmacopeia (USP), an influential collection of
 standards for the pharmaceutical industry, as well as the
 testimony of the parties’ experts, to conclude that in the
 art, and in the context of the patents at issue, “unless oth-
 erwise specified,” pH values recited mean the pH measure-
 ment at the standard temperature of 25±2°C. J.A. 46
 (quoting J.A. 6799); see J.A. 35–49. There being no evi-
 dence for finding that Mylan’s ANDA product had a pH of
 13 or higher at that temperature, the court found no literal
 infringement by Mylan’s ANDA product.
      Regarding infringement by an equivalent, the district
 court made three rulings. First, it held that Actelion was
 barred by the disclosure-dedication rule from capturing
 bulk solutions with (standard-temperature) pH less than
 13, because Actelion’s specification discloses, but does not
 claim, pH ranges for bulk solutions including values under
 13, e.g., pH 12–13 and 12.5–13. J.A. 81–82. Second, the
 court held that, during prosecution, Actelion had, in re-
 sponse to an obviousness rejection, amended the pH limi-
 tation to reduce the claimed range to 13 or above, so it had
 surrendered, and was estopped from attempting to recap-
 ture as an equivalent, pH values lower than 13. J.A. 82–
 85. Finally, the court reasoned that, even taken on its mer-
 its, Actelion’s equivalents-infringement argument failed,
 because Actelion had evaluated the function of Mylan’s ge-
 neric and the way it achieves its function “at an impermis-
 sibly high level of generality.” J.A. 86–87.
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 ACTELION PHARMACEUTICALS LTD v.                              9
 MYLAN PHARMACEUTICALS INC.


     The district court entered final judgment on March 18,
 2024. Actelion timely appealed. We have jurisdiction un-
 der 

28 U.S.C. § 1295

(a)(1).
                               II
     Actelion makes two primary arguments on appeal.
 First, challenging the finding of no literal infringement, it
 contends that the district court erred by construing the
 claim term “pH of 13 or higher” to refer to a pH measure-
 ment made at 25±2°C. Second, Actelion argues that the
 district court incorrectly held that Actelion was barred
 from asserting the doctrine of equivalents and that the al-
 ternative finding of no proved equivalent was clearly erro-
 neous.
     We review the district court’s ultimate claim construc-
 tion and analysis of the intrinsic record without deference,
 but we review subsidiary findings of fact based on extrinsic
 evidence for clear error. Teva Pharmaceuticals USA, Inc.
 v. Sandoz, Inc., 

574 U.S. 318

, 331–33 (2015). Clear error
 exists if we are left with “a definite and firm conviction that
 a mistake has been committed.” Pacific Gas & Electric Co.
 v. United States, 

668 F.3d 1346

, 1350–51 (Fed. Cir. 2012)
 (cleaned up). A judge’s finding of noninfringement is a fac-
 tual finding that we review for clear error. Insituform
 Technologies, Inc. v. Cat Contracting, Inc., 

161 F.3d 688, 692

 (Fed. Cir. 1998). Whether assertion of the doctrine of
 equivalents is barred by either prosecution history estoppel
 or the disclosure-dedication rule is a legal issue resolved
 without deference. Eli Lilly and Co. v. Hospira, Inc., 

933 F.3d 1320

, 1330–31 (Fed. Cir. 2019); Eagle Pharmaceuti-
 cals Inc. v. Slayback Pharma LLC, 

958 F.3d 1171, 1177

 (Fed. Cir. 2020).
                               A
     Actelion argues that the district court’s standard-tem-
 perature construction of the claim phrase “formed from a
 bulk solution having a pH of 13 or higher” is incorrect.
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 10                          ACTELION PHARMACEUTICALS LTD v.
                                 MYLAN PHARMACEUTICALS INC.


 According to Actelion, the phrase covers a solution with pH
 measured at the solution’s actual temperature, which
 might be well below standard temperature; that is the
 phrase’s ordinary meaning to a relevant artisan, Actelion
 contends, and the district court’s construction is contrary
 to dispositive intrinsic evidence and rests on a clearly erro-
 neous evaluation of the extrinsic evidence. Actelion Open-
 ing Br. at 21–36. Mylan, for its part, suggests that the
 district court did not construe the claim phrase at all,
 Mylan Br. at 27–43, but that, if it did, its construction was
 correct, 

id.

 at 43–48.
      Contrary to Mylan’s suggestion, we think that the dis-
 trict court did construe the phrase—determining what the
 phrase meant in the context of the patent and of relevant
 artisans’ understanding. On the other hand, we see no
 harmful denial to Actelion of notice and opportunity to pre-
 sent arguments and evidence relevant to the phrase’s
 scope, matters that have been fully briefed here. Only the
 correctness of the district court’s determination of the
 phrase’s scope therefore need to be decided. And on the
 merits, we agree with Mylan that the district court made
 no reversible error.
      The claim language, standing alone, does not resolve
 the question of the proper interpretation of “a pH of 13 or
 higher.” That phrase, on its face, simply does not specify
 the conditions for taking the pH measurement necessary to
 determine whether a bulk solution meets the claims; nor
 does the remainder of claim 1 or any of the other claims of
 either patent. See ’802 patent, col. 18, line 45, through col.
 20, line 27; ’227 patent, col. 18, line 28, through col. 21, line
 31. Actelion points to the word “having” in the phrase
 “formed from a bulk solution having a pH of 13 or higher,”
 but if a solution’s pH would be understood (in the context
 of the patent and in the art) to be measured at standard
 temperature, then the phrase means that the bulk solution
 “ha[s]” the property that its pH, so measured, is 13 or
 higher. The word “having” does not imply use of a pH
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 ACTELION PHARMACEUTICALS LTD v.                            11
 MYLAN PHARMACEUTICALS INC.


 measuring device on a solution as is, with no temperature
 adjustment of the solution for measurement, or of samples
 taken from the solution for measurement. See J.A. 76,
 6938 (indicating use of samples for measurement). The
 same is true even if, as Actelion insists (in tension with the
 claim language), what matters is the pH of the solution
 “during manufacture.” See Actelion Opening Br. at 26. If
 pH is understood to be the value for a solution measured at
 standard temperature, that is the meaning of pH of the so-
 lution during manufacture or “when made” (an expression
 used by the examiner, as indicated infra).
      With the claim language not supplying a clear answer
 on its own, we turn to other intrinsic evidence. The speci-
 fication favors the district court’s construction over
 Actelion’s. The specification never states outright the con-
 ditions of any of the (many) pH measurements reported in
 its examples. In particular, when, at the top of the many
 tables, it lists pH numbers near temperatures, the temper-
 atures are for the storage of samples, not for the measure-
 ment of pH. But the specification clearly identifies “an
 alkaline environment” as one with “pH>7,” a definition
 that undisputedly is accurate only at standard tempera-
 ture. That identification therefore implicitly conveys an
 assumption about pH measurements, and that assumption
 is nowhere contradicted in the specification’s many refer-
 ences to pH.
      Moreover, the specification consists chiefly of reported
 results of comparative experiments testing mostly for sta-
 bility (of powder or of solutions) of old and assertedly new
 solutions, where, e.g., pH values are being compared. The
 reports give simple, straightforward comparisons of results
 for the different listed pH values, without any suggestion
 of accommodating the complications of measuring pH at
 different temperatures. The reports are thus more reason-
 ably understood as indicating use of a uniform approach to
 measuring pH. As it is clear from the expert evidence that
 at least some (even most) of the tables reflect pH measured
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 12                          ACTELION PHARMACEUTICALS LTD v.
                                 MYLAN PHARMACEUTICALS INC.


 at standard temperature, see J.A. 36–38, it is inferable that
 all the pH values are so measured. The specification as a
 whole therefore provides considerable support for the dis-
 trict court’s conclusion that the relevant claim language re-
 fers to a pH measurement at standard temperature.
      Actelion relies on two additional pieces of intrinsic evi-
 dence—the examiner’s statement of reasons for allowance
 and the supposed purpose of the invention—for its actual-
 temperature reading of the claims, but neither persua-
 sively supports Actelion’s construction. The examiner’s
 statement that “the pH of the bulk solution when made im-
 parts a critical function” to the composition, like the claim
 language itself, is consistent with the idea that pH as
 claimed means a pH measured at standard temperature.
 J.A. 4012. On that understanding, the import of the exam-
 iner’s statement was that raising the pH of the bulk solu-
 tion by means other than temperature to a certain
 threshold results in, e.g., the improved stabilities of the
 powder and reconstituted forms of the composition. That
 understanding is also consistent with how the specification
 describes the purpose of the invention. The stated purpose
 of the invention, relevant here, is to provide a “stable epo-
 prostenol composition,” and the specification indicates that
 the amount of base added to the bulk solution (which would
 affect the standard-temperature pH), and not the bulk so-
 lution’s temperature (which, definitionally, would not), is
 relevant to whether the freeze-dried or reconstituted epo-
 prostenol composition is stable. See ’802 patent, Abstract;
 col. 1, lines 11–14; col. 4, lines 8–46; col. 9, line 46, through
 col. 18, line 34.
      For those reasons, the intrinsic evidence favors the dis-
 trict court’s construction. In this case, however, we do not
 stop there, though intrinsic evidence typically resolves
 claim-construction disputes. Under the general rule that
 we give a term its ordinary and customary meaning, “the
 ordinary and customary meaning of a claim term is the
 meaning that the term would have to a person of ordinary
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 MYLAN PHARMACEUTICALS INC.


 skill in the art” in the context of the patent, Phillips
 v. AWH Corp., 

415 F.3d 1303, 1313

 (Fed. Cir. 2005) (en
 banc), and on that field-specific-understanding issue, ex-
 trinsic evidence—evidence outside the intrinsic record—
 may sometimes be informative, 

id.

 at 1318–19; see Seabed
 Geosolutions (US) Inc. v. Magseis FF LLC, 

8 F.4th 1285, 1287

 (Fed. Cir. 2021); Vitronics Corp. v. Conceptronic, Inc.,
 

90 F.3d 1576

, 1584–85 (Fed. Cir. 1996). Evidence that rel-
 evant artisans use a claim term in an established and con-
 sistent way, including evidence of a “[w]ell known industry
 standard[ ],” see Wellman, Inc. v. Eastman Chemical Co.,
 

642 F.3d 1355, 1367

 (Fed. Cir. 2011), can be persuasive of
 the term’s meaning, cf. Canatex Completion Solutions, Inc.
 v. Wellmatics, LLC, 

159 F.4th 39

, 45 (Fed. Cir. 2025). That
 is so in this case—where the extrinsic evidence strongly re-
 inforces what is already indicated by the intrinsic evidence.
      The district court here properly relied on just that sort
 of extrinsic evidence to find that those skilled in making
 pharmaceutical compositions, when referring to pH, mean
 a measurement at standard temperature unless they indi-
 cate otherwise, and we discern no clear error in how the
 district court evaluated the record. The court referred to
 the USP, which both the parties and their experts agreed
 is an important set of standards in the pharmaceutical in-
 dustry. See J.A. 32–33 (citing portion of Actelion’s expert’s
 trial testimony agreeing that the USP is “influential” and
 is “consulted” by relevant artisans). The USP, the court
 found, prescribes a default understanding that, “unless
 otherwise specified,” pH measurements are made at
 25±2°C. J.A. 46 (quoting J.A. 6799). The court, further,
 reasonably found that several general chemistry textbooks
 support the proposition that “pH values when generally de-
 scribed assume [standard ambient temperature and pres-
 sure] measurement.” J.A. 47 (citations omitted).
     As already noted, moreover, the experts agreed that
 the vast majority of the pH measurements described in the
 specification refer to standard-temperature values,
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 14                         ACTELION PHARMACEUTICALS LTD v.
                                MYLAN PHARMACEUTICALS INC.


 reflecting the default understanding. See J.A. 36, 38–42.
 Indeed, the experts agreed that every reference to a bulk
 solution with pH 13 in the specification’s experimental re-
 sults conforms to this default—that is, the specification’s
 references to a pH 13 bulk solution undisputedly connote
 adjusting the temperature of the bulk solution to 25±2°C
 and then measuring pH as 13. See J.A. 36, 38–42; ’802 pa-
 tent, col. 9, line 46, through col. 14, line 37. The district
 court properly concluded, based on the evidence of an influ-
 ential industry standard that is undisputedly followed by
 the most relevant embodiments of the invention, that the
 term “pH of 13 or higher” refers to a standard-temperature
 pH measurement.
     The contrary evidence marshalled by Actelion does not
 leave us with a definite and firm conviction that the district
 court made a mistake. See Actelion Opening Br. at 28 (cit-
 ing J.A. 6021, 4545, 5986, 5950–51). The district court rea-
 sonably viewed the USP as more probative of the
 understanding of a relevant artisan than some of Actelion’s
 evidence, namely “generalized scientific textbooks.” See
 J.A. 45. And Actelion’s evidence does not actually contra-
 dict the district court’s finding—that a statement of a pH
 value in the art is understood to refer to standard-temper-
 ature measurements “unless otherwise specified,” thus rec-
 ognizing that a particular statement might specify
 otherwise. J.A. 46. Actelion’s cited evidence merely shows
 instances of such specification; none of it says that a pH
 value without identification of a temperature should be as-
 sumed to mean anything other than a pH measured at
 standard temperature. See J.A. 6021, 4545, 5986, 5950–
 51.
     Actelion also criticizes the district court’s decision as
 internally inconsistent, but this criticism is unpersuasive.
 Actelion notes that the court found that the claims “require
 that the bulk solution have a pH of 13 or higher” and such
 a “high pH can be achieved through any technique . . . in-
 cluding cold temperature.” J.A. 36. We do not read the
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 ACTELION PHARMACEUTICALS LTD v.                            15
 MYLAN PHARMACEUTICALS INC.


 district court, in context, to have found that the claims both
 do and do not require a standard-temperature pH meas-
 urement. Instead, we understand the court to have been
 laying out an undisputed scientific fact about tempera-
 ture’s effect on pH—before it went on, in the next several
 paragraphs of its decision, to more narrowly interpret the
 claim language in light of the relevant extrinsic evidence.
 See J.A. 36–38 (observing that “pH measurements, includ-
 ing those of bulk solutions, have a plain and ordinary
 meaning in pharmaceutical manufacturing” of being taken
 at “standard temperature”).
     For all the foregoing reasons, we discern no error in the
 district court’s conclusion that the phrase at issue, as a
 matter of claim construction, refers to a standard-temper-
 ature measurement. Under that construction, there is un-
 disputedly no literal infringement. We therefore affirm the
 finding that Mylan does not literally infringe.
                               B
     Actelion challenges the district court’s determination
 that Actelion was barred from asserting and also failed to
 prove that Mylan infringes by an equivalent to the claimed
 invention. Actelion Opening Br. at 36–61. We discern no
 error in the district court’s application of both the prosecu-
 tion history estoppel and disclosure-dedication bars and af-
 firm its equivalents-infringement ruling on those grounds.
                               1
      When a patent applicant responds to an examiner’s re-
 jection on patentability grounds “by narrowing his claims,
 this prosecution history estops him from later arguing that
 the subject matter covered by the original, broader claim
 was nothing more than an equivalent.” Festo Corp. v. Sho-
 ketsu Kinzoku Kogyo Kabushiki Co., 

535 U.S. 722, 727

 (2002). Such “a narrowing amendment made for a reason
 of patentability” presumptively “surrenders the entire ter-
 ritory between the original claim limitation and the
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 16                         ACTELION PHARMACEUTICALS LTD v.
                                MYLAN PHARMACEUTICALS INC.


 amended claim limitation.”         Festo Corp. v. Shoketsu
 Kinzoku Kogyo Kabushiki Co., 

344 F.3d 1359, 1365

 (Fed.
 Cir. 2003). Of relevance here, there is a “‘very narrow’” ex-
 ception to such scope of surrender, Eli Lilly, 933 F.3d at
 1330–31 (quoting Integrated Technology Corp. v. Rudolph
 Technologies, Inc., 

734 F.3d 1352, 1358

 (Fed. Cir. 2013)),
 that applies if the patentee shows “that the way in which
 the alleged equivalent departs from what the claim limita-
 tion literally requires is tangential to the discernible objec-
 tive reason for the narrowing amendment,” Ajinomoto Co.,
 Inc. v. International Trade Commission, 

932 F.3d 1342, 1354

 (Fed. Cir. 2019).
     Actelion relies entirely on the tangentiality exception
 to argue that prosecution history estoppel does not apply
 here, but its arguments are unpersuasive. The application
 that issued as the ’802 patent was amended during prose-
 cution with respect to the pH limitation several times, with
 the final amendment that resulted in the claims as allowed
 narrowing claim 1’s pH limitation from “a pH of greater
 than 12” to “a pH of 13 or higher.” See J.A. 3981–97. That
 amendment followed the examiner’s rejection of the claims,
 on obviousness grounds, because no “unexpected results”
 had been demonstrated for “a bulk solution having a pH of
 12 or greater,” together with the examiner’s indication that
 claims “limited to using a bulk solution with a pH of 13 or
 higher” would be allowable because, for those bulk-solution
 pH values, unexpected results had been shown. J.A. 3982.
 Referring to the stabilities of the freeze-dried powder and
 reconstituted solution, the examiner further noted that the
 applicant had not shown improved stability for “a pH of
 greater than 12,” J.A. 3983, and “it is the lack of stability
 at even pH [ ] 12 which demonstrates the significance of [ ]
 pH 13,” J.A. 3984.
     Actelion contends that the claim amendment comes
 within the tangentiality exception because the rationale for
 the amendment was not to surrender a “functionally equiv-
 alent bulk solution having the same relevant chemical
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 ACTELION PHARMACEUTICALS LTD v.                            17
 MYLAN PHARMACEUTICALS INC.


 properties” and “identical benefits,” namely “impact on ep-
 oprostenol degradation.” Actelion Opening Br. at 56. That
 contention is incorrect. The prosecution history demon-
 strates that the examiner viewed pH 13 as the threshold
 for which unexpected results, necessary for nonobvious-
 ness here, had been shown: That is the “discernible objec-
 tive reason for the narrowing amendment.” Ajinomoto, 

932 F.3d at 1354

. We thus agree with the district court that
 Actelion failed to show that the claim amendment is only
 tangential to the differences between the alleged equiva-
 lent and the literal claim scope, and we conclude that
 Actelion is estopped from asserting the doctrine of equiva-
 lents here.
                               2
     The disclosure-dedication rule independently bars
 Actelion’s theory of infringement by an equivalent.
 “[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 as an
 equivalent. Johnson & Johnston Associates Inc. v. R.E.
 Service Co., 

285 F.3d 1046, 1054

 (Fed. Cir. 2002) (en banc).
 “[T]he disclosure must be of such specificity that one of or-
 dinary skill in the art could identify the subject matter that
 had been disclosed and not claimed.” SanDisk Corp.
 v. Kingston Technology Co., 

695 F.3d 1348, 1363

 (Fed. Cir.
 2012) (quoting PSC Computer Products v. Foxconn Inter-
 national, Inc., 

355 F.3d 1353, 1360

 (Fed. Cir. 2004)). And
 the “unclaimed subject matter must have been identified
 by the patentee as an alternative to a claim limitation.” 

Id.

 at 1364 (quoting Pfizer, Inc. v. Teva Pharmaceuticals USA,
 Inc., 

429 F.3d 1364, 1379

 (Fed. Cir. 2005)).
     Actelion’s patents disclose that “[t]he pH of the bulk so-
 lution is preferably adjusted to about 12.5–13.5, most pref-
 erably 13.” ’802 patent, col. 5, lines 41–43; see 

id.,

 col. 5,
 lines 35–37 (“Preferably, the base is added so that the pH
 of the bulk solution is greater than 11, preferably greater
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 18                         ACTELION PHARMACEUTICALS LTD v.
                                MYLAN PHARMACEUTICALS INC.


 than 12, and, most preferably greater than 13.”). Those
 disclosures are sufficiently specific to identify the ranges of
 pH 12.5 to 13, 12 to 13, and greater than 12. Moreover,
 those disclosures plainly correspond to, and are expressly
 identified as alternatives to, the claim limitation requiring
 a pH of 13 or higher. 

Id.,

 col. 5, lines 36–37 (“preferably
 greater than 12, and, most preferably greater than 13”).
 Actelion cites no support in our case law for its suggestion
 that the disclosure-dedication rule should not apply here
 because the disclosed alternatives are not mutually exclu-
 sive with each other. And that suggestion is contrary to
 the purpose of the rule, which, consistent with ordinary
 principles of claim interpretation, seeks to give effect to
 how relevant artisans would understand what has, and
 more importantly what has not, been claimed. That prin-
 ciple does not require that the disclosed alternatives be mu-
 tually exclusive; overlapping alternatives are readily
 susceptible of being clearly disclosed and yet partially un-
 claimed. See Johnson & Johnston, 

285 F.3d at 1054

. We
 therefore agree with the district court that the disclosure-
 dedication rule bars Actelion’s assertion of the doctrine of
 equivalents, and we affirm the district court’s decision on
 that ground, as well.
                               III
      We have considered Actelion’s remaining arguments
 and find them unpersuasive. For the foregoing reasons, we
 affirm the judgment of the district court.
                         AFFIRMED