It has long been understood that claim construction can, and frequently is, dispositive in patent litigation.  This truism was the basis for the Federal Circuit affirming the District Court's decision against a generic drug producer in its recent decision in Par Pharmaceutical, Inc. v. Hospira, Inc.  And the case being decided on whether Hospira's formulation described in its ANDA would constructively infringe Par's patented formulation, the clear error standard of view also had a part to play in the outcome.

These issues arose in ANDA litigation, wherein Plaintiffs asserted U.S. Patent Nos. 9,119,876 and 9,925,657 against Hospira over Par's Adrenalin® product (epinephrine) and methods for administering the drug (by injection).  Hospira asserted non-infringement and invalidity as defenses (the District Court ruled against Hospira on the latter and they were not on appeal).  The Par patents were directed to formulations that overcame deficiencies in prior art epinephrine formulations, principally short shelf life due to three different routes of degradation (oxidation, racemization, and sulfonation).  Claim 1 of the '876 patent is representative:

A composition comprising:
    in the range of about 0.5 to 1.5 mg/mL of epinephrine and/or salts thereof,
    in the range of about 6 to 8 mg/mL of a tonicity regulating agent,
    in the range of about 2.8 to 3.8 mg/mL of a pH raising agent,
    in the range of about 0.1 to 1.1 mg/mL of an antioxidant,
    in the range of about 0.001 to 0.010 mL/mL of a pH lowering agent, and
    in the range of about 0.01 to 0.4 mg/mL of a transition metal complexing agent,
    wherein the antioxidant comprises sodium bisulfite and/or sodium metabisulfite.

(where boldface type is used in the opinion to designate limitations relevant to Hospira's appeal).  After defining these limitations, the opinion set forth the District Court's construction of the word "about" as it was used for each limitation.  Specifically, the parties agreed that this term be given its plain and ordinary meaning, i.e., "approximately"; significantly for the Federal Circuit in this appeal, Hospira did not assert a contrary construction.

The parties proffered expert testimony regarding the three limitations emphasized above.  Par's expert testified that the tonicity range -- 6-8 mg/mL -- could be satisfied for the court's infringement determination by 9 mg/mL sodium chloride (Hospira's concentration, although concentrations as low a 8.55 mg/mL were also used) because it would suffice for the intended purpose, i.e., "maintain[ing] the integrity of living cells following the injection of epinephrine into the bloodstream."  Hospira's expert only disputed his counterpart with regard to whether the skilled artisan would consider 9 mg/mL to fall within the range of "about" 6-8 mg/mL.

For the transition metal complexing limitation, the District Court relied on evidence that citric acid was a known chelating agent, and that the amount of elemental impurities (metals) was represented by Hospira in its ANDA as being within international standards (specifically, the ICH Q3D guidelines).  The correspondence between this standard and the concentration of metal chelating agent recited in the claim was attested by Par's expert to fall within the claimed range.  Hospira's expert again did not contest Par's expert in general but did testify that the upper limit of the ICH Q3D guidelines were an inappropriate standard for the District Court to apply.  Rather, in his view the proper amount should be derived from Hospira's test batches, which he opined would require a much lower amount of citric acid as a chelator.

The parties contested the concentration of the pH lowering agent, Hospira's ANDA specifying citric acid as a buffer (with its sodium citrate salt), which together are considered in the art to be pH raising (whereas it was undisputed that citric acid by itself is a pH lowering agent).  According to Par's expert, subtracting the amount of citric acid in Hospira's formulation left sufficient citric acid to fall within the range of Par's claimed pH lowering agent, "even while those same citric-acid molecules would be part of the buffer system (citric acid combined with sodium citrate) that would serve as a pH raising agent."  (Despite the apparent paradox it is helpful to remember that infringement is a question of fact and the Federal Circuit reviews factual determinations by the District Court in a bench trial for clear error.)  Hospira's expert disagreed with Par's expert, testifying (reasonably, on its face) that the citric acid molecules in the formulation should not be considered as both pH-lowering and pH raising components of the formulation.  Nevertheless, the District Court ruled in Par's favor, that Hospira's formulation would infringe Par's patent claims.  This appeal followed.

The Federal Circuit affirmed, in an opinion by Judge Taranto, joined by Judges Dyk and Stoll.  Hospira addressed on appeal the District Court's determinations for each of the three limitations at issue.  The Federal Circuit in its opinion first affirmed the District Court's finding that Hospira's 9 mg/mL sodium chloride concentration in its formulation fell literally within Par's claim limitation of "about" 6-8 mg/mL.  The panel noted that when the term "about" is used, it "avoids a strict numerical boundary to the specified parameter," citing Cohesive Techs. v. Water Corp., 543 F.3d 1351 (Fed. Cir. 2008), relying on Pall Corp. v. Micron Separations, Inc., 66 F.3d 1211, 1217 (Fed. Cir. 1995).  The extent to which a claimed numerical range can extend outside that range when modified by "about" in a claim is limited to what the skilled worker would "reasonably consider" the claim would encompass according to the opinion, citing Monsanto Tech. LLC v. E.I. DuPont de Nemours & Co., 878 F.3d 1336, 1342 (Fed. Cir. 2018).  In cases like these, where no party argues for a narrower claim construction, the determination is governed by the Cohesive standard.  The elements of this standard include whether the accused infringing formulation differs from the claimed range by a "modest amount" (Conopco, Inc. v. May Dep't Stores Co., 46 F.3d 1556, 1562 (Fed. Cir. 1994)), and how critical the claimed range is to the purpose of the limitation (not the invention) itself.  Although recognizing the contribution of claim construction to a Court's decisions on this question, the Federal Circuit stated that "it is a question of technologic fact whether the accused device meets a reasonable meaning of 'about' in the particular circumstances," citing Modine Manufacturing Co. v. U.S. Int'l Trade Comm'n, 75 F.3d 1545, 1554 (Fed. Cir. 1996).  Here, the panel opined that the District Court had properly applied its precedent as set forth herein, and that its basis for the decision was dependent on expert testimony.  The District Court found Par's expert to be more persuasive than Hospira's, particularly to the extent that it was dependent on "the technological facts, the importance of the purpose of the limitation, and the limitation's noncriticality."  In contrast, the District Court found that Hospira's expert "did not provide a meaningful analysis of the technologic context or the function of the claimed amount of tonicity regulating agent."  On these facts the panel found no clear error.

With regard to the transition metal complexing agent limitation, the Federal Circuit rejected Hospira's argument that the District Court should have focused on its proposed generic formulation rather than on what was set forth in its ANDA.  The panel found that the District Court correctly considered citric acid to be a transition metal complexing agent as recited in the claim, which was consistent with the expert testimony from both parties.  The opinion rejected Hospira's argument that it did not intend citric acid to function as a chelating agent, in light of testimony that citric acid actually does act as a chelating agent.  The standard for finding infringement in ANDA litigation under 35 U.S.C. § 271(e)(2) is what is described in the ANDA (the filing of which is, as the Court noted, the constructive act of infringement), citing Sunovion Pharm., Inc. v. Teva Pharm., USA, Inc., 731 F.3d 1271, 1279 (Fed. Cir. 2013).  And Hospira's reliance on the ICH Q3D standard for its ANDA supported the District Court's finding, not at least because this citation was added to the ANDA after the FDA requested "alternative information" in this regard.  The ANDA not being silent on this question the Federal Circuit held that the District Court had sufficient evidence for finding that Hospira's formulation literally corresponded to this limitation.

Finally, with respect to pH-affecting properties of citric acid and buffers made therefrom, the Federal Circuit affirmed based on Hospira not having preserved a claim-construction argument on this issue.  Moreover, the Federal Circuit understood that the (identical) specifications of the '876 and '657 patents, in the panel's view "at least strongly suggest[ed] the opposite."  Because it had not challenged claim construction on this (or any other) point, the Federal Circuit held that the District Court had not clearly erred in concluding that Hospira's formulation infringed the claims as construed (which, inter alia, depended on the disclosures in the specification), and affirmed.

Par Pharmaceutical, Inc. v. Hospira, Inc. (Fed. Cir. 2020)
Panel: Circuit Judges Dyk, Taranto, and Stoll
Opinion by Circuit Judge Taranto