Tris Pharma, Inc. v. Actavis Labs. FL, Inc.

Quillivant XR® (methylphenidate (“MPH”))

November 30, 2020

GENERICally Speaking: A Hatch Waxman Litigation Bulletin

Case Name: Tris Pharma, Inc. v. Actavis Labs. FL, Inc., No. 14-1309-CFC, 2020 WL 7028456 (D. Del. Nov. 30, 2020) (Connolly, J.)

Drug Product and Patent(s)-in-Suit: Quillivant XR® (methylphenidate (“MPH”)); U.S. Patents Nos. 8,465,765 (“the ’765 patent”), 8,563,033 (“the ’033 patent”), 8,778,390 (“the ’390 patent”), 8,956,649 (“the ’649 patent”), and 9,040,083 (“the ’083 patent”)

Nature of the Case and Issue(s) Presented: Tris sued Actavis alleging infringement of 21 claims from the five patents-in-suit. In response, Actavis challenged the validity of the asserted claims based on obviousness and obviousness-type double patenting. After a five-day bench trial, the trial court found all the asserted claims invalid as obvious. The trial court did not address infringement or double patenting. Tris appealed the trial court’s finding of invalidity for seven asserted claims: claims 4 and 10 of the ‘033 patent; claims 6 and 20 of the ’765 patent; and claims 15, 16, and 20 of the ‘390 patent. The Federal Circuit vacated the judgment “[b]ecause [the judge]’s obviousness decision lack[ed] the requisite fact-finding, and because the [judge] erred in rejecting Tris’s evidence of objective indicia of nonobviousness.” The Federal Circuit remanded the obviousness analysis to the trial court. After remand, Actavis dropped its obviousness-type double-patenting challenge and the parties agreed that the trial court should make further findings of fact based on the existing written record. The remand court found that the asserted claims were not invalid and that Defendants directly infringed, contributorily infringed, and induced the infringement of each of the asserted claims.

Why Tris Prevailed: The court found that Actavis did not prove by clear and convincing evidence that a skilled artisan would have been motivated to combine with a reasonable expectation of success a liquid MPH formulation with a single mean peak, 12-hour duration, and 45-minute onset, or the combination recited in claim 20 of the ’765 patent. Actavis argued that a skilled artisan “would have been indifferent to the choice between a single peak and bimodal peak profile and that this indifference does not undermine motivation.” In rejecting Actavis’s argument, the court reasoned that a skilled artisan would not have viewed the single peak profile as a suitable option because the prior art taught away from using a single peak.

Further, the court found that Actavis did not prove by clear and convincing evidence that a skilled artisan would have been motivated to combine with a reasonable expectation of success a liquid MPH formulation with a single mean peak, 12-hour duration, and the claimed Tmax range, or the combination recited in claim 4 of the ’033 patent, claim 6 of the ’765 patent, and claims 15, 16, and 20 of the ’390 patent. Actavis argued that the Scicinski prior-art reference disclosed the claimed PK and PD limitations, thereby establishing a presumption of obviousness that the plaintiffs had not rebutted. But the court explained that the presumption attaches only when “the range or value of a particular variable” is “the difference between the claimed invention and the prior art.” Here, the single mean peak, 12-hour duration, and claimed Tmax range were not individually or collectively the difference between the claimed invention and Scicinski. The asserted claims required that the invention be a liquid formulation of MPH, and Actavis had not met its burden to show that Scicinski taught a liquid MPH formulation, and, therefore, was not entitled to a presumption of obviousness.

On the issue of infringement, all the asserted claims either explicitly required or depended from claims that explicitly required “a single mean average plasma concentration peak.” This term was given its plain and ordinary meaning. It was undisputed that Actavis’s generic MPH formulations had the same plasma profile as Quillivant, which was depicted in graphs found in the labels of the two drugs and in Figure 3 of the written description shared by the asserted patents. The only issue was whether that plasma profile had one or two peaks. Tris’s expert testified that the profile showed a single mean peak. One of the inventors of the patents-in-suit similarly represented in a sworn declaration filed with the PTO that the profile had a single peak. Actavis’s expert also conceded that Figure 3 had a single mean peak. Thus, the court found that Actavis’s proposed ANDA products met that limitation. Actavis argued that Pfizer, which marketed Quillivant for Tris, put forward in a 2014 Citizen Petition evidence that Quillivant’s plasma profile had two peaks—a ‘shoulder’ followed by a second peak. This evidence, Actavis argued, judicially estopped Tris from asserting in this litigation that Quillivant had a single peak profile. The court rejected this argument because the Citizen Petition in question referred to this feature of the plasma profile only as a “shoulder” and never as a peak. The parties agreed that a shoulder “refers to the region where the rate of increase or decrease in drug plasma concentration slows or flattens for a period of time.” Tris’s expert testified that a shoulder can be a peak only if it is followed by a second, accelerating, phase of drug release, and that no second, accelerating, phase was present in the data presented in Pfizer’s Citizen Petition. Thus, the court found that Tris had demonstrated by a preponderance of the evidence that Actavis’s generic product met the single, mean-peak, limitation found in the asserted claims.

Oren D. Langer

Partner

Managing Partner, New York Office
Member of Executive Board

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