A certain amount of comment has recently been evinced from the patent bar by the voicing from several members of the Federal Circuit, including the Chief Judge, of their dismay over the number of patent cases coming to the Court. In particular, this increase in the patent case census in Court is due in not some small degree to the number of cases arising from decisions by the Patent Trial and Appeal Board (PTAB) that the Court is tasked with reviewing regarding the validity vel non of patents from the various post-grant review proceedings (the largest number of which arise from inter partes reviews, IPRs). Perhaps in reaction to its dismay, the Court in several cases has remanded PTAB decisions based on failure of the Board to properly support their decisions to be amenable to appellate review; see, for example, Securus Tech v. Global Tel*Link (Fed. Cir. 2017) (IPR2014-01278) (Pat. No. 7,860,222); Ultratec v. CaptionCall and Matal (Fed. Cir. 2017). This basis for eschewing review has been much more rare in district court appeals but arose last week in the Court's decision in Tris Pharma Inc. v. Actavis Laboratories FL, Inc.
The case arose in ANDA litigation regarding Quillivant XR®, an extended release methylphenidate (MPH) formulation for the treatment of Attention Deficit Hyperactive Disorder (ADHD). The District Court found the asserted claims of U.S. Patent Nos. 8,465,765 ('765 patent), 8,563,033 ('033 patent), 8,778,390 ('390 patent), 8,956,649 ('649 patent), and 9,040,083 ('083 patent) were invalid as being obvious under 35 U.S.C. § 103. As explained in the opinion, MPH is a widely used psychostimulant that has been used for treating ADHD since the 1950's. Both immediate-release (IR) and extended-release (ER) formulations of the drug were also known in the art, and sustained-release (SR) formulations were developed more recently to overcome drawbacks of both IR and ER formulations. Unfortunately, prior art SR formulations were disadvantageous for having slow onset action properties. The claimed invention was a combination formulation comprising an IR component and an SR component that showed "a 45-minute therapeutic onset and 12 hours of therapeutic effect."
Asserted claim 6 (dependent on claim 1) was at issue in the litigation and is representative:
1. A methylphenidate aqueous extended release oral suspension comprising (1) an immediate release methylphenidate component, (2) a sustained release methylphenidate component comprising a water-insoluble, water-permeable, pH-independent, barrier coated methylphenidate-ion exchange resin complex, and (3) water, wherein said suspension has a pH of about 3.5 to about 5 and said suspension provides a single mean average plasma concentration peak for methylphenidate and a therapeutically effective plasma profile for methylphenidate for about 12 hours.
6. The suspension according to claim 1, wherein the suspension has a pharmacokinetic profile in which the single mean plasma concentration peak for d-methylphenidate has an area under the curve (AUC)0-∞ of about 114 ng-hr/mL to about 180 ng-hr/mL, Cmax of about 11 ng/mL to about 17 ng/mL, Tmax of about 4 hours to about 5.25 hours and T1/2 of about 5 hours to about 7 hours following a single oral administration of an aqueous suspension at a dose equivalent to 60 mg racemic methylphenidate HCl in adults.
The prior art considered by the District Court included several commercially available, extended-release MPH formulations (Concerta®, Daytrana®, Focalin XR®, Metadate CD®, and Ritalin LA®), U.S. Patent Application Publication No. 2010/0260844, and certain scientific publications. The commercial products all exhibited various pharmacokinetic and pharmacodynamics properties regarding a single or multiple PK peak profile, initial onset time and total duration. The '844 patent publication disclosed "a formulation of MPH that provides a rapid onset of action within 1 to 1.5 hours, a single Tmax of 5.5 to 7.5 hours, and a therapeutic duration of about 12 to 14 hours." Actavis relied on the '844 application in combination with Concerta®, Daytrana®, and Metadate CD® as teaching "a single mean peak PK profile, exhibiting an early onset of action, and exhibiting an extended duration of effect" that would have suggested to the skilled worker the early onset and extended duration formulation in the asserted claims. Tris Pharma argued to the contrary that the prior at taught combinations of IR and ER MPH formulations that resulted in a bimodal PK profile. This feature of combined IR and ER MPH formulations was designed to "mimic the peaks and valleys of multiple immediate release dosing regimens" which was not a feature of the claimed invention. In addition, the commercially available formulations showed a later Tmax that was important to achieve the longer duration.
The District Court disagreed (too cryptically, according to the Court's opinion) stating that "'[w]hile [it] believe[d] Tris'[s] evidence regarding the second generation products [wa]s persuasive, it [wa]s not dispositive on the obviousness inquiry.'" The District Court also found that the '844 application taught "an oral form of MPH with a long duration of action, rapid onset, and a single mean peak PK profile" and thus the skilled worker would have been motivated to produce the claimed formulations despite these formulations in the application had not in fact been made. The opinion also notes that the District Court relied on Actavis's expert's testimony regarding how a skilled worker would have interpreted the cited art and the meaning of specific terms and relationships between the features recited in the claims. Finally, the District Court rejected Tris Pharma's assertion of unexpected results, long-felt need, commercial success, and copying. The Court's opinion did not find that Tris Pharma had performed the requisite comparison experiments to show the results were unexpected, and that the existence of some of the commercially available formulations (specifically, Concerta®, Metadate CD®, and Ritalin LA®) rebutted long-felt need based on Tris Pharma's own expert testimony. The District Court also found only modest commercial success and that evidence of copying was "not compelling." This appeal followed.
The Federal Circuit vacated the District Court's decision and remanded, in an opinion by Judge Chen, joined by Judges Newman and O'Malley. The opinion is based on Fed. R. Civ. P. 52(a)(1), which stated that "[i]n an action tried on the facts without a jury or with an advisory jury, the court must find the facts specially and state its conclusions of law separately." Citing Gechter v. Davidson, 116 F.3d 1454, 1457 (Fed. Cir. 1997), the opinion notes that "[w]hen the opinion explaining the decision lacks adequate fact-findings, meaningful review is not possible, frustrating the very purpose of appellate review as well as this court's compliance with its statutory mandate." And fact finding is adequate only when "they are sufficiently comprehensive and pertinent to the issue to form a basis for the decision," citing Medtronic, Inc. v. Daig Corp., 789 F.2d 903, 906 (Fed. Cir. 1986) (quoting Loctite Corp. v. Ultraseal Ltd., 781 F.2d 861, 873 (Fed. Cir. 1985)). These considerations are important in this case because the paucity of the District Court's fact-finding made it impossible for the panel to properly assess the correctness of its legal conclusion of obviousness. Specifically, the panel found it incapable of evaluating Tris Pharma's three arguments on appeal. First, "that a skilled artisan would not have reasonably expected to successfully combine the claimed single mean peak PK profile with the claimed 45-minute onset of action and 12-hour duration of effect (PD characteristics) because the PK-PD relationship was unknown." Second, "that the district court failed to address why the combination of an early Tmax and a 12-hour duration of effect would have been obvious." Third, that "the district court mistakenly disregarded Tris's evidence of unexpected results based on a belief that Tris's experts did not compare the claimed invention to the closest prior art." The panel opinion summarizes these deficiencies as follows:
[T]he district court failed to make the necessary factual findings and provide sufficient analysis of the parties' arguments to permit effective appellate review. Specifically, the district court's opinion merely recites the parties' arguments but fails to explain or identify which arguments it credits or rejects. We thus cannot reach the merits of whether the Quillivant XR® formulation would have been obvious over the prior art. Rather, we identify gaps in the district court's opinion and remand for the district court to conduct further fact-findings and detailed analysis consistent with this opinion.
For example, regarding the obviousness of producing an MPH formulation having the characteristics of a single mean peak profile, 45-minute onset, and 12-hour duration, the Federal Circuit found that the District Court's opinion was devoid of adequate fact finding to support the conclusion that formulations having these properties would have been obvious. For example, although the District Court found that the prior art would provide the skilled worker with an expectation that "a single mean peak PK profile could provide for rapid onset of action and extended duration of effect" it "never articulated which prior art references do so and how." Even when asserting the factual bases for its opinion, the panel stated that "it is unclear if these statements amount to actual fact-findings as opposed to a mere recounting of Actavis's arguments." The panel also found "holes" in the District Court's opinion, for example, "the district court never made explicit findings that Daytrana®, Concerta®, Metadate CD®, and/or the '844 application] also teach a 45-minute onset of action or 12-hour duration of effect." The panel opinion also characterized certain portions of the District Court's opinion as being "vague" and "imprecise[]" regarding "central, disputes issues on appeal."
The Court's opinion also criticized the District Court for not addressing "why a skilled artisan would have been motivated to use a single mean peak PK profile to achieve a formulation with a 45-minute onset of action and/or a 12- hour duration of effect with a reasonable expectation of success," particularly with regard to arguments both parties made on appeal. And:
Without the requisite factual findings and adequate explanation for such findings, we cannot affirm the district court's conclusion that a formulation with (1) a single mean peak PK profile, (2) 45-minute onset of action, and (3) 12-hour duration of effect would have been obvious over the prior art. We thus vacate those portions of the district court's opinion and remand those issues to the district court for specific factual findings [citations omitted].
The Federal Circuit found similar deficiencies in the District Court's opinion regarding issues related to the relationship between "early Tmax and [the] 12-hour duration of effect." The District Court's opinion on these elements was "very cursory," according to the Federal Circuit, and "[t]he entirety of the district court's discussion of Tmax appears amounts to a mere recitation of Actavis's experts' testimony regarding how (1) Tmax does not control the onset or duration of effect and (2) Tmax ranges in the prior art formulations overlap with the claimed Tmax range of 3.6 to 5.78 hours (factoring in the district court's construction of "about")."
Turning to the District Court's treatment of the objective indicia of non-obviousness, the Federal Circuit agreed with Tris Pharma that the District Court did not compare the properties of Tris Pharma's claimed invention with the prior art with regard to whether the invention showed unexpected results. Regarding long-felt but unmet need the Federal Circuit criticized the District Court for finding prior art products each having properties of "(1) a liquid MPH product that does not require swallowing a tablet; (2) a 45-minute onset of action; and (3) 12-hour duration of effect" but did not find a product having all three of these properties.
Based on all these deficiencies the Federal Circuit remanded to the District Court for "further fact-finding." Whether an increased frequency of these types of decisions based on Rule 52(a) in appeals from District Court opinions by a beleaguered Federal Circuit remains to be seen.
Tris Pharma, Inc. v. Actavis Laboratories FL, Inc. (Fed. Cir. 2018)
Nonprecedential disposition
Panel: Circuit Judges Newman, O'Malley, and Chen
Opinion by Circuit Judge Chen
