NOTE: This disposition is nonprecedential.

 

United States Court of Appeals 

for the Federal Circuit ______________________ 

TRIS PHARMA, INC.,

Plaintiff-Appellant

v.

ACTAVIS LABORATORIES FL, INC.,

Defendant-Appellee

______________________ 

2017-2557, 2017-2559, 2017-2560

______________________ 

Appeals from the United States District Court for the 

District of Delaware in Nos. 1:14-cv-01309-GMS, 1:15-cv00393-GMS, 1:15-cv-00969-GMS, Judge Gregory M. Sleet.

______________________ 

Decided: November 20, 2018

______________________ 

ERROL TAYLOR, Milbank, Tweed, Hadley & McCloy, 

LLP, New York, NY, argued for plaintiff-appellant. Also 

represented by ANNA BROOK, JORDAN P. MARKHAM,

FREDERICK ZULLOW. 

 WILLIAM M. JAY, Goodwin Procter LLP, Washington, 

DC, argued for defendant-appellee. Also represented by 

BRIAN TIMOTHY BURGESS, WILLIAM G. JAMES, II; DAVID 

ZIMMER, Boston, MA; ELIZABETH HOLLAND, LINNEA P.

CIPRIANO, MICHAEL B. COTTLER, CYNTHIA LAMBERT 
2 TRIS PHARMA, INC. v. ACTAVIS LABORATORIES FL, INC. 

HARDMAN, TIFFANY MAHMOOD, ALEXANDRA D. VALENTI, 

New York, NY. 

 ______________________ 

Before NEWMAN, O’MALLEY, and CHEN, Circuit Judges.

CHEN, Circuit Judge.

Tris Pharma, Inc. (Tris) holds the approved New Drug 

Application for Quillivant XR®, an extended release 

methylphenidate (MPH) formulation for the treatment of 

Attention Deficit Hyperactive Disorder (ADHD). When 

Actavis Laboratories, Inc. (Actavis) submitted an Abbreviated New Drug Application (ANDA) to the U.S. Food & 

Drug Administration (FDA) seeking approval to market 

generic versions of Quillivant XR®, Tris sued Actavis for 

infringement 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). After a five-day 

bench trial, the district court found all asserted claims of 

the patents-in-suit invalid under 35 U.S.C. § 103. Tris 

appealed. Because the district court’s conclusions of law 

are based on inadequate fact-findings, we vacate and 

remand. 

BACKGROUND

MPH is one of the most widely prescribed psychostimulants and has been used to treat ADHD since the mid1950s. Early formulations of MPH were immediate 

release (IR) forms of the drug that exhibited clinical 

benefits within 20 to 60 minutes after dosing and whose 

effects lasted 2–4 hours. IR forms of MPH, however, had 

drawbacks because they had to be administered multiple 

times a day, making it challenging for patients to adhere 

to the dosing schedule. Sustained release (SR) formulations of MPH were thus developed and available in the 

early 1980s for greater dosing convenience and patient 

compliance. But those first-generation SR formulations 

had their own shortcoming: a slow onset of action. Tris’s 
TRIS PHARMA, INC. v. ACTAVIS LABORATORIES FL, INC. 3

Quillivant XR® is an extended release formulation of MPH 

comprising an IR component and a SR component. It is a

formulation that achieves a 45-minute therapeutic onset 

and 12 hours of therapeutic effect. 

Actavis challenged the validity of twenty-one claims 

from five patents at the district court, which found all 

these claims invalid under 35 U.S.C. § 103. On appeal, 

Tris requests that we reverse the district court’s judgment 

for seven claims in three patents: ’765, ’033, and ’390 

patents. These seven appealed claims are: 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. All of the

appealed claims are directed to pharmacokinetic (PK) and 

pharmacodynamic (PD) properties of the Quillivant XR®

extended release formulation.1 These properties include: 

(1) an extended duration of action of about 12 hours; (2) a 

single mean peak PK profile; (3) a Tmax of about 4 to 5.25 

hours (early Tmax); and (4) a 45-minute onset of action/therapeutic effects. All of the claims on appeal recite, 

among other properties, a single mean peak PK profile 

and 12-hour duration of effect limitation. All of the 

claims except for claim 20 of the ’765 patent recite the 

early Tmax limitation, and claim 10 of the ’033 patent and 

claim 20 of the ’765 patent are the only two claims that 

require a 45-minute onset of action. Claim 10 of the ’033 

 

1 Pharmacokinetics is the study of what a person’s 

body does to a drug after administration. PK values are 

measurements of a drug’s behavior in a patient’s blood 

plasma. One such value relevant for this appeal, Tmax, 

represents the time after administration when the maximum concentration of the drug in the blood plasma (Cmax) 

occurs. The shape of the PK profile, which reflects the 

plasma concentration of the drug in the patient’s body 

over time, is also an issue in dispute in this case. 
4 TRIS PHARMA, INC. v. ACTAVIS LABORATORIES FL, INC. 

patent is thus the only asserted claim that recites all four 

properties.

A. Prior Art

The district court found that the various combinations 

of the PK characteristics (single mean peak and early 

Tmax) and PD characteristics (a 45-minute onset of action 

and a 12-hour duration of effect) claimed in the patentsin-suit would have been obvious over the prior art. The 

prior art consists of a number of commercially available, 

second-generation, extended release formulations of MPH 

including Concerta®, Daytrana®, Focalin XR®, Metadate 

CD®, and Ritalin LA®;2 scientific articles; and U.S. Patent 

Application Publication No. 2010/0260844 (Scicinski). 

Below, we briefly describe the prior art relevant to this 

appeal. 

Concerta® is an extended release MPH tablet with a 

12-hour duration of effect. J.A. 18, 23. The parties dispute whether or not Concerta® exhibits the single mean 

peak PK profile limitation because its plasma concentration profile exhibits a sharp initial increase followed by a 

second increase. J.A. 19, 25. The parties also dispute 

whether Concerta® exhibits a 45-minute onset of action. 

Tris’s expert testified that the clinical efficacy study he 

performed showed that Concerta® has a 2-hour onset of 

action, J.A. 2213–14, while Actavis’s expert testified that 

second-generation products like Concerta® generally have

an onset of action between 30 minutes to 2 hours. J.A. 

 

2 The district court also listed Methylin ER as a 

commercially available controlled-release formulation. 

J.A. 16. Confusingly, it later presented PK data for 

Methylin Oral Solution. J.A. 22. We decline to discuss 

the Methylin prior art reference because it is unclear on 

which version the district court is relied. 
TRIS PHARMA, INC. v. ACTAVIS LABORATORIES FL, INC. 5

2069. Concerta® has a later Tmax of around 6.8 ± 1.8 

hours. J.A. 2098. 

Daytrana® is an MPH patch that exhibits a single 

mean peak PK profile and a 12-hour duration of effect. 

J.A. 2215, 2069. However, Daytrana® has a 2-hour onset

of action, and the record as to its Tmax is unclear. J.A. 

2069. 

Focalin XR® is an extended release MPH capsule. 

While it achieves the claimed 12-hour duration of effect, 

JA 2069, and 45-minute onset of action, J.A. 3923, its PK

profile does not exhibit a single mean peak, and it exhibits a later Tmax around 6.5 hours. J.A. 2080, 2214–15, 

2297. Moreover, Tris notes that Focalin XR® only consists 

of a single enantiomer d-MPH as the active ingredient 

whereas Quillivant XR® and the appealed claims include

both enantiomers. 

Metadate CD® is a capsule version of MPH. J.A. 19. 

While it has an early Tmax of about 4.5 hours, J.A. 2297,

and a 45-minute onset of action, J.A. 2069, the parties 

disagree as to whether its PK profile exhibits a single 

mean peak and whether it has a 12-hour duration of 

effect. J.A. 22–23. Like Concerta®, Metadate CD®’s PK 

profile exhibits a sharp initial increase followed by a 

second increase in MPH levels at a later time. J.A. 19. 

As for its duration of effect, Tris presented testimony that 

Metadate CD®’s effects only last 6 to 8 hours. J.A. 2069, 

2204. 

Ritalin LA® is a capsule version of MPH. J.A. 21. Ritalin LA® exhibits an early Tmax at 5.5 hours and an early 

onset of action. J.A. 2069, 2099. Its PK profile exhibits 

two peaks (bimodal), J.A. 2615, and it only has 6–8 hours 

of effect. J.A. 2069. 

Scincinski describes a formulation of MPH that provides a rapid onset of action within 1 to 1.5 hours, a single 
6 TRIS PHARMA, INC. v. ACTAVIS LABORATORIES FL, INC. 

Tmax of 5.5 to 7.5 hours, and a therapeutic duration of 

about 12 to 14 hours. J.A. 3644. 

B. District Court Opinion

Actavis characterized Scincinski as well as the Daytrana®, Concerta®, and Metadate CD® formulations as all 

disclosing a single mean peak PK profile, exhibiting an

early onset of action, and exhibiting an extended duration 

of effect. This, Actavis argued, would have suggested to a 

skilled artisan that a single mean peak PK profile could 

provide the claimed early onset of action and extended 

duration of effect. Tris disagreed for two primary reasons. 

First, the prior art formulations were developed using 

two components: IR and ER formulations of MPH. These

two components together in a formulation typically resulted in two peaks, or a bimodal profile, with the first 

peak resulting from the IR component of the formulation 

and the second from the ER component. Further, Tris 

asserted that this bimodal profile was important to counteract “acute tolerance” or “tachyphylaxis.” Acute tolerance is the theory that as the day progresses, higher

levels of the drug in the blood are required to produce the 

same therapeutic effects. Thus, in order to achieve sustained effects, the formulations in the prior art, according 

to Tris, were designed to mimic the peaks and valleys of 

multiple immediate release dosing regimens—one peak 

for the IR formulation and a second peak for the ER 

formulation. 

Second, Tris argued that prior art formulations of 

MPH have a late Tmax to achieve the sustained duration of 

action. To support this position, Tris pointed to Metadate 

CD® and Ritalin LA®, both of which have an early Tmax

but a shorter duration of action of around 6 to 8 hours. 

Concerta®, on the other hand, achieves the 12-hour duration of effect but has a later Tmax that is outside the 

claimed range of about 4 to 5.25. 
TRIS PHARMA, INC. v. ACTAVIS LABORATORIES FL, INC. 7

The district court stated 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.” J.A. 39. Rather, the district court found 

that Daytrana® clearly exhibits a single mean peak PK 

profile, and thus Actavis had demonstrated that a prior 

art reference taught this particular claim limitation. 

Importantly, the district court found that Scicinski 

describes an oral form of MPH with a long duration of 

action, rapid onset, and a single mean peak PK profile. 

The district court reasoned that a skilled artisan would 

have undoubtedly looked to Scicinski when formulating 

an extended release MPH drug because Scicinski’s purpose of a fast onset, long-lasting MPH formulation aligned 

with what the parties agreed a skilled artisan would have 

been motivated to achieve. The district court acknowledged that Scicinski describes a hypothetical product but 

declined to discount Scicinski simply because it contains a 

prophetic example. The district court also credited Actavis’s expert’s testimony that skilled artisans would have 

used the known technique of deconvolution to achieve a 

product that meets the target PK profile like that described in Scicinski: 

Q: Now, once a person of ordinary skill in the art 

has decided on a target PK profile, at a very general level, what are the next steps towards making a product? 

A: Okay. The next steps would be to take this 

pharmacokinetic profile, this plasma profile and, 

utilizing certain mathematical techniques that are 

known as deconvolution, separate out the profile 

into its elimination characteristics and its absorption characteristics, and once you define then 

simply the absorption characteristics of that 

product, then you can design a product that has 

dissolution characteristics that could match then 
8 TRIS PHARMA, INC. v. ACTAVIS LABORATORIES FL, INC. 

the absorption characteristics that you get by doing this deconvolution technique.

J.A. 40 (citing J.A. 2095). 

Further, the district court appeared to credit Actavis’s 

expert’s testimony regarding the relationship between 

Tmax and duration of effect. Actavis’s expert testified that 

a skilled artisan would not have targeted a specific Tmax

because that parameter does not control the onset or 

duration of the drug. He noted, moreover, that the 

claimed Tmax ranges in the prior art of 4.4 to 7 hours 

overlapped with the claimed range of 3.6 to 5.78 hours, 

taking into account the court’s construction of “about.” 

The district court then addressed Tris’s expert’s testimony that a skilled artisan would not have expected a 

formulation with a single mean peak PK profile to achieve 

both early onset and extended duration of action. Because Tris’s expert testified that he would defer to a 

formulator in terms of what sort of PK curve could be 

achieved, the district court found Actavis’s formulator’s

expert testimony that a skilled artisan would have no 

trouble achieving early onset of action and extended 

duration of effect with a single mean peak PK profile 

persuasive. The district court ultimately found that 

“Tris’[s] nonobvious[ness] argument hinges primarily on 

the [single peak] plasma profile and fails to sufficiently 

weigh the pharmacokinetic details that would have been 

known to skilled artisans or the prior art teachings that 

disclosed how to optimize an MPH product.” J.A. 42. 

The district court then examined objective indicia of 

nonobviousness, including unexpected results, long-felt 

need, commercial success, and copying. As to unexpected 

results, the district court held that Tris failed to demonstrate that the Quillivant XR® formulation exhibited some 

superior property or advantage that a skilled artisan 

would have found surprising or unexpected. J.A. 45 

(citing Procter & Gamble Co. v. Teva Pharm. USA, Inc., 
TRIS PHARMA, INC. v. ACTAVIS LABORATORIES FL, INC. 9

566 F.3d 989, 997 (Fed. Cir. 2009)). Tris argued that its 

formulation unexpectedly provided (1) a 45-minute onset

of action and a 12-hour duration of effect with a single 

mean peak PK profile and (2) a 12-hour duration of effect 

with an early Tmax of about 4 to 5.25 hours. The district 

court found these arguments irrelevant because Tris had 

not performed the proper comparison to the closest prior 

art. Id. (citing Kao Corp. v. Unilever U.S. Inc., 441 F.3d 

963, 970 (Fed. Cir. 2006)). And even considering Tris’s 

unexpected results argument, the district court observed 

that the prior art would have led a skilled artisan to 

expect that a single peak PK profile could provide for 

rapid onset and extended duration of action. Thus, the 

district court concluded that Quillivant XR®’s 12-hour 

duration of effect and single mean peak PK profile was 

not unexpected. 

Regarding long-felt need, the district court found that 

the claimed Quillivant XR® formulation did not serve a 

long-felt but unmet need. The district court pointed to 

Tris’s own expert testimony that Metadate CD®, Ritalin 

LA®, and Concerta® had already achieved the goal of once 

daily dosing. Additionally, Tris’s expert also testified that 

some second-generation MPH formulations could have an 

onset of action in as early as 30 minutes. J.A. 2069. And 

while Tris’s expert testified that there was a long-felt 

need for a drug for children who had trouble swallowing 

pills that the Daytrana® patch did not meet due to skin 

irritation issues, J.A. 2272, the district court found that 

his own writings undermined this contention. J.A. 47 

(“This contention is undermined by Dr. McGough’s own 

writings where in the book he authored entitled ‘ADHD,’ 

the doctor writes that Daytrana is a product that is ‘particularly useful when swallowing is difficult.’”). 

As to commercial success, the district court found that 

Tris’s evidence only showed a modest level of commercial 

success. Finally, the district court found that evidence of 

copying was not compelling. 
10 TRIS PHARMA, INC. v. ACTAVIS LABORATORIES FL, INC. 

Accordingly, the district court found all of Tris’s asserted claims invalid for being obvious over the prior art. 

Tris appealed. We have jurisdiction pursuant to pursuant 

to 28 U.S.C. § 1295(a)(1).

DISCUSSION

“Obviousness is a question of law based on underlying 

findings of fact.” Perfect Web Techs., Inc. v. InfoUSA, Inc., 

587 F.3d 1324, 1327 (Fed. Cir. 2009) (citing In re Kubin, 

561 F.3d 1351, 1355 (Fed. Cir. 2009)). We review the 

district court’s conclusions of law de novo. Eli Lilly & Co. 

v. Teva Parenteral Meds., Inc., 845 F.3d 1357, 1372 (Fed. 

Cir. 2017). And we review the district court’s factual 

findings for clear error. Par Pharm. Inc. v. TWI Pharm., 

Inc., 773 F.3d 1186, 1194–95 (Fed. Cir. 2014). 

Under Fed. R. Civ. P. 52(a)(1), “[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.” Rule 52(a) lays out the separate and 

distinct roles of the trial and the appellate court. 

“[F]actfinding is the basic responsibility of district courts, 

rather than appellate courts. Pullman-Standard v. 

Swint, 456 U.S. 273, 291–92 (1982) (citing DeMarco v. 

United States, 415 U.S. 449, 450 n.* (1974)). A court of 

appeals should not resolve in the first instance a factual 

dispute which has not been considered by the district 

court. See id. “When 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.” Gechter v. Davidson, 116 F.3d 1454, 1457 (Fed. 

Cir. 1997) (citation omitted). Findings of fact are adequate when “they are sufficiently comprehensive and 

pertinent to the issue to form a basis for the decision.” 

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)). Although Rule 52(a)(1) does 
TRIS PHARMA, INC. v. ACTAVIS LABORATORIES FL, INC. 11

not require detailed factual findings on every issue raised, 

it does require findings on “as many of the subsidiary 

facts as are necessary to disclose to the appellate court 

the steps by which the trial court determined factual 

issues and reached its ultimate conclusions.” Atlantic 

Thermoplastics Co., Inc. v. Faytex Corp., 5 F.3d 1477, 

1479 (Fed. Cir. 1993). 

Tris raises three primary issues on appeal. First, Tris 

argues 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.3 Second, 

 

3 On appeal, Tris cites In re Cyclobenzaprine Hydrochloride Extended-Release Capsule Patent Litigation, 

as being on all fours with this case. 676 F.3d 1063 (Fed. 

Cir. 2012). In Cyclobenzaprine, we reversed the district 

court’s judgment of obviousness, holding that its “failure 

to appreciate the lack of a known PK/PD relationship for 

any formulation of cyclobenzaprine rendered deficient its 

analysis of the evidence . . . and its analysis of the implications of that evidence on its legal conclusions of obviousness.” Id. at 1071. However, in Cyclobenzaprine, no 

extended release formulation of the drug was present in 

the prior art, and we found that without a known PK/PD 

relationship, “immediate-release PK values are of little 

use in calculating extended-release values, because there 

is no proof that a skilled artisan would expect the extended release values to produce a therapeutic effect solely 

because they are drawn from immediate-release values.” 

Id. The present case is different because the prior art 

disclosed numerous existing extended-release formulations, some with one or a combination of single mean peak 

PK profile, extended duration, early onset, and early Tmax. 
12 TRIS PHARMA, INC. v. ACTAVIS LABORATORIES FL, INC. 

Tris contends 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, Tris claims 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. Rather, Tris compared the Quillivant XR® formulation with the commercially available prior art formulations identified by the parties. 

As we explain below, the 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 factfindings and detailed analysis consistent with this opinion. 

A. Single Mean Peak PK Profile, 45-Minute Onset, and 

12-Hour Duration of Effect

Claim 10 of the ’033 patent and claim 20 of the ’765 

patent require a liquid MPH formulation with (1) a single 

mean peak PK profile, (2) a 45-minute onset of action, and 

(3) a 12-hour duration of effect. ’033 patent col. 38 ll. 34–

35; ’765 patent col. 39 ll. 16–17. The district court held

that a skilled artisan would have found it obvious to use a 

formulation with a single mean peak PK profile to achieve 

a 45-minute onset of action and a 12-hour duration of 

 

Cyclobenzaprine is thus, factually distinguishable from 

this case. 
TRIS PHARMA, INC. v. ACTAVIS LABORATORIES FL, INC. 13

effect. But the district court failed to make adequate 

findings of fact to support this holding. 

First, while the district court found that one would 

have expected from the prior art that a single mean peak 

PK profile could provide for rapid onset of action and 

extended duration of effect, J.A. 46, it never articulated 

which prior art references do so and how. The district 

court’s only clear finding on this point was its statement 

that formulations in the prior art such as Daytrana®

exhibit a single mean peak PK profile. J.A. 37. The 

district court also recited Actavis’s expert’s testimony that 

Concerta® and Metadate CD® also have a single mean 

peak PK profile, despite having a slight initial peak or 

shoulder in their plasma concentration profiles followed 

by a larger single peak, and that Scicinski also teaches a 

single mean peak PK profile. J.A. 37, 41. 

But it is unclear if these statements amount to actual 

fact-findings as opposed to a mere recounting of Actavis’s 

arguments. Even if we were to interpret these statements 

as findings of fact, there are still holes in the district 

court’s analysis. For instance, the district court never 

made explicit findings that Daytrana®, Concerta®, Metadate CD®, and/or Scicinski also teach a 45-minute onset of 

action or 12-hour duration of effect. And with respect to 

the 45-minute onset of action limitation, the district court 

cited a concession by Tris’s expert that second-generation 

MPH formulations could have an onset of action in as 

early as 30 minutes, but it did not explain the significance 

of this concession.4 J.A. 47. And the district court did not 

 

4 Actavis argues that the Biederman article, a prior 

art reference relied upon by Tris’s expert, describes Concerta® as having an onset of action in as early as 30 

minutes and a 12-hour duration of effect. J.A. 3446 

(Biederman, J. “New-Generation Long-Acting Stimulants 
14 TRIS PHARMA, INC. v. ACTAVIS LABORATORIES FL, INC. 

specifically identify which second-generation products 

have an onset of action around 30 minutes or state 

whether it believed that all second-generation MPH 

products, except Daytrana®, had this onset of action time. 

As for the 12-hour duration of effect limitation, the district court’s opinion is vague as to whether any of the 

prior art formulations actually teach the 12-hour duration 

of effect limitation. Throughout its analysis, the district 

court imprecisely states that certain prior art discloses 

“efficacy that last[s] throughout the day,” a “long duration 

of effect,” or an “extended duration of action.” See e.g., 

J.A. 16, 36, 46. It is unclear, however, whether the district court intended this language to equate to the claimed 

12-hour duration of effect. We identify these issues 

because whether a particular prior art formulation 

achieves a 45-minute onset of action and/or a 12-hour 

duration of effect are central, disputed issues on appeal. 

And it is the role of the district court to resolve these 

specific fact issues with an explanation to support those 

findings. 

Second, and importantly, the district court does not 

address a fundamental aspect of the obviousness in-

 

for the Treatment of Attention-Deficit/Hyperactivity 

Disorder,” Medscape Psychiatry 8(2) (Nov. 2003)). However, the district court never cited this passage in its 

opinion. Also, the record is unclear as to whether Scicinski actually teaches the 45-minute onset of action limitation. Scicinski reports that its formulation would be 

effective “within about 1 to 1.5 hours post administration.” ’844 application ¶ 0016. While Actavis’s expert 

testified that a skilled artisan would have viewed this 

disclosure as consistent with a 45-minute onset, the 

district court never directly made this fact-finding. J.A. 

2102. 
TRIS PHARMA, INC. v. ACTAVIS LABORATORIES FL, INC. 15

quiry—i.e. 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.5 Tris argued below and to us on appeal that the 

acute tolerance theory as well as the prior art taught 

away from using a single mean peak PK profile to achieve 

a 45-minute onset and a 12-hour duration of effect. 

According to Tris, the prior art extended release products 

with a single mean peak PK profile do not achieve either 

a 45-minute onset of action, a 12-hour duration of effect, 

or both. Tris argues that this is due to the acute tolerance 

theory, which postulates that the plasma concentration of 

a drug must be higher in a patient as the day progresses 

to achieve therapeutic efficacy, and therefore a bimodal

(two-peak) plasma concentration curve is required. On 

appeal, Actavis argues that the acute tolerance theory is 

irrelevant to whether a drug has a single or bimodal peak 

PK profile, attempts to discredit the theory, and asserts 

that skilled artisans did not regard the number of peaks 

as important when formulating a drug. But the district 

court made none of these findings below. Other than 

explaining what the acute tolerance theory is, J.A. 38 n.8, 

 

5 We understand that one of Actavis’s arguments on 

appeal is that Quillivant XR®’s single mean peak PK 

profile and early Tmax range are incidental properties of 

the formulation. That is, these PK limitations played no 

role in Quillivant XR®’s development. The PK characteristics are specifically claimed in the patents-in-suit, 

however, and Actavis has not suggested that these limitations are not entitled to patentable weight. Thus, Actavis 

needs to demonstrate that a skilled artisan would have 

been motivated to create a liquid formulation of MPH 

with these claimed PK characteristics and specific PD 

properties.
16 TRIS PHARMA, INC. v. ACTAVIS LABORATORIES FL, INC. 

and reciting Tris’s expert testimony explaining why acute 

tolerance was one of the reasons a first-generation MPH 

formulation like Ritalin-SR® could not achieve the desired 

clinical effects of a fast onset and extended duration, J.A. 

38, the district court did not address the acute tolerance 

theory. It is thus unclear whether the district court found

that (1) the theory is not applicable because it does not 

affect the shape of the plasma concentration curve; (2) the 

theory is unreliable; or (3) the theory is applicable, but 

even acknowledging it, a skilled artisan would have a 

reasonable expectation of success to combine a single 

mean peak curve with a 45-minute onset of action and a 

12-hour duration of effect. And we decline to guess at 

what the district court meant. 

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. See Golden Blount, Inc. v. Robert H. 

Peterson Co., 365 F.3d 1054, 1061 (Fed. Cir. 2004) (“Because the district court’s sparse opinion provides this 

court with only bald conclusions for review, we conclude 

that the district court’s judgment . . . is insufficient under 

Rule 52(a). We thus vacate those portions of the district 

court’s opinion and remand those issues to the district 

court for specific factual findings.”); see also Atlantic 

Thermoplastics Co., 5 F.3d at 1479 (finding the court’s 

opinion too conclusory and sparse to provide a factual 

basis for determining whether the invention was on sale 

within the meaning of 35 U.S.C. § 102(b)). Accordingly, 

we remand this issue to the district court for further factfinding. 

B. Early Tmax and 12-Hour Duration of Effect

Claims 4 and 10 of the ’033 patent; claim 6 of the ’765 

patent; and claims 15, 16, and 20 of the ’390 patent recite 
TRIS PHARMA, INC. v. ACTAVIS LABORATORIES FL, INC. 17

a liquid formulation of MPH with a single Tmax of about 4 

to 5.25 hours and a 12-hour duration of effect. ’033 patent 

col. 38 ll. 3–5, 34–35; ’765 patent col. 38 ll. 4–13; ’390 at 

col. 39 ll. 3–11, 27–29. On appeal, Tris argues that the 

district court never provided its assessment of the obviousness of a MPH formulation with both an early Tmax

and 12-hour duration of effect. We agree. 

The district court’s analysis with respect to Tmax is 

very cursory. The 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”). J.A. 41. And, yet 

again, the district court fails to articulate whether it 

credited this testimony or explain why and how the 

testimony supports its conclusion. Even if we were to 

assume that these statements were actual findings of fact, 

the district court’s analysis still fails to explain why a 

skilled artisan would have reasonably expected to achieve 

a formulation with the claimed 12-hour duration of effect 

and an early Tmax. 

The district court’s opinion lacks any response to 

Tris’s argument that formulations with an early Tmax

(such as Metadate CD® and Ritalin LA®) did not achieve 

12 hours of effect while those with 12 hours of effect 

(Concerta® and Focalin XR®) had later Tmax values. Tris’s 

expert explained that this was because oral formulations 

only contain a certain amount of any drug; if the formulation releases a substantial amount of the drug to obtain 

an early Tmax, then the formulation would not be expected 

to achieve extended effects for the whole day. J.A. 2204. 

While Actavis’s expert responded to this in his testimony, 

J.A. 2101, the district court opinion does not discuss or 

cite Tris’s testimony. 
18 TRIS PHARMA, INC. v. ACTAVIS LABORATORIES FL, INC. 

As with the single mean peak PK profile, 45-minute 

onset of action, and 12-hour duration of effect combination 

of limitations, we also remand the obviousness of the 

combination of an early Tmax with a 12-hour duration of 

effect to the district court for further consideration. 

C. Objective Indicia of Nonobviousness

Tris argues on appeal that the district court incorrectly rejected Tris’s experts’ testimony on unexpected results 

because they purportedly failed to compare the Quillivant 

XR® formulation with the closest prior art. We agree. 

Tris’s experts compared the Quillivant XR® formulation to 

all prior art products whose PK and PD values were cited 

by Actavis or known to Tris. J.A. 2708–13. While Kao

stands for the proposition that “when unexpected results 

are used as evidence of nonobviousness, the results must 

be shown to be unexpected compared with the closest 

prior art,” we do not read Kao so rigidly as to require Tris

to identify and focus on just one prior art product when 

multiple, similar extended release formulations of MPH 

existed or were described in the prior art. 441 F.3d at 

970. Because the patents-in-suit claim multiple PK and 

PD characteristics, different prior art references are 

closer on different PK and PD characteristics, and none of 

the parties asserted that one of the references or products 

represented the closest art. Under the circumstances 

here, the district court should have considered Tris’s 

evidence that its claimed invention enjoyed unexpected 

properties compared to the known, extended release 

formulations. 

Moreover, even though the district court went on to 

consider the merits of Tris’s unexpected results argument, 

the district court’s analysis is deficient because it, at best, 

only addresses the single mean peak PK limitation. J.A. 

46. The district court does not explain why—separately, 

and more importantly together with the single mean peak 

PK profile limitation—the Tmax, 45-minute onset, and 12-
TRIS PHARMA, INC. v. ACTAVIS LABORATORIES FL, INC. 19

hour duration of effect limitations were not unexpected. 

Thus, we remand the issue of unexpected results to the 

district court for further analysis. 

Additionally, Tris also argues that the district court 

incorrectly rejected its evidence of long-felt need based on 

second-generation products that lack one or more of the 

long-felt needs Tris identified. Below, Tris argued that 

there was a long-felt need for a product having several 

desired properties: (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. None of the 

prior art products, Tris contends, satisfied this alleged 

long-felt need because none of them possess all three of 

these properties. 

In rejecting Tris’s long-felt need argument, the district court opinion identified various prior art products 

that meet each of the three individual needs above, but 

never identified a prior art product that contains all three 

properties. For instance, Daytrana® can be administered 

to individuals without requiring them to swallow a pill; 

Metadate CD®, Ritalin LA®, and Concerta® are administered once daily. J.A. 44. The district court also found 

that second generation prior art products generally have 

an onset of action of as early as 30 minutes. Id. But 

finding each of the properties in separate prior art products does not adequately address Tris’s specific theory as 

to a long-felt need for all three desired properties to be 

contained a single product. Actavis contends that any 

differences in onset, duration, and formulation between 

Quillivant XR® and particular prior art products were too 

insignificant to establish any unsolved long-felt need, but 

the district court did not make such a finding for us to 

review. Accordingly, we remand the long-felt need issue 

to the district court for further consideration.
20 TRIS PHARMA, INC. v. ACTAVIS LABORATORIES FL, INC. 

In view of the errors we identified above, we invite the 

district court to reconsider all the evidence of objective 

indicia in its overall determination of obviousness. 

CONCLUSION

Because district court’s obviousness decision lacks the 

requisite fact-finding, and because the district court erred 

in rejecting Tris’s evidence of objective indicia of nonobviousness, we remand the obviousness analysis to the 

district court for further fact-finding. We have considered 

the parties’ other arguments and find them unpersuasive. 

VACATED AND REMANDED

COSTS

No Costs.