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

503 F.Supp.3d 183

TRIS PHARMA, INC., Plaintiff,

v.ACTAVIS LABORATORIES FL, INC., Defendant.

Civil Action No. 14-1309-CFC

United States District Court, D. Delaware.

Signed November 30, 2020

Jack B. Blumenfeld, Derek J. Fahnestock, MORRIS, NICHOLS, ARSHT & TUNNELL LLP, Wilmington, Delaware; Errol B. Taylor, MILBANK LLP, New York, New York; Lauren Drake, Monica Arnold, MILBANK LLP, Los Angeles, California, Counsel for Plaintiff.

David A. Bilson, John C. Phillips, Jr., PHILLIPS, MCLAUGHLIN & HALL, P.A., Wilmington, Delaware; Alexandra D. Valenti, Cynthia L. Hardman, Elizabeth J. Holland, Michael B. Cottler, Tiffany Mahmood, William G. James, Goodwin Procter LLP, Counsel for Defendant.

MEMORANDUM OPINION

COLM F. CONNOLLY, UNITED STATES DISTRICT JUDGE

This Hatch-Waxman patent suit filed by Plaintiff Tris Pharma, Inc. against Defendant Actavis Laboratories FL, Inc. comes to me on remand as a result of the Federal Circuit's decision in Tris Pharma, Inc. v. Actavis Labs. FL, Inc. (Tris II ), 755 F. App'x 983 (Fed. Cir. 2019). In Tris II , the Federal Circuit vacated the judgment entered by the now-retired district court judge who originally presided over the case.

Tris alleged at trial that Actavis's generic versions of Quillivant XR®, an extended release liquid formulation of methylphenidate (MPH) for the treatment of Attention Deficit Hyperactive Disorder (ADHD), infringed 21 claims recited in five patents: U.S. Patent 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). Tris Pharma, Inc. v. Actavis Labs. FL, Inc. (Tris I ), 276 F. Supp. 3d 226, 230–31 (D. Del. 2017). Actavis challenged the validity of the asserted claims based on obviousness and obviousness-type double patenting. After a five-day bench trial, the original judge found all the asserted claims to be invalid for obviousness under 35 U.S.C. § 103. The judge did not address infringement or double patenting. See id. at 249 n.2.

Tris appealed the judge's finding of invalidity for seven of the 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." 755 F. App'x at 993. The Federal Circuit "remand[ed] the obviousness analysis to the district court for further fact-finding." Id. It "considered the parties’ other arguments [but] f[ound] them unpersuasive." Id.

After remand, the case was assigned to me and Actavis dropped its obviousness-type double patenting challenge to the asserted claims. Although I had not observed the witnesses at trial, neither party asked for an opportunity to present testimony so that I could make independent credibility determinations. Instead, both parties insisted that I make the "further fact-finding" called for by the Federal Circuit and any fact-finding with respect to infringement issues based on the existing written record. D.I. 180 at 5; D.I. 181 at 5–6; Tr. of Aug. 25, 2020 Hr'g at 7:16–21.

The parties submitted simultaneous post-remand briefs on the fact-finding issues. Tr. of Apr. 10, 2019 Hr'g at 12:1–4. I have reviewed those briefs, the parties’ post-trial briefing, the trial record, and the Pretrial Order. I set forth below my findings of fact and conclusions of law.

I. BACKGROUND

A. Relevant Pharmacological Concepts

Pharmacology, the study of the interactions between a drug and the body, has two broad areas: pharmacokinetics (PK) and pharmacodynamics (PD). PK is sometimes described as the study of what the body does to a drug. It examines the movement of a drug through the body after administration. Thus, it measures, for example, how fast a drug is absorbed, distributed, metabolized, and ultimately excreted from the body. PD, sometimes described as the study of what a drug does to the body, examines the biochemical, physiologic, and molecular effects of a drug on the body. It measures, for example, the onset, duration, and intensity of a drug's effect on the body. Following the parties’ lead, I will often refer to PD characteristics as "clinical effects."

Three PK metrics relevant on remand are C_max, T_max, and PK profile. C_max is the maximum concentration of a drug in the body's blood plasma. T_max is the time after administration when C_max is reached. A drug's PK profile is the graphed depiction of the drug's concentration in the blood plasma over time. Two PD characteristics relevant on remand are duration and onset of effect.

B. MPH, Quillivant XR®, and the Relevant Asserted Claims

The Federal Circuit provided in its opinion this helpful background statement on MPH, Quillivant XR®, and the seven appealed claims which are now before me on remand:

MPH is one of the most widely prescribed psychostimulants and has been used to treat ADHD since the mid-1950s. 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 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.

... The[ ] 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. These properties include: (1) an extended duration of action of about 12 hours; (2) a single mean peak PK profile; (3) a T_max of about 4 to 5.25 hours (early T_max); 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 T_max 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 patent is thus the only asserted claim that recites all four properties.

Tris II , 755 F. App'x at 984.

Three additional points about the asserted claims require mention. First, all the asserted claims teach a "methylphenidate aqueous extended release oral suspension." #765 patent at claim 1 (37:40–41) (claims 6 and 20 ultimately depend from claim 1); #033 patent at claim 1 (37:45–46) (claims 4 and 10 ultimately depend from claim 1); #390 patent at claim 1 (37:54–55) (claims 15, 16 and 20 ultimately depend from claim 1). The parties and the Federal Circuit treated this aqueous oral suspension limitation as requiring a liquid formulation. I will do the same and for ease of reference will at times call it the "liquid formulation limitation." Second, although claims 10 of the #033 patent and 20 of the #765 patent actually recite an onset of "within 45 minutes," for ease of reference I will follow the Federal Circuit's lead and call this limitation at times the "early onset" or "45-minute onset" limitation. Third, the parties stipulated that "about" means "[v]ariability of as much as 10%." D.I. 78 at A-1. Thus, the extended duration-of-effect limitation of "about 12 hours" is met by a 10.8-hour duration of effect; and the T_max range limitation of "about 4 to 5.25 hours" is satisfied by a T_max range of 3.6 to 5.78 hours. For ease of reference, I will at times call these limitations respectively the "12-hour duration" and the "claimed T_max range" limitations.

C. The Federal Circuit's Remand Instructions

As noted, the Federal Circuit "remand[ed] the obviousness analysis to the district court for further fact-finding." Tris II , 755 F. App'x at 993. In addition to this general instruction, the Federal Circuit directed the district court "to resolve [certain] specific fact issues with an explanation to support those findings." Id. at 990. In particular, the Federal Circuit ordered further fact-finding to address whether a liquid MPH formulation with a single mean PK profile, 12-hour duration of effect, and 45-minute onset of action would have been obvious over the prior art. Id. at 991. The court directed that this additional fact-finding specifically include findings about whether certain prior art MPH formulations "teach a 45-minute onset of action and 12-hour duration of effect." Id. at 989. The court also remanded for "further consideration" the obviousness of a liquid MPH formulation with a single mean peak PK profile, 12-hour duration of effect, and a T_max range of 4 to 5.25 hours. Id. at 991–92. And it directed the district court to address whether Tris's evidence adduced at trial established that (1) its claimed invention enjoyed unexpected results and (2) there was a long-felt need for a liquid MPH product that does not require swallowing a tablet and has a 12-hour duration of effect and 45-minute onset of action. Id. at 992.

II. OBVIOUSNESS

A. Legal Standards

Under § 103 of the Patent Act, codified at 35 U.S.C. § 1 et seq. , a patent "may not be obtained ... if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which...