Tris Pharma, Inc. v. Teva Pharm. U.S.

• Decision Date: 06 September 2022
• Docket Number: Civ. 20-05212 (KM)(ESK)
• Parties: TRIS PHARMA, INC., Plaintiff, v. TEVA PHARMACEUTICALS USA, INC., Defendant.
• Court: U.S. District Court — District of New Jersey

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TRIS PHARMA, INC., Plaintiff,
v.
TEVA PHARMACEUTICALS USA, INC., Defendant.

Civ. No. 20-05212 (KM)(ESK)

United States District Court, D. New Jersey

September 6, 2022

OPINION (AMENDED)

KEVIN McNULTY, UNITED STATES DISTRICT JUDGE

This is a Hatch-Waxman action for infringement of five patents: United States Patent No. 9,545,399 (“the '399 patent”), United States Patent No. 9,844,544 (“the '544 patent”), United States Patent No. 9,844,545 (“the '545 patent”), United States Patent No. 11,103,494 (“the '494 patent”), and United States Patent No. 11,103,495 (“the '495 patent”) (collectively, the “asserted patents”).

The action is brought by Tris Pharma Inc. (“Tris”), a pharmaceutical company that holds the asserted patents and sells an embodiment of the patents, a chewable extended-release medication for attention deficit hyperactivity disorder (“ADHD”) called QuilliChew ER® (“QuilliChew”). The defendant is Teva Pharmaceuticals USA, Inc. Teva has filed Abbreviated New Drug Application No. 214202 (“ANDA”), seeking to produce and sell a generic version of QuilliChew. Tris alleges that Teva's proposed generic product would infringe claims 22 and 24 of the '399 patent; claim 37 of the '544 patent; claims 17, 23, 24, and 28 of the '545 patent; claim 28 of the '494 patent; and claim 23 of the '495 patent (collectively the “asserted claims”). Teva asserts that those patent claims are invalid for obviousness or indefiniteness. Assuming the claims are valid, Teva generally denies that its ANDA product would infringe,

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except that it concedes infringement of claim 28 of the '494 patent and claim 23 of the '495 patent. (DE 165 ¶ 125-26.)^[1]

The Court conducted a bench trial on these issues beginning on May 23, 2022 and concluding on May 26, 2022. The parties have submitted post-trial briefing. (DE 197, 199, 201, 204.) This Opinion constitutes the Court's findings of fact and conclusions of law pursuant to Federal Rule of Civil Procedure 52(a). The findings of fact are based on the Court's observations and credibility determinations of the witnesses who testified at trial and a thorough review of all the evidence.

My validity conclusions are as follows:

1) The additional AUC0-3 element of Claim 24 of the '545 patent is invalid for obviousness, but Claim 24 as a whole is valid because it is dependent on claim 1

2) the AUC0-∞ and Cmax elements, insofar as they are incorporated in dependent claims 22 and 24 of the '399 patent, claim 37 of the '544 patent, claims 17, 23, 24 and 28 of the '545 patent, and claim 28 of the '494 patent, are invalid;^[2]

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3) Claim 23 of the '495 patent, which does not include any limitations related to AUC0-3, AUC0-∞, or Cmax, is fully valid

4) Teva's claims of indefiniteness are rejected

On the infringement issue,^[3] I find that Teva's ANDA product infringes all of the asserted claims.^[4]

I. FINDINGS OF FACT

A. Procedural Background

On April 28, 2020, Tris filed a complaint for infringement of the asserted patents based on Teva's ANDA filing, which sought approval to market a generic version of QuilliChew (the “ANDA product”). (DE 1.) The complaint alleged direct infringement as well as induced and contributory infringement of the asserted patents. At trial, however, Tris's arguments focused solely on direct infringement.

Following discovery, a Markman hearing was held on July 13, 2021. (DE 100.) I issued a claim construction opinion on August 25, 2021. (DE 106.) On May 9, 2022, both parties filed motions in limine, which I have held in abeyance and will resolve as necessary in this Opinion.^[5] (DE 153, 155.) On

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May 18, 2022, Judge Kiel issued a final pretrial order (DE 165), and the bench trial began on May 23, 2022. I accepted affidavits in lieu of direct testimony; the bench trial thus consisted of four days of cross and redirect examination of various expert witnesses, and introduction of exhibits. (DE 173, 175, 176, 177.) After the trial concluded, both parties filed opening post-trial briefs on June 27, 2022, and responsive post-trial briefs on July 18, 2022. (DE 197, 199, 201, 204.)

B. ADHD Treatment

ADHD is characterized by a lack of attention, hyperactivity, and impulsivity. It affects millions of children, impairing their ability to perform necessary activities and, vitally, interfering with their performance in school. (PTX-519 ¶ 36-37; DTX-458 ¶ 16.) Counterintuitively, ADHD has long been treated by use of stimulants, most importantly methylphenidate (“MPH”). (PTX-520 ¶ 137; DTX-458 ¶ 17.) Ritalin®, released in 1955, was the first MPH medication. (PTX-520 ¶ 137; DTX-458 ¶ 18.) As originally formulated, Ritalin® and other similar medications were immediate release (“IR”) medications, i.e., the MPH they contained was immediately introduced to the patient's bloodstream. (PTX-520 ¶ 138; DTX-458 ¶ 18.) IR formulations featured a quick onset, but lasted only a few hours, and hence required repeated dosing to maintain symptom relief throughout the day. (PTX-520 ¶ 139-41; DTX-458 ¶ 21.) The need for repeated dosing, particularly at school, had obvious drawbacks, which led to the development of extended release (“ER”) formulations in the 1980s. (DTX-458 ¶ 21-23.)

The first of these ER products, released in 1982, was Ritalin SR®. (PTX-520 ¶ 143.) Ritalin SR® had a flat pharmacokinetic (“PK”) profile with a single mean peak. (Id. ¶ 146.) Ritalin SR®, however, was a commercial failure because it turned out that such a profile generally results in acute tolerance, making the drug less effective than immediate release formulations. (Id. ¶ 147- 50; 157-59.)

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The search for ER formulations continued, however, and resulted in the ER formulations of Concerta®, Metadate CD®, Focalin XR®, and Ritalin LA®, all released between 2000 and 2005. (DTX-458 ¶ 28.) Having learned from the failure of Ritalin SR®, the creators of these new drugs avoided a flat PK profile with a single mean peak, and instead opted for a bimodal^[6] PK profile which became more pronounced over time. (PTX-520 ¶ 162-65, 225; 2T at 324:23-328:18; Tris Pharma, Inc. v. Actavis Lab'ys FL, Inc., No. 2021-1495, 2022 WL 2525318, at *3 (Fed. Cir. July 7, 2022) (upholding a finding that Concerta is bimodal).)

These four ER medications are all designed to be swallowed in pill form. (PTX-520 ¶ 166, 174, 180, 185.) In addition, for three of them (Metadate CD®, Ritalin LA®, and Focalin XR®, but not Concerta®) it is possible to open the capsule and sprinkle its contents on applesauce to avoid the necessity of swallowing a pill, but this approach has its own drawbacks. (PTX-520 ¶ 206- 07; DTX-458 ¶ 57.) In addition, there is Daytrana®, a transdermal patch which delivers MPH to the patient over the course of the day. (PTX-520 ¶ 208-09.) The only ADHD medications available in chewable form were IR formulations such as Methylin Chewable Tablets, which have the same drawbacks as other IR Formulations. (PTX-520 ¶ 140-41; DTX-458 ¶ 58.)

In short, before QuilliChew, the available forms of MPH medications were as follows: There were ER pill formulations designed to be swallowed, and there

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were chewable IR formulations, but there were not any chewable ER formulations.

C. The Asserted Patents and Asserted Claims

Tris alleges that Teva's ANDA product directly infringes nine claims of five separate patents. I review them briefly.

Tris alleges that Teva's ANDA product infringes claims 22 and 24 of the '399 patent, which are both dependent on claim 1 of the '399 patent. Those three claims read as follows:

1. An extended release racemic methylphenidate chewable tablet, wherein said chewable tablet is a uniform solid dispersion comprising: a sustained release racemic methylphenidate component comprising a water-insoluble, water-permeable, pH-independent barrier coated, racemic methylphenidate-cation exchange resin complex in an optional polymeric matrix, wherein said barrier coating is present in an amount of about 20% w/w to about 50% w/w % which provides a sustained release profile to the racemic methylphenidate and is over the racemic methylphenidate-cation exchange resin complex-optional matrix, and wherein when present the polymeric matrix comprises the methylphenidate-cation exchange resin complex and a water-insoluble polymer or copolymer or a water-soluble polymer or copolymer; and at least one immediate release racemic methylphenidate component which provides a release in less than about 30 minutes as determined in an in vitro dissolution assay; wherein about 50% w/w to about 90% w/w of the racemic methylphenidate active component is provided by the sustained release component based on the total amount of racemic methylphenidate in the tablet; wherein said chewable tablet is capable of being divided and providing tablet portions which retain a therapeutically effective extended release profile, and a pharmacokinetic profile in which the methylphenidate has at least one of: a geometric mean for area under the curve (AUC)0-∞ of about 110 ng-hr/mL to about 140 ng-hr/mL or a geometric mean Cmax of about 10 ng/mL to about 15 ng/mL, under fasted and fed conditions in adults following a single oral administration of a chewable tablet which comprises the equivalent of 40 mg racemic methylphenidate HCl.

22. The extended release racemic methylphenidate chewable tablet according to claim 1, wherein the chewable tablet has a pharmacokinetic profile for racemic methylphenidate comprising a single mean plasma concentration peak.

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24. The extended release racemic methylphenidate chewable tablet according to claim 1, wherein the methylphenidate plasma concentration, as determined under fasted and fed conditions following a single oral administration of said chewable tablet at a dose equivalent to 40 mg racemic methylphenidate HCl in adults, is equivalent to the plasma concentration curve of FIG. 1 from about 0

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