Orexo AB v. Sun Pharm. Indus.

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OREXO AB and OREXO US, INC., Plaintiffs/Counterclaim Defendants, v. SUN PHARMACEUTICAL INDUSTRIES LIMITED, SUN PHARMA GLOBAL FZE, SUN PHARMA GLOBAL, INC., and SUN PHARMACEUTICAL INDUSTRIES, INC., Defendants/Counterclaim Plaintiffs.

Civil Action No. 3:20-cv-12588 (GC) (DEA)

United States District Court, D. New Jersey

July 12, 2023

NOT FOR PUBLICATION

OPINION

GEORGETTE CASTNER, UNITED STATES DISTRICT JUDGE.

THIS MATTER comes before the Court upon a Complaint for patent infringement brought by Plaintiffs Orexo AB and Orexo US, Inc. (collectively, “Orexo” or “Plaintiffs”) against Defendants Sun Pharmaceutical Industries Limited, Sun Pharma Global FZE, Sun Pharma Global, Inc., and Sun Pharmaceutical Industries, Inc. (collectively, “Sun” or “Defendants”) arising from Sun's filing of Abbreviated New Drug Application (“Sun's ANDA”) No. 214737 with the United States Food and Drug Administration (“FDA”) seeking approval to commercially market a generic version of Orexo's Zubsolv®, a drug approved for the treatment of opioid dependence. (See generally ECF No. 1.) Zubsolv®, is covered by U.S Patent Nos. 9,439,900 (“the '900 patent”) and 11,020,387 (“the '387 patent”), which, among other patents, are listed for Zubsolv®, in the FDA's publication, Approved Drug Products with Therapeutic Equivalence Evaluations (the “Orange Book”). (See, e.g., ECF No. 341 ¶¶ 28, 40.) The '900 and '387 patents are asserted in this case (the “asserted patents”). (ECF No 352.) U.S. Patent No. 8,940,330 (“the '330 patent”) is in the same family as the asserted patents, and all three patents share substantially the same specification. (Davies Tr. 453:17-21.)

Before the Court are the issues of infringement and validity of the asserted patents, including Orexo's two oral motions under Federal Rule of Civil Procedure (“Rule”) 52(c) on both the invalidity and infringement issues. (Tr. 964:16-21, 1094:19-24). Specifically, Orexo asserts the following claims: claims 2 and 16 of the '900 patent; and claims 6 and 13 of the '387 patent (collectively, the “asserted claims”). (ECF No. 341 ¶¶ 29, 41; see also ECF No. 351 at 1-2.) This Opinion constitutes the Court's findings of fact and conclusions of law pursuant to Rule 52(a) following a bench trial. The findings of fact are based on the Court's observations and credibility determinations of the witnesses who testified, and a thorough review of all of the evidence admitted at trial as well as the parties' post-trial briefing.

For the reasons set forth below, and for good cause shown, the Court finds that Sun's ANDA Products INFRINGE on the asserted patents and that the asserted patents are VALID.^[1]

I. BACKGROUND

A. Parties

Orexo is a pharmaceutical company that manufacturers Zubsolv®, a drug used to treat opioid dependence. (DeLuca Tr. 84:18-23, 85:26-86:10.) Orexo AB is based in Sweden and Orexo US, Inc. is based in Morristown, New Jersey. (Id. at 85:9-13.) Orexo specializes in innovative pharmaceuticals that focus on mental health and substance use diss. (Id. at 84:18-23.) Orexo is identified as the assignee of the asserted patents. (JTX-0003.0001, JTX-0005.0001.)

Sun is one of the largest generic pharmaceutical companies in the world. (Singh Tr. 777:2-6.) Sun's corporate office is based in Princeton, New Jersey. (Id. at 777:13-15) This case is a patent litigation stemming from Sun's ANDA for a generic version of Orexo's brand product, Zubsolv®. (ECF No. 341 ¶¶ 1, 14, 19-20.)

B. Suboxone®

In 2002, the FDA approved the use of Suboxone® tablets for the treatment of opioid dependence. (Crowley Tr. 1028:14-24; DTX-0027.0001, 0002, 0007.) Suboxone® was a sublingual tablet containing 2 milligrams (“mg”) of buprenorphine^[2] with .5 mg of naloxone^[3]. (Crowley Tr. 1028:16-24; DTX-0027.0001, 0002, 0007.) Suboxone® also included inactive ingredients, including citric acid and sodium citrate. (DTX-0027.0001, 0002, 0007.) Following its approval in 2002, Suboxone® tablets became the “gold standard treatment for opiate dependence.” (Crowley Tr. 1029:4-7.)

However, as of 2011, there were approximately 4.3 million opioid addicts around the world, and the “diversion and illicit use of Suboxone [was] frequently [] reported.” (JTX-0001.0013.) Additionally, Suboxone® was reported to have several significant limitations including insufficient bioavailability, poor disintegration, dissolution, and taste, and a gritty mouthfeel. (Id.; Fischer Tr. 118:19-119:3; Sumner Tr. 249:24-250:17, 252:18-25.) Suboxone® film was a new dosage form of the same buprenorphine and naloxone active ingredients intended to improve upon the shortcomings of Suboxone® tablets, but like the tablets, Suboxone® film has limited bioavailability and dissolves slowly. (Forrest Tr. 882:25-883:15; DeLuca Tr. 94:20-26; Sumner Tr. 256:23-257:10; JTX-0001.0013.) As such, a clinical need developed for “an abuse-resistant product for use in opioid addiction substitution therapy” with “increase[ed] [] bioavailability of buprenorphine” such that “it might be possible to reduce the amount of [buprenorphine], giving rise to less opioid in the formulation and so reducing the amount available for injection if diverted by way of intravenous abuse.” (JTX-0001.0013.)

C. Zubsolv®

Orexo is the New Drug Application (“NDA”) holder and manufacturer of Zubsolv®. (ECF No. 341 ¶ 14.) Zubsolv® was approved for the treatment of opioid dependence in 2013. (DeLuca Tr. 97:19-21; Sumner Tr. 270:1-3.) Andreas Fischer was the formulator responsible for Zubsolv® and he was tasked with preparing a formulation that improved the bioavailability of Suboxone®. (Fischer Tr. 173:22-25.) Fischer considered the following design choices related to Zubsolv®: (1) dosage form and route of administration; (2) ingredients (both active and inactive); (3) the arrangement of the ingredients; and (4) the formulation method to obtain the arrangement. (Id. at 119:19-120:12.) Mr. Fischer used a sublingual tablet for Zubsolv®, which is administered under the tongue. (Id. at 120:13-122:5; JTX-0001.0017.) He used buprenorphine and naloxone as the two active pharmaceutical ingredients (“APIs”) as well as a number of inactive ingredients. (Fischer Tr. 122:6-22; JTX-0001.0014.) Mr. Fischer used citric acid, a weak acid, which can be used to lower pH and facilitate dissolution of an opioid; croscarmellose sodium to accelerate the tablets disintegration when exposed to saliva; and carrier particles, such as mannitol and lactose, which is a large particle that has the ability to carry smaller particles, such as buprenorphine, on its surface. (Fischer Tr. 125:21-129:16, 129:24-130:4-7.)

There is no dispute the patents for Zubsolv® were issued because Mr. Fischer's formulation of Zubsolv® “unexpected[ly], [and] significantly improved” bioavailability compared to the prior-art Suboxone®. (JTX-0001, JTX-0006.0944.) In fact, the Patent Examiner stated that Orexo: “persuasively demonstrated that the instant tablet exhibits unexpectedly superior sublingual buprenorphine bioavailability due to the ingredients as well as the structural characteristics recited in the instant claims.” (JTX-0011.171.) The separateness of the buprenorphine microparticles and weak acid particles promotes a “pH-timing effect.” (Davies Tr. 575:15-21.) Saliva surrounds and quickly dissolves the separate weak-acid particles, which causes pH to be lowered by “about .05 to 5 pH units” for a short period, after which the original pH is restored, “resulting in improved and/or more rapid dissolution of microparticles of buprenorphine.” (JTX-0001.0019-0020.)

With respect to the arrangement of the ingredients, Mr. Fischer used an ordered mixture in Zubsolv®. (Fischer Tr. 150:10-14.) Ordered mixtures are made up of ordered units, in which small particles associate with large particles and the individual particles retain their identity. (Id. at 130:25-131:17, 123:12-19; JTX-0001.0015-0016; Davies Tr. 461:17-462:21.) Composite mixtures, by contrast, dissolve together and the ingredients comingle together in the same particle and do not retain their identities. (Fischer Tr. 131:8-22; Davies Tr. 462:23-463:11.) Finally, Mr. Fischer used dry mixing in his formulation of Zubsolv®. (Fischer Tr. 151:1-8, 223:12-19.) Dry mixing combines the particles together without fluid, and the particles adhere to each other by interactive forces. (Id. at 142:10-144:5, 151:1-8; JTX-0001.0018.) However, Mr. Fischer testified that the asserted patents teach that compositions of the invention may also be formulated by way of so “the particles end up in the same way as when you did dry mixing.” (Fisher Tr. 144:2-24; JTX-0001.0015.)

D. Sun's ANDA Products

Sun filed ANDA No. 214737 pursuant to 21 U.S.C. § 355(j)(2)(A)(vii)(IV) (the Federal Food, Drug and Cosmetic Act (“FFDCA”)) with the FDA which sought approval to commercially market a generic version of Zubsolv® (buprenorphine/naloxone sublingual tablets at doses of 1.4/0.36 mg, 2.9/0.71 mg, 5.7/1.4 mg, 8.6/2.1 mg, and 11.4/2.9 mg) (“Sun's ANDA Products”) before the expiration of the asserted patents. (ECF No. 341 ¶ 19.) In connection with Sun's ANDA and pursuant to 21 U.S.C. § 355(j)(2)(A)(vii)(IV), Sun filed written certifications which alleged that the asserted claims and asserted patents are invalid and unenforceable. (Id. at ¶ 20.) Additionally, Sun certified that Sun's ANDA Products do not infringe on the asserted patents. (Id.)

As part of seeking approval of its ANDA Products, Sun was required by the FDA to demonstrate that its ANDA Products were therapeutically equivalent or “bioequivalent” to Zubsolv®, i.e., that they result in the same therapeutic response. (Davies Tr. 515:15-516:3.) To do so Sun conducted a bioequivalence study in the same dose strength of Zubsolv®. (Id. at 514:8-517:8, 518:15-18.) Sun'...