Forest Labs. Holdings Ltd. v. Mylan Inc.

• Citation: 206 F.Supp.3d 957
• Decision Date: 11 July 2016
• Docket Number: Civ. No. 13-1602-SLR
• Parties: FOREST LABORATORIES HOLDINGS LTD., and Royalty Pharma Collection Trust, Plaintiffs, v. MYLAN INC., and Mylan Pharmaceuticals Inc., Defendants.
• Court: U.S. District Court — District of Delaware

206 F.Supp.3d 957

FOREST LABORATORIES HOLDINGS LTD., and Royalty Pharma Collection Trust, Plaintiffs,
v.
MYLAN INC., and Mylan Pharmaceuticals Inc., Defendants.

Civ. No. 13-1602-SLR

United States District Court, D. Delaware.

Signed July 11, 2016

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Jack B. Blumenfield, Esquire, and Maryellen Noreika, Esquire of Morris, Nichols, Arsht & Tunnell LLP, Wilmington, Delaware. Counsel for Plaintiffs. Of Counsel: Charles E. Lipsey, Esquire, Howard Levine, Esquire, Sanya Sukduang, Esquire, Courtney B. Casp, Esquire, Aaron Gleaton Clay, Esquire, Finnegan Henderson, Farabow, Garrett & Dunner, LLP.

Richard L. Horwitz, Esquire, David E. Moore, Esquire, and Bindu A. Palapura, Esquire, of Potter Anderson & Corroon, LLP, Wilmington, Delaware. Counsel for Defendants. Of Counsel: Poopak (Paki) Banky, Esquire, Thomas J. Parker, Esquire, Natalie C. Clayton, Esquire, and Andrew J. Ligotti, Esquire of Alston & Bird LLP.

OPINION

ROBINSON, District Judge

I. INTRODUCTION

This action arises out of the filing of an Abbreviated New Drug Application ("ANDA") by defendants Mylan Pharmaceuticals, Inc. and Mylan, Inc. (collectively, "Mylan") seeking to market generic versions of Savella^®, a selective serotonin and norepinephrine reuptake inhibitor ("SNRI") indicated for the management of fibromyalgia. Plaintiffs Forest Laboratories Holdings, Ltd. ("Forest") and Royalty Pharma Collection Trust ("Royalty Pharma") (collectively, "plaintiffs") filed suit against Mylan, alleging infringement of U.S. Patent Nos. 6,602,911 ("the '911 patent"), 7,888,342 ("the '342 patent"), and 7,994,220 ("the '220 patent") (collectively, "the patents-in-suit"). The patents-in-suit are currently assigned to Royalty Pharma (D.I. 1 at ¶¶ 23-25) and Forest is the exclusive licensee (Id. at ¶ 27). New Drug Application ("NDA") No. 022256 is directed to the use of Savella^® in the management of fibromyalgia and was approved by the FDA on January 14, 2009. (D.I. 1 at ¶ 26) The patents-in-suit are listed in the Food and Drug Administration's ("FDA's") publication titled "Approved Drug Products with Therapeutic Equivalence Evaluations" (known as the "Orange Book") for Savella^®. (Id. ) Plaintiff Forest is the exclusive

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distributor of Savella^® tablets containing 12.5 mg, 25 mg, 50 mg, and 100 mg of the active ingredient milnacipran hydrochloride in the United States. (D.I. 1 at ¶ 27)

Pursuant to 21 U.S.C. § 355(j) ), Mylan submitted ANDA No. 205367, seeking approval to commercially manufacture, use, and sell generic milnacipran hydrochloride tablets in 12.5 mg, 25 mg, 50 mg, and 100 mg dosage strengths with a paragraph IV certification stating that the patents-in-suit are invalid and not infringed. (Civ. No. 13-1605, D.I. 1 at ¶¶ 25-26) On August 27, 2013, Mylan informed plaintiffs that an ANDA had been filed and alleged non-infringement and invalidity of claims 1-7 of the '911 patent, claims 1-10 of the '342 patent, and claims 1-7 of the '220 patent. (Civ. No. 13-1604, D.I. 1 at ¶ 27) Plaintiffs responded on September 23, 2013 by filing this suit for infringement of the '911, '342, and '220 patents.

On December 15, 2015, the court held a claim construction hearing and a final pretrial conference. The court subsequently held a six-day bench trial from January 19-26, 2016 on the issues of infringement and validity, and the parties have since completed their post-trial briefing. The 30-month stay of FDA final approval expires on July 14, 2016. The court has jurisdiction over this matter pursuant to 28 U.S.C. §§ 1331, 1338(a), and 1400(b). Having considered the documentary evidence and testimony, the court makes the following findings of fact and conclusions of law pursuant to Federal Rule of Civil Procedure 52(a).¹

II. FINDINGS OF FACT AND CONCLUSIONS OF LAW

A. The Technology at Issue

1. Technical background and treatments of fibromyalgia

Fibromyalgia, also referred to as fibromyalgia syndrome or "FMS" and previously referred to as fibrositis,² is a complex, systemic disorder characterized by widespread musculoskeletal pain, a reduced threshold for pain at specified tender points, fatigue, sleep disturbance, cognitive dysfunction, and additional comorbidities to include irritable bowel syndrome and depression. (D.I. 276 at 76:22-77:17, 433:10-14, JTX 099; JTX 101) Patients suffering from FMS are marked by hypersensitivity to external influences and everyday sensations, to include physical contact, clothing, and scents that may not bother individuals without the disorder, leading not only to pain, but the inability of patients to function normally in everyday life. (D.I. 276 at 78:5-16, 76:22-78:1; D.I. 281 at 965:25-966:11) This hypersensitivity also makes treating FMS difficult, as patients with fibromyalgia are particularly susceptible to the side effects associated with drug therapy, typically resulting in the need to start medications on a low dose and slowly increase the dose over time to achieve a therapeutically effective dose. (D.I. 276 at 77:9-78:1; D.I. 278 at 668:7-669:25; D.I. 281 at 965:25-966:24; 978:8-17; 987:2-989:2; 1037:6-20; 582:8-19; JTX 079 at 659, 664; JTX 038 at 104)

By 2001, FMS was well described, but the etiology and pathophysiology of the disease were poorly understood. (D.I. 277 at 434:2-15; D.I. 278 at 682:4-18) Some

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considered fibromyalgia as "a psychological disorder, or perhaps, a local myofascial pain syndrome," while others believed that fibromyalgia results from dysregulation of pain processing within the central nervous system ("CNS"). (JTX 99 at 161) "This disarray in construct has led to a blurring of the margins of the disorder and the consequent idea that fibromyalgia means something different to every observer." (D.I. 276 at 76:22-78:16; D.I. 278 at 666:8-669:25; JTX 071 at 1-2; JTX 038 at 104)

The lack of a known etiology of fibromyalgia made diagnosing and studying the disorder very difficult. It is not uncommon for patients to seek help from a variety of specialists, including gastroenterologists, neurologists, oral surgeons, and urologists seeking a diagnosis, with each specialist citing a different condition. (D.I. 278 at 668:11-670:4) It may be years later when a patient seeks help from a pain specialist who diagnoses the patient with fibromyalgia. (Id. ) The first diagnostic criteria for FMS were established in 1990 by the American College of Rheumatology. (D.I. 277 at 434:2-15) These criteria require: (1) a history of widespread pain for at least three months; and (2) pain in at least 11 of 18 defined tender point sites.³ (D.I. 277 at 434:16-435:1) Additionally, patients with FMS typically experience a variety of other symptoms, including sleep disturbance, fatigue, stiffness, cognitive dysfunction (fibrofog), and depression. (D.I. 277 at 302:17-22, 344:19-345:2)

Treatment of FMS is tailored to the individual patient and their individual symptoms. Although all FMS patients have pain, physicians must also assess and treat patients' other potential symptoms such as fatigue, cognitive dysfunction, insomnia, nonrestorative sleep, depression, anxiety, and stiffness in order to successfully manage a patient's FMS. (D.I. 277 at 315:3-317:21, 411:2-13) Although there are currently three drugs specifically approved to treat FMS, no single treatment is effective to treat all symptoms of FMS, and individual FMS patients respond differently to treatments. (D.I. 277 at 315:3-317:21, 411:2-13; D.I. 280 at 795:21-23)

Before 2001, physicians were successfully treating FMS patients' symptoms with a variety of compounds. (D.I. 277 at 440:7-17) Antidepressants, particularly tricyclic antidepressants ("TCAs"), were commonly prescribed by doctors. (D.I. 277 at 310:3-10, 316:14-317:17, 440:7-17, 441:5-442:11; D.I. 278 at 730:2-7) Doctors prescribed TCAs such as amitriptyline, newer compounds such as selective serotonin reuptake inhibitors ("SSRIs"), and the first-approved serotonin and norepinephrine reuptake inhibitor ("SNRI"), venlafaxine. (D.I. 277 at 440:7-17, 764:15-765:19) Amitriptyline, at the time, was the most commonly prescribed drug for the treatment of FMS. (D.I. 277 at 240:24-241:18, 440:7-17)

The majority of studies evaluating pharmacological treatments of FMS focused on antidepressants. (JTX 79; JTX 38) Studies suggested that patients taking antidepressants were four times more likely to improve compared to patients taking placebo and that about 25 percent of all patients taking antidepressants improved. (JTX 79 at 663) Studies of antidepressants for the treatment of FMS recognized improvements in fatigue, sleep, and overall well-being, as well as pain severity. (Id. at 664) Amitriptyline and cyclobenzaprine, tricyclic medications that inhibit both serotonin and norepinephrine reuptake, were two of the most studied drugs for the treatment of FMS, and about 33 percent of patients

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had a clinically meaningful response to the use of these compounds.⁴ (D.I. 277 at 446:21-447:3) Given the success of TCAs like amitriptyline, the prior art suggested that "certain symptoms of [FMS] may respond...