IP Law Daily Mylan infringed three patents for fibromyalgia drug Savella
Tuesday, July 12, 2016

Mylan infringed three patents for fibromyalgia drug Savella

By Mark Engstrom, J.D.

Mylan Inc. and Mylan Pharmaceuticals infringed multiple claims of three patents for the fibromyalgia drug Savella, the federal district court in Wilmington, Delaware, has ruled. None of the three patents, which were held by Royalty Pharma and licensed to Forest Laboratories, were invalid for obviousness or indefiniteness (Forest Laboratories Holdings Ltd. v. Mylan Inc., July 11, 2016, Robinson, S.).

Lawsuit. Forest Laboratories Holdings and Royalty Pharma Collection Trust sued Mylan Inc. and Mylan Pharmaceuticals (collectively, "Mylan") for the infringement of U.S. Patent Nos. 6,602,911; 7,888,342; and 7,994,220. Forest is the exclusive U.S. distributor of Savella tablets containing 12.5 mg, 25 mg, 50 mg, and 100 mg of the active ingredient milnacipran hydrochloride. The lawsuit arose from an Abbreviated New Drug Application (ANDA) that was filed by Mylan, which sought to market generic versions of Savella, a selective serotonin and norepinephrine reuptake inhibitor (SNRI), for the management of fibromyalgia.

Patents in Suit. At issue were three claims of the ’911 patent, three claims of the ’342 patent, and one claim of the ’220 patent. The ’911 patent, titled "Methods of Treating Fibromyalgia," was directed to the use of milnacipran in the treatment of fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS). The ’342 patent, titled "Methods of Treating Fibromyalgia Syndrome, Chronic Fatigue Syndrome and Pain" was also directed to the use of milnacipran in the treatment of FMS and CFS. The ’220 patent, titled "Milnacipran for the Long-Term Treatment of Fibromyalgia Syndrome," was directed to the long-term treatment of fibromyalgia. It claimed a method of administering milnacipran using an escalated dose or titration schedule.

Induced Infringement. Mylan argued that it did not induce the infringement of the asserted claims of the ’911 patent because Mylan did not instruct physicians to use milnacipran only as a monotherapy treatment. The court disagreed.

Milnacipran was the only drug on Mylan’s labels for the management of fibromyalgia, the court explained, and the clinical studies that were described therein were performed using milnacipran as a monotherapy. Neither the plaintiffs nor Mylan could tell doctors that milnacipran was approved for combination therapy because no such studies were submitted to the FDA and no such approval had been obtained. For those reasons, the court concluded that Mylan’s labels would "inevitably lead some consumers to practice" the label’s recommended use of milnacipran for the monotherapy treatment of fibromyalgia. According to the court, Mylan had the requisite intent to induce the infringement of all three of the asserted claims of the ’911 patent.

With respect to the ’342 patent, Mylan’s labels recommended 100 mg or 200 mg dose of milnacipran, which was an "effective amount" for treating fibromyalgia, according to Mylan. Unlike the ’911 patent, the ’342 patent was not limited to monotherapy. Instead, the ’342 patent allowed for both monotherapy and combination therapy for the treatment of fibromyalgia, as long as the other combination drug was not phenylalanine, tyrosine, or tryptophan.

Mylan argued that its products would be used with those three amino acids, and that its labels did not specifically instruct one to avoid those amino acids. Consequently, Mylan reasoned, Mylan could not be held liable for the induced infringement of the asserted claims. In reality, however, Mylan’s labels specifically warned against the co-administration of serotonergic agents such as "triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone and St. John's Wort" with drugs that impaired the metabolism of serotonin. Further, Mylan’s labels warned against the use of milnacipran with phenylalanine, tyrosine, or tryptophan, stating that those combinations could lead to potentially life-threatening side effects and could be potentially very dangerous for fibromyalgia patients.

Given Mylan’s express warnings about the potentially life-threatening side effects of milnacipran in combination with phenylalanine, tyrosine, or tryptophan, Mylan’s labels could not be read to condone those combinations.

Regarding the ’220 patent, Mylan argued that physicians and patients were not instructed to follow the titration schedule on its labels because the schedule on the labels was preceded by the following sentence: "Based on efficacy and tolerability, dosing may be titrated according to the following schedule." The court noted, however, that both Mylan’s labels and the plaintiffs’ Savella label included the very titration schedule that was recited in claim 1 of the ’220 patent.

Moreover, the titration schedule on Mylan’s labels was the only schedule that the FDA had evaluated and deemed safe and effective for the initiation of treatment with milnacipran. That fact was particularly important due to the increased susceptibility of fibromyalgia patients to the side effects of drug therapy, the court explained, which further warranted the use of the labeled titration schedule.

According to the court, Mylan induced the infringement of the ’220 patent because doctors and patients would inevitably follow the titration schedule on Mylan’s labels using Mylan’s available dosage strengths according to the claimed method.

Contributory Infringement. Mylan identified several substantial non-infringing uses, including the use of its milnacipran products in combination with another drug, to treat fibromyalgia. However, the court reiterated that the use of milnacipran in combination with another drug for the management of fibromyalgia would constitute an off-label use that would not qualify as a substantial non-infringing use. Mylan presented no credible evidence regarding the extent to which milnacipran was actually used in combination with another drug.

Invalidity. Mylan argued that U.S. Patent No. 6,441,038 ("Horrobin") anticipated, and thus invalidated, the asserted claims of the ’911 and ’342 patents because Horrobin disclosed each and every asserted limitation. Mylan relied on two combinations: (1) the Horrobin reference in combination with Dwight ("An Open Clinical Trial of Venlafaxine Treatment of Fibromyalgia"), Sarkin ("The Management Challenges of Chronic Pain: The Role of Antidepressants"), and PCT Publication No. WO 2000/15223 ("Treatment of Persistent Pain") and (2) Goldenberg and Fishbain (which taught the use of tricyclic antidepressants to treat fibromyalgia syndrome) combined with Briley II and Kasper (which taught that milnacipran was an SNRI and a suitable replacement for TCAs).

Regarding the ’220 patent, Mylan argued that the asserted claim would have been obvious in combination with U.S. Publication No. 2004/0106681 (which discussed phase II trials using milnacipran to treat fibromyalgia), Ansseau (which discussed the use of milnacipran to treat other conditions) and the ’911 patent.

The court noted that a concrete understanding of the cause of fibromyalgia—and thus a clear course of treatment—was currently lacking. According to the court, the teaching of the art was "multidirectional" at best, with no clear motivation to pursue milnacipran as an effective treatment for fibromyalgia. Significantly, no FDA-approved treatments for fibromyalgia existed at the time of the asserted patents. Consequently, the inventors’ decision to treat fibromyalgia with milnacipran was "the antithesis of anticipation and obviousness."

The case is No. 13-1602-SLR.

Attorneys: Jack B. Blumenfield and Maryellen Noreika (Morris, Nichols, Arsht & Tunnell LLP) and Charles E. Lipsey, Howard Levine, Sanya Sukduang, Courtney B. Casp, Aaron Gleaton Clay (Finnegan, Henderson, Farabow, Garrett & Dunner, LLP) for Forest Laboratories Holdings Ltd. and Royalty Pharma Collection Trust. Richard L. Horwitz, David E. Moore, and Bindu A. Palapura (Potter, Anderson & Corroon, LLP) and Poopak Banky, Thomas J. Parker, Natalie C. Clayton, and Andrew J. Ligotti (Alston & Bird LLP) for Mylan Inc. and Mylan Pharmaceuticals Inc.

Companies: Forest Laboratories Holdings Ltd.; Royalty Pharma Collection Trust; Mylan Inc.; Mylan Pharmaceuticals Inc.

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