DCT

1:18-cv-00690

Vanda Pharma Inc v. MSN Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-00690, D. Del., 12/11/2018
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant MSN Pharmaceuticals is incorporated in Delaware, and Defendant MSN Labs is an Indian corporation subject to personal jurisdiction in the district.
  • Core Dispute: Plaintiff alleges that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's HETLIOZ® (tasimelteon) product infringes seven patents related to methods of using tasimelteon and to purified forms of the compound.
  • Technical Context: The technology relates to pharmaceutical treatments for Non-24-Hour Sleep-Wake Disorder (Non-24), a circadian rhythm disorder primarily affecting blind individuals who cannot synchronize their internal body clock to a 24-hour day.
  • Key Procedural History: This is a Hatch-Waxman action triggered by Defendants’ filing of ANDA No. 211654 with a Paragraph IV Certification, asserting that Plaintiff’s patents are invalid, unenforceable, and/or will not be infringed. Plaintiff received a Notice Letter regarding this certification on April 2, 2018, and commenced this action within the statutory 45-day window.

Case Timeline

Date Event
2012-01-26 Priority Date for RE46,604; 9,060,995; 9,539,234; 9,549,913; 9,730,910; 9,855,241 Patents
2014-01-31 FDA approval of HETLIOZ® New Drug Application
2014-02-12 Priority Date for 10,071,977 Patent
2015-06-23 Issue Date of U.S. Patent No. 9,060,995
2017-01-10 Issue Date of U.S. Patent No. 9,539,234
2017-01-24 Issue Date of U.S. Patent No. 9,549,913
2017-08-15 Issue Date of U.S. Patent No. 9,730,910
2017-11-14 Issue Date of U.S. Patent No. RE46,604
2018-01-02 Issue Date of U.S. Patent No. 9,855,241
2018-04-02 Plaintiff receives Defendants’ ANDA Notice Letter and Paragraph IV Certification
2018-09-11 Issue Date of U.S. Patent No. 10,071,977
2018-12-11 Complaint Filing Date

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. RE46,604 - "Treatment of Circadian Rhythm Disorders"

  • Patent Identification: U.S. Patent No. RE46,604, "Treatment of Circadian Rhythm Disorders," issued November 14, 2017.

The Invention Explained

  • Problem Addressed: The patents address Non-24-Hour Sleep-Wake Disorder (Non-24), a condition where individuals, "primarily blind with no light perception, are unable to synchronize their endogenous circadian pacemaker to the 24-hour light/dark cycle" (Compl. ¶38). This causes their sleep drive to drift later each day, resulting in "abnormal night sleep patterns, accompanied by difficulty staying awake during the day" (’995 Patent, col. 1:53-58; Compl. ¶38).
  • The Patented Solution: The invention is a method to "entrain or synchronize" a patient's circadian rhythms using tasimelteon, a "circadian regulator which binds specifically to two high affinity melatonin receptors" (’995 Patent, col. 2:35-37; Compl. ¶39). The RE604 patent specifically claims treating Non-24 by orally administering 20 mg of tasimelteon once daily before a target bedtime to entrain the patient to a 24-hour sleep-wake cycle (Compl. ¶43).
  • Technical Importance: The technology provides a targeted pharmacological intervention to entrain the sleep-wake cycle for a patient population that lacks the primary environmental cue (light) for circadian synchronization (Compl. ¶38).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claims 6 and 7 (Compl. ¶73).
  • Independent Claim 1 requires:
    • A method of entraining a patient suffering from Non-24 to a 24 hour sleep-wake cycle in which the patient awakens at or near a target wake time following a daily sleep period of approximately 7 to 9 hours, and maintaining said 24 hour sleep-wake cycle
    • The method comprises treating the patient by orally administering to the patient 20 mg of tasimelteon once daily before a target bedtime

U.S. Patent No. 9,060,995 - "Treatment of Circadian Rhythm Disorders"

  • Patent Identification: U.S. Patent No. 9,060,995, "Treatment of Circadian Rhythm Disorders," issued June 23, 2015.

The Invention Explained

  • Problem Addressed: This patent addresses the same Non-24 disorder as the RE604 patent but focuses on a specific drug-drug interaction. Co-administration of tasimelteon with strong CYP1A2 inhibitors, such as fluvoxamine, can cause a "large increase in tasimelteon exposure and greater risk of adverse reactions" (Compl. ¶64, 86).
  • The Patented Solution: The patent claims a method of treating a Non-24 patient who is also being treated with fluvoxamine. The method involves discontinuing the fluvoxamine treatment and then initiating treatment with 20 mg of tasimelteon, "thereby avoiding the use of tasimelteon in combination with fluvoxamine" (’995 Patent, col. 34:11-15; Compl. ¶46).
  • Technical Importance: This method provides a specific protocol to manage a potentially harmful drug interaction, enhancing the safety profile for treating Non-24 patients who may be on other medications.

Key Claims at a Glance

  • The complaint asserts the sole claim, claim 1 (Compl. ¶91).
  • Independent Claim 1 requires:
    • A method of entraining a light perception impaired patient suffering from Non-24-Hour Sleep-Wake Disorder to a 24-hour sleep-wake cycle, wherein the patient is being treated with fluvoxamine
    • The method comprises: (A) discontinuing the fluvoxamine treatment and then (B) orally treating the patient with 20 mg of tasimelteon once daily before a target bedtime, thereby avoiding the use of tasimelteon in combination with fluvoxamine

Multi-Patent Capsule: U.S. Patent No. 9,539,234

  • Patent Identification: U.S. Patent No. 9,539,234, "Treatment of Circadian Rhythm Disorders," issued January 10, 2017 (Compl. ¶47).
  • Technology Synopsis: The patent claims methods for treating Non-24 by avoiding the use of tasimelteon in combination with a "strong CYP1A2 inhibitor" in light perception impaired patients (Compl. ¶48). This is a broader version of the concept in the ’995 patent.
  • Asserted Claims: At least claim 3 is asserted (Compl. ¶113).
  • Accused Features: The proposed product label for MSN's generic tasimelteon instructs physicians to "[a]void use of HETLIOZ in combination with fluvoxamine or other strong CYP1A2 inhibitors" (Compl. ¶108).

Multi-Patent Capsule: U.S. Patent No. 9,549,913

  • Patent Identification: U.S. Patent No. 9,549,913, "Treatment of Circadian Rhythm Disorders," issued January 24, 2017 (Compl. ¶49).
  • Technology Synopsis: The patent claims methods of entraining and maintaining a patient's 24-hour cortisol circadian rhythm by orally administering tasimelteon once daily before a target bedtime (Compl. ¶50).
  • Asserted Claims: At least claims 1 and 4 are asserted (Compl. ¶134).
  • Accused Features: The proposed product label instructs use of 20 mg generic tasimelteon for treatment of Non-24, which is alleged to entrain cortisol rhythms (Compl. ¶128-129, 132).

Multi-Patent Capsule: U.S. Patent No. 9,730,910

  • Patent Identification: U.S. Patent No. 9,730,910, "Treatment of Circadian Rhythm Disorders," issued August 15, 2017 (Compl. ¶51).
  • Technology Synopsis: The patent claims methods of treating a patient for a circadian rhythm disorder by avoiding a drug-drug interaction with rifampicin (also known as rifampin), a CYP3A4 inducer that can reduce exposure to tasimelteon (Compl. ¶52-53).
  • Asserted Claims: At least claim 2 is asserted (Compl. ¶156).
  • Accused Features: The proposed product label instructs physicians to "[a]void use of HETLIOZ in combination with rifampin or other CYP3A4 inducers" (Compl. ¶151).

Multi-Patent Capsule: U.S. Patent No. 9,855,241

  • Patent Identification: U.S. Patent No. 9,855,241, "Treatment of Circadian Rhythm Disorders," issued January 2, 2018 (Compl. ¶54).
  • Technology Synopsis: The patent claims methods of synchronizing a patient's abnormal cortisol and melatonin circadian rhythms with a natural day/night cycle by administering an effective amount of tasimelteon (Compl. ¶55).
  • Asserted Claims: At least claim 4 is asserted (Compl. ¶177).
  • Accused Features: The proposed product label instructs the use of generic tasimelteon for Non-24, which the complaint alleges performs the claimed synchronization (Compl. ¶171-172, 175).

Multi-Patent Capsule: U.S. Patent No. 10,071,977

  • Patent Identification: U.S. Patent No. 10,071,977, "Highly Purified Pharmaceutical Grade Tasimelteon," issued September 11, 2018 (Compl. ¶56).
  • Technology Synopsis: This patent claims "purified tasimelteon and processes for preparing the same" (Compl. ¶57). The patent explains that tasimelteon synthesis can result in impurities that "must be controlled to ppm levels" for the drug to be suitable for pharmaceutical use (’977 Patent, col. 3:60-65; Compl. ¶41).
  • Asserted Claims: At least claims 1, 18, 22, 23, and 24 are asserted (Compl. ¶201).
  • Accused Features: The complaint alleges that MSN intends to use the processes claimed in the ’977 patent to prepare the purified tasimelteon for its ANDA product and that the resulting product is covered by the patent's composition claims (Compl. ¶195, 199).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is Defendants' generic tasimelteon 20 mg oral capsules, for which they seek FDA approval via ANDA No. 211654 (the "MSN ANDA Product") (Compl. ¶11, 66).
  • Functionality and Market Context: The MSN ANDA Product is a generic drug intended to be a therapeutic equivalent to Vanda's HETLIOZ® (Compl. ¶1, 9, 30). Its functionality is defined by its proposed product label, which the complaint alleges "essentially copies the HETLIOZ® Label" (Compl. ¶69). The label allegedly instructs physicians to use the product for the treatment of Non-24 at a dose of 20 mg per day taken before bedtime (Compl. ¶62, 63, 66). It also allegedly provides instructions regarding co-administration with other drugs, such as avoiding use with strong CYP1A2 inhibitors (e.g., fluvoxamine) and CYP3A4 inducers (e.g., rifampin) (Compl. ¶64, 151). The complaint also accuses the purified tasimelteon active pharmaceutical ingredient (API) itself and the process for making it (Compl. ¶195, 203).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

RE46,604 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of entraining a patient suffering from Non-24 to a 24 hour sleep-wake cycle... The proposed label for MSN's ANDA Product indicates the product for the treatment of Non-24-Hour Sleep-Wake Disorder (Non-24). ¶62, ¶66 col. 1:18-21
said method comprising: treating the patient by orally administering to the patient 20 mg of tasimelteon once daily before a target bedtime. The proposed label for MSN's ANDA Product instructs a recommended dosage of 20 mg per day taken before bedtime. ¶63, ¶66 col. 2:27-34
  • Identified Points of Contention:
    • Scope Questions: The infringement theory is based on inducement, where the proposed drug label allegedly encourages physicians to perform the claimed method. A central question may be whether the instructions on the proposed label for the MSN ANDA Product are sufficient to demonstrate that MSN specifically intended for physicians to infringe the patent.
    • Technical Questions: A potential issue is the meaning of "entraining." The dispute may focus on whether prescribing the drug according to the label inherently results in "entraining" the patient, or if a specific clinical outcome must be demonstrated for the claim limitation to be met.

9,060,995 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of entraining a light perception impaired patient suffering from Non-24-Hour Sleep-Wake Disorder... wherein the patient is being treated with fluvoxamine, MSN's proposed label allegedly instructs physicians to avoid using the product in combination with fluvoxamine, which is a treatment scenario contemplated by the claim. ¶86, ¶91 col. 34:5-15
the method comprising: (A) discontinuing the fluvoxamine treatment and then (B) orally treating the patient with 20 mg of tasimelteon once daily before a target bedtime, thereby avoiding the use of tasimelteon in combination with fluvoxamine. MSN's proposed label allegedly instructs physicians to "[a]void use of HETLIOZ in combination with fluvoxamine" and to prescribe a 20 mg daily dose of tasimelteon before bedtime. ¶85, ¶86 col. 34:5-15
  • Identified Points of Contention:
    • Scope Questions: This claim includes a negative limitation ("avoiding the use...in combination with fluvoxamine"). A key legal question will be whether a label that instructs physicians not to combine the drugs can induce infringement of a claim that requires this avoidance as a step.
    • Technical Questions: The complaint alleges infringement by inducement. The factual question will be whether the language of MSN's proposed label would lead a physician to perform the claimed steps for a patient already on fluvoxamine, including the act of discontinuing the fluvoxamine treatment before administering tasimelteon.

V. Key Claim Terms for Construction

  • The Term: "entraining" (from RE604 Claim 1; ’995 Claim 1)

  • Context and Importance: This term describes the therapeutic outcome of the claimed methods. Its construction is critical because it could define whether infringement requires proof of a specific clinical result or if merely administering the drug for the stated purpose is sufficient. Practitioners may focus on this term because it links the administrative step of giving the drug to the functional outcome patented.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification describes the "ultimate treatment goal for individuals with Non-24" as being "to entrain or synchronize their circadian rhythms" (’995 Patent, col. 2:30-32). This suggests "entraining" may refer to the intended purpose and mechanism of the treatment itself.
    • Evidence for a Narrower Interpretation: The specification describes clinical study results where entrainment was measured by analyzing a patient's urinary metabolites of melatonin ('995 Patent, col. 9:1-24). This could support an argument that "entraining" is a measurable clinical endpoint that must be demonstrated to have occurred.

  • The Term: "avoiding the use of tasimelteon in combination with fluvoxamine" (from ’995 Claim 1)

  • Context and Importance: This negative limitation is the core of the asserted claim of the ’995 patent. The infringement analysis hinges on whether the instructions on MSN's proposed label to avoid this combination constitute inducement of this claimed step.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The plain language of the claim includes both discontinuing a prior treatment ("(A) discontinuing the fluvoxamine treatment") and the result ("thereby avoiding the use...in combination"). This suggests that a physician following a label warning not to combine the drugs is performing the claimed method.
    • Evidence for a Narrower Interpretation: An argument could be made that the term requires an affirmative act of cessation for a patient already taking both drugs, and that a general warning on a label does not instruct that specific sequence of actions for every patient.

VI. Other Allegations

  • Indirect Infringement: The complaint's allegations for the six method-of-use patents are based on induced infringement (Compl. ¶73, 95, 117, 138, 160, 181). It is alleged that by submitting an ANDA with a proposed label that "essentially copies" the HETLIOZ® label, MSN instructs and encourages physicians to perform the patented methods (Compl. ¶69, 70). MSN's knowledge and specific intent are alleged based on its filing of the ANDA and its receipt of Vanda's patent information via the Orange Book listing (Compl. ¶68) and the subsequent Notice Letter (Compl. ¶61). For the '977 patent, inducement is alleged based on MSN actively aiding and abetting manufacturers and others to make and use the patented composition and process (Compl. ¶203).
  • Willful Infringement: While not pleaded as a separate count, the complaint alleges that MSN's statement regarding invalidity and noninfringement "is devoid of an objective good faith basis in either the facts or the law," alleges the case is "exceptional," and seeks attorneys' fees under 35 U.S.C. § 285 and damages under § 284, which encompasses enhancement for willful infringement (Compl. ¶78, 79, 100, 101). The allegations are based on knowledge obtained through the ANDA process and the subsequent litigation.

VII. Analyst’s Conclusion: Key Questions for the Case

  • A core issue will be one of inducement for negative limitations: Can a generic drug label that instructs physicians to avoid a specific drug combination be construed as actively inducing infringement of a patent claim that requires this avoidance as a method step?
  • A key evidentiary question will be one of process and composition proof: For the ’977 patent, which covers the drug substance and its manufacturing process, the case will likely depend on whether discovery yields evidence that MSN's confidential process infringes the patent's process claims and that its final API infringes the patent's composition claims.
  • The central dispute may be one of patent validity: The complaint repeatedly notes that MSN's basis for non-infringement is tied to its argument that the patents are invalid (e.g., Compl. ¶14, 65, 87). This suggests the case may focus less on claim construction and more on the strength of Defendants' prior art and other invalidity challenges to Vanda's extensive patent portfolio covering HETLIOZ®.