DCT

1:18-cv-00651

Vanda Pharma Inc v. Teva Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-00651, D. Del., 12/11/2018
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Teva is a corporation incorporated in the State of Delaware.
  • Core Dispute: Plaintiff alleges that Defendant's filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the drug tasimelteon constitutes an act of infringement of seven U.S. patents related to methods of using tasimelteon and to the purified drug itself.
  • Technical Context: The technology concerns the pharmaceutical compound tasimelteon (marketed as HETLIOZ®), a treatment for Non-24-Hour Sleep-Wake Disorder, a circadian rhythm disorder that primarily affects totally blind individuals.
  • Key Procedural History: This patent infringement action was initiated under the Hatch-Waxman Act following Defendant’s submission of an ANDA to the FDA seeking approval to market a generic tasimelteon product. Plaintiff received a Paragraph IV Certification notice letter from Defendant on March 23, 2018, regarding six of the patents-in-suit, and a supplemental notice letter on October 25, 2018, regarding the recently issued seventh patent.

Case Timeline

Date Event
2012-01-26 Earliest Priority Date for Method Patents (RE604, ’995, ’234, ’913, ’910, ’241)
2014-01-31 FDA approves Vanda’s New Drug Application for Hetlioz® (tasimelteon)
2014-02-12 Earliest Priority Date for Composition Patent (’977)
2015-06-23 U.S. Patent No. 9,060,995 Issues
2017-01-10 U.S. Patent No. 9,539,234 Issues
2017-01-24 U.S. Patent No. 9,549,913 Issues
2017-08-15 U.S. Patent No. 9,730,910 Issues
2017-11-14 U.S. Patent No. RE46,604 Issues
2018-01-02 U.S. Patent No. 9,855,241 Issues
2018-03-23 Vanda receives Teva’s ANDA Notice Letter and Paragraph IV Certification
2018-09-11 U.S. Patent No. 10,071,977 Issues
2018-10-25 Vanda receives Teva’s Supplemental Notice Letter regarding the ’977 Patent
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"

The Invention Explained

  • Problem Addressed: The patent describes Non-24-Hour Sleep-Wake Disorder ("Non-24"), a condition where individuals, primarily those who are blind with no light perception, are unable to synchronize their internal biological clock to a 24-hour day (Compl. ¶28). This causes their natural sleep-wake cycle, which is typically slightly longer than 24 hours, to drift later each day, resulting in abnormal sleep patterns and difficulty staying awake during the daytime (Compl. ¶28; RE46,604 Patent, col. 2:5-20).
  • The Patented Solution: The invention claims to solve this problem by providing a method to "entrain or synchronize" the patient's circadian rhythms to a 24-hour cycle (RE46,604 Patent, col. 2:36-41). This is achieved by orally administering a specific 20 mg dose of the drug tasimelteon once per day before a target bedtime, with the goal of increasing sleepiness at night and wakefulness during the day (Compl. ¶33; RE46,604 Patent, Abstract).
  • Technical Importance: The patented method provides a specific therapeutic regimen for a circadian regulator, tasimelteon, that binds to melatonin receptors in the suprachiasmatic nucleus of the brain, the body's master clock responsible for synchronizing the sleep/wake cycle (Compl. ¶29).

Key Claims at a Glance

  • The complaint asserts infringement of at least claims 1, 6, and 7 (Compl. ¶59). Claim 1 is independent.
  • The essential elements of independent claim 1 are:
    • 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
    • said method comprising: treating the patient by orally administering to the patient 20 mg of tasimelteon once daily before a target bedtime.
  • The complaint explicitly asserts dependent claims 6 and 7, which add limitations related to the concurrent use of tasimelteon with a CYP1A2 inhibitor (Compl. ¶¶34, 59).

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

The Invention Explained

  • Problem Addressed: In addition to Non-24, this patent addresses the specific clinical scenario where a patient is already being treated with fluvoxamine (’995 Patent, Claim 1). Fluvoxamine is a strong inhibitor of the CYP1A2 enzyme, which can lead to a "potentially large increase in tasimelteon exposure and greater risk of adverse reactions" if the two drugs are taken concurrently (Compl. ¶76; ’995 Patent, col. 18:30-45).
  • The Patented Solution: The patented method provides a specific protocol for safely treating a Non-24 patient who is currently taking fluvoxamine. The method comprises discontinuing the fluvoxamine treatment and then beginning treatment with 20 mg of tasimelteon, thereby "avoiding the use of tasimelteon in combination with fluvoxamine" (Compl. ¶36; ’995 Patent, Claim 1).
  • Technical Importance: This invention provides a method for managing a known drug-drug interaction, allowing physicians to transition patients to tasimelteon therapy while mitigating the risk of adverse events associated with elevated drug exposure (Compl. ¶76).

Key Claims at a Glance

  • The complaint asserts infringement of the patent's sole claim, claim 1 (Compl. ¶80).
  • The essential elements of independent claim 1 are:
    • 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 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.

U.S. Patent No. 9,539,234 - "Treatment of Circadian Rhythm Disorders"

  • Technology Synopsis: This patent claims methods of treating Non-24 by avoiding the concurrent use of tasimelteon with a "strong CYP1A2 inhibitor," a broader category of drugs that includes fluvoxamine (Compl. ¶¶38, 97). The method is intended to prevent a large increase in tasimelteon exposure and risk of adverse reactions (Compl. ¶97).
  • Asserted Claims: At least claim 3 (dependent on independent claim 1) (Compl. ¶101).
  • Accused Features: The proposed label for Teva's ANDA Product, which allegedly instructs physicians to avoid using the product in combination with strong CYP1A2 inhibitors (Compl. ¶¶97, 101).

U.S. Patent No. 9,549,913 - "Treatment of Circadian Rhythm Disorders"

  • Technology Synopsis: This patent claims a method of entraining a patient's cortisol circadian rhythm to a 24-hour cycle by orally administering tasimelteon daily before bedtime (Compl. ¶40). Cortisol rhythm is another key biological marker that becomes desynchronized in Non-24 patients.
  • Asserted Claims: At least claims 1 and 4 (Compl. ¶121).
  • Accused Features: The use of Teva's ANDA product for the treatment of Non-24, as the dependent claim 4 specifies that the patient suffers from Non-24-Hour Sleep-Wake Disorder (Compl. ¶¶40, 119, 121).

U.S. Patent No. 9,730,910 - "Treatment of Circadian Rhythm Disorders"

  • Technology Synopsis: This patent claims a method for treating a circadian rhythm disorder in a patient being treated with rifampicin (also known as rifampin), a strong inducer of the CYP3A4 enzyme (Compl. ¶¶42-43). The method involves discontinuing rifampicin and then treating with tasimelteon, thereby avoiding reduced exposure and efficacy of tasimelteon (Compl. ¶¶42, 138).
  • Asserted Claims: At least claim 2 (dependent on independent claim 1) (Compl. ¶142).
  • Accused Features: The proposed label for Teva's ANDA Product, which allegedly instructs physicians to avoid using the product in combination with rifampin or other CYP3A4 inducers (Compl. ¶¶138, 142).

U.S. Patent No. 9,855,241 - "Treatment of Circadian Rhythm Disorders"

  • Technology Synopsis: This patent claims a method of synchronizing both a patient's abnormal cortisol circadian rhythm and abnormal melatonin circadian rhythm with a natural day/night cycle (Compl. ¶45). The method comprises orally administering an effective amount of tasimelteon daily before bedtime.
  • Asserted Claims: At least claim 4 (dependent on independent claim 1) (Compl. ¶162).
  • Accused Features: The use of Teva's ANDA product for the treatment of Non-24, as dependent claim 4 specifies that the patient suffers from Non-24-Hour Sleep-Wake Disorder (Compl. ¶¶45, 160).

U.S. Patent No. 10,071,977 - "Highly Purified Pharmaceutical Grade Tasimelteon"

  • Technology Synopsis: This patent claims not a method of use, but rather a composition of matter and a process for its synthesis (Compl. ¶47). The invention covers highly purified tasimelteon that does not contain certain enumerated impurities above a specified concentration (e.g., about 0.15%), addressing the problem that the synthesis process can result in potentially genotoxic impurities that must be controlled (’977 Patent, col. 3:1-12; Compl. ¶31).
  • Asserted Claims: At least claims 1, 18, 22, 23, and 24 (Compl. ¶186).
  • Accused Features: Teva's ANDA Product itself is alleged to be an infringing purified composition, and the process Teva intends to use to manufacture its product is alleged to infringe the claimed synthesis process (Compl. ¶¶181, 185).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is Teva's proposed generic tasimelteon oral capsules, 20 mg strength, for the treatment of Non-24, as described in Teva's Abbreviated New Drug Application No. 211601 ("Teva's ANDA Product") (Compl. ¶6).
  • Functionality and Market Context:
    • The complaint alleges that infringement occurs under 35 U.S.C. § 271(e)(2)(A) by the very act of Teva filing its ANDA seeking FDA approval to market the generic product prior to the expiration of the patents-in-suit (Compl. ¶16).
    • For the method of use patents, the infringement theory is based on the future, post-approval commercial product. The complaint alleges that, as required by FDA regulations, the label for Teva's ANDA Product will "essentially cop[y]" the FDA-approved label for Vanda's HETLIOZ® product (Compl. ¶59, 80). This copied label will allegedly instruct, recommend, and encourage physicians to perform the patented methods, including administering a 20 mg daily dose for Non-24 and avoiding combinations with specific interacting drugs (Compl. ¶¶53-55, 59).
    • For the ’977 Patent, the infringement theory is based on the composition of Teva's ANDA product itself and the process used to create it. The complaint alleges on information and belief that Teva intends to use the claimed processes to prepare its product and that the resulting tasimelteon will be the purified composition covered by the patent claims (Compl. ¶¶181, 185).
    • 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 Teva's ANDA Product states that the product is indicated for the treatment of Non-24-Hour Sleep-Wake Disorder (Non-24). ¶53, ¶56 col. 2:36-41
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 Teva's ANDA Product instructs a recommended dosage of 20 mg per day taken before bedtime. ¶54 col. 18:30-45
  • Identified Points of Contention:
    • Scope Questions: A potential issue for litigation may be the scope of the term "entraining." A defendant could argue that a generic label which simply indicates a product for "treatment" of Non-24 does not necessarily instruct the specific outcome of "entraining... to a 24 hour sleep-wake cycle," potentially raising the question of whether "treating" is coextensive with "entraining" as used in the claim.
    • Technical Questions: In this Hatch-Waxman context, the primary questions are legal rather than technical. The dispute centers on whether the instructions on Teva's proposed label, which are expected to mirror the HETLIOZ® label, will induce physicians to perform the claimed method steps.

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 to a 24-hour sleep-wake cycle... wherein the patient is being treated with fluvoxamine... Teva's proposed label allegedly instructs physicians to "[a]void use of HETLIOZ in combination with fluvoxamine," which the complaint alleges will encourage infringement in the clinical setting where a patient is already being treated with fluvoxamine. ¶76, ¶80 col. 18:30-34
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... The complaint alleges that the instruction to avoid the drug combination will induce physicians treating patients already on fluvoxamine to discontinue it before starting tasimelteon, thereby performing the claimed steps. ¶76, ¶80 col. 18:34-45
  • Identified Points of Contention:
    • Scope Questions: A central dispute may be whether a label's instruction to "avoid" a drug combination constitutes inducement of the specific, affirmative two-step method of "discontinuing" one drug and "then" administering another. A defendant may argue that a warning against co-administration does not affirmatively instruct or encourage the claimed sequence of actions.
    • Technical Questions: The complaint does not provide sufficient detail for analysis of technical points of contention regarding the ’995 Patent. The dispute appears to be centered on the legal interpretation of the proposed product label's language.

V. Key Claim Terms for Construction

  • The Term: "entraining"

  • Context and Importance: This term appears in the preambles of the independent claims of both the RE604 and ’995 Patents and defines the therapeutic goal of the method. The construction of "entraining" is critical because it may determine whether merely labeling a drug for the "treatment" of Non-24 is sufficient to induce infringement of a method to "entrain" a patient's circadian rhythm. Practitioners may focus on this term to dispute whether the accused label teaches the specific outcome required by the claims.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent specification describes the "ultimate treatment goal for individuals with Non-24 is to entrain or synchronize their circadian rhythms" (’995 Patent, col. 2:36-39). This could support an interpretation where any effective treatment of Non-24 inherently achieves "entrainment."
    • Evidence for a Narrower Interpretation: The claims recite a "method of entraining... said method comprising: treating the patient..." (RE604 Patent, Claim 1). This phrasing could support an argument that "treating" and "entraining" are distinct concepts, and that entrainment is a specific, measurable result of the treatment that must be shown. The specification describes methods of measuring circadian rhythms, such as aMT6s analysis, which may support a narrower definition requiring proof of actual synchronization (’995 Patent, col. 11:1-12:51).

  • The Term: "avoiding the use of tasimelteon in combination with fluvoxamine"

  • Context and Importance: This negative limitation in claim 1 of the ’995 Patent is central to the inducement allegation. The case may turn on whether a product label that warns against concurrent use of two drugs "induces" the specific method claimed. Practitioners may focus on whether "avoiding" requires the specific two-step process of discontinuing one drug before starting another, as opposed to simply not prescribing them together from the outset.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The claim preamble sets the context as a patient "being treated with fluvoxamine." Within that context, the only way to "avoid" the combination while starting tasimelteon is to first discontinue the fluvoxamine, potentially supporting the view that the claim's steps are implicitly required by the term "avoiding."
    • Evidence for a Narrower Interpretation: A defendant may argue that the plain meaning of "avoiding" is simply to not use together, and that it does not actively teach the multi-step method of discontinuing one therapy then starting another. The claim language recites the discontinuing/treating steps as the method "comprising" this outcome, which could be interpreted to mean the steps are separate from the act of "avoiding."

VI. Other Allegations

  • Indirect Infringement: The allegations for the six method-of-use patents are primarily for induced infringement under 35 U.S.C. § 271(b). The complaint alleges that Teva, with knowledge of the patents, will induce infringement by physicians and patients through the instructions on its proposed ANDA product label, which will direct users to perform the claimed methods (Compl. ¶¶ 59, 62, 80, 83). Knowledge is alleged based on Teva's Paragraph IV Certifications and the notice letters sent to Vanda (Compl. ¶¶ 9, 13, 51, 72).
  • Willful Infringement: The complaint does not use the word "willful." However, for each patent, it alleges that Teva's statement of its invalidity and non-infringement positions "is devoid of an objective good faith basis in either the facts or the law" and that the "case is exceptional" and warrants attorneys' fees under 35 U.S.C. § 285 (Compl. ¶¶ 67, 88, 109, 129, 150, 170, 200). These allegations form the basis for a potential future finding of enhanced damages or exceptional case status.

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

  • A central legal issue will be one of induced infringement: Does a generic drug label that is required by regulation to mirror the brand-name label, and which instructs on dosages and warns against specific drug combinations, rise to the level of actively encouraging or instructing physicians to perform the patented methods, particularly the multi-step methods involving discontinuing a prior therapy?
  • A key question of claim scope will be whether negative limitations, such as "avoiding the use of tasimelteon in combination with" another drug, can be infringed by inducement when the accused label contains a corresponding warning against such a combination.
  • A critical evidentiary question will relate to the ’977 composition of matter patent: What will discovery reveal about the chemical composition of Teva's ANDA product and the process used to manufacture it, and does that product and process fall within the ’977 patent's specific claims directed to purity levels and enumerated impurities?