DCT

1:19-cv-00685

Vanda Pharma Inc v. Apotex Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-00685, D. Del., 04/12/2019
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Apotex Corp. is a Delaware corporation.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of tasimelteon constitutes an act of infringement of a patent covering methods for its administration.
  • Technical Context: The technology relates to pharmaceutical methods for treating Non-24-Hour Sleep-Wake Disorder (Non-24), a serious circadian rhythm disorder that primarily affects totally blind individuals.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of an ANDA with a Paragraph IV certification for a generic version of Plaintiff's HETLIOZ® (tasimelteon) product. The complaint was filed within the 45-day statutory window after Plaintiff received Defendants' notice letter, triggering a 30-month stay on FDA approval of the generic product.

Case Timeline

Date Event
2012-01-26 '829 Patent - Earliest Priority Date
2014-01-31 FDA Approval of HETLIOZ® NDA
2018-12-11 U.S. Patent No. 10,149,829 Issued
2019-02-28 Vanda receives Apotex's ANDA Notice Letter
2019-04-12 Complaint Filed

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

U.S. Patent No. 10,149,829 - "Treatment of Circadian Rhythm Disorders"

  • Patent Identification: U.S. Patent No. 10,149,829, “Treatment of Circadian Rhythm Disorders,” issued December 11, 2018.

The Invention Explained

  • Problem Addressed: The patent describes Non-24-Hour Sleep-Wake Disorder (Non-24), a condition where individuals, particularly those who are blind and lack light perception, are unable to synchronize their internal biological clock to a 24-hour day. This causes their natural sleep-wake cycles to progressively drift, leading to abnormal sleep patterns and difficulty staying awake during the day (Compl. ¶29; ’829 Patent, col. 2:52-65).
  • The Patented Solution: The patent discloses treating Non-24 by administering tasimelteon, a melatonin agonist that binds to specific receptors in the brain's suprachiasmatic nucleus (SCN) to help entrain the body's clock to a 24-hour cycle (’829 Patent, col. 2:40-50). The claims at issue are specifically directed to managing a drug-drug interaction; they claim a method of treating a patient who is also taking a strong CYP1A2 inhibitor (a class of drugs that affects how tasimelteon is metabolized) by first reducing the dose of the inhibitor and then administering tasimelteon, thereby reducing the patient’s exposure to tasimelteon (Compl. ¶32; ’829 Patent, col. 38:6-19).
  • Technical Importance: The claimed method provides a specific protocol for mitigating potentially harmful drug-drug interactions, which could otherwise lead to a "large increase in tasimelteon exposure and greater risk of adverse reactions" (Compl. ¶39).

Key Claims at a Glance

  • The complaint asserts infringement of claims 1-14, with a focus on independent claim 1 (Compl. ¶32, ¶43).
  • The essential elements of independent claim 1 are:
    • A method of treating a patient for a circadian rhythm disorder or for a sleep disorder.
    • The patient is concurrently being treated with a "strong CYP1A2 inhibitor" from a specific list (fluvoxamine, ciprofloxacin, verapamil).
    • The method comprises the sequential steps of: (A) "reducing the dose of the strong CYP1A2 inhibitor treatment" and then (B) "treating the patient with tasimelteon."
    • The result of this method is that "the exposure to tasimelteon... is reduced."
  • The complaint reserves the right to assert dependent claims (Compl. ¶43, ¶46).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Apotex's ANDA Product: a generic 20 mg oral capsule of tasimelteon intended for the treatment of Non-24 (Compl. ¶9, ¶40).

Functionality and Market Context

  • As a generic equivalent to Vanda's HETLIOZ®, the Apotex ANDA Product is intended to have the same active ingredient, dosage form, and strength (Compl. ¶9). The core of the infringement allegation is that the proposed product label for Apotex's generic will essentially copy the FDA-approved label for HETLIOZ® (Compl. ¶43).
  • The complaint alleges that the HETLIOZ® label, and by extension the proposed Apotex label, instructs physicians to "[a]void use of HETLIOZ® in combination with fluvoxamine or other strong CYP1A2 inhibitors because of a potentially large increase in tasimelteon exposure and greater risk of adverse reactions" (Compl. ¶39). Plaintiff alleges this instruction encourages infringement of the ’829 patent (Compl. ¶43).
  • The complaint asserts that Apotex's product, if approved, will be sold in Delaware and nationwide, where it will compete with and displace sales of HETLIOZ® (Compl. ¶24, ¶25).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The infringement theory is one of inducement under 35 U.S.C. § 271(b), based on the instructions that will be provided in the proposed label for Apotex's ANDA product (Compl. ¶43).

'829 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating a patient for a circadian rhythm disorder or for a sleep disorder... The proposed label for Apotex's generic tasimelteon will instruct that the product is indicated for the treatment of Non-24-Hour Sleep-Wake Disorder, a circadian rhythm disorder. ¶37, ¶40 col. 38:6-8
...wherein the patient is being treated with a strong CYP1A2 inhibitor selected from a group consisting of fluvoxamine, ciprofloxacin, and verapamil... The proposed label will instruct physicians on how to manage patients who are concurrently taking strong CYP1A2 inhibitors like fluvoxamine. ¶39, ¶43 col. 38:8-12
...the method comprising: (A) reducing the dose of the strong CYP1A2 inhibitor treatment and then (B) treating the patient with tasimelteon... The complaint alleges that the label's instruction to "[a]void use of HETLIOZ® in combination with" a strong CYP1A2 inhibitor instructs, recommends, or suggests that physicians perform the claimed steps. ¶39, ¶43 col. 38:12-16
...wherein the exposure to tasimelteon in a patient being treated with tasimelteon for a circadian rhythm disorder or for a sleep disorder is reduced. The proposed label allegedly notes that avoiding co-administration is necessary "because of a potentially large increase in tasimelteon exposure," aligning with the stated outcome of the claimed method. ¶39 col. 38:16-19

Identified Points of Contention

  • Scope Questions: The central point of contention will likely be whether the label's instruction to "avoid use" of tasimelteon in combination with a strong CYP1A2 inhibitor (Compl. ¶39) meets the claim limitation requiring the affirmative, sequential steps of "reducing the dose of the... inhibitor... and then treating the patient with tasimelteon." A defendant may argue that "avoid" instructs physicians not to perform the claimed method, while a plaintiff may argue that "avoid" encourages a physician who deems tasimelteon necessary to first reduce or stop the inhibitor before starting tasimelteon, thus performing the patented method.
  • Technical Questions: What evidence does the complaint provide that the proposed label would lead a physician to perform the specific sequence of steps recited in the claim? The infringement analysis will turn on whether the label is interpreted as a warning against co-administration or as an instruction for a specific therapeutic pathway that matches the claim.

V. Key Claim Terms for Construction

The Term

  • "reducing the dose of the strong CYP1A2 inhibitor treatment and then (B) treating the patient with tasimelteon"

Context and Importance

  • The viability of Vanda's induced infringement claim depends entirely on whether Apotex's proposed label, with its instruction to "avoid use," can be found to encourage or recommend performing this specific sequence of actions. Practitioners may focus on this term because its construction will determine whether there is any act of direct infringement for Apotex to induce.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: A party could argue that the patent’s overall purpose is to manage a dangerous drug interaction. The specification explains that co-administration of tasimelteon with a CYP1A2 inhibitor like fluvoxamine leads to a significant increase in tasimelteon exposure (’829 Patent, Table 6, col. 29:34-30:4). Therefore, one might argue that any instruction aimed at preventing that outcome, such as "avoid use," inherently teaches the principle of the invention and would lead a skilled artisan to perform the claimed steps if tasimelteon treatment were required.
  • Evidence for a Narrower Interpretation: A party could argue the claim language recites a clear and specific sequence of affirmative acts: first a reduction, then a treatment. This is distinct from a simple prohibition like "avoid use." The patent itself uses different language in a separate claim, which recites "discontinuing treatment with the strong CYP1A2 inhibitor" (’829 Patent, col. 38:56-62), suggesting the patentee knew how to claim different actions. An argument could be made that "avoid use" does not require the specific "reduce... and then treat" sequence and could be satisfied by not prescribing tasimelteon at all to such patients.

VI. Other Allegations

Indirect Infringement

  • The complaint alleges induced infringement, stating that Apotex's proposed product label "instructs, recommends, encourages, and/or suggests physicians to infringe claims 1–14" (Compl. ¶43). It also alleges contributory infringement, asserting that the accused product is "not a staple article of commerce and has no substantial uses that do not infringe" (Compl. ¶44).

Willful Infringement

  • The complaint alleges that Apotex had actual knowledge of the '829 patent, at least as of the date of its Notice Letter, and that its non-infringement and invalidity positions are devoid of an objective good faith basis, making the case exceptional (Compl. ¶36, ¶51).

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

The resolution of this case will likely depend on the court’s answers to two central questions:

  • A core issue will be one of induced infringement: Can a drug label that instructs physicians to "avoid use" of two drugs in combination be legally interpreted as actively encouraging infringement of a method patent that claims a specific, affirmative sequence of reducing the dose of one drug and then administering the other?
  • A related evidentiary question will be one of specific intent: What evidence can be presented to show that Apotex, by creating its proposed label, intended for physicians to perform the patented method, rather than simply intending for them to heed the label's warning and refrain from prescribing tasimelteon to the specified patient population?