DCT

1:24-cv-00941

Harmony Biosciences LLC v. AET Pharma US Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-00941, D. Del., 08/13/2024
  • Venue Allegations: Venue is asserted based on Defendant AET Pharma US, Inc. being a Delaware corporation and the foreign co-defendants being subject to personal jurisdiction in the district, making them suable in any judicial district.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the narcolepsy drug WAKIX® (pitolisant hydrochloride) constitutes an act of infringement of two U.S. patents.
  • Technical Context: The dispute centers on pharmaceutical compositions containing pitolisant, a histamine H3-receptor antagonist/inverse agonist used to treat excessive daytime sleepiness associated with narcolepsy.
  • Key Procedural History: This action follows a related case filed in November 2023 between the same parties concerning the same patents and ANDA. The current lawsuit was initiated after Plaintiffs received a second notice letter from the Defendants regarding their ANDA submission. The complaint notes that Defendants' notice letters did not dispute infringement of the specific patent claims asserted in this action.

Case Timeline

Date Event
2005-02-10 ’197 Patent Priority Date
2005-04-01 ’947 Patent Priority Date
2012-06-26 ’197 Patent Issue Date
2013-07-16 ’947 Patent Issue Date
2019-08-14 FDA Approval of WAKIX®
2023-10-14 Defendants Send First Paragraph IV Notice Letter to Plaintiffs
2023-11-21 Plaintiffs File Related Lawsuit (No. 23-cv-1340)
2024-08-07 Defendants Send Second Paragraph IV Notice Letter to Plaintiffs
2024-08-13 Complaint Filing Date

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

U.S. Patent No. 8,207,197 - "Monohydrochloride Salt of 1-[3-[3-(4-Chlorophenyl) Propoxy]Propyl] -Piperidine"

The Invention Explained

  • Problem Addressed: The patent's background section states that the active pharmaceutical ingredient, 1-[3-[3-(4-chlorophenyl)propoxy]propyl]-piperidine (pitolisant), is limited in its utility as a free base because of its "oily nature" and as an oxalate salt because of its "low aqueous solubility" (’197 Patent, col. 1:12-23).
  • The Patented Solution: The invention is a novel crystalline monohydrochloride salt of pitolisant. This specific salt form is described as having an "unexpectedly much higher" aqueous solubility and a "better profile of stability" compared to previously known forms, making it a "more suitable salt for its use as a pharmaceutical ingredient" (’197 Patent, Abstract; col. 1:57-col. 2:4).
  • Technical Importance: The development of a stable and highly soluble salt form is a critical step in pharmaceutical formulation, enabling the creation of an effective and manufacturable oral drug product from an otherwise difficult-to-handle compound (’197 Patent, col. 1:57-col. 2:4).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 (Compl. ¶79).
  • Independent Claim 1 requires:
    • Crystalline 1-[3-[3-(4-chlorophenyl)propoxy]propyl]-piperidine monohydrochloride of formula (I)
    • Optionally comprising water up to 6%
    • Having an X-ray diffractogram that comprises characteristic peaks (2θ) at 11.2°, 19.9°, 20.7° and 34.1° ±0.2°
  • The complaint does not explicitly reserve the right to assert other claims, but the prayer for relief requests judgment on "one or more claims" (Compl., Prayer for Relief ¶B).

U.S. Patent No. 8,486,947 - "Treatment of Parkinson's Disease, Obstructive Sleep Apnea, Dementia with Lewy Bodies, Vascular Dementia with Non-Imidazole Alkylamines Histamine H3-Receptor Ligands"

The Invention Explained

  • Problem Addressed: The patent explains that neurodegenerative conditions like Parkinson's disease (PD) and breathing disorders like obstructive sleep apnea (OSA) are often accompanied by significant "sleep and vigilance disorders," including excessive daytime sleepiness, for which existing treatments are "poorly efficient" (’947 Patent, col. 2:35-55).
  • The Patented Solution: The patent discloses a method for treating these conditions by administering a non-imidazole histamine H3-receptor antagonist. The specification describes how such compounds, specifically pitolisant, can normalize sleep-wakefulness patterns and improve daytime sleepiness in relevant patient populations, thereby addressing a key unmet need (’947 Patent, col. 43:21-44:52; col. 46:12-30).
  • Technical Importance: The invention provided a new pharmacological approach for treating debilitating non-motor symptoms, like excessive sleepiness, that are common in patients with certain neurological and sleep disorders but were not adequately addressed by prior therapies (’947 Patent, col. 2:49-55).

Key Claims at a Glance

  • The complaint asserts infringement of claims 1-5 and 10-14 (Compl. ¶65).
  • Independent Claim 1 requires:
    • A method for treating excessive daytime sleepiness
    • Comprising administering to a patient in need thereof a compound of formula (IIa), which covers a class of non-imidazole alkylamines
    • Wherein said patient is suffering from Parkinson's disease, narcolepsy, or sleep apnea
  • Independent Claim 12 is similar but recites a specific list of compounds, including pitolisant, rather than a general formula.

III. The Accused Instrumentality

Product Identification

  • Defendants' proposed generic pitolisant hydrochloride tablets, for which Abbreviated New Drug Application (ANDA) No. 218892 was submitted to the FDA (Compl. ¶1, ¶46). The tablets are identified as having dosages of 4.45 mg and 17.8 mg (Compl. ¶47).

Functionality and Market Context

  • The accused product is a generic version of Plaintiffs' WAKIX® drug, which is indicated for the treatment of excessive daytime sleepiness (EDS) or cataplexy in adults with narcolepsy (Compl. ¶3). The complaint alleges that Defendants' ANDA seeks approval to manufacture and market this generic product before the expiration of the Asserted Patents (Compl. ¶46-47). The complaint further alleges that Defendants' notice letters confirm the ANDA product contains pitolisant hydrochloride (Compl. ¶66). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

’197 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
Crystalline 1-[3-[3-(4-chlorophenyl)propoxy]propyl]-piperidine monohydrochloride of formula (I) Defendants' ANDA product contains pitolisant hydrochloride, the compound of formula (I). ¶66 col. 1:30-38
optionally comprising water up to 6% The complaint does not provide sufficient detail for analysis of this element. N/A col. 7:21-23
and having an X-ray diffractogram that comprises characteristic peaks (2θ) at 11.2°, 19.9°, 20.7° and 34.1° ±0.2° The complaint alleges that Defendants' notice letter did not dispute infringement of any claims of the ’197 patent. ¶50, ¶78 col. 7:9-15

’947 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating excessive daytime sleepiness Upon approval, Defendants will market their ANDA product with a label instructing its use for treating excessive daytime sleepiness, as it is a generic version of WAKIX®, which is approved for that indication. ¶3, ¶70 col. 44:53-56
comprising administering to a patient in need thereof a compound of formula (IIa)... Defendants' ANDA product contains pitolisant hydrochloride, which is a compound falling within the scope of formula (IIa). ¶66 col. 9:1-col. 13:32
wherein said patient is suffering from Parkinson's disease, narcolepsy, or sleep apnea. The proposed product label for the ANDA product will instruct its use for narcolepsy, which is one of the patient populations specified in the claim. ¶3, ¶70 col. 44:53-56
  • Identified Points of Contention:
    • Technical Questions: A primary technical question for the ’197 patent is whether Defendants' proposed generic product is, in fact, the specific "crystalline" form claimed, possessing the characteristic X-ray diffraction peaks recited in claim 1. The complaint alleges that Defendants have not provided the ANDA materials that would allow for this analysis (Compl. ¶55).
    • Scope Questions: For the ’947 patent, the infringement analysis raises a strategic legal question. The complaint alleges that Defendants did not dispute infringement of the asserted method-of-use claims in their notice letters (Compl. ¶64). This raises the question of what factual or legal basis Defendants will assert for their Paragraph IV certification of non-infringement, especially concerning whether the proposed product label carves out the patented indications.

V. Key Claim Terms for Construction

  • The Term: "crystalline" (’197 Patent, Claim 1)

  • Context and Importance: The patentability of the invention in the ’197 patent is predicated on the discovery of a specific crystalline form of pitolisant monohydrochloride that overcomes the problems of the oily free base and the poorly soluble oxalate salt. Therefore, the definition of "crystalline," as defined by the specific analytical data in the claim, is central to the infringement analysis.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification notes that the crystalline form "may show a variable content of water" and that different samples "correspond to the same crystal structure, except for small variations" (’197 Patent, col. 2:1-6), which may support an argument that the claim scope is not rigidly fixed.
    • Evidence for a Narrower Interpretation: Claim 1 explicitly defines the crystalline form by requiring an X-ray diffractogram with four specific characteristic peaks at defined 2θ values (±0.2°). This provides a precise, narrow, and testable definition of the claimed structure (’197 Patent, col. 7:9-15).

  • The Term: "treating" (’947 Patent, Claim 1)

  • Context and Importance: As a method-of-use claim, the scope of "treating" is critical. In the ANDA context, this term's meaning will be evaluated primarily by what is stated on the proposed product label. Practitioners may focus on this term because infringement will hinge on whether the label instructions encourage, recommend, or promote administration of the drug for the claimed purpose.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification provides an explicit and broad definition, stating that "treating" or "treatment" means "reversing, alleviating, inhibiting the progress of, or preventing the disorder or condition" (’947 Patent, col. 42:15-20). This language could encompass a wide variety of label statements beyond a direct instruction to "treat."
    • Evidence for a Narrower Interpretation: A defendant could argue that infringement requires the proposed label to explicitly recite one of the patent's listed diseases (e.g., "narcolepsy") in direct connection with the therapeutic benefit (e.g., "excessive daytime sleepiness"). The strength of this argument would depend on the precise wording of the final proposed label.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon FDA approval, Defendants will induce infringement of the ’947 and ’197 patents by including a product label and insert with instructions for administering the generic product for the patented uses, thereby encouraging physicians and patients to perform the claimed methods (Compl. ¶70, ¶83).
  • Willful Infringement: The complaint seeks a finding that the case is "exceptional" under 35 U.S.C. § 285, which is the statutory basis for enhanced damages and attorney's fees often associated with willfulness. This is based on allegations that Defendants had actual knowledge of the patents prior to filing the ANDA and submitted their Paragraph IV certifications "without a reasonable basis," particularly given their failure to dispute infringement of the asserted claims in their notice letters (Compl. ¶72-73, ¶85-86).

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

  • A core issue will be one of polymorphic identity: Will discovery and expert testing reveal that Defendants' proposed generic product is the specific crystalline monohydrochloride salt defined by the characteristic X-ray diffraction peaks recited in the ’197 patent, or does it utilize a different, non-infringing crystal form?
  • A key question of induced infringement will center on Defendants' labeling strategy for the ’947 patent: Given that Defendants allegedly did not contest infringement of the method-of-use claims in their notice letters, what factual or legal basis will they assert for their non-infringement certification, and will the final proposed label contain language that constitutes inducement to infringe?
  • Finally, a central procedural question will be the reasonableness of Defendants' litigation position: Did Defendants' submission of a Paragraph IV certification, while allegedly failing to provide a basis for non-infringement in their notice letters, render this case "exceptional" and expose them to potential enhanced damages and attorney's fees?