DCT

1:23-cv-01340

Harmony Biosciences LLC v. AET Pharma US Inc

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I. Executive Summary and Procedural Information

Case Timeline

Date Event
2005-02-10 ’197 and ’430 Patents Priority Date
2005-04-01 ’947 Patent Priority Date
2012-06-26 ’197 Patent Issue Date
2013-01-15 ’430 Patent Issue Date
2013-07-16 ’947 Patent Issue Date
2019-08-14 WAKIX® (pitolisant hydrochloride) receives FDA approval
2023-10-12 Novitium sends Paragraph IV Notice Letter
2023-10-12 Zenara sends Paragraph IV Notice Letter
2023-10-14 AET sends Paragraph IV Notice Letter
2023-10-16 Annora sends Paragraph IV Notice Letter
2023-11-21 Complaint Filing Date

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

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 describes a need for new therapeutic approaches for neurological disorders including Parkinson's disease, obstructive sleep apnea (OSA), and narcolepsy, noting the limitations of existing treatments ('947 Patent, col. 2:9-34).
  • The Patented Solution: The invention claims methods of treating these disorders by administering non-imidazole alkylamine derivatives that act as antagonists of histamine H₃-receptors ('947 Patent, Abstract). This approach is intended to modulate histamine levels in the brain to address symptoms like excessive daytime sleepiness associated with conditions like narcolepsy and OSA ('947 Patent, col. 1:15-18, col. 2:56-67).
  • Technical Importance: The use of non-imidazole compounds is presented as an improvement over prior imidazole-based H₃-receptor ligands, potentially avoiding issues such as poor blood-brain barrier penetration and adverse interactions with metabolic enzymes like cytochrome P-450 ('947 Patent, col. 2:42-47).

Key Claims at a Glance

  • The complaint asserts independent claims 1 and 10, among others (Compl. ¶142, ¶169).
  • Essential elements of independent claim 10 include:
    • A method for treating narcolepsy,
    • comprising administering to a patient in need thereof a therapeutically effective amount of 3-(4-Chlorophenyl)propyl 3-piperidinopropyl ether, or a pharmaceutically acceptable salt thereof.
  • The complaint reserves the right to assert dependent claims.

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 free base form of the active pharmaceutical ingredient is an oil, which limits its utility in solid dosage forms, while the previously known oxalate salt form has very low aqueous solubility, hindering its bioavailability and pharmaceutical use ('197 Patent, col. 1:12-23).
  • The Patented Solution: The invention discloses a new crystalline monohydrochloride salt of the compound. This specific salt form is described as having unexpectedly high aqueous solubility (over 160 times greater than the oxalate salt) and improved stability, making it a "more suitable salt for its use as a pharmaceutical ingredient" ('197 Patent, col. 2:57-65). The invention is defined by its unique crystallographic fingerprint, identified by specific peaks in an X-ray powder diffraction pattern ('197 Patent, col. 1:52-56).
  • Technical Importance: By creating a salt form with superior physicochemical properties, the invention enabled the development of a stable, soluble, and effective oral tablet formulation for the drug.

Key Claims at a Glance

  • The complaint asserts independent claim 1, among others (Compl. ¶156, ¶183, ¶222, ¶259).
  • Essential elements of independent claim 1 include:
    • Crystalline 1-[3-[3-(4-chlorophenyl)propoxy]propyl]-piperidine monohydrochloride of formula (I)
    • optionally comprising water up to 6%, 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 reserves the right to assert dependent claims.

U.S. Patent No. 8,354,430 - "Monohydrochloride Salt of 1-[3-[3-(4-Chlorophenyl) Propoxy]Propyl] -Piperidine"

  • Technology Synopsis: This patent is a divisional of the application that led to the ’197 patent and addresses the same technical problem of creating a pharmaceutically suitable solid form of pitolisant ('430 Patent, col. 1:8-14). While the ’197 patent claims the crystalline compound itself, the ’430 patent claims methods of treating specific sleep disorders, such as sleep apnea and diurnal somnolence, by administering that specific crystalline monohydrochloride salt.
  • Asserted Claims: The complaint asserts infringement of at least claims 3 and 4 against various defendants (Compl. ¶196, ¶234, ¶271).
  • Accused Features: The accused features are the Defendants' proposed generic pitolisant hydrochloride tablets and their accompanying labels, which allegedly instruct for uses that overlap with the claimed methods of treatment for sleep disorders (Compl. ¶200, ¶238, ¶275).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are the proposed generic pitolisant hydrochloride tablets described in ANDA Nos. 218892 (AET), 218832 (Annora), 218495 (Novitium), and 218796 (Zenara) (Compl. ¶16, ¶25, ¶30, ¶39).

Functionality and Market Context

  • The proposed products are generic versions of WAKIX®, a drug approved for treating excessive daytime sleepiness or cataplexy in adults with narcolepsy (Compl. ¶2). The active ingredient is pitolisant hydrochloride, which functions as an antagonist/inverse agonist of the histamine-3 (H3) receptor (Compl. ¶4). The complaint alleges that the Defendants intend to commercially manufacture and sell these products in the United States upon receiving FDA approval, thereby displacing sales of the branded WAKIX® product before the expiration of the patents-in-suit (Compl. ¶1, ¶50, ¶58).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

8,486,947 Infringement Allegations

Claim Element (from Independent Claim 10) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating narcolepsy, The Defendants' proposed generic products are bioequivalent to WAKIX®, a drug indicated for treating narcolepsy. The product labels will allegedly instruct administration for this purpose. ¶2, ¶147, ¶174 col. 24:12-14
comprising administering to a patient in need thereof a therapeutically effective amount of 3-(4-Chlorophenyl)propyl 3-piperidinopropyl ether, or a pharmaceutically acceptable salt thereof. The Defendants' ANDA products contain pitolisant hydrochloride, which is the hydrochloride salt of the recited chemical compound. ¶143, ¶170, ¶210, ¶247 col. 24:14-18
  • Identified Points of Contention:
    • Scope Questions: The complaint notes that Defendants' Paragraph IV letters did not dispute infringement of many claims of the ’947 patent (Compl. ¶141, ¶168). This suggests that the primary contention will not be over claim scope or infringement, but rather over the patent's validity (e.g., obviousness of the claimed method of treatment).

8,207,197 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) The Defendants' ANDA products are alleged to contain the monohydrochloride salt of 1-[3-[3-(4-chlorophenyl)propoxy]propyl]-piperidine, also known as pitolisant hydrochloride. ¶143, ¶156, ¶170 col. 8:20-24
optionally comprising water up to 6% The accused products are alleged to be the same crystalline form, which the patent describes as potentially containing a variable amount of water up to 6±0.5%. ¶143, ¶156, ¶170 col. 2:4-6
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 the Defendants' generic products infringe all claims of the patent, which requires that they possess the specific crystalline structure defined by these characteristic X-ray diffraction peaks. ¶156, ¶183, ¶222, ¶259 col. 8:25-28
  • Identified Points of Contention:
    • Technical Questions: A central evidentiary question will be whether the Defendants' ANDA products are, in fact, the specific crystalline polymorph claimed in the ’197 patent. What evidence will discovery yield regarding the X-ray diffraction patterns of the accused products, and do those patterns meet the claim limitation requiring characteristic peaks at the specified 2θ angles within the ±0.2° margin?

V. Key Claim Terms for Construction

  • The Term: "having an X-ray diffractogram that comprises characteristic peaks (2θ) at 11.2°, 19.9°, 20.7° and 34.1°±0.2°" (’197 Patent, Claim 1)
  • Context and Importance: This term is the primary structural limitation defining the patented crystalline form. The infringement analysis will depend entirely on whether the accused generic products exhibit this specific crystallographic fingerprint. Practitioners may focus on this term because disputes over polymorphic identity are common in pharmaceutical patent litigation.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim language uses the word "comprises," which may suggest that the presence of these four peaks is sufficient for infringement, even if other peaks in the diffractogram differ from the patent's examples ('197 Patent, col. 8:26). The specification also notes that the crystal may show "small variations related to different water contents" ('197 Patent, col. 2:5-6), which could support some tolerance in the overall pattern.
    • Evidence for a Narrower Interpretation: The patent specification provides a longer list of "additional characteristic peaks" beyond the four recited in the claim ('197 Patent, col. 7:11-15). A party could argue that these additional peaks are essential features of the invention and that a product lacking them, even if it has the four claimed peaks, does not infringe. The detailed description of the crystal structure in Table 1 may also be cited to argue for a more rigid interpretation of the required crystalline form ('197 Patent, col. 5:37-65).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement of the ’947 and ’430 method patents. The basis for this allegation is that the Defendants, upon approval, will market and sell their generic products with product labels and inserts that instruct physicians and patients to administer the drug for the treatment of narcolepsy and its symptoms, thereby encouraging direct infringement by end-users (Compl. ¶147, ¶174, ¶200).
  • Willful Infringement: The complaint alleges that Defendants had actual, pre-suit knowledge of the patents-in-suit, evidenced by their sending of Paragraph IV certification letters (Compl. ¶149, ¶176, ¶202). It further alleges that Defendants submitted their ANDAs without a reasonable basis for their assertions of invalidity or non-infringement, pointing to the fact that Defendants' notice letters did not dispute infringement of numerous asserted claims. This conduct is alleged to make the case "exceptional" under 35 U.S.C. § 285 (Compl. ¶150, ¶177, ¶203).

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

  • A key evidentiary question will be one of polymorphic identity: Will physical analysis of the Defendants' proposed generic products confirm that they embody the specific crystalline structure defined by the X-ray diffraction peaks recited in the ’197 patent, or do they utilize a different, non-infringing crystal form of pitolisant hydrochloride?
  • A core legal issue will be one of validity: Given that the complaint alleges Defendants have not disputed infringement of many claims, the case will likely center on Defendants' assertions that the patents are invalid. The central question for the court will be whether the claimed methods of using pitolisant for narcolepsy or the specific crystalline salt form itself were obvious in light of the prior art at the time of the invention.