DCT

1:25-cv-00102

Harmony Biosciences Management Inc v. Lupin Ltd

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:25-cv-00102, D. Del., 01/24/2025
  • Venue Allegations: Venue is alleged to be proper for Lupin Pharmaceuticals, Inc. as it is a Delaware corporation. For Lupin Limited, an Indian corporation, venue is alleged based on its purposeful availment of and systematic contacts with Delaware, its intent to sell products in the state, and its status as a foreign corporation subject to suit in any judicial district.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of WAKIX® (pitolisant hydrochloride) tablets constitutes an act of infringement of two patents covering the drug's composition and methods of use.
  • Technical Context: The technology relates to pitolisant, a histamine-3 (H3) receptor antagonist/inverse agonist, used for treating excessive daytime sleepiness or cataplexy in adult patients with narcolepsy.
  • Key Procedural History: This action follows a prior lawsuit filed on November 9, 2023, by the same plaintiffs against Lupin, also concerning infringement of the asserted patents by the same ANDA submission. The current suit was filed within 45 days of Plaintiffs receiving a second notice letter from Lupin dated December 12, 2024. The complaint notes that Lupin's notice letters did not dispute infringement of the asserted claims.

Case Timeline

Date Event
2005-04-01 Earliest Priority Date for ’947 Patent
2005-02-10 Earliest Priority Date for ’197 Patent
2012-06-26 ’197 Patent Issued
2013-07-16 ’947 Patent Issued
2019-08-14 WAKIX® (pitolisant hydrochloride) first received FDA approval
2023-09-27 Lupin sent first Paragraph IV Notice Letter to Plaintiffs
2023-11-09 Plaintiffs filed related action against Lupin (1:23-cv-1286)
2024-12-12 Lupin sent second Paragraph IV Notice Letter to Plaintiffs
2025-01-24 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, issued July 16, 2013

The Invention Explained

  • Problem Addressed: The patent identifies that a large proportion of patients with diseases like Parkinson's, obstructive sleep apnea (OSA), and certain dementias suffer from significant sleep and vigilance disorders, such as excessive daytime sleepiness, and that existing treatments are poorly efficient (’947 Patent, col. 2:35-55). It notes that the role of the histamine H3-receptor in these specific diseases had not been previously reported (’947 Patent, col. 2:5-7).
  • The Patented Solution: The invention claims a method of treating these conditions, particularly their associated sleep disorders, by administering non-imidazole alkylamine compounds that act as antagonists or inverse agonists of the histamine H3-receptor (’947 Patent, Abstract; col. 45:6-9). The patent posits that these compounds can markedly improve major symptoms of these diseases by, for example, inducing "an extended wakefulness" (’947 Patent, col. 1:15-18, col. 3:3-5).
  • Technical Importance: The patent claims a new therapeutic use for a class of compounds, linking the H3-receptor pathway to the treatment of sleep disorders in specific neurodegenerative and respiratory conditions where such a link was not previously established.

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claims 2-5 and 10-14 (Compl. ¶56).
  • Independent Claim 1 requires:
    • A method for treating excessive daytime sleepiness.
    • Comprising administering to a patient in need thereof a compound of formula (IIa).
    • Wherein the compound has a specific chemical structure including a saturated nitrogen-containing ring, an ether linkage (-O-), and a phenyl group.
    • And wherein the patient is suffering from Parkinson's disease, narcolepsy, or sleep apnea.

U.S. Patent No. 8,207,197 - Monohydrochloride Salt of 1-[3-[3-(4-Chlorophenyl) Propoxy]Propyl]-Piperidine, issued June 26, 2012

The Invention Explained

  • Problem Addressed: The patent’s background section explains that the free base form of the active pharmaceutical ingredient is an oil, limiting its utility, while a previously known oxalate salt form is crystalline but has very low aqueous solubility, which also limits its use as a pharmaceutical ingredient (’197 Patent, col. 1:18-28).
  • The Patented Solution: The invention is a specific crystalline monohydrochloride salt of the compound 1-[3-[3-(4-chlorophenyl)propoxy]propyl]-piperidine (pitolisant) (’197 Patent, Abstract). This novel salt form is described as having "surprisingly" much higher aqueous solubility and a better stability profile compared to prior forms, making it a "more suitable salt for its use as a pharmaceutical ingredient" (’197 Patent, col. 2:57-65). The patent provides extensive characterization data, including specific X-ray diffraction (XRD) peak locations that define the crystalline structure (’197 Patent, Fig. 1; col. 4:10-16).
  • Technical Importance: The creation of a new salt form with improved physical properties like high solubility and stability is a critical innovation in pharmaceutical development, as it can enable the creation of a viable, effective, and manufacturable drug product.

Key Claims at a Glance

  • The complaint asserts at least independent claim 1 (Compl. ¶71).
  • 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°, each with a tolerance of ±0.2°.

III. The Accused Instrumentality

Product Identification

  • Lupin’s proposed generic pitolisant hydrochloride tablets, as described in its ANDA No. 218846 (Compl. ¶1).

Functionality and Market Context

  • The accused products are film-coated tablets containing 5 mg or 20 mg of pitolisant hydrochloride, the same active ingredient as WAKIX® (Compl. ¶¶9, 57). According to the complaint, Lupin’s proposed package insert states the product will be indicated for the treatment of excessive daytime sleepiness (EDS) in adult patients with narcolepsy (Compl. ¶58). The complaint alleges that upon approval, Lupin intends to manufacture, market, and sell these products in the United States, directly competing with and displacing sales of WAKIX® (Compl. ¶¶23, 32).
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint’s primary infringement theory is statutory under 35 U.S.C. § 271(e)(2)(A), which defines the submission of an ANDA seeking approval to market a generic drug before patent expiration as an act of infringement (Compl. ¶59, ¶72). A notable feature of the complaint is its repeated allegation that Lupin’s notice letters did not dispute infringement of the asserted claims (Compl. ¶¶42, 46, 55, 70). This suggests the core of the dispute may center on patent validity rather than non-infringement.

8,486,947 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating excessive daytime sleepiness... wherein said patient is suffering from... narcolepsy Lupin's proposed package insert for its ANDA Products states that the product will be indicated for the treatment of excessive daytime sleepiness ("EDS") in adult patients with narcolepsy. Lupin will induce infringement by providing instructions for this patented use. ¶58, ¶62 col. 45:6-9
comprising administering to a patient in need thereof a compound of formula (IIa)... wherein... X" is --O--; the chain B" is an unbranched alkyl comprising 3 carbon atoms; and the group Y" represents a phenyl group... Lupin's ANDA Products contain pitolisant hydrochloride, which is the hydrochloride salt of 3-(4-Chlorophenyl)propyl 3-piperidinopropyl ether. This compound falls within the scope of the chemical structure defined by formula (IIa) in the claim. The complaint alleges Lupin did not dispute that its product meets these structural limitations. ¶57, ¶55 col. 45:10-44
wherein R¹ and R² form together with the nitrogen atom to which they are attached a saturated nitrogen-containing ring: N-(CRR)m i) with m ranging from 2 to 8 The pitolisant compound in Lupin's ANDA Product contains a piperidine ring, which is a saturated, six-membered nitrogen-containing ring (m=5), meeting this limitation. ¶57 col. 45:14-22
  • Identified Points of Contention: Since the complaint alleges infringement was not disputed, the primary challenge to the ’947 Patent will likely be on validity grounds, such as obviousness. A question for the court will be whether it was obvious to use an H3-receptor antagonist like pitolisant to treat excessive daytime sleepiness in narcolepsy patients at the time of the invention.

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 Lupin ANDA Products are alleged to contain pitolisant hydrochloride (Compl. ¶57). The complaint alleges infringement of this claim, which requires the compound to be in a specific crystalline monohydrochloride salt form. The complaint notes that Lupin did not dispute infringement of any claim of the '197 patent in its notice letter (Compl. ¶70). ¶57, ¶70, ¶71 col. 1:32-43
and having an X-ray diffractogram that comprises characteristic peaks (2θ) at 11.2°, 19.9°, 20.7° and 34.1° ±0.2° By alleging infringement of Claim 1, Plaintiffs implicitly allege that Lupin's proposed generic product will possess the same crystalline form defined by these specific X-ray diffraction peaks. ¶71 col. 13:25-28
  • Identified Points of Contention:
    • Technical Questions: While infringement is allegedly not disputed, a key evidentiary question remains: what proof will establish that Lupin’s ANDA product is, in fact, the specific crystalline polymorph claimed in the ’197 Patent? Evidence from Lupin's ANDA submission will be central to resolving this.
    • Scope Questions: The validity of the patent will likely be challenged. A question for the court will be whether the claimed crystalline form was non-obvious over the prior art, which disclosed the compound as an oil and as a poorly soluble oxalate salt (’197 Patent, col. 1:18-28).

V. Key Claim Terms for Construction

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

    • Context and Importance: This term is the lynchpin of the ’197 patent, distinguishing the invention from the prior art oily free base and a different, less soluble salt form. The definition of "crystalline" and the scope of the accompanying XRD peak limitations will be critical for both infringement (does Lupin's product meet the definition?) and validity (is the claimed form patentably distinct from the prior art?).
    • Intrinsic Evidence for a Broader Interpretation: A party could argue for the plain and ordinary meaning of "crystalline" as a solid material whose constituents are arranged in a highly ordered microscopic structure.
    • Intrinsic Evidence for a Narrower Interpretation: The claim itself explicitly defines the crystalline form by reference to four specific X-ray diffraction peaks (11.2°, 19.9°, 20.7°, and 34.1° ±0.2°). The specification provides significant detail on this structure, stating that the salt "has an X-ray powder diffraction pattern with characteristic peaks" at these locations (’197 Patent, col. 2:53-56) and provides a full diffractogram in Figure 1. A party could argue that "crystalline" in the context of this patent is not a general term but is strictly limited to the specific polymorphic form that produces these peaks.

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

    • Context and Importance: As a method of treatment claim, the meaning of "treating" defines the scope of the infringing act. Practitioners may focus on this term because its scope (e.g., covering prophylaxis vs. only ameliorating existing symptoms) could influence the analysis of induced infringement based on a product's label.
    • Intrinsic Evidence for a Broader Interpretation: A related patent in the same family states that the term "treatment" encompasses "both treatment and prophylaxis of diseases or pathologic conditions" (’197 Patent, col. 4:21-23), suggesting the patentee intended a broad meaning.
    • Intrinsic Evidence for a Narrower Interpretation: The ’947 Patent repeatedly frames the invention in terms of improving or normalizing existing conditions, such as causing "an extended wakefulness" or improving "major symptoms" (’947 Patent, col. 1:16, col. 3:5). A party could argue this context limits "treating" to the alleviation of present symptoms, not prevention.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement of the ’947 method patent. It asserts that by marketing the ANDA products with a label and package insert containing instructions for administration, Lupin will knowingly and intentionally encourage and instruct physicians, pharmacies, and patients to perform the patented method of treating EDS in narcolepsy patients (Compl. ¶62, ¶75).
  • Willful Infringement: The complaint alleges that Lupin had actual knowledge of the Asserted Patents prior to filing its ANDA, as evidenced by its Paragraph IV certifications (Compl. ¶64, ¶77). It further alleges that Lupin acted without a reasonable basis for asserting invalidity or non-infringement, pointing specifically to the fact that Lupin's notice letters did not dispute infringement of the asserted claims. This conduct is alleged to render the case "exceptional" under 35 U.S.C. § 285, which could entitle Plaintiffs to attorneys' fees (Compl. ¶65, ¶78).

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

Given that the complaint alleges infringement is not in dispute, the litigation will likely pivot to the validity of the asserted patents.

  • A core issue will be one of patentable distinction: For the ’197 Patent, can Lupin prove by clear and convincing evidence that the claimed crystalline monohydrochloride salt was obvious in view of prior art disclosing the same compound as an oil and as a different, less soluble oxalate salt? The outcome may depend on whether the improved solubility and stability are deemed "unexpected" results sufficient to support non-obviousness.
  • A second central question will concern the obviousness of a new use: For the ’947 Patent, was it obvious to try using an H3-receptor antagonist to treat excessive daytime sleepiness in narcolepsy patients? The case may turn on the level of skill in the art and whether there was a recognized motivation to explore this specific therapeutic pathway at the time of the invention.
  • Finally, an important procedural and financial question will be one of exceptionality: Does Lupin’s act of filing a Paragraph IV certification while allegedly failing to contest infringement in its notice letters amount to litigation misconduct that renders the case "exceptional" under 35 U.S.C. § 285, potentially exposing it to an award of attorneys' fees?