DCT

1:23-cv-01675

MSN Laboratories Private Ltd v. Bioprojet Societe Civile De Recherche

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-01675, E.D. Va., 12/08/2023
  • Venue Allegations: Venue is alleged to be proper because both parties are non-U.S. residents, and Defendant may be sued in any judicial district. The complaint also alleges Defendant has purposefully availed itself of the forum by selling products (WAKIX®) in Virginia and by previously litigating other patent rights in the district.
  • Core Dispute: Plaintiff seeks a declaratory judgment that its proposed generic pitolisant hydrochloride product will not infringe, and that the claims are invalid for, three of Defendant's Orange Book-listed patents.
  • Technical Context: The technology relates to pharmaceutical formulations of pitolisant, a histamine H3-receptor inverse agonist, and methods of its use for treating sleep-related and neurological disorders.
  • Key Procedural History: This declaratory judgment action arises under the Hatch-Waxman Act. Plaintiff MSN Laboratories filed an Abbreviated New Drug Application (ANDA) with a Paragraph IV certification, asserting that Defendant Bioprojet's patents for the reference drug WAKIX® are invalid or not infringed. After receiving notice, Bioprojet did not file an infringement suit within the statutory 45-day window, foregoing a 30-month stay of FDA approval. MSN filed this action to obtain legal certainty and clear its path to market its generic product prior to the patents' expiration.

Case Timeline

Date Event
2005-02-10 Priority Date for '’197 and '’430 Patents
2005-04-01 Priority Date for '’947 Patent
2012-06-26 '197 Patent Issue Date
2013-01-15 '430 Patent Issue Date
2013-07-16 '947 Patent Issue Date
2019-09-11 Patents-in-suit listed in Orange Book for NDA 211150
2023-08-14 MSN files ANDA No. 218873
2023-09-26 MSN receives FDA's Paragraph IV Acknowledgement Letter
2023-10-18 Bioprojet receives MSN's notice letter
2023-12-04 45-day deadline for Bioprojet to sue expires
2023-12-08 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,” issued June 26, 2012

The Invention Explained

  • Problem Addressed: The patent describes prior forms of the active pharmaceutical ingredient pitolisant as being unsuitable for pharmaceutical use; the free base form is an oil, and the oxalate salt form has very low aqueous solubility (’197 Patent, col. 1:12-23). These properties limit the development of effective oral dosage forms.
  • The Patented Solution: The invention is a novel crystalline monohydrochloride salt of pitolisant that is described as being unexpectedly much more soluble in water than the prior oxalate salt form (’197 Patent, col. 2:57-62). The patent details the specific X-ray powder diffraction (XRPD) pattern and other physical characteristics that define this specific crystalline form, or polymorph, which is more suitable for use as a pharmaceutical ingredient (’197 Patent, col. 1:49-56; col. 2:62-65).
  • Technical Importance: Developing a stable, highly soluble crystalline form of a drug is a critical step in pharmaceutical manufacturing, as it enables reliable formulation, bioavailability, and dosing.

Key Claims at a Glance

  • The complaint does not identify specific asserted claims. Claim 1, an independent claim, is directed to the crystalline composition of matter itself.
  • Claim 1 Elements:
    • 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 seeks a declaration of non-infringement of "one or more valid and enforceable claim" of the patent, which could include dependent claims (Compl. ¶ 50).

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 background identifies a need for new treatments for several neurological and sleep-related disorders, including Parkinson's disease (PD), obstructive sleep apnea (OSA), dementia with Lewy bodies (DLB), and vascular dementia (VD) (’947 Patent, col. 2:9-12). It notes that while the histamine H3-receptor was a known target, its role in these specific diseases had not been previously reported (’947 Patent, col. 2:5-8).
  • The Patented Solution: The invention is a method of treating these specific diseases by administering a non-imidazole alkylamine that acts as a histamine H3-receptor antagonist or inverse agonist, such as pitolisant (’947 Patent, col. 43:55-64). By increasing histamine release in the brain, these compounds are asserted to improve symptoms like excessive daytime sleepiness associated with these conditions (’947 Patent, col. 2:15-19; col. 44:1-4).
  • Technical Importance: The invention proposes a new therapeutic use for a known class of compounds, targeting a biological pathway (histaminergic system) not traditionally associated with the primary mechanisms of disorders like Parkinson's disease.

Key Claims at a Glance

  • The complaint does not identify specific asserted claims. Claim 1 is an independent method of use claim.
  • Claim 1 Elements:
    • A method for treating excessive daytime sleepiness
    • comprising administering to a patient in need thereof a compound of formula (IIa)
    • wherein R¹ and R² form together with the nitrogen atom to which they are attached a saturated nitrogen-containing ring
    • ... [further defining the chemical structure to encompass pitolisant] ...
    • wherein said patient is suffering from Parkinson's disease, narcolepsy, or sleep apnea.
  • The complaint seeks a declaration of non-infringement of "one or more valid and enforceable claim" of the patent (Compl. ¶ 42).

U.S. Patent No. 8,354,430 - “Monohydrochloride Salt of 1-[3-[3-(4-Chlorophenyl) Propoxy]Propyl] -Piperidine,” issued January 15, 2013

  • Technology Synopsis: This patent is a divisional of the application that led to the ’197 patent. It claims methods of treating various conditions, including sleep apnea and diurnal somnolence, by administering the specific crystalline monohydrochloride salt of pitolisant that is described in the ’197 patent (’430 Patent, Abstract; col. 3:9-16).
  • Asserted Claims: The complaint does not specify claims. Independent claims 1 and 3 are directed to methods of treating sleep apnea and diurnal somnolence, respectively.
  • Accused Features: The complaint alleges that the manufacture and sale of its ANDA Product will not infringe the claims of the ’430 patent (Compl. ¶ 54). This implies that the proposed labeling for MSN's product does not align with the patented methods of use.

III. The Accused Instrumentality

Product Identification

The accused instrumentality is MSN Laboratories' generic pitolisant tablet (“MSN’s ANDA Product”), for which it seeks FDA approval under ANDA No. 218873 (Compl. ¶27).

Functionality and Market Context

The complaint describes MSN's ANDA Product as a generic version of the brand-name drug WAKIX® (Compl. ¶21, 27). WAKIX® is available in film-coated tablets containing 5 mg or 20 mg of pitolisant hydrochloride (Compl. ¶22). The purpose of the product is to provide a lower-cost, generic alternative to WAKIX® for the public upon receiving FDA approval (Compl. ¶35). The complaint does not provide further technical details on the composition or manufacturing of MSN's specific product. No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The declaratory judgment complaint asserts non-infringement but does not provide specific factual allegations or claim charts detailing its non-infringement theories. The complaint makes the conclusory statement that the "manufacture, use, offer for sale, sale, and/or importation into the United States of MSN's ANDA Product... does not infringe one or more valid and enforceable claim" of each of the patents-in-suit (Compl. ¶¶ 42, 50, 54). Therefore, a claim chart summary cannot be constructed from the pleading. The analysis below identifies the likely points of contention based on the nature of the patents and the context of ANDA litigation.

Identified Points of Contention

  • ’197 Patent (Crystalline Form): A central factual question for non-infringement will be whether MSN's ANDA Product contains the exact crystalline form of pitolisant monohydrochloride claimed in the ’197 patent. The dispute will likely focus on whether the XRPD pattern of MSN's product matches the characteristic peaks recited in the claims, such as those in Claim 1. MSN’s non-infringement position would be that its product either uses a different salt form, an amorphous form, or a different polymorph of pitolisant monohydrochloride that does not fall within the scope of the asserted claims.
  • ’947 and ’430 Patents (Methods of Use): For the method of use patents, infringement is typically assessed by determining whether the ANDA applicant's proposed drug label will induce physicians to prescribe the drug for the patented indications. A key question will be whether MSN's proposed label "carves out" the specific uses claimed in the ’947 and ’430 patents. MSN's non-infringement position would be that its proposed label omits any indication for treating the specific conditions claimed (e.g., Parkinson's disease, obstructive sleep apnea), thereby not encouraging, recommending, or promoting an infringing use.

V. Key Claim Terms for Construction

For the ’197 and ’430 Patents

  • The Term: "crystalline...monohydrochloride...having an X-ray diffractogram that comprises characteristic peaks (2θ) at 11.2°, 19.9°, 20.7° and 34.1° ±0.2°"
  • Context and Importance: This term defines the specific polymorph of the drug substance. The infringement analysis for the composition claims (’197 patent) and method of use claims for that composition (’430 patent) will depend entirely on whether MSN's product has this exact crystalline structure. Practitioners may focus on the term "comprises" and the "±0.2°" range to argue for or against infringement, as minor variations in measurement can be critical.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The use of the open-ended term "comprises" may support an interpretation that the diffractogram can include other peaks in addition to the ones listed, as long as the recited characteristic peaks are present (’197 Patent, col. 13:27-29). The specification also notes that the crystal may show a "variable content of water," which could be argued to affect peak positions slightly and support a flexible reading of the "±0.2°" tolerance (’197 Patent, col. 2:1-2).
    • Evidence for a Narrower Interpretation: The patent repeatedly emphasizes the specific "characteristic peaks" as the defining feature of this novel crystalline form (’197 Patent, col. 2:53-56). A party could argue that these specific peaks, within the specified tolerance, are essential and that any significant deviation or absence of these peaks places a product outside the claim scope. The detailed tables and Figure 1 provide a precise fingerprint that could be used to argue for a narrow definition tied strictly to the disclosed data (’197 Patent, FIG. 1; col. 5, Table 1).

For the ’947 Patent

  • The Term: "treating excessive daytime sleepiness ... wherein said patient is suffering from Parkinson's disease, narcolepsy, or sleep apnea" (from Claim 1)
  • Context and Importance: This method of use claim is limited to a specific symptom ("excessive daytime sleepiness") within a specific set of patient populations. A finding of induced infringement will require evidence that MSN's proposed label instructs or encourages physicians to prescribe its generic drug for this symptom in one of these diseases.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification broadly discusses the role of H3-receptor antagonists in promoting wakefulness and improving cognitive processes, which could support a view that "treating" encompasses general improvements in alertness beyond a formal diagnosis (’947 Patent, col. 1:15-19).
    • Evidence for a Narrower Interpretation: The claim explicitly links the treatment of the symptom to the underlying disease. The specification provides detailed examples of clinical trials for these specific conditions, suggesting the invention is tied to these particular, defined patient populations (’947 Patent, col. 43-44, Examples 2, 4, 5). A party would argue that a generic label must target this specific patient subgroup to induce infringement.

VI. Other Allegations

The complaint is for declaratory judgment and does not contain allegations of indirect or willful infringement against the Defendant.

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

  • A central evidentiary question will be one of polymorphic identity: Does MSN's ANDA product, intended as a generic version of WAKIX®, utilize the specific crystalline monohydrochloride salt defined by the XRPD peaks in the ’197 and ’430 patents, or does it employ a non-infringing alternative form (e.g., amorphous or a different polymorph)?
  • A key legal question will be one of induced infringement via labeling: Will the final, FDA-approved label for MSN's generic product contain indications for use that overlap with the methods of treating specific patient populations (e.g., those with obstructive sleep apnea or Parkinson's disease) as claimed in the ’947 and ’430 patents, or will MSN successfully "carve out" these patented uses to avoid inducing infringement?
  • A foundational issue for the invalidity counts will be one of obviousness: Given the prior art disclosing pitolisant and the general knowledge of salt selection and polymorph screening in the pharmaceutical arts, were the claimed crystalline form (’197 patent) and its use for treating conditions like sleep apnea (’947 and ’430 patents) an obvious development to a person of ordinary skill in the art?