DCT

1:18-cv-00148

H Lundbeck As v. Prinston Pharmaceutical Inc

Log In
Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-00148, D. Del., 01/25/2018
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendants Prinston Pharmaceutical and Solco Healthcare are incorporated in Delaware, and all Defendants are alleged to conduct systematic business in the state and intend to sell the accused products there.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA, seeking approval to market generic versions of the antidepressant TRINTELLIX®, constitutes an act of patent infringement.
  • Technical Context: The technology involves a specific compound, vortioxetine, in a particular crystalline salt form, used as an oral antidepressant for treating Major Depressive Disorder.
  • Key Procedural History: The litigation was triggered by Defendants' submission of ANDA No. 211024 and their subsequent sending of a Notice Letter with a Paragraph IV certification to Plaintiffs on December 15, 2017, asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed.

Case Timeline

Date Event
2006-06-16 Earliest Patent Priority Date (’684, ’355, ’946 Patents)
2013-09-30 FDA approves New Drug Application for TRINTELLIX®
2014-05-13 U.S. Patent No. 8,722,684 issues
2015-03-03 U.S. Patent No. 8,969,355 issues
2016-01-05 U.S. Patent No. 9,227,946 issues
2017-12-15 Defendants send Paragraph IV Notice Letter to Plaintiffs
2018-01-25 Complaint for Patent Infringement filed

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

U.S. Patent No. 8,722,684 - “1-[2-(2,4-dimethylphenylsulfanyl)-phenyl] piperazine as a Compound with Combined Serotonin Reuptake, 5-HT3 and 5-HT1A Activity for the Treatment of Cognitive Impairment”

The Invention Explained

  • Problem Addressed: The patent’s background section describes the limitations of then-existing Selective Serotonin Reuptake Inhibitors (SSRIs) for treating depression, including a slow onset of therapeutic effect and a high percentage of non-responders. It also notes that depression is often co-morbid with cognitive impairment, which may require a different therapeutic approach. (’684 Patent, col. 1:31-46; col. 2:1-6).
  • The Patented Solution: The invention is the compound 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine (known as vortioxetine) and its crystalline salt forms. The patent discloses that this single compound uniquely combines three distinct pharmacological activities: serotonin transporter (SERT) inhibition, 5-HT3 receptor antagonism, and 5-HT1A receptor partial agonism. This combination is asserted to provide a faster onset for antidepressant effects while also treating associated cognitive deficits. (’684 Patent, col. 2:29-34). The patent specifically identifies and characterizes several crystalline forms, or polymorphs, of the compound's salts, noting that the beta form of the hydrobromide salt is particularly stable and well-suited for tablet formulations (’684 Patent, col. 5:5-10; Fig. 3).
  • Technical Importance: The invention provided a single-molecule, multi-modal approach to treating depression, suggesting a potential for improved efficacy and faster onset compared to traditional SSRIs. (’684 Patent, Abstract).

Key Claims at a Glance

  • The complaint asserts infringement of claims 1, 2, 3, and 5, with claim 2 being the key independent claim defining the specific crystalline form (Compl. ¶53).
  • Essential elements of independent claim 2 include:
    • A compound which is the hydrobromide salt of 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine
    • The compound is in a crystalline form
    • The crystalline form is characterized by X-ray powder diffraction (XRPD) reflections at specific angles: 6.89, 9.73, 13.78 and 14.62 +/-0.10° 2θ
  • The complaint does not explicitly reserve the right to assert dependent claims for this patent, but asserts dependent claims 3 and 5.

U.S. Patent No. 8,969,355 - “1-[2-(2,4-dimethylphenylsulfanyl)-phenyl] piperazine as a Compound with Combined Serotonin Reuptake, 5-HT3 and 5-HT1A Activity for the Treatment of Cognitive Impairment”

The Invention Explained

  • Problem Addressed: As a continuation of the application leading to the ’684 Patent, the ’355 Patent addresses the same technical problems: the limitations of existing SSRIs and the need for treatments that address both depression and co-morbid cognitive impairment. (’355 Patent, col. 1:37-52; col. 2:5-12).
  • The Patented Solution: The ’355 Patent claims methods of using the specific crystalline form of vortioxetine hydrobromide identified in the ’684 Patent to treat a range of CNS disorders, including major depressive disorder. The solution is the therapeutic application of the specific, stable crystalline polymorph for treating these conditions. (’355 Patent, col. 2:32-41).
  • Technical Importance: This patent extends protection from the compound itself to its specific medical uses, securing the therapeutic market for the novel multi-modal antidepressant. (’355 Patent, Abstract).

Key Claims at a Glance

  • The complaint asserts infringement of claims 1, 2, 4, 5, and 7, with claim 1 being the lead independent claim (Compl. ¶66).
  • Essential elements of independent claim 1 include:
    • A method of treating a disease selected from a list including major depressive disorder
    • The method comprises administering a therapeutically effective amount of a crystalline hydrobromide salt of 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine
    • The crystalline salt is characterized by specific XRPD reflections at 6.89, 9.73, 13.78 and 14.64 +/-0.10° 2θ
  • The complaint asserts dependent claims 2, 4, 5, and 7.

U.S. Patent No. 9,227,946 - “1-[2-(2,4-dimethylphenylsulfanyl)-phenyl] piperazine as a Compound with Combined Serotonin Reuptake, 5-HT3 and 5-HT1A Activity for the Treatment of Cognitive Impairment”

  • Technology Synopsis: This patent is part of the same family as the ’684 and ’355 patents and is directed to the same core invention: the compound vortioxetine and its use. It claims methods of using the specific beta crystalline form of vortioxetine hydrobromide to treat CNS disorders by alleviating symptoms or delaying disease progression.
  • Asserted Claims: Independent claim 1 and dependent claims 2, 4, and 5 are asserted (Compl. ¶79).
  • Accused Features: The accused feature is the future sale and administration of Defendants' generic vortioxetine hydrobromide tablets, which will be indicated for treating major depressive disorder in accordance with a proposed product label, thereby practicing the claimed method (Compl. ¶¶ 78-81).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are the “vortioxetine hydrobromide tablets” described in Defendants’ Abbreviated New Drug Application (ANDA) No. 211024, which are proposed generic versions of Plaintiffs’ TRINTELLIX® product (Compl. ¶¶ 1, 17).

Functionality and Market Context

  • The ANDA Products are oral tablets containing vortioxetine hydrobromide as the active ingredient (Compl. ¶¶ 17, 33). The complaint alleges that upon FDA approval, the proposed labeling for the ANDA Products will indicate them for the treatment of major depressive disorder (MDD), the same indication as TRINTELLIX® (Compl. ¶45). Plaintiffs allege that Defendants intend to commercially manufacture and sell these products in the United States, which would directly compete with and displace sales of TRINTELLIX® (Compl. ¶¶ 17, 28).

IV. Analysis of Infringement Allegations

The complaint alleges infringement under 35 U.S.C. § 271(e)(2)(A), which defines the submission of an ANDA seeking approval to market a generic drug prior to patent expiration as a statutory act of infringement. A central allegation is that Defendants did not contest infringement of certain claims in their Paragraph IV Notice Letter (Compl. ¶¶ 53, 66, 79).

8,722,684 Patent Infringement Allegations

Claim Element (from Independent Claim 2) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt... The ANDA product is a tablet containing vortioxetine hydrobromide as the active ingredient. ¶17 col. 4:3-4
...in a crystalline form... The ANDA product, as a proposed generic equivalent in solid tablet form, allegedly contains the active ingredient in the claimed crystalline form. ¶52 col. 4:8-10
...which is characterized by XRPD reflections at 6.89, 9.73, 13.78 and 14.62 +/-0.10° 2θ The complaint alleges that the ANDA Product falls within one or more claims and that Defendants do not contest infringement of claim 2. ¶52, ¶53 col. 5:11-13

8,969,355 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating a disease selected from the group consisting of...major depressive disorder... The proposed labeling for the ANDA product will set forth the indication for the treatment of major depressive disorder (MDD). ¶45, ¶65 col. 7:35-37
...comprising administering a therapeutically effective amount of...crystalline 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt... The proposed labeling will instruct physicians and patients to administer the ANDA product, which contains the claimed crystalline salt. ¶17, ¶45, ¶68 col. 4:3-10
...characterized by XRPD reflections at 6.89, 9.73, 13.78 and 14.64+/-0.10° 2θ The ANDA product allegedly contains the specific crystalline form of the active ingredient, and the complaint states that Defendants do not contest that its use would constitute infringement. ¶64, ¶66 col. 5:16-18
  • Identified Points of Contention:
    • Scope Questions: Since the complaint alleges that infringement of the core claims is not contested, the primary dispute may shift to patent validity. However, a latent infringement question remains: Does the term "therapeutically effective amount" as used in the method claims require any specific dosage strengths that might differ from those in the ANDA?
    • Technical Questions: The central technical question is one of verification: What evidence will confirm that the vortioxetine hydrobromide in Defendants' ANDA product is, in fact, the specific crystalline "beta form" characterized by the XRPD reflections required by the asserted claims? The complaint relies heavily on the alleged non-contest in the Notice Letter rather than on direct technical analysis of the proposed generic product.

No probative visual evidence provided in complaint.

V. Key Claim Terms for Construction

  • The Term: "crystalline form"
  • Context and Importance: The patents-in-suit grant protection not to the chemical compound in the abstract, but specifically to its "crystalline form," with key claims directed to a single, specific polymorph (the beta form). The definition of this term is critical because amorphous or different crystalline forms of the same compound would not infringe these claims. Practitioners may focus on this term to determine if the scope of protection is limited only to highly ordered solids suitable for pharmaceutical formulation, or if it could encompass materials with lower degrees of crystallinity.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification discloses and provides data for numerous distinct crystalline forms, including an alpha, beta, gamma, and hemihydrate form of the hydrobromide salt, suggesting the inventors viewed "crystalline form" as a general category for any solid-state ordered structure. (’684 Patent, Figs. 2-5).
    • Evidence for a Narrower Interpretation: The specification explicitly praises the "beta form" as being "the more stable," with an "attractive combination of low hygroscopicity and solubility, which makes this compound particularly suited for making tablets." (’684 Patent, col. 5:5-10). This could support an argument that the term, in the context of the invention, implies a form with properties that make it pharmaceutically viable.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement under 35 U.S.C. § 271(b), stating that upon approval, Defendants' product labeling will instruct medical professionals and patients to administer the drug for treating MDD, thereby causing infringement of the method-of-use claims (’355 and ’946 patents) (Compl. ¶¶ 69, 82). It also alleges contributory infringement under § 271(c), asserting the ANDA products are especially adapted for an infringing use and have no substantial non-infringing uses (Compl. ¶¶ 70, 83).
  • Willful Infringement: The complaint alleges that Defendants had actual notice of the patents prior to filing their ANDA and proceeded without adequate justification (Compl. ¶¶ 58-59, 71-72, 84-85). This conduct is alleged to render the case "exceptional" under 35 U.S.C. § 285, forming a basis for seeking enhanced damages and attorneys' fees.

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

Given the complaint's assertion that direct infringement of key claims is not contested by Defendants, the litigation will likely focus on the following core questions:

  • A primary issue will be one of patent validity: Can Defendants prove by clear and convincing evidence that the asserted claims, directed to a specific polymorph of vortioxetine hydrobromide discovered after the compound itself, are invalid as obvious over the prior art or for failing to meet the written description and enablement requirements for that specific crystalline form?
  • A key evidentiary question will be one of structural identity: What factual record will establish that the active pharmaceutical ingredient in Defendants' proposed generic product is the specific 'beta' crystalline polymorph defined by the XRPD peaks recited in the asserted claims, thereby satisfying the elements of both the compound and method-of-use claims?