DCT

1:24-cv-00154

AbbVie Inc v. Zenara Pharma Pvt Ltd

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-00154, D. Del., 02/05/2024
  • Venue Allegations: Venue is alleged to be proper because Defendants are foreign corporations organized under the laws of India and may be sued in any U.S. judicial district.
  • Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's ORILISSA® product constitutes an act of infringement of two patents directed to methods of administering elagolix.
  • Technical Context: The technology involves methods of using elagolix, a gonadotropin-releasing hormone (GnRH) receptor antagonist, to treat gynecological conditions such as endometriosis and heavy menstrual bleeding associated with uterine fibroids.
  • Key Procedural History: This case follows two prior lawsuits filed by Plaintiff against the same Defendants concerning the same ANDA. The first suit, filed in October 2022, asserted three different patents. A second suit asserting a fourth patent was filed in August 2023 and later consolidated into the first. The current action asserts two patents that issued in July 2023 and were not included in the prior litigations.

Case Timeline

Date Event
2018-04-19 ’854 Patent Priority Date
2018-07-23 ORILISSA® FDA Approval
2020-03-05 ’845 Patent Priority Date
2023-07-04 ’845 Patent Issue Date
2023-07-04 ’854 Patent Issue Date
2024-02-05 Complaint Filing Date

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

U.S. Patent No. 11,690,845 - "Methods of Administering Elagolix," issued July 4, 2023

The Invention Explained

  • Problem Addressed: The patent addresses the potential for drug-drug interactions when elagolix is administered concomitantly with other drugs, specifically substrates of the enzyme CYP2B6, such as the antidepressant bupropion (’845 Patent, col. 1:21-34). The background notes that peak plasma concentrations of bupropion have been linked to certain adverse events, making the management of its pharmacokinetic profile critical (’845 Patent, col. 1:35-37).
  • The Patented Solution: The invention describes a method for treating gynecological disorders by co-administering elagolix and a CYP2B6 substrate. The patent discloses that co-administration of elagolix with bupropion results in an increased peak plasma concentration (Cmax) of bupropion and its primary metabolite, hydroxybupropion (’845 Patent, col. 8:50-59). The claims define methods of administration using specific dosages that result in particular, quantified pharmacokinetic ratios, providing a basis for managing the co-administration of these drugs (’845 Patent, col. 2:49-65).
  • Technical Importance: Quantifying specific drug-drug interaction effects is crucial for ensuring patient safety, allowing physicians to make informed decisions about co-prescribing medications for patients with co-morbid conditions, and for obtaining regulatory approval for combination use (’845 Patent, col. 1:21-34).

Key Claims at a Glance

  • The complaint alleges infringement of at least one claim (Compl. ¶59, 62). Independent claim 1 is representative.
  • Essential elements of Independent Claim 1:
    • A method for treating a gynecological disorder in a patient in need thereof.
    • The method comprises orally administering elagolix sodium in an amount equivalent to 300 mg of elagolix free acid twice daily.
    • The patient also receives a once daily dose of 150 mg of bupropion.
    • The co-administration results in a specific pharmacokinetic profile defined by ratios of Cmax and AUCinf for bupropion and/or hydroxybupropion, as compared to administration of bupropion alone.
  • The complaint does not explicitly reserve the right to assert dependent claims but makes a general allegation of infringement.

U.S. Patent No. 11,690,854 - "Methods of Treating Heavy Menstrual Bleeding," issued July 4, 2023

The Invention Explained

  • Problem Addressed: The patent addresses the treatment of heavy menstrual bleeding (HMB), a condition often associated with uterine fibroids and defined as menstrual blood loss greater than 80 mL per cycle (’854 Patent, col. 1:32-44). The patent also addresses related symptoms of endometriosis, such as fatigue and the need for pain medication (’854 Patent, col. 2:34-37).
  • The Patented Solution: The invention provides methods of treating HMB and other gynecological symptoms by administering elagolix, a GnRH antagonist, in combination with an estrogen and a progestogen (’854 Patent, Abstract; col. 2:46-50). This "add-back" therapy is intended to reduce bleeding while mitigating the hypoestrogenic side effects (e.g., bone mineral density loss) that can result from administering a GnRH antagonist alone, thereby enabling a more favorable risk-benefit profile for long-term treatment (’854 Patent, col. 3:19-24).
  • Technical Importance: The claimed methods provide a non-surgical, oral therapeutic option that balances the efficacy of GnRH antagonists in reducing HMB and pain with the management of treatment-related side effects, potentially offering a long-term medical alternative to surgery (’854 Patent, col. 1:50-53).

Key Claims at a Glance

  • The complaint alleges infringement of at least one claim (Compl. ¶83, 86). Independent claim 1 is representative.
  • Essential elements of Independent Claim 1:
    • A method of reducing the volume of menstrual blood loss in a subject with uterine fibroids who has a baseline blood loss greater than 80 mL per cycle.
    • The method comprises administering 300 to 600 mg per day of elagolix or a salt thereof.
    • The elagolix is administered in combination with an estrogen and a progestogen.
    • The method results in the subject's menstrual blood loss being reduced to less than 80 mL per cycle.
  • The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is "Zenara's Generic Product," identified as a generic version of ORILISSA® (elagolix sodium) oral tablets (Compl. ¶1). Defendants' ANDA No. 217760 seeks FDA approval to market 150 mg and 200 mg (base equivalent) dosage forms of the tablets (Compl. ¶1, 53).

Functionality and Market Context

  • The complaint alleges that Zenara's Generic Product is pharmaceutically and therapeutically equivalent to ORILISSA®, a GnRH receptor antagonist used for the management of moderate to severe pain associated with endometriosis (Compl. ¶6, 60, 84). The lawsuit arises from Defendants' filing of the ANDA, which seeks approval to market this generic product in the U.S. before the expiration of the patents-in-suit, an act of infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶1, 2).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

'845 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating a gynecological disorder in a patient in need thereof Zenara’s ANDA seeks approval to market a generic version of ORILISSA®, which is indicated for the treatment of pain associated with endometriosis, a gynecological disorder. ¶1, 6, 64 col. 2:50-51
the method comprises orally administering to the patient sodium 4-({(1R)-2-[5-(2-fluoro-3-methoxyphenyl)-3-{[2-fluoro-6-(trifluoromethyl)phenyl]methyl]-4-methyl-2,6-di-oxo-3,6-dihydropyrimidin-1(2H)-yl]-1-phenylethyl}amino) butanoate (“elagolix sodium”), wherein elagolix sodium is administered in an amount equivalent to 300 mg of elagolix free acid twice daily Zenara’s ANDA seeks approval for elagolix sodium tablets. The complaint alleges Zenara will induce infringement of the patented method, which requires this specific dosage. ¶53, 66 col. 2:51-54
wherein the patient receives a once daily dose of 150 mg of bupropion The complaint alleges Zenara will induce infringement by patients and healthcare providers, who will co-administer the generic product with bupropion as instructed by Zenara's promotional activities and proposed package insert. ¶65, 66 col. 2:54-55
wherein: (i) a ratio of Cmax for bupropion following co-administration of bupropion with elagolix to Cmax for bupropion following administration of bupropion alone is between about 1.104 and about 1.407... and/or (iv) a ratio of AUCinf for hydroxybupropion... is between about 0.993 and about 1.137... The complaint alleges that Zenara’s product is therapeutically equivalent to ORILISSA®. Therefore, its administration according to the patented method will inherently result in the claimed pharmacokinetic outcomes. ¶60 col. 2:56-65, col. 3:1-4

'854 Patent Infringement Allegations

The complaint does not provide the exact language of the asserted claims of the ’854 patent or include a claim chart exhibit. The infringement theory is based on inducement under 35 U.S.C. § 271(b) (Compl. ¶87). The complaint alleges that Zenara's submission of its ANDA for a generic version of elagolix constitutes an act of infringement because the proposed product will be used to practice the patented methods (Compl. ¶83). The ’854 Patent is directed to methods of treating heavy menstrual bleeding by administering elagolix in combination with an estrogen and a progestogen (’854 Patent, Abstract). The complaint alleges that Zenara knows and intends for its generic product to be prescribed for this use, with the proposed package insert instructing or encouraging healthcare professionals to direct patients to use the product in an infringing manner (Compl. ¶88, 90). The allegation relies on the assertion that Zenara's product is therapeutically equivalent to ORILISSA®, and its use as described in the patent will therefore achieve the patented therapeutic result (Compl. ¶84).

Identified Points of Contention

  • Dosage Mismatch: A primary technical question for the ’845 Patent is the feasibility of direct infringement. The asserted independent claim requires administering elagolix at "300 mg... twice daily," but the accused ANDA is for 150 mg and 200 mg tablets (Compl. ¶1; ’845 Patent, col. 2:53-54). This raises the question of whether any asserted claim reads on a dosage achievable with the accused product.
  • Scope of Labeled Indication: A central legal question for both patents is whether the proposed label for Zenara’s generic product will induce infringement of the patented methods. Since ORILISSA® is formally indicated for endometriosis pain, the court may need to determine if Zenara's label is sufficiently broad to encourage off-label use for treating heavy menstrual bleeding (for the ’854 Patent) or co-administration with bupropion (for the ’845 Patent), or if such uses are so well-established that infringement would be inevitable upon launch.

V. Key Claim Terms for Construction

  • Term: "in combination with" (’854 Patent, Claim 1)

    • Context and Importance: The infringement allegation for the ’854 Patent depends on elagolix being used "in combination with" an estrogen and a progestogen. The construction of this term is critical to determining whether co-prescription of separate products, as opposed to a fixed-dose co-formulation, falls within the scope of the claim.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification of the related ’845 Patent provides a definition for "co-administration" that includes administration "in a sequential manner" and where the agents "need not be, administered in a substantially simultaneous manner," which may support a broad reading that covers separate prescriptions (’845 Patent, col. 5:45-63).
      • Evidence for a Narrower Interpretation: A defendant might argue that the term implies a closer temporal or functional link than mere concurrent prescriptions, though the specification provides evidence to the contrary.

  • Term: "treating a gynecological disorder" (’845 Patent, Claim 1)

    • Context and Importance: Practitioners may focus on this term because the scope of "gynecological disorder" will define the boundaries of the claimed method. While the accused ANDA product is for endometriosis pain, the patent covers a wider range of conditions.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent specification explicitly lists "endometriosis, uterine fibroids, polycystic ovary syndrome (PCOS), or adenomyosis" as examples of gynecological disorders to which the disclosure pertains, supporting a broad construction (’845 Patent, col. 1:12-16).
      • Evidence for a Narrower Interpretation: A defendant is unlikely to find strong evidence for a narrower construction of the term itself, but may argue that the infringement allegation is deficient because the proposed label does not induce treatment of the full scope of such disorders in the claimed manner.

VI. Other Allegations

  • Indirect Infringement: The complaint's primary theory of liability for these method-of-use patents is indirect infringement. It alleges inducement for both patents, asserting that Zenara knows and intends for its generic product to be used in an infringing manner, with this intent evidenced by its promotional activities and the instructions in its proposed package insert (Compl. ¶65, 66, 89, 90). The complaint also alleges contributory infringement for the ’854 patent, stating the product is especially adapted for an infringing use and lacks substantial non-infringing uses (Compl. ¶92, 93).
  • Willful Infringement: The complaint does not contain an explicit count for willful infringement. However, it alleges that Zenara has "knowledge and is aware of the ’845 and ’854 patents," including through their listing in the FDA Orange Book, and that its actions "indicate a refusal to change the course of their actions in the face of knowledge of the" patents (Compl. ¶56, 74, 100). These allegations may form the basis for a future claim of post-suit willfulness.

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

  • A core issue will be one of infringement by inducement: Can AbbVie demonstrate that Zenara’s proposed product label, for a generic version of a drug indicated for endometriosis pain, will actively encourage physicians and patients to practice the patented methods of treating heavy menstrual bleeding (’854 Patent) or co-administering the drug with bupropion (’845 Patent)?
  • A key evidentiary question will be one of infringement feasibility: For the ’845 Patent, does any asserted claim cover a dosage regimen that is achievable using the 150 mg and 200 mg tablets in Zenara's ANDA, or is there a fundamental mismatch between the patent's required "300 mg... twice daily" dose and the accused product?
  • A central legal and factual question will be one of label scope vs. inevitable use: Will the court's analysis be limited to the four corners of the proposed label, or will it consider extrinsic evidence suggesting that certain infringing uses are so common or foreseeable that the marketing of the generic product will inevitably result in infringement, regardless of a narrowly tailored label?