DCT

1:23-cv-00470

AbbVie Inc v. Prinston Pharmaceutical Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00470, D. Del., 04/28/2023
  • 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 Defendant Zhejiang Huahai is a foreign corporation that may be sued in any 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® (elagolix) product constitutes an act of patent infringement under the Hatch-Waxman Act.
  • Technical Context: The patents-in-suit relate to methods of treating endometriosis by administering the drug elagolix concurrently with other specific medications, resulting in particular pharmacokinetic outcomes.
  • Key Procedural History: This lawsuit is the second action filed by AbbVie against Prinston concerning ANDA No. 217296. A prior suit, filed in October 2022, involves different patents related to the same ORILISSA® product. The current action was triggered by a Paragraph IV notice letter from Prinston dated March 14, 2023, concerning the two patents asserted in this complaint. Both patents-in-suit are listed in the FDA's Orange Book for ORILISSA®.

Case Timeline

Date Event
2015-09-01 Priority Date for '572 and '351 Patents
2018-07-23 ORILISSA® (NDA No. 210450) FDA Approval Date
2020-01-21 U.S. Patent No. 10,537,572 Issued
2020-06-16 U.S. Patent No. 10,682,351 Issued
2022-10-27 First Suit Filed by AbbVie against Prinston re: ANDA 217296
2023-03-14 Prinston's Second Paragraph IV Notice Letter Sent to AbbVie
2023-04-28 Complaint Filing Date

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

U.S. Patent No. 10,537,572 - Methods of Administering Elagolix

The Invention Explained

  • Problem Addressed: The patent addresses the challenge of administering elagolix, a treatment for endometriosis, to patients who are also taking other medications. Specifically, it notes that rifampin, an antibiotic, is a known enzyme inducer that typically leads to "decreased exposure levels of many other drugs that are CYP enzyme substrates when co-administered" (’572 Patent, col. 1:26-33). This creates uncertainty in achieving a therapeutic dose of elagolix.
  • The Patented Solution: The inventors discovered a "surprising" result: co-administration of rifampin with elagolix significantly increased elagolix plasma concentrations, contrary to typical expectations (’572 Patent, col. 4:8-12). The patented method involves the specific co-administration of elagolix and rifampin to treat endometriosis, which is defined by the resulting, quantitatively specified increase in elagolix plasma concentration (Cmax) and total drug exposure (AUC) (’572 Patent, claims 1-2).
  • Technical Importance: This discovery provides specific pharmacokinetic data for a counter-intuitive drug-drug interaction, informing how physicians can dose elagolix for patients who also require rifampin therapy (’572 Patent, col. 4:18-26).

Key Claims at a Glance

  • The complaint asserts infringement of at least one claim, with independent claims 1 and 2 being the broadest.
  • Independent Claim 1 recites a method of treating endometriosis comprising:
    • Orally administering 150 mg of elagolix once daily.
    • The patient receives a single dose of 600 mg of rifampin.
    • Resulting in a 4.4-fold increase in maximum elagolix plasma concentration (Cmax) and a 5.6-fold increase in area-under-the-curve (AUC) relative to elagolix administered alone.
  • Independent Claim 2 recites a method of treating endometriosis comprising:
    • Orally administering 150 mg of elagolix once daily.
    • The patient receives 600 mg of rifampin once daily.
    • Resulting in a 2.0-fold increase in Cmax and a 1.65-fold increase in AUC relative to elagolix administered alone.

U.S. Patent No. 10,682,351 - Methods of Administering Elagolix

The Invention Explained

  • Problem Addressed: Similar to the ’572 patent, this patent addresses drug-drug interactions with elagolix. It identifies ketoconazole, an antifungal drug, as a "potent CYP3A and P-gp inhibitor," which can alter the metabolism and exposure levels of co-administered drugs (’351 Patent, col. 2:35-39).
  • The Patented Solution: The invention is based on the discovery that co-administering ketoconazole with elagolix increases elagolix exposure levels (’351 Patent, col. 9:14-16, Example 2). The patent claims a method of treating endometriosis by orally administering elagolix and ketoconazole, where the method is defined by the specific, measured pharmacokinetic outcome of increased elagolix Cmax and AUC (’351 Patent, claim 1).
  • Technical Importance: The invention provides clinicians with precise data on the effect of ketoconazole on elagolix levels, which may allow for dose adjustments to ensure safety and efficacy when both drugs are required (’351 Patent, col. 6:40-44).

Key Claims at a Glance

  • The complaint asserts infringement of at least one claim, with claim 1 being the sole independent claim.
  • Independent Claim 1 recites a method of treating endometriosis comprising:
    • Orally administering 150 mg of elagolix once daily.
    • The patient receives a once-daily dose of 400 mg of ketoconazole.
    • Resulting in a 1.8-fold increase in Cmax and a 2.2-fold increase in AUC relative to elagolix administered alone.

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Prinston’s proposed generic version of ORILISSA®, described as "elagolix sodium oral tablets (eq. 150 mg base and eq. 200 mg base)," for which Prinston has filed ANDA No. 217296 with the FDA (Compl. ¶¶1-2, 57).

Functionality and Market Context

The complaint alleges that Prinston's product is a GnRH receptor antagonist intended for the management of moderate to severe pain associated with endometriosis (Compl. ¶5, ¶8). It is further alleged that Prinston has represented to the FDA that its generic product is "pharmaceutically and therapeutically equivalent" to AbbVie's ORILISSA® (Compl. ¶65). Upon approval, Prinston’s product would compete directly with ORILISSA® in the U.S. market (Compl. ¶39, ¶61).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint alleges infringement based on the submission of the ANDA itself, an act of infringement under 35 U.S.C. § 271(e)(2)(A), and induced infringement under § 271(b). The complaint does not contain claim charts or provide specific details from Prinston's proposed product labeling to map onto the claim elements.

  • '572 Patent Infringement Allegations: The narrative theory is that Prinston's proposed product label for its generic elagolix will instruct or encourage physicians and patients to co-administer the drug with rifampin for the treatment of endometriosis (Compl. ¶¶68-70). The complaint alleges that following these instructions will directly infringe the asserted method claims by causing the specific pharmacokinetic profile (i.e., the increased Cmax and AUC values) recited therein (Compl. ¶69). The complaint does not provide the text of the proposed label to substantiate this theory.

  • '351 Patent Infringement Allegations: The infringement theory for the ’351 patent mirrors that for the ’572 patent. The complaint alleges that the proposed product label for Prinston's generic will induce infringement by instructing or encouraging the co-administration of elagolix with ketoconazole for treating endometriosis (Compl. ¶¶81-83). AbbVie alleges this will result in the pharmacokinetic outcomes claimed in the ’351 patent (Compl. ¶82). As with the ’572 patent, the complaint does not include specific factual allegations drawn from the proposed label.

V. Key Claim Terms for Construction

  • The Term: "treating endometriosis"

    • Context and Importance: As part of the preamble in a method claim, its limiting effect is a common point of dispute. The case may turn on whether the instructions in Prinston's proposed label constitute "treating endometriosis" in the manner claimed, particularly in the specific co-administration contexts.
    • Intrinsic Evidence for a Broader Interpretation: The specification describes the general field as "the use of GnRH receptor antagonists used in the treatment of endometriosis or uterine fibroids," suggesting a conventional medical meaning (’572 Patent, col. 1:15-18).
    • Intrinsic Evidence for a Narrower Interpretation: The claims tie the act of "treating" to a method that includes co-administration of a second drug and results in a specific pharmacokinetic profile. A party could argue that "treating" under the claim requires not just administration, but administration that achieves the claimed PK result.

  • The Term: "wherein maximum plasma concentration for elagolix is increased by [X] fold ... and wherein plasma area-under-the-curve for elagolix is increased by [Y] fold"

    • Context and Importance: These "wherein" clauses recite a result of the claimed method. A critical issue will be whether infringement requires proof that following the generic label's instructions will necessarily and consistently produce these exact numerical results in patients. Practitioners may focus on this term because it represents the primary point of novelty but also the greatest evidentiary challenge for the patentee.
    • Intrinsic Evidence for Interpretation (as an inherent result): The patents present these values as the measured outcome of clinical studies detailed in the examples (’572 Patent, col. 7:66-col. 8:2; ’351 Patent, col. 10:4-7). A party could argue that if the antecedent steps (co-administration of the specified doses) are performed, the claimed result is an inherent and automatic consequence.
    • Intrinsic Evidence for Interpretation (as a strict limitation): The claims recite highly specific numerical fold-increases. A party could argue these are not merely descriptive but are hard limitations of the claim scope, and that infringement requires proof that these specific results are achieved, not just that the drugs are co-administered.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement of infringement under 35 U.S.C. § 271(b) for both patents. The factual basis alleged is that Prinston's "promotional activities and proposed package insert" for its generic product will instruct or encourage healthcare providers and patients to use the product in a manner that directly infringes the method claims (Compl. ¶¶69, 82).
  • Willful Infringement: The complaint does not use the word "willful" but does request a finding that the case is "exceptional" and seeks attorney fees, which is the functional equivalent in this context (Compl. Request for Relief ¶G). The basis for this allegation is Prinston’s alleged knowledge of the patents, evidenced by its March 14, 2023 notice letter, and its continued pursuit of FDA approval for an allegedly infringing product (Compl. ¶¶71, 84).

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

  • A central evidentiary question will be one of inducement via labeling: What does Prinston’s proposed generic drug label state regarding interactions with rifampin and ketoconazole? The entire infringement case hinges on whether the label's language is sufficient to instruct or encourage the specific co-administration methods claimed in the patents.
  • A key issue of claim scope will be: Are the numerically-defined pharmacokinetic outcomes in the "wherein" clauses strict limitations on the claims? The court’s construction of these clauses will determine the evidentiary burden on AbbVie—whether it must simply prove the label instructs co-administration or must go further and prove that following the instructions necessarily results in the specific fold-increases in drug exposure recited in the claims.
  • The case will also involve a question of validity: Did the discovery of the specific pharmacokinetic results of combining elagolix with known metabolic inducers/inhibitors like rifampin and ketoconazole represent a non-obvious advance over the prior art? Prinston's defense will likely focus on whether it was obvious to try these combinations and whether the resulting data, now claimed, were unexpected enough to warrant patent protection.