DCT

3:24-cv-04852

AbbVie Inc v. Hetero USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:24-cv-04852, D.N.J., 04/11/2024
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Hetero USA has its principal place of business in New Jersey, and the other foreign-based Hetero entities may be sued in any U.S. judicial district.
  • Core Dispute: Plaintiffs allege that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to market generic versions of Plaintiffs' migraine drug UBRELVY® constitutes an act of infringement of four patents covering the drug's formulation and methods of use.
  • Technical Context: The technology concerns pharmaceutical formulations and specific dosing regimens for ubrogepant, a calcitonin gene-related peptide (CGRP) receptor antagonist used for the acute treatment of migraine.
  • Key Procedural History: This action was triggered by Defendants' submission of ANDA No. 219113 to the U.S. Food and Drug Administration (FDA) seeking approval to market generic ubrogepant tablets. The ANDA submission included a Paragraph IV certification alleging that two of the patents-in-suit are invalid, unenforceable, or will not be infringed by the proposed generic product, which constitutes a statutory act of infringement under the Hatch-Waxman Act.

Case Timeline

Date Event
2014-02-05 Earliest Priority Date for ’836 and ’709 Patents
2018-11-06 U.S. Patent No. 10,117,836 Issues
2019-12-23 FDA Approves New Drug Application for UBRELVY®
2020-12-22 Earliest Priority Date for ’515 and ’542 Patents
2023-08-08 U.S. Patent No. 11,717,515 Issues
2024-01-02 U.S. Patent No. 11,857,542 Issues
2024-02-26 Date of Hetero's Notice Letter to AbbVie
2024-03-12 U.S. Patent No. 11,925,709 Issues
2024-04-11 Complaint Filing Date

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

U.S. Patent No. 10,117,836 - "Tablet Formulation for CGRP Active Compounds"

The Invention Explained

  • Problem Addressed: The patent’s background section explains that certain CGRP antagonist compounds, while promising for migraine treatment, have low aqueous solubility, making them difficult to formulate into a solid oral dosage form like a tablet that can be effectively absorbed by the body (Compl. ¶43; ’836 Patent, col. 1:57-2:14). Furthermore, these compounds can be thermally sensitive and degrade during common formulation processes like hot-melt extrusion, particularly when combined with standard cellulosic polymers (’836 Patent, col. 7:31-44).
  • The Patented Solution: The invention describes a formulation created through a hot-melt extrusion (HME) process where the active pharmaceutical ingredient (API) is dispersed as a solid solution within a specific water-soluble polymer matrix—a polyvinylpyrrolidone/vinyl acetate (PVP-VA) copolymer. This specific polymer was found to avoid the thermal degradation seen with other polymers (’836 Patent, col. 7:45-8:14). The formulation also incorporates a dispersing agent to aid the HME process and a novel "disintegration system" containing powdered sodium chloride, which allows the final tablet to disintegrate rapidly upon ingestion, overcoming the gelling tendency of the polymer matrix (’836 Patent, Abstract; col. 11:25-54).
  • Technical Importance: This technology provides a method to formulate a poorly soluble and thermally sensitive class of drugs into a stable, rapidly-dissolving oral tablet suitable for acute therapies.

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims without specifying them (Compl. ¶79). Independent claim 1 is representative and includes the following essential elements:
    • A tablet comprising:
    • An extrudate that includes a water-soluble polymer matrix, a dispersing agent, and the active compound (of Formula I);
    • A disintegration system;
    • Wherein the tablet has a specified hardness (from about 12 kP to about 18 kP); and
    • Wherein the tablet achieves complete disintegration in less than about 5 minutes in a standard test.
  • The complaint reserves the right to assert additional claims, including dependent claims (Compl. ¶79).

U.S. Patent No. 11,717,515 - "Treatment of Migraine"

The Invention Explained

  • Problem Addressed: The patent addresses the clinical challenge of safely and effectively treating migraine in patients with severe hepatic (liver) impairment. Such patients may metabolize drugs differently, potentially leading to increased drug exposure and adverse effects if given a standard dose (’515 Patent, col. 1:18-24).
  • The Patented Solution: The invention claims a specific method of treating migraine in this patient population. It consists of administering a first dose of 50 mg of ubrogepant to a patient with severe hepatic impairment, defined as having a Child-Pugh score of Class C. The method also provides for an optional second 50 mg dose to be administered at least two hours later if needed (’515 Patent, Abstract; col. 2:50-64). This dosing regimen was determined to provide a safe and effective therapeutic profile for this specific group.
  • Technical Importance: This invention provides a clinically validated dosing protocol for a vulnerable patient population that might otherwise be denied treatment or receive a dose that is either unsafe or ineffective.

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims without specifying them (Compl. ¶112). Independent claim 1 is representative and recites:
    • A method for the acute treatment of migraine with or without aura in a patient with severe hepatic impairment,
    • The method comprising administering a first dose of 50 mg of ubrogepant to the patient,
    • Wherein the patient has a Child-Pugh score of Child-Pugh Class C.
  • The complaint reserves the right to assert additional claims, including dependent claims (Compl. ¶112).

U.S. Patent No. 11,857,542 - "Treatment of Migraine"

  • Technology Synopsis: Similar to the ’515 Patent, this patent is directed to a method of use for a specific patient population. The invention provides a method for the acute treatment of migraine in patients with severe renal (kidney) impairment by administering a 50 mg dose of ubrogepant. This specific dosing is intended to be safe and effective for patients whose ability to clear the drug is compromised by kidney disease (’542 Patent, Abstract; col. 2:1-12).
  • Asserted Claims: The complaint does not specify claims, but independent claim 1 covers the method of administering 50 mg of ubrogepant to a patient with severe renal impairment (Compl. ¶140).
  • Accused Features: The proposed labeling for Hetero's generic product, which is alleged to instruct for the same conditions of use as UBRELVY®, including its use in patients with severe renal impairment (Compl. ¶¶ 69, 143).

U.S. Patent No. 11,925,709 - "Tablet Formulation for CGRP Active Compounds"

  • Technology Synopsis: This patent is related to the ’836 Patent and claims pharmaceutical tablet formulations for CGRP active compounds like ubrogepant. The invention is directed to the specific composition of a tablet comprising an extrudate (the active drug in a PVP-VA copolymer matrix with a dispersing agent) combined with a specific disintegration system that ensures rapid dissolution and release of the drug (’709 Patent, Abstract; claim 1).
  • Asserted Claims: The complaint does not specify claims, but independent claim 1 covers the core tablet composition (Compl. ¶169).
  • Accused Features: The physical composition of Hetero's proposed generic ubrogepant tablets. The complaint alleges these tablets are pharmaceutically equivalent to UBRELVY® and therefore embody the claimed formulation (Compl. ¶¶ 68, 167).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentalities are Defendants’ proposed generic ubrogepant oral tablets in 50 mg and 100 mg dosage forms, for which Hetero filed Abbreviated New Drug Application (ANDA) No. 219113 with the FDA (Compl. ¶¶ 1, 61).
  • Functionality and Market Context: The proposed products are generic versions of Plaintiffs’ commercial UBRELVY® tablets, which are approved for the acute treatment of migraine (Compl. ¶¶ 1, 38). Under the Hatch-Waxman Act, to gain FDA approval, Hetero's generic products must be bioequivalent to UBRELVY® (Compl. ¶68). The complaint alleges that Hetero’s products will therefore be pharmaceutically and therapeutically equivalent, and that their proposed labeling for conditions of use will be the same as that approved for UBRELVY® (Compl. ¶¶ 69, 77). The filing of the ANDA itself is the statutory act of infringement alleged for all asserted patents (Compl. ¶¶ 78, 111, 139, 168).
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

U.S. Patent No. 10,117,836 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A tablet comprising: (a) an extrudate comprising: (i) a water-soluble polymer matrix; (ii) a dispersing agent; and (iii) a compound of Formula I... Hetero's generic tablets are alleged to be pharmaceutically equivalent to UBRELVY® and therefore to contain an extrudate of ubrogepant in a polymer matrix with a dispersing agent. ¶77 col. 16:36-42
...and (b) a disintegration system, The generic tablets are alleged to contain a disintegration system necessary to achieve bioequivalence with the rapid-release UBRELVY® product. ¶77 col. 16:58-59
wherein said tablet has a hardness of from about 12 kP to about 18 kP... Bioequivalence requirements suggest the generic product will have similar physical properties, including hardness, to the brand-name drug. ¶77 col. 16:60-61
...and wherein said tablet achieves complete disintegration in less than about 5 minutes in a tablet disintegration test... The complaint alleges that to be bioequivalent, the generic product must have a rapid disintegration profile that meets the claimed limitation. ¶68 col. 16:61-65
  • Identified Points of Contention:
    • Scope Questions: A primary question will be whether Hetero’s formulation falls within the scope of the term "disintegration system" as used in the patent. The dispute may center on whether Hetero uses the specific combination of excipients taught in the specification or a different, non-infringing combination.
    • Technical Questions: Since the complaint is based on "information and belief" pending discovery of the ANDA's contents, a key factual question is whether Hetero's formulation actually uses a "water-soluble polymer matrix" and "dispersing agent" as claimed, or if it achieves bioequivalence through an alternative technological approach that designs around the patent.

U.S. Patent No. 11,717,515 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for the acute treatment of migraine with or without aura in a patient with severe hepatic impairment, Hetero's proposed product label is alleged to instruct physicians and patients to use the generic drug for the acute treatment of migraine in this specific patient population. ¶113 col. 17:1-3
the method comprising administering a first dose of 50 mg of ubrogepant to the patient, The proposed label is alleged to instruct the administration of a 50 mg dose, mirroring the dosage specified for this patient group on the UBRELVY® label. ¶115 col. 17:3-4
wherein the patient has a Child-Pugh score of Child-Pugh Class C. To match the reference drug label, Hetero's proposed labeling is alleged to define "severe hepatic impairment" in a manner consistent with a Child-Pugh Class C score. ¶113 col. 17:5-6
  • Identified Points of Contention:
    • Scope Questions: The infringement theory for this method patent is inducement. A key issue will be whether the language in Hetero's final, FDA-approved label will contain instructions that directly correspond to each element of the asserted claims.
    • Technical Questions: A potential defense strategy in ANDA litigation is the use of a "skinny label," where a generic manufacturer carves out patented methods of use from its proposed labeling. A central question will be whether Hetero will be permitted by the FDA to, and will in fact, omit the patented indication for patients with severe hepatic impairment from its label.

V. Key Claim Terms for Construction

  • The Term: "disintegration system" (’836 Patent, Claim 1)

  • Context and Importance: This term is critical because the patent distinguishes its invention from prior art based on its ability to achieve rapid tablet disintegration despite using a polymer matrix prone to gelling. The definition of this term will determine whether Hetero’s formulation, which must also be rapid-dissolving to be bioequivalent, infringes.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The claim language itself is broad, simply reciting "a disintegration system" without specifying its components. A defendant may argue this should be given its plain and ordinary meaning, covering any combination of excipients that aids tablet breakup.
    • Evidence for a Narrower Interpretation: The specification provides substantial detail on a preferred embodiment, teaching that a combination of "Powdered Sodium Chloride" and a conventional disintegrant like croscarmellose sodium is surprisingly effective (’836 Patent, col. 11:36-54). Plaintiffs may argue that the term should be construed in light of these specific disclosures, which are presented as the solution to the technical problem of polymer gelling.

  • The Term: "severe hepatic impairment" (’515 Patent, Claim 1)

  • Context and Importance: The scope of the patent is explicitly limited to this patient population. While the claim itself provides a definition, the way this term is presented and defined in Hetero's proposed drug label will be central to the induced infringement analysis.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: A party could argue the term should encompass any clinical diagnosis of severe liver disease that a physician might make, regardless of the specific scoring system used.
    • Evidence for a Narrower Interpretation: The claim itself explicitly defines the term: "wherein the patient has a Child-Pugh score of Child-Pugh Class C" (’515 Patent, col. 17:5-6). This provides strong intrinsic evidence that the term is not open to a broader interpretation and is limited to patients who meet this specific clinical criterion. Practitioners may focus on whether the accused label uses this precise terminology.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement for all four patents. For the method-of-use patents (’515 and ’542), this is the central infringement theory. The allegations are based on the contention that Hetero's proposed package insert and promotional activities will instruct and encourage healthcare providers and patients to prescribe and use the generic product in a manner that directly infringes the patented methods (e.g., Compl. ¶¶ 81-82, 96-97, 114-115).
  • Willful Infringement: The complaint does not contain a separate count for willful infringement. However, it alleges that Hetero had knowledge of the ’836 and ’515 patents as evidenced by its Paragraph IV Notice Letter (Compl. ¶¶ 81, 114) and that the complaint itself provides notice of the ’709 patent (Compl. ¶165). The prayer for relief requests a declaration that the case is "exceptional" and an award of attorneys' fees, which can be associated with findings of willfulness or other litigation misconduct (Compl., Prayer for Relief ¶G).

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

This litigation presents two primary areas of dispute typical in ANDA cases involving both formulation and method-of-use patents.

  • A key evidentiary question will be one of compositional identity: For the formulation patents (’836 and ’709), will discovery of Hetero’s ANDA reveal a generic product that is a literal copy of the UBRELVY® formulation, thus falling squarely within the claims, or has Hetero developed a composition with different excipients (e.g., a different polymer or disintegration system) that achieves bioequivalence while remaining outside the patents' technical scope?
  • A core issue will be one of induced infringement via labeling: For the method patents (’515 and ’542), the case will likely turn on the final language of Hetero’s FDA-approved label. Will Hetero be required to adopt a label that instructs the specific, patented dosing regimens for patients with severe hepatic and renal impairment, or will it be able to carve out these patented uses via a "skinny label," potentially negating the evidence of intent required to prove inducement?