DCT

3:24-cv-04603

AbbVie Inc v. Zydus Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:24-cv-04603, D.N.J., 04/05/2024
  • Venue Allegations: Venue is alleged as proper in the District of New Jersey because Defendant Zydus Pharmaceuticals is incorporated in and maintains its principal place of business in New Jersey. Defendant Zydus Lifesciences, an Indian corporation, may be sued in any U.S. judicial district.
  • Core Dispute: Plaintiffs allege that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to the FDA, seeking to market generic versions of Plaintiffs’ UBRELVY® migraine treatment, constitutes an act of patent infringement.
  • Technical Context: The technology concerns pharmaceutical formulations and specific methods for treating migraine using ubrogepant, a calcitonin gene-related peptide (CGRP) receptor antagonist.
  • Key Procedural History: The litigation was triggered by a Notice Letter dated February 20, 2024, in which Zydus provided a Paragraph IV certification alleging that claims of the asserted patents are invalid, unenforceable, or will not be infringed by its proposed generic product. This letter, and the underlying ANDA submission, form the basis for the infringement action under the Hatch-Waxman Act.

Case Timeline

Date Event
2014-02-05 Earliest Priority Date (’836, ’709 Patents)
2018-11-06 U.S. Patent No. 10,117,836 Issues
2019-12-23 FDA Approves UBRELVY® (NDA No. 211765)
2020-12-22 Earliest Priority Date (’515, ’542 Patents)
2023-08-08 U.S. Patent No. 11,717,515 Issues
2024-01-02 U.S. Patent No. 11,857,542 Issues
2024-02-20 Zydus sends Paragraph IV Notice Letter
2024-03-12 U.S. Patent No. 11,925,709 Issues
2024-04-05 Complaint Filed

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 addresses the challenge of formulating certain potent CGRP antagonist compounds for oral delivery. These compounds are characterized as poorly water-soluble "class II" drugs that do not readily form salts, making them difficult to formulate into a stable, solid tablet that allows for effective absorption in the gastrointestinal tract. (’836 Patent, col. 2:7-14, 60-64).
  • The Patented Solution: The invention is a solid oral tablet created through a multi-step process. First, the active pharmaceutical ingredient (API) is dispersed in a water-soluble polymer matrix using a hot melt extrusion (HME) process, creating a composition referred to as an "extrudate." (’836 Patent, Abstract; col. 9:32-36). This extrudate is then combined with a specialized "disintegration system" designed to ensure the tablet breaks apart rapidly when ingested, which is critical for an acute treatment like a migraine medication. (’836 Patent, col. 4:5-12). The patent notes the surprising discovery that using a polyvinylpyrrolidone/vinyl acetate (PVP-VA) copolymer as the matrix polymer, rather than more common cellulosic polymers, reduces thermal degradation of the API during the HME process. (’836 Patent, col. 7:31-41).
  • Technical Importance: This formulation technology enables the creation of a stable, fast-acting oral tablet for a promising class of poorly soluble anti-migraine compounds, overcoming significant bioavailability and manufacturing challenges. (’836 Patent, col. 12:4-8).

Key Claims at a Glance

  • The complaint asserts at least one claim of the ’836 Patent; independent claim 1 is representative of the formulation technology. (Compl. ¶79).
  • The essential elements of independent claim 1 include:
    • A tablet comprising (a) an extrudate and (b) a disintegration system.
    • The extrudate comprises (i) a water-soluble polymer matrix, (ii) a dispersing agent, and (iii) a compound of Formula I (the active ingredient).
    • The tablet has a hardness of from about 12 kP to about 18 kP.
    • The tablet achieves complete disintegration in less than about 5 minutes in a specified standard test.
  • The complaint does not specify assertion of dependent claims but makes a general allegation of infringement of "one or more claims." (Compl. ¶79).

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

The Invention Explained

  • Problem Addressed: While ubrogepant is an effective migraine treatment, there is a need for optimized and safe dosing regimens for specific patient populations. The patent identifies patients with severe hepatic (liver) impairment as a group requiring a specialized treatment approach, as standard doses may pose safety risks or be less effective. (’515 Patent, col. 1:22-30).
  • The Patented Solution: The patent claims a specific method for the acute treatment of migraine in patients with severe hepatic impairment. The method consists of administering a first dose of 50 mg of ubrogepant to a patient identified as having a "Child-Pugh score of Child-Pugh Class C," a clinical standard for severe liver disease. (’515 Patent, Abstract; col. 2:50-55). The patent discloses clinical data demonstrating that this adjusted dose provides a safe and effective pharmacokinetic profile for this patient population, as illustrated by data showing ubrogepant plasma concentrations in patients with varying degrees of hepatic impairment. (’515 Patent, FIG. 1; col. 13:1-12).
  • Technical Importance: The invention provides a clinically validated, safe, and effective dosing regimen for treating acute migraine in a vulnerable patient population for whom other oral treatments may be contraindicated or require caution. (Compl. ¶41).

Key Claims at a Glance

  • The complaint asserts at least one claim of the ’515 Patent; independent claim 1 is representative of the method of treatment. (Compl. ¶112).
  • The essential elements of independent claim 1 include:
    • A method for the acute treatment of migraine with or without aura in a patient with severe hepatic impairment.
    • The method comprises administering a first dose of 50 mg of ubrogepant.
    • The patient has a Child-Pugh score of Child-Pugh Class C.
  • The complaint does not specify assertion of dependent claims but makes a general allegation of infringement of "one or more claims." (Compl. ¶112).

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

  • Patent Identification: U.S. Patent No. 11,857,542, “Treatment of Migraine,” issued January 2, 2024. (Compl. ¶52).
  • Technology Synopsis: This patent addresses the technical problem of providing a safe and effective dosing regimen for ubrogepant in patients with severe renal (kidney) impairment. The patented solution is a method of treating migraine in this population by administering a 50 mg dose of ubrogepant to a patient whose creatinine clearance is within the specific range of 15-29 mL/min. (’542 Patent, Abstract; col. 2:1-9).
  • Asserted Claims: Independent claim 1 is asserted. (Compl. ¶141).
  • Accused Features: The complaint alleges that Zydus's proposed generic product, to gain FDA approval, will have labeling that instructs for the administration of a 50 mg dose to patients with severe renal impairment, thereby inducing infringement of the patented method. (Compl. ¶¶69, 142-143).

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

  • Patent Identification: U.S. Patent No. 11,925,709, “Tablet Formulation for CGRP Active Compounds,” issued March 12, 2024. (Compl. ¶56).
  • Technology Synopsis: This patent, related to the ’836 Patent, is directed to a specific tablet formulation for CGRP active compounds like ubrogepant. The claims cover a tablet comprising an extrudate (containing the API in a polymer matrix with a dispersing agent) and a disintegration system, which is characterized by its ability to release at least 90% of the active compound in less than 20 minutes under specified dissolution test conditions. (’709 Patent, Abstract; col. 17:40-67 (claim 1)).
  • Asserted Claims: Independent claim 1 is asserted. (Compl. ¶170).
  • Accused Features: The complaint alleges that Zydus’s proposed generic ubrogepant tablets are formulated in a way that meets the structural and functional limitations of the asserted claims. (Compl. ¶¶168-169).

III. The Accused Instrumentality

  • Product Identification: The accused products are Zydus's proposed generic ubrogepant oral tablets in 50 mg and 100 mg dosage forms, for which Zydus is seeking FDA approval via ANDA No. 218662. (Compl. ¶1).
  • Functionality and Market Context: The complaint alleges that Zydus's generic products are represented to the FDA as "pharmaceutically and therapeutically equivalent" to Plaintiffs' commercial product, UBRELVY® Tablets. (Compl. ¶77). As such, the accused products contain ubrogepant as the active ingredient and are intended for the acute treatment of migraine with or without aura in adults. (Compl. ¶¶38, 68). To secure FDA approval, the proposed generic product's labeling must recommend the same conditions of use as UBRELVY®, including specific dosing instructions for patients with severe hepatic or renal impairment. (Compl. ¶69). UBRELVY® is described as one of only two orally available CGRP receptor antagonists approved for acute migraine treatment and the only one indicated for patients with severe hepatic impairment. (Compl. ¶41).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

10,117,836 Patent 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... On information and belief, Zydus’s generic tablets are formulated with ubrogepant (a compound of Formula I) in an extrudate containing a polymer matrix and dispersing agent. ¶77 col. 16:35-57
and (b) a disintegration system, On information and belief, Zydus’s generic tablets contain a disintegration system to promote rapid tablet breakup and drug release. ¶77 col. 4:5-12
wherein said tablet has a hardness of from about 12 kP to about 18 kP, On information and belief, Zydus’s generic tablets are manufactured to have physical properties, including hardness, that ensure bioequivalence with UBRELVY® and fall within the claimed range. ¶68, ¶77 col. 4:6-7
and wherein said tablet achieves complete disintegration in less than about 5 minutes in a standard tablet disintegration test... On information and belief, Zydus’s generic tablets are formulated to achieve rapid disintegration characteristics that ensure bioequivalence with UBRELVY® and meet the claimed functional limitation. ¶68, ¶77 col. 4:7-12
  • Identified Points of Contention:
    • Scope Questions: A central question may be whether the term "extrudate" requires the use of a hot melt extrusion process, as described in the patent’s examples, or if it can be construed more broadly to cover solid dispersions created by other manufacturing methods that Zydus may have used.
    • Technical Questions: The infringement analysis will depend on the precise composition and physical characteristics of Zydus’s product, which are detailed in its confidential ANDA. A key factual question will be whether the Zydus tablet’s specific combination of excipients constitutes a "disintegration system" as that term is understood in the patent, and whether the tablet factually meets the claimed hardness and disintegration time limitations.

11,717,515 Patent 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, Zydus’s proposed product label will instruct physicians to prescribe, and patients to take, its ubrogepant tablets for the acute treatment of migraine. ¶69, ¶113 col. 31:1-2
the method comprising administering a first dose of 50 mg of ubrogepant to a patient, Zydus’s proposed label will instruct for the administration of a 50 mg dose of its generic product to this specific patient population. ¶69, ¶113-114 col. 31:2-3
wherein the patient has a Child-Pugh score of Child-Pugh Class C. Zydus’s proposed label will instruct this specific dosing for patients identified as having severe hepatic impairment, which corresponds to Child-Pugh Class C. ¶69, ¶113 col. 31:4-6
  • Identified Points of Contention:
    • Legal Questions: The analysis will center on induced infringement. The primary question is whether the language in Zydus’s proposed product label, which must mirror the UBRELVY® label, provides sufficient instruction and encouragement to physicians and patients to perform the claimed method, thereby establishing Zydus's specific intent to induce infringement.
    • Factual Questions: A factual question for the court will be whether the acts of prescribing and taking the Zydus generic product according to the anticipated label will result in direct infringement by physicians and patients.

V. Key Claim Terms for Construction

  • The Term: "disintegration system" (’836 Patent, claim 1)
  • Context and Importance: This term is central to the formulation patents (’836 and ’709). The definition will determine whether Zydus’s specific combination of inactive ingredients, designed to make its tablet fall apart, is covered by the claims. Practitioners may focus on this term because Zydus could argue its formulation uses a different combination of excipients that does not function in the manner described and claimed in the patent.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification describes the system functionally as providing "beneficial antigellation effects." (’836 Patent, col. 13:36-43). It also gives "for example" lists of components, such as "croscarmellose sodium or crospovidone, and Powdered Sodium Chloride," suggesting the claim is not limited to only those specific ingredients. (’836 Patent, col. 9:50-54).
    • Evidence for a Narrower Interpretation: The patent repeatedly highlights the surprising efficacy of the specific combination of "Powdered Sodium Chloride" and croscarmellose sodium in a 1:1 ratio. (’836 Patent, col. 11:30-40). A defendant could argue that the invention is defined by this specific, inventive combination and that the term "disintegration system" should be construed to require, at a minimum, "Powdered Sodium Chloride" as a necessary component.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement for all four patents. The basis for this allegation is that Zydus's promotional activities and its proposed package insert will instruct healthcare professionals and patients to use the generic product in a manner that directly infringes the claims, such as by administering the tablet (’836, ’709 Patents) or by administering specific doses to specific patient populations (’515, ’542 Patents). (Compl. ¶¶80-82, 113-115, 142-144, 171-173).
  • Willful Infringement: The complaint does not explicitly use the term "willful infringement." However, it alleges that Zydus has knowledge of the patents-in-suit, as evidenced by its February 20, 2024 Notice Letter. (Compl. ¶¶81, 114, 143). This allegation of pre-suit knowledge could potentially support a later claim for enhanced damages or a finding that the case is "exceptional" for the purpose of awarding attorney fees, which Plaintiffs request. (Compl. p. 32, ¶G).

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

This case will likely center on the interplay between FDA regulatory requirements for generic drugs and the scope of the asserted patent claims. The key questions for the court appear to be:

  • A core issue will be one of claim scope versus product reality: For the formulation patents (’836 and ’709), can Plaintiffs demonstrate that Zydus’s specific formulation, as detailed in its confidential ANDA, falls within the scope of claim terms like "extrudate" and "disintegration system," or will Zydus be able to establish a meaningful technical difference in its manufacturing process or composition?
  • A second central question is one of induced infringement via labeling: For the method-of-use patents (’515 and ’542), does Zydus’s proposed product label, which by regulation must largely mirror the brand-name label, contain sufficient instructional language to prove that Zydus possessed the specific intent to encourage physicians to prescribe, and patients to perform, the patented methods of treating specific patient populations?