DCT

3:21-cv-06964

Supernus Pharma Inc v. Ajanta Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:21-cv-06964, D.N.J., 03/26/2021
  • Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendant Ajanta Pharma USA Inc. maintains its principal place of business in the district, and both defendants have purposefully availed themselves of the privilege of doing business in New Jersey by placing goods into the stream of commerce.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's Trokendi XR® product infringes ten U.S. patents related to sustained-release formulations of topiramate.
  • Technical Context: The patents relate to pharmaceutical formulations of topiramate, an antiepileptic and migraine-prevention drug, designed for once-daily administration to improve patient compliance and reduce side effects associated with immediate-release versions.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 215663 seeking FDA approval for a generic topiramate product. The filing of the ANDA with a Paragraph IV certification constitutes a statutory act of infringement. Plaintiff received a Paragraph IV notice letter from Defendants on or about February 10, 2021, prompting this lawsuit.

Case Timeline

Date Event
2006-11-17 Priority Date for all ten Patents-in-Suit
2012-10-30 U.S. Patent No. 8,298,576 Issued
2012-10-30 U.S. Patent No. 8,298,580 Issued
2014-03-04 U.S. Patent No. 8,663,683 Issued
2014-11-04 U.S. Patent No. 8,877,248 Issued
2014-11-18 U.S. Patent No. 8,889,191 Issued
2015-03-31 U.S. Patent No. 8,992,989 Issued
2017-01-24 U.S. Patent No. 9,549,940 Issued
2017-01-31 U.S. Patent No. 9,555,004 Issued
2017-04-18 U.S. Patent No. 9,622,983 Issued
2019-06-11 U.S. Patent No. 10,314,790 Issued
2021-02-10 Ajanta sends Paragraph IV Notice Letter to Supernus
2021-03-26 Complaint Filed

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

U.S. Patent No. 8,298,576 - “Sustained-Release Formulations of Topiramate,” Issued October 30, 2012

The Invention Explained

  • Problem Addressed: The patent’s background section describes that immediate-release topiramate requires multiple daily doses, which is cumbersome for patients and can lead to missed doses. This dosing regimen also results in undesirable peaks and troughs in blood plasma concentrations, with the peaks being associated with severe side effects such as dizziness and psychomotor slowing (’576 Patent, col. 1:49-61).
  • The Patented Solution: The invention is a once-daily formulation of topiramate that provides a sustained, non-pulsatile release of the drug. It achieves this by combining different populations of drug-coated beads: an optional immediate-release (IR) component for initial effect and one or more extended-release (XR) components with specific coatings that dissolve at different rates to prolong the drug's effect over a 24-hour period (’576 Patent, col. 2:3-14, Abstract). This design is intended to improve patient compliance and reduce the severity of side effects by smoothing the plasma concentration curve (’576 Patent, col. 2:5-10).
  • Technical Importance: This approach allows for a once-daily dosage regimen that can improve therapeutic outcomes by increasing patient adherence and reducing the adverse events linked to the high peak plasma levels seen with immediate-release formulations (’576 Patent, col. 1:61-64).

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims (Compl. ¶57). Independent claim 1 is representative.
  • Claim 1 of the ’576 Patent recites:
    • A sustained release formulation for oral administration comprising three distinct bead populations: an immediate release (IR) population, a first extended release (XR1) population, and a second extended release (XR2) population.
    • The IR bead population comprises up to 10% of the total topiramate by weight, is coated on an inert carrier, is not coated with a release controlling material, and releases at least 80% of its topiramate in one hour or less.
    • The XR1 bead population comprises up to 20% of the total topiramate, is coated on an inert carrier, is further coated with a release controlling material, and releases 80% of its topiramate in four hours or less.
    • The XR2 bead population comprises at least 80% of the total topiramate, is coated on an inert carrier, is further coated with a release controlling material, and releases 80% of its topiramate in eight hours or less.
    • The release controlling coating materials are selected from cellulosic or acrylic polymers.

U.S. Patent No. 8,298,580 - “Sustained-Release Formulations of Topiramate,” Issued October 30, 2012

The Invention Explained

  • Problem Addressed: The specification of the ’580 Patent is substantially identical to that of the ’576 Patent and addresses the same problems of poor patient compliance and side effects associated with peak plasma concentrations of immediate-release topiramate (’580 Patent, col. 1:49-61).
  • The Patented Solution: The patented solution is also a once-daily, sustained-release formulation. However, the claims of the ’580 Patent are directed toward a formulation that includes specific types of excipients in the immediate-release component to improve the drug's properties (’580 Patent, col. 2:3-14). The formulation combines at least two extended-release components with an immediate-release component that contains a "complexing agent" and/or an "enhancing agent" (’580 Patent, col. 20:25-30).
  • Technical Importance: The use of complexing or enhancing agents in the immediate-release portion of the formulation is intended to improve the solubility and/or bioavailability of the initial dose, potentially leading to a more rapid and reliable onset of therapeutic effect (’580 Patent, col. 9:8-12).

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims (Compl. ¶65). Independent claim 1 is representative.
  • Claim 1 of the ’580 Patent recites:
    • A sustained release formulation of topiramate for oral administration.
    • The formulation comprises at least two different extended release (XR) topiramate-containing components.
    • The formulation also comprises an immediate release (IR) topiramate-containing component.
    • The IR component further comprises a complexing agent (such as a cyclodextrin) and/or an enhancing agent (such as Vitamin E TPGS, a surfactant, or a sugar).
    • The formulation must exhibit an in vivo steady state maximum plasma concentration of topiramate at 3 or more hours after administration.

Multi-Patent Capsule: U.S. Patent No. 8,663,683

  • Patent Identification: U.S. Patent No. 8,663,683, “Sustained-Release Formulations of Topiramate,” Issued March 4, 2014.
  • Technology Synopsis: This patent is part of the same family and discloses sustained-release topiramate formulations for once-daily administration. The claims are directed to specific pharmacokinetic (PK) profiles, such as achieving a maximum plasma concentration (Cmax) within a specified range relative to immediate-release products, providing a particular therapeutic window.
  • Asserted Claims: One or more claims (Compl. ¶73).
  • Accused Features: The Ajanta Products, which are generic topiramate extended-release capsules (Compl. ¶70).

Multi-Patent Capsule: U.S. Patent No. 8,877,248

  • Patent Identification: U.S. Patent No. 8,877,248, “Sustained-Release Formulations of Topiramate,” Issued November 4, 2014.
  • Technology Synopsis: This patent continues the same technology of once-daily topiramate formulations. Its claims focus on methods of treating neurological or psychiatric conditions by administering a formulation comprising at least two extended-release components and an optional immediate-release component containing specific enhancing or complexing agents.
  • Asserted Claims: One or more claims (Compl. ¶81).
  • Accused Features: The Ajanta Products, whose proposed labeling allegedly instructs for the patented methods of treatment (Compl. ¶¶ 43-44, 78).

Multi-Patent Capsule: U.S. Patent No. 8,889,191

  • Patent Identification: U.S. Patent No. 8,889,191, “Sustained-Release Formulations of Topiramate,” Issued November 18, 2014.
  • Technology Synopsis: This patent covers methods of treating neurological or psychiatric conditions by administering a sustained-release formulation of topiramate where at least 85% of the drug is in an extended-release component comprising at least two bead populations with different release profiles.
  • Asserted Claims: One or more claims (Compl. ¶89).
  • Accused Features: The Ajanta Products and their proposed use for patented therapeutic methods (Compl. ¶¶ 43-44, 86).

Multi-Patent Capsule: U.S. Patent No. 8,992,989

  • Patent Identification: U.S. Patent No. 8,992,989, “Sustained-Release Formulations of Topiramate,” Issued March 31, 2015.
  • Technology Synopsis: This patent claims sustained-release formulations with specific pharmacokinetic parameters, such as achieving a Cmax at 16 or more hours after a single initial dose, indicating a very prolonged release profile. The claims cover formulations with and without an immediate-release component.
  • Asserted Claims: One or more claims (Compl. ¶97).
  • Accused Features: The Ajanta Products, which are alleged to meet the claimed pharmacokinetic profiles (Compl. ¶94).

Multi-Patent Capsule: U.S. Patent No. 9,549,940

  • Patent Identification: U.S. Patent No. 9,549,940, “Sustained-Release Formulations of Topiramate,” Issued January 24, 2017.
  • Technology Synopsis: This patent claims sustained-release topiramate formulations comprising at least two extended-release components, with or without an immediate-release component, that exhibit a specific Cmax between 4 and 8.5 hours after a single initial dose.
  • Asserted Claims: One or more claims (Compl. ¶105).
  • Accused Features: The Ajanta Products, which are alleged to meet the claimed pharmacokinetic profiles (Compl. ¶102).

Multi-Patent Capsule: U.S. Patent No. 9,555,004

  • Patent Identification: U.S. Patent No. 9,555,004, “Sustained-Release Formulations of Topiramate,” Issued January 31, 2017.
  • Technology Synopsis: This patent claims methods of treatment using sustained-release formulations containing micronized topiramate particles. The claims are directed to formulations that achieve specific pharmacokinetic profiles, such as a Cmax between 4 and 8.5 hours.
  • Asserted Claims: One or more claims (Compl. ¶113).
  • Accused Features: The Ajanta Products and their proposed use, alleged to be made with micronized topiramate and to meet the claimed pharmacokinetic profiles (Compl. ¶110).

Multi-Patent Capsule: U.S. Patent No. 9,622,983

  • Patent Identification: U.S. Patent No. 9,622,983, “Sustained-Release Formulations of Topiramate,” Issued April 18, 2017.
  • Technology Synopsis: This patent is directed to sustained-release formulations comprising topiramate in the form of micronized particles. The claims cover formulations with specific compositions of extended-release and immediate-release components containing particular enhancing agents.
  • Asserted Claims: One or more claims (Compl. ¶121).
  • Accused Features: The Ajanta Products, which are alleged to be formulated with micronized topiramate and contain the claimed components (Compl. ¶118).

Multi-Patent Capsule: U.S. Patent No. 10,314,790

  • Patent Identification: U.S. Patent No. 10,314,790, “Sustained-Release Formulations of Topiramate,” Issued June 11, 2019.
  • Technology Synopsis: This patent claims sustained-release formulations comprising at least two extended-release components and an immediate-release component containing specific complexing and/or enhancing agents. The claims require a specific pharmacokinetic profile of achieving a Cmax at 3 or more hours post-administration.
  • Asserted Claims: One or more claims (Compl. ¶129).
  • Accused Features: The Ajanta Products, which are alleged to contain the claimed components and exhibit the claimed pharmacokinetic profile (Compl. ¶126).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentalities are generic topiramate extended-release capsules in 25 mg, 50 mg, 100 mg, and 200 mg dosage strengths ("the Ajanta Products"), for which Defendant Ajanta Pharma Ltd. filed Abbreviated New Drug Application (ANDA) No. 215663 with the U.S. Food and Drug Administration (FDA) (Compl. ¶9).
  • Functionality and Market Context: The complaint alleges that the Ajanta Products are extended-release formulations designed to be bioequivalent to Plaintiff's Trokendi XR® product, which is the Reference Listed Drug (Compl. ¶41). The proposed prescribing information allegedly indicates the same uses as Trokendi XR®: monotherapy and adjunctive therapy for certain seizures and preventive treatment of migraine (Compl. ¶43). The complaint further alleges the Ajanta Products contain specific inactive ingredients including Sugar Spheres, Hypromellose, Mannitol, Docusate Sodium, and Ethylcellulose, among others (Compl. ¶46). As a generic drug product submitted via an ANDA, the Ajanta Products are intended to be a lower-cost, substitutable alternative to the branded Trokendi XR® upon receiving FDA approval.

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

  • 8,298,576 Patent Infringement Allegations
Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A sustained release formulation of topiramate for oral administration ... comprising an immediate release bead population (IR), a first extended release bead population (XR1), and a second extended release bead population (XR2) The Ajanta Product is an extended-release capsule formulation of topiramate, which is alleged to contain different populations of beads designed to achieve a sustained-release profile bioequivalent to the reference drug (Trokendi XR®) ¶9, ¶41, ¶42 col. 19:50-55
the IR bead population comprises topiramate up to 10% by wt of the total amount of topiramate ... wherein the IR bead population releases greater than or equal to 80% of its topiramate ... in less than or equal to 1 hour The complaint alleges, on information and belief, that to achieve bioequivalence with the reference drug, the Ajanta Product must contain an immediate-release component with a corresponding drug load and release profile ¶41, ¶57 col. 19:56-65
the XR1 bead population comprises topiramate up to 20% by wt ... wherein the XR1 bead population releases 80% of its topiramate ... over less than or equal to 4 hours The complaint alleges, on information and belief, that the Ajanta Product contains a first type of extended-release beads designed to release topiramate over an initial extended period. Ingredients like Hypromellose and Ethylcellulose are alleged to be used to create the release-controlling coating ¶41, ¶46, ¶57 col. 20:1-8
the XR2 bead population comprises topiramate at least 80% by weight of the total amount of topiramate ... wherein the XR2 bead population releases 80% of its topiramate ... over less than 8 hours The complaint alleges, on information and belief, that the Ajanta Product contains a second, more slowly releasing population of extended-release beads, which constitutes the bulk of the dosage, to maintain therapeutic levels over a 24-hour period ¶41, ¶57 col. 20:9-16
wherein the release controlling coating materials comprise methylcellulose, ethylcellulose ... or copolymers thereof The complaint alleges the Ajanta Products contain inactive ingredients such as Ethylcellulose and Hypromellose, which are cellulosic polymers named in the patent as suitable for creating release-controlling coatings ¶46 col. 20:17-23
  • 8,298,580 Patent Infringement Allegations
Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A sustained release formulation of topiramate for oral administration ... comprising: (a) at least two different extended release (XR) topiramate-containing components ... and, optionally, (b) an immediate release (IR) topiramate-containing component The Ajanta Product is an extended-release capsule formulation of topiramate, alleged to contain multiple bead populations to achieve a sustained-release profile ¶9, ¶41, ¶42 col. 20:21-27
wherein the IR component comprises: (i) a complexing agent selected from the group consisting of ... cyclodextrin ... and/or (ii) an enhancing agent selected from the group consisting of Vitamin E TPGS, ... sodium lauryl sulfate ... and combinations thereof The complaint alleges the Ajanta Products contain inactive ingredients such as Docusate Sodium, a surfactant alleged to function as an "enhancing agent" as defined by the patent by, for example, enhancing solubility or dissolution ¶46, ¶65 col. 20:28-48
wherein the formulation exhibits an in vivo steady state maximum plasma concentration of topiramate at 3 or more hours after administration As the Ajanta Product is an extended-release formulation intended to be bioequivalent to Trokendi XR®, it is alleged that it will necessarily exhibit a delayed time to maximum plasma concentration (Tmax) of 3 hours or more, consistent with a sustained-release profile rather than an immediate-release one ¶41, ¶42, ¶65 col. 20:49-52
  • Identified Points of Contention:
    • Scope Questions: A central question for the ’576 Patent will be whether the Ajanta Product contains the specifically claimed three-bead-population architecture (IR, XR1, XR2) with the claimed weight percentages and release rates. For the ’580 Patent, a key issue may be whether an excipient like "Docusate Sodium," listed in the accused product's alleged formulation, meets the patent's definition of an "enhancing agent," or if it is merely a conventional processing aid without the claimed enhancing effect.
    • Technical Questions: As the plaintiff has not yet received the defendant's ANDA submission (Compl. ¶53), the infringement allegations are based on the product's reference drug and a list of inactive ingredients. A primary technical question will be what evidence the complaint provides that the specific combination of excipients in the Ajanta Products (Compl. ¶46) results in bead populations that meet the quantitative release profile limitations recited in the asserted claims.

V. Key Claim Terms for Construction

  • The Term: "enhancing agent" (’580 Patent, Claim 1)
    • Context and Importance: Infringement of key claims of the ’580 Patent and several related patents depends on whether any excipients in the Ajanta Product fall within the scope of this term. Practitioners may focus on this term because the defendant may argue that its excipients, such as Docusate Sodium, are conventional surfactants used for standard formulation purposes and do not "enhance" the drug in the manner contemplated by the patent.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification provides a broad definition: "an enhancing agent ('enhancer') is defined as any non-pharmaceutically active ingredient that improves the therapeutic potential of a formulation" (’580 Patent, col. 3:25-28). The patent provides an extensive, non-limiting list of enhancers, which includes "surface active agents" and specific examples like "sodium lauryl sulfate," suggesting that common surfactants are contemplated (’580 Patent, col. 9:36-40).
      • Evidence for a Narrower Interpretation: A defendant might argue that the context of the invention requires the "enhancing agent" to solve a specific problem beyond routine formulation, such as overcoming poor solubility in a way that provides a non-obvious therapeutic benefit. Language describing enhancers as providing "multiple enhancement effects" or "synergistic enhancement" could be cited to argue that a mere incidental effect of a standard excipient is insufficient (’580 Patent, col. 9:49-55).
  • The Term: "a first extended release bead population (XR1)" and "a second extended release bead population (XR2)" (’576 Patent, Claim 1)
    • Context and Importance: Infringement of Claim 1 of the ’576 Patent requires the presence of two distinct extended-release populations with different compositions (by weight percent of total drug) and different release rates. The construction of these terms will determine whether a formulation with a continuous distribution of bead properties, rather than two clearly distinct batches, would infringe.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The claim language requires two "populations," which could be interpreted functionally. If the accused product contains beads that can be sorted into two groups that meet the respective weight and release rate limitations, that may be sufficient, even if they were not manufactured as two separate batches. The specification's general discussion of combining bead populations to achieve a "pre-determined release profile" supports a functional interpretation (’576 Patent, col. 5:34-45).
      • Evidence for a Narrower Interpretation: The detailed description of the invention explains preparing and coating separate "population[s] of beads" and then "incorporating the beads into the formulation," which could imply that the populations must be physically distinct batches created during manufacturing (’576 Patent, col. 3:1-10). The claim's distinct limitations for XR1 (up to 20% wt.) and XR2 (at least 80% wt.) further suggest two discrete and identifiable groups of beads.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement against both defendants. The basis for this allegation is that the defendants' proposed product labeling and prescribing information will actively instruct physicians and patients to administer the Ajanta Products for the patented methods of treating seizures and preventing migraines, thereby encouraging direct infringement by end-users (Compl. ¶¶ 58, 66, 74).
  • Willful Infringement: The complaint seeks a judgment of an "exceptional case" under 35 U.S.C. § 285, which is analogous to a willfulness claim in this pre-launch ANDA context. The allegation is based on the defendants' knowledge of the patents-in-suit via their listing in the FDA's Orange Book and the allegation that the defendants' Paragraph IV notice letter failed to provide a good-faith basis for their non-infringement and/or invalidity positions, suggesting they acted "without a reasonable basis for believing that they would not be liable for infringement" (Compl. ¶¶ 59-60, 67-68).

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

  • A core issue will be one of compositional identity: once discovery on the ANDA is complete, does the Ajanta Product's formulation actually contain the specific multi-particulate systems required by the claims—such as the distinct IR, XR1, and XR2 bead populations of the ’576 Patent—or is there a fundamental mismatch in the formulation's architecture?
  • A key legal question will be one of definitional scope: can common pharmaceutical surfactants and solubilizers, such as the docusate sodium allegedly used in the Ajanta Product, be construed to fall within the patent term "enhancing agent," or is the term limited to ingredients that provide a non-obvious therapeutic improvement beyond their conventional formulation function?
  • A central evidentiary question will concern pharmacokinetics: what evidence will be presented to demonstrate whether the Ajanta Product, as formulated, meets the specific quantitative pharmacokinetic (e.g., Cmax at >3 hours) and in vitro dissolution (e.g., 80% release in <4 hours) limitations that are recited as essential elements in various asserted claims?