DCT

1:17-cv-00649

Upsher Smith Laboratories Inc v. Glenmark Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00649, D. Del., 05/26/2017
  • Venue Allegations: Plaintiff asserts that venue is proper in the District of Delaware because Defendant Glenmark USA is a Delaware corporation and because both defendants conduct substantial business in the district.
  • Core Dispute: Plaintiff alleges that Defendants' proposed generic extended-release topiramate capsules, for which they seek FDA approval via an Abbreviated New Drug Application (ANDA), infringe four U.S. patents covering Plaintiff's branded drug, QUDEXY® XR.
  • Technical Context: The technology concerns pharmaceutical formulations that provide extended release of topiramate, an active ingredient used for treating epilepsy, which allows for once-daily dosing to improve patient compliance and therapeutic effect.
  • Key Procedural History: The litigation was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 210278 to the FDA. This submission included a "Paragraph IV Certification" alleging that Plaintiff's patents are invalid and/or would not be infringed by the proposed generic product.

Case Timeline

Date Event
2013-03-13 Earliest Priority Date for all Patents-in-Suit
2014-02-18 U.S. Patent No. 8,652,527 Issues
2014-11-18 U.S. Patent No. 8,889,190 Issues
2015-08-11 U.S. Patent No. 9,101,545 Issues
2017-01-31 U.S. Patent No. 9,555,005 Issues
2017-04-13 Defendants' ANDA Notice Letter to Plaintiff
2017-05-26 Complaint Filing Date

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

U.S. Patent No. 8,652,527

  • Patent Identification: U.S. Patent No. 8,652,527, “Extended-Release Topiramate Capsules,” issued February 18, 2014.
  • The Invention Explained:
    • Problem Addressed: The patent background section notes that for many drug products, patient compliance with a dosing schedule is critical for efficacy, and that once-daily, extended-release dosages can offer better long-term efficacy than multidose regimens (’527 Patent, col. 1:18-22).
    • The Patented Solution: The invention is a capsule for extended release of the drug topiramate, containing what is described as a "single population of coated particles" (’527 Patent, col. 3:27-29). Each particle consists of a core, where the topiramate is mixed homogeneously with other ingredients, and a functional coating that controls the drug's release over time (’527 Patent, Abstract; col. 3:45-48). This approach of using a single, uniform type of particle may simplify the manufacturing process compared to formulations that require blending multiple distinct particle populations (e.g., immediate-release and extended-release beads).
    • Technical Importance: This formulation technology enables a once-daily dosing option for topiramate, an established anti-epileptic drug, which may improve patient adherence and provide a more stable pharmacokinetic profile over a 24-hour period.
  • Key Claims at a Glance:
    • The complaint asserts "one or more Claims" without specifying them (Compl. ¶29). Independent claim 1 is representative of the core compositional invention.
    • Claim 1 of the ’527 Patent requires:
      • An extended-release topiramate capsule comprising a capsule shell containing a single population of coated particles.
      • Each particle has a core and a coating thereon.
      • The particle core comprises a homogeneous mixture of specific components within defined weight percentage ranges: 40-50 wt-% topiramate, 45-55 wt-% filler(s), and 3-7 wt-% binder(s).
      • The coating comprises specific components within defined weight percentage ranges: 55-65 wt-% release control agent(s), 20-25 wt-% pore former(s), and 10-20 wt-% plasticizer(s).
      • The particles are coated in an amount sufficient to provide a weight gain of 8% to 14%.
    • The complaint does not explicitly reserve the right to assert dependent claims, but this is standard practice.

U.S. Patent No. 8,889,190

  • Patent Identification: U.S. Patent No. 8,889,190, “Extended-Release Topiramate Capsules,” issued November 18, 2014.
  • The Invention Explained:
    • Problem Addressed: As a continuation of the application leading to the ’527 Patent, the ’190 Patent addresses the same technical problem of improving patient compliance and efficacy through a once-daily, extended-release formulation (’190 Patent, col. 1:14-22).
    • The Patented Solution: The patented solution is structurally similar to that of the ’527 Patent, involving a capsule with a single population of coated particles containing topiramate (’190 Patent, Abstract). However, the claims of the ’190 Patent introduce limitations based on the formulation's in-vivo pharmacokinetic (PK) performance in addition to its physical composition.
    • Technical Importance: By claiming specific pharmacokinetic outcomes, the patent attempts to protect not just the physical drug product but also the specific therapeutic profile it achieves in the human body.
  • Key Claims at a Glance:
    • The complaint asserts "one or more Claims" (Compl. ¶38). Independent claim 1 is representative.
    • Claim 1 of the ’190 Patent requires:
      • An extended-release topiramate capsule comprising a single population of coated particles with a core (topiramate, filler, binder) and a coating (release agent, pore former, plasticizer).
      • A pharmacokinetic limitation: "wherein, when a single dose is given to a healthy human subject, an AUCo-inf of 170 to 210 h·µg/mL within a 95% confidence interval, and a Cmax of 2 to 4 µg/mL within a 95% confidence interval are achieved in the subject's plasma."
    • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 9,101,545

  • Patent Identification: U.S. Patent No. 9,101,545, “Extended-Release Topiramate Capsules,” issued August 11, 2015.
  • Technology Synopsis: This patent, part of the same family, claims an extended-release topiramate capsule containing a single population of coated particles. The invention is directed at a specific formulation designed to provide a stable, once-daily release profile for topiramate, addressing the need for improved patient dosing regimens (Compl. ¶18).
  • Asserted Claims: The complaint asserts "one or more Claims" (Compl. ¶47). Independent claims of the patent are 1, 19, and 21.
  • Accused Features: The complaint alleges that Defendants' "Proposed ANDA Product" will infringe the patent (Compl. ¶47).

U.S. Patent No. 9,555,005

  • Patent Identification: U.S. Patent No. 9,555,005, “Extended-Release Topiramate Capsules,” issued January 31, 2017.
  • Technology Synopsis: This patent continues the same technology, claiming an extended-release topiramate capsule with a single population of coated particles. The claims cover specific compositional features and the resulting pharmacokinetic performance, intended to provide a bioequivalent and therapeutically effective once-daily dosage form (Compl. ¶19).
  • Asserted Claims: The complaint asserts "one or more Claims" (Compl. ¶56). Independent claims of the patent are 1 and 27.
  • Accused Features: The complaint alleges that Defendants' "Proposed ANDA Product" will infringe the patent (Compl. ¶56).

III. The Accused Instrumentality

  • Product Identification: The accused product is Defendants' "Proposed ANDA Product," identified as the subject of Abbreviated New Drug Application No. 210278 (Compl. ¶5-6). It is described as topiramate extended-release capsules in 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg strengths (Compl. ¶6).
  • Functionality and Market Context: The complaint alleges that the Proposed ANDA Product is a generic version of Plaintiff's QUDEXY® XR extended-release capsules (Compl. ¶6). The ANDA filing contains data intended to demonstrate the "bioequivalence" of the proposed generic product to QUDEXY® XR (Compl. ¶26). Upon expected FDA approval, Defendants intend to engage in the commercial manufacture and sale of this product in the United States as a lower-cost generic alternative to the branded drug (Compl. ¶6, ¶13).

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart or provide specific factual allegations mapping elements of the accused product to the patent claims. The infringement theory is predicated on Defendants' ANDA submission, which seeks approval for a product alleged to be bioequivalent to Plaintiff's patented QUDEXY® XR product (Compl. ¶26). The following chart summarizes the infringement allegations that can be inferred from this assertion of bioequivalence.

’527 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
a capsule shell comprising a single population of coated particles The Proposed ANDA Product is an extended-release capsule alleged to be bioequivalent to QUDEXY® XR, which contains such particles. ¶6, ¶26, ¶29 col. 3:27-29
each particle core comprises a homogeneous mixture... comprising: 40 wt-% to 50 wt-% of topiramate... 45 wt-% to 55 wt-% of... filler(s)... 3 wt-% to 7 wt-% of... binder(s) To achieve bioequivalence, the core of the particles in the Proposed ANDA Product must allegedly contain topiramate, fillers, and binders in the claimed proportions. ¶26, ¶29 col. 4:51-65
the coating comprises: 55 wt-% to 65 wt-% of... release control agent(s)... 20 wt-% to 25 wt-% of... pore former(s)... 10 wt-% to 20 wt-% of... plasticizer(s) To achieve the same extended-release profile, the coating on the particles in the Proposed ANDA Product must allegedly contain release agents, pore formers, and plasticizers in the claimed proportions. ¶26, ¶29 col. 6:8-13
the particles are coated in an amount sufficient to provide a weight gain of 8% to 14% The coating thickness of the particles in the Proposed ANDA Product, necessary for bioequivalence, allegedly results in a weight gain falling within the claimed range. ¶26, ¶29 col. 4:27-28

’190 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
An extended-release topiramate capsule comprising... a single population of coated particles The Proposed ANDA Product is an extended-release capsule alleged to be bioequivalent to QUDEXY® XR, which contains such particles. ¶6, ¶26, ¶38 col. 3:29-31
wherein, when a single dose is given to a healthy human subject, an AUCo-inf of 170 to 210 h·µg/mL... and a Cmax of 2 to 4 µg/mL... are achieved Defendants' ANDA submission contains data that allegedly demonstrates the bioequivalence of the Proposed ANDA Product, which requires it to meet pharmacokinetic parameters that fall within the claimed ranges. ¶26, ¶38 col. 8:50-56
  • Identified Points of Contention:
    • Scope Questions: A central question for the composition-focused claims of the ’527 Patent will be whether Defendants' formulation literally meets the specified weight percentage ranges for each component. Defendants may argue their product achieves bioequivalence while using a formulation that falls outside these claimed ranges, thereby "designing around" the patent.
    • Technical Questions: For the pharmacokinetic-focused claims of the ’190 Patent, a potential dispute may arise over the conditions and results of Defendants' bioequivalence studies. The analysis will question whether the data submitted to the FDA definitively proves that the Proposed ANDA Product meets the specific AUC and Cmax ranges recited in the claim when tested in a population that meets the claim’s definition of a "healthy human subject."

No probative visual evidence provided in complaint.

V. Key Claim Terms for Construction

  • The Term: "a single population of coated particles" (’527 Patent, cl. 1)

  • Context and Importance: This term is foundational to the claimed invention, distinguishing it from formulations that blend different types of beads. Its construction is critical because if Defendants can demonstrate their product contains more than one "population" of particles—even if due to normal manufacturing variations—they may argue non-infringement. Practitioners may focus on this term to dispute whether minor variations in particle size, coating thickness, or composition between manufacturing batches create distinct "populations."

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification suggests some variability is permitted, stating that particles in a single population are the same "within reasonable manufacturing variability" and can be made in "multiple batches using identical processes" (’527 Patent, col. 3:30-34).
    • Evidence for a Narrower Interpretation: The description emphasizes that "different populations of particles... do not need to be manufactured for one product," which could be used to argue for a strict interpretation where any meaningful compositional or functional difference between particle groups creates more than a single population (’527 Patent, col. 3:39-41).

  • The Term: "homogeneous mixture" (’527 Patent, cl. 1)

  • Context and Importance: This term defines the structure of the particle core. Infringement requires topiramate to be evenly distributed throughout the core, not, for example, layered on a sugar sphere. The dispute will likely center on the degree of uniformity required to be "homogeneous."

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent does not provide an explicit definition, suggesting the term should be given its plain and ordinary meaning, which would likely tolerate minor, microscopic variations in drug concentration within the core.
    • Evidence for a Narrower Interpretation: The Examples section describes a specific high-shear granulation and extrusion process to form the cores (’527 Patent, col. 13:50-58). A party could argue that "homogeneous mixture" should be construed as being limited to the type of mixture that results from this disclosed process.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement under 35 U.S.C. § 271(b) (Compl. ¶33). The factual basis is the allegation that the product labeling for the Proposed ANDA Product will "substantially copy the instructions" for QUDEXY® XR and will direct physicians and patients to administer the product in an infringing manner (Compl. ¶27, ¶31).
  • Willful Infringement: The complaint alleges that the case is "exceptional" and that Defendants' Paragraph IV certification was "wholly unjustified" (Compl. ¶36). This is based on alleged pre-suit knowledge of the patents, which Defendants were "necessarily aware of" when filing the ANDA with the Paragraph IV certification (Compl. ¶25, ¶34).

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

  • A core issue will be one of formulation scope: does Glenmark's proposed generic product, despite its asserted bioequivalence, utilize a formulation with component weight percentages, excipients, or a particle structure that falls outside the specific compositional boundaries defined in claims like Claim 1 of the ’527 Patent?
  • A key evidentiary question will be one of bioequivalence as proof: to what extent can the plaintiff rely on the defendant's own FDA submission and bioequivalence data as sufficient evidence to demonstrate, on a prima facie basis, that the accused product necessarily meets both the structural and the pharmacokinetic limitations of the asserted patents?
  • A central claim construction dispute will likely concern the term "single population," and whether routine, acceptable variations in a pharmaceutical manufacturing process can be characterized as creating multiple distinct populations of particles, thereby avoiding the literal scope of the claims.