Upsher Smith Laboratories LLC v. AMTA Labs Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Upsher-Smith Laboratories, LLC (Minnesota)
  • Defendant: AMTA Labs Limited (Hong Kong)
  • Plaintiff’s Counsel: Lewis Brisbois Bisgaard & Smith, LLP
• Case Identification: 1:24-cv-00058, D. Del., 01/17/2024
• Venue Allegations: Plaintiff alleges venue is proper based on Defendant’s marketing and sale of products throughout the United States, including in Delaware, and its purposeful availment of the rights and benefits of Delaware law.
• Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff’s QUDEXY® XR extended-release capsules constitutes an act of infringement of a patent covering the drug’s formulation.
• Technical Context: The technology relates to pharmaceutical formulations that provide for the extended release of an active ingredient, topiramate, allowing for once-daily dosing which can improve patient compliance and therapeutic outcomes.
• Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant’s submission of ANDA No. 218695 with a Paragraph IV certification. This certification asserts that the patent-in-suit will not be infringed by Defendant’s proposed generic product. Plaintiff states the patent-in-suit is listed in the FDA’s “Approved Drug Products with Therapeutic Equivalence Evaluations” (the “Orange Book”) for its branded drug, QUDEXY® XR. Defendant provided notice of its ANDA filing to Plaintiff on December 4, 2023.

Case Timeline

Date	Event
2013-03-13	'224 Patent Priority Date
2019-07-30	'224 Patent Issue Date
2023-12-04	Defendant's ANDA Notice Letter to Plaintiff
2024-01-17	Complaint Filing Date

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

U.S. Patent No. 10,363,224 - "Extended-Release Topiramate Capsules"

(Issued July 30, 2019)

The Invention Explained

• Problem Addressed: The patent background notes that the efficacy of many drugs depends on patient compliance with dosing schedules and that once-per-day, extended-release formulations can offer better long-term efficacy than regimens requiring multiple doses per day (’224 Patent, col. 2:20-31).
• The Patented Solution: The invention is an extended-release capsule containing a "single population of coated particles" designed for once-daily administration (’224 Patent, col. 3:31-36). Each particle consists of a core, where the active ingredient (topiramate) is blended in a "homogeneous mixture" with other excipients, and an outer coating containing a "release controlling agent" that governs how quickly the drug is released into the body (’224 Patent, Abstract; col. 16:13-19).
• Technical Importance: This formulation technology enables the conversion of an immediate-release drug, topiramate, into a once-daily product, which can improve adherence to treatment for chronic conditions like epilepsy (’224 Patent, col. 2:26-31).

Key Claims at a Glance

• The complaint asserts infringement of "one or more Claims" of the '224 Patent (Compl. ¶24). Independent claim 1 is a representative method of use claim.
• Independent Claim 1 is directed to a method of dosing for the treatment of convulsions, which requires:
  • Administering an extended-release topiramate capsule once daily
  • The capsule comprises a shell containing a "single population of coated particles"
  • Each particle has a core with a "homogeneous mixture" of topiramate and a coating
  • The coating comprises one or more "release controlling agent(s)"
  • The capsule, when given as a single dose, achieves specific pharmacokinetic (PK) parameters: an area-under-the-curve (AUC₀-inf) of 170 to 210 h·µg/mL and a maximum concentration (Cmax) of 2 to 4 µg/mL.

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Defendant AMTA's proposed generic topiramate extended-release capsules in 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg strengths, as described in ANDA No. 218695 (Compl. ¶5).

Functionality and Market Context

The proposed product is a generic version of Plaintiff's branded drug, QUDEXY® XR, which is approved for treating certain types of seizures (Compl. ¶¶ 5, 15). The complaint alleges that Defendant's ANDA contains data to demonstrate that its proposed product is bioequivalent to QUDEXY® XR (Compl. ¶21). It further alleges that the product's instructions for use will "substantially copy" those of the branded drug, directing physicians and patients to administer it for the same approved indications (Compl. ¶22).

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart or detailed infringement contentions. The infringement theory is based on the allegation that by seeking approval for a bioequivalent generic, Defendant’s product will necessarily practice the patented invention.

'224 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A method of dosing a subject for the treatment of convulsions, the method comprising: administering an extended-release topiramate capsule once daily to the subject...	Defendant's product is intended for the same indications as QUDEXY® XR, including seizures, and its label will allegedly instruct for once-daily administration.	¶¶ 15, 22	col. 15:48-52
...wherein the extended-release topiramate capsule comprises: a capsule shell comprising a single population of coated particles;	To achieve bioequivalence with QUDEXY® XR, which is covered by the '224 patent, the proposed generic product is alleged to have the same capsule structure containing a single population of coated particles.	¶¶ 17, 21	col. 16:9-10
...wherein each particle core comprises a homogeneous mixture comprising topiramate throughout its core; and	The proposed generic product is alleged to utilize particle cores containing a homogeneous mixture of topiramate to match the release profile of the branded drug.	¶¶ 17, 21	col. 16:13-16
...wherein the coating comprises one or more release controlling agent(s);	To achieve an extended-release profile, the proposed generic product's particles are alleged to be coated with one or more release controlling agents.	¶¶ 5, 21	col. 16:17-19
...wherein the...capsule...achieves an AUC₀-inf of 170 to 210 h·µg/mL...and a Cmax of 2 to 4 µg/mL...	Defendant’s ANDA allegedly includes data demonstrating bioequivalence, which implies that its product meets the specific pharmacokinetic performance parameters required by the claim.	¶21	col. 16:20-27

No probative visual evidence provided in complaint.

Identified Points of Contention

• Scope Questions: A primary issue will be whether a finding of "bioequivalence" by the FDA is legally equivalent to meeting the specific pharmacokinetic ranges recited in Claim 1. The court will have to determine if Defendant can be bioequivalent yet fall outside the literal scope of the claim's PK limitations.
• Technical Questions: The core factual dispute will concern the precise formulation contained in Defendant’s confidential ANDA. Does it use a "single population" of particles? Is the drug distributed in a "homogeneous mixture" within the core? The ability of Plaintiff to prove infringement will depend on the answers to these questions, which can only be determined through discovery of the ANDA's contents.

V. Key Claim Terms for Construction

"single population of coated particles"

• Context and Importance: This term defines the fundamental architecture of the claimed formulation. Infringement may turn on whether Defendant's product, for example, uses a mixture of particles with different coatings or compositions, which would constitute more than a "single population." Practitioners may focus on this term to determine if the defendant has designed around this core structural element.
• Evidence for a Broader Interpretation: The patent defines this as "all the particles in one capsule are the same (within reasonable manufacturing variability) with respect to composition" ('224 Patent, col. 3:36-39). This could be argued to cover any set of particles produced by a consistent process.
• Evidence for a Narrower Interpretation: The specification notes that the particles in a single population are made "in a single batch process or in multiple batches using identical processes" ('224 Patent, col. 3:39-42). A defendant could argue that if its manufacturing process introduces systematic differences between particle batches that are later combined, the result is not a "single population."

"achieves an AUC₀-inf of 170 to 210 h·µg/mL...and a Cmax of 2 to 4 µg/mL"

• Context and Importance: This functional limitation defines the invention by its clinical performance. Its construction is critical because the infringement case hinges on whether the ANDA product's performance falls within this range.
• Evidence for a Broader Interpretation: A plaintiff would likely argue that these ranges define the performance of the reference listed drug, and any product deemed bioequivalent by the FDA must, by definition, meet these criteria. The patent links these values to clinical study results of its formulation ('224 Patent, col. 15:2-12).
• Evidence for a Narrower Interpretation: A defendant may argue that the FDA's standard for bioequivalence (which relies on a 90% confidence interval for the ratio of PK parameters) is not the same as falling within the specific, fixed numerical range of the claim. It may be possible for a product to be deemed bioequivalent while its measured average AUC or Cmax falls outside the "170-210" or "2-4" ranges, respectively.

VI. Other Allegations

Indirect Infringement

The complaint alleges that Defendant will induce infringement by providing product labeling that "substantially copy[s] the instructions for QUDEXY® XR" (Compl. ¶22). These instructions allegedly will direct physicians and patients to administer the generic product in a manner that directly infringes the asserted method claims (Compl. ¶28).

Willful Infringement

While not pleaded as a separate count, the complaint alleges facts to support a finding of willfulness. It states that Defendant had "knowledge of the '224 Patent" when it filed its ANDA and "lacked a good faith basis" for its Paragraph IV certification that the patent would not be infringed (Compl. ¶¶ 29, 31). These allegations form the basis for a request that the case be found "exceptional" under 35 U.S.C. § 285, which would permit an award of attorneys' fees (Compl. ¶31; Prayer for Relief ¶f).

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

• A core issue will be one of evidentiary proof versus regulatory standards: Does the data in Defendant’s confidential ANDA, submitted to the FDA to prove bioequivalence, constitute a direct admission of infringement of the specific structural and pharmacokinetic limitations of the asserted claims? Or can the Defendant's product be FDA-approved as bioequivalent while simultaneously falling outside the literal scope of the patent?
• A key question will be one of formulation identity: Upon discovery, will the Defendant’s formulation be revealed as a direct copy of the embodiment described in the '224 patent, or has Defendant developed a novel, non-infringing formulation that achieves the same clinical result, thereby successfully "designing around" the patent?
• A central legal question will be the interpretation of functional claims: How will the court construe the claim limitations defined by pharmacokinetic parameters (AUC and Cmax)? The case may turn on whether meeting the FDA’s regulatory test for bioequivalence is legally dispositive of infringement of these claim elements.