DCT

1:18-cv-00960

Belcher Pharma LLC v. Intl Medication Systems Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-00960, D. Del., 06/28/2018
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because the Defendant is a Delaware corporation.
  • Core Dispute: Plaintiff alleges that Defendant’s submission of a New Drug Application to the FDA for an epinephrine injection product constitutes an act of infringement of a patent directed to stable, low-impurity epinephrine formulations.
  • Technical Context: The technology concerns pharmaceutical formulations of l-epinephrine, a critical drug for emergency medicine, designed to minimize chemical degradation and improve safety and potency.
  • Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Defendant’s submission of New Drug Application (NDA) No. 211363 with a Paragraph IV certification. The certification asserts that U.S. Patent No. 9,283,197, which is listed in the FDA’s Orange Book for Plaintiff's approved epinephrine product, is invalid, unenforceable, or will not be infringed by the commercial manufacture, use, or sale of Defendant’s proposed product. The complaint was filed within the 45-day statutory window following receipt of the Defendant's notice letter, which triggers an automatic 30-month stay on the FDA’s approval of the Defendant's NDA.

Case Timeline

Date Event
2014-08-15 ’197 Patent Priority Date
2016-03-15 ’197 Patent Issue Date
2018-05-16 Plaintiff receives Defendant's Paragraph IV Notice Letter
2018-06-28 Complaint Filing Date

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

U.S. Patent No. 9,283,197 - “More Potent And Less Toxic Formulations Of Epinephrine And Methods Of Medical Use”

  • Issued: March 15, 2016

The Invention Explained

  • Problem Addressed: The patent’s background section states that existing liquid formulations of epinephrine suffer from two major degradation problems: oxidation and racemization (’197 Patent, col. 2:56-57). Racemization converts the potent l-epinephrine isomer into the significantly less potent d-epinephrine isomer, reducing the drug's effectiveness (’197 Patent, col. 2:57-61). Prior art solutions often involved adding sulfites as antioxidants, which can cause severe allergic reactions in some patients, or using excess amounts of the active ingredient (“overages”) to compensate for degradation, which could lead to hazardous dosing (’197 Patent, col. 2:15-40).
  • The Patented Solution: The invention is a preservative-free and sulfite-free epinephrine formulation that achieves superior stability by controlling the solution’s pH within a narrow range of 2.8 to 3.3 (’197 Patent, col. 4:50-59). The inventors discovered, contrary to expectations, that this slightly higher pH range significantly reduced racemization, which they identified as a more critical problem than oxidation in sulfite-free solutions. This allows for a formulation with minimal impurities and reduced overages, improving safety and reliability (’197 Patent, col. 4:50-62).
  • Technical Importance: The invention provided a method to create a safer and more stable formulation of a critical, life-saving drug, addressing the dual risks of allergic reactions from sulfites and inconsistent potency from degradation (’197 Patent, col. 2:50-56).

Key Claims at a Glance

  • The complaint asserts independent claim 6 and dependent claim 7 (’197 Patent, col. 7:1-12; Compl. ¶20).
  • Essential elements of independent claim 6 include:
    • An injectable liquid pharmaceutical formulation of l-epinephrine sterile solution;
    • The formulation has a pH between 2.8 and 3.3;
    • The formulation is compounded in an aqueous solution as 1.0 to 1.06 mg/mL l-epinephrine and includes a tonicity agent;
    • The formulation includes no more than about 6% d-epinephrine and no more than about 0.5% adrenalone at release; and
    • The formulation includes no more than about 12% d-epinephrine and no more than about 0.5% adrenalone over a shelf-life of at least 12 months.
  • The complaint does not explicitly reserve the right to assert other claims.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendant IMS’s “Epinephrine Injection USP, Luer-Jet, Luer-Lock Prefilled Syringe 1mg/10mL,” which is the subject of NDA No. 211363 (the “NDA Product”) (Compl. ¶8).

Functionality and Market Context

  • The NDA Product is a pharmaceutical injection indicated to increase mean arterial blood pressure in adult patients with hypotension associated with septic shock and for other emergency uses (Compl. ¶14). The complaint alleges that the manufacture of this product is covered by the claims of the ’197 Patent (Compl. ¶20). As the product is pending FDA approval, the infringement allegation is based on the statutory act of filing the NDA under 35 U.S.C. § 271(e)(2), not on commercial sales (Compl. ¶23).

IV. Analysis of Infringement Allegations

The complaint makes a general allegation that the manufacture of the NDA Product is covered by claims 6 and 7, but does not provide a detailed, element-by-element breakdown of infringement. The following chart is based on the necessary inferences from the complaint’s conclusory allegations.

No probative visual evidence provided in complaint.

’197 Patent Infringement Allegations

Claim Element (from Independent Claim 6) Alleged Infringing Functionality Complaint Citation Patent Citation
An injectable liquid pharmaceutical formulation of l-epinephrine sterile solution; The complaint alleges that the NDA Product is an injectable liquid pharmaceutical formulation of l-epinephrine sterile solution. ¶8, ¶20 col. 7:1-2
said liquid pharmaceutical formulation having a pH between 2.8 and 3.3; The complaint does not provide specific detail on the pH of the NDA Product, but alleges its manufacture is covered by the claim, which requires this pH range. ¶20 col. 7:3-4
said injectable liquid pharmaceutical formulation compounded in an aqueous solution as 1.0 to 1.06 mg/mL l-epinephrine, and further including a tonicity agent; The complaint does not provide specific detail on the concentration or the presence of a tonicity agent in the NDA Product, but alleges its manufacture is covered by the claim. ¶20 col. 7:4-8
said liquid pharmaceutical formulation including no more than about 6% d-epinephrine and no more than about 0.5% adrenalone at release, The complaint does not provide specific detail on the impurity profile of the NDA Product at release, but alleges its manufacture is covered by the claim. ¶20 col. 7:8-10
and no more than about 12% d-epinephrine and no more than about 0.5% adrenalone over a shelf-life of at least 12 months. The complaint does not provide specific detail on the stability and impurity profile of the NDA Product over its shelf-life, but alleges its manufacture is covered by the claim. ¶20 col. 7:10-12
  • Identified Points of Contention:
    • Technical Questions: The primary dispute will concern the specific, confidential characteristics of the defendant's NDA Product. The central question is whether the product, as described in NDA No. 211363, meets every limitation of claim 6. This raises several factual questions for discovery:
      • What is the precise pH of the accused formulation as manufactured?
      • What are the measured levels of d-epinephrine and adrenalone at the time of batch release?
      • What do stability studies for the accused product show regarding impurity levels after 12 months of storage?
      • Does the formulation contain an excipient that qualifies as a "tonicity agent" under the claim?

V. Key Claim Terms for Construction

The Term: "pH between 2.8 and 3.3"

  • Context and Importance: This pH range is the central feature of the invention, purported to be the key to reducing racemization. Infringement will depend on whether the accused product’s pH falls strictly within this range.
  • Intrinsic Evidence for Interpretation: The patent repeatedly identifies this range as the solution to the prior art's problems (’197 Patent, col. 4:50-59). The specification describes a specific embodiment having an in-process pH of "approximately 3.0" (’197 Patent, col. 4:59-62). This specificity may support a narrow construction, while the use of "between" may lead to arguments about whether the endpoints (2.8 and 3.3) are inclusive.

The Term: "at release"

  • Context and Importance: This term defines the time point for measuring the initial impurity levels. Its construction is critical for determining whether the accused product meets the limitation of having "no more than about 6% d-epinephrine."
  • Intrinsic Evidence for Interpretation: The patent does not explicitly define "at release." A party seeking a narrower interpretation might argue it refers to a specific, documented event, such as the final quality control sign-off for a manufacturing batch. The patent uses the term when describing the analysis of a prior art product, linking it to testing after production is complete but before storage studies begin (’197 Patent, col. 4:24-26).

The Term: "tonicity agent"

  • Context and Importance: Practitioners may focus on this term because if the defendant's product achieves proper tonicity using excipients not typically classified as "tonicity agents," it may avoid infringement.
  • Intrinsic Evidence for Interpretation: The patent provides "sodium chloride as a tonicity agent" as a specific example (’197 Patent, col. 3:31-32). This could support a narrower interpretation limited to substances whose primary purpose is to adjust tonicity. A broader interpretation could argue that any component that contributes to the solution's tonicity meets the limitation, regardless of its primary function.

VI. Other Allegations

  • Indirect Infringement: The complaint includes formal allegations of induced and contributory infringement that would occur upon commercialization of the NDA product (Compl. ¶24). However, it does not plead specific facts to support these claims, such as referencing product labeling or instructions that would encourage an infringing use. The core of the action is the statutory infringement claim under 35 U.S.C. § 271(e)(2).
  • Willful Infringement: The complaint alleges that the Defendant knew of the ’197 Patent when it submitted its NDA, basing this on the patent's listing in the FDA Orange Book and the required Paragraph IV certification (Compl. ¶19, ¶25). This allegation of pre-suit knowledge forms the basis for a claim of willful infringement.

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

  • A core issue will be one of factual correspondence: Does the defendant's formulation, as confidentially described in its NDA, meet every numerical limitation of the asserted claims? The case will likely depend on expert analysis of the defendant’s manufacturing specifications and stability data, focusing on the precise pH range and the specific impurity thresholds at release and over time.
  • The dispute may also turn on a question of claim construction: How will the court define the temporal window for testing "at release," and can the term "tonicity agent" be interpreted to exclude one of the excipients used in the defendant's formulation?
  • Finally, a key question for damages will be objective reasonableness: Given the required Paragraph IV certification, was the defendant's position of non-infringement or invalidity objectively reasonable at the time of its NDA submission? The answer will determine its exposure to enhanced damages for willful infringement if its product is ultimately found to infringe.