Merz Pharma LLC v. Annora Pharma Private Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Merz Pharmaceuticals, LLC and Merz North America, Inc. (North Carolina)
  • Defendant: Annora Pharma Private Ltd. (India)
  • Plaintiff’s Counsel: McCarter & English, LLP; Hogan Lovells US LLP
• Case Identification: 1:19-cv-02165, D. Del., 11/20/2019
• Venue Allegations: Venue is alleged to be proper based on Defendant's submission of an Abbreviated New Drug Application (ANDA) seeking to market its product throughout the United States, including Delaware, and Defendant's previous submission to the jurisdiction of the court in prior ANDA cases.
• Core Dispute: Plaintiff alleges that Defendant’s filing of an ANDA for a generic glycopyrrolate oral solution constitutes an act of infringement of two patents covering methods of increasing the drug's bioavailability by administering it under fasted conditions.
• Technical Context: The technology concerns a method-of-use for the drug glycopyrrolate—used to treat conditions such as excessive drooling (sialorrhea)—by controlling food intake to improve the drug's absorption and therapeutic effect.
• Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiff’s receipt of a notice letter from Defendant dated October 8, 2019. The letter contained a Paragraph IV certification for ANDA No. 213698, asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed by Defendant's proposed generic product. The patents are listed in the FDA's "Orange Book" as covering Plaintiff's branded product, CUVPOSA®.

Case Timeline

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

U.S. Patent No. 7,638,552 - Method for Increasing The Bioavailability of Glycopyrrolate, issued December 29, 2009

The Invention Explained

• Problem Addressed: The patent addresses the problem that food intake can have a variable and often negative effect on the bioavailability of orally administered drugs, making their therapeutic effects unpredictable ('552 Patent, col. 1:41-48). For a drug like glycopyrrolate, it is desirable to increase its oral bioavailability to improve efficacy ('552 Patent, col. 1:43-45).
• The Patented Solution: The invention is based on the "unexpected finding that administration of glycopyrrolate under fasted conditions (i.e., without food), increases the extent of absorption" ('552 Patent, col. 2:13-16). The patent claims methods of treating certain conditions by administering glycopyrrolate without food, which results in significantly higher maximum plasma concentration (Cmax) and area under the curve (AUC), as illustrated in pharmacokinetic data comparing fasted and fed states ('552 Patent, Figs. 1-2, col. 2:17-22).
• Technical Importance: This dosing regimen provides a method to achieve more consistent and higher levels of glycopyrrolate in the bloodstream, thereby improving its efficacy for treating conditions like peptic ulcers or sialorrhea ('552 Patent, col. 1:59-62).

Key Claims at a Glance

• The complaint asserts "one or more claims" of the patent (Compl. ¶24). Independent claim 1 is representative.
• Claim 1 of the ’552 Patent recites:
  • A method of treating sialorrhea in a human patient,
  • which comprises orally administering about 1 mg to about 10 mg of glycopyrrolate in a liquid solution to the human patient under fasted conditions,
  • wherein said administration results in an increase of the maximum plasma concentration (Cmax) and the extent of absorption at 24 hours (AUC0-24hrs) compared to administration under fed conditions,
  • wherein the ratio of Cmax (without food to with food) is greater than 1.1, and
  • wherein the ratio of AUC0-24hrs (without food to with food) is greater than 1.8.

U.S. Patent No. 7,816,396 - Method for Increasing The Bioavailability of Glycopyrrolate, issued October 19, 2010

The Invention Explained

• Problem Addressed: The ’396 Patent, which shares a nearly identical specification with the ’552 Patent, also addresses the problem of variable and reduced drug bioavailability of glycopyrrolate when administered with food ('396 Patent, col. 1:45-50).
• The Patented Solution: The solution is a method of administering glycopyrrolate to a patient who has not consumed food for a specified period before and after taking the drug, thereby increasing absorption ('396 Patent, col. 2:15-24). The patent claims a method that recites a specific fasting window, which corresponds to the "fasted conditions" described in the specification's clinical studies ('396 Patent, col. 4:32-37).
• Technical Importance: The method provides a defined dosing instruction that allows practitioners and patients to achieve the improved bioavailability discovered by the inventors, leading to more reliable treatment outcomes ('396 Patent, col. 1:62-65).

Key Claims at a Glance

• The complaint asserts "one or more claims" of the patent (Compl. ¶36). Independent claim 1 is representative.
• Claim 1 of the ’396 Patent recites:
  • A method of treating sialorrhea in a human patient,
  • which comprises orally administering about 1 mg to about 10 mg of glycopyrrolate in a liquid solution to the human patient under fasted conditions,
  • wherein the ratio of the extent of absorption at infinity (AUC0-∞) following administration without food to with food is greater than 1.8, and
  • wherein the patient has not consumed food during the period from 30 minutes prior to administration to 1 hour after administration.

III. The Accused Instrumentality

Product Identification

Defendant’s proposed generic version of CUVPOSA®, which is a glycopyrrolate, 1mg/5mL oral solution, as described in ANDA No. 213698 (Compl. ¶¶ 1, 19).

Functionality and Market Context

The complaint alleges that Defendant seeks FDA approval to manufacture and sell a generic equivalent to Plaintiff's CUVPOSA® product (Compl. ¶¶ 1, 20). The infringement alleged is statutory, arising from the filing of the ANDA itself under 35 U.S.C. § 271(e)(2). The core of the infringement allegation is that the proposed product, if approved, will be sold with a label that instructs or encourages its use for treating sialorrhea in a manner that practices the patented methods (Compl. ¶¶ 29, 41).

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart or detailed infringement contentions. The analysis below is based on the infringement theory implied by the complaint's allegations for a method-of-use patent in an ANDA context.

No probative visual evidence provided in complaint.

’552 Patent Infringement Allegations

’396 Patent Infringement Allegations

• Identified Points of Contention:
  • Scope Questions: A central dispute may be whether the pharmacokinetic (PK) ratio limitations recited in the claims (e.g., "ratio of Cmax... is greater than 1.1") are met by Defendant's specific formulation. Defendant may argue that its bioequivalence data does not satisfy these specific claimed ratios, even if it meets overall FDA bioequivalence standards.
  • Factual Questions: The case will likely turn on the precise language of Defendant's proposed product label submitted with its ANDA. A key question is whether the label's instructions are specific enough to meet the "fasted conditions" or the explicit fasting window limitations of the claims, thereby supporting Plaintiff's theory of induced infringement.

V. Key Claim Terms for Construction

• The Term: "under fasted conditions" (’552 Patent, Claim 1)

  • Context and Importance: This term is at the core of the invention. Its construction will determine whether the dosing instructions on the accused product's label fall within the scope of the claim. Practitioners may focus on this term because the '396 patent provides a more explicit definition for what appears to be the same concept, which could be used to inform the interpretation of this term.
  • Evidence for a Broader Interpretation: The specification provides a general definition: "the condition of not having consumed food during the period between from at least about 30 minutes prior to the administration of glycopyrrolate to at least about 1 hour after the administration of glycopyrrolate" ('552 Patent, col. 4:29-34).
  • Evidence for a Narrower Interpretation: The patent also describes a more specific regimen for the clinical study that generated the patent's data: an overnight fast of approximately 10 hours ('552 Patent, col. 7:38-40). A party could argue the term should be limited to a regimen consistent with that example.

• The Term: "liquid solution" (’552 and ’396 Patents, Claim 1)

  • Context and Importance: The claims are limited to administration via a "liquid solution." The physical state of the accused product is therefore a potentially dispositive issue. Practitioners may focus on this term if there is any basis to argue that the accused product is, for example, a suspension or emulsion rather than a true solution.
  • Evidence for a Broader Interpretation: The patent does not provide a specific definition, which may support an argument that the term should be given its plain and ordinary meaning in the pharmaceutical arts, which could be relatively broad.
  • Evidence for a Narrower Interpretation: Example 1 of the specification describes a "preferred liquid formulation" containing specific components like sorbitol solution, glycerin, and purified water, in which the active ingredient is dissolved ('552 Patent, col. 7:6-22). A party might argue that the term "liquid solution" should be construed as being limited to formulations with similar characteristics to this disclosed embodiment.

VI. Other Allegations

• Indirect Infringement: The complaint alleges induced infringement under 35 U.S.C. § 271(b). The factual basis is the allegation that Defendant, with knowledge of the patents, will market and sell its glycopyrrolate product with labeling that will intentionally encourage and instruct medical professionals and patients to administer the drug in a manner that directly infringes the claimed methods (Compl. ¶¶ 29, 41).
• Willful Infringement: The complaint alleges that Defendant was aware of the patents-in-suit prior to filing its ANDA, as evidenced by its Paragraph IV certification letter (Compl. ¶¶ 31, 43). It further alleges that Defendant "acted without reasonable basis for a good faith belief" that it would not be liable for infringement, which forms the basis for a claim of willful infringement and a request for enhanced damages and attorneys' fees (Compl. ¶¶ 32, 44, Prayer for Relief E).

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

• A core issue will be one of inducement and labeling: will the specific instructions and indications on Defendant's proposed product label be found to actively encourage or instruct administration in a way that meets every limitation of the asserted method claims, particularly the "fasted conditions" and explicit fasting window requirements? The outcome will depend on a direct comparison of the label's text to the construed claim language.
• A key evidentiary question will be one of pharmacokinetic scope: does Defendant’s proposed generic product, when administered according to its label, actually exhibit the specific pharmacokinetic ratios (e.g., Cmax ratio > 1.1) required by the claims of the ’552 patent? This question may require the Court to weigh the data presented in the patent specification against the bioequivalence data from Defendant's ANDA submission.