DCT

1:23-cv-00683

Merck Sharp & Dohme LLC v. Biocon Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00683, D. Del., 06/23/2023
  • Venue Allegations: Venue is alleged to be proper in Delaware as to Defendant Biocon Pharma, Inc. because it is a Delaware corporation, and as to the foreign defendants because they are subject to personal jurisdiction in the district.
  • Core Dispute: Plaintiff alleges that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to the FDA, seeking to market a generic version of Plaintiff's JANUVIA® (sitagliptin) product, constitutes an act of infringement of a patent covering a specific salt form of the active ingredient.
  • Technical Context: The dispute centers on the specific crystalline salt form of sitagliptin, an active pharmaceutical ingredient used as a DPP-IV inhibitor for the treatment of Type 2 diabetes.
  • Key Procedural History: The action was precipitated by a notice letter dated May 9, 2023, in which Defendants informed Plaintiff of their ANDA submission containing a Paragraph IV certification, asserting that the patent-in-suit is invalid, unenforceable, or will not be infringed by the proposed generic product. The patent-in-suit is listed in the FDA's Orange Book for JANUVIA®.

Case Timeline

Date Event
2003-06-24 ’708 Patent Priority Date
2008-02-05 '708 Patent Issue Date
2023-05-09 Biocon's Notice Letter to Merck
2023-06-23 Complaint Filing Date

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

U.S. Patent No. 7,326,708 - "Phosphoric Acid Salt of a Dipeptidyl Peptidase-IV Inhibitor," issued February 5, 2008

The Invention Explained

  • Problem Addressed: While the compound sitagliptin, a potent DPP-IV inhibitor for treating Type 2 diabetes, was known, the patent addresses the need for a form of this compound with properties suitable for pharmaceutical manufacturing and formulation ('708 Patent, col. 1:45-62). Developing a stable, manufacturable form of an active pharmaceutical ingredient (API) is a common challenge in drug development.
  • The Patented Solution: The invention is a specific dihydrogenphosphate salt of sitagliptin, and particularly a crystalline monohydrate of that salt ('708 Patent, Abstract; col. 2:1-4). This specific salt form is described as having advantageous properties, including "improved physical and chemical stability" and "improved physicochemical properties, such as solubility and rate of solution," which make it "particularly suitable for the manufacture of various pharmaceutical dosage forms." ('708 Patent, col. 2:8-16).
  • Technical Importance: The creation of a stable, consistent, and soluble crystalline salt of an API is a critical step in transforming a chemical compound into a reliable and effective medicine.

Key Claims at a Glance

  • The complaint asserts "at least claim 1" (Compl. ¶35).
  • Independent Claim 1:
    • A dihydrogenphosphate salt
    • of the compound 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (sitagliptin)
    • of structural formula I
    • or a hydrate thereof.
  • The complaint's allegation of infringement of "one or more claims" suggests the right to assert additional claims, including dependent claims, may be reserved (Compl. ¶35, ¶38).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is "Biocon's ANDA Product," a generic version of sitagliptin phosphate oral tablets, for which Defendants have sought FDA approval via ANDA No. 218441 (Compl. ¶1, ¶3).

Functionality and Market Context

  • The complaint alleges that Biocon's ANDA Product contains "sitagliptin phosphate as an active ingredient" and is a generic version of Merck's JANUVIA® product (Compl. ¶3, ¶34). The act of infringement giving rise to the suit is the submission of the ANDA itself, which seeks approval to market this product prior to the expiration of the '708 patent (Compl. ¶36).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint does not provide a detailed claim chart. The following summary is based on the narrative allegations.

'708 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A dihydrogenphosphate salt Biocon's ANDA Product contains "sitagliptin phosphate as an active ingredient." ¶34 col. 4:34-40
of 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine of structural formula I The active ingredient in Biocon's ANDA Product is sitagliptin phosphate, which the complaint alleges is covered by the claim. ¶35 col. 2:45-62
or a hydrate thereof The complaint does not specify whether the accused product is a hydrate, but this element provides a potential basis for infringement if the product contains water of hydration. ¶35 col. 2:1-4
  • Identified Points of Contention:
    • Scope Questions: A primary question will be whether the "sitagliptin phosphate" in Biocon's product (Compl. ¶34) is the specific "dihydrogenphosphate salt" recited in Claim 1. The patent specification describes this salt as comprising "one molar equivalent of mono-protonated [sitagliptin] cation and one molar equivalent of dihydrogenphosphate (biphosphate) anion" ('708 Patent, col. 4:34-40). The infringement analysis may turn on the precise stoichiometry and ionic state of the salt in the accused product.
    • Technical Questions: A key technical question, for which the complaint provides no detail, is the specific solid-state form of Biocon's sitagliptin phosphate. The '708 patent heavily details the properties of a "crystalline monohydrate" ('708 Patent, Abstract; FIG. 1-5). Discovery will be needed to determine if the accused product is anhydrous, the claimed monohydrate, or another hydrate or solvate, which will be central to determining infringement of the "or a hydrate thereof" limitation.

V. Key Claim Terms for Construction

  • The Term: "dihydrogenphosphate salt"

  • Context and Importance: This term defines the specific counter-ion of the claimed salt. Practitioners may focus on this term because infringement will depend on whether Biocon's "sitagliptin phosphate" (Compl. ¶34) meets the specific chemical definition of a "dihydrogenphosphate salt" (H₂PO₄⁻), as opposed to other possible phosphate salts (e.g., a hydrogenphosphate salt, HPO₄²⁻, or a phosphate salt, PO₄³⁻).

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The complaint's simple allegation of "sitagliptin phosphate" may suggest an argument that the term should encompass any pharmaceutically acceptable phosphate salt of sitagliptin.
    • Evidence for a Narrower Interpretation: The patent specification provides a precise definition, stating the salt "is comprised of one molar equivalent of mono-protonated [sitagliptin] cation and one molar equivalent of dihydrogenphosphate (biphosphate) anion" ('708 Patent, col. 4:34-40). This language may support a construction limited to this specific 1:1 salt.

  • The Term: "a hydrate thereof"

  • Context and Importance: This term is critical as it extends the claim's scope beyond the anhydrous salt form. The case may turn on whether Biocon's product, if not the anhydrous salt, qualifies as "a hydrate."

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: A party could argue this term covers any form of the salt containing water molecules, regardless of stoichiometry or crystallinity.
    • Evidence for a Narrower Interpretation: The specification's extensive focus on and characterization of a specific "crystalline monohydrate" ('708 Patent, Abstract; col. 2:3-4, FIG. 1-5) could be used to argue that "a hydrate thereof" should be limited to this specific, well-defined crystalline form, or at least to stable, crystalline hydrates rather than amorphous or non-stoichiometric ones.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Biocon will induce infringement because its proposed product labeling will instruct physicians and patients to use the ANDA product in an infringing manner (Compl. ¶39). It further alleges contributory infringement, stating the product is especially made for an infringing use and is not a staple article of commerce suitable for substantial noninfringing use (Compl. ¶41).
  • Willful Infringement: The complaint alleges that Biocon has acted with "full knowledge of the '708 patent" and without a reasonable basis for its non-infringement positions, which may form the basis for a willfulness claim (Compl. ¶44).

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

The resolution of this case will likely depend on the answers to a few central questions that will require technical evidence obtained through discovery.

  • A core issue will be one of chemical identity: Does the "sitagliptin phosphate" in Biocon's ANDA product correspond to the specific "dihydrogenphosphate salt" recited in Claim 1, particularly with respect to the 1:1 molar ratio between the sitagliptin cation and the dihydrogenphosphate anion described in the patent?
  • A second determinative issue will be one of solid-state characterization: What is the precise crystalline form and hydration state of the API in Biocon's product? The analysis will focus on whether this form falls within the scope of the claimed salt "or a hydrate thereof," a question whose answer may depend on how narrowly that phrase is construed in light of the patent's detailed description of a specific crystalline monohydrate.