DCT

1:19-cv-00313

Merck Sharp & Dohme Corp v. Apotex Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-00313, D. Del., 02/13/2019
  • Venue Allegations: Venue is alleged to be proper as to Apotex Corp. because it is a Delaware corporation and as to Apotex Inc. because it is a Canadian corporation subject to personal jurisdiction in the district.
  • Core Dispute: Plaintiff alleges that Defendants' submission of Abbreviated New Drug Applications (ANDAs) to the FDA for generic versions of the diabetes drugs JANUVIA®, JANUMET®, and JANUMET XR® constitutes an act of infringement of a patent covering the drugs' active pharmaceutical ingredient.
  • Technical Context: The patent relates to a specific phosphate salt form of sitagliptin, an inhibitor of the dipeptidyl peptidase-IV (DPP-IV) enzyme used for the treatment of Type 2 diabetes.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' notification to Plaintiff of their ANDA filings. These notifications included Paragraph IV certifications asserting that the patent-in-suit is invalid, unenforceable, and/or will not be infringed by the proposed generic products. The complaint notes that Defendants' notification letters, sent as early as 2010, did not contest infringement of the primary asserted claim. Post-complaint Inter Partes Review (IPR) proceedings at the USPTO resulted in a confirmation of the patentability of the key claims asserted in this litigation.

Case Timeline

Date Event
2003-06-24 '708 Patent Priority Date
2008-02-05 '708 Patent Issue Date
2010-12-13 Apotex sends notice letter for '425 ANDA (generic JANUVIA®)
2010-12-13 Apotex sends notice letter for '426 ANDA (generic JANUMET®)
2013-12-17 Apotex sends notice letter for '369 ANDA (generic JANUMET XR®)
2019-02-13 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

  • Patent Identification: 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: The patent operates in the context of developing DPP-IV inhibitors for treating Type 2 diabetes ('708 Patent, col. 1:31-48). While the base compound was known, developing a drug product requires a form of the active ingredient that is stable, soluble, and suitable for large-scale manufacturing ('708 Patent, col. 2:5-16).
  • The Patented Solution: The invention is a specific dihydrogenphosphate salt of the DPP-IV inhibitor 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, also known as sitagliptin ('708 Patent, Abstract). The specification describes a crystalline monohydrate form of this salt, which is purported to have advantageous properties such as improved physical and chemical stability and favorable physicochemical characteristics for creating pharmaceutical dosage forms ('708 Patent, col. 2:5-16).
  • Technical Importance: The selection of a specific salt form, particularly a stable crystalline polymorph, is a critical step in pharmaceutical development that can determine a drug's shelf-life, bioavailability, and manufacturability.

Key Claims at a Glance

  • The complaint asserts "one or more claims of the ’708 patent, including at least claim 1" (Compl. ¶41, ¶61, ¶81).
  • Independent Claim 1 recites:
    • A dihydrogenphosphate salt 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
    • or a hydrate thereof.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are Defendants' proposed generic drug products identified in ANDA No. 202425 (a generic version of JANUVIA®), ANDA No. 202426 (a generic version of JANUMET®), and ANDA No. 205369 (a generic version of JANUMET XR®) (Compl. ¶¶1, 3, 5, 7).

Functionality and Market Context

  • The complaint alleges that the active ingredient in each of the accused ANDA products is "sitagliptin phosphate" (Compl. ¶40, ¶60, ¶80). These products are intended to be substitutes for Merck's branded drugs and compete in the U.S. market for Type 2 diabetes treatments upon receiving FDA approval (Compl. ¶17).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

Claim Chart Summary

  • The complaint’s infringement theory is based on the chemical identity of the active pharmaceutical ingredient in the accused products.
Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A dihydrogenphosphate salt 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, or a hydrate thereof. The complaint states that Apotex's ANDA products each contain "sitagliptin phosphate as an active ingredient." (Sitagliptin is the common name for the chemical structure recited in the claim). ¶40, ¶60, ¶80 col. 2:44-52

Identified Points of Contention

  • Scope Questions: The complaint states that in its notice letters, "Apotex did not contest infringement of claim 1" (Compl. ¶42, ¶62, ¶82). However, Apotex’s formal Paragraph IV certification preserves the right to argue non-infringement (Compl. ¶39, ¶59, ¶79). This raises the question of whether Apotex will develop a non-infringement theory, for example, by arguing its product contains an anhydrous or different polymorphic form of sitagliptin phosphate that falls outside the proper construction of the claim.
  • Technical Questions: A central evidentiary question will be the precise chemical and physical characterization of the sitagliptin phosphate API in Apotex's proposed generic products.

V. Key Claim Terms for Construction

  • The Term: "a dihydrogenphosphate salt ... or a hydrate thereof"
  • Context and Importance: The construction of this phrase is central to the scope of infringement. Practitioners may focus on this term because the '708 patent specification places significant emphasis on a specific crystalline monohydrate form, while the claim language itself is not explicitly limited to that form. The definition will determine whether the claim covers other potential forms, such as amorphous salt or different crystalline polymorphs.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The plain language of Claim 1 recites "a dihydrogenphosphate salt" and "a hydrate thereof" without express limitation to a particular crystalline structure or stoichiometric formula ('708 Patent, col. 16:63-65). This language may support a construction that encompasses any form of the dihydrogenphosphate salt, including amorphous or alternative crystalline polymorphs.
    • Evidence for a Narrower Interpretation: The patent's abstract, summary, and detailed description heavily feature the "crystalline monohydrate" of the salt ('708 Patent, Abstract; col. 2:3-5). Figures 1-5 and the associated examples exclusively characterize this specific monohydrate form. A party could argue that the claims should be construed as limited to the specific, well-characterized crystalline monohydrate disclosed and enabled in the specification.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement, asserting that Defendants' proposed product labeling will instruct medical professionals and patients to administer the drug, thereby inducing infringement (Compl. ¶46-47, ¶66-67, ¶86-87). It also alleges contributory infringement on the basis that the accused products are not staple articles of commerce and are especially made for an infringing use (Compl. ¶48, ¶68, ¶88).
  • Willful Infringement: Willfulness is alleged based on Defendants' "full knowledge of the '708 patent," evidenced by the notice letters, and their continued pursuit of FDA approval "without a reasonable basis for believing" they would not be liable for infringement (Compl. ¶51, ¶71, ¶91).

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

  • The primary battleground will likely be patent validity. Defendants' Paragraph IV certifications assert that the '708 patent is invalid and/or unenforceable. The fact that the asserted claims survived post-grant IPR proceedings will be a significant factor, potentially creating estoppel issues for Defendants regarding invalidity arguments they raised or could have raised in that forum.
  • A second critical issue will be one of infringement scope. Should the case proceed past validity challenges, the key question will be whether the specific form of sitagliptin phosphate used in Defendants' generic products—whatever its crystalline or hydrous state may be—falls within the legally construed scope of Claim 1, particularly given the specification's focus on a single crystalline monohydrate form.