DCT

1:21-cv-01173

Merck Sharp Dohme Co Inc v. Laurus Labs Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:21-cv-01173, D. Del., 08/12/2021
  • Venue Allegations: Venue is alleged as proper because Defendant Laurus Generics is a Delaware corporation, and Defendant Laurus Labs is allegedly subject to personal jurisdiction in the district through its subsidiary's activities and its own business contacts.
  • Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of the diabetes drug JANUVIA® constitutes an act of infringement of a patent covering a specific phosphate salt form of the active ingredient, sitagliptin.
  • Technical Context: The technology concerns a specific crystalline salt form of sitagliptin, a dipeptidyl peptidase-IV (DPP-IV) inhibitor, developed to provide improved stability and manufacturing characteristics for pharmaceutical formulations used to treat Type 2 diabetes.
  • Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act following a July 8, 2021 notice letter from Laurus, which informed Merck of its ANDA filing (No. 216057) containing a Paragraph IV certification against the patent-in-suit. The complaint alleges that Laurus did not contest infringement of claim 1 in its notice. The patent-in-suit was subject to subsequent Inter Partes Review (IPR) proceedings, which concluded with a certificate issued September 19, 2023, confirming the patentability of all asserted independent and dependent claims.

Case Timeline

Date Event
2003-06-24 ’708 Patent Priority Date
2008-02-05 ’708 Patent Issue Date
2021-07-08 Laurus Sends Notice Letter of ANDA Filing to Merck
2021-08-12 Complaint Filing Date
2023-09-19 IPR Certificate Issued Confirming Patentability of Claims 1-4

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: The patent's background acknowledges that while the base compound for inhibiting the DPP-IV enzyme was known, there was a need to develop specific salt forms of the compound suitable for pharmaceutical development ('708 Patent, col. 1:31-56). Such development requires identifying forms with advantageous properties, including physical and chemical stability, solubility, and ease of processing, which are critical for creating a viable drug product ('708 Patent, col. 2:8-18).
  • The Patented Solution: The invention is a specific dihydrogenphosphate salt of the active pharmaceutical ingredient sitagliptin. The patent particularly describes a crystalline monohydrate of this salt, which is claimed to possess improved physicochemical properties that render it "particularly suitable for the manufacture of various pharmaceutical dosage forms" ('708 Patent, Abstract; col. 2:13-18).
  • Technical Importance: The creation of a stable, crystalline salt form is a crucial step in pharmaceutical chemistry, as the physical form of an active ingredient directly impacts the drug's manufacturing process, shelf life, and the consistency of the final oral dosage form ('708 Patent, col. 2:4-18).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims of the '708 patent, including at least claim 1" (Compl. ¶32).
  • Independent Claim 1:
    • 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 instrumentality is "Laurus's ANDA Product," a generic version of JANUVIA® (sitagliptin phosphate tablets) for which Laurus seeks FDA approval via ANDA No. 216057 (Compl. ¶¶1, 3).

Functionality and Market Context

The ANDA product is an oral tablet that "contains sitagliptin phosphate as an active ingredient" (Compl. ¶31). The filing of the ANDA is a statutory act of infringement under 35 U.S.C. § 271(e)(2) and represents a commercial effort to market a generic equivalent to Merck's branded JANUVIA® product before the expiration of the ’708 Patent (Compl. ¶1, 29). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

’708 Patent Infringement Allegations

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 Laurus's ANDA Product is alleged to contain "sitagliptin phosphate as an active ingredient." The complaint further alleges that Laurus did not contest infringement of this claim in its notice letter. ¶31, ¶32, ¶33 col. 7:50-65
or a hydrate thereof. The complaint alleges the ANDA product is covered by one or more claims, including Claim 1, which explicitly recites hydrates. The patent specification heavily emphasizes a "crystalline monohydrate" form. ¶32 col. 16:68

Identified Points of Contention

  • Scope Questions: The central dispute appears to concern patent validity rather than infringement, given the allegation that Laurus did not contest infringement of Claim 1 (Compl. ¶33). However, should infringement become a contested issue, a question of scope may arise: Does the term "a hydrate thereof" in Claim 1, which is not further defined, cover any and all hydrated forms of the salt, or is its scope limited by the patent's specific disclosure and characterization of a "crystalline monohydrate"? ('708 Patent, Abstract; Fig. 1).
  • Technical Questions: The primary evidentiary question for infringement will be: What specific form of sitagliptin phosphate is described in Laurus’s confidential ANDA submission? Confirmation of its chemical structure and hydration state would be necessary to determine if it falls within the scope of the asserted claims.

V. Key Claim Terms for Construction

  • The Term: "a dihydrogenphosphate salt"

    • Context and Importance: This term defines the fundamental chemical identity of the claimed composition. Its construction is critical to determining whether the active ingredient in the accused product meets the claim’s primary limitation. Practitioners may focus on this term because the specific salt form is the basis of the patent's purported innovation over the prior art base compound.
    • Intrinsic Evidence for a Broader Interpretation: The specification describes the salt as being "comprised of one molar equivalent of mono-protonated... cation and one molar equivalent of dihydrogenphosphate (biphosphate) anion," which could support a construction based on this stoichiometric relationship regardless of crystalline form ('708 Patent, col. 4:46-53).
    • Intrinsic Evidence for a Narrower Interpretation: The patent's examples, figures, and technical discussion focus almost exclusively on a specific "crystalline monohydrate" form ('708 Patent, Abstract, col. 8:20-27, Fig. 1). A party could argue that the term should be construed in light of these specific, stable embodiments that represent the inventive contribution.

  • The Term: "a hydrate thereof"

    • Context and Importance: This term broadens Claim 1 beyond the anhydrous salt. Defining its scope is essential for determining infringement, as many pharmaceutical compounds can exist in various hydrated states. Its meaning is central because the patent's preferred embodiment is a specific monohydrate.
    • Intrinsic Evidence for a Broader Interpretation: On its face, the term "a hydrate" is not limited to a specific stoichiometry and could be argued to encompass any substance containing water of crystallization, including monohydrates, dihydrates, or other forms.
    • Intrinsic Evidence for a Narrower Interpretation: The specification repeatedly highlights the advantages and characteristics of a specific "crystalline monohydrate" ('708 Patent, col. 3:55-56). An argument could be made that the term "a hydrate thereof" should be limited to the specific monohydrate form that the patent enables and describes in detail.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement of infringement, stating that Laurus intends for its ANDA product to be used in an infringing manner and that its "proposed product labeling" will direct such use (Compl. ¶¶37, 38).
  • Willful Infringement: Willfulness is alleged based on Laurus having "full knowledge of the '708 patent" at the time of its ANDA submission, as evidenced by its Paragraph IV certification and notice letter, and its continued intent to commercialize the product before patent expiration (Compl. ¶¶40, 42).

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

  • A core issue will be one of patent validity: The complaint alleges that while Laurus certified the '708 patent as invalid or unenforceable, it did not contest that its product would infringe Claim 1. This procedural posture suggests the primary legal battle will be over the patent's validity, likely focusing on arguments such as obviousness or lack of written description, rather than on infringement. The recent IPR decision finding the asserted claims patentable will be a significant factor in this analysis.
  • A key secondary question will be one of structural identity: Assuming infringement becomes a point of contention, the case may turn on whether the specific polymorphic form of "sitagliptin phosphate" detailed in Laurus's confidential ANDA is coextensive with the "dihydrogenphosphate salt ... or a hydrate thereof" as claimed, particularly given the patent’s extensive focus on a specific crystalline monohydrate.