DCT

1:22-cv-01348

Merck Sharp & Dohme LLC v. Laurus Labs Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:22-cv-01348, D. Del., 10/12/2022
  • Venue Allegations: Venue is alleged to be proper as to Laurus Generics Inc. because it is a Delaware corporation. Venue is alleged to be proper as to Laurus Labs Limited, an Indian corporation, because it is subject to personal jurisdiction in the district.
  • Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) for a generic version of the diabetes drug JANUMET® constitutes an act of infringement of a patent claiming a specific phosphate salt form of the active ingredient sitagliptin.
  • Technical Context: The technology concerns pharmaceutical chemistry, specifically a crystalline salt form of a dipeptidyl peptidase-IV (DPP-IV) inhibitor, which is a class of compounds used to treat Type 2 diabetes.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 217545 and a corresponding Paragraph IV certification to the FDA. The certification asserts that the patent-in-suit is invalid, unenforceable, and/or will not be infringed by the proposed generic product. Notably, the patent-in-suit was the subject of subsequent Inter Partes Review (IPR) proceedings, which concluded with a certificate issued on September 19, 2023, confirming the patentability of the asserted independent claim, among others.

Case Timeline

Date Event
2003-06-24 ’708 Patent Priority Date
2008-02-05 ’708 Patent Issue Date
2022-08-29 Laurus sends Notice Letter to Merck regarding ANDA submission
2022-10-12 Complaint Filing Date
2023-09-19 IPR Certificate confirms patentability of asserted claims

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's background acknowledges the existence of a class of beta-amino tetrahydrotriazolopyrazines as potent DPP-IV inhibitors for treating Type 2 diabetes ('708 Patent, col. 1:49-54). The unstated problem addressed by the invention is the need for a form of a specific one of these compounds that possesses optimal characteristics for formulation into a stable and effective drug product.
  • The Patented Solution: The invention is a specific salt of the known inhibitor: the 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 ('708 Patent, Abstract). The specification describes this salt, particularly its crystalline monohydrate form, as having "improved physical and chemical stability" and "improved physicochemical properties," which render it "particularly suitable for the manufacture of various pharmaceutical dosage forms" ('708 Patent, col. 2:10-16).
  • Technical Importance: By creating a stable, crystalline salt form, the invention facilitates the development of a consistent, manufacturable, and therapeutically effective solid dosage form of the drug.

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 consists of the following essential elements:
    • 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's phrasing suggests it reserves the right to assert additional claims, including dependent claims.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is "Laurus's ANDA Product," identified as a generic version of JANUMET® containing sitagliptin phosphate (Compl. ¶¶ 1, 3, 31). The formal act of infringement alleged is the submission of ANDA No. 217545 to the FDA (Compl. ¶1).

Functionality and Market Context

  • The product is a proposed generic drug intended for the treatment of Type 2 diabetes in the U.S. market (Compl. ¶¶ 3, 6-7). The complaint alleges that the purpose of the ANDA submission is to gain FDA approval to "commercially manufacture, use, offer for sale, sell, and/or import" this generic product prior to the expiration of the ’708 Patent (Compl. ¶1). 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, or a hydrate thereof. The complaint alleges that Laurus's Notice Letter stated its ANDA Product "contains sitagliptin phosphate as an active ingredient." It further alleges that this sitagliptin phosphate is covered by claim 1. The complaint notes that Laurus did not contest infringement of claim 1 in its Notice Letter. ¶31, ¶32, ¶33 col. 15:64-16:16
  • Identified Points of Contention:
    • Scope Questions: While the complaint alleges that Laurus did not contest infringement of Claim 1, the core of ANDA litigation often involves challenging the patent's validity (Compl. ¶30, ¶33). A potential point of contention, should non-infringement be argued, is whether the "sitagliptin phosphate" in Laurus's ANDA product is the specific "dihydrogenphosphate salt" recited in the claim. This raises the question of whether there are any structural or polymorphic differences between the accused product and the claimed invention that would place it outside the literal scope of the claims.
    • Technical Questions: A dispositive technical question will be the precise chemical nature of the active pharmaceutical ingredient described in Laurus's ANDA. The court's analysis will require a direct comparison of the chemical and physical characteristics (e.g., stoichiometry, crystalline structure) of the accused compound as specified in the ANDA with the limitations of Claim 1.

V. Key Claim Terms for Construction

  • The Term: "a dihydrogenphosphate salt"
  • Context and Importance: This term is the chemical centerpiece of the claim, defining the specific counter-ion that forms the salt with the active drug molecule. The patent's specification distinguishes this particular salt from the free base and other potential salts by highlighting its "improved physical and chemical stability" ('708 Patent, col. 2:10-11). The outcome of the infringement analysis depends on whether the defendant's proposed product falls within the precise definition of this salt.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim language "or a hydrate thereof" explicitly broadens the scope beyond a single anhydrous form to include hydrated versions ('708 Patent, col. 16:16). One might argue this suggests an intent to cover the salt in various physical forms.
    • Evidence for a Narrower Interpretation: The specification provides extensive detail on a specific "crystalline monohydrate" of the dihydrogenphosphate salt, including characteristic X-ray powder diffraction, NMR, TGA, and DSC data ('708 Patent, col. 2:26-39; Figs. 1-5). A party could argue that the claims should be construed in light of these specific, well-characterized embodiments, potentially limiting the scope to the forms explicitly disclosed and characterized in the patent. The specification also defines the salt as comprising "one molar equivalent" of the cation and "one molar equivalent" of the dihydrogenphosphate anion, a precise stoichiometric definition ('708 Patent, col. 4:46-52).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement, stating that upon FDA approval, Laurus intends to cause infringement by medical professionals and patients through its proposed product labeling, which will direct the use of the product in an infringing manner (Compl. ¶¶ 37-38). It also alleges contributory infringement, asserting that the ANDA product is not a staple article of commerce and is especially made for use in infringing the patent (Compl. ¶39).
  • Willful Infringement: The complaint alleges that Laurus has acted with "full knowledge of the '708 patent," based on the ANDA notification process, and "without a reasonable basis for believing that it would not be liable for infringement" (Compl. ¶42). This forms the basis for a claim of willful infringement.

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

  1. A central issue will be one of validity resilience: Laurus has asserted in its Paragraph IV certification that the '708 Patent is invalid. Given that the asserted claims were subsequently confirmed as patentable in an IPR proceeding, can Laurus present clear and convincing evidence of invalidity—based on prior art or arguments not previously considered by the PTO—sufficient to overcome the patent's strengthened presumption of validity?
  2. The case may also present a question of infringement and chemical identity: Assuming the patent is valid, does the sitagliptin phosphate active ingredient as specified in Laurus's ANDA meet every limitation of Claim 1? The analysis will likely focus on whether the accused product is the specific "dihydrogenphosphate salt" in the correct stoichiometric ratio, or if it constitutes a different salt or polymorphic form falling outside the claim's scope.
  3. A final key question will concern willfulness and objective reasonableness: Was Laurus's position that the '708 Patent was invalid or not infringed, as articulated in its Paragraph IV certification, objectively reasonable at the time it was made? The answer will determine its exposure to enhanced damages for willful infringement.