Merck Sharp & Dohme LLC v. Prinston Pharmaceutical Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Merck Sharp & Dohme LLC (New Jersey)
  • Defendant: Prinston Pharmaceutical Inc. (Delaware)
  • Plaintiff’s Counsel: McCarter & English, LLP
• Case Identification: 1:22-cv-01300, D. Del., 10/03/2022
• Venue Allegations: Venue is asserted as proper in the District of Delaware on the basis that Defendant is a Delaware corporation.
• Core Dispute: Plaintiff alleges that Defendant's submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the diabetes drug JANUMET® constitutes an act of infringement of a patent covering a specific salt form of the active ingredient sitagliptin.
• Technical Context: The technology concerns a specific phosphate salt form of a dipeptidyl peptidase-IV (DP-IV) inhibitor, designed to possess improved stability and handling properties for use in pharmaceutical formulations.
• Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant's submission of an ANDA with a Paragraph IV certification, asserting the patent-in-suit is invalid, unenforceable, or not infringed. An Inter Partes Review (IPR) certificate for the patent-in-suit, issued after the complaint was filed, indicates that the asserted claims survived a validity challenge at the Patent Trial and Appeal Board, a fact that may influence the current litigation.

Case Timeline

Date	Event
2003-06-24	'708 Patent Priority Date
2008-02-05	'708 Patent Issue Date
2022-08-19	Prinston sends Notice Letter to Merck regarding its ANDA submission
2022-10-03	Complaint Filing Date
2023-09-19	IPR Certificate issued confirming 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," issued February 5, 2008

The Invention Explained

• Problem Addressed: The patent background identifies a class of potent DP-IV inhibitors useful for treating Type 2 diabetes, specifically referencing the compound that would become known as sitagliptin ('708 Patent, col. 1:50-55). While the therapeutic compound was known, the patent addresses the subsequent technical challenge of developing a form of this compound with properties suitable for large-scale manufacturing and formulation into a stable, effective drug product ('708 Patent, col. 2:4-15).
• The Patented Solution: The invention is a specific salt of the sitagliptin compound—the dihydrogenphosphate salt. The patent describes this salt form, particularly a crystalline monohydrate version, as possessing advantageous characteristics such as "improved physical and chemical stability" and "ease of processing, handling, and dosing," which are critical for pharmaceutical development ('708 Patent, col. 2:4-15). The specification provides detailed data from X-ray diffraction and other analytical techniques to characterize this specific crystalline monohydrate form ('708 Patent, Figs. 1-5).
• Technical Importance: Creating a specific, stable, and crystalline salt form of an active pharmaceutical ingredient is a critical step in drug development, as it directly impacts the drug's shelf-life, bioavailability, and the ability to manufacture consistent dosages ('708 Patent, col. 2:9-19).

Key Claims at a Glance

• The complaint asserts at least Claim 1 (Compl. ¶27, ¶31).
• 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.
• The complaint alleges infringement of "one or more claims," reserving the right to assert other claims, including dependent claims (Compl. ¶27).

III. The Accused Instrumentality

Product Identification

• Defendant's proposed generic version of JANUMET®, referred to as "Prinston's ANDA Product," which is a metformin hydrochloride and sitagliptin phosphate oral tablet (Compl. ¶1-3).

Functionality and Market Context

• The accused product is a generic drug for which Prinston is seeking FDA approval to manufacture and sell in the U.S. market (Compl. ¶1). The infringement allegation is based on the active ingredient sitagliptin phosphate. The complaint alleges that Prinston, in its notice letter, "stated that Prinston's ANDA Product contains sitagliptin phosphate as an active ingredient" (Compl. ¶26). This identification of the active ingredient forms the basis of the infringement claim.

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

'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...or a hydrate thereof.	The complaint alleges that Defendant’s ANDA product "contains sitagliptin phosphate as an active ingredient." It further alleges that Claim 1 of the '708 patent "covers the sitagliptin phosphate contained in Prinston's ANDA Product."	¶26, ¶27	col. 14:63-col. 15:16

• Identified Points of Contention:
  • Scope Questions: The complaint alleges that Defendant "did not contest infringement of claim 1" in its notice letter (Compl. ¶28). If infringement does become a point of dispute, the central question will be one of definitional scope. For instance, does the term "dihydrogenphosphate salt... or a hydrate thereof" read on the specific polymorph, solvate, or hydration state of the sitagliptin phosphate used in Defendant's ANDA product? The patent's specification places significant emphasis on a "crystalline monohydrate" form ('708 Patent, col. 2:2-4), which raises the question of whether the claims could be interpreted as limited to that specific form.
  • Technical Questions: A key technical question, should it arise, is whether there are any subtle but legally significant chemical or physical differences between the "sitagliptin phosphate" in the ANDA product (Compl. ¶26) and the specific salt claimed in the patent. This could involve detailed analysis of stoichiometry, crystal structure, and hydration levels.

V. Key Claim Terms for Construction

• The Term: "dihydrogenphosphate salt"

  • Context and Importance: This term defines the fundamental chemical nature of the invention. Its construction is critical because even minor variations in salt chemistry can create a basis for a non-infringement argument. Practitioners may focus on this term because the patent distinguishes its novel salt from the prior art free base, and the properties of this specific salt form are presented as a key inventive aspect ('708 Patent, col. 2:4-15).
  • Intrinsic Evidence for a Broader Interpretation: Claim 1 recites "a dihydrogenphosphate salt," which could be argued to encompass any salt form meeting that general chemical description, regardless of its specific crystalline structure.
  • Intrinsic Evidence for a Narrower Interpretation: The specification describes the salt with high specificity as being "comprised of one molar equivalent of mono-protonated...cation and one molar equivalent of dihydrogenphosphate (biphosphate) anion" ('708 Patent, col. 3:42-49). A party could argue this language limits the claim to a 1:1 stoichiometric salt.

• The Term: "a hydrate thereof"

  • Context and Importance: This term is central to the scope of infringement for any accused product that is not anhydrous. Its construction will determine whether the claim covers only the specific "crystalline monohydrate" detailed in the patent or a wider range of hydrated forms.
  • Intrinsic Evidence for a Broader Interpretation: The plain language of "a hydrate" is not explicitly limited and could be argued to cover various hydration states, including stoichiometric and non-stoichiometric hydrates.
  • Intrinsic Evidence for a Narrower Interpretation: The specification's abstract, figures, and detailed description focus almost exclusively on a "crystalline monohydrate" form ('708 Patent, Abstract; col. 2:2-4; Figs. 4-5). An argument could be made that this is the only hydrate form fully disclosed and enabled, potentially limiting the claim scope to that specific embodiment.

VI. Other Allegations

• Indirect Infringement: The complaint alleges active inducement, asserting that Prinston's proposed product labeling will direct and instruct physicians and patients to administer the infringing product, and that Prinston acts with specific intent to cause infringement (Compl. ¶33). The complaint also alleges contributory infringement, stating that the ANDA product is not a staple article of commerce and lacks substantial non-infringing uses (Compl. ¶34).
• Willful Infringement: Willfulness is alleged based on Prinston's knowledge of the '708 patent, which arises from the patent's listing in the FDA's Orange Book and the statutory notice letter process (Compl. ¶37). The complaint alleges that Prinston's actions are taken "without a reasonable basis for believing that it would not be liable" (Compl. ¶37).

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

• A central issue will be the impact of the prior IPR proceeding. The patent-in-suit’s claims have already been adjudicated as patentable by the PTAB. A key question for the court will be whether Defendant's validity challenges, asserted in its Paragraph IV certification, are based on new prior art or arguments that were not, and could not have been, raised during the IPR.
• Should infringement be contested, the case will likely turn on chemical equivalence and claim scope. A core question will be whether the specific crystalline form and hydration state of the "sitagliptin phosphate" in Defendant's ANDA product falls within the scope of the claimed "dihydrogenphosphate salt... or a hydrate thereof," particularly in light of the patent's detailed focus on a specific monohydrate form.
• The final key question relates to willfulness in the ANDA context. Given that the asserted claims have survived an IPR challenge, the court will have to consider whether Defendant's continued pursuit of its ANDA constitutes objective recklessness, potentially exposing it to enhanced damages if infringement is found.