DCT

2:24-cv-10820

Merck Sharp & Dohme LLC v. Aic246 Ag & Co KG

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:24-cv-10820, D.N.J., 11/27/2024
  • Venue Allegations: Venue is alleged to be proper as to Zydus Lifesciences Limited, an Indian corporation, because it may be sued in any judicial district. Venue is alleged to be proper as to Zydus Pharmaceuticals (USA) Inc. because it has its principal place of business in New Jersey.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of the antiviral drug PREVYMIS® (letermovir) constitutes an act of infringement of a reissued patent covering the letermovir compound.
  • Technical Context: The technology concerns a specific class of chemical compounds, substituted dihydroquinazolines, used as antiviral agents for the prophylaxis of cytomegalovirus (CMV) infection, a significant risk for immunocompromised patients such as transplant recipients.
  • Key Procedural History: The action was filed under the Hatch-Waxman Act following Plaintiffs' receipt of a Notice Letter from Zydus, dated October 16, 2024, which stated that Zydus had filed an ANDA with a Paragraph IV certification asserting that the patent-in-suit is invalid, unenforceable, or will not be infringed.

Case Timeline

Date Event
2003-05-02 RE '791 Patent Priority Date
2018-04-17 RE '791 Patent Issue Date
2024-10-16 Zydus sends Notice Letter to Plaintiffs
2024-11-27 Complaint Filing Date

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

U.S. Reissued Patent No. RE 46,791 - "Substituted Dihydroquinazolines"

The Invention Explained

  • Problem Addressed: The patent background explains that while antiviral agents are available, the potential for viruses to develop resistance necessitates the discovery of novel agents to ensure effective therapy (’791 Patent, col. 1:19-24).
  • The Patented Solution: The invention provides a class of chemical compounds, specifically substituted dihydroquinazolines, that exhibit antiviral activity, particularly against cytomegalovirus (CMV) (’791 Patent, col. 1:12-17, 1:29-31). The core of the invention is a general chemical structure, Formula (I), and specific compounds derived from it that can be used for treating or preventing viral diseases (’791 Patent, col. 2:32-47).
  • Technical Importance: The development of a new class of antiviral compounds offers an alternative therapeutic pathway, which is critical in managing infections like CMV that pose a life-threatening risk to immunosuppressed patients, such as those undergoing organ or stem cell transplantation (Compl. ¶18; ’791 Patent, col. 11:26-32).

Key Claims at a Glance

  • The complaint asserts dependent claims 23 and 24, which depend on independent claim 1.
  • Independent Claim 1 defines a broad genus of compounds of Formula (I), characterized by:
    • A core dihydroquinazoline structure.
    • An aryl group (Ar) attached to a piperazine ring, which itself may be substituted.
    • Multiple variable substituent groups (R¹ through R⁸) at various positions on the core structure, allowing for a vast number of potential compounds.
  • Dependent Claim 23 narrows the scope of claim 1 to a specific compound (letermovir) or a "physiologically acceptable salt thereof."
  • Dependent Claim 24 narrows the scope of claim 1 to the specific compound (letermovir) itself.

III. The Accused Instrumentality

Product Identification

The accused instrumentality is "Zydus's ANDA Product," identified as a generic version of PREVYMIS® tablets containing letermovir in 240 mg and 480 mg dosages, submitted for FDA approval under ANDA No. 216799 (Compl. ¶ on p. 2, ¶37).

Functionality and Market Context

  • The Zydus ANDA Product is an oral antiviral tablet whose active pharmaceutical ingredient (API) is letermovir (Compl. ¶37). It is intended for the prophylaxis of CMV infection and disease in certain high-risk transplant recipients (Compl. ¶18).
  • The complaint alleges that Zydus's ANDA relies on the safety and efficacy data of Plaintiffs' PREVYMIS® product and includes data demonstrating bioequivalence (Compl. ¶38). The product is intended to be a direct market competitor to PREVYMIS® upon receiving FDA approval (Compl. ¶ on p. 2).

IV. Analysis of Infringement Allegations

’791 Patent Infringement Allegations

Claim Element (from Independent Claim 1, as narrowed by Claim 23) Alleged Infringing Functionality Complaint Citation Patent Citation
The compound of claim 1, wherein said compound is: (S)-{8-fluoro-2-[4-(3-methoxyphenyl)-1-piperazinyl]-3-[2-methoxy-5-(trifluoromethyl)-phenyl]-3,4-dihydro-4-quinazolinyl}acetic acid The active pharmaceutical ingredient in Zydus's ANDA Product is alleged to be letermovir, which the complaint identifies by the same chemical name and structure. The complaint includes a chemical diagram of this structure. (Compl. ¶30) ¶¶19, 37 col. 7:29-31, col. 124:25-54
or a physiologically acceptable salt thereof The complaint alleges infringement by Zydus's ANDA Product, which comprises oral tablets. Pharmaceutical tablets may be formulated with the API in its free acid/base form or as a salt. This element covers infringement by a salt form of letermovir. ¶¶32-33, 37 col. 3:44-46

Identified Points of Contention

  • Scope Questions: The infringement analysis for claims 23 and 24, which recite a specific chemical species, is typically straightforward. A primary question is whether the term "physiologically acceptable salt thereof" in claim 23 encompasses the specific formulation described in Zydus's ANDA, should it utilize a salt form of letermovir.
  • Technical Questions: A foundational technical question is one of chemical identity. While the complaint alleges that Zydus's product contains the claimed compound, the definitive proof will depend on the chemical characterization of the API in the ANDA. The complaint's assertion that Zydus did not provide a basis for non-infringement in its notice letter suggests this may not be a point of significant dispute (Compl. ¶35).

V. Key Claim Terms for Construction

  • The Term: "physiologically acceptable salt"
  • Context and Importance: This term, appearing in claim 23, is important because its scope determines the range of letermovir salt forms covered by the patent. If Zydus were to use a novel salt form, the definition of this term would be central to determining literal infringement of claim 23. Practitioners may focus on this term because it directly implicates the potential for a non-infringing "design-around" formulation.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification provides a broad, exemplary list of "physiologically acceptable salts," including "acid addition salts of mineral acids, carboxylic acids and sulphonic acids" and "salts of customary bases, such as... alkali metal salts" (’791 Patent, col. 3:51-63). This non-limiting list supports an expansive construction covering a wide variety of conventional pharmaceutical salts.
    • Evidence for a Narrower Interpretation: A party seeking a narrower construction might argue that the term implies a specific level of safety or tolerability that must be proven for a given salt, potentially limiting the claim to only those salts with established physiological profiles. However, the specification does not appear to impose such an explicit requirement beyond what is conventional in the pharmaceutical arts.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement of infringement, stating that Zydus plans to sell its ANDA Product with a label that instructs and encourages its administration for the prophylaxis of CMV infection, the patented use (Compl. ¶¶42-43).
  • Willful Infringement: The complaint does not contain an explicit allegation of willful infringement. However, it alleges that Zydus has knowledge of the ’791 Patent due to its listing in the FDA's Orange Book (Compl. ¶41) and requests a declaration that the case is "exceptional" and an award of attorneys' fees pursuant to 35 U.S.C. § 285 (Compl., Prayer for Relief ¶(e)), which are remedies often associated with findings of egregious infringement.

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

This dispute, brought under the Hatch-Waxman Act, will likely focus more on patent validity than on infringement, given the specificity of the asserted claims.

  • A primary issue is one of chemical identity and concession: will Zydus contest that its ANDA product contains the specific letermovir compound recited in claims 23 and 24, or will infringement be stipulated? The complaint's reliance on Zydus's own regulatory filings makes a non-infringement defense appear challenging.
  • The central question will likely be one of patent validity: can Zydus prove by clear and convincing evidence that claims to the specific letermovir compound are invalid over the prior art? As the complaint notes Zydus's Paragraph IV certification alleged invalidity, the substantive dispute will likely revolve around arguments of anticipation or obviousness.
  • Finally, a key remedial question for the court will be whether the statutory stay on FDA approval should be converted into an injunction that bars the marketing of Zydus's generic product until the expiration of the RE '791 Patent and any applicable extensions.