DCT

1:20-cv-20217

Merck Sharp & Dohme Corp v. Actavis Laboratories FL Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: Merck Sharp & Dohme Corp. v. Actavis Laboratories FL, Inc., 1:20-cv-20217, S.D. Fla., 01/17/2020
  • Venue Allegations: Venue is alleged to be proper in the Southern District of Florida because Defendant Actavis Laboratories FL, Inc. has its principal place of business in Davie, Florida, and all defendants are alleged to have systematic contacts with the state.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for approval to market generic fidaxomicin tablets constitutes an act of infringement of five U.S. patents associated with Plaintiffs' brand-name drug, DIFICID®.
  • Technical Context: The patents relate to the antibiotic fidaxomicin, which is used to treat Clostridium difficile-associated diarrhea, a significant cause of hospital-acquired infections.
  • Key Procedural History: This action follows Defendants' submission of an Amended ANDA in late 2019. The complaint notes that Plaintiffs previously filed suit in 2015 based on the original ANDA submission, but that case was dismissed. Plaintiffs also filed a parallel action in the District of New Jersey one day before filing this suit, characterizing the instant Florida case as a "protective suit" to preserve their rights under the Hatch-Waxman Act in the event of a jurisdictional challenge in New Jersey.

Case Timeline

Date Event
2004-05-14 Earliest Priority Date for ’489 and ’551 Patents
2005-01-31 Earliest Priority Date for ’508, ’249, and ’510 Patents
2008-05-27 ’508 Patent Issued
2011-01-04 ’249 Patent Issued
2011-03-15 ’489 Patent Issued
2013-11-19 ’551 Patent Issued
2014-10-14 ’510 Patent Issued
2015-07-23 Date of Notice Letter for Original ANDA Submission
2019-12-06 Date of Notice Letter for Amended ANDA Submission
2020-01-16 Parallel Lawsuit Filed in D.N.J.
2020-01-17 Complaint Filing Date

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

U.S. Patent No. 7,906,489 - "18-Membered Macrocycles and Analogs Thereof"

The Invention Explained

  • Problem Addressed: The patent background describes the need for new antibiotic treatments for gastrointestinal infections, particularly those caused by toxin-producing strains of Clostridium difficile, as well as other drug-resistant bacteria like methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant enterococci (VRE) (’489 Patent, col. 4:40-67).
  • The Patented Solution: The invention is a method of treating C. difficile infections using a specific, substantially pure stereoisomer of an 18-membered macrocyclic antibiotic known as Tiacumicin B (fidaxomicin) (’489 Patent, Abstract). The patent explains that this particular isomer, designated R-Tiacumicin B, has been discovered to have surprisingly greater biological activity than other related compounds produced during fermentation, making its isolation and use in a highly pure form a significant therapeutic advance (’489 Patent, col. 5:25-44).
  • Technical Importance: Isolating and claiming the use of a single, highly active stereoisomer from a complex mixture of fermentation products allows for a more potent and consistent drug with a predictable therapeutic profile.

Key Claims at a Glance

  • The complaint asserts "one or more claims" of the ’489 Patent, and notes that Defendants' notice letter allegedly provided no basis for non-infringement of claims 1–2, 4–10, and 12–14 (Compl. ¶ 67, 70). The lead independent claim is Claim 1.
  • Independent Claim 1:
    • A method of treating a C. difficile gastrointestinal infection in a human patient in need thereof
    • comprising orally administering to said patient a therapeutically effective amount of a compound having the formula (IV) [chemical structure of fidaxomicin], or a pharmaceutically acceptable salt thereof combined with one or more pharmaceutically acceptable carriers,
    • wherein the compound of the formula (IV) is greater than 90% by weight stereomerically pure.
  • The complaint does not foreclose assertion of other claims.

U.S. Patent No. 8,586,551 - "18-Membered Macrocycles and Analogs Thereof"

The Invention Explained

  • Problem Addressed: As a continuation of the application leading to the ’489 Patent, this patent addresses the same need for effective treatments for serious gastrointestinal infections like C. difficile-associated diarrhea (’551 Patent, col. 5:49-67).
  • The Patented Solution: Rather than claiming a method of treatment, this patent claims the composition of matter itself: the isolated R-Tiacumicin B compound (fidaxomicin), specified as being "free from other stereoisomers of the compound" (’551 Patent, Abstract; col. 30:8-35). This provides direct protection over the active pharmaceutical ingredient.
  • Technical Importance: Obtaining composition of matter claims on a purified, highly active stereoisomer provides a foundational layer of patent protection for the drug substance, distinct from protection over methods of its use or specific formulations.

Key Claims at a Glance

  • The complaint asserts "one or more claims" and states no non-infringement basis was provided for claims 1-6 (Compl. ¶ 67, 84). The lead independent claim is Claim 1.
  • Independent Claim 1:
    • An isolated compound having the formula [chemical structure of fidaxomicin], free from other stereoisomers of the compound.
  • The complaint does not foreclose assertion of other claims.

U.S. Patent No. 7,378,508 - "Polymorphic Crystalline Forms of Tiacumicin B"

  • Technology Synopsis: The patent addresses the technical problem that the same chemical compound can exist in different solid-state crystalline forms, or polymorphs, which can affect critical pharmaceutical properties like stability, manufacturing, and bioavailability (’508 Patent, col. 2:1-26). The invention provides specific, stable polymorphic crystalline forms of fidaxomicin, characterized by data such as X-ray powder diffraction (XRD) patterns, to ensure a consistent and effective drug product (’508 Patent, Abstract).
  • Asserted Claims: Claims 1-2, 8-9, 11-12, and 15-20 are referenced as lacking a non-infringement rationale from Defendants (Compl. ¶ 67). Independent claims include 1 and 11.
  • Accused Features: The crystalline structure of the active pharmaceutical ingredient in Defendants' proposed generic product (Compl. ¶ 98).

U.S. Patent No. 7,863,249 - "Macrolide Polymorphs, Compositions Comprising Such Polymorphs, and Methods of Use and Manufacture Thereof"

  • Technology Synopsis: This patent is from the same family as the ’508 Patent and addresses the same technical problem of identifying stable crystalline forms of fidaxomicin (’249 Patent, col. 2:1-20). The invention claims pharmaceutical compositions that contain a specific polymorphic form of fidaxomicin, which is defined by its characteristic XRD pattern (’249 Patent, Abstract; claim 1).
  • Asserted Claims: Claims 1-3, 6, and 10-12 are referenced as lacking a non-infringement rationale from Defendants (Compl. ¶ 67). Independent claim is 1.
  • Accused Features: The formulation of Defendants' ANDA product, which is alleged to contain a claimed polymorphic form of fidaxomicin (Compl. ¶ 112).

U.S. Patent No. 8,859,510 - "Macrocyclic Polymoprhs, Compositions Comprising Such Polymorphs, and Methods of Use and Manufacture Thereof"

  • Technology Synopsis: Also in the polymorph family, this patent addresses the challenge of ensuring consistent drug properties by controlling the solid-state form (’510 Patent, col. 2:1-20). The invention claims methods of treating C. difficile infections by administering compositions containing a specific, defined polymorphic form of fidaxomicin (’510 Patent, Abstract; claim 1).
  • Asserted Claims: Claims 1-13 are referenced as lacking a non-infringement rationale from Defendants (Compl. ¶ 67). Independent claim is 1.
  • Accused Features: The proposed use of Defendants' ANDA product to treat C. difficile, which allegedly practices the claimed method of administration (Compl. ¶ 126).

III. The Accused Instrumentality

Product Identification

  • Defendants' "Fidaxomicin Tablets" for which an original and an Amended Abbreviated New Drug Application (ANDA) No. 208443 was submitted to the FDA (Compl. ¶ 1, 53, 58).

Functionality and Market Context

  • The accused product is a generic version of Plaintiffs' DIFICID® tablets (Compl. ¶ 58). The complaint alleges that by filing the ANDA, Defendants represented to the FDA that their product has the same active ingredient, method of administration, dosage form, and strength as DIFICID®, and is bioequivalent (Compl. ¶ 56, 61). The product is intended for treating Clostridium difficile-associated diarrhea, positioning it to compete directly with DIFICID® upon FDA approval (Compl. ¶ 63). The complaint further alleges that the Amended ANDA seeks to "change the physical form or crystalline structure of the active ingredient," directly implicating the asserted polymorph patents (Compl. ¶ 60).

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or a detailed, element-by-element infringement analysis. The central theory of infringement is statutory under 35 U.S.C. § 271(e)(2)(A), which defines the submission of an ANDA seeking approval to market a generic version of a patented drug as an act of infringement (Compl. ¶ 71, 85, 99, 113, 127). The complaint alleges that Defendants' proposed product, if approved and marketed, will directly and indirectly infringe the asserted patents.

For the method of treatment claims (e.g., ’489 Patent, Claim 1), infringement is premised on the allegation that Defendants' proposed product labeling will instruct medical professionals and patients to administer the drug in a manner that practices the claimed methods (Compl. ¶ 73-74). For the composition claims (e.g., ’551 Patent, Claim 1), infringement is based on the allegation that the drug product itself contains the claimed highly pure fidaxomicin compound (Compl. ¶ 84). For the polymorph patents (e.g., ’508 Patent), infringement is based on the allegation that the fidaxomicin active ingredient in Defendants' product possesses the claimed crystalline structure (Compl. ¶ 98).

  • Identified Points of Contention:
    • Scope Questions: A central dispute for the ’489 Patent may concern whether Defendants' proposed generic product meets the purity limitation of "greater than 90% by weight stereomerically pure." For the polymorph patents (’508, ’249, ’510), the primary scope question will be whether the crystalline structure of the fidaxomicin in Defendants' product is "characterized by" the specific X-ray diffraction peaks recited in the claims.
    • Technical Questions: The core technical question for the polymorph patents will be a comparison of the physical form of fidaxomicin in the accused product against the forms defined in the patents. The allegation that the Amended ANDA seeks to "change the physical form or crystalline structure" suggests this will be a key area of dispute (Compl. ¶ 60). A significant evidentiary question is raised by the complaint's allegation that for numerous asserted claims, Defendants' notice letter "did not identify any non-infringement basis," which may suggest that the primary dispute for those claims will be over validity rather than infringement (Compl. ¶ 67).

No probative visual evidence provided in complaint.

V. Key Claim Terms for Construction

  • The Term: "polymorphic form ... characterized by a powder x-ray diffraction pattern wherein said x-ray diffraction pattern comprises peaks at diffraction angles 2θ of 7.7°, 15.0°, and 18.8°±0.2" (from U.S. Patent 7,378,508, claim 1)

    • Context and Importance: This term, and similar terms in the related polymorph patents, defines the patented invention by its physical properties. The entire infringement analysis for the ’508, ’249, and ’510 patents will depend on whether the crystalline form in Defendants' product falls within the scope of this definition. Practitioners may focus on this term because demonstrating that an accused product has a different, non-infringing crystalline form is a common defense strategy in pharmaceutical patent litigation.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The use of the open-ended term "comprises peaks at" could support an interpretation that the presence of the three recited peaks is sufficient for infringement, regardless of what other peaks may be present in the accused product's diffraction pattern (’508 Patent, col. 32:1-2).
      • Evidence for a Narrower Interpretation: The specification provides a detailed figure (FIG. 1) and table (TABLE 2) showing a full diffraction pattern for a specific polymorph (’508 Patent, FIG. 1; col. 30, TABLE 2). A party could argue that the term should be construed to cover only a polymorph exhibiting this overall pattern, not just any crystal that happens to have peaks at the three recited angles.

  • The Term: "greater than 90% by weight stereomerically pure" (from U.S. Patent 7,906,489, claim 1)

    • Context and Importance: This term sets a specific purity threshold for the active ingredient. Infringement of the method claim requires that the administered compound meet this limitation. The dispute may turn on the purity level of Defendants' proposed product and the analytical methods used to measure it.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The claim uses a clear numerical cutoff. The specification emphasizes the goal of producing a highly pure R-isomer, describing preparations that are "almost entirely (i.e., >90%) R-Tiacumicin" (’489 Patent, col. 26:48-49). This supports reading the term as a straightforward quantitative requirement.
      • Evidence for a Narrower Interpretation: The patent does not specify a particular analytical method (e.g., a specific type of HPLC) for measuring stereoisomeric purity. A party could argue that the term's meaning is implicitly tied to the analytical capabilities and conventions at the time of the invention, potentially limiting its scope or introducing ambiguity into how the 90% threshold is determined.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges inducement of infringement for the method claims, asserting that Defendants' proposed product labeling will instruct medical professionals to perform the claimed methods of treatment (Compl. ¶ 74, 130). It also alleges contributory infringement, stating the accused product is especially made for an infringing use and is not suitable for a substantial noninfringing use (Compl. ¶ 77, 133).
  • Willful Infringement: Willfulness is alleged based on Defendants' knowledge of the patents-in-suit at least as early as their original ANDA submission in 2015 (Compl. ¶ 78, 92, 106, 120, 134). The complaint alleges that Defendants "acted without a reasonable basis for believing that they would not be liable for infringing" the patents (Compl. ¶ 79, 93, 107, 121, 135).

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

  • A central technical issue will be one of physical identity: does the crystalline form of fidaxomicin in Defendants’ proposed generic product exhibit the specific X-ray powder diffraction characteristics required by the claims of the polymorph patents (’508, ’249, ’510), or can Defendants prove it is a distinct, non-infringing form?
  • A key strategic question will be the primary battleground of the case: given the allegation that Defendants’ notice letter failed to provide a non-infringement basis for a substantial number of claims, will the litigation focus primarily on Defendants' asserted defenses of invalidity and unenforceability, or will there be substantive technical disputes over infringement of claims related to stereoisomeric purity and crystalline structure?