DCT

2:20-cv-00534

Merck Sharp & Dohme Corp v. Actavis Laboratories FL Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:20-cv-00534, D.N.J., 01/16/2020
  • Venue Allegations: Plaintiffs allege venue is proper in the District of New Jersey based on Defendants' continuous and systematic contacts with the state, including principal places of business, registration to do business, and prior submission to the jurisdiction of the court in related litigation.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of the antibiotic drug DIFICID® (fidaxomicin) infringes five U.S. patents covering the drug's active ingredient, specific crystalline forms, and methods of use.
  • Technical Context: The technology relates to macrocyclic antibiotics used for the treatment of Clostridium difficile-associated diarrhea, a significant and potentially life-threatening infection often acquired in healthcare settings.
  • Key Procedural History: The complaint notes that this action is a follow-on to a prior case (2:15-cv-06541-CCC-CLW) filed in response to Defendants' original ANDA submission. The present lawsuit arises from Defendants' submission of an amended ANDA that, according to the complaint, seeks to change the physical form or crystalline structure of the active ingredient.

Case Timeline

Date Event
2004-05-14 Priority Date for ’489 and ’551 Patents
2007-01-22 Priority Date for ’508, ’249, and ’510 Patents
2008-05-27 U.S. Patent No. 7,378,508 Issues
2011-01-04 U.S. Patent No. 7,863,249 Issues
2011-03-15 U.S. Patent No. 7,906,489 Issues
2013-11-19 U.S. Patent No. 8,586,551 Issues
2014-10-14 U.S. Patent No. 8,859,510 Issues
2015-07-23 Date of Actavis Notice Letter for Original ANDA Submission
2019-12-06 Date of Second Actavis Notice Letter for Amended ANDA Submission
2020-01-16 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 describes a need for improved treatments for C. difficile-associated diarrhea (CDAD), noting that existing therapies such as vancomycin and metronidazole are associated with issues including the promotion of antibiotic resistance and significant adverse effects (’489 Patent, col. 5:1-31).
  • The Patented Solution: The invention is directed to the discovery that a specific stereoisomer of the macrocycle Tiacumicin B—the R-isomer, depicted in Formula IV—is surprisingly more biologically active against C. difficile than other related compounds or isomers (’489 Patent, col. 5:21-32). The patent claims methods of treating CDAD by administering this substantially pure R-isomer, which is the active ingredient in fidaxomicin (’489 Patent, Fig. 1; col. 29:62-col. 30:40).
  • Technical Importance: By identifying and claiming a method using the specific, highly potent R-stereoisomer, the invention provided a more targeted therapeutic approach for treating C. difficile infections than previously understood mixtures of related compounds (’489 Patent, col. 15:47-56).

Key Claims at a Glance

  • The complaint alleges infringement of claims including independent claims 1 and 9 (Compl. ¶61, ¶67).
  • Essential elements of Independent Claim 1:
    • A method of treating diarrhea caused by C. difficile gastrointestinal infection in a human patient
    • Comprising orally administering to the patient a therapeutically effective amount of a compound having the formula (IV)
    • Wherein the compound is greater than 90% by weight stereomerically pure
  • Essential elements of Independent Claim 9:
    • A method of treating diarrhea caused by C. difficile gastrointestinal infection in a human patient
    • Consisting of orally administering to the patient a therapeutically effective amount of a compound having the formula (IV)
    • Wherein the compound is greater than 93% by weight stereomerically pure
  • The complaint also alleges infringement of dependent claims 2, 4-8, 10, and 12-14 (Compl. ¶61, ¶67).

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

The Invention Explained

  • Problem Addressed: The patent addresses the same technical problem as its parent '489 patent: the need for more effective treatments for CDAD (’551 Patent, col. 5:1-51).
  • The Patented Solution: Rather than claiming a method of use, this patent claims the composition of matter itself: the isolated R-isomer of Tiacumicin B, free from its other stereoisomers (’551 Patent, Abstract; col. 29:65-col. 30:33). The claimed compound is depicted in the patent's Figure, which shows the molecular structure determined by X-ray crystallography (’551 Patent, p. 59).
  • Technical Importance: This patent provides composition-of-matter protection for the specific, highly active stereoisomer, which is generally considered a stronger form of patent protection than a method-of-use claim covering the same molecule.

Key Claims at a Glance

  • The complaint alleges infringement of claims including independent claim 1 (Compl. ¶61, ¶67).
  • Essential elements of Independent Claim 1:
    • An isolated compound
    • Having the formula [depicted as Formula IV]
    • Free from other stereoisomers of the compound
  • The complaint also alleges infringement of dependent claims 2-6 (Compl. ¶61, ¶67).

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

  • Technology Synopsis: The patent addresses the technical challenge that a single drug compound can exist in different solid crystalline structures, or polymorphs, which can affect its stability, manufacturability, and therapeutic performance (’508 Patent, col. 2:1-24). The invention claims novel crystalline forms of Tiacumicin B (fidaxomicin), defining them by their characteristic peaks in an X-ray powder diffraction (XRPD) pattern (’508 Patent, Abstract). The patent provides a representative XRPD pattern for a claimed polymorph (’508 Patent, Fig. 1).
  • Asserted Claims: Independent claims 1, 9, and 11, and dependent claims 2, 8, 12, and 15-20 (Compl. ¶61, ¶67).
  • Accused Features: The specific crystalline structure of the fidaxomicin active pharmaceutical ingredient in Defendants' Amended ANDA Product (Compl. ¶60, ¶98).

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

  • Technology Synopsis: Continuing the work of the ’508 Patent, this invention discloses and claims additional polymorphic forms of Tiacumicin B (’249 Patent, Abstract). The patent defines these forms by their unique XRPD patterns and differential scanning calorimetry (DSC) profiles, which measure how the substance absorbs heat (’249 Patent, col. 32:51-60; Fig. 1; Fig. 3).
  • Asserted Claims: Independent claims 1 and 12, and dependent claims 2-3, 6, and 10-11 (Compl. ¶61, ¶67).
  • Accused Features: The specific crystalline structure of the fidaxomicin active pharmaceutical ingredient in Defendants' Amended ANDA Product (Compl. ¶60, ¶112).

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

  • Technology Synopsis: This patent is in the same family as the ’508 and ’249 patents and further claims methods of treating bacterial infections by administering compositions containing specific polymorphic forms of Tiacumicin B (’510 Patent, Abstract). The claims again rely on XRPD data to define the specific crystalline form of the compound at issue (’510 Patent, col. 34:1-4).
  • Asserted Claims: Independent claims 1 and 10, and dependent claims 2-9 and 11-13 (Compl. ¶61, ¶67).
  • Accused Features: The specific crystalline structure of the fidaxomicin active pharmaceutical ingredient in Defendants' Amended ANDA Product, and the proposed use of that product to treat C. difficile infections (Compl. ¶60, ¶126).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendants' "Fidaxomicin Tablets," for which they filed an amended ANDA (No. 208443) seeking FDA approval for commercialization as a generic copy of Plaintiffs' DIFICID® tablets (Compl. ¶53, ¶58).

Functionality and Market Context

  • The complaint alleges that the Defendants' Amended ANDA Product contains the same active ingredient (fidaxomicin), is administered by the same method (oral tablet), and has the same strength and bioequivalence as DIFICID® (Compl. ¶61).
  • The product is intended for the treatment of Clostridium difficile-associated diarrhea in adults (Compl. ¶63).
  • The complaint alleges that the amended ANDA seeks to "change the physical form or crystalline structure of the active ingredient" from that described in the original ANDA submission (Compl. ¶60).

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed claim chart or specific evidence mapping product features to claim limitations. The infringement theory is based on the act of filing the ANDA under 35 U.S.C. § 271(e)(2), which necessarily represents that the generic product meets the limitations of the patents under which the branded drug is listed in the FDA's Orange Book.

'489 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating diarrhea caused by C. difficile...in a human patient The Amended ANDA Product is intended for the treatment of Clostridium difficile-associated diarrhea (Compl. ¶63) and its proposed labeling will instruct this use (Compl. ¶73). ¶63, ¶73 col. 29:62-64
comprising orally administering to the patient...a therapeutically effective amount The Amended ANDA Product is a tablet for oral use containing fidaxomicin (Compl. ¶53), which is represented as bioequivalent to DIFICID® (Compl. ¶61). ¶53, ¶61 col. 29:65-66
of a compound having the formula (IV)...wherein the compound...is greater than 90% by weight stereomerically pure The active ingredient in the Amended ANDA Product is fidaxomicin (Compl. ¶56, ¶61), which is the compound of formula (IV). Infringement of this claim implies the API meets the >90% purity limitation. ¶56, ¶61 col. 30:3-36

'551 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
An isolated compound The Amended ANDA Product contains fidaxomicin as its active pharmaceutical ingredient. ¶56 col. 29:65-66
having the formula [Formula IV] The active ingredient is alleged to be fidaxomicin, which corresponds to Formula IV. ¶56 col. 29:67-col. 30:33
free from other stereoisomers of the compound The act of filing the ANDA for a product containing fidaxomicin is alleged to infringe this claim, implying the API meets the claimed purity standard. ¶84, ¶85 col. 29:65-col. 30:33
  • Identified Points of Contention:
    • Purity and Identity Questions: For the ’489 and ’551 patents, a central factual question will be whether the fidaxomicin in Defendants' product possesses the stereoisomeric purity required by the claims (e.g., ">90% pure" or "free from other stereoisomers").
    • Polymorph Scope Questions: For the ’508, ’249, and ’510 patents, the dispute will likely concern whether the specific crystalline form in Defendants' product, which the complaint suggests is new (Compl. ¶60), falls within the scope of the XRPD peaks defined in the asserted patent claims. The interpretation of claim terms like "comprises peaks at" and the numerical range of "±0.2" degrees 2θ will be critical.

V. Key Claim Terms for Construction

  • The Term: "free from other stereoisomers of the compound" (’551 Patent, Claim 1)

  • Context and Importance: The definition of this term is central to the infringement analysis of the composition-of-matter patent. Practitioners may focus on this term because its construction will determine the level of purity required for infringement, which may be dispositive if Defendants' product contains any detectable level of other stereoisomers.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: Plaintiffs may point to the specification's use of phrases like "stereomerically pure," which is defined as containing "90-100% of the R-stereoisomer, preferably at least 93%...more preferably 95%...even more preferably 99%" (’551 Patent, col. 13:62-67). This could support a construction that does not require absolute 100% purity.
    • Evidence for a Narrower Interpretation: Defendants may argue that the plain language "free from" in the claim itself imposes an absolute standard of 100% purity, distinct from the potentially broader term "stereomerically pure" used elsewhere in the specification.

  • The Term: "consisting of" (’489 Patent, Claim 9)

  • Context and Importance: This transitional phrase is strongly limiting and typically means the claim covers methods with only the listed steps and no others. Its construction is critical because Defendants' formulation will contain inactive excipients, which could be argued to be additional elements of the "administering" step.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: Plaintiffs may argue that "consisting of" applies to the active therapeutic step of administering the claimed compound and does not exclude pharmaceutically acceptable carriers or excipients, which are described extensively in the specification as necessary for formulation (’489 Patent, col. 16:61-col. 17:40).
    • Evidence for a Narrower Interpretation: Defendants may argue that the term should be given its strict, closed meaning, and that the presence of excipients in their tablets constitutes additional components in the administration step not recited in the claim, thereby avoiding infringement.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges inducement and contributory infringement for all five patents. The basis for inducement is the allegation that Defendants' proposed product labeling will instruct medical professionals and patients to perform the infringing methods of treatment (Compl. ¶74, ¶88, ¶102, ¶116, ¶130). Contributory infringement is alleged on the basis that the product is especially made for an infringing use and is not suitable for a substantial non-infringing use (Compl. ¶77, ¶91, ¶105, ¶119, ¶133).
  • Willful Infringement: Willfulness is alleged for all five patents. The complaint asserts that Defendants had knowledge of the patents at least as of the date of their original ANDA submission and acted without a reasonable basis for believing they would not be liable for infringement (Compl. ¶78-79, ¶92-93, ¶106-107, ¶120-121, ¶134-135).

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

  • A core issue will be one of structural identity: does the crystalline form of fidaxomicin in Defendants' Amended ANDA Product exhibit an X-ray powder diffraction pattern that falls within the scope of the peaks claimed in the ’508, ’249, and ’510 patents? This is a primarily factual question that will be resolved through expert analysis and empirical testing.
  • A second key issue will be one of definitional scope: how will the court construe the purity limitation "free from other stereoisomers" in the ’551 Patent? The outcome will determine whether a standard of absolute purity is required or if a "substantially free" standard, potentially met by Defendants' product, is sufficient for infringement.
  • A central question for the method claims will be functional equivalence and claim construction: can the use of Defendants' product, which contains multiple excipients, be found to infringe method claims with the highly restrictive "consisting of" transitional phrase in the ’489 Patent?