DCT

1:19-cv-00101

Merck Sharp & Dohme LLC v. Mylan Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-00101, N.D. W. Va., 05/02/2019
  • Venue Allegations: Venue is alleged to be proper as Defendant Mylan Pharmaceuticals Inc. is a West Virginia corporation, and Defendant Mylan Inc. has previously consented to venue in the district.
  • Core Dispute: Plaintiff alleges that Defendants' submission of Abbreviated New Drug Applications (ANDAs) seeking to market generic versions of the diabetes drugs JANUVIA® and JANUMET® constitutes an act of infringement of two patents covering a specific salt form of the active ingredient sitagliptin and a fixed-dose combination formulation with metformin.
  • Technical Context: The technology relates to pharmaceutical compositions for the treatment of Type 2 diabetes, a prevalent metabolic disorder.
  • Key Procedural History: The litigation was triggered by notice letters sent by Mylan to Merck in 2010 and 2013, which included Paragraph IV certifications asserting that the patents-in-suit are invalid, unenforceable, and/or not infringed by Mylan's proposed generic products. Subsequent to the filing of this complaint, the '708' patent was the subject of Inter Partes Review (IPR) proceedings at the USPTO, which confirmed the patentability of asserted claims 1-4.

Case Timeline

Date Event
2003-06-24 '708 Patent Priority Date
2005-12-16 '921' Patent Priority Date
2008-02-05 '708 Patent Issue Date
2010-12-28 Mylan's '473 and First '478 ANDA Notice Letters to Merck
2013-04-09 '921 Patent Issue Date
2013-09-13 Mylan's Second '478 ANDA Notice Letter to Merck
2019-05-02 Complaint Filing Date

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 Feb. 5, 2008)

The Invention Explained

  • Problem Addressed: While the underlying active compound for inhibiting dipeptidyl peptidase-IV (DP-IV) was known, the patent addresses the need for a specific salt form of that compound with advantageous properties for manufacturing a stable and effective pharmaceutical product (Compl. ¶28; '708 Patent, col. 1:52-57, col. 2:5-10).
  • The Patented Solution: The invention is a specific dihydrogenphosphate salt of the DP-IV inhibitor sitagliptin, particularly its crystalline monohydrate form. This salt is described as having improved physical and chemical stability and superior physicochemical properties (such as solubility), making it particularly suitable for processing, handling, and formulation into various dosage forms ('708 Patent, Abstract; col. 2:5-18).
  • Technical Importance: The development of a stable, consistently reproducible salt form is a critical step in converting a promising chemical entity into a commercially viable drug with a reliable dosage profile and long-term shelf life ('708 Patent, col. 2:5-18).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 (Compl. ¶¶43, 63).
  • 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’s allegation of infringement of "one or more claims" suggests the right to assert dependent claims is reserved (Compl. ¶¶43, 63).

U.S. Patent No. 8,414,921 - "Pharmaceutical Compositions of Combinations of Dipeptidyl Peptidase-4 Inhibitors with Metformin" (Issued Apr. 9, 2013)

The Invention Explained

  • Problem Addressed: The patent's background describes that long-term treatment of Type 2 diabetes often requires combination therapy. Co-prescribing multiple oral medications can result in complex regimens that are difficult for patients to follow, potentially reducing adherence ('921 Patent, col. 2:20-29).
  • The Patented Solution: The invention provides a fixed-dose combination tablet that includes both a DPP-4 inhibitor (sitagliptin) and metformin. The claims define specific formulations with precise weight-percentage ranges for the active ingredients and key excipients (e.g., lubricant, binding agent, surfactant, diluent) to create a stable, immediate-release product ('921 Patent, Abstract; col. 4:55-65).
  • Technical Importance: A single-tablet, fixed-dose combination simplifies treatment, which can improve patient compliance and, consequently, therapeutic outcomes ('921 Patent, col. 2:29-34).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 (Compl. ¶82).
  • Claim 1 recites a pharmaceutical composition comprising:
    • (a) about 3 to 20% by weight of sitagliptin, or a pharmaceutically acceptable salt thereof;
    • (b) about 25 to 94% by weight of metformin hydrochloride;
    • (c) about 0.1 to 10% by weight of a lubricant;
    • (d) about 0 to 35% by weight of a binding agent;
    • (e) about 0.5 to 1% by weight of a surfactant; and
    • (f) about 5 to 15% by weight of a diluent.
  • The complaint’s allegation of infringement of "one or more claims" suggests the right to assert dependent claims is reserved (Compl. ¶82).

III. The Accused Instrumentality

Product Identification

  1. Sitagliptin phosphate oral tablets ("Mylan's '473 ANDA Product"), a generic version of Merck's JANUVIA® (Compl. ¶¶1, 3).
  2. Metformin hydrochloride and sitagliptin phosphate oral tablets ("Mylan's '478 ANDA Product"), a generic version of Merck's JANUMET® (Compl. ¶¶1, 6).

Functionality and Market Context

The complaint alleges that Mylan has filed ANDAs with the U.S. Food and Drug Administration (FDA) seeking approval to manufacture, use, and sell these products for the treatment of Type 2 diabetes (Compl. ¶1). The filing of an ANDA is an artificial act of infringement under the Hatch-Waxman Act, intended to resolve patent disputes before a generic drug enters the market (Compl. ¶45). The products contain sitagliptin phosphate, alone or in combination with metformin hydrochloride, as their active pharmaceutical ingredient(s) (Compl. ¶¶42, 62).

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...or a hydrate thereof The complaint alleges that Mylan stated in its notice letters that both its '473 ANDA Product and its '478 ANDA Product contain "sitagliptin phosphate as an active ingredient." ¶¶42, 62 col. 2:44-51
  • Identified Points of Contention:
    • Scope Questions: The complaint states that Mylan's notice letters did not contest infringement of claim 1 (Compl. ¶¶44, 64). However, it also states that Mylan filed a Paragraph IV certification asserting non-infringement (Compl. ¶¶41, 61). A primary question for the court will be to resolve this apparent inconsistency and determine if a bona fide infringement dispute exists.
    • Technical Questions: The infringement analysis may focus on the specific form of sitagliptin phosphate in Mylan's products. While claim 1 broadly covers the salt "or a hydrate thereof," a dispute could arise over whether Mylan's specific formulation, including its exact hydration state and polymorphic form, falls within the scope of the claims, especially if Merck asserts dependent claims directed to the crystalline monohydrate.

'921 Patent Infringement Allegations

The complaint does not provide sufficient detail for a full claim chart analysis, alleging only that "the composition of Mylan's '478 ANDA Product includes the same or equivalent ingredients as recited in claim 1 of the '921 patent in the same or equivalent amounts" (Compl. ¶82).

  • Identified Points of Contention:
    • Evidentiary Questions: The core issue is factual and will depend on evidence obtained in discovery. The key question is whether the precise formulation disclosed in Mylan's '478 ANDA meets every quantitative limitation of claim 1. Merck's complaint relies on a conclusory allegation rather than a detailed breakdown of Mylan's formulation.
    • Scope Questions: The interpretation of the term "about," which qualifies the percentage ranges for multiple components in claim 1, will be critical. The parties may dispute whether Mylan's formulation, if it falls near the boundaries of the claimed ranges, literally infringes.

V. Key Claim Terms for Construction

  • The Term: "a hydrate thereof" (from '708 Patent, claim 1)

    • Context and Importance: The scope of this term is central to infringement. Practitioners may focus on this term because the '708 patent's specification extensively details a "crystalline monohydrate," and the infringement analysis could depend on whether "a hydrate" is construed broadly to include any associated water or narrowly to mean a stable, crystalline form like the one disclosed.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The plain language of claim 1, "a hydrate thereof," does not inherently limit the term to a specific stoichiometry or crystalline structure ('708 Patent, col. 17:1).
      • Evidence for a Narrower Interpretation: The abstract and detailed description repeatedly emphasize the "crystalline monohydrate" as the inventive entity, providing detailed characterization data for that specific form, which could be used to argue that the claims should be understood in light of this specific disclosure ('708 Patent, Abstract; col. 2:64-65).

  • The Term: "about" (from '921 Patent, claim 1)

    • Context and Importance: This term is case-dispositive for infringement of the '921 patent, as it defines the permissible boundaries for the weight percentages of all key ingredients. If Mylan's formulation is close to, but not exactly matching, the recited percentages, the meaning of "about" will determine the outcome of the infringement analysis.
    • Intrinsic Evidence for Interpretation: The patent does not provide an explicit definition. The parties will likely rely on the numerous specific formulations in the patent's examples to argue for the degree of variability a person of ordinary skill in the art would understand the term "about" to permit in this context ('921 Patent, cols. 9-12).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Mylan will actively induce infringement of both patents. The basis for this allegation is that Mylan's proposed product labeling will instruct physicians and patients to use the generic drugs in a manner that infringes the patents (Compl. ¶¶49, 69, 87).
  • Willful Infringement: Willfulness is alleged based on Mylan's knowledge of the patents, evidenced by the ANDA notice letters it sent to Merck (Compl. ¶¶53, 73, 91). The complaint alleges that Mylan acted "without a reasonable basis for believing that it would not be liable for infringement," which, if proven, could support an award of enhanced damages (Compl. ¶53).

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

  1. A central issue will be patent validity. Mylan's Paragraph IV certifications challenge the validity of both patents. For the '708 patent, a key question will be whether Mylan can advance invalidity arguments by clear and convincing evidence that were not raised, and are not precluded by, the IPR proceedings that previously confirmed the patentability of the asserted claims.

  2. For the '921 patent, the case will turn on a question of factual infringement. Once the details of Mylan's formulation are produced in discovery, the dispositive question will be whether its composition meets every percentage-based limitation of claim 1, an analysis that will heavily depend on the court's construction of the term "about."

  3. A final procedural and substantive question will be the effect of Mylan's alleged pre-suit admission of infringement. The court will need to weigh the complaint's allegation that Mylan did not contest infringement of the '708 patent's claim 1 in its notice letters against Mylan's formal assertion of non-infringement in its Paragraph IV certification.