DCT

1:19-cv-00310

Merck Sharp & Dohme Corp v. Alvogen Pine Brook LLC

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-00310, D. Del., 02/13/2019
  • Venue Allegations: Venue is asserted based on Defendant Alvogen Pine Brook LLC being a Delaware limited liability company, and on all defendants allegedly being subject to personal jurisdiction in the district through systematic business contacts, purposeful availment of Delaware's laws, and a history of engaging in litigation in the district.
  • Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the diabetes drug JANUMET XR® 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 of a dipeptidyl peptidase-IV (DP-IV) inhibitor, a class of small-molecule drugs used to treat Type 2 diabetes, with the claimed salt form selected for its advantageous pharmaceutical properties.
  • Key Procedural History: The action arises under the Hatch-Waxman Act, triggered by a notice letter dated June 25, 2014, in which Alvogen informed Merck of its ANDA filing containing a Paragraph IV certification. The complaint alleges that in this notice letter, Alvogen did not contest that its proposed generic product would infringe Claim 1 of the asserted patent.

Case Timeline

Date Event
2003-06-24 '708 Patent Priority Date
2008-02-05 U.S. Patent No. 7,326,708 Issued
2014-06-25 Alvogen's ANDA Notice Letter Sent
2019-02-13 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: The patent's background describes a class of compounds that are potent DP-IV inhibitors useful for treating Type 2 diabetes ('708 Patent, col. 1:49-55). The implicit technical problem is developing a specific form of one of these compounds that possesses superior properties for formulation into a drug product, such as enhanced stability and solubility ('708 Patent, col. 2:10-14).
  • The Patented Solution: The invention is a specific dihydrogenphosphate salt of the DP-IV inhibitor 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, also known as sitagliptin ('708 Patent, Abstract). The patent particularly describes a crystalline monohydrate form of this salt, which is claimed to have advantages in "ease of processing, handling, and dosing" and improved "physical and chemical stability" compared to other forms, making it suitable for manufacturing pharmaceutical dosage forms ('708 Patent, col. 2:5-18).
  • Technical Importance: Creating a salt form of an active pharmaceutical ingredient with optimal stability, solubility, and manufacturing characteristics is a critical step in converting a promising chemical entity into a commercially viable and reliable drug.

Key Claims at a Glance

  • The complaint asserts infringement of at least independent Claim 1 (Compl. ¶37).
  • The essential elements of Claim 1 are:
    • 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 states that Alvogen's product is covered by "one or more claims of the '708 patent, including at least claim 1" (Compl. ¶37).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is "Alvogen's ANDA Product," a proposed generic version of Merck's JANUMET XR® (metformin hydrochloride; sitagliptin phosphate extended release tablets) (Compl. ¶¶1, 3).
  • Functionality and Market Context: The complaint alleges that the accused product "contains sitagliptin phosphate as an active ingredient" (Compl. ¶36). The product is intended to be a therapeutically equivalent, lower-cost alternative to the branded JANUMET XR® drug for the treatment of Type 2 diabetes, and its commercial launch is contingent upon FDA approval of Alvogen's ANDA No. 205341 (Compl. ¶¶1-2).

IV. Analysis of Infringement Allegations

The complaint's infringement theory is statutory, based on the submission of an ANDA seeking approval to market a drug claimed in a patent before its expiration, which constitutes infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶39). 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 of structural formula I... or a hydrate thereof. Alvogen's ANDA Product is alleged to contain "sitagliptin phosphate as an active ingredient," which the complaint asserts is covered by Claim 1. ¶36, ¶37 col. 2:45-63
  • Identified Points of Contention:
    • Infringement Concession: A significant allegation is that "Alvogen did not contest infringement of claim 1 of the '708 patent" in its notice letter (Compl. ¶38). If this is accurate, the primary focus of the litigation may shift from infringement analysis to the validity and/or enforceability of the patent, which Alvogen challenged in its Paragraph IV certification (Compl. ¶35).
    • Technical Questions: While infringement of Claim 1 is allegedly uncontested, a potential dispute could still arise regarding the specific form of sitagliptin phosphate in Alvogen's ANDA product. The court may need to consider evidence regarding the precise crystalline structure (polymorph) and hydration state of the accused active ingredient to determine if it meets the claim limitations as construed.

V. Key Claim Terms for Construction

  • The Term: "a dihydrogenphosphate salt"

    • Context and Importance: This term defines the core chemical identity of the claimed composition. The scope of this term will be critical if Alvogen argues that its specific salt form, while being a "phosphate" salt, is not the claimed "dihydrogenphosphate" salt.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification describes the salt as comprising "one molar equivalent of mono-protonated... cation and one molar equivalent of dihydrogenphosphate (biphosphate) anion," which could support a construction covering any composition meeting this 1:1 stoichiometry ('708 Patent, col. 4:35-42).
      • Evidence for a Narrower Interpretation: The patent's examples and detailed characterization data (e.g., X-ray diffraction, NMR) focus heavily on a specific crystalline monohydrate form ('708 Patent, Figs. 1-5; col. 13:21-51). A party could argue that the claims, viewed in light of the specification, are implicitly limited to this well-characterized form.

  • The Term: "a hydrate thereof"

    • Context and Importance: This term extends the claim scope beyond the anhydrous salt form. Its construction is important because the patent's disclosure is heavily weighted toward a specific "crystalline monohydrate" ('708 Patent, Abstract; col. 2:3-4).
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: A party could argue that the plain meaning of "a hydrate" is not limited to a monohydrate and could encompass other stoichiometric or even non-stoichiometric hydrates.
      • Evidence for a Narrower Interpretation: A defendant might argue that the specification's repeated and detailed focus on the monohydrate is the only enabled and described hydrate, effectively limiting the scope of "a hydrate thereof" to the disclosed monohydrate form.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement, asserting that Alvogen plans and intends for its ANDA product to be manufactured and sold with proposed labeling that will direct users to infringe the '708 patent (Compl. ¶¶42-43).
  • Willful Infringement: The complaint alleges that Alvogen has acted with full knowledge of the '708 patent and "without a reasonable basis for believing that it would not be liable for infringement," which provides a basis for a finding of willfulness (Compl. ¶47).

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

  • A central issue will be one of patent validity: Given the complaint's assertion that infringement of Claim 1 is not contested, the litigation will likely focus on Alvogen's defenses that the patent is invalid or unenforceable. The key question for the court will be whether Alvogen can prove by clear and convincing evidence that the claims to the specific sitagliptin dihydrogenphosphate salt are invalid, for instance, due to obviousness over the prior art base compound.
  • A secondary but potentially dispositive question will be the scope of the asserted claims: Should Alvogen reverse its position or contest infringement of other claims, the case may turn on claim construction. The court would need to determine if the term "dihydrogenphosphate salt... or a hydrate thereof" is limited to the specific crystalline monohydrate form heavily detailed in the patent's specification, or if it has a broader scope that would cover other potential salt forms or hydrates.