ViiV Healthcare Co v. Mylan Pharma Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: ViiV Healthcare Company (Delaware), Shionogi & Co., Ltd. (Japan), and ViiV Healthcare UK (No. 3) Limited (United Kingdom)
  • Defendant: Mylan Pharmaceuticals Inc. (West Virginia) and Mylan Laboratories Ltd. (India)
  • Plaintiff’s Counsel: McCarter & English, LLP
• Case Identification: 1:17-cv-01671, D. Del., 11/17/2017
• Venue Allegations: Plaintiffs allege venue is proper because Defendants conduct business in Delaware, including marketing and selling generic pharmaceutical products, thereby deriving substantial revenue from the state. The complaint further alleges that Defendant Mylan Pharmaceuticals Inc. is registered to do business in Delaware, has appointed a registered agent, and has availed itself of the jurisdiction by previously filing counterclaims in the district.
• Core Dispute: Plaintiffs allege that Defendants' filing of an Abbreviated New Drug Application (ANDA) for a generic version of the HIV drug TRIUMEQ® constitutes an act of infringement of a patent claiming specific crystalline forms of dolutegravir sodium, an active ingredient in the drug.
• Technical Context: The technology lies in the field of pharmaceutical chemistry, specifically concerning distinct solid-state crystalline forms (polymorphs) of an active pharmaceutical ingredient used as an HIV integrase inhibitor.
• Key Procedural History: This action was initiated under the Hatch-Waxman Act, triggered by Defendants' submission of ANDA No. 210925 to the FDA. The ANDA included a "Paragraph IV Certification" alleging that the patent-in-suit is invalid, unenforceable, and/or will not be infringed by the proposed generic product. The patent-in-suit is listed in the FDA's "Approved Drug Products with Therapeutic Equivalence Evaluations" (the "Orange Book") for the branded drug TRIUMEQ®.

Case Timeline

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

U.S. Patent No. 9,242,986 - Synthesis of carbamoylpyridone HIV integrase inhibitors and intermediates

• Issued: January 26, 2016

The Invention Explained

• Problem Addressed: The patent background describes previously known multi-step processes for synthesizing a class of HIV integrase inhibitors. These prior art methods involved either attaching a key sidechain before the formation of the core ring structure or performing a key chemical reaction (bromination) after the core ring structure was already formed ('986 Patent, col. 1:13-33). The patent suggests a need for modified or alternative synthetic routes.
• The Patented Solution: The patent discloses specific crystalline forms of a final compound, dolutegravir sodium (referred to as a sodium salt of "formula AA"), which is an HIV integrase inhibitor ('986 Patent, col. 10:36-41). Rather than claiming a full synthetic process in the asserted claims, the patent claims these specific, stable solid-state forms of the final drug substance, characterized by unique data from analytical techniques like X-ray powder diffraction (XRPD) and infrared (IR) spectroscopy ('986 Patent, col. 10:1-2, FIG. 1-5).
• Technical Importance: For a pharmaceutical compound, having a specific, stable, and well-characterized crystalline form is critical for ensuring consistent purity, solubility, stability, and bioavailability in a final drug product ('986 Patent, col. 11:52-58).

Key Claims at a Glance

• The complaint alleges infringement of one or more claims from 1-12 of the '986 Patent (Compl. ¶31, ¶35). Independent claims in this range include Claims 1, 4, 6, 7, and 10.
• Independent Claim 1:
  • A crystal form
  • of a sodium salt
  • of a compound of formula AA
  • having characteristic diffraction peaks at 6.4°±0.2°, 9.2°±0.2°, 13.8°±0.2°, 19.2°±0.2° and 21.8°±0.2° degrees two-theta in an X-ray powder diffraction pattern.
• The complaint reserves the right to assert other claims, including dependent claims (Compl. ¶35).

III. The Accused Instrumentality

Product Identification

• Defendants' proposed generic version of ViiV's TRIUMEQ® tablets, which is the subject of ANDA No. 210925 ("Proposed ANDA Product") (Compl. ¶9).

Functionality and Market Context

• The Proposed ANDA Product is a fixed-dose combination tablet containing dolutegravir, abacavir, and lamivudine, intended for the treatment of HIV-1 infection (Compl. ¶9, ¶20). The complaint alleges that the Proposed ANDA Product contains "dolutegravir sodium" (Compl. ¶26).
• The complaint states that Defendants' ANDA submission contains data intended to demonstrate the bioequivalence of the Proposed ANDA Product to TRIUMEQ®, and that Defendants seek FDA approval for commercial manufacture and sale in the United States (Compl. ¶24, ¶27).

IV. Analysis of Infringement Allegations

The complaint pleads infringement generally and does not provide a detailed, element-by-element analysis. The core theory is that the dolutegravir sodium to be used in Defendants' Proposed ANDA Product will have the specific crystalline properties claimed in the '986 Patent (Compl. ¶26, ¶35).

’986 Patent Infringement Allegations

No probative visual evidence provided in complaint.

Identified Points of Contention

• Technical Question: A central question is factual: what is the actual crystalline structure of the dolutegravir sodium in Mylan's Proposed ANDA Product? The case will likely depend on the results of analytical characterization (e.g., XRPD) of Mylan's product sample and whether that data matches the data points recited in any asserted claim.
• Scope Question: If Mylan's product uses dolutegravir sodium, can it be a different, non-infringing polymorph or an amorphous form? This raises the question of whether Mylan can "design around" the patent by producing a form of the active ingredient that falls outside the specific physical characterization parameters defined in the claims.

V. Key Claim Terms for Construction

• The Term: "crystal form"

  • Context and Importance: The patent's claims are directed not to the chemical compound dolutegravir itself, but to specific solid "crystal forms" of its sodium salt. The definition of this term is critical because infringement hinges entirely on whether the accused product contains the specific polymorph claimed, as opposed to an amorphous form or a different, unclaimed polymorph.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent does not provide an explicit definition, which may suggest the term should be given its plain and ordinary meaning in the field of chemistry, referring to a solid in which the constituent atoms, molecules, or ions are packed in a regularly ordered, repeating pattern.
    • Evidence for a Narrower Interpretation: The specification consistently ties the claimed "crystal forms" to very specific sets of analytical data (XRPD peaks, IR spectra) and figures ('986 Patent, col. 10:3-51, FIGs. 1-7). A party could argue that the term, in the context of this patent, is implicitly defined by and limited to the forms that exhibit these precise, enumerated characteristics.

• The Term: "substantially as shown in"

  • Context and Importance: This term appears in claims that define the invention by reference to figures depicting analytical data (e.g., Claim 6: "X-ray powder diffraction pattern substantially as shown in FIG. 1"). Practitioners may focus on this term because its construction will determine how closely the accused product's analytical data must match the patent's figures to be considered infringing.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party might argue that "substantially" is a term of approximation, intended to cover minor, immaterial variations in the measured patterns that can result from differences in sample preparation or instrumentation, as long as the overall pattern is clearly identifiable as that in the figure.
    • Evidence for a Narrower Interpretation: A party could argue that the patent provides highly specific peak data in other independent claims (e.g., Claim 1), suggesting that "substantially as shown" should be interpreted narrowly to require a very close correspondence to the depicted figure, including all major peaks and their relative intensities.

VI. Other Allegations

• Indirect Infringement: The complaint alleges that Defendants will induce and contribute to infringement by third parties (Compl. ¶39). This allegation is based on the assertion that the product labeling for the Proposed ANDA Product will instruct physicians and patients on the use of the product, thereby encouraging its infringing use (Compl. ¶28, ¶37).
• Willful Infringement: The complaint alleges that Defendants lacked a good faith basis for their Paragraph IV certification and that their non-infringement assertions were "conclusory" (Compl. ¶30, ¶42). This is alleged to support a finding that the case is exceptional under 35 U.S.C. § 285. The basis for willfulness stems from Defendants' alleged knowledge of the '986 Patent at the time of their ANDA submission (Compl. ¶40).

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

• A primary issue will be a factual and evidentiary one of polymorphic identity: does the dolutegravir sodium in Defendants' Proposed ANDA Product exhibit the specific physical characteristics (e.g., the X-ray diffraction peaks) recited in the asserted claims? The dispute will turn on a direct comparison of analytical data from the accused product against the claimed parameters.
• A second core question will be one of claim scope and interpretation: for claims that define the crystal form by reference to a figure "substantially as shown," how much deviation in analytical data is permissible? The court's construction of this term will determine whether a similar, but not identical, crystalline form falls within the scope of the patent's claims.