DCT

1:17-cv-00375

Bristol Myers Squibb Co v. Breckenridge Pharmaceutical Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00375, D. Del., 04/05/2017
  • Venue Allegations: Venue is based on Defendant Breckenridge’s agreement, communicated via email, not to contest jurisdiction or venue in the District of Delaware.
  • Core Dispute: Plaintiffs allege that Defendant’s proposed generic version of the anticoagulant drug Eliquis®, for which it seeks FDA approval via an Abbreviated New Drug Application (ANDA), will infringe a patent covering specific formulations of the active ingredient apixaban.
  • Technical Context: The case involves pharmaceutical formulation technology for anticoagulants (Factor Xa inhibitors), where drug particle size and dissolution characteristics are controlled to ensure consistent bioavailability and therapeutic effect.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following a notification letter from Breckenridge, which certified that its proposed generic product would not infringe the patent-in-suit or that the patent is invalid. The complaint notes a dispute over the terms of confidential access to Breckenridge's ANDA, which Plaintiffs allege were unreasonably restrictive.

Case Timeline

Date Event
2010-02-25 ’945 Patent Priority Date
2016-05-03 ’945 Patent Issue Date
2017-02-23 Breckenridge sends ANDA Notice Letter
2017-04-05 Complaint Filing Date

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

U.S. Patent No. 9,326,945, “Apixaban Formulations,” Issued May 3, 2016

The Invention Explained

  • Problem Addressed: The patent addresses a challenge in formulating the anticoagulant drug apixaban. Based on its aqueous solubility, established pharmaceutical principles (the Biopharmaceutics Classification System) would predict that the size of the drug particles should not be critical for achieving consistent absorption in patients (Compl. Ex. A, '945 Patent, col. 1:44-58). However, the inventors discovered that formulations made with larger apixaban particles resulted in "less than optimal exposures," which could compromise consistent therapeutic effect and create "quality control challenges" (’945 Patent, col. 1:58-63).
  • The Patented Solution: The inventors "surprisingly and unexpectedly" found that controlling the apixaban particle size to a specific maximum threshold is critical for consistent drug absorption (’945 Patent, col. 1:64-2:6). The invention is a solid pharmaceutical composition where the crystalline apixaban particles have a D90 (meaning 90% of the particles by volume are smaller than this diameter) of 89 microns (µm) or less. This specific formulation is claimed to produce consistent in-vivo dissolution, leading to a reliable therapeutic effect (’945 Patent, Abstract; col. 2:34-43).
  • Technical Importance: The invention provides a method to overcome unpredicted bioavailability issues for a low-solubility drug, establishing a specific particle size threshold that ensures consistent drug exposure, a critical factor for anticoagulants where dosing precision is paramount.

Key Claims at a Glance

  • The complaint asserts independent claims 1 and 12, among others (Compl. ¶19).
  • Independent Claim 1 requires:
    • A solid pharmaceutical composition comprising crystalline apixaban particles and a pharmaceutically acceptable diluent or carrier.
    • The crystalline apixaban particles have a D90 equal to or less than about 89 µm.
    • At least 77 wt % of apixaban dissolves within 30 minutes in a pH 6.8 phosphate buffer containing 0.05% sodium lauryl sulfate.
  • Independent Claim 12 has a similar scope but is framed to include the dissolution requirement as a primary feature, specifying it is measured using a USP Apparatus 2 at 75 rpm in 900 mL of the specified medium at 37° C.
  • The complaint also asserts dependent claims 9-11, 20-23, 25, 27, 29, 31, 33, 35, and 37, which add further limitations such as specific apixaban dosages (2.5 mg or 5 mg), the form of the composition (tablet or capsule), and the inclusion of specific surfactants (Compl. ¶19).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Breckenridge’s proposed generic 2.5 mg and 5 mg apixaban tablets, for which it seeks FDA approval in ANDA No. 209845 (the "Breckenridge ANDA product") (Compl. ¶2).

Functionality and Market Context

  • The Breckenridge ANDA product is intended to be a generic version of Plaintiffs’ Eliquis® drug product (Compl. ¶2). By filing an ANDA, Breckenridge has represented to the FDA that its product has the same active ingredient, dosage form, strength, and is bioequivalent to Eliquis® (Compl. ¶13). Eliquis® is a Factor Xa inhibitor used to reduce the risk of stroke and treat thromboembolic disorders, and the complaint alleges Breckenridge seeks approval for these same indications (Compl. ¶10, ¶14).

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed, element-by-element infringement analysis or claim chart. The infringement allegation is based on the statutory act of filing ANDA No. 209845, which constitutes a technical act of infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶19). The complaint alleges that upon approval, the commercial manufacture, use, or sale of the Breckenridge ANDA product will infringe the ’945 patent (Compl. ¶20). The complaint’s infringement theory rests on the premise that for Breckenridge’s product to be bioequivalent to Eliquis®, it must necessarily practice the formulation technology claimed in the ’945 patent.

  • Identified Points of Contention:
    • Technical Questions: The central factual dispute will concern the physical characteristics of the Breckenridge ANDA product. A primary question is whether discovery will confirm that the apixaban particles in Breckenridge's formulation have a D90 particle size distribution that falls within the claimed "equal to or less than about 89 µm" limitation (’945 Patent, col. 11:50-54). Figure 3 of the ’945 Patent illustrates the claimed correlation between drug substance particle size (D90) and the percentage dissolved in 30 minutes for 2.5-mg tablets (Compl. Ex. A, Fig. 3). A second key question is whether the Breckenridge product exhibits the dissolution profile required by the claims—specifically, whether at least 77% of the apixaban dissolves within 30 minutes under the precise test conditions specified in Claim 1 (’945 Patent, col. 11:55-58). Figure 4 of the ’945 patent provides a similar dissolution rate graph for 5-mg tablets, which is also a subject of the ANDA (Compl. Ex. A, Fig. 4).
    • Scope Questions: The interpretation of the term "about 89 µm" may become a point of contention. The parties may dispute the degree of variance from 89 µm that "about" permits, a determination that could be informed by the data presented in the patent’s specification showing a clear performance drop-off at larger particle sizes.

V. Key Claim Terms for Construction

  • The Term: "crystalline apixaban particles have a D90 equal to or less than about 89 µm" (Claim 1)

    • Context and Importance: This term defines the core structural characteristic of the invention. The entire infringement case will depend on whether Breckenridge's product meets this particle size limitation. Practitioners may focus on this term because the patent explicitly frames the 89 µm threshold as a surprising discovery that solves a previously unrecognized bioavailability problem.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The use of the word "about" suggests the 89 µm value is not an absolute, razor-sharp cutoff, potentially allowing for some minor variation due to measurement tolerances or manufacturing variability.
      • Evidence for a Narrower Interpretation: The specification defines D90 as "90% of the volume of particles have a diameter less than a specified diameter D" and notes that the sizes were determined using a specific "laser light scattering technique" (’945 Patent, col. 2:15-18, 23-24). The patent also discloses clinical data linking dissolution rates to specific particle sizes, with Figures 3 and 4 showing a clear trend where dissolution drops as D90 increases toward and beyond 89 µm. A defendant may argue this data supports a strict interpretation of the upper limit (’945 Patent, col. 10:20-46; Figs. 3-4).

  • The Term: "at least 77 wt % of apixaban dissolves within 30 minutes" (Claim 1)

    • Context and Importance: This functional limitation links the claimed particle size to a specific, measurable performance outcome. It is described in the patent as the "threshold for achieving consistent exposure" based on clinical data, making it critical for both infringement and validity arguments (’945 Patent, col. 10:26-29).
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: A plaintiff might argue this is a performance floor and that any product achieving this rate or higher infringes, regardless of the exact mechanism, so long as the particle size limitation is also met.
      • Evidence for a Narrower Interpretation: The patent ties the 77% value directly to a specific clinical trial result where a tablet with this dissolution profile was compared to others (’945 Patent, Table 6; col. 10:18-26). A defendant could argue this ties the claim to the specific context of that study, potentially limiting its scope if their product's behavior, while meeting the 77% threshold, differs in other material ways from the formulation tested in the patent.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon FDA approval, Breckenridge will actively induce infringement by marketing and selling its ANDA product in the U.S. with labeling that instructs medical professionals and patients to administer the drug, thereby causing them to directly infringe (Compl. ¶21). It also alleges contributory infringement.
  • Willful Infringement: The complaint does not contain an explicit count for willful infringement. However, the prayer for relief requests "damages or other monetary relief, including costs, fees, pre and post-judgment interest" and other relief deemed proper, including under 35 U.S.C. § 285 for exceptional cases (Compl. p. 6-7, ¶4-5). Any potential willfulness claim would be predicated on Breckenridge's continued conduct after receiving notice of infringement via the filing of this lawsuit.

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

  1. A Central Evidentiary Question: The case hinges on a core factual question of technical compliance: does Breckenridge's proposed generic apixaban formulation, as detailed in its confidential ANDA, contain crystalline particles with a D90 of 89 µm or less and, concurrently, achieve a dissolution rate of at least 77% in 30 minutes under the specific conditions recited in the patent? The resolution of this question will likely require analysis of confidential ANDA data and expert testing.

  2. A Key Validity Question: The case will likely feature a significant dispute over obviousness. Breckenridge has certified the patent is invalid (Compl. ¶15). A court will need to determine whether, at the time of the invention, it would have been obvious for a skilled formulator to control apixaban’s particle size to the claimed D90 ≤ 89 µm threshold to achieve consistent bioavailability. The patent's assertion that this discovery was "surprising" and contrary to the expectations of the Biopharmaceutics Classification System will be a central point of contention in this analysis.