Bristol Myers Squibb Co v. Sun Pharmaceutical Industries Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Bristol-Myers Squibb Company (Delaware) and Pfizer Inc. (Delaware)
  • Defendant: Sun Pharmaceutical Industries Inc. (Michigan)
  • Plaintiff’s Counsel: Farnan, LLP; Wilmer Cutler Pickering Hale and Dorr LLP
• Case Identification: 1:17-cv-00409, D. Del., 04/10/2017
• Venue Allegations: Venue is asserted as proper in the District of Delaware, and the complaint states that Defendant Sun agreed not to contest jurisdiction or venue in this matter.
• Core Dispute: Plaintiffs allege that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the anticoagulant drug Eliquis® constitutes an act of infringement of a patent covering specific formulations of the active ingredient, apixaban.
• Technical Context: The technology relates to pharmaceutical formulations for low-solubility drugs, specifically focusing on controlling drug particle size to ensure consistent absorption by the body and a reliable therapeutic effect.
• Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act following Defendant’s submission of ANDA No. 210171 to the FDA. This ANDA included a "Paragraph IV certification," a statutory declaration that the patent-in-suit is invalid, unenforceable, or will not be infringed by the proposed generic product.

Case Timeline

Date	Event
2010-02-25	'945 Patent Priority Date
2016-05-03	'945 Patent Issue Date
2017-02-28	Date of Sun's ANDA Notice Letter to Plaintiffs
2017-03-01	Earliest Date Plaintiffs Received Sun's Notice Letter
2017-04-10	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 the problem of inconsistent patient drug absorption for the anticoagulant apixaban (’945 Patent, col. 1:56-60). Although biopharmaceutical models predicted that apixaban's particle size should not be critical for consistent absorption, the inventors found that formulations with larger drug particles led to "less than optimal exposures," creating potential challenges for quality control and consistent therapeutic effect (’945 Patent, col. 1:47-60).
• The Patented Solution: The invention is a pharmaceutical composition where the crystalline apixaban particles are controlled to a specific, fine size. The patent asserts that by ensuring 90% of the particle volume (a metric known as D90) is equal to or less than 89 micrometers (µm), the formulation achieves "consistent in-vivo dissolution" and, consequently, a more reliable and predictable therapeutic effect for patients (’945 Patent, col. 1:61-col. 2:4). This finding was described as surprising because it contradicted expectations from the Biopharmaceutics Classification System (’945 Patent, col. 2:48-54).
• Technical Importance: For an anticoagulant, predictable pharmacokinetics are critical for maintaining a balance between therapeutic efficacy (preventing clots) and safety (avoiding excessive bleeding); the invention purports to provide a formulation that ensures this consistency (’945 Patent, col. 2:1-4).

Key Claims at a Glance

• The complaint asserts infringement of claims including independent claims 1 and 12 (Compl. ¶19).
• Independent Claim 1 recites a solid pharmaceutical composition comprising:
  • a therapeutically effective amount of crystalline apixaban particles;
  • a pharmaceutically acceptable diluent or carrier;
  • wherein the crystalline apixaban particles have a D90 equal to or less than about 89 µm; and
  • wherein 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 is similar but more precisely defines the dissolution testing conditions, specifying the use of a "USP Apparatus 2 at a paddle rotation speed of 75 rpm in 900 mL, of a dissolution medium at 37° C."
• The complaint reserves the right to assert additional claims, including numerous dependent claims (Compl. ¶19).

III. The Accused Instrumentality

Product Identification

• The accused instrumentality is Defendant Sun's proposed generic apixaban tablets, as described in its ANDA No. 210171 submitted to the FDA (Compl. ¶2).

Functionality and Market Context

• The complaint alleges that Sun’s ANDA product is a generic version of Plaintiffs' Eliquis® drug product (Compl. ¶2). As part of the ANDA process, Sun has necessarily represented to the FDA that its product contains the same active ingredient, has the same dosage form and strength, and is bioequivalent to Eliquis® (Compl. ¶13). Sun is seeking approval to market its product for the same medical indications as Eliquis®, which include the treatment and prevention of thromboembolic disorders (Compl. ¶14). The filing of the ANDA seeks FDA approval to market this product prior to the expiration of the ’945 Patent (Compl. ¶2).

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or specific factual allegations detailing how the accused product infringes the patent claims. The infringement allegation is made under 35 U.S.C. § 271(e)(2), which defines the submission of an ANDA seeking approval to market a generic drug before patent expiration as a statutory act of infringement (Compl. ¶19). The central allegation is that the product described in Sun’s ANDA, if manufactured and sold, would meet all limitations of the asserted claims of the ’945 Patent (Compl. ¶19). The specific details of Sun's formulation are contained within the confidential ANDA and are not public.

No probative visual evidence provided in complaint.

• Identified Points of Contention: Based on the claims and the nature of the dispute, the infringement analysis will likely focus on several key questions that must be answered by examining the confidential ANDA data.
  • Technical Question (Particle Size): Does the formulation specified in Sun’s ANDA No. 210171 utilize crystalline apixaban particles with a D90 particle size distribution that is "equal to or less than about 89 µm," as required by independent claims 1 and 12?
  • Technical Question (Dissolution Rate): Does Sun’s proposed product, when tested under the conditions specified in the claims, exhibit a dissolution profile where "at least 77 wt %" of the apixaban dissolves within 30 minutes? This is a factual question of performance that will be determined by reviewing Sun's bioequivalence studies and/or independent testing.
  • Scope Question: A dispute may arise over the proper interpretation of "about 89 µm." The extent to which "about" allows for deviation from the 89 µm value could be a critical issue if Sun's formulation uses a particle size at or very near this threshold.

V. Key Claim Terms for Construction

• The Term: "D90 equal to or less than about 89 µm" (from Claim 1)

  • Context and Importance: This term is the core of the invention and defines the primary physical characteristic of the patented formulation. The infringement analysis will turn on whether Sun's product falls within the scope of this limitation, and the meaning of "about" is central to that determination.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: Plaintiffs may argue that "about" should be interpreted to encompass normal manufacturing and measurement variability, consistent with the patent's stated goal of achieving "consistent exposure" rather than a rigid numerical cutoff (’945 Patent, col. 2:1-4).
    • Evidence for a Narrower Interpretation: Defendants may argue that 89 µm represents a critical, experimentally-derived threshold. The specification states, "It has surprisingly been found, however, that the particle size that impacts apixaban absorption rate is about a D90 of 89 µm" (’945 Patent, col. 2:51-54). This could be presented as a definitional statement that limits the scope of "about" to a very narrow range around 89 µm.

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

  • Context and Importance: This functional limitation defines the required performance of the claimed composition. Infringement requires that Sun’s product meets this dissolution benchmark.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent explicitly links this 77% dissolution value to a clinical outcome, defining it as "the threshold for achieving consistent exposure" based on a bioequivalence study (’945 Patent, col. 9:20-29). Plaintiffs will likely argue that any formulation meeting this performance metric, regardless of its exact composition (beyond the other claim limits), infringes.
    • Evidence for a Narrower Interpretation: A defendant's primary challenge to this term would likely be factual—arguing its product does not meet the 77% threshold. Arguments to narrow the term's scope are less apparent from the intrinsic evidence, as the claim is written in functional terms and is not limited to a specific manufacturing process or set of excipients.

VI. Other Allegations

• Indirect Infringement: The complaint alleges that upon approval, Sun's commercial activities would induce and contribute to infringement by others (Compl. ¶¶ 20, 21). The alleged basis for inducement is that Sun would market the product with a label and instructions that direct medical professionals and patients to use the product in its intended, and allegedly infringing, manner.
• Willful Infringement: The complaint does not contain an explicit allegation of willful infringement. However, it alleges that Sun received notice of the ’945 Patent via a letter dated February 28, 2017 (Compl. ¶11), thereby establishing knowledge. The prayer for relief also seeks "any appropriate relief under 35 U.S.C. § 285," a statute that allows for an award of attorney's fees in "exceptional cases," which can be predicated on a finding of willful infringement based on post-filing conduct (Compl., Prayer for Relief ¶5).

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

The resolution of this case will likely depend on the answers to a few central questions:

• A primary issue will be factual and technical: does the generic apixaban formulation described in Sun’s confidential ANDA meet the two quantitative limitations recited in the patent claims—a particle size (D90) of about 89 µm or less, and a dissolution rate of at least 77% in 30 minutes? The outcome will depend entirely on the evidence contained within the ANDA and any subsequent testing.
• A key legal question will be one of claim scope: can the term "about," as used in the "about 89 µm" limitation, be interpreted to cover a particle size that is numerically greater than 89 µm? The court's construction of this single word could be dispositive if Sun's formulation is engineered to be near the claimed threshold.
• Finally, the case will present a validity challenge, as asserted in Sun's Paragraph IV certification (Compl. ¶15). A core question for the court will be whether it was obvious to a person of ordinary skill in the art to control apixaban's particle size to the claimed range to achieve consistent bioavailability, especially in light of the patent's own characterization of this discovery as "surprising" and contrary to the predictions of standard pharmaceutical models.