DCT

1:17-cv-00411

Bristol Myers Squibb Co v. Wockhardt Bio AG

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00411, D. Del., 04/10/2017
  • Venue Allegations: Plaintiffs allege venue is proper and note that Defendant, via email, agreed not to contest jurisdiction or venue in the District of Delaware.
  • Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) for a generic version of the anticoagulant drug Eliquis® constitutes an act of infringement of a patent covering specific formulations of apixaban.
  • Technical Context: The technology relates to pharmaceutical formulations of the active ingredient apixaban, focusing on controlling particle size to ensure consistent drug dissolution and bioavailability for treating thromboembolic disorders.
  • Key Procedural History: This is a Hatch-Waxman action triggered by Wockhardt's filing of ANDA No. 210110 and a corresponding Paragraph IV certification notice letter, received by Plaintiffs on or after March 2, 2017, which asserted 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
2017-03-01 Wockhardt sends ANDA Paragraph IV notice letter
2017-03-24 Wockhardt agrees not to contest venue in D. Del.
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 unexpected discovery that, contrary to predictions based on apixaban's aqueous solubility, formulations made with large particles of the drug substance or through certain manufacturing processes (wet granulation) resulted in "less than optimal exposures" in humans, creating potential quality control and therapeutic consistency challenges (’945 Patent, col. 1:56-62).
  • The Patented Solution: The invention is a solid pharmaceutical composition comprising crystalline apixaban particles with a specific, controlled particle size distribution, where 90% of the particles by volume have a diameter (D90) of 89 microns (µm) or less (’945 Patent, Abstract; col. 2:7-13). This specific formulation is described as leading to "consistent in-vivo dissolution in humans" and, consequently, a more reliable therapeutic effect, and is particularly suited for a dry granulation manufacturing process (’945 Patent, col. 2:1-6, 55-62).
  • Technical Importance: For an anticoagulant like apixaban, achieving consistent plasma concentration is critical for safety and efficacy; the patented formulation provides a method to control a key variable (particle size) to ensure this consistency (’945 Patent, col. 2:1-3).

Key Claims at a Glance

  • The complaint asserts independent claims 1 and 12, along with multiple dependent claims (Compl. ¶21).
  • Independent Claim 1 recites:
    • A solid pharmaceutical composition with a therapeutically effective amount of crystalline apixaban particles.
    • The particles have a D90 "equal to or less than about 89 µm."
    • At least 77% of the apixaban dissolves within 30 minutes in a specified buffer solution.
  • Independent Claim 12 recites:
    • A solid pharmaceutical composition with a therapeutically effective amount of crystalline apixaban particles.
    • The particles have a D90 "equal to or less than about 89 µm."
    • A dissolution limitation of at least 77% in 30 minutes, specified with testing parameters including USP Apparatus 2 at 75 rpm in 900 mL of a specific dissolution medium.
  • The complaint reserves the right to assert additional claims (’945 Patent, cls. 1, 12; Compl. ¶21).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Wockhardt’s proposed 2.5 mg and 5 mg apixaban tablets, for which it seeks FDA approval via Abbreviated New Drug Application (ANDA) No. 210110 (the "Wockhardt ANDA product") (Compl. ¶2).

Functionality and Market Context

  • The Wockhardt ANDA product is a generic version of Plaintiffs’ Eliquis® brand apixaban tablets (Compl. ¶2).
  • By filing its ANDA, Wockhardt has represented to the FDA that its product contains the same active ingredient, dosage form, and strength as Eliquis® and is bioequivalent to Eliquis® (Compl. ¶15).
  • Wockhardt seeks approval to market its product for the same indications as Eliquis®, which include the treatment and prevention of various thromboembolic disorders (Compl. ¶¶12, 16). The filing of the ANDA itself is the statutory act of infringement alleged under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶21).

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed element-by-element infringement analysis, which is typical for an initial complaint in an ANDA case filed before discovery. The infringement theory is predicated on the allegation that for Wockhardt’s product to be bioequivalent to Eliquis®, as represented in its ANDA, it must necessarily possess the formulation characteristics claimed in the ’945 patent.

’945 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A solid pharmaceutical composition comprising a therapeutically effective amount of crystalline apixaban particles... The Wockhardt ANDA product is a solid tablet containing apixaban, intended as a generic version of Eliquis®. ¶2, ¶15 col. 9:50-52
wherein the crystalline apixaban particles have a D90 equal to or less than about 89 µm... The complaint alleges that Wockhardt’s product is bioequivalent to Eliquis®; the infringement theory implies that achieving this bioequivalence requires the use of apixaban particles meeting this size limitation. ¶15 col. 9:53-55
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. The complaint alleges that Wockhardt’s product is bioequivalent to Eliquis®; the infringement theory implies that this requires meeting the claimed dissolution rate, which the patent identifies as the threshold for consistent in-vivo exposure. ¶15 col. 9:56-59

Identified Points of Contention

  • Technical Question: The complaint does not provide direct evidence of the accused product's physical characteristics. A central factual question is whether the Wockhardt ANDA product actually has a particle size D90 of "about 89 µm" or less and meets the claimed dissolution profile. The patent includes Figure 3, a graph plotting the percentage of apixaban dissolved in 30 minutes against the drug substance particle size (D90), which illustrates the claimed relationship between smaller particle size and faster dissolution (’945 Patent, Fig. 3). The case will depend on whether discovery into the confidential ANDA file confirms that Wockhardt's formulation falls within the parameters taught and claimed by the patent.
  • Legal & Factual Question: A key dispute may center on whether achieving bioequivalence necessarily requires infringement. Wockhardt could argue that it "designed around" the patent, achieving bioequivalence through an alternative, non-infringing formulation (e.g., by using different excipients or a manufacturing process that yields a bioequivalent profile without meeting the D90 and dissolution limitations).

V. Key Claim Terms for Construction

  • The Term: "a D90 equal to or less than about 89 µm"
  • Context and Importance: This term is the primary quantitative limitation of the independent claims and is central to the patent's purported solution for achieving consistent bioavailability. Practitioners may focus on the word "about" because its scope could be dispositive if the accused product's particle size is near the 89 µm threshold.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent's use of the term "about" suggests the patentee did not intend a strict, absolute numerical cutoff (’945 Patent, col. 2:53). Further, data in the patent shows some variability, which a party might argue supports a more flexible range around the stated value (’945 Patent, Fig. 4).
    • Evidence for a Narrower Interpretation: The specification repeatedly identifies 89 µm as the key discovery: "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). A party could argue that this specific value, derived from the patentee's experimental work, represents a critical threshold and that "about" should be given a very narrow scope.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon approval, Wockhardt's commercial manufacture, use, and sale would induce and/or contribute to infringement by others (Compl. ¶¶22, 23). This allegation is based on the premise that the product's labeling would instruct medical professionals and patients to administer the drug for its approved indications, leading to direct infringement by the end-users.
  • Willful Infringement: The complaint does not explicitly use the term "willful infringement." However, it establishes a basis for pre-suit knowledge of the ’945 patent by citing Wockhardt's Paragraph IV notice letter, received by Plaintiffs on or after March 2, 2017 (Compl. ¶13). It also seeks relief under 35 U.S.C. § 285, which pertains to exceptional cases (Compl. Prayer for Relief ¶5).

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

  1. A central issue will be one of factual proof: does the Wockhardt ANDA product, the formulation of which is detailed in its confidential FDA filing, actually meet the particle size (D90 ≤ "about" 89 µm) and dissolution rate (≥77% in 30 min) limitations of the asserted claims?
  2. The case will likely involve a key question of causal linkage: can Plaintiffs demonstrate that achieving bioequivalence to the Eliquis® product necessarily requires practicing the claimed invention, or can Wockhardt show that it engineered a bioequivalent formulation that successfully "designs around" the patent's specific limitations?
  3. A critical legal question for the court will be one of definitional scope: how should the term "about 89 µm" be construed? The interpretation of this term will define the boundary of the claim and may determine whether Wockhardt’s product, if its particle size is close to the line, is ultimately found to infringe.