DCT

1:17-cv-00401

Bristol Myers Squibb Co v. DR Reddys Laboratories Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00401, D. Del., 04/10/2017
  • Venue Allegations: Venue is based on Defendants’ agreement, via email, not to contest jurisdiction or venue in the District of Delaware.
  • Core Dispute: Plaintiffs allege that Defendants’ 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 apixaban.
  • Technical Context: The case concerns pharmaceutical formulations for apixaban, a Factor Xa inhibitor used to treat and prevent thromboembolic disorders, focusing on how particle size affects the drug's dissolution and bioavailability.
  • Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act, triggered by a notice letter from Defendants informing Plaintiffs of the submission of ANDA No. 210082. This ANDA contains a Paragraph IV certification, asserting that the patent-in-suit is invalid, unenforceable, or will not be infringed by the proposed generic product. Such a filing is a statutory act of infringement under 35 U.S.C. § 271(e)(2).

Case Timeline

Date Event
2010-02-25 ’945 Patent Priority Date
2016-05-03 ’945 Patent Issue Date
2017-03-09 Defendant sent ANDA Notice Letter to Plaintiffs
2017-03-10 Plaintiffs received ANDA Notice Letter
2017-03-27 Defendant agreed not to contest jurisdiction or venue
2017-04-10 Complaint Filing Date

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

U.S. Patent No. 9,326,945 - “Apixaban Formulations”

  • Patent Identification: 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 apixaban formulations made with large drug particles, or through a wet granulation process, resulted in "less than optimal exposures" in patients, despite predictions that particle size would not be critical based on the drug's aqueous solubility (’945 Patent, col. 1:46-62). This variability could present "quality control challenges" and lead to inconsistent therapeutic effects.
  • The Patented Solution: The invention is a solid pharmaceutical composition of crystalline apixaban where the particles have a D90 (meaning 90% of the particles by volume have a diameter less than this value) of no more than approximately 89 micrometers (µm). This specific particle size control, preferably combined with a dry granulation process, is disclosed to achieve "consistent in-vivo dissolution" and therefore consistent and predictable drug absorption in patients (’945 Patent, col. 2:1-5, col. 2:56-62).
  • Technical Importance: The invention provides a method to ensure reliable bioavailability for an orally administered antithrombotic agent, overcoming previously observed inconsistencies in drug exposure that could compromise patient safety and therapeutic efficacy (’945 Patent, col. 1:40-44).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶20).
  • Essential elements of independent claim 1 include:
    • A solid pharmaceutical composition comprising a therapeutically effective amount of 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.
  • The complaint reserves the right to assert dependent claims, including claims 9-12, 20-23, 25, 27, 29, 31, 33, 35, and 37 (Compl. ¶20-22).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is the proposed generic apixaban product in 2.5 mg and 5 mg tablet form, as described in Defendants’ ANDA No. 210082 ("DRL ANDA product") (Compl. ¶2).

Functionality and Market Context

  • The DRL ANDA product is intended as a generic substitute for Plaintiffs' Eliquis® drug product (Compl. ¶2).
  • The complaint alleges that by filing the ANDA, Defendants have represented to the FDA that their product has the same active ingredient, dosage form, and strength as Eliquis®, and is bioequivalent to Eliquis® (Compl. ¶14).
  • The product is intended for the same approved indications as Eliquis®, which include the treatment and prevention of various thromboembolic disorders (Compl. ¶11, ¶15).

IV. Analysis of Infringement Allegations

The complaint does not contain a detailed claim chart. The infringement theory is predicated on the allegation that Defendants’ ANDA product, in order to be bioequivalent to Eliquis® as represented to the FDA, must necessarily practice the claims of 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 and a pharmaceutically acceptable diluent or carrier The DRL ANDA product is a solid tablet formulation containing apixaban in 2.5 mg and 5 mg strengths, which are therapeutically effective amounts (Compl. ¶2). ¶2, ¶14 col. 9:63-65
wherein the crystalline apixaban particles have a D90 equal to or less than about 89 µm The complaint alleges the DRL ANDA product is bioequivalent to Eliquis® (Compl. ¶14). The patent links this particle size limitation directly to achieving the consistent exposure necessary for bioequivalence (’945 Patent, col. 10:24-29). ¶14 col. 2:8-12
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 the DRL ANDA product is bioequivalent to Eliquis® (Compl. ¶14). The patent identifies this dissolution rate as the "threshold for achieving consistent exposure" (’945 Patent, col. 10:27-29). Figure 3 of the ’945 patent, attached as Exhibit A to the complaint, plots dissolution rates against drug substance particle size, illustrating the claimed relationship between these two parameters (’945 Patent, Fig. 3). ¶14 col. 10:24-29

Identified Points of Contention

  • Technical Questions: A primary question is evidentiary: what are the actual physical characteristics of the DRL ANDA product? Specifically, does the apixaban in Defendants' proposed generic have a particle size distribution (D90) of ≤ 89 µm and does it meet the claimed dissolution profile? The complaint relies on the legal representation of "bioequivalence" to infer these technical facts.
  • Scope Questions: The interpretation of "about 89 µm" may be a central dispute. The case may explore whether a product with a D90 marginally above 89 µm could still fall within the claim's scope. Similarly, the precise conditions of the dissolution test ("at least 77 wt %") could be scrutinized.

V. Key Claim Terms for Construction

The Term: "about 89 µm"

Context and Importance

This term defines the upper boundary for the particle size of the active ingredient, which the patent identifies as a critical parameter for achieving consistent drug exposure. The infringement analysis will likely depend on whether the particle size in Defendants' product falls within the range encompassed by "about 89 µm." Practitioners may focus on this term because infringement for numerical ranges often turns on the flexibility afforded by modifiers like "about."

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The patent’s use of the word "about" itself suggests the inventors did not intend a rigid, absolute cutoff. The specification notes the "typical variability (RSD=2 to 3%) in the dissolution results," which could be used to argue that the 89 µm figure is not an exact limit but rather a central point in a narrow range (’945 Patent, col. 10:43-46).
  • Evidence for a Narrower Interpretation: The patent repeatedly and specifically identifies 89 µm as the key value. The Summary of the Invention 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. 2:52-54). Figures 3 and 4 present experimental data showing a performance drop-off around this value. A party could argue that "about 89 µm" was intended to mean 89 µm, plus or minus standard experimental error, and not a significantly larger value.

VI. Other Allegations

Indirect Infringement

  • The complaint alleges that Defendants' future commercial activities would constitute induced and contributory infringement (Compl. ¶21, ¶22). The factual basis for these allegations is Defendants’ stated intent to market the DRL ANDA product for the same indications as Eliquis®, which would actively encourage and enable medical professionals and patients to use the product in an infringing manner (Compl. ¶15).

Willful Infringement

  • The complaint does not explicitly allege willful infringement or seek enhanced damages under 35 U.S.C. § 284. However, it establishes a basis for pre-suit knowledge of the patent by noting that Defendants sent Plaintiffs a notice letter on March 9, 2017, which included a certification asserting that the ’945 patent would not be infringed (Compl. ¶12, ¶16).

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

  • A primary issue will be one of evidentiary proof: Can Plaintiffs demonstrate, through discovery into Defendants’ ANDA, that the proposed generic apixaban product in fact contains crystalline particles with a D90 of "about 89 µm" or less and meets the claimed dissolution profile? The case will test the strength of inferring these technical properties from a regulatory representation of "bioequivalence."
  • The case will also involve a central question of claim scope: How will the court construe the term "about 89 µm"? The outcome of this construction could determine infringement, particularly if the particle size of the accused product is close to, but not exactly at or below, the 89 µm value.
  • A final question relates to the link between regulation and patent law: To what extent can the patentee rely on the alleged bioequivalence of an ANDA product to its own branded drug to establish, at the pleading and summary judgment stages, that the accused product meets the specific quantitative limitations of the asserted patent claims?