Bristol Myers Squibb Co v. Emcure Pharma Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Bristol-Myers Squibb Company (Delaware); Pfizer Inc. (Delaware)
  • Defendant: Emcure Pharmaceuticals Ltd. (India)
  • Plaintiff’s Counsel: Farnan, LLP; Wilmer Cutler Pickering Hale and Dorr LLP
• Case Identification: 1:17-cv-00402, D. Del., 04/10/2017
• Venue Allegations: Defendant, through counsel, agreed not to contest jurisdiction or venue in the District of Delaware.
• Core Dispute: Plaintiffs allege that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for a generic version of the anticoagulant drug Eliquis® constitutes a technical act of infringement of a patent related to specific apixaban formulations.
• Technical Context: The technology concerns pharmaceutical formulations for low-solubility drugs, specifically how controlling the active ingredient's particle size distribution can ensure consistent dissolution rates and predictable bioavailability.
• Key Procedural History: This action is a Hatch-Waxman lawsuit initiated in response to a "Notice Letter" from the Defendant. In that letter, Defendant made a "Paragraph IV certification" asserting that the patent-in-suit is invalid, unenforceable, and/or will not be infringed by its proposed generic product.

Case Timeline

Date	Event
2010-02-25	’945 Patent Priority Date
2016-05-03	U.S. Patent No. 9,326,945 Issued
2017-03-06	Defendant sends Paragraph IV Certification 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"

• Patent Identification: U.S. Patent No. 9,326,945, "Apixaban Formulations," issued May 3, 2016.

The Invention Explained

• Problem Addressed: The patent addresses a challenge with the oral administration of apixaban, a Factor Xa inhibitor with low aqueous solubility. Standard biopharmaceutical models predicted that particle size would not be critical for achieving consistent drug absorption. However, the inventors found that formulations using large particles of apixaban resulted in "less than optimal exposures," creating potential quality control and therapeutic consistency problems (’945 Patent, col. 1:43-62).
• The Patented Solution: The patent discloses the "surprising and unexpected" discovery that controlling the crystalline apixaban particle size distribution to a D90 (where 90% of particles are smaller than a given diameter) of less than 89 microns (µm) leads to consistent in-vivo dissolution and reliable therapeutic effect (’945 Patent, col. 2:6-15, 45-59). The invention is thus a solid pharmaceutical formulation containing apixaban particles meeting this specific size requirement, which in turn achieves a minimum dissolution rate (’945 Patent, Abstract).
• Technical Importance: This approach provides a method for formulating a low-solubility drug to ensure consistent patient exposure, which is particularly critical for an anticoagulant where under- or over-dosing can have severe clinical consequences (’945 Patent, col. 2:1-5).

Key Claims at a Glance

• The complaint asserts independent claim 1.
• The essential elements of independent claim 1 are:
  • A solid pharmaceutical composition comprising a therapeutically effective amount of crystalline apixaban particles and 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.
• The complaint reserves the right to assert dependent claims 9-12, 20-23, 25, 27, 29, 31, 33, 35, and 37 (Compl. ¶19).

III. The Accused Instrumentality

Product Identification

The "Emcure ANDA product," which comprises proposed 2.5 mg and 5 mg tablets of apixaban intended as generic versions of Plaintiffs' Eliquis® drug product (Compl. ¶2).

Functionality and Market Context

The complaint alleges that by filing ANDA No. 209849, Defendant has represented to the FDA that its product has the same active ingredient, dosage form, and strength as Eliquis®, and that it is bioequivalent to Eliquis® (Compl. ¶13). The act of infringement alleged is the submission of the ANDA itself under 35 U.S.C. § 271(e)(2)(A), which allows for infringement litigation to occur before the generic product is marketed (Compl. ¶19). The accused product seeks to compete with Eliquis®, a treatment for thromboembolic disorders (Compl. ¶¶5, 10).

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart. The infringement allegations are based on the premise that to be approved as a generic equivalent to Eliquis®, Defendant's product must necessarily meet the physical and functional limitations of the asserted claims, which Plaintiffs allege cover the commercial Eliquis® product. No probative visual evidence provided in complaint.

’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...	Defendant’s ANDA product is a solid tablet formulation containing apixaban as the active pharmaceutical ingredient.	¶¶2, 13	col. 11:50-52
wherein the crystalline apixaban particles have a D90 equal to or less than about 89 µm...	The complaint alleges, upon information and belief, that Defendant's product contains apixaban particles meeting this size limitation, asserting this is necessary to achieve bioequivalence with the branded Eliquis® product.	¶¶13, 19	col. 11:53-55
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, upon information and belief, that Defendant's product meets this dissolution profile, a characteristic also asserted as necessary for establishing bioequivalence.	¶¶13, 19	col. 11:56-59

Identified Points of Contention

• Technical Questions: A central question is factual: does the formulation described in Defendant's confidential ANDA actually meet the D90 particle size and dissolution rate limitations of claim 1? The litigation will depend on the comparison of the accused product's physical characteristics, as revealed in discovery, with the specific claim requirements.
• Scope Questions: The case may raise the question of whether Defendant's formulation must infringe in order to be "bioequivalent" to Eliquis®. Defendant may argue that it can achieve bioequivalence through an alternative formulation that does not meet every limitation of the asserted claims.

V. Key Claim Terms for Construction

The Term

"D90 equal to or less than about 89 µm"

Context and Importance

This term is the central, structural limitation of the invention. The infringement analysis will likely depend entirely on whether the particle size of Defendant's product falls within the scope of this limitation. Practitioners may focus on this term because the word "about" introduces a degree of ambiguity, and the outcome could hinge on how much deviation from "89 µm" is permitted.

Intrinsic Evidence for Interpretation

• Evidence for a Broader Interpretation: The use of "about" itself suggests the patentee did not intend to be limited to a precise value. The specification also notes that dissolution results have "typical variability (RSD=2 to 3%)" (’945 Patent, col. 9:44-46), which could be argued to support a wider numerical range around 89 µm.
• Evidence for a Narrower Interpretation: The specification repeatedly identifies 89 µm as the key threshold discovered by the inventors, stating "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). The patent also highlights preferable embodiments with much smaller particle sizes (e.g., less than 50 µm or 25 µm), which could be used to argue that the inventive contribution is centered on particles well below the 89 µm ceiling (’945 Patent, col. 2:19-22).

VI. Other Allegations

Indirect Infringement

The complaint alleges that upon approval, Defendant's commercial activities would induce infringement by healthcare providers and patients and contribute to infringement by others (Compl. ¶¶20-21). The basis for inducement is the allegation that Defendant would market its product with prescribing information for the same indications as Eliquis®, thereby instructing users to infringe (Compl. ¶14).

Willful Infringement

The complaint does not contain an explicit allegation of willful infringement. However, it establishes a basis for knowledge by noting that Defendant sent a notice letter acknowledging the patent-in-suit prior to the litigation (Compl. ¶¶11, 15). Plaintiffs request damages and relief under 35 U.S.C. § 285 for exceptional cases (Compl. p. 6, ¶5).

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

• A central issue will be one of factual evidence: Does Defendant's proposed generic formulation, as described in its confidential ANDA, possess the claimed particle size distribution (a D90 of "about 89 µm" or less) and the corresponding dissolution profile (at least 77% in 30 minutes)? The case outcome will heavily rely on the results of testing Defendant's product.
• A second core issue will be one of claim construction: How broadly will the court interpret the term "about 89 µm"? The resolution of this question could be dispositive if Defendant's product has a particle size that is close to, but not strictly below, the 89 µm value.
• A third key question will be one of validity: Although not detailed in the complaint, Defendant has certified that the patent is invalid. The court will need to assess whether the claimed formulation was obvious over the prior art, weighing the patent's narrative of "surprising and unexpected" results against what a person of ordinary skill would have expected from standard pharmaceutical development principles.