Bristol Myers Squibb Co v. Sunshine Lake Pharma Co Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Bristol-Myers Squibb Company (Delaware) and Pfizer Inc (Delaware)
  • Defendant: Sunshine Lake Pharma Co., Ltd. (China); Sunshine Lake LLC (Delaware); and HEC Pharm USA Inc. (New Jersey)
  • Plaintiff’s Counsel: Farnan LLP
• Case Identification: 1:17-cv-00380, D. Del., 04/05/2017
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendants are subject to personal jurisdiction in the district, have allegedly committed acts of infringement there, and one Defendant (Sunshine LLC) is a Delaware entity.
• Core Dispute: Plaintiffs allege that Defendants' Abbreviated New Drug Application (ANDA) to market a generic version of the anticoagulant drug Eliquis® (apixaban) constitutes an act of infringement of a patent directed to specific apixaban formulations.
• Technical Context: The technology concerns pharmaceutical formulations for the poorly water-soluble drug apixaban, focusing on controlling particle size to ensure consistent drug absorption, which is critical for the safety and efficacy of an anticoagulant.
• Key Procedural History: This lawsuit was initiated under the Hatch-Waxman Act following Defendants' submission of an ANDA with a Paragraph IV certification, which asserts 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	U.S. Patent No. 9,326,945 Issued
2017-03-06	Defendants sent Eliquis® Notice Letter to Plaintiffs
2017-04-05	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. (Compl. ¶18).

The Invention Explained

• Problem Addressed: The patent addresses the problem of inconsistent patient exposure to the drug apixaban. Although theoretical models suggested that particle size should not be critical for low-dose apixaban tablets, the inventors determined that formulations using large drug particles or certain manufacturing processes resulted in "less than optimal exposures," creating "quality control challenges." ('945 Patent, col. 1:46-62).
• The Patented Solution: The invention is a pharmaceutical formulation of apixaban that uses crystalline drug particles with a specific, controlled maximum size (D90 less than 89 microns). The inventors state it was "surprisingly and unexpectedly" found that this particle size control leads to "consistent in-vivo dissolution in humans," ensuring a predictable and consistent therapeutic effect similar to that of a liquid solution. ('945 Patent, col. 1:63-col. 2:5).
• Technical Importance: For an antithrombotic agent like apixaban, achieving consistent drug absorption is critical to maintain a therapeutic window that balances preventing blood clots with avoiding the risk of severe bleeding. ('945 Patent, col. 1:39-45).

Key Claims at a Glance

• The complaint asserts independent claims 1 and 12, among others. (Compl. ¶28).
• Independent Claim 1 is directed to a solid pharmaceutical composition with three key elements:
  • It contains a therapeutically effective amount of crystalline apixaban particles.
  • The crystalline apixaban particles have a D90 (a measure where 90% of the particle volume has a diameter below a certain value) equal to or less than about 89 µm.
  • The composition exhibits a specific dissolution profile: at least 77% of the apixaban dissolves within 30 minutes under specified test conditions.
• Independent Claim 12 is similar but recites the dissolution testing conditions in greater detail. (Compl. ¶28; '945 Patent, col. 11:12-28).
• The complaint reserves the right to assert numerous dependent claims. (Compl. ¶¶28-30).

III. The Accused Instrumentality

Product Identification

• The accused instrumentality is the "Sunshine ANDA product," which consists of 2.5 mg and 5 mg tablets of apixaban as described in Abbreviated New Drug Application (ANDA) No. 209944. (Compl. ¶2).

Functionality and Market Context

• The product is a proposed generic version of Plaintiffs' Eliquis® drug product. (Compl. ¶2). By filing the ANDA, Defendants have represented to the U.S. Food and Drug Administration (FDA) that their product has the same active ingredient, dosage form, and strength as Eliquis®, and is bioequivalent to it. (Compl. ¶22). The product is intended for the same medical indications as Eliquis®, including the reduction of stroke risk and treatment of thromboembolic disorders, and seeks to enter the market prior to the expiration of the '945 Patent. (Compl. ¶¶2, 19, 23).

IV. Analysis of Infringement Allegations

The complaint does not contain a detailed claim chart but bases its infringement allegations on Defendants' representation of bioequivalence to the FDA. The theory is that a product bioequivalent to Eliquis® must necessarily practice the invention claimed in the '945 Patent. (Compl. ¶22).

'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 accused Sunshine ANDA product is a solid tablet containing apixaban. The complaint alleges that by seeking approval for a generic version of Eliquis®, Defendants' product is intended to have a therapeutic effect.	¶2	col. 5:6-14
wherein the crystalline apixaban particles have a D90 equal to or less than about 89 µm...	The complaint alleges that because the Sunshine ANDA product is represented as bioequivalent to Eliquis®, it must have the same characteristics that provide consistent exposure, which the patent teaches is achieved by controlling the particle size to have a D90 of less than about 89 µm.	¶22	col. 2:9-12
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's bioequivalence allegation suggests that the Sunshine ANDA product must exhibit the dissolution profile required by the claim, as the patent identifies this dissolution rate as the "threshold for achieving consistent exposure" and thus bioequivalence with the originator product.	¶22	col. 11:25-28

Identified Points of Contention

• Scope Questions: The infringement analysis may turn on the interpretation of "about 89 µm." The extent to which this term permits deviation from the 89 µm value could be a central point of dispute, depending on the precise particle size specifications contained in Defendants' confidential ANDA.
• Technical Questions: A key evidentiary question is whether Defendants' representation of bioequivalence is sufficient to prove infringement of the specific claim limitations. The case will likely require an examination of the confidential ANDA file to determine if the specified formulation for the "Sunshine ANDA product" explicitly meets the particle size and dissolution rate limitations of the asserted claims.
• No probative visual evidence provided in complaint.

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 technical limitation of the invention. Practitioners may focus on this term because the infringement determination will likely depend on whether the particle size distribution of the accused generic product, as defined in its ANDA, falls within the scope of this limitation, with the word "about" being a key area of potential dispute.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The patent's use of the word "about" suggests the 89 µm value is not an absolute, sharp cutoff. The specification notes that the "invention can indeed be viewed in alternative terms as a composition comprising crystalline apixaban particles having a mean particle size equal to or less than about 89 µm." ('945 Patent, col. 4:60-63). This phrasing may support a more flexible boundary.
  • Evidence for a Narrower Interpretation: The specification repeatedly emphasizes the 89 µm figure as a critical discovery. The abstract recites "D90 equal to or less than 89 µm," and the summary of the invention states, "[i]t has surprisingly been found, however, that the particle size that impacts apixaban absorption rate is about a D90 of 89 µm." ('945 Patent, Abstract; col. 2:52-54). The patent's figures also graphically depict this value as a key inflection point for achieving desired dissolution. ('945 Patent, Figs. 3 & 4).

VI. Other Allegations

• Indirect Infringement: The complaint alleges that Defendants' future commercial sale of the ANDA product will induce infringement by medical professionals and patients who use the product according to its FDA-approved label. (Compl. ¶¶29-30). It also alleges contributory infringement. (Compl. ¶29).
• Willful Infringement: While the complaint does not use the word "willful," it alleges Defendants had knowledge of the '945 Patent through its listing in the FDA's Orange Book and through the notice letter sent by Plaintiffs. (Compl. ¶¶19-20). The prayer for relief requests an award of attorneys' fees under 35 U.S.C. § 285, a remedy typically sought in cases involving allegations of egregious infringement conduct. (Compl. p. 9, ¶5).

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

• A central issue will be one of definitional scope: can the term "about 89 µm" be construed to cover the particle size distribution specified in the Defendants' ANDA? The outcome may hinge on whether the Defendants' formulation is found to be on the borderline of this limitation, making the interpretation of "about" determinative.
• The case will also present a key evidentiary question: is the allegation of bioequivalence, as stated in the ANDA filing, a sufficient basis to establish that the accused product meets the specific, quantitative limitations of the asserted claims? The dispute will likely move beyond the general representation of bioequivalence to a direct comparison of the product specifications in the confidential ANDA with the patent's claim limitations.