Bristol Myers Squibb Co v. ScieGen Pharma Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Bristol-Myers Squibb Company (Delaware) and Pfizer Inc. (Delaware)
  • Defendant: ScieGen Pharmaceuticals, Inc. (New York)
  • Plaintiff’s Counsel: Farnan, LLP; Wilmer Cutler Pickering Hale and Dorr LLP
• Case Identification: 1:23-cv-00393, D. Del., 04/06/2023
• Venue Allegations: The complaint asserts that Defendant, through counsel, agreed by email not to contest personal 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 an act of patent infringement under the Hatch-Waxman Act.
• Technical Context: The technology concerns pharmaceutical formulations of apixaban, a Factor Xa inhibitor, focusing on specific particle size and dissolution characteristics to ensure consistent drug exposure in patients.
• Key Procedural History: The complaint notes that the patent-in-suit was previously the subject of litigation in the District of Delaware, where it was found to be valid and infringed, a decision that was subsequently affirmed by the U.S. Court of Appeals for the Federal Circuit.

Case Timeline

Date	Event
2010-02-25	’945 Patent Priority Date
2016-05-03	’945 Patent Issue Date
2020-08-05	Prior litigation finding '945 patent valid and infringed (D. Del.)
2021-09-13	Prior litigation decision affirmed on appeal (Fed. Cir.)
2023-03-03	Defendant sent ANDA notice letter to Plaintiffs
2023-04-06	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 an unexpected issue with the oral drug apixaban. Based on its aqueous solubility, standard biopharmaceutical principles predicted that the particle size of the drug substance should not be critical for achieving consistent absorption in the body (’945 Patent, col. 1:44-55). However, the inventors discovered that formulations made using certain processes (wet granulation) or with larger apixaban particles resulted in "less than optimal exposures," creating potential "quality control challenges" (’945 Patent, col. 1:55-62).
• The Patented Solution: The invention is a solid pharmaceutical formulation comprising crystalline apixaban particles where 90% of the particles by volume ("D90") have a diameter no larger than approximately 89 microns (µm) (’945 Patent, Abstract; col. 2:7-17). The specification explains that controlling the particle size to this fine level, especially when combined with a dry granulation manufacturing process, facilitates "consistent in-vivo dissolution," which in turn leads to consistent and predictable drug exposure and therapeutic effect in patients (’945 Patent, col. 2:1-6, 55-62).
• Technical Importance: For an anticoagulant like apixaban, inconsistent absorption can be dangerous, leading to either an increased risk of blood clots (under-dosing) or bleeding (over-dosing); the invention provides a formulation strategy to ensure reliable therapeutic performance.

Key Claims at a Glance

• The complaint asserts independent claims 1 and 12, among other dependent claims (Compl. ¶ 20).
• Independent Claim 1:
  • 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.
• Independent Claim 12:
  • A solid pharmaceutical composition comprising a therapeutically effective amount of apixaban and a pharmaceutically acceptable diluent or carrier,
  • wherein apixaban comprises crystalline apixaban particles,
  • wherein the crystalline apixaban particles have a "D90" equal to or less than about 89 µm, and
  • wherein, as measured using a USP Apparatus 2 at a paddle rotation speed of 75 rpm in 900 mL, of a dissolution medium at 37° C., at least 77 wt % of apixaban in the pharmaceutical composition dissolves within 30 minutes in the dissolution medium, and the dissolution medium is 0.05 M sodium phosphate at a pH 6.8 containing 0.05% sodium lauryl sulfate.
• The complaint reserves the right to assert additional claims (Compl. ¶ 20).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Defendant ScieGen’s proposed generic apixaban product in 2.5 mg and 5 mg tablets, as described in ANDA No. 218119 (Compl. ¶ 2).

Functionality and Market Context

The complaint alleges that by filing its ANDA, ScieGen has necessarily represented to the FDA that its proposed product has the same active ingredient, dosage form, and strength as Plaintiffs' "Eliquis®" product and is bioequivalent to it (Compl. ¶ 14). The product is intended to be marketed for the same medical indications as "Eliquis®", namely the treatment and prevention of thromboembolic disorders (Compl. ¶¶ 11, 15). The filing of the ANDA itself, seeking approval to market this product before the expiration of the ’945 patent, constitutes the act of infringement alleged in the complaint (Compl. ¶ 20).

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed, element-by-element infringement analysis or a claim chart exhibit. The infringement allegation is premised on the statutory framework of the Hatch-Waxman Act, where the submission of an ANDA is a technical act of infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶ 20). The central theory is that for ScieGen’s ANDA product to be approved as a generic equivalent of "Eliquis®", it must necessarily possess the same formulation characteristics, including the particle size and dissolution profile, that are claimed in the ’945 patent, which is listed in the FDA's Orange Book as covering the "Eliquis®" product (Compl. ¶¶ 11, 14). The complaint alleges that upon FDA approval, ScieGen will directly and indirectly infringe the ’945 patent by making, using, and selling the ANDA product (Compl. ¶ 22).

No probative visual evidence provided in complaint.

V. Key Claim Terms for Construction

• The Term: "a D90 equal to or less than about 89 µm"
• Context and Importance: This limitation is the central technical feature of the invention, defining the specific particle size discovered to be critical for consistent drug absorption. The infringement analysis will depend entirely on whether the particle size in ScieGen's ANDA product falls within the scope of this term. Practitioners may focus on this term because the word "about" introduces indefiniteness, and the 89 µm value is presented as a specific, empirically derived threshold.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The use of the word "about" suggests the 89 µm value is not a rigid, absolute ceiling, but rather a close approximation (’945 Patent, col. 11:10). The specification also discloses several more preferred, smaller particle size ranges (e.g., "D90 less than 50 µm"), which could imply that 89 µm is an approximate outer boundary of a broader inventive concept (’945 Patent, col. 2:19-22).
  • Evidence for a Narrower Interpretation: The specification repeatedly and specifically identifies the 89 µm "D90" value as the key discovery that "impacts apixaban absorption rate" (’945 Patent, col. 2:56-58). Figures 3 and 4 graphically depict dissolution rates as a function of particle size, appearing to show a performance drop-off for particles larger than this size, and the patent states that controlling size to "less than 89 microns will result in a dissolution rate that will ensure consistent in-vivo exposures" (’945 Patent, col. 9:30-34). This could support an argument that 89 µm is a critical, meaningful threshold.

VI. Other Allegations

Indirect Infringement

The complaint alleges that ScieGen's future commercial activities would constitute induced and contributory infringement (Compl. ¶¶ 21-22). The basis for this allegation is that ScieGen will market its product with a label instructing medical professionals and patients to administer the drug for its approved indications, thereby encouraging and enabling an infringing use.

Willful Infringement

While the complaint does not explicitly use the term "willful," it establishes a basis for such a claim. It pleads that ScieGen had knowledge of the ’945 patent no later than its receipt of the notice letter on March 4, 2023 (Compl. ¶ 12). Furthermore, the complaint highlights the prior federal court decisions upholding the patent's validity and infringement, suggesting that Defendant was or should have been aware of the patent and the high risk of infringement before filing its ANDA (Compl. ¶ 10).

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

• A primary issue will be one of factual proof: does ScieGen's proposed generic formulation, as described in its confidential ANDA submission, in fact contain crystalline apixaban particles with a "D90" of "about 89 µm" or less and exhibit the dissolution profile required by the asserted claims? The case will likely depend on the comparison of ScieGen’s product specifications against the patent’s claim limitations.

• A second central question will be legal preclusion: given that the ’945 patent has already survived a validity and infringement challenge in the same court, to what extent can ScieGen raise defenses that were, or could have been, litigated in the prior case? The court will likely have to determine if ScieGen can present a novel non-infringement argument or a legally distinct invalidity theory that is not barred by the earlier adjudication.