DCT

1:24-cv-01089

Bristol Myers Squibb Co v. Umedica Laboratories Pvt Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-01089, D. Del., 09/30/2024
  • Venue Allegations: Venue is asserted on the basis that the defendant is a foreign corporation subject to personal jurisdiction in the district, to which it has consented.
  • Core Dispute: Plaintiffs allege that Defendant’s 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 technology concerns pharmaceutical formulations for apixaban, a poorly water-soluble drug, defining specific particle size and dissolution characteristics to ensure consistent bioavailability and therapeutic effect in patients.
  • Key Procedural History: This is a Hatch-Waxman action triggered by an ANDA filing. The complaint notes that the patent-in-suit was previously litigated in the District of Delaware, where it was found valid and infringed, a decision that was subsequently affirmed by the U.S. Court of Appeals for the Federal Circuit. This history may significantly influence claim construction and validity analyses in the current case.

Case Timeline

Date Event
2010-02-25 ’945 Patent Priority Date
2016-05-03 '945 Patent Issue Date
2024-09-04 Umedica ANDA Notice Letter Date
2024-09-06 Plaintiffs' Receipt of ANDA Notice Letter
2024-09-30 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 challenge of achieving consistent drug exposure for apixaban, a Factor Xa inhibitor. Although apixaban's dose and low aqueous solubility would not typically suggest that particle size is critical, the inventors determined that formulations using certain processes or larger drug particles led to "less than optimal exposures" and potential "quality control challenges" ('945 Patent, col. 1:45-62).
  • The Patented Solution: The inventors "surprisingly and unexpectedly" discovered that controlling the crystalline apixaban particle size to a D90 (where 90% of the particles by volume are smaller than a given diameter) of less than 89 microns (µm) results in "consistent in-vivo dissolution in humans" ('945 Patent, col. 1:63-68; col. 2:8-12). This specific particle size control, combined with a defined dissolution rate, ensures a consistent therapeutic effect ('945 Patent, col. 2:1-5).
  • Technical Importance: For a potent anticoagulant, consistent bioavailability is critical to balance efficacy (preventing blood clots) and safety (avoiding bleeding events); the invention purports to provide a formulation that reliably achieves this consistency for an oral solid dosage form ('945 Patent, col. 2:1-5).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claims 9-12, 20-23, 25, 27, 29, 31, 33, 35, and 37 (Compl. ¶21).
  • 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.

III. The Accused Instrumentality

Product Identification

  • Umedica’s proposed generic apixaban tablets (2.5 mg and 5 mg), as described in its Abbreviated New Drug Application (ANDA) No. 219640 (Compl. ¶2).

Functionality and Market Context

  • The accused instrumentality is an ANDA filing seeking FDA approval to market a generic version of Plaintiffs' Eliquis® drug product (Compl. ¶2). By filing the ANDA, Umedica represents that its product has the same active ingredient (apixaban), dosage form, and strength as Eliquis®, and is bioequivalent to it (Compl. ¶15). The product is intended for the same indications, including the treatment and prevention of thromboembolic disorders (Compl. ¶16).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

  • Claim Chart Summary: The complaint’s infringement allegations for the sole asserted independent claim are summarized below.

’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 Umedica ANDA product is alleged to be an "oral tablet" containing 2.5 mg or 5 mg of apixaban, which is a "solid pharmaceutical composition" with a "therapeutically effective amount of crystalline apixaban" and a "pharmaceutically acceptable diluent or carrier." ¶24 col. 2:8-12
wherein the crystalline apixaban particles have a D90 equal to or less than about 89 µm The Umedica ANDA product allegedly contains crystalline apixaban particles that "have a D90 equal to or less than about 89 µm." ¶24 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 Umedica ANDA product allegedly meets the dissolution profile where "at least 77 wt % of apixaban dissolves with 30 minutes in a pH 6.8 phosphate buffer containing 0.05% sodium lauryl sulfate." ¶24 col. 10:25-29
  • Identified Points of Contention:
    • Scope Questions: The primary infringement dispute may focus on the term "about 89 µm." The actual particle size distribution in Umedica’s ANDA product will determine whether it falls within the scope of this limitation, including any range afforded by the word "about."
    • Technical Questions: The central technical question is whether Umedica's product, as detailed in its confidential ANDA submission, factually meets the claimed D90 particle size and dissolution rate limitations. The complaint alleges that Umedica’s notice letter "did not substantively contest infringement of any claim of the '945 patent," suggesting this may not be the primary area of dispute (Compl. ¶24).

V. Key Claim Terms for Construction

  • The Term: "D90 equal to or less than about 89 µm"
    • Context and Importance: This term defines the core of the invention. Its construction, particularly the scope of "about," is central to the infringement analysis. Practitioners may focus on this term because it was likely a key issue in the prior litigation involving the '945 patent (Compl. ¶11).
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent's discussion of a particle size of 119 µm yielding dissolution "marginally greater than 77%" and the statement that the claimed threshold "allows for the typical variability" in testing could support a construction where "about" provides some flexibility above the 89 µm value ('945 Patent, col. 10:40-46).
      • Evidence for a Narrower Interpretation: The specification repeatedly identifies 89 µm as the key threshold discovered by the inventors (e.g., "the particle size that impacts apixaban absorption rate is about a D90 of 89 µm") and uses the phrase "not exceeding 89 µm," which could support a construction that gives "about" little to no range ('945 Patent, col. 2:13-14, col. 2:56-58).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges inducement of and contribution to infringement (Compl. ¶22). The factual basis is Umedica's future sale of its ANDA product with a label that will necessarily instruct physicians and patients to use the product in an infringing manner for its approved indications (Compl. ¶23).
  • Willful Infringement: The complaint does not contain an explicit allegation of willful infringement. However, it pleads facts that could support a finding of knowledge, including the listing of the '945 patent in the FDA's Orange Book and Umedica's September 4, 2024 notice letter acknowledging the patent (Compl. ¶¶12, 13, 17).

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

  • The Precedential Effect of Prior Litigation: A dispositive issue will be the impact of the prior federal court rulings that upheld the validity of the '945 patent. The court will need to determine whether principles of collateral estoppel bar Umedica from re-litigating validity issues and, if not, how much deference to give the prior reasoned claim construction and validity findings.
  • The Viability of a New Invalidity Challenge: The central conflict will likely be Umedica's attempt to invalidate the patent, as asserted in its notice letter (Compl. ¶17). The key question is whether Umedica can introduce new prior art or arguments sufficiently distinct and compelling to overcome not only the patent's statutory presumption of validity but also the weight of the previous judicial affirmations of its validity.
  • The Factual Basis of Infringement: While the complaint suggests infringement may not be substantively contested, a key evidentiary question remains: does the technical data within Umedica's confidential ANDA submission demonstrate that its proposed generic product meets the specific "D90" particle size and dissolution rate limitations recited in the asserted claims?