DCT
1:23-cv-00392
Bristol Myers Squibb Co v. Biocon Pharma Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Bristol-Myers Squibb Company (Delaware) and Pfizer Inc. (Delaware)
- Defendant: Biocon Pharma Limited (India)
- Plaintiff’s Counsel: Farnan, LLP; Wilmer Cutler Pickering Hale and Dorr LLP
- Case Identification: Bristol-Myers Squibb Co. v. Biocon Pharma Ltd., 1:23-cv-00392, D. Del., 04/06/2023
- Venue Allegations: Venue is asserted to be proper in the District of Delaware, and Defendant Biocon, through counsel, has agreed not to contest jurisdiction or venue in this matter.
- Core Dispute: Plaintiffs allege that Defendant’s proposed generic apixaban product, for which it seeks FDA approval via an Abbreviated New Drug Application (ANDA), will infringe a patent covering the formulation of Plaintiffs' branded drug, Eliquis®.
- Technical Context: The technology concerns pharmaceutical formulations for apixaban, an oral anticoagulant (Factor Xa inhibitor), designed to ensure consistent drug absorption and therapeutic effect.
- Key Procedural History: The complaint notes that the patent-in-suit was previously the subject of Hatch-Waxman litigation in the same court, where it was found to be valid and infringed by other generic drug manufacturers, a finding that was affirmed on appeal. This history may introduce questions of issue preclusion or 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 |
| 2020-08-05 | D. Del. finds ’945 patent valid and infringed in prior litigation |
| 2021-08-16 | Federal Circuit affirms D. Del. judgment in prior litigation |
| 2023-02-24 | Plaintiffs receive Biocon's Eliquis Notice Letter regarding its ANDA |
| 2023-04-06 | 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’s background section notes that while apixaban’s aqueous solubility would suggest that particle size should not be critical for consistent drug absorption, it was discovered that formulations made with a wet granulation process or using large particles of the drug substance resulted in "less than optimal exposures" (’945 Patent, col. 1:56-62). This created a risk of inconsistent therapeutic effects.
- The Patented Solution: The invention addresses this problem by defining a specific formulation for solid oral dosage forms of apixaban. The solution is a composition containing crystalline apixaban particles with a "D90" (meaning 90% of the particles by volume have a diameter less than this value) equal to or less than approximately 89 micrometers (µm) (’945 Patent, col. 2:6-16). This specific particle size limitation, combined with a defined dissolution rate, is taught to achieve "consistent in-vivo dissolution in humans" and thus a reliable therapeutic effect (’945 Patent, col. 2:1-5).
- Technical Importance: For an anticoagulant, ensuring consistent and predictable blood concentration is critical for balancing the drug's efficacy in preventing clots against the risk of causing dangerous bleeding; the patented formulation claims to provide this consistency (’945 Patent, col. 2:1-5).
Key Claims at a Glance
- The complaint asserts independent claims 1 and 12, along with numerous dependent claims (Compl. ¶20).
- Independent Claim 1 requires:
- 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 other claims, including dependent claims 9-11, 20-23, 25, 27, 29, 31, 33, 35, and 37 (Compl. ¶20).
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is the "Biocon ANDA product," which consists of 2.5 mg and 5 mg tablets of apixaban for which Biocon seeks FDA approval in ANDA No. 218106 (Compl. ¶2).
Functionality and Market Context
- The complaint alleges that by filing its ANDA, Biocon has represented to the FDA that its product has the same active ingredient (apixaban), dosage form, and strength as Plaintiffs' Eliquis® product and is bioequivalent to Eliquis® (Compl. ¶14). The product is intended to be a generic substitute for Eliquis®, marketed for the same approved indications, which include reducing the risk of stroke and treating thromboembolic disorders (Compl. ¶11, ¶15).
IV. Analysis of Infringement Allegations
The complaint does not contain a detailed claim chart. The infringement theory is based on the statutory framework of the Hatch-Waxman Act, where filing an ANDA for a generic drug that is bioequivalent to a branded product is a technical act of infringement if the branded product is covered by a valid patent. The core allegation is that because Biocon's product is represented as bioequivalent to Eliquis®, it will necessarily possess the formulation characteristics claimed in the ’945 patent (Compl. ¶14, ¶20).
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... | The Biocon ANDA product is alleged to be a solid tablet composition containing a therapeutically effective amount of crystalline apixaban, represented as having the same active ingredient and dosage form as Eliquis®. | ¶14, ¶20 | col. 11:50-53 |
| wherein the crystalline apixaban particles have a D90 equal to or less than about 89 µm... | The complaint alleges that because the Biocon ANDA product is represented as bioequivalent to Eliquis®, it will infringe the claims covering the Eliquis® formulation, which requires this particle size. | ¶14, ¶20 | col. 11:54-55 |
| 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 alleges that because the Biocon ANDA product is represented as bioequivalent to Eliquis®, it will infringe the claims covering the Eliquis® formulation, which requires this dissolution rate to achieve consistent exposure. | ¶14, ¶20 | col. 11:56-59 |
Identified Points of Contention
- Technical Questions: The primary dispute will be factual. Biocon has certified in its notice letter that the ’945 patent will not be infringed by its product (Compl. ¶16). This raises the question: what are the actual physical characteristics (i.e., particle size distribution and dissolution profile) of the Biocon ANDA product? The case will likely depend on expert testimony and testing of Biocon’s proposed generic tablets to determine if they meet the specific "D90" and dissolution rate limitations of the asserted claims.
- Scope Questions: The interpretation of the term "about 89 µm" could become a point of contention. The parties may dispute the degree of variance from 89 µm that is permissible under the term "about," which could be critical if Biocon’s product has a "D90" particle size close to this claimed boundary.
V. Key Claim Terms for Construction
- The Term: "crystalline apixaban particles have a D90 equal to or less than about 89 µm"
- Context and Importance: This term is the central technical limitation of the patent, defining the particle size required to achieve consistent drug absorption. The infringement analysis will turn entirely on whether Biocon’s product falls within this claimed range. Practitioners may focus on this term because the patent explicitly identifies it as the surprising solution to the problem of variable drug exposure (’945 Patent, col. 2:51-54).
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The use of the word "about" suggests the patentee did not intend 89 µm to be a strict, absolute cutoff. The specification describes a range of preferred sizes, such as "less than 50 µm" and "less than 30 µm," which could suggest that 89 µm is an outer boundary, not a precise figure (’945 Patent, col. 2:19-21).
- Evidence for a Narrower Interpretation: The patent 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). Figures 3 and 4 of the patent graphically illustrate the relationship between particle size and dissolution, tying performance directly to this numeric value.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that upon FDA approval, Biocon will induce and contribute to infringement by marketing and selling its generic product in the United States. The basis for this is that the product's labeling will instruct medical providers and patients to use it for the same patented indications as Eliquis®, thereby encouraging infringing acts (Compl. ¶22).
- Willful Infringement: The complaint does not contain an explicit allegation of willful infringement or a request for enhanced damages under 35 U.S.C. § 284.
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of factual infringement: Given Biocon's certification of non-infringement, the case will likely turn on a factual battle of experts and empirical data. Does the specific formulation in Biocon’s ANDA in fact have crystalline apixaban particles with a "D90" of "about 89 µm" or less and the claimed dissolution rate, or has Biocon designed a bioequivalent formulation that avoids these specific patented parameters?
- A second key issue will be the strategic impact of prior litigation: The complaint highlights that the ’945 patent has already survived a validity and infringement challenge against other generic manufacturers. A key question is how this history will shape the present case. While Biocon was not a party to that litigation, the prior court’s claim construction and validity findings may be highly persuasive, potentially narrowing the scope of available defenses.