1:17-cv-00377
Bristol Myers Squibb Co v. Invagen Pharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Bristol-Myers Squibb Company (Delaware) and Pfizer Inc. (Delaware)
- Defendant: InvaGen Pharmaceuticals, Inc. (New York)
- Plaintiff’s Counsel: Farnan LLP; Wilmer Cutler Pickering Hale and Dorr LLP
- Case Identification: 1:17-cv-00377, D. Del., 04/05/2017
- Venue Allegations: Venue is alleged to be proper in the District of Delaware based on Defendant’s purported systematic and continuous business contacts within the state, its previous use of Delaware courts, and the act of infringement which is directed at Delaware-based Plaintiffs.
- Core Dispute: Plaintiffs allege that Defendant’s submission of an 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 the drug apixaban.
- Technical Context: The dispute is in the field of pharmaceutical formulation, where the physical characteristics of a drug substance, such as particle size, are controlled to ensure consistent dissolution and absorption by the body, which is critical for safety and efficacy.
- Key Procedural History: The litigation was initiated under the Hatch-Waxman Act following Defendant’s notification to Plaintiffs, via a Paragraph IV certification letter, of its ANDA filing. The letter asserts that the patent-in-suit is invalid, unenforceable, or will not be infringed by Defendant's proposed generic product.
Case Timeline
| Date | Event |
|---|---|
| 2010-02-25 | U.S. Patent No. 9,326,945 Priority Date |
| 2016-05-03 | U.S. Patent No. 9,326,945 Issue Date |
| 2017-02-24 | InvaGen sent Notice Letter regarding its ANDA filing |
| 2017-04-05 | 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 formulating the anticoagulant drug apixaban. While pharmaceutical classification systems predicted that apixaban's particle size should not be critical for achieving consistent plasma profiles at therapeutic doses, the inventors determined that formulations made with larger particles or through certain manufacturing processes led to "less than optimal exposures" in patients, creating potential quality control and consistency issues ('945 Patent, col. 1:45-60).
- The Patented Solution: The inventors state they "surprisingly and unexpectedly" discovered that controlling the particle size of crystalline apixaban is key to achieving consistent drug absorption ('945 Patent, col. 2:1-4). The patented solution is a solid pharmaceutical composition comprising apixaban particles where 90% of the particles by volume have a diameter (D90) of 89 microns (µm) or less. This specific particle size control is claimed to lead to "consistent in-vivo dissolution in humans" and reliable therapeutic effect ('945 Patent, col. 2:1-5, Abstract). The patent further links this particle size to a specific in-vitro dissolution rate ('945 Patent, col. 9:15-28).
- Technical Importance: The invention provides a method to ensure reliable and consistent bioavailability for a low-solubility drug, which is particularly important for an anticoagulant where incorrect dosing can have severe safety consequences ('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. ¶23).
- Independent Claim 1 includes the following essential elements:
- 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 additional claims, including dependent claims 9-11, 20-23, 25, 27, 29, 31, 33, 35, and 37 (Compl. ¶23).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is the "InvaGen ANDA product," identified as 2.5 mg and 5 mg tablets of apixaban for which InvaGen seeks FDA approval via ANDA No. 209984 (Compl. ¶2).
Functionality and Market Context
The complaint alleges that by filing its ANDA, InvaGen has represented to the FDA that its product contains the same active ingredient (apixaban), has the same dosage form and strength, and is bioequivalent to Plaintiffs' Eliquis® product (Compl. ¶17). The accused product is intended for the same medical indications as Eliquis®, which include reducing the risk of stroke and treating thromboembolic disorders (Compl. ¶14, 18).
IV. Analysis of Infringement Allegations
The complaint alleges that the act of filing the ANDA constitutes infringement but does not provide a detailed claim chart or specific factual allegations mapping the accused product's characteristics to the claim limitations. The infringement theory appears to be that for the InvaGen ANDA product to be bioequivalent to Eliquis® as claimed in its FDA submission, it must necessarily meet the limitations of the ’945 Patent.
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 accused "InvaGen ANDA product" is a solid tablet formulation containing apixaban as the active ingredient. | ¶2, 17 | col. 9:50-52 |
| wherein the crystalline apixaban particles have a D90 equal to or less than about 89 µm, | The complaint alleges infringement without specifying the particle size of apixaban in the accused product. The central question for the court will be whether the product described in ANDA No. 209984 meets this limitation. | ¶23 | col. 9:53-54 |
| 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 does not provide the dissolution profile for the accused product. A key issue will be whether the product, to be bioequivalent, must meet this claimed dissolution profile. | ¶17, 23 | col. 9:55-57 |
Identified Points of Contention
- Technical Question: The primary question is factual: what are the physical characteristics of the apixaban formulation described in InvaGen's confidential ANDA submission? Specifically, does the drug substance have a D90 particle size of "about 89 µm" or less, and does the final product exhibit the claimed dissolution rate? The complaint does not provide this evidence.
- Scope Questions: A central legal question will be the proper construction of "about 89 µm." The outcome of this construction could be dispositive if the accused product’s particle size is near this boundary.
V. Key Claim Terms for Construction
- The Term: "D90 equal to or less than about 89 µm"
- Context and Importance: This term is the core of the asserted claims and represents the main point of novelty described in the patent. The infringement analysis will likely depend entirely on whether the particle size of the accused product falls within the scope of this limitation. Practitioners may focus on this term because the word "about" introduces a degree of uncertainty that will be critical to defining the boundary of infringement.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent specification notes that for 5-mg tablets, a particle size of 119 µm resulted in a dissolution rate "marginally greater than 77%," the claimed threshold ('945 Patent, col. 9:40-43). A party could argue this suggests that "about 89 µm" is not a rigid cutoff and should encompass values somewhat above 89 µm, so long as the formulation achieves the functional goal of consistent exposure.
- Evidence for a Narrower Interpretation: The patent repeatedly characterizes the 89 µm threshold as a "surprising and unexpected" discovery ('945 Patent, col. 2:1-4). The abstract, summary of the invention, and claims all point to 89 µm as the specific solution to the technical problem ('945 Patent, Abstract; col. 2:53-54; col. 9:54). A party could argue that this specific value is definitional to the invention and that "about" should therefore be given a very narrow construction.
VI. Other Allegations
Indirect Infringement
The complaint includes allegations of future induced and contributory infringement that would occur if the InvaGen ANDA product is approved and marketed (Compl. ¶¶ 24, 25). The alleged basis for inducement would be the commercial sale and promotion of the generic product for its approved indications, which would cause doctors and patients to infringe the claims (Compl. ¶25).
VII. Analyst’s Conclusion: Key Questions for the Case
The disposition of this case will likely depend on the answers to two central questions:
A core issue will be one of claim construction: how should the term "about 89 µm" be defined? The court's interpretation of the flexibility afforded by "about" will set the literal boundary for infringement and may be the most significant legal battle in the case.
A key evidentiary question will be whether the product detailed in InvaGen's confidential ANDA filing has physical properties—specifically, an apixaban particle size distribution and a dissolution profile—that fall within the scope of the asserted claims as construed by the court. The complaint is filed without this direct evidence, making discovery of the ANDA's contents the critical next step.