DCT
1:17-cv-00398
Bristol Myers Squibb Co v. Accord Healthcare Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Bristol-Myers Squibb Company (Delaware) and Pfizer Inc. (Delaware)
- Defendant: Accord Healthcare Inc. (North Carolina)
- Plaintiff’s Counsel: Farnan, LLP
- Case Identification: 1:17-cv-00398, D. Del., 04/10/2017
- Venue Allegations: Defendant Accord Healthcare Inc., through its counsel, agreed not to contest jurisdiction or venue in the District of Delaware.
- Core Dispute: Plaintiffs allege that Defendant’s Abbreviated New Drug Application (ANDA) to market a generic version of the anticoagulant drug Eliquis® (apixaban) constitutes an act of infringement of two patents covering the apixaban compound and specific pharmaceutical formulations thereof.
- Technical Context: The technology relates to Factor Xa inhibitors, a class of direct oral anticoagulants used for the treatment and prevention of thromboembolic disorders such as stroke, deep vein thrombosis, and pulmonary embolism.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following a notice letter from Accord, received by Plaintiffs on or after March 1, 2017, which contained a Paragraph IV certification asserting that the patents-in-suit are invalid, unenforceable, and/or will not be infringed by the proposed generic product. The complaint notes a dispute regarding the terms of Accord's offer of confidential access to its ANDA materials.
Case Timeline
| Date | Event |
|---|---|
| 2001-09-21 | ’208 Patent Priority Date |
| 2005-11-22 | ’208 Patent Issue Date |
| 2010-02-25 | ’945 Patent Priority Date |
| 2016-05-03 | ’945 Patent Issue Date |
| 2017-02-28 | Accord sends ANDA Notice Letter |
| 2017-04-10 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 6,967,208 - "Lactam-Containing Compounds and Derivatives thereof as Factor Xa Inhibitors," issued November 22, 2005
The Invention Explained
- Problem Addressed: The patent describes a need in medicine for effective and safe anticoagulant agents to treat thromboembolic disorders. Specifically, it sought to develop new, potent, and selective inhibitors of Factor Xa, a critical enzyme in the blood coagulation cascade. (’208 Patent, col. 5:22-29).
- The Patented Solution: The invention discloses a genus of novel lactam-containing compounds, described by the general structure "P-M-M1," that function as Factor Xa inhibitors. By inhibiting Factor Xa, these compounds are designed to interrupt the formation of blood clots. The patent discloses numerous specific chemical structures within this genus, including the compound that would become known as apixaban. (’208 Patent, col. 6:1-3; col. 62:38-52).
- Technical Importance: The invention aimed to provide compounds with improved pharmacological or pharmacokinetic properties over existing antithrombotic agents, offering a new therapeutic option for managing conditions prone to dangerous blood clotting. (’208 Patent, col. 5:30-34).
Key Claims at a Glance
- The complaint asserts claims 8, 13, 26-27, and 55-61 (Compl. ¶20-22). The key composition claim is claim 13, which depends from claim 8.
- Claim 13 recites a single chemical entity:
- "A compound according to claim 8, wherein the compound is 1-(4-methoxyphenyl)-6-[4-(2-oxo-1-piperidinyl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridin-7-one, or a pharmaceutically acceptable salt form thereof."
- The complaint reserves the right to assert additional claims.
U.S. Patent No. 9,326,945 - "Apixaban Formulations," issued May 3, 2016
The Invention Explained
- Problem Addressed: The patent explains that although apixaban's dose and solubility characteristics would not predict dissolution problems under the Biopharmaceutics Classification System, it was discovered that formulations made with certain processes or with large drug particles led to "less than optimal exposures" in humans. (’945 Patent, col. 1:45-62). This variability could compromise consistent therapeutic effect.
- The Patented Solution: The invention is a solid pharmaceutical formulation of crystalline apixaban where the drug particles have a specific, controlled size: a D90 (the diameter where 90% of the particles' volume is smaller) of "equal to or less than about 89 µm." This specific particle size distribution is claimed to ensure "consistent in-vivo dissolution," leading to reliable drug exposure and therapeutic performance. (’945 Patent, col. 2:6-12, 45-48).
- Technical Importance: This technology addresses the challenge of formulating a low-solubility drug into a reliable oral tablet, which is critical for an anticoagulant where predictable blood levels are necessary for both safety and efficacy. (’945 Patent, col. 2:1-5).
Key Claims at a Glance
- The complaint asserts claims 1, 9-12, 20-23, 25, 27, 29, 31, 33, 35, and 37 (Compl. ¶26). The lead independent claims are 1 and 12.
- The essential elements of independent claim 1 include:
- 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;
- Wherein at least 77 wt % of apixaban dissolves within 30 minutes in a specified buffer solution.
- The complaint reserves the right to assert additional claims.
III. The Accused Instrumentality
Product Identification
- Accord's proposed generic apixaban tablets in 2.5 mg and 5 mg strengths, for which it filed Abbreviated New Drug Application (ANDA) No. 210180 (Compl. ¶1-2).
Functionality and Market Context
- The complaint alleges that by filing its ANDA, Accord has represented that its product contains the same active ingredient (apixaban), has the same dosage form and strength, and is bioequivalent to Plaintiffs' Eliquis® drug product (Compl. ¶14).
- The accused product is intended to be a generic substitute for Eliquis® for the same approved indications, which include the treatment and prevention of thromboembolic disorders (Compl. ¶11, ¶15). As a generic, its market purpose is to provide a lower-cost alternative upon receiving FDA approval.
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint. The infringement allegations are based on the statutory act of filing an ANDA seeking approval to market a drug prior to patent expiry. The complaint does not contain detailed infringement contentions or claim charts.
’208 Patent Infringement Allegations
| Claim Element (from Claim 13) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A compound... wherein the compound is 1-(4-methoxyphenyl)-6-[4-(2-oxo-1-piperidinyl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridin-7-one... | The complaint alleges that Accord's proposed product contains apixaban, the compound identified in the claim, as its active ingredient. | ¶14 | col. 266:39-45 |
| ...or a pharmaceutically acceptable salt form thereof. | The ANDA product is alleged to have the same active ingredient as Eliquis®, which is apixaban. | ¶14 | col. 266:45-46 |
Identified Points of Contention
- Validity: Accord’s notice letter asserts that the ’208 Patent is invalid (Compl. ¶16). The primary dispute for this patent will likely center on validity challenges, such as obviousness or anticipation, rather than infringement.
- Scope Questions: Because claim 13 covers the specific apixaban molecule, infringement analysis will be relatively direct. The question is whether Accord's ANDA specifies the manufacture and sale of that exact compound or its salt, which is a required showing for a generic drug application.
’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... | Accord's ANDA seeks approval for solid tablets of apixaban in 2.5 mg and 5 mg dosage strengths. | ¶2 | col. 10:49-52 |
| ...wherein the crystalline apixaban particles have a D90 equal to or less than about 89 µm, | The complaint alleges Accord's product is bioequivalent to Eliquis® (¶14), which Plaintiffs contend necessitates the claimed particle size for consistent bioavailability as taught in the patent (’945 Patent, col. 2:45-59). | ¶14 | col. 10:53-55 |
| and wherein at least 77 wt % of apixaban dissolves within 30 minutes in a pH 6.8 phosphate buffer... | The complaint alleges the Accord product is bioequivalent to Eliquis® (¶14), which Plaintiffs contend requires meeting this dissolution profile to achieve consistent exposure (’945 Patent, col. 11:20-28). | ¶14 | col. 10:56-59 |
Identified Points of Contention
- Technical Questions: A central factual dispute will be whether the formulation described in Accord’s confidential ANDA submission actually meets the D90 ≤ 89 µm particle size and ≥ 77% dissolution limitations.
- Scope Questions: The interpretation of "about 89 µm" may be a point of contention, raising the question of whether a product with a D90 slightly above 89 µm still falls within the claim's scope.
- Invalidity/Obviousness: A likely defense strategy for Accord will be to argue that optimizing particle size and dissolution for a low-solubility drug like apixaban was a routine and obvious activity for a skilled formulator, and that the claimed 89 µm and 77% values are arbitrary or obvious-to-try thresholds rather than non-obvious discoveries.
V. Key Claim Terms for Construction
Term from the ’945 Patent: "a D90 equal to or less than about 89 µm"
Context and Importance
- This term is the central technical limitation of the ’945 Patent's formulation claims. The patentability of the claims and the infringement analysis both depend heavily on the meaning and scope of this particle size threshold. Practitioners may focus on this term because the inclusion of "about" creates ambiguity that is frequently litigated.
Intrinsic Evidence for Interpretation
- Evidence for a Broader Interpretation: The patent’s consistent use of the word "about" in relation to the 89 µm value suggests the inventors did not intend it as a strict, absolute cutoff, but rather as a practical target that could accommodate normal manufacturing and measurement variability (’945 Patent, col. 2:10).
- Evidence for a Narrower Interpretation: The patent presents data linking specific particle sizes to dissolution rates and bioavailability, with 89 µm identified as a key inflection point. A party could argue that the data in the patent's figures, such as Figure 3, defines the term's meaning and limits the scope of "about" to values that demonstrate the same consistent dissolution profile taught by the invention. (’945 Patent, col. 2:56-59).
VI. Other Allegations
Indirect Infringement
- The complaint alleges inducement of and contribution to infringement for both patents (Compl. ¶21, ¶27). For the method claims of the ’208 Patent (e.g., claims 55-61), this allegation is likely based on the premise that Accord's product labeling will instruct physicians and patients to administer the drug for patented therapeutic uses, thereby inducing infringement.
Willful Infringement
- The complaint does not contain a formal count for willful infringement. However, it establishes that Accord had knowledge of the patents-in-suit at least as of its February 28, 2017 notice letter (Compl. ¶12), which could form the basis for a later claim of post-filing willfulness if infringement is found.
VII. Analyst’s Conclusion: Key Questions for the Case
This case appears to present two distinct sets of legal and factual questions, one for each patent.
- A question of fundamental validity: For the ’208 Patent, which claims the apixaban compound itself, the central issue will likely be whether Accord can establish by clear and convincing evidence that the molecule was anticipated or obvious in light of prior art existing before the 2001 priority date.
- A question of non-obviousness for a formulation parameter: For the ’945 Patent, the case will likely turn on whether the claimed particle size threshold of "D90...less than about 89 µm" represents a non-obvious solution to a documented problem of inconsistent bioavailability, or if it was merely the result of routine, obvious-to-try optimization that a skilled formulator would have performed.
- An evidentiary question of infringement: A key factual dispute for the ’945 Patent will be whether the product formulation specified in Accord's confidential ANDA meets the particle size and dissolution rate limitations recited in the claims.