Sanofi v. Aurobindo Pharma USA Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: SANOFI (France) and SANOFI-AVENTIS U.S. LLC (Delaware)
  • Defendant: Aurobindo Pharma USA, Inc. (Delaware)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
• Case Identification: Sanofi v. Aurobindo Pharma USA, Inc., 1:17-cv-01247, D. Del., 08/31/2017
• Venue Allegations: Venue is asserted based on Defendant’s incorporation in the state of Delaware, its alleged continuous and systematic business contacts within the district, and its purported previous consent to personal jurisdiction in the district.
• Core Dispute: Plaintiff alleges that Defendant's filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's Multaq® (dronedarone) constitutes an act of infringement of two patents covering methods of using the drug.
• Technical Context: The patents relate to methods of using the anti-arrhythmic drug dronedarone to reduce the risk of cardiovascular hospitalization in specific populations of patients with a history of atrial fibrillation.
• Key Procedural History: This action was filed under the Hatch-Waxman Act, triggered by Defendant's submission of ANDA No. 210678 and its associated Paragraph IV Certification notifying Plaintiff of its intent to market a generic product prior to the expiration of Plaintiff's patents. The patents-in-suit are listed in the U.S. Food and Drug Administration's "Orange Book" for Multaq®.

Case Timeline

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 8,410,167 - "Use of Dronedarone for the Preparation of a Medicament for Use in the Prevention of Cardiovascular Hospitalization or of Mortality"

• Patent Identification: U.S. Patent No. 8,410,167, "Use of Dronedarone for the Preparation of a Medicament for Use in the Prevention of Cardiovascular Hospitalization or of Mortality," issued April 2, 2013.

The Invention Explained

• Problem Addressed: The patent identifies atrial fibrillation (AF) as a growing public health concern that increases the risk of stroke and congestive heart failure ('167 Patent, col. 2:35-53). It also highlights the danger of decreased blood potassium levels (hypokalemia), which can be exacerbated by certain diuretic or anti-arrhythmic treatments and can lead to potentially fatal cardiac rhythm disorders ('167 Patent, col. 1:55-63, col. 2:13-27).
• The Patented Solution: The invention is a method for reducing the risk of cardiovascular hospitalization or mortality by administering the drug dronedarone to a specific subset of patients with a history of AF ('167 Patent, Abstract). The patent asserts that dronedarone achieves this, in part, through its ability to modulate blood potassium levels, thereby mitigating a key risk factor for cardiac events in this population ('167 Patent, col. 1:25-30). Clinical trial data is presented to demonstrate a statistically significant reduction in cardiovascular hospitalizations for patients treated with dronedarone compared to a placebo ('167 Patent, FIG. 1, col. 20:15-24).
• Technical Importance: The invention claims a therapeutic method to proactively manage a high-risk patient population (AF patients with other cardiovascular risk factors) to prevent severe outcomes, rather than only treating the arrhythmia itself.

Key Claims at a Glance

• The complaint asserts independent claim 1 and dependent claims 2-4, 6, 8-13, and 16 (Compl. ¶26).
• Independent Claim 1 requires:
  • A method of decreasing a risk of cardiovascular hospitalization in a patient.
  • The method comprises administering an effective amount of dronedarone twice a day with a meal.
  • The patient must not have severe heart failure, as defined by specific criteria (NYHA Class IV or hospitalization for heart failure within the last month).
  • The patient must have a history of, or current, paroxysmal or persistent non-permanent atrial fibrillation or flutter.
  • The patient must have at least one cardiovascular risk factor selected from a specific list (e.g., age ≥ 75, hypertension, diabetes).

U.S. Patent No. 9,107,900 - "Use of Dronedarone for the Preparation of a Medicament for Use in the Prevention of Cardiovascular Hospitalization or of Morality [sic]"

• Patent Identification: U.S. Patent No. 9,107,900, "Use of Dronedarone for the Preparation of a Medicament for Use in the Prevention of Cardiovascular Hospitalization or of Morality [sic]," issued August 18, 2015.

The Invention Explained

• Problem Addressed: As a continuation of the application leading to the '167 Patent, the '900 Patent addresses the same technical problem: the need to reduce cardiovascular events and mortality in patients with a history of atrial fibrillation, particularly those with other underlying cardiac pathologies ('900 Patent, col. 2:39-55).
• The Patented Solution: The '900 Patent claims a method of reducing the risk of cardiovascular hospitalization by administering dronedarone to a distinct, but related, patient population ('900 Patent, Abstract). The method targets patients with both a history of AF and "structural heart disease," providing a therapeutic strategy for this specific high-risk subgroup ('900 Patent, col. 4:41-51).
• Technical Importance: The invention purports to provide a targeted method-of-use for dronedarone in patients with co-existing atrial fibrillation and structural heart disease, a population at significant risk for adverse cardiovascular outcomes.

Key Claims at a Glance

• The complaint asserts independent claim 1 and dependent claims 6-9 and 14 (Compl. ¶37).
• Independent Claim 1 requires:
  • A method of reducing a risk of cardiovascular hospitalization in a patient.
  • The method comprises administering an effective amount of dronedarone twice a day with a meal.
  • The patient must not have severe heart failure, as defined by specific criteria.
  • The patient must have a history of, or current, paroxysmal or persistent non-permanent atrial fibrillation or flutter.
  • The patient must have structural heart disease, which is coronary heart disease.
  • The patient must have an age greater than or equal to 75, OR an age greater than or equal to 70 plus at least one other specified cardiovascular risk factor.

III. The Accused Instrumentality

Product Identification

• Defendant's "Proposed Generic Product" is identified as dronedarone hydrochloride tablets, 400 mg, for which Defendant submitted ANDA No. 210678 to the FDA (Compl. ¶10, ¶18).

Functionality and Market Context

• The complaint alleges that the Proposed Generic Product is a generic version of Plaintiff's Multaq® tablets (Compl. ¶10, ¶13). It further alleges that Defendant is seeking FDA approval for the same indication as Multaq®: "reducing the risk of hospitalization for atrial fibrillation in patients in sinus rhythm with a history of paroxysmal or persistent atrial fibrillation" (Compl. ¶19). The infringement theory is predicated on the intended use of the generic product, as will be described in its FDA-approved labeling, which Plaintiffs allege will instruct medical professionals and patients to use the drug in a manner that infringes the patented methods (Compl. ¶29, ¶40).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

8,410,167 Infringement Allegations

9,107,900 Infringement Allegations

Identified Points of Contention

• Scope Questions: A central question will be whether the patient population defined by Defendant's proposed product label is coextensive with the patient populations recited in the asserted claims. For infringement to be induced, the label must encourage, recommend, or promote an infringing use. The dispute may focus on whether the label requires a patient to have the specific combination of "non-severe heart failure," "paroxysmal or persistent AF," and the particular "cardiovascular risk factors" or "structural heart disease" recited in the independent claims.
• Technical Questions: Since this is an ANDA case, there is no dispute that the accused product contains the same active ingredient. The key questions are legal and related to the scope of the method claims vis-à-vis the proposed label. A secondary question, likely to be raised in defense, is one of validity: whether the claimed methods, targeting specific patient sub-populations, were obvious over the prior art or lack adequate written description and enablement in the patent specifications.

V. Key Claim Terms for Construction

• The Term: "severe heart failure" ('167 Patent, cl. 1; '900 Patent, cl. 1)

• Context and Importance: This is a negative limitation that defines a patient population excluded from the claimed method. Its construction is critical because the size of this excluded group directly impacts the size of the covered (and potentially infringed) group. Practitioners may focus on this term because if the definition is construed narrowly (excluding fewer patients), the claim scope is broader, potentially making infringement easier for Sanofi to prove.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation (more patients excluded): The specification describes a class of patients for whom dronedarone is contraindicated, including those with "worsening symptoms of heart failure at rest or with minimal exertion" or those with recent hospitalization for heart failure ('167 Patent, col. 7:30-45). A defendant might argue this language supports a broad definition of "severe."
  • Evidence for a Narrower Interpretation (fewer patients excluded): The claims themselves define "severe heart failure" with specificity as "indicated by: a) NYHA Class IV heart failure or b) hospitalization for heart failure within the last month" ('167 Patent, cl. 1). A plaintiff will likely argue that the definition is expressly and exhaustively defined in the claim itself, limiting the scope of the exclusion to only these two specific conditions.

• The Term: "at least one cardiovascular risk factor" ('167 Patent, cl. 1)

• Context and Importance: This term is a positive limitation defining the required characteristics of the patient. The interpretation of what qualifies as a "risk factor" under the claim is central to the infringement analysis. The dispute will be whether Defendant's proposed label directs use in patients who necessarily have one of the listed factors.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The specification provides a list of risk factors and includes language suggesting the list is exemplary, such as "at least one of the following risk factors" ('167 Patent, col. 13:19-20). This could support an argument that other, unlisted factors may also qualify.
  • Evidence for a Narrower Interpretation: Claim 1 provides a "Markush group" listing specific factors: "i. an age greater than or equal to 75; ii. hypertension; iii. diabetes; iv. a history of cerebral stroke or of systemic embolism; v. a left atrial diameter greater than or equal to 50 mm; and vi. a left ventricular ejection fraction less than 40%." A defendant will argue that this language limits the term to only those factors explicitly recited in the claim.

VI. Other Allegations

• Indirect Infringement: The complaint alleges that Defendant will induce infringement by "actively and intentionally" encouraging and instructing healthcare providers and patients to use the Proposed Generic Product in an infringing manner (Compl. ¶31-33, ¶42-44). The primary basis for this allegation is the content of the defendant's proposed product label, which allegedly mirrors the patented methods of use (Compl. ¶29, ¶40).
• Willful Infringement: The complaint does not contain a formal count for willful infringement. However, it does allege that Defendant was aware of the patents-in-suit at the time it submitted its ANDA, based on its statutory obligation to provide a Paragraph IV certification (Compl. ¶27, ¶38). This allegation of pre-suit knowledge could form the basis for a later claim for enhanced damages.

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

• A core issue will be one of label-based infringement: Will the final, FDA-approved label for Aurobindo's generic dronedarone inevitably instruct physicians to prescribe the drug to a patient population that satisfies every positive and negative limitation of the asserted method claims? The analysis will require a meticulous comparison between the claim language and the label's indication, contraindications, and patient selection criteria.
• A second key issue will be claim construction: The case will likely turn on the court's interpretation of patient-defining terms such as "severe heart failure," "at least one cardiovascular risk factor," and "structural heart disease." Whether these terms are limited to the explicit examples in the patents or are construed more broadly will be determinative of the claims' scope and, consequently, the infringement analysis.
• A final dispositive question will be patent validity: While not detailed in the complaint, Aurobindo's Paragraph IV certification puts the validity of the '167 and '900 patents directly at issue. The central validity challenge will likely question whether carving out these specific patient subpopulations for treatment was non-obvious in light of prior art knowledge regarding dronedarone and the management of atrial fibrillation.