Sanofi Aventis US LLC v. Glenmark Pharma Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Sanofi-Aventis U.S. LLC (Delaware), Aventisub LLC (Delaware), Sanofi (France), and Genzyme Corporation (Massachusetts)
  • Defendant: Glenmark Pharmaceuticals Inc., USA (Delaware), Glenmark Pharmaceuticals SA (Switzerland), and Glenmark Pharmaceuticals Limited (India)
  • Plaintiff’s Counsel: RatnerPrestia
• Case Identification: 1:16-cv-01326, D. Del., 12/29/2016
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Glenmark USA is a Delaware corporation and all defendants are alleged to have systematic contacts with the state and intend to market the accused products there.
• Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the multiple sclerosis drug Aubagio® constitutes an act of infringement of patents covering methods of using the drug to treat multiple sclerosis and to manage its interaction with another common medication.
• Technical Context: The technology is in the field of pharmaceuticals, specifically concerning oral therapeutics for treating relapsing forms of multiple sclerosis (MS), a chronic, inflammatory, autoimmune disease of the central nervous system.
• Key Procedural History: The complaint notes that U.S. Patent No. 6,794,410 was subject to a reexamination proceeding, which resulted in the cancellation of original claim 1 and the issuance of new claims 2-22. The infringement allegation for this patent is based on one of these new claims, which may suggest a refined claim scope that will be a focus of the litigation.

Case Timeline

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

U.S. Patent No. 6,794,410 - “Use of (Z)-2-cyano-3-hydroxy-but-2-enoic Acid-(4'-trifluoromethylphenyl)-amide for Treating Multiple Sclerosis,” Issued September 21, 2004

The Invention Explained

• Problem Addressed: The patent describes a need for new treatments for multiple sclerosis (MS), noting that existing therapies have significant side-effect liabilities, limited ability to prevent disease exacerbation, and can induce neutralizing antibodies that reduce efficacy over time (’410 Patent, col. 3:40-58).
• The Patented Solution: The invention is a method of treating MS by administering teriflunomide. The patent specification explains that MS is hypothesized to be a T-cell-mediated autoimmune disease and that teriflunomide has been shown to have antiproliferative effects on immune cells, thereby addressing a potential cause of the disease’s pathology (’410 Patent, col. 3:21-34, 61-65).
• Technical Importance: The invention provided a method of using a specific oral compound for treating MS, offering an alternative to injectable therapies.

Key Claims at a Glance

• The complaint asserts infringement of at least independent claim 10, which was added during reexamination (Compl. ¶58).
• The essential elements of claim 10 are:
  • A method of treating multiple sclerosis
  • comprising orally administering to a patient that has manifested clinical disease
  • a therapeutically effective amount of a compound of Formula I (teriflunomide), its stereoisomer, or a pharmaceutically acceptable salt thereof.
• The complaint alleges infringement of "at least one of the claims, including but not limited to claim 10," reserving the right to assert other claims (Compl. ¶58).

U.S. Patent No. 9,186,346 - “Methods for Reducing the Risk of an Adverse Teriflunomide and Rosuvastatin Interaction in Multiple Sclerosis Patients,” Issued November 17, 2015

The Invention Explained

• Problem Addressed: The patent identifies a specific drug-drug interaction, stating that when teriflunomide is administered with rosuvastatin (a widely used cholesterol-lowering medication), it causes a significant increase in the plasma concentration of rosuvastatin, creating a potential safety risk for patients (’346 Patent, col. 3:54-58).
• The Patented Solution: To mitigate this risk, the invention provides a method of co-administration that involves a specific dose adjustment. The method comprises administering teriflunomide while capping the daily dose of rosuvastatin at 10 mg, which is below its standard maximum dosage (’346 Patent, col. 2:50-54; col. 5:20-26).
• Technical Importance: This method provides a defined protocol to allow patients with MS who also have high cholesterol to be treated with both drugs simultaneously while managing the risk of adverse effects from elevated rosuvastatin levels.

Key Claims at a Glance

• The complaint asserts infringement of at least independent claim 5 (Compl. ¶77).
• The essential elements of claim 5 are:
  • A method for treating multiple sclerosis while managing the risk of teriflunomide and rosuvastatin interaction
  • wherein rosuvastatin is co-administered with teriflunomide
  • comprising administering to the patient about 7 or 14 mg of teriflunomide daily
  • and administering to the patient rosuvastatin at a dose that does not exceed 10 mg once daily.
• The complaint alleges infringement of "at least one of the claims, including but not limited to claim 5," reserving the right to assert other claims (Compl. ¶77).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are Defendants' "Teriflunomide ANDA Products" in 7 mg and 14 mg tablet form, and the act of filing Abbreviated New Drug Application (ANDA) No. 209663 with the U.S. Food and Drug Administration (FDA) (Compl. ¶¶ 1, 11).

Functionality and Market Context

The complaint alleges that the Teriflunomide ANDA Products contain the same active ingredient as Plaintiff's Aubagio® product and are asserted to be bioequivalent (Compl. ¶¶ 37, 38). The ANDA seeks FDA approval to market these products for the same indication as Aubagio®: the treatment of patients with relapsing forms of MS (Compl. ¶41). The infringement allegations are based on the contention that the proposed prescribing information for the generic product will instruct physicians and patients to use it in a manner that practices the methods claimed in the patents-in-suit (Compl. ¶¶ 46-48).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

’410 Patent Infringement Allegations

’346 Patent Infringement Allegations

Identified Points of Contention

• Scope Questions: A central question for the '410 patent will be the interpretation of the phrase "a patient that has manifested clinical disease," which was added during reexamination. The infringement analysis may turn on whether the patient population described in Defendants' proposed label falls within the scope of this limitation.
• Technical Questions: For the '346 patent, a key question is whether the instructions in Defendants' proposed product label will direct or "instruct" users to limit the rosuvastatin dose to a maximum of 10 mg daily, as required by the claim. The dispute may center on whether the label's language constitutes an infringing instruction for a specific method of risk management or merely a general precaution that falls short of the claimed method.

V. Key Claim Terms for Construction

Term: "a patient that has manifested clinical disease" (’410 patent, claim 10)

Context and Importance

This limitation was added to claim 10 during reexamination, suggesting it was critical for establishing patentability over prior art. Its construction will be central to the infringement analysis. Practitioners may focus on this term because its interpretation could narrow the claim scope and determine whether the patient population targeted by the generic's label is covered by the patent.

Intrinsic Evidence for Interpretation

• Evidence for a Broader Interpretation: The patent does not appear to offer an explicit definition, which could support an argument for applying its plain and ordinary meaning: any patient who has been diagnosed with and is showing symptoms of MS.
• Evidence for a Narrower Interpretation: The patent's description of its animal model study states that treatment was initiated on day 10 post-inoculation, a time point chosen to "represent the initial phase of an acute episode of MS" (’410 Patent, col. 6:18-23). A party could argue this context limits the term to patients experiencing an active relapse, as opposed to those in remission.

Term: "managing the risk" (’346 patent, claim 5)

Context and Importance

This phrase defines the purpose of the claimed method. The dispute will likely involve whether the language in the accused product label rises to the level of actively "managing the risk" as claimed, or is merely a warning.

Intrinsic Evidence for Interpretation

• Evidence for a Broader Interpretation: The patent's title and summary frame the invention as a method for "reducing the risk" (’346 Patent, Title; col. 3:60-61). This could support a reading where any instruction that leads to a reduction in risk, such as the claimed dose cap, satisfies the limitation.
• Evidence for a Narrower Interpretation: The patent quantifies the underlying risk, citing clinical data showing a 2.51-fold increase in rosuvastatin exposure (’346 Patent, Table I, col. 4). An argument could be made that "managing the risk" requires an instruction specifically aimed at counteracting this known pharmacokinetic effect, rather than a more general precautionary statement.

VI. Other Allegations

Indirect Infringement

The complaint alleges that Defendants will induce infringement by knowingly providing a product with prescribing information that instructs physicians and patients to use the generic drug in ways that directly infringe the method claims of the ’410 and ’346 patents (Compl. ¶¶ 46, 55, 70, 89). The complaint also alleges contributory infringement, stating that the Teriflunomide ANDA Products are not staple articles of commerce suitable for substantial non-infringing use and are especially adapted for use in an infringing manner (Compl. ¶¶ 54, 71, 90).

Willful Infringement

The complaint alleges that Defendants had knowledge of the patents-in-suit prior to and during their infringing activities, citing the Paragraph IV certification process and the Orange Book listing (Compl. ¶¶ 29, 31, 35). Based on this alleged knowledge, the complaint asserts that Defendants' infringement "has been, and continues to be, deliberate" (Compl. ¶¶ 60, 79).

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

• A core issue will be one of label-claim correspondence: In this Hatch-Waxman context, the case will turn on whether the language of the FDA-approved label for Defendants' generic teriflunomide product will inevitably instruct medical professionals and patients to perform all elements of the asserted method claims. The outcome may depend on the precise wording of the indications and dosage instructions.
• A key legal question will be the scope of reexamined claims: The court's construction of the phrase "a patient that has manifested clinical disease" in the ’410 patent, which was added during reexamination, will be critical. This interpretation will determine whether the scope of the patent is broad enough to cover the entire patient population targeted by the generic product's proposed label.
• A central conflict will be over patent validity: Defendants filed a Paragraph IV certification, asserting that the patents are invalid and/or not infringed (Compl. ¶35). While the complaint focuses on infringement, a primary element of the defense will likely be an attempt to prove, by clear and convincing evidence, that the asserted claims are invalid under grounds such as obviousness or lack of adequate written description.