DCT

1:19-cv-01975

Sanofi Aventis US LLC v. Shilpa Medicare Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-01975, D. Del., 10/17/2019
  • Venue Allegations: Plaintiffs allege venue is proper in the District of Delaware because Defendant develops and markets generic pharmaceuticals for the U.S. market, including in Delaware; submitted an Abbreviated New Drug Application (ANDA) seeking approval to sell its product throughout the United States, including Delaware; and has previously consented to jurisdiction in the district in unrelated litigation.
  • Core Dispute: Plaintiffs allege that Defendant’s submission of an ANDA to market a generic version of the multiple sclerosis drug Aubagio® (teriflunomide) constitutes an act of infringement of two patents covering methods of using the drug.
  • Technical Context: The technology concerns pharmaceutical method-of-use claims for treating multiple sclerosis (MS) and for managing a specific drug-drug interaction to ensure patient safety when co-administering with a common cholesterol medication.
  • Key Procedural History: The complaint notes that U.S. Patent 6,794,410 underwent ex parte reexamination, which resulted in the cancellation of its original claim 1 and the issuance of new claims 2-22. This procedural event may be relevant to the interpretation and validity of the asserted claims of that patent.

Case Timeline

Date Event
2001-04-05 '410 Patent Priority Date
2004-09-21 '410 Patent Issue Date
2013-02-04 '346 Patent Priority Date
2013-07-31 '410 Patent Reexamination Certificate Issued
2015-11-17 '346 Patent Issue Date
2019-09-04 Defendant’s ANDA Notice Letter Sent to Plaintiffs
2019-10-17 Complaint Filing Date

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"

  • Patent Identification: 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 multiple sclerosis as a debilitating, inflammatory neurological disease for which existing therapies had significant limitations, including adverse side effects, limited efficacy in preventing relapses, and the potential to induce neutralizing antibodies that reduce therapeutic effectiveness, creating a "strong need for new drugs" ('410 Patent, col. 2:4-6, 48-58).
  • The Patented Solution: The invention claims a method of treating multiple sclerosis by administering the compound teriflunomide ('410 Patent, Abstract). The patent explains that "treating" can include alleviating symptoms, preventing their appearance, or slowing the progression of the disease in a patient ('410 Patent, col. 4:45-50). The claims added during reexamination specify that the method is for a "patient that has manifested clinical disease" ('410 C1 Patent, col. 2:22-23).
  • Technical Importance: The invention provided a novel oral therapeutic approach for treating multiple sclerosis, an area where treatment options were limited and often involved injectables with challenging side-effect profiles ('410 Patent, col. 2:40-55).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 10, which was added during reexamination (Compl. ¶47).
  • 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 does not explicitly reserve the right to assert dependent claims, but the infringement allegations are not limited to claim 10 (Compl. ¶47).

U.S. Patent No. 9,186,346 - "Methods for Reducing the Risk of an Adverse Teriflunomide and Rosuvastatin Interaction in Multiple Sclerosis Patients"

  • Patent Identification: 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 explains that teriflunomide inhibits certain drug transporters in the body (BCRP and OATP1B1/B3) ('346 Patent, col. 1:42-47). A commonly prescribed statin, rosuvastatin, is a substrate for these same transporters. Consequently, co-administration "causes an increase in the plasma concentration of rosuvastatin," creating a risk of an adverse drug interaction ('346 Patent, col. 1:52-58).
  • The Patented Solution: The invention addresses this interaction risk by claiming a specific method of co-administration. The method involves treating an MS patient with a daily dose of teriflunomide while also administering rosuvastatin at a reduced dose that "does not exceed 10 mg once daily" ('346 Patent, col. 6:23-26). This dosing regimen is intended to provide the therapeutic benefits of both drugs while managing the risk from the interaction ('346 Patent, col. 2:41-49).
  • Technical Importance: The claimed method provides a protocol to enable the safe concurrent use of an important MS therapy and a widely used cholesterol-lowering medication, which might otherwise be contraindicated or require more complex patient monitoring ('346 Patent, col. 1:12-16).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 5 (Compl. ¶65).
  • The essential elements of Claim 5 are:
    • A method for treating multiple sclerosis while managing the risk of teriflunomide and rosuvastatin interaction in a patient having multiple sclerosis
    • 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 does not explicitly reserve the right to assert dependent claims but makes general allegations of infringement of the '346 patent (Compl. ¶65).

III. The Accused Instrumentality

Product Identification

  • Defendant Shilpa’s "Teriflunomide ANDA Product," a proposed generic version of Aubagio® (Compl. ¶¶1, 7).

Functionality and Market Context

  • The accused product is a 14 mg tablet containing teriflunomide as its active ingredient (Compl. ¶¶7, 28). The complaint alleges that Shilpa's ANDA filing asserts that its product is bioequivalent to Plaintiffs’ approved Aubagio® drug product (Compl. ¶29). Shilpa is seeking FDA approval to market its product for the same indication as Aubagio®: the treatment of patients with relapsing forms of multiple sclerosis (Compl. ¶32). The complaint further alleges that Shilpa is seeking approval for its product to be used when co-administered with rosuvastatin in a manner where the rosuvastatin dose will not exceed 10 mg daily (Compl. ¶33).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

'410 Patent Infringement Allegations

Claim Element (from Independent Claim 10) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating multiple sclerosis Defendant is seeking approval to market its Teriflunomide ANDA Product for the treatment of patients with relapsing forms of multiple sclerosis. ¶32 col. 2:61-65
comprising orally administering The accused ANDA product is a tablet intended for oral administration. ¶7 col. 5:1-3
to a patient that has manifested clinical disease The proposed indication is for "relapsing forms of multiple sclerosis," which the complaint alleges meets this limitation. ¶32 col. 2:22-29
a therapeutically effective amount of a compound of Formula I... Defendant's ANDA product contains teriflunomide and is alleged to be bioequivalent to the approved Aubagio® product, which is administered in a therapeutically effective amount. ¶¶28-30 col. 4:51-54

'346 Patent Infringement Allegations

Claim Element (from Independent Claim 5) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating multiple sclerosis while managing the risk of teriflunomide and rosuvastatin interaction... Defendant is seeking approval to market its product for treating MS, and the proposed use instructions will allegedly cover co-administration with rosuvastatin. ¶¶32, 33, 37 col. 1:12-16
wherein rosuvastatin is co-administered with teriflunomide The complaint alleges Defendant's prescribing information will instruct users on the co-administration of the two drugs. ¶37 col. 2:21-24
comprising administering to the patient about 7 or 14 mg of teriflunomide daily Defendant's ANDA product is a 14 mg tablet. ¶7 col. 6:23-24
and administering to the patient rosuvastatin at a dose that does not exceed 10 mg once daily. The complaint alleges Defendant is seeking approval for its product to be used such that the co-administered dose of rosuvastatin will not exceed 10 mg once daily. ¶33 col. 6:25-26
  • Identified Points of Contention:
    • Evidentiary Questions: As this is an ANDA case based on a future product, the infringement analysis will depend entirely on the contents of Shilpa’s ANDA filing and its proposed product label. A central question for the court will be whether the instructions on the proposed label will induce physicians and patients to perform each and every step of the claimed methods.
    • Scope Questions ('410 Patent): The language "patient that has manifested clinical disease" was added during reexamination. A potential dispute may arise over whether the accused indication for "relapsing forms of multiple sclerosis" necessarily meets this limitation, or if the term requires a more specific clinical presentation (e.g., an active, acute episode).
    • Technical Questions ('346 Patent): The infringement allegation for the '346 patent hinges on the specific dosing instructions. A key question will be what evidence the complaint and the ANDA itself provide that Shilpa's proposed label will instruct a rosuvastatin dose of "not more than 10 mg once daily" specifically for the purpose of "managing the risk" of the pharmacokinetic interaction described in the patent.

V. Key Claim Terms for Construction

  • Term 1 ('410 Patent): "a patient that has manifested clinical disease"

    • Context and Importance: This limitation was added to the independent claims during reexamination and is central to defining the scope of the patient population covered by the '410 patent. Its construction will be critical to both infringement and validity analyses, as it distinguishes the claims from prior art that may have disclosed the use of teriflunomide for MS more broadly.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: A party could argue the term is met by any patient who has received a clinical diagnosis of MS, as a diagnosis itself is a confirmation that the disease has "manifested." The patent specification discusses MS generally as a "debilitating, inflammatory, neurological illness" ('410 Patent, col. 2:4-6).
      • Evidence for a Narrower Interpretation: The reexamination certificate also includes dependent claims that further specify the treatment as alleviating or slowing the progression of an "acute episode of MS" ('410 C1 Patent, col. 2:28-29, 38-39). A party could argue this context suggests "manifested clinical disease" should be construed more narrowly to mean a patient actively experiencing symptoms or a relapse, consistent with the complaint's focus on "relapsing forms of MS" (Compl. ¶32).

  • Term 2 ('346 Patent): "managing the risk of...interaction"

    • Context and Importance: This phrase defines the stated purpose and benefit of the claimed method. Proving infringement will require showing that the accused method is performed for this purpose. Practitioners may focus on this term because it links the claimed dosing regimen to a specific technical problem.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: A party might argue this phrase covers any action taken to reduce any general risk associated with combining the two drugs.
      • Evidence for a Narrower Interpretation: The patent specification provides strong evidence for a narrower construction. The background explicitly defines the interaction as an "increase in the plasma concentration of rosuvastatin" ('346 Patent, col. 1:55-58). The "Summary of the Invention" frames the method as one for "managing the risk of teriflunomide and rosuvastatin interaction" by co-administering the drugs with a specific dose reduction ('346 Patent, col. 1:61-65). This suggests "managing the risk" refers specifically to mitigating this identified pharmacokinetic effect.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement for both patents. The factual basis asserted is that Defendant will, upon receiving FDA approval, knowingly sell its Teriflunomide ANDA Product with prescribing information that substantially copies the label for Aubagio® and will instruct physicians and patients to perform the patented methods (Compl. ¶¶35, 37, 44). This includes instructing the treatment of relapsing MS ('410 patent) and the specific dosing regimen for co-administration with rosuvastatin ('346 patent) (Compl. ¶¶36, 37).
  • Willful Infringement: The complaint alleges that Defendant's infringement is and has been "deliberate" (Compl. ¶¶48, 66). The asserted basis for this claim is that Defendant had pre-suit knowledge of the patents, at least from the time it sent its Paragraph IV certification notice letter to Plaintiffs (Compl. ¶23).

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

This Hatch-Waxman litigation presents several key questions for the court's determination:

  1. A central issue will be one of induced infringement: Will the proposed product label in Defendant's ANDA instruct medical professionals and patients to administer the generic drug in a way that practices every element of the asserted method claims? The outcome will likely depend on a meticulous comparison of the proposed label's language against the specific limitations of the patent claims.

  2. A second question will concern claim scope and validity: For the '410 patent, the analysis may focus on the patentability of the method claim added during reexamination. The court may need to decide if the limitation "a patient that has manifested clinical disease" renders the claim non-obvious over prior art that may have disclosed treating MS with teriflunomide more generally.

  3. Finally, a key evidentiary question for the '346 patent will be one of intent and purpose: Does the proposed label for the accused product instruct the specified dosing regimen for the explicit purpose of "managing the risk" of the pharmacokinetic drug interaction described in the patent, or is the dosing instruction presented for a different reason, potentially creating a dispute over whether the intent element of inducement is met?