DCT

1:17-cv-00003

Sanofi Aventis US LLC v. Biocon Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00003, D. Del., 01/03/2017
  • Venue Allegations: Plaintiffs allege venue is proper based on Defendant’s intent to market and sell its generic pharmaceutical products in Delaware, its maintenance of a distributorship network in the state, and its previous consent to jurisdiction in the district in unrelated litigation.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for 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 patents relate to pharmaceutical methods for treating multiple sclerosis with the active ingredient teriflunomide and for managing a specific drug-drug interaction when teriflunomide is co-administered with rosuvastatin.
  • Key Procedural History: The complaint arises from Defendant's filing of ANDA No. 209639 and its subsequent "Paragraph IV" certification notice letter to Plaintiffs, asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed. The complaint notes that the lead patent, U.S. 6,794,410, underwent reexamination, resulting in the cancellation of its original claim and the addition of new claims.

Case Timeline

Date Event
2001-04-05 U.S. Patent 6,794,410 Priority Date
2004-09-21 U.S. Patent 6,794,410 Issue Date
2013-02-04 U.S. Patent 9,186,346 Priority Date
2013-07-31 U.S. Patent 6,794,410 Reexamination Certificate Issued
2015-11-17 U.S. Patent 9,186,346 Issue Date
2016-11-21 Defendant's ANDA Notice Letter Dated
2017-01-03 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," issued September 21, 2004

The Invention Explained

  • Problem Addressed: The patent describes multiple sclerosis (MS) as a debilitating, inflammatory neurological disease for which existing treatments have significant side-effect liabilities, limited efficacy, and the potential to induce neutralizing antibodies, creating a 'strong need for new drugs' (’410 Patent, col. 2:5-59).
  • The Patented Solution: The invention is a method of treating MS by administering the compound teriflunomide. The patent specification explains that teriflunomide has 'antiproliferative effects on a wide variety of immune cells,' targeting the T-cell-mediated autoimmune reaction believed to be responsible for the nerve demyelination characteristic of MS ('410 Patent, col. 2:23-24; col. 2:62-65).
  • Technical Importance: The invention provided a novel therapeutic approach for an oral medication to treat MS by inhibiting the proliferation of specific immune cells involved in the disease's pathology ('410 Patent, col. 2:60-65).

Key Claims at a Glance

  • The complaint asserts infringement of at least claim 10 (Compl. ¶47). Claim 10 is an independent claim added during reexamination.
  • The essential elements of independent claim 10 are:
    • A method of treating multiple sclerosis which comprises 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 reserves the right to assert other claims (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," issued November 17, 2015

The Invention Explained

  • Problem Addressed: The patent identifies a specific drug-drug interaction risk. Teriflunomide inhibits certain drug transporters (BCRP and OATP1B1/B3), and rosuvastatin (a cholesterol-lowering drug) is a substrate for these transporters. Co-administration was found to cause a significant 'increase in the plasma concentration of rosuvastatin,' creating a potential for adverse effects (’346 Patent, col. 1:42-59).
  • The Patented Solution: The invention provides a method to manage this interaction by implementing a specific dosing regimen. When teriflunomide and rosuvastatin are co-administered, the method involves reducing the 'normal dose of rosuvastatin by about 50%' or, more specifically, ensuring the rosuvastatin dose does not exceed 10 mg daily ('346 Patent, Abstract; claim 5).
  • Technical Importance: This method enables patients with MS who also require cholesterol management to be treated with both drugs more safely by providing a defined protocol to mitigate the risk of elevated rosuvastatin exposure ('346 Patent, col. 1:12-19).

Key Claims at a Glance

  • The complaint asserts infringement of at least claim 5 (Compl. ¶65). Claim 5 is an independent claim.
  • The essential elements of independent claim 5 are:
    • A method for treating multiple sclerosis while managing the risk of teriflunomide and rosuvastatin interaction in a patient.
    • Rosuvastatin is co-administered with teriflunomide.
    • The method comprises administering about 7 or 14 mg of teriflunomide daily.
    • The method further comprises administering rosuvastatin at a dose that does not exceed 10 mg once daily.
  • The complaint reserves the right to assert other claims (Compl. ¶65).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentalities are Defendant Biocon's proposed "Teriflunomide ANDA Products," specifically 7 mg and 14 mg tablets intended as a generic version of Plaintiffs' Aubagio® drug product (Compl. ¶1, ¶7).
  • Functionality and Market Context: The complaint alleges that Biocon’s ANDA products contain teriflunomide as the active ingredient, are bioequivalent to Aubagio®, and seek approval for the same indication: "the treatment of patients with relapsing forms of multiple sclerosis" (Compl. ¶28, ¶29, ¶32). A central allegation is that the prescribing information for Biocon's product will "substantially copy the instructions for Aubagio®," including instructions for managing the drug interaction when co-administered with rosuvastatin (Compl. ¶33, ¶35, ¶37).

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 which comprises orally administering... Defendant's ANDA seeks approval to market its teriflunomide tablets for the treatment of patients with relapsing forms of MS, and the proposed label will instruct users on its oral administration. ¶32, ¶36 col. 2:5-7
...to a patient that has manifested clinical disease... Defendant seeks approval for the same approved indication as Aubagio®, which is for treating patients with "relapsing forms of multiple sclerosis," a condition that represents a manifested clinical disease. ¶31, ¶32 col. 7:19-22
...a therapeutically effective amount of a compound of Formula I... Defendant's ANDA is for 7 mg and 14 mg tablets of teriflunomide, which are therapeutic dosage strengths for treating MS. ¶7, ¶28 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... The proposed prescribing information for Defendant's product will allegedly instruct users on managing the risk of the drug interaction when co-administered with rosuvastatin. ¶37 col. 2:60-65
...wherein rosuvastatin is co-administered with teriflunomide... The proposed label allegedly contains instructions for use when the two drugs are co-administered. ¶33, ¶37 col. 1:12-19
...comprising administering to the patient about 7 or 14 mg of teriflunomide daily... Defendant's ANDA seeks approval for 7 mg and 14 mg teriflunomide tablets. ¶7 claim 5
...and administering to the patient rosuvastatin at a dose that does not exceed 10 mg once daily. Defendant allegedly seeks approval to market its product with instructions that, upon co-administration, "the dose of rosuvastatin will not exceed 10 mg once daily in patients." ¶33 claim 5
  • Identified Points of Contention:
    • Scope Questions: As this is an ANDA case based on a proposed generic, the dispute is not over what a product does but what its label will instruct users to do. The central question is whether following the instructions in the proposed label for Biocon's product would result in direct infringement of the method claims by physicians and patients.
    • Technical Questions: A key factual question will be whether the language in Biocon's proposed label is coextensive with the limitations of the asserted claims. For the '346 patent, the analysis may focus on whether the label's language on rosuvastatin dosing constitutes an instruction to perform the claimed method of "managing the risk," or if it could be framed as a mere precaution or warning that falls short of inducing infringement.

V. Key Claim Terms for Construction

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

    • Context and Importance: This phrase was added during the reexamination of the '410 patent and is part of the asserted independent claim. Practitioners may focus on this term because its precise scope could be a point of dispute. The case could turn on whether the patient population described in the defendant's proposed label falls squarely within this definition.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent’s general description of MS as a "debilitating, inflammatory, neurological illness" could support a broad reading that includes any patient diagnosed with a symptomatic form of the disease ('410 Patent, col. 2:5-7).
      • Evidence for a Narrower Interpretation: The description of the animal model, where treatment began when disease symptoms "typically appear," could be used to argue that the term requires the presence of an active, acute episode, potentially excluding patients in remission ('410 Patent, col. 7:19-22).

  • The Term: "managing the risk" ('346 patent, claim 5)

    • Context and Importance: This term defines the purpose of the claimed method. Practitioners may focus on this term because its construction will be critical to determining whether the instructions on a drug label can satisfy this active-sounding limitation.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent’s title is "Methods for Reducing the Risk," and the summary explains the invention is a "method for managing the risk... comprising administering" specific doses ('346 Patent, Title; col. 2:60-65). This language directly links the act of administering the recommended doses to the act of "managing."
      • Evidence for a Narrower Interpretation: A defendant could argue that "managing" implies a more involved clinical process by a healthcare provider beyond simply prescribing a reduced dose, such as active monitoring for adverse effects. However, the claim body itself appears to define the "managing" step by the subsequent administration limitations.

VI. Other Allegations

  • Indirect Infringement: The complaint's core theory is indirect infringement. It alleges that Biocon's filing of its ANDA with a proposed label that copies the branded drug's instructions constitutes inducement to infringe under 35 U.S.C. § 271(b) (Compl. ¶¶ 58, 76). The complaint alleges Biocon designed its product for these infringing uses and knows its label will induce infringement by doctors and patients (Compl. ¶39, ¶42). It also pleads contributory infringement, alleging the product is not a staple article of commerce suitable for substantial non-infringing use (Compl. ¶¶ 60, 78).
  • Willful Infringement: The complaint alleges willful and deliberate infringement based on Biocon's pre-suit knowledge of the patents, evidenced by their listing in the FDA's Orange Book and Biocon's Paragraph IV certification letter (Compl. ¶22, ¶26, ¶48, ¶66). Plaintiffs request that damages be trebled and that the case be found "exceptional" to warrant an award of attorney fees (Compl. ¶50, ¶63, ¶81).

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

  • A core issue will be one of induced infringement: Will the specific instructions and indications for use contained within the proposed label for Biocon’s generic teriflunomide product, if approved, inevitably lead medical professionals and patients to perform the patented methods of treatment and dose management, thereby satisfying the requirements for infringement under 35 U.S.C. § 271(e)(2)?
  • A key evidentiary question will be the correspondence between label and claim: Does the text of Biocon’s proposed prescribing information contain language that maps directly onto every element of the asserted method claims? Specifically for the ’346 patent, does the label’s instruction regarding a maximum 10 mg daily dose of rosuvastatin when co-administered with teriflunomide suffice to prove an intent to induce the claimed method of “managing the risk”?