DCT

1:17-cv-00024

Sanofi Aventis US LLC v. Mylan Pharma Inc

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00024, D. Del., 01/10/2017
  • Venue Allegations: Venue is asserted based on Defendants' registration to do business in Delaware, substantial and continuous contacts with the state, and intent to market and sell the accused products to Delaware residents. The complaint also notes that Defendants have previously consented to jurisdiction in the district by asserting counterclaims in prior litigation.
  • Core Dispute: Plaintiffs allege that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiffs' Aubagio® (teriflunomide) drug product constitutes an act of infringement of three U.S. patents covering methods of use and stable formulations.
  • Technical Context: The technology relates to pharmaceutical treatments for multiple sclerosis (MS), specifically concerning the active ingredient teriflunomide, its formulation for stability, and methods for managing its interaction with other drugs.
  • Key Procedural History: This is a Hatch-Waxman action initiated in response to a Paragraph IV certification notice letter from Mylan. The complaint notes that U.S. Patent No. 6,794,410 was the subject of a reexamination that resulted in the allowance of new claims, and that the patent's term was extended under 35 U.S.C. § 156. The suit was filed within the 45-day period provided by the Hatch-Waxman Act, triggering a statutory stay of FDA approval for the generic product.

Case Timeline

Date Event
2001-04-05 U.S. Patent No. 6,794,410 Priority Date
2004-09-21 U.S. Patent No. 6,794,410 Issued
2009-09-18 U.S. Patent No. 8,802,735 Priority Date
2013-02-04 U.S. Patent No. 9,186,346 Priority Date
2013-07-31 Reexamination Certificate for U.S. Patent No. 6,794,410 Issued
2014-08-12 U.S. Patent No. 8,802,735 Issued
2015-11-17 U.S. Patent No. 9,186,346 Issued
2016-11-28 Mylan sends ANDA Notice Letter to Plaintiffs
2017-01-10 Complaint Filed

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’s background section describes multiple sclerosis (MS) as a debilitating neurological disease for which there was no cure at the time of invention. It notes that existing therapies had significant side effects and limited efficacy, creating a "strong need for new drugs" to combat the disease's progression and symptoms (’410 Patent, col. 2:4-54).
  • The Patented Solution: The invention is a method for treating MS by administering the compound teriflunomide. Teriflunomide, an active metabolite of the known drug leflunomide, is described as having antiproliferative effects on immune cells, which are hypothesized to be the cause of the demyelination characteristic of MS (’410 Patent, col. 2:22-30, 61-66). The specification defines "treating" broadly to include alleviating symptoms and slowing the progression of the disease (’410 Patent, col. 4:45-51).
  • Technical Importance: The invention provided a novel therapeutic use for a known compound, offering a new mechanism of action for patients suffering from MS (’410 Patent, col.2:51-54).

Key Claims at a Glance

  • The complaint asserts infringement of at least claim 10, which was added during reexamination (Compl. ¶57).
  • Independent Claim 10:
    • 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 does not explicitly reserve the right to assert other claims of the ’410 Patent but makes general allegations of infringement of "one or more claims" (Compl. ¶57).

U.S. Patent No. 8,802,735 - "(Z)-2-cyano-3-hydroxy-but-2-enoic Acid-(4'-trifluoromethylphenyl)-amide Tablet Formulations with Improved Stability"

  • Issued: August 12, 2014

The Invention Explained

  • Problem Addressed: The patent discloses that solid pharmaceutical formulations of teriflunomide were found to be unstable, showing a "strong increase in one degradant," identified as 2-cyano-N-(4-trifluoromethyl-phenyl)-acetamide, during stability studies (’735 Patent, col. 1:65-col. 2:3).
  • The Patented Solution: The invention claims a specific solid pharmaceutical composition that improves the stability of teriflunomide. The core of the solution is the complete omission of colloidal silicon dioxide from the formulation, which also comprises teriflunomide and other excipients within specified weight-percentage ranges (’735 Patent, col. 2:25-30, col. 2:42-45).
  • Technical Importance: By providing a more stable tablet, the invention ensures consistent dosing, proper shelf-life, and product safety, which are critical requirements for a commercially viable pharmaceutical product (’735 Patent, col. 2:18-24).

Key Claims at a Glance

  • The complaint asserts infringement of at least claims 1 and 10 (Compl. ¶76). Claim 1 is an independent composition claim.
  • Independent Claim 1:
    • A solid pharmaceutical composition comprising:
    • about 1% to 30% weight:weight Teriflunomide, or a pharmaceutically acceptable basic addition salt thereof,
    • about 5% to 20% weight:weight disintegrant,
    • about 0% to 40% weight:weight binder,
    • about 0.1% to 2% weight:weight lubricant, and
    • the remaining percentage comprising diluents;
    • wherein the solid pharmaceutical composition does not contain colloidal silicon dioxide.
  • The complaint does not explicitly reserve the right to assert dependent claims but makes general allegations of infringement of "one or more claims" (Compl. ¶78).

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 (Compl. ¶22)

Technology Synopsis

The patent addresses a clinically significant drug-drug interaction where co-administration of teriflunomide was found to cause an increase in the plasma concentration of rosuvastatin, a widely used cholesterol-lowering medication (’346 Patent, col. 2:53-59). The claimed invention is a method for managing this risk by reducing the normal dose of rosuvastatin by approximately 50% when it is co-administered with teriflunomide to a patient (’346 Patent, col. 2:1-4).

Asserted Claims

Independent claim 5 is asserted (Compl. ¶84).

Accused Features

The complaint alleges that Defendants' proposed prescribing information will instruct users on managing the drug interaction when co-administered with rosuvastatin, thereby inducing infringement of the patented method (Compl. ¶41, ¶47).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are Defendants’ "Teriflunomide ANDA Products," for which Mylan Pharmaceuticals Inc. filed Abbreviated New Drug Application (ANDA) No. 209702 (Compl. ¶9). These products are proposed generic versions of the Aubagio® (teriflunomide) 7 mg and 14 mg tablets (Compl. ¶9).

Functionality and Market Context

The products are solid oral tablets containing teriflunomide as the active pharmaceutical ingredient (Compl. ¶34). The complaint alleges that Defendants are seeking FDA approval to market the products for the same indication as Aubagio®, namely the treatment of patients with relapsing forms of multiple sclerosis (Compl. ¶37, ¶38). It is further alleged that Defendants' ANDA asserts that their proposed products are bioequivalent to Aubagio® (Compl. ¶35).

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 Defendants are seeking approval to market the accused products for treating patients with relapsing forms of multiple sclerosis, and the proposed prescribing information will instruct this use. ¶38, ¶46 col. 2:56-59
which comprises orally administering to a patient that has manifested clinical disease The accused products are oral tablets. The proposed label will direct their administration to patients diagnosed with multiple sclerosis. ¶9, ¶46 col. 4:56-61
a therapeutically effective amount of a compound of Formula I ... The accused products are formulated as 7 mg and 14 mg tablets, which the complaint alleges are a therapeutically effective amount of teriflunomide, the active ingredient. ¶9, ¶40 col. 4:52-54

'735 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A solid pharmaceutical composition comprising... Defendants' proposed product is a solid oral tablet. ¶9 col. 2:38-45
about 1% to 30% weight:weight Teriflunomide... On information and belief, the accused product is formulated with 1% to 30% by weight of teriflunomide. ¶39 col. 2:39-41
about 5% to 20% weight:weight disintegrant... On information and belief, the accused product is formulated with 5% to 20% by weight of disintegrant. ¶39 col. 2:41-42
about 0.1% to 2% weight:weight lubricant, the remaining percentage comprising diluents... On information and belief, the accused product is formulated with 0.1% to 2% lubricant and the remainder as diluents. ¶39 col. 2:43-44
wherein the solid pharmaceutical composition does not contain colloidal silicon dioxide. On information and belief, the accused product is formulated without colloidal silicon dioxide. ¶39 col. 2:44-45

Identified Points of Contention

  • Scope Questions: For the ’410 Patent, a potential issue is whether the acts described in Defendants' proposed product label constitute "treating" as defined in the patent. For the ’735 Patent, a central question may be the interpretation of the negative limitation "does not contain colloidal silicon dioxide," specifically whether it requires absolute absence or merely the absence of the substance as an intentionally added excipient.
  • Technical Questions: A primary factual dispute for the ’735 Patent will be whether the formulation detailed in Defendants' confidential ANDA actually meets the specific weight-percentage ranges for each category of excipient as claimed in the patent. The infringement allegations for the ’735 Patent are made "on information and belief" and will depend on evidence obtained from the ANDA during discovery (Compl. ¶39).

V. Key Claim Terms for Construction

Term: "treating" (from Claim 10 of the ’410 Patent)

  • Context and Importance: As this is a method of treatment claim, the scope of the term "treating" is fundamental to the infringement analysis. Practitioners may focus on this term because its definition will determine whether the instructions on the accused product's label fall within the claim's scope.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification provides an explicit and broad definition: "Treat or treating means any treatment, including, but not limited to, alleviating symptoms, eliminating the causation of the symptoms either on a temporary or permanent basis, or preventing or slowing the appearance of symptoms and progression of the named disorder or condition" (’410 Patent, col. 4:45-51).
    • Evidence for a Narrower Interpretation: A defendant could argue that the term should be limited by the specific outcomes demonstrated in the patent's examples, such as the effects shown in the animal EAE model (’410 Patent, col. 6:4-11). However, the explicit definition in the specification presents a significant hurdle to such an argument.

Term: "does not contain colloidal silicon dioxide" (from Claim 1 of the ’735 Patent)

  • Context and Importance: This negative limitation is a critical distinguishing feature of the claimed stable formulation. Infringement of the ’735 patent hinges on the factual question of the accused product's composition, and the interpretation of this absolute-sounding term will be key.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation (i.e., not intentionally added): The patent's background explains that the problem of degradation arose in prior formulations and that the invention solves this by omitting the ingredient, suggesting the key is its absence as a functional excipient rather than absolute chemical purity (’735 Patent, col. 1:65-col. 2:30).
    • Evidence for a Narrower Interpretation (i.e., absolute absence): The plain language of the claim is absolute. A defendant might argue that the claim requires the complete absence of the substance, even at trace or impurity levels that could be present from manufacturing processes or other raw materials.

VI. Other Allegations

Indirect Infringement

The complaint alleges induced infringement for all three patents, asserting that Defendants' proposed prescribing information will instruct physicians and patients to use the generic drug in a way that directly infringes the patented methods and compositions (Compl. ¶¶ 49, 58, 67, 85, 94). The complaint also pleads contributory infringement for the ’410 and ’346 patents, alleging that the product is especially made for an infringing use and is not a staple article of commerce with substantial non-infringing uses (Compl. ¶¶ 70-71, 97-98).

Willful Infringement

Willfulness is alleged based on Defendants' knowledge of the patents-in-suit, purportedly gained from the patents' listing in the FDA's Orange Book and from the Paragraph IV certification notice letter itself (Compl. ¶¶ 28, 31). The complaint alleges that Defendants' infringement "has been, and continues to be, deliberate" (Compl. ¶¶ 59, 80, 86).

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

  • A central issue will be one of compositional fact: does the formulation detailed in Mylan's confidential ANDA actually fall within the specific compositional limitations of U.S. Patent No. 8,802,735, particularly with respect to the claimed weight-percent ranges and the negative limitation requiring the absence of colloidal silicon dioxide? This question is purely evidentiary and will depend on discovery.
  • The case will also turn on a question of induced infringement: will the instructions for use in Mylan’s proposed product label be sufficient to prove that Mylan specifically intended for physicians and patients to perform the patented methods of treating MS (the ’410 patent) and managing the rosuvastatin drug interaction (the ’346 patent)?
  • A key legal question will be one of definitional scope: how will the court construe the negative limitation "does not contain colloidal silicon dioxide" in the ’735 patent? The determination of whether this term requires absolute purity or simply the absence of the substance as an intentionally added excipient could be dispositive for infringement of that patent.