DCT

1:17-cv-00019

Sanofi Aventis US LLC v. Breckenridge Pharmaceutical Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00019, D. Del., 01/05/2017
  • Venue Allegations: Plaintiffs allege venue is proper in the District of Delaware based on Defendant’s alleged intent to market and sell its generic product in the state, its maintenance of a distributorship network, and its prior submission to the court's jurisdiction in other cases.
  • Core Dispute: Plaintiffs allege that Defendant's filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiffs' Aubagio® (teriflunomide) drug product infringes three patents related to the drug's use, formulation, and co-administration.
  • Technical Context: The technology concerns teriflunomide, an oral therapy for treating relapsing forms of multiple sclerosis (MS), a debilitating autoimmune disease of the central nervous system.
  • Key Procedural History: The complaint notes that the '410 patent was the subject of a reexamination proceeding, which resulted in the cancellation of original claim 1 and the addition of new claims, including asserted claim 10. Defendant filed a Paragraph IV certification for the '410 and '735 patents, asserting they are invalid or will not be infringed, but the complaint states Defendant did not address the '346 patent in its notice letter.

Case Timeline

Date Event
2001-04-05 '410 Patent Priority Date
2004-09-21 '410 Patent Issue Date
2010-07-12 '735 Patent Priority Date
2013-03-12 '346 Patent Priority Date
2013-07-31 '410 Patent Reexamination Certificate (C1) Issue Date
2014-08-12 '735 Patent Issue Date
2015-11-17 '346 Patent Issue Date
2016-11-22 Plaintiffs received Defendant's ANDA Notice Letter
2017-01-05 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 existing therapies for multiple sclerosis (MS) as having significant liabilities, including side effects and the potential for patients to develop neutralizing antibodies that decrease the therapy's efficacy over time, creating a "strong need for new drugs" ('410 Patent, col. 2:54-59).
  • The Patented Solution: The invention is a method for treating MS by orally administering a therapeutically effective amount of the compound teriflunomide. The specification explains that teriflunomide, an active metabolite of the drug leflunomide, exhibits antiproliferative effects on immune cells, which are believed to be responsible for the demyelination characteristic of MS ('410 Patent, col. 2:18-34; col. 3:60-66).
  • Technical Importance: The invention provides a novel oral small-molecule treatment for MS, offering an alternative to injectable biologic therapies prevalent at the time.

Key Claims at a Glance

  • The complaint asserts independent claim 10, which was added during reexamination (Compl. ¶56).
  • Essential elements of independent claim 10 include:
    • 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. ¶56).

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 notes that during stability studies of a solid pharmaceutical formulation of teriflunomide, "a strong increase in one degradant" was observed, creating a need for a more stable formulation ('735 Patent, col. 2:1-3).
  • The Patented Solution: The invention is a solid pharmaceutical composition that achieves improved stability by omitting a specific common excipient, colloidal silicon dioxide. The patent explains that formulating teriflunomide without this ingredient limits the formation of degradants like 2-cyano-N-(4-trifluoromethyl-phenyl)-acetamide ('735 Patent, Abstract; col. 2:25-29).
  • Technical Importance: Ensuring the chemical stability of a drug product is critical for its safety, efficacy, and commercial viability, as it prevents the formation of potentially harmful impurities and ensures a consistent shelf life.

Key Claims at a Glance

  • The complaint asserts independent claims 1 and 10 (Compl. ¶74).
  • Essential elements of independent claim 1 include:
    • A solid pharmaceutical composition comprising about 1% to 30% by weight of Teriflunomide
    • about 5% to 20% by weight of a disintegrant
    • about 0% to 40% by weight of a binder
    • about 0.1% to 2% by weight of a lubricant
    • the remaining percentage comprising diluents
    • a negative limitation: "provided that said solid pharmaceutical composition does not contain colloidal silicon dioxide."
  • The complaint reserves the right to assert other claims (Compl. ¶76).

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

Technology Synopsis

The patent addresses a drug-drug interaction discovered between teriflunomide and rosuvastatin (a common cholesterol-lowering medication). Administration of teriflunomide was found to increase a patient's plasma concentration of rosuvastatin ('346 Patent, col. 1:13-19, col. 3:55-59). The invention provides a method for managing this risk by reducing the normal dose of rosuvastatin by approximately 50% when it is co-administered with teriflunomide ('346 Patent, col. 2:5-8).

Asserted Claims

The complaint asserts at least claim 5 (Compl. ¶85). Claim 5 is an independent claim.

Accused Features

The complaint alleges that Defendant’s proposed product labeling will instruct for the co-administration of the generic teriflunomide product with rosuvastatin, thereby inducing infringement of the patented method (Compl. ¶¶ 42, 86).

III. The Accused Instrumentality

Product Identification

Defendant Breckenridge's proposed 7 mg and 14 mg "Teriflunomide ANDA Products," which are generic versions of Plaintiffs' Aubagio® drug product (Compl. ¶7).

Functionality and Market Context

The accused product is a pharmaceutical tablet for the treatment of patients with relapsing forms of multiple sclerosis (Compl. ¶36). The complaint alleges, on information and belief, that the ANDA product contains the same active ingredient (teriflunomide), is bioequivalent to Aubagio®, and will be sold with a "substantially the same" label for the same approved indications (Compl. ¶¶ 30-31, 33, 35). The complaint notes that at the time of filing, Plaintiffs had not been given access to the confidential details of the ANDA filing itself (Compl. ¶¶ 27-28). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

'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 to a patient that has manifested clinical disease Defendant's proposed product label will allegedly instruct physicians and patients to administer the Teriflunomide ANDA Products to treat relapsing forms of multiple sclerosis, an indication for a patient that has manifested clinical disease. ¶¶36, 41 '410 C1, col. 2:62-65
a therapeutically effective amount of a compound of Formula I... Defendant's ANDA Products are alleged to contain a therapeutically effective amount of teriflunomide, the compound of Formula I, as the active ingredient. ¶30 '410 C1, col. 2:63-65
  • Identified Points of Contention:
    • Scope Questions: The primary dispute may center on whether the instructions for use in Defendant's proposed label constitute a method of treatment that falls within the scope of claim 10. This is particularly relevant as the complaint alleges Defendant's Notice Letter did not provide a detailed statement regarding infringement and was silent on how it might avoid the '346 patent, raising the question of whether a "skinny label" or other "carve out" strategy is being employed (Compl. ¶¶ 50-53).
    • Technical Questions: A factual question exists as to whether "relapsing forms of multiple sclerosis," the indication sought by Defendant (Compl. ¶36), is coextensive with treating "a patient that has manifested clinical disease" as required by the claim, a term added during reexamination.

'735 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A solid pharmaceutical composition comprising about 1% to 30% weight:weight Teriflunomide... The complaint alleges on information and belief that the ANDA Product is formulated with 1% to 30% by weight of teriflunomide. ¶37 '735, col. 3:1-3
about 5% to 20% weight:weight disintegrant, The complaint alleges on information and belief that the ANDA Product is formulated with 5% to 20% by weight of a disintegrant. ¶37 '735, col. 3:4-5
about 0% to 40% weight:weight binder, The complaint alleges on information and belief that the ANDA Product is formulated with 0% to 40% by weight of a binder. ¶37 '735, col. 3:6
about 0.1% to 2% weight:weight lubricant, The complaint alleges on information and belief that the ANDA Product is formulated with 0.1% to 2% by weight of a lubricant. ¶37 '735, col. 3:7
the remaining percentage comprising diluents, The complaint alleges on information and belief that the remainder of the ANDA Product's formulation consists of diluents. ¶37 '735, col. 3:8
provided that said solid pharmaceutical composition does not contain colloidal silicon dioxide. The complaint alleges on information and belief that the ANDA Product is specifically formulated "without colloidal silicon dioxide." ¶37 '735, col. 3:9-10
  • Identified Points of Contention:
    • Evidentiary Questions: The infringement analysis for the '735 patent is entirely dependent on the actual, confidential formulation in Defendant's ANDA. Since Plaintiffs state they have not reviewed the ANDA (Compl. ¶27), the key contention will be evidentiary: does the Defendant's product, once revealed in discovery, actually meet the specific weight-percentage ranges and, most critically, is it completely free of colloidal silicon dioxide? The complaint's allegations on these points are made on "information and belief" (Compl. ¶37).

V. Key Claim Terms for Construction

For the '410 Patent:

  • The Term: "a patient that has manifested clinical disease" (from claim 10)
  • Context and Importance: This phrase was added to the claims during reexamination and defines the specific patient population covered by the patented method. Its construction will be critical to determining the scope of the method claim and whether the indication on Defendant's proposed label induces infringement. Practitioners may focus on this term to understand the scope of the claim as narrowed during the reexamination process.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification's background section discusses MS in general terms, including the four clinical patterns of the disease, which could support an interpretation that any patient exhibiting symptoms of MS has "manifested clinical disease" ('410 Patent, col. 2:11-16).
    • Evidence for a Narrower Interpretation: The patent's experimental example describes an animal model where treatment began after immunization at a time point considered to "represent the initial phase of an acute episode of MS" ('410 Patent, col. 7:17-21). This could be argued to narrow the claim's scope to patients at a specific stage of the disease. The prosecution history of the reexamination, though not provided, would be a primary source for arguments about why this language was added.

For the '735 Patent:

  • The Term: "colloidal silicon dioxide" (from claim 1)
  • Context and Importance: This is a negative limitation that is central to the patent's claim of improved stability. The precise definition of what constitutes "colloidal silicon dioxide" is therefore essential, as the presence of any substance meeting that definition in the accused product would allow Defendant to escape infringement of this claim.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party could argue for a functional definition, where any silica-based compound that does not cause the degradation problem would fall outside the scope of the excluded term.
    • Evidence for a Narrower Interpretation: The specification provides a highly specific definition: "submicroscopic fumed silica, also known as pyrogenic silica... Primary particle size is from 5 nm to 50 nm... It can be obtained for example under the trade name Aeorsil 200 Pharma..." ('735 Patent, col. 3:11-18). This explicit definition, including physical properties and commercial examples, provides strong evidence for a very specific and limited meaning of the term.

VI. Other Allegations

  • Indirect Infringement: The complaint's allegations for the '410 and '346 patents are primarily based on theories of indirect infringement. It alleges that Defendant will induce infringement by physicians and patients who will directly infringe the method claims by following the instructions on the accused product's label (Compl. ¶¶ 44-46, 86). It further alleges contributory infringement, stating that the accused products are not staple articles of commerce suitable for substantial non-infringing use (Compl. ¶¶ 48, 87).
  • Willful Infringement: The complaint alleges that Defendant had knowledge of the patents prior to its infringing activity, citing the Orange Book listing and the Notice Letter it sent to Plaintiffs (Compl. ¶¶ 20, 22-23). Based on this alleged pre-suit knowledge, the complaint asserts that Defendant's infringement "has been, and continues to be, deliberate" (Compl. ¶¶ 57, 77, 88).

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

  • A core issue will be one of regulatory-driven infringement: For the '410 and '346 method-of-use patents, the case will likely turn on the final language of Defendant's FDA-approved label. A key question for the court will be whether Defendant's label successfully "carves out" the patented methods of treatment, or if the instructions for the approved indication will inevitably induce physicians and patients to practice the claimed methods.
  • A key evidentiary question will be one of compositional fact: For the '735 formulation patent, the dispute hinges on the confidential details of the ANDA. The central question is whether Defendant's actual product formulation falls within the claimed weight-percentage ranges and, critically, is entirely free of "colloidal silicon dioxide," a fact Plaintiffs have alleged on information and belief but have not yet verified.
  • A third question will be one of claim scope post-reexamination: The interpretation of the '410 patent will require the court to construe the scope of claim 10, particularly the phrase "a patient that has manifested clinical disease," which was added during reexamination. Resolving this will likely involve a detailed analysis of the patent's reexamination history to determine the precise boundaries of the narrowed claim.