DCT

1:17-cv-00040

Sanofi Aventis US LLC v. Par Pharmaceutical Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:

  • Case Identification: 1:17-cv-00040, D. Del., 01/12/2017

  • Venue Allegations: Venue is alleged based on Defendants being incorporated in Delaware, conducting business in the state, and filing an Abbreviated New Drug Application (ANDA) seeking approval to sell the accused products throughout the United States, including in Delaware.

  • Core Dispute: Plaintiffs allege that Defendants' filing of an ANDA to market a generic version of the multiple sclerosis drug Aubagio® (teriflunomide) constitutes an act of infringement of three U.S. patents covering methods of use, stable tablet formulations, and methods for managing drug-drug interactions.

  • Technical Context: The technology concerns oral pharmaceutical treatments for multiple sclerosis (MS), a chronic autoimmune disease of the central nervous system.

  • Key Procedural History: The complaint notes that U.S. Patent No. 6,794,410 underwent reexamination, resulting in the issuance of a certificate on July 31, 2013, which allowed new claims 2-22. The complaint also states that the term of the '410 patent was extended under 35 U.S.C. § 156. This reexamination history will be significant for construing the scope of the new claims.

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 Issue Date
2010-07-12 U.S. Patent No. 8,802,735 Priority Date
2013-02-04 U.S. Patent No. 9,186,346 Priority Date
2013-07-31 U.S. Patent No. 6,794,410 Reexamination Certificate (C1) Issued
2014-08-12 U.S. Patent No. 8,802,735 Issue Date
2015-11-17 U.S. Patent No. 9,186,346 Issue Date
2016-11-29 Date of Defendants' ANDA Notice Letter
2017-01-12 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, issued September 21, 2004.

The Invention Explained

  • Problem Addressed: The patent describes multiple sclerosis (MS) as a debilitating inflammatory neurological illness for which there was no cure at the time of the invention. It notes that existing therapies had significant drawbacks, including side-effect liabilities, limited efficacy, and the potential for patients to develop neutralizing antibodies that reduce treatment effectiveness (’410 Patent, col. 2:4-56).
  • The Patented Solution: The invention provides a method for treating MS by administering teriflunomide, the active metabolite of the known anti-rheumatic drug leflunomide. The patent proposes using teriflunomide directly as a treatment to alleviate symptoms and arrest the progression of MS (’410 Patent, Abstract; col. 2:57-65).
  • Technical Importance: The invention represented a method of using an oral compound for MS, offering a potential alternative to the injectable therapies that were standard at the time.

Key Claims at a Glance

  • The complaint asserts at least claim 10, which is an independent method claim added during reexamination (Compl. ¶63).
  • 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 does not explicitly reserve the right to assert dependent claims.

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

  • Patent Identification: U.S. Patent No. 8,802,735, issued August 12, 2014.

The Invention Explained

  • Problem Addressed: The patent identifies a stability issue with solid tablet formulations of teriflunomide. Specifically, it notes that during storage, the active ingredient can degrade, leading to an increase in the concentration of a degradant known as 2-cyano-N-(4-trifluoromethyl-phenyl)-acetamide (’735 Patent, col. 2:1-18).
  • The Patented Solution: The invention claims to solve this stability problem through specific formulations. One embodiment describes a solid pharmaceutical composition that, counter-intuitively, achieves improved stability by omitting colloidal silicon dioxide, a commonly used pharmaceutical excipient (’735 Patent, col. 2:25-31; col. 3:1-9). Other embodiments involve adding an acidic compound to control the formulation's pH (’735 Patent, col. 2:30-34).
  • Technical Importance: This technology addresses the critical pharmaceutical challenge of ensuring drug product purity and stability over its shelf life, which is essential for safety and efficacy.

Key Claims at a Glance

  • The complaint asserts at least claim 10, which is an independent method claim, and also alleges that the accused product is "covered by one or more claims" of the patent, suggesting assertion of composition claims as well (Compl. ¶¶ 82, 85). Independent claim 1 is a composition claim.
  • The essential elements of independent claim 1 are:
    • A solid pharmaceutical composition comprising
    • a) about 1% to 30% weight:weight Teriflunomide, or a pharmaceutically acceptable basic addition salt thereof,
    • b) about 5% to 20% weight:weight disintegrant,
    • c) about 0% to 40% weight:weight binder,
    • d) about 0.1% to 2% weight:weight lubricant and
    • e) 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.

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, issued November 17, 2015.

Technology Synopsis

The patent addresses a previously unknown adverse drug-drug interaction. The inventors discovered that co-administering teriflunomide with rosuvastatin (a widely used cholesterol-lowering drug) significantly increases a patient's exposure to rosuvastatin (’346 Patent, col. 2:41-49). The patented solution is a method for managing this risk by reducing the normal dose of rosuvastatin by about 50% when it is co-administered with teriflunomide (’346 Patent, col. 2:49-54).

Asserted Claims

The complaint asserts at least claim 5, which is an independent method claim (Compl. ¶89).

Accused Features

The complaint alleges that the prescribing information for Defendants' ANDA product will instruct users on how to manage the drug interaction when co-administering teriflunomide and rosuvastatin, thereby inducing infringement of the patented method (Compl. ¶¶ 47, 51, 53).

III. The Accused Instrumentality

Product Identification

The accused products are Defendants' 7 mg and 14 mg "Teriflunomide ANDA Products," which are proposed generic versions of Plaintiffs' Aubagio® drug product (Compl. ¶11).

Functionality and Market Context

The Teriflunomide ANDA Products contain the active ingredient teriflunomide and are intended for the treatment of patients with relapsing forms of MS, the same indication as Aubagio® (Compl. ¶¶ 41, 45). The complaint alleges that Defendants' ANDA asserts that their products are bioequivalent to Aubagio® (Compl. ¶42). It further alleges, on information and belief, that the accused products are formulated to have a pH of no more than 2.2 (Compl. ¶46). The action is based on Defendants’ filing of ANDA No. 209681 with the FDA seeking approval for commercial manufacture and sale in the United States (Compl. ¶11).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

U.S. Patent No. 6,794,410 Infringement Allegations

Claim Element (from Independent Claim 10) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating multiple sclerosis which comprises Defendants seek approval to market the Teriflunomide ANDA Products for the treatment of patients with relapsing forms of multiple sclerosis. ¶45 col. 2:57-59
orally administering The accused ANDA products are formulated as tablets for oral administration. ¶11 col. 8:21-26
to a patient that has manifested clinical disease The proposed indication is for treating "patients with relapsing forms of multiple sclerosis," which implies patients with manifested clinical disease. ¶45 col. 8:22-23
a therapeutically effective amount of a compound of Formula I, its stereoisomer, or a pharmaceutically acceptable salt thereof The active ingredient of the Teriflunomide ANDA Products is alleged to be teriflunomide. ¶41 col. 2:57-62
  • Identified Points of Contention:
    • Scope Questions: The term "a patient that has manifested clinical disease" was added during reexamination. A potential dispute may arise over whether the scope of patients described in the Defendants' proposed label aligns precisely with the definition of this claim term as construed by the court.
    • Technical Questions: The infringement allegation relies on induced infringement, where Defendants' product label instructs physicians and patients to perform the claimed method. The central question will be whether the language of the proposed label, once produced in discovery, directs administration in a manner that satisfies all limitations of claim 10.

U.S. Patent No. 8,802,735 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A solid pharmaceutical composition comprising... The Teriflunomide ANDA Products are solid tablets. ¶11 col. 2:25-26
...about 1% to 30% weight:weight Teriflunomide... and specified percentages of disintegrant, binder, lubricant, and diluents The complaint alleges that the specific formulation of the ANDA product infringes, but states that the information provided by Defendants so far is insufficient to confirm the exact composition. ¶¶ 39, 58 col. 3:1-9
...wherein the solid pharmaceutical composition does not contain colloidal silicon dioxide. The complaint alleges infringement but notes that the absence or presence of this specific excipient in the accused formulation is subject to discovery. ¶¶ 39, 41, 58 col. 3:8-9
  • Identified Points of Contention:
    • Scope Questions: A central dispute will be over the negative limitation "does not contain colloidal silicon dioxide." The case will likely turn on whether discovery reveals the presence of any amount of this excipient in the accused product.
    • Technical Questions: The primary question is factual: what is the precise formulation of the Teriflunomide ANDA Products? The complaint explicitly states that Plaintiffs lack the information needed to confirm infringement and will rely on discovery (Compl. ¶¶ 39-40). This suggests the infringement analysis will be heavily dependent on the chemical analysis of Defendants' product and the contents of the ANDA filing.

V. Key Claim Terms for Construction

For the ’410 Patent

  • The Term: "a patient that has manifested clinical disease"
  • Context and Importance: This phrase was added to the independent claims during reexamination and is therefore a critical limitation on the scope of the patented method. Its construction will determine which patient populations fall within the claim. Practitioners may focus on this term because limitations added during reexamination are often scrutinized to determine the extent to which the patentee surrendered subject matter.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification describes MS in general terms as a "debilitating, inflammatory, neurological illness" and discusses its various symptoms, which could support a broad reading to include any patient exhibiting such signs (’410 Patent, col. 2:4-11).
    • Evidence for a Narrower Interpretation: The specification explicitly lists four clinical patterns of the disease: "relapsing-remitting, secondary progressive, primary-progressive and progressive-relapsing" (’410 Patent, col. 2:11-14). A defendant might argue that "manifested clinical disease" should be limited to these formally recognized patterns or to patients who have experienced an acute episode, as discussed in the claims added during reexamination (’410 Patent, Reexam. Cert., claim 5).

For the ’735 Patent

  • The Term: "pH of no more than about 2.2" (from asserted independent claim 10)
  • Context and Importance: The complaint specifically alleges that the accused product has "a pH of no more than 2.2" (Compl. ¶46), making this property a key battleground. The construction of "about 2.2" will be critical. A narrow range could allow Defendants to design around the claim, while a broader range would make infringement more likely.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The use of the word "about" itself suggests the patentee did not intend the value to be an exact cutoff. A plaintiff would argue it encompasses a range of values that achieve the same result (improved stability) and accounts for normal measurement variability.
    • Evidence for a Narrower Interpretation: The specification provides a specific protocol for measuring the pH: "suspending one tablet in about 1 ml of purified water. The pH of the supernatant is determined with a pH sensitive probe" (’735 Patent, col. 5:51-54). A defendant may argue that the term "about 2.2" must be interpreted strictly in the context of this specific measurement method and the examples provided in the patent, which show tested pH values of 2.2, 2.9, and 3.3 (Table 2), suggesting 2.2 is a meaningful endpoint.

VI. Other Allegations

  • Indirect Infringement: The complaint heavily relies on theories of induced infringement for the method claims in the ’410 and ’346 patents. It alleges that Defendants know their product will be used to infringe and that the proposed prescribing information will actively instruct physicians and patients to perform the claimed methods, such as administering the drug to treat MS (for the ’410 patent) and managing the rosuvastatin interaction (for the ’346 patent) (Compl. ¶¶ 51-57, 60).
  • Willful Infringement: Plaintiffs allege that Defendants had notice of all three patents-in-suit prior to the infringing activity (the ANDA submission) and that the infringement is and will continue to be deliberate (Compl. ¶¶ 33, 65, 86, 91).

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

  • A central question will be one of compositional fact: will discovery confirm that Defendants’ generic teriflunomide formulation contains the specific combination of excipients claimed in the ’735 patent—most critically, whether it omits colloidal silicon dioxide (implicating claim 1) or is formulated to a pH of no more than 2.2 (implicating claim 10)?
  • A key evidentiary issue will be one of induced infringement: does the language of the proposed label for Defendants' generic product provide sufficient instruction to prove that Defendants specifically intend for physicians to prescribe the drug in a manner that directly infringes the method claims of the ’410 and ’346 patents?
  • A final legal question will concern claim scope: how will the court construe the term "a patient that has manifested clinical disease," which was added to the ’410 patent claims during reexamination, and will the instructions on the accused product's label fall within that scope?