DCT

1:17-cv-00039

Sanofi Aventis US LLC v. Amneal Pharma LLC

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00039, D. Del., 01/12/2017
  • Venue Allegations: Plaintiff alleges venue is proper in Delaware because Defendants conduct business in the state, have availed themselves of the state's laws, and intend to market the accused products in Delaware.
  • Core Dispute: Plaintiff alleges that Defendant's filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the multiple sclerosis drug Aubagio® (teriflunomide) constitutes an act of infringement of three patents covering methods of use, stable formulations, and management of drug interactions.
  • Technical Context: The patents relate to treatments for multiple sclerosis (MS), a chronic autoimmune disease of the central nervous system, and specifically to formulations and methods involving the active ingredient teriflunomide.
  • Key Procedural History: This lawsuit was triggered by Defendant Amneal's submission of ANDA No. 209613 and its associated Paragraph IV certification, which asserted that Plaintiff's patents are invalid, unenforceable, or will not be infringed by Amneal's proposed generic product. The U.S. Patent and Trademark Office previously granted a reexamination certificate for the ’410 patent, allowing 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 Issued
2010-07-12 U.S. Patent No. 8,802,735 Priority Date
2013-03-12 U.S. Patent No. 9,186,346 Priority Date
2013-07-31 Reexamination Certificate for U.S. Patent No. 6,794,410 Granted
2014-08-12 U.S. Patent No. 8,802,735 Issued
2015-11-17 U.S. Patent No. 9,186,346 Issued
2016-11-29 Date of Defendant's ANDA Notice Letter
2017-01-12 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 Sep. 21, 2004

The Invention Explained

  • Problem Addressed: The patent’s background section identifies multiple sclerosis (MS) as a debilitating inflammatory neurological illness for which, at the time, there was no cure (ʼ410 Patent, col. 3:5-8). It notes that existing therapies had significant limitations, including side effects and limited efficacy, creating a need for new drugs to combat the disease (ʼ410 Patent, col. 3:40-54).
  • The Patented Solution: The invention provides a method of treating MS by administering a specific compound, (Z)-2-cyano-3-hydroxy-but-2-enoic acid-(4'-trifluoromethylphenyl)-amide, known as teriflunomide (ʼ410 Patent, Abstract). The patent describes that teriflunomide produces antiproliferative effects on immune cells by inhibiting the enzyme dihydroorotate dehydrogenase, which is essential for pyrimidine synthesis, thereby addressing the T-cell-mediated autoimmune reaction hypothesized to cause MS (ʼ410 Patent, col. 3:22-34, 62-67).
  • Technical Importance: The invention proposed a new oral therapeutic agent with a distinct mechanism of action for treating a serious disease with limited treatment options (ʼ410 Patent, col. 3:55-59).

Key Claims at a Glance

  • The complaint asserts infringement of at least claim 10, which depends from independent claim 2 (as added by reexamination) (Compl. ¶59).
  • Independent Claim 2 (Reexamined):
    • A method of treating multiple sclerosis (MS)
    • 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
    • wherein the treating alleviates the symptoms of an acute episode of MS.
  • The complaint reserves the right to assert other claims (Compl. ¶59).

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 Aug. 12, 2014

The Invention Explained

  • Problem Addressed: The patent’s background discloses that a solid pharmaceutical formulation of teriflunomide developed for clinical studies exhibited instability, showing a "strong increase in one degradant" during stability testing (’735 Patent, col. 2:1-3).
  • The Patented Solution: The invention is a solid pharmaceutical composition of teriflunomide with improved stability. The key feature of one embodiment is the absence of colloidal silicon dioxide, an excipient commonly used in tablet formulations ('735 Patent, col. 2:43-46). Another embodiment involves formulating the composition to have a low pH, for example, by adding an acidic reacting compound ('735 Patent, col. 2:47-54).
  • Technical Importance: This technology provided a more stable oral dosage form for teriflunomide, which is critical for ensuring product safety, efficacy, and adequate shelf-life for a commercial pharmaceutical product ('735 Patent, col. 2:19-24).

Key Claims at a Glance

  • The complaint asserts infringement of at least claim 10 (Compl. ¶78, ¶81).
  • Independent Claim 10:
    • A solid pharmaceutical composition
    • comprising a therapeutically effective amount of teriflunomide or a pharmaceutically acceptable basic addition salt thereof
    • wherein the pH of the solid pharmaceutical composition is no more than about 2.2.
  • The complaint reserves the right to assert other claims (Compl. ¶81).

Multi-Patent Capsule: U.S. Patent No. 9,186,346 - “Methods for Reducing the Risk of an Adverse Teriflunomide and Rosuvastatin Interaction in Multiple Sclerosis Patients,” Issued Nov. 17, 2015

  • Technology Synopsis: The patent addresses an adverse drug-drug interaction. The specification explains that co-administration of teriflunomide and rosuvastatin (a widely used cholesterol-lowering drug) causes a significant increase in the plasma concentration of rosuvastatin, creating a safety risk (’346 Patent, col. 3:52-59). The patented solution is a method for managing this risk by instructing that when the two drugs are co-administered, the normal dose of rosuvastatin should be reduced by about 50% ('346 Patent, col. 2:1-4).
  • Asserted Claims: The complaint asserts infringement of at least independent claim 5 (Compl. ¶85).
  • Accused Features: The complaint alleges that Defendant’s prescribing information for its generic teriflunomide product will instruct users on managing co-administration with rosuvastatin in a way that infringes claim 5, such as by recommending a dose of rosuvastatin not to exceed 10 mg once daily (Compl. ¶43, ¶49).

III. The Accused Instrumentality

Product Identification

  • Defendant Amneal’s proposed "Teriflunomide ANDA Products," which are 7 mg and 14 mg generic teriflunomide tablets for which Amneal seeks FDA approval under ANDA No. 209613 (Compl. ¶10).

Functionality and Market Context

  • The accused products are intended to be a generic substitute for Plaintiff's Aubagio® drug (Compl. ¶10). The complaint alleges the products contain the same active ingredient, teriflunomide, and are intended for the same indication: the treatment of patients with relapsing forms of multiple sclerosis (Compl. ¶37, ¶40). The complaint further alleges, on information and belief, that the accused products are formulated to have a pH of no more than 2.2 and that their prescribing information will instruct on co-administration with rosuvastatin (Compl. ¶42, ¶43). The products are intended for commercial manufacture, use, and sale throughout the United States (Compl. ¶10).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

’410 Patent Infringement Allegations

Claim Element (from Independent Claim 2) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating multiple sclerosis (MS) comprising orally administering to a patient that has manifested clinical disease Defendant is seeking approval to market its product for treating relapsing forms of MS, and the product's prescribing information will instruct physicians and patients to orally administer it to such patients. ¶40, ¶41, ¶48 col. 6:8-12; col. 3:11-16
a therapeutically effective amount of a compound of Formula I [teriflunomide], its stereoisomer, or a pharmaceutically acceptable salt thereof The accused product contains a therapeutically effective amount of teriflunomide as its active ingredient. ¶37, ¶42 col. 3:20-22
wherein the treating alleviates the symptoms of an acute episode of MS The accused product's prescribing information will instruct users to administer the product to alleviate and/or slow the appearance of symptoms of an acute episode of MS. ¶41, ¶48 col. 6:13-15

’735 Patent Infringement Allegations

Claim Element (from Independent Claim 10) Alleged Infringing Functionality Complaint Citation Patent Citation
A solid pharmaceutical composition comprising a therapeutically effective amount of teriflunomide... Defendant's accused ANDA product is a solid tablet containing a therapeutically effective amount of teriflunomide. ¶10, ¶42 col. 2:38-43
wherein the pH of the solid pharmaceutical composition is no more than about 2.2. The complaint alleges that Defendant is seeking approval for products that have a pH of no more than 2.2. ¶42 col. 5:51-54
  • Identified Points of Contention:
    • Factual Question (’735 Patent): The infringement allegation for the '735 patent hinges on the factual assertion that Amneal's formulation has a pH of "no more than 2.2." (Compl. ¶42). As this is pleaded on "information and belief," a primary point of contention will be whether discovery confirms this specific chemical property in the accused product.
    • Scope Question (’410 and ’346 Patents): For the method claims in the ’410 and ’346 patents, the analysis will turn on the specific language in the FDA-approved label for Amneal's product. A key question will be whether the final label language is found to actively encourage, recommend, or promote the specific patented methods, thereby inducing infringement by physicians and patients.

V. Key Claim Terms for Construction

For the ’410 Patent (Claim 2): "patient that has manifested clinical disease"

  • Context and Importance: This term defines the patient population for the claimed method. Its construction is critical because it determines whether the method applies broadly to anyone diagnosed with MS or is limited to patients at a specific clinical stage (e.g., currently experiencing an acute episode). Practitioners may focus on this term to argue for a broader or narrower scope of infringement.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification describes MS in general terms, listing the four standard clinical patterns of the disease, which could support an interpretation that "manifested clinical disease" refers to any patient with a formal MS diagnosis ('410 Patent, col. 3:11-16).
    • Evidence for a Narrower Interpretation: The reexamined claim links the treatment to alleviating symptoms of an "acute episode." A party could argue that "manifested clinical disease" should be read in that context, limiting it to patients actively showing symptoms as demonstrated in the patent's EAE animal model, which mimics an acute flare-up ('410 Patent, col. 6:18-21).

For the ’735 Patent (Claim 10): "pH of the solid pharmaceutical composition"

  • Context and Importance: This limitation is a precise, quantitative measure defining the invention. The method of measuring this pH is central to the infringement analysis, as different measurement techniques could yield different results.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim itself does not recite a specific method for measuring the pH. A party might argue that any scientifically reasonable and standard method for determining the pH of such a composition should suffice, giving the term its plain and ordinary meaning.
    • Evidence for a Narrower Interpretation: The specification explicitly describes a protocol for measurement: "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 party could argue this description defines the specific procedure required to assess infringement, potentially narrowing the claim's scope to only what is measurable by that exact method.

VI. Other Allegations

  • Indirect Infringement: The complaint heavily relies on theories of induced infringement for the method claims of the ’410 and ’346 patents. It alleges that Defendants know of the patents and intend for physicians and patients to infringe by following the instructions on the proposed product label, which will allegedly mirror the label for Aubagio® (Compl. ¶47-49, ¶51, ¶56). The complaint also alleges that the product is not a staple article suitable for substantial non-infringing use (Compl. ¶55).
  • Willful Infringement: The complaint alleges that Defendants' infringement "has been, and continues to be, deliberate" (Compl. ¶61, ¶82, ¶87). This allegation is based on pre-suit knowledge of the patents, evidenced by Defendants' filing of a Paragraph IV certification against the patents-in-suit as part of their ANDA submission (Compl. ¶33).

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

  • A key evidentiary question will be one of compositional identity: Will discovery confirm the complaint's allegation that Amneal's proposed generic formulation possesses the specific physiochemical properties claimed in the ’735 patent, namely a pH of "no more than 2.2"? The method for measuring this pH will likely be a central point of dispute.
  • A core issue for the method patents ('410 and '346) will be one of inducement: Will the language of the final, FDA-approved label for Amneal's product be found to contain instructions that actively direct or encourage physicians and patients to perform the patented methods, specifically alleviating symptoms of an acute MS episode and reducing a co-administered rosuvastatin dose by approximately 50%?
  • The case also raises a question of patent portfolio strategy: How will the claims of the three distinct patents—covering a method of use ('410), a stable formulation ('735), and a method to manage a drug interaction ('346)—interact to create overlapping fields of protection, and can Amneal design a product and label that avoids infringement of all three?