DCT

3:17-cv-08825

Boehringer Ingelheim Pharma Inc v. Sandoz Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:17-cv-08825, D.N.J., 10/20/2017
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey on the basis that Defendant Sandoz has a regular and established principal place of business in the state.
  • Core Dispute: Plaintiff alleges that Defendant's submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the cancer drug GILOTRIF® (afatinib) constitutes an act of infringement of three patents covering the drug's active ingredient, its manufacturing process, and its method of use.
  • Technical Context: The technology concerns afatinib, a kinase inhibitor used for the targeted therapy of specific forms of metastatic non-small cell lung cancer (NSCLC).
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiff's receipt of a Paragraph IV certification notice letter from Sandoz, which stated its belief that the patents-in-suit are invalid, unenforceable, or will not be infringed by its proposed generic product. The complaint notes that other similar actions have been filed against different generic manufacturers involving at least one of the patents-in-suit.

Case Timeline

Date Event
2000-12-28 U.S. Patent No. RE 43,431 Priority Date
2003-10-17 U.S. Patent No. 8,426,586 Priority Date
2005-11-11 U.S. Patent No. 9,539,258 Priority Date
2012-05-29 U.S. Patent No. RE 43,431 Issued
2013-04-23 U.S. Patent No. 8,426,586 Issued
2013-07-XX FDA approves NDA No. 201292 for GILOTRIF®
2017-01-10 U.S. Patent No. 9,539,258 Issued
2017-09-07 Sandoz sends Paragraph IV Notice Letter
2017-10-20 Complaint Filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Reissue Patent No. RE 43,431 - Quinazoline Derivatives and Pharmaceutical Compositions Containing Them

The Invention Explained

  • Problem Addressed: The patent describes a class of chemical compounds intended to treat diseases mediated by tyrosine kinases, which are enzymes involved in cellular signal transduction pathways often implicated in cancer (RE43431 Patent, col. 2:32-40).
  • The Patented Solution: The invention provides novel quinazoline derivatives, defined by a general chemical structure, that possess an inhibitory effect on signal transduction mediated by these tyrosine kinases. The patent discloses specific compounds of this class and their use in pharmaceutical compositions for treating tumoral diseases and diseases of the lungs and airways (RE43431 Patent, Abstract; col. 2:32-40). The active ingredient in GILOTRIF®, afatinib, is one such specific compound.
  • Technical Importance: The development of small-molecule tyrosine kinase inhibitors represented a significant advancement in oncology, enabling targeted therapies that could interfere with specific molecular pathways driving cancer growth (RE43431 Patent, Abstract).

Key Claims at a Glance

  • The complaint alleges infringement of one or more unspecified claims (Compl. ¶31). The patent’s independent claims include claims to a genus of compounds (Claim 1) and specific compounds (Claims 8 and 12). Claim 8 recites the specific chemical entity afatinib.
  • Independent Claim 8 consists of a single element:
    • The compound 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-((S)-(tetrahydrofuran-3-yl)oxy)quinazoline.

U.S. Patent No. 8,426,586 - Process for Preparing Amino Crotonyl Compounds

The Invention Explained

  • Problem Addressed: The patent’s background section states that a prior known process for synthesizing the active ingredient afatinib resulted in a low yield (at most 50%) and required purification by column chromatography, rendering it unsuitable for industrial-scale production (’586 Patent, col. 2:22-32). The prior process also relied on starting materials that were not commercially available in high purity or large quantities (’586 Patent, col. 2:32-39).
  • The Patented Solution: The invention provides an improved, high-yield manufacturing process that produces afatinib with high chemical purity and a low content of the undesired cis-isomer byproduct. The patented method is a multi-step synthesis, including a Wittig-Horner-Emmons reaction, designed to be suitable for commercial-scale manufacturing (’586 Patent, col. 2:40-56; col. 3:55-65).
  • Technical Importance: This invention provides an industrially practicable and efficient method for manufacturing a valuable pharmaceutical compound, overcoming the yield and purity limitations of prior art synthesis methods (’586 Patent, col. 2:40-49).

Key Claims at a Glance

  • The complaint asserts one or more unspecified claims (Compl. ¶48). Independent claims include a process claim (Claim 1) and product-by-process/crystalline form claims (Claims 9-11).
  • Independent Claim 1, a process claim, includes the following essential elements:
    • A process for preparing a specified class of aminocrotonyl compounds.
    • Step (a): reacting a specific aminoaryl compound (formula V) with di-(C1-4-alkyl)-phosphonoacetic acid after "corresponding activation".
    • Step (b): reacting the resulting intermediate compound (formula VI) with a specific aldehyde using suitable organic or inorganic bases.

U.S. Patent No. 9,539,258 - Quinazoline Derivatives for the Treatment of Cancer Diseases

  • Patent Identification: U.S. Patent No. 9539258, issued January 10, 2017 (Compl. ¶18).
  • Technology Synopsis: This patent claims methods of treating a specific cancer patient population. The invention is directed to a method of treating metastatic non-small cell lung cancer (NSCLC) of squamous histology in a second-line patient (i.e., one who has failed at least one prior chemotherapy regimen) by administering a therapeutically effective amount of afatinib or its salt (’258 Patent, Abstract; col. 23:1-10).
  • Asserted Claims: The complaint asserts one or more unspecified claims (Compl. ¶65). Independent Claim 1 is directed to the method of treatment.
  • Accused Features: The accused feature is the future sale and marketing of Sandoz's generic afatinib product for the patented indication. The complaint alleges that Sandoz’s product label will instruct healthcare professionals and patients to use the generic drug in a manner that directly infringes the claimed method of treatment (Compl. ¶¶65-66).

III. The Accused Instrumentality

Product Identification

Sandoz's proposed generic "afatinib dimaleate tablets" described in its Abbreviated New Drug Application (ANDA) No. 210703 (the "ANDA Product") (Compl. ¶¶19-20).

Functionality and Market Context

The ANDA Product is a generic version of Plaintiff's GILOTRIF® tablets, which contain the active pharmaceutical ingredient afatinib (Compl. ¶¶13, 19). GILOTRIF® is a kinase inhibitor approved for two indications: the first-line treatment of patients with metastatic NSCLC whose tumors have specific EGFR mutations, and the treatment of patients with metastatic, squamous NSCLC that is progressing after platinum-based chemotherapy (Compl. ¶13). The complaint alleges Sandoz intends to commercially manufacture and sell its generic product for these uses upon receiving FDA approval (Compl. ¶8).
No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail for analysis of infringement on a claim-element-by-claim-element basis. The infringement allegations are based on the act of filing the ANDA under 35 U.S.C. § 271(e)(2)(A), which creates a technical act of infringement for jurisdictional purposes (Compl. ¶¶29, 46, 63). The substantive infringement theories are summarized below.

  • ’431 Patent (Compound): The complaint alleges that the ANDA Product, if commercially manufactured and sold, would directly infringe because its active ingredient, afatinib dimaleate, is or contains the compound claimed in the ’431 Patent (Compl. ¶30).

    • Identified Points of Contention:
      • Scope Questions: A primary question will be whether the active pharmaceutical ingredient in Sandoz's ANDA Product is identical to the chemical structure recited in the asserted claims, including the specified (S)-stereoisomer configuration.
      • Technical Questions: What evidence does the ANDA submission contain regarding the precise chemical structure, including stereochemistry, of the afatinib Sandoz intends to manufacture?

  • ’586 Patent (Process): The complaint alleges that Sandoz’s commercial manufacture of the ANDA Product would infringe the process claims of the ’586 Patent (Compl. ¶48).

    • Identified Points of Contention:
      • Scope Questions: The key dispute will likely center on whether the synthesis method Sandoz uses or intends to use falls within the scope of the claimed process. This may involve disputes over the meaning of terms such as "corresponding activation."
      • Technical Questions: A central evidentiary question will be uncovering the specific steps of Sandoz's proprietary manufacturing process and comparing them to the steps recited in the asserted claims of the ’586 patent.

V. Key Claim Terms for Construction

  • The Term: "corresponding activation" (from Claim 1 of the ’586 Patent)
  • Context and Importance: This term appears in the first step of the claimed manufacturing process. The definition of what constitutes "activation" of the phosphonoacetic acid reagent is critical, as it will determine whether a range of potential chemical synthesis routes, including any used by Sandoz, fall within the claim's scope. Practitioners may focus on this term because Sandoz could argue its process uses a different activation agent or method that is not "corresponding" to that disclosed in the patent.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification provides "1,1-carbonyldiimidazole, 1,1-carbonylditriazole or propanephosphonic anhydride" as examples of activating agents, suggesting the term is not limited to a single compound (’586 Patent, col. 3:5-8). A party could argue "corresponding activation" refers functionally to any chemical step that prepares the phosphonoacetic acid for amide linking with the aniline compound.
    • Evidence for a Narrower Interpretation: A party could argue that the term should be limited to the specific activating agents disclosed in the patent's examples, particularly since the patent distinguishes its process from a prior art method using oxalyl chloride (’586 Patent, col. 2:32-39). This may support an interpretation that the term excludes older, less efficient activation methods.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Sandoz will induce and contribute to infringement of all three patents (Compl. ¶¶31, 48, 65). The allegation is most specific for the ’258 method-of-use patent, for which the complaint alleges Sandoz will knowingly induce infringement by healthcare professionals and end-users by providing a product label and insert with instructions for the patented use (Compl. ¶66).
  • Willful Infringement: The complaint does not explicitly use the word "willful." However, it alleges that Sandoz had "actual and constructive notice" of the patents prior to filing its ANDA and was aware its actions would constitute infringement (Compl. ¶¶32, 49, 67). It further alleges Sandoz's conduct makes the case "exceptional" under 35 U.S.C. § 285, which forms the basis for seeking enhanced damages and attorneys' fees (Compl. ¶¶34, 51, 69).

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

  • A core issue will be one of process infringement: what specific chemical synthesis pathway does Sandoz plan to use for its generic afatinib, and will discovery reveal that this process practices every step of the method claimed in the ’586 patent?
  • A second central question will be one of patent validity: although not detailed in the complaint, Sandoz’s Paragraph IV certification alleges invalidity and/or unenforceability. A key focus of the litigation will be whether Sandoz can prove by clear and convincing evidence that the asserted claims covering the compound, its manufacturing process, and its method of use are invalid over the prior art.
  • Finally, for the ’258 patent, the case may turn on a question of induced infringement: does Sandoz's proposed product labeling contain sufficient instructions and encouragements to prove that Sandoz intends for its generic drug to be used in the specific, patented method for treating second-line metastatic squamous NSCLC?