DCT

3:17-cv-08819

Boehringer Ingelheim Pharma Inc v. Sun Pharmaceutical Industries Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:17-cv-08819, D.N.J., 10/20/2017
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey based on Defendant Sun Pharmaceutical Industries, Inc. having a regular and established principal place of business in the state, and Defendant Sun Pharmaceutical Industries Ltd. being a foreign corporation.
  • Core Dispute: Plaintiff alleges that Defendant's filing of an Abbreviated New Drug Application (ANDA) for a generic version of the cancer drug GILOTRIF® constitutes infringement of a patent covering a process for preparing the drug and a specific crystalline form of the drug.
  • Technical Context: The technology concerns synthetic chemistry processes and crystalline forms (polymorphs) for afatinib, an active pharmaceutical ingredient used in oncology.
  • Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Defendant's submission of an ANDA with a Paragraph IV certification challenging the patent-in-suit. The complaint notes that Plaintiff's branded drug, GILOTRIF®, was approved by the FDA in July 2013. The complaint also certifies that related litigation is pending against other generic drug manufacturers concerning the same patent and drug product.

Case Timeline

Date Event
2003-10-17 ’586 Patent Priority Date
2013-04-23 ’586 Patent Issue Date
2013-07-01 GILOTRIF® (afatinib) NDA Approval
2017-09-05 Approximate Date of SUN's ANDA Notice Letter
2017-10-20 Complaint Filing Date

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

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

  • Patent Identification: U.S. Patent No. 8,426,586, "Process for Preparing Amino Crotonyl Compounds," issued April 23, 2013 (’586 Patent, p. 1; Compl. ¶18).

The Invention Explained

  • Problem Addressed: The patent describes prior art methods for synthesizing the active pharmaceutical ingredient afatinib as being unsuitable for industrial-scale manufacturing. These prior methods reportedly suffered from low yields, required difficult purification steps (column chromatography), and relied on starting materials that were not commercially available in high purity or large quantities (’586 Patent, col. 2:22-38).
  • The Patented Solution: The invention provides an improved, multi-step synthesis that is commercially viable. The process reacts a specific aminoaryl compound with an activated phosphonoacetic acid to create an intermediate, which is then reacted with an aldehyde to produce the final afatinib compound (’586 Patent, col. 3:1-4:3; Diagram 2; Diagram 3). The patent also claims a specific dimaleate salt of afatinib that exists in a single, stable, and anhydrous crystalline form, making it particularly suitable for use in a pharmaceutical product (’586 Patent, col. 8:29-35).
  • Technical Importance: This improved process and stable crystalline form allowed for the synthesis of afatinib with high yields, very good chemical purity, and a low level of impurities, which are critical requirements for commercial-scale pharmaceutical production (’586 Patent, col. 2:50-56).

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" of the ’586 Patent without specifying which ones (Compl. ¶31, 39). The lead independent claims are:
  • Independent Claim 1 (Process Claim):
    • A process for preparing a compound of the formula (VII)
    • comprising the step of reacting a compound of the formula (V) in suitable solvents after "corresponding activation" with di-(C₁-₄-alkyl)-phosphonoacetic acid, and
    • reacting the resulting intermediate compound with a specific aldehyde or aldehyde equivalent using suitable bases.
  • Independent Claim 9 (Composition of Matter Claim):
    • A crystalline form of afatinib dimaleate,
    • which is "characterized by" a specific set of 2Θ values obtained from X-ray powder diffraction (XRPD) analysis, as enumerated in a table within the patent.

III. The Accused Instrumentality

Product Identification

  • The "ANDA Product" is identified as "Afatinib Dimaleate Oral Tablets" in 20 mg, 30 mg, and 40 mg strengths, as described in SUN's Abbreviated New Drug Application (ANDA) No. 210814 (Compl. ¶19-20).

Functionality and Market Context

  • The accused ANDA Product is a purported generic version of Plaintiff's branded drug, GILOTRIF® (afatinib) (Compl. ¶19).
  • GILOTRIF® is a kinase inhibitor indicated for the first-line treatment of patients with certain types of metastatic non-small cell lung cancer (NSCLC) (Compl. ¶15; Compl. Ex. B, p. 1).
  • The complaint alleges that SUN submitted its ANDA to obtain FDA approval to manufacture and sell this generic version in the United States prior to the expiration of the ’586 patent (Compl. ¶19-20).

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed claim chart or a specific, element-by-element mapping of infringement allegations. The primary basis for the suit is statutory infringement under 35 U.S.C. § 271(e)(2)(A), which makes the act of submitting an ANDA for a patented drug an act of infringement to create federal court jurisdiction (Compl. ¶29). The complaint further alleges that the future commercial manufacture and sale of SUN's ANDA Product, if approved, would directly infringe, contribute to, and/or induce infringement of the ’586 patent (Compl. ¶30-31).

The infringement theory for the process claims, such as Claim 1, is that the manufacturing process described in SUN's confidential ANDA will practice the patented method. For composition of matter claims, such as Claim 9, the theory is that SUN's final drug product will be the specific crystalline form of afatinib dimaleate claimed in the patent. The patent's Figure 1 provides the X-ray powder diffractogram that serves as a technical fingerprint for this claimed crystalline form (’586 Patent, Fig. 1).

  • Identified Points of Contention:
    • Scope Questions: A primary legal question for the process claims will be the proper construction of the term "corresponding activation," which may determine whether SUN's synthesis method falls within the scope of Claim 1.
    • Technical Questions: A key factual question for the composition claims will be whether SUN's ANDA product is, in fact, the specific crystalline polymorph defined by the XRPD peaks in Claim 9. The case may turn on a comparison of the analytical data for SUN's product against the data recited in the patent.

V. Key Claim Terms for Construction

  • The Term: "corresponding activation" (from Claim 1)

    • Context and Importance: This term is central to the scope of the process claim. The infringement analysis will depend on whether SUN’s method for preparing one of the reactants for amide linking constitutes "activation" that "corresponds" to the patented process. Practitioners may focus on this term because its breadth could capture—or fail to capture—a range of known chemical activation techniques.
    • Intrinsic Evidence for a Broader Interpretation: The specification provides a non-exhaustive list of potential activation methods, including the use of "1,1-carbonyldiimidazole, 1,1-carbonylditriazole, DCC..., EDC..., TBTU...," which suggests the term is not limited to a single reagent but may encompass a class of functionally similar activating agents (’586 Patent, col. 3:11-17).
    • Intrinsic Evidence for a Narrower Interpretation: The specification states that activation is "particularly preferably with 1,1-carbonyldiimidazole," and the detailed working example uses this specific reagent. A party could argue this language limits the term to the preferred or exemplified embodiment (’586 Patent, col. 3:8-9, Example 1).

  • The Term: "Crystalline...dimaleate, characterized by 2Θ[°] values obtained by X-ray powder diffraction..." (from Claim 9)

    • Context and Importance: This phrase defines the patented crystalline form. The infringement analysis for this claim will be an empirical comparison of the accused product's physical structure to the claim language. The term "characterized by" is often a point of contention in polymorph litigation, raising the question of whether an accused product must show all listed peaks, or only a subset, to infringe.
    • Intrinsic Evidence for Interpretation: The patent provides a specific table of XRPD peaks and their corresponding intensities that define the claimed crystalline form (’586 Patent, col. 9:46-10:40). Figure 1, the X-ray powder diffractogram, provides a graphical "fingerprint" of this data (’586 Patent, Fig. 1). The debate will likely center on how closely an accused product's XRPD pattern must match the pattern defined by this data to meet the "characterized by" limitation.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon FDA approval, SUN would induce infringement by providing a product with a label that will instruct healthcare professionals and patients to use it in an infringing manner. It also alleges contributory infringement (Compl. ¶31, 39).
  • Willful Infringement: The complaint alleges that SUN had "actual and constructive notice" of the ’586 patent prior to filing its ANDA and that its certification of non-infringement or invalidity lacked a reasonable basis, rendering the case "exceptional" and justifying an award of attorneys' fees (Compl. ¶32, 34).

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

  • A central issue will be one of process equivalence: does the confidential manufacturing process described in SUN’s ANDA utilize the specific two-step reaction sequence of Claim 1, including the "corresponding activation" step, or does it employ a chemically distinct, non-infringing synthetic pathway?
  • A key evidentiary question will be one of polymorphic identity: does analytical data for SUN's final drug product demonstrate that it is the specific crystalline dimaleate salt defined by the X-ray powder diffraction peaks in Claim 9, or will discovery reveal it to be a different, non-infringing polymorph?