DCT

2:22-cv-07454

Takeda Pharma America Inc v. Teva Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:22-cv-07454, D.N.J., 01/17/2023
  • Venue Allegations: Venue is based on Defendant Teva having a regular and established physical place of business in New Jersey, and having conducted and continuing to conduct business in the district.
  • Core Dispute: Plaintiff alleges that Defendant’s Abbreviated New Drug Application (ANDA) to market a generic version of the leukemia drug ICLUSIG® (ponatinib hydrochloride) infringes four patents related to specific crystalline forms of the active pharmaceutical ingredient.
  • Technical Context: The patents concern polymorphs—distinct crystalline structures of the same chemical compound—which can affect a drug's stability, solubility, and manufacturing consistency.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act, triggered by Defendant’s submission of ANDA No. 217825 to the U.S. Food and Drug Administration (FDA) seeking approval to market a generic drug prior to the expiration of Plaintiff's patents, which are listed in the FDA's "Orange Book."

Case Timeline

Date Event
2012-12-12 Earliest Priority Date for all Patents-in-Suit
2016-11-15 U.S. Patent No. 9,493,470 Issued
2021-12-07 U.S. Patent No. 11,192,895 Issued
2021-12-07 U.S. Patent No. 11,192,897 Issued
2022-07-12 U.S. Patent No. 11,384,086 Issued
2022-11-10 Date of Teva's letter notifying Plaintiffs of ANDA submission
2023-01-17 Complaint Filing Date

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

U.S. Patent No. 9,493,470 - “Crystalline forms of 3-(imidazo[1,2-B] pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl) methyl]-3-(trifluoromethyl)phenyl}benzamide and its mono hydrochloride salt”

  • Patent Identification: U.S. Patent No. 9,493,470, “Crystalline forms of 3-(imidazo[1,2-B] pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl) methyl]-3-(trifluoromethyl)phenyl}benzamide and its mono hydrochloride salt,” issued November 15, 2016 (’470 Patent).

The Invention Explained

  • Problem Addressed: The patent addresses the challenge that an active pharmaceutical ingredient (API), such as ponatinib hydrochloride, can exist in various physical forms, including different crystalline structures (polymorphs) or non-crystalline (amorphous) forms ('470 Patent, col. 3:5-18). These different forms can possess distinct physical properties, such as stability and solubility, which can impact the manufacturing process and the ultimate performance of the drug product.
  • The Patented Solution: The invention discloses the discovery and characterization of novel crystalline forms of ponatinib hydrochloride, designated as Forms A through K ('470 Patent, col. 4:51-60). The patent provides detailed physical characterization data for these forms, most notably their X-ray powder diffraction (XRPD) patterns, which serve as a fingerprint for the specific crystal structure (e.g., ’470 Patent, Fig. 4; col. 14:1-5). By identifying and claiming a specific, stable crystalline form (Form A), the patent provides a consistent and reproducible solid form of the API suitable for pharmaceutical formulation.
  • Technical Importance: Identifying a stable, pure crystalline form of an API is critical for ensuring lot-to-lot consistency in drug manufacturing, as well as predictable shelf life and bioavailability for patients.

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claims 1 and 8 (Compl. ¶49).
  • Independent Claim 1: A composition claim for a specific crystalline form of ponatinib hydrochloride, with essential elements including:
    • Crystalline Form A of ponatinib hydrochloride
    • Characterized by an x-ray powder diffraction pattern comprising at least five 2θ values (±0.3)
    • Where the values are chosen from the list: 5.9, 7.1, 10.0, 12.5, 16.4, 19.3, 21.8, 23.8, and 26.1
  • Independent Claim 8: A method of use claim for treating leukemia, with essential elements including:
    • A method for treating chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia
    • Comprising administering a therapeutically effective amount of a pharmaceutical composition
    • Wherein the composition comprises Crystalline Form A according to claim 1 and a pharmaceutically acceptable carrier
  • The complaint notes that Defendant seeks approval for methods of treatment covered by other claims and that discovery may show infringement of additional claims (Compl. ¶46).

U.S. Patent No. 11,192,895 - “Crystalline forms of 3-(imidazo[1,2-B] pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl) methyl]-3-(trifluoromethyl)phenyl}benzamide and its mono hydrochloride salt”

  • Patent Identification: U.S. Patent No. 11,192,895, “Crystalline forms of 3-(imidazo[1,2-B] pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl) methyl]-3-(trifluoromethyl)phenyl}benzamide and its mono hydrochloride salt,” issued December 7, 2021 (’895 Patent).

The Invention Explained

  • Problem Addressed: Similar to the ’470 patent, this patent addresses the need to identify and utilize specific polymorphic forms of ponatinib hydrochloride for pharmaceutical use, which is described as "useful in the development of drugs" (’895 Patent, col. 3:9-12).
  • The Patented Solution: The invention claims methods of treating specific types of leukemia by administering a composition that contains "at least one crystalline form of ponatinib hydrochloride" (’895 Patent, Abstract). The claims define the required crystalline form not by a single identity (like "Form A") but through a Markush group structure, where the form is characterized by meeting one of ten different criteria (subparts a-j), each based on a distinct set of XRPD peaks or by reference to a specific figure in the patent (’895 Patent, col. 73:15-74:44). This structure allows the patent to cover methods of treatment using a variety of different, specifically defined polymorphs or mixtures thereof.
  • Technical Importance: This patent extends protection beyond a single crystalline form to methods of use involving a broader class of specified crystalline materials, enhancing the intellectual property portfolio for the drug product.

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claims 1, 7, 13, and 19 (Compl. ¶63).
  • Independent Claim 1: A method of use claim for treating chronic phase chronic myeloid leukemia, with essential elements including:
    • A method of treating a specific leukemia in a subject
    • Comprising administering a pharmaceutical composition
    • Wherein the composition comprises at least one crystalline form of ponatinib hydrochloride
    • The crystalline form is characterized by satisfying at least one of ten alternative definitions (a-j), each specifying a set of characteristic XRPD peaks or referencing a figure (e.g., "an x-ray powder diffraction pattern comprising at least three 2θ values (±0.3) chosen from 5.9, 7.1, 10.0...")
  • The complaint states that discovery may show infringement of additional claims (Compl. ¶58).

U.S. Patent No. 11,192,897 - “Crystalline forms of 3-(imidazo[1,2-B] pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl) methyl]-3-(trifluoromethyl)phenyl}benzamide and its mono hydrochloride salt”

  • Patent Identification: U.S. Patent No. 11,192,897, with the same title, issued December 7, 2021 (’897 Patent) (Compl. ¶12).
  • Technology Synopsis: This patent claims crystalline forms of ponatinib hydrochloride defined by physical properties beyond just XRPD patterns. The claims recite forms characterized by stability under specific thermal and humidity stress conditions (e.g., no change as measured by XRPD after exposure to 70°C) and by a specific onset melting temperature range, as well as by XRPD data (’897 Patent, claims 1, 5, 11).
  • Asserted Claims: The complaint asserts at least independent claims 1, 5, 11, 13, 15, and 22 (Compl. ¶79).
  • Accused Features: The Teva ANDA Product is alleged to be or contain one or more crystalline forms of ponatinib hydrochloride that meet the claimed criteria for XRPD patterns, thermal/humidity stability, and/or melting point (Compl. ¶72).

U.S. Patent No. 11,384,086 - “Crystalline forms of 3-(imidazo[1,2-B] pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl) methyl]-3-(trifluoromethyl)phenyl}benzamide and its mono hydrochloride salt”

  • Patent Identification: U.S. Patent No. 11,384,086, with the same title, issued July 12, 2022 (’086 Patent) (Compl. ¶13).
  • Technology Synopsis: This patent is directed to a "Crystalline anhydrous ponatinib hydrochloride," distinguishing it as a non-hydrated form. It is characterized by an XRPD pattern with a specific set of six 2θ values (’086 Patent, claim 1). The patent also claims methods of treating chronic myeloid leukemia by administering this specific anhydrous form (Compl. ¶90; ’086 Patent, claim 7).
  • Asserted Claims: The complaint asserts at least independent claims 1 and 7 (Compl. ¶91).
  • Accused Features: The Teva ANDA Product is alleged to be a pharmaceutical composition containing the claimed crystalline anhydrous form of ponatinib hydrochloride (Compl. ¶88).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Defendant's generic ponatinib hydrochloride drug product ("the Teva ANDA Product") for which Teva submitted Abbreviated New Drug Application No. 217825 to the FDA (Compl. ¶1).

Functionality and Market Context

The Teva ANDA Product is intended to be a generic version of Plaintiff's ICLUSIG® tablets, available in 10 mg, 15 mg, 30 mg, and 45 mg dosages (Compl. ¶1, 42). The product is indicated for the treatment of adult patients with specific forms of chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia (Compl. ¶14, 17-19). The complaint alleges that the filing of the ANDA itself constitutes an act of infringement under 35 U.S.C. § 271(e)(2), as it seeks approval to market the generic product before the expiration of the patents-in-suit (Compl. ¶1). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

’470 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
Crystalline Form A of ponatinib hydrochloride characterized by an x-ray powder diffraction pattern comprising at least five 2θ values (±0.3) chosen from 5.9, 7.1, 10.0, 12.5, 16.4, 19.3, 21.8, 23.8, and 26.1. The complaint alleges, on information and belief, that the Teva ANDA Product is a pharmaceutical composition that includes one or more crystalline forms of ponatinib hydrochloride that meet the characterization of Form A as recited in the claim. ¶46, ¶49 col. 14:1-5

’895 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating chronic phase chronic myeloid leukemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition... The complaint alleges that Teva is seeking FDA approval for this and other methods of treatment and that its product labeling will instruct users to perform the claimed method, thereby inducing infringement. ¶17, ¶58 col. 3:20-27
...comprising at least one crystalline form of ponatinib hydrochloride characterized by: a) an x-ray powder diffraction pattern comprising at least three 2θ values (±0.3) chosen from [list]...; or b)... or c)... [etc., through j)] The complaint alleges, on information and belief, that the Teva ANDA Product contains at least one crystalline form of ponatinib hydrochloride that meets the criteria of at least one of the ten alternative definitions provided in the claim's Markush group. ¶58, ¶63 col. 73:15-74:44
  • Identified Points of Contention:
    • Factual Questions: The central dispute will be empirical and dependent on discovery. The primary question is whether Teva’s ANDA product actually contains a crystalline form of ponatinib hydrochloride that exhibits the specific XRPD peaks, stability properties, and/or melting points required by the asserted claims of the four patents.
    • Scope Questions: For claims requiring "at least" a certain number of peaks from a list, a potential point of contention is whether the presence of other, non-listed peaks in the accused product's diffraction pattern affects the infringement analysis. Further, for method claims, the analysis will depend on the content of Teva's proposed product labeling and whether it instructs or encourages administration for the claimed indications.

V. Key Claim Terms for Construction

  • The Term: "characterized by"

  • Context and Importance: This term introduces the lists of XRPD 2θ values that define the claimed crystalline forms (e.g., ’470 Patent, claim 1). The interpretation of this term is critical because it determines whether the claim requires only the presence of the listed peaks (an open-ended definition) or if it requires an overall XRPD pattern that is substantially defined by those peaks (a more closed-ended definition). Practitioners may focus on this term because the presence of additional peaks in Teva's product could be used to argue for non-infringement under a narrower construction.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The claims use the transitional phrase "comprising" (e.g., "comprising at least five 2θ values"), which is strongly presumed in patent law to be open-ended, meaning the presence of additional, unrecited elements (or peaks) does not avoid infringement.
    • Evidence for a Narrower Interpretation: The patent specification repeatedly refers to figures showing "a characteristic" XRPD pattern for the claimed forms (e.g., ’470 Patent, col. 5:1-3, describing FIG. 4). A defendant may argue that "characterized by" requires the overall pattern of an accused product to be substantially similar to these depicted patterns, not just to contain a subset of the listed peaks.

  • The Term: "crystalline form"

  • Context and Importance: This term is the subject of most asserted composition claims. The dispute may turn on the required degree of crystallinity or purity. If Teva's product is a mixture of crystalline and amorphous material, or a mixture of different polymorphs, the question of whether it infringes a claim to a specific "crystalline form" will be central.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patents distinguish between "crystalline" and "amorphous" forms, suggesting any detectable crystalline structure could suffice (’895 Patent, col. 11:24-27). Some claims recite compositions comprising "at least one" or "at least two" crystalline forms, expressly contemplating mixtures (’897 Patent, claim 13).
    • Evidence for a Narrower Interpretation: The specification provides a potential definition for "substantially pure" as meaning "greater than about 80%," which, while not in the claims, could be argued to inform the meaning of "crystalline form" as a predominantly single-phase material (’895 Patent, col. 11:52-55).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon FDA approval, Teva will induce infringement of the asserted method claims by marketing the Teva ANDA Product with labeling that instructs physicians and patients on its FDA-approved (and allegedly infringing) uses (Compl. ¶51, ¶65, ¶81, ¶93). The complaint also alleges contributory infringement, stating that the Teva ANDA Product is especially adapted for infringing uses and has no substantial non-infringing use (Compl. ¶52, ¶66, ¶82, ¶94).
  • Willful Infringement: The complaint does not use the term "willful," but it alleges that Teva has had "knowledge of the [asserted patents] since at least the date it submitted the Teva ANDA" (Compl. ¶53, ¶67, ¶83, ¶95). This allegation establishes a basis for potential enhanced damages for any post-suit infringement. The complaint also seeks a declaration that the case is "exceptional," which is the standard for an award of attorneys' fees under 35 U.S.C. § 285 (Compl. ¶55, ¶69, ¶85, ¶97).

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

This case appears to center on a classic ANDA dispute over pharmaceutical polymorphs. The outcome will likely be determined by the answers to two primary questions:

  • A core issue will be one of empirical evidence: Will scientific analysis (primarily XRPD) of Teva's generic product, once produced in discovery, show that it contains a crystalline form of ponatinib hydrochloride that falls within the specific numerical ranges defined in any of the asserted patent claims?
  • A key legal question will be one of claim construction: How broadly will the court interpret terms like "characterized by" and "crystalline form"? The resolution of these terms will define the scope of the patents and determine whether minor variations in Teva's product—such as the presence of additional XRPD peaks or a mixture of crystalline and amorphous material—are sufficient to avoid infringement.