DCT

1:17-cv-02754

Otsuka Pharmaceutical Co Ltd v. Zydus Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-02754, D.N.J., 04/21/2017
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey based on Defendant Zydus USA Inc. being incorporated and having its principal place of business in the district.
  • Core Dispute: Plaintiff alleges that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market generic aripiprazole tablets constitutes an act of infringement of a patent directed to a specific low-hygroscopicity crystalline form of the drug.
  • Technical Context: The technology concerns a specific crystalline polymorph of the active pharmaceutical ingredient aripiprazole, an atypical antipsychotic, engineered to have improved stability and handling properties for manufacturing.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiff’s receipt of a Notice of Certification letter from Defendant Zydus USA regarding its ANDA No. 90-472, which seeks FDA approval to market a generic version of Plaintiff's aripiprazole product, Abilify®, prior to the asserted patent's expiration.

Case Timeline

Date Event
2001-09-25 U.S. Patent No. 9,359,302 Priority Date
2002-11-15 FDA approves Otsuka's New Drug Application for Abilify®
2016-06-07 U.S. Patent No. 9,359,302 issues
2017-03-09 Otsuka receives Notice of Certification letter from Zydus
2017-04-21 Complaint filed

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

U.S. Patent No. 9,359,302 - "Low Hygroscopic Aripiprazole Drug Substance and Processes for the Preparation Thereof"

  • Patent Identification: U.S. Patent No. 9,359,302, "Low Hygroscopic Aripiprazole Drug Substance and Processes for the Preparation Thereof," issued June 7, 2016 (the "’302 Patent").

The Invention Explained

  • Problem Addressed: The patent's background section describes that conventional anhydrous aripiprazole crystals are "significantly hygroscopic" (i.e., they readily absorb moisture from the air) (’302 Patent, col. 1:49-50). This property makes the drug substance difficult to handle during manufacturing, can lead to costly processing measures, and risks converting the drug into a less bioavailable hydrous form, potentially compromising the final product's stability and shelf-life (’302 Patent, col. 1:50-col. 2:12).
  • The Patented Solution: The invention provides a novel crystalline form of aripiprazole, termed "Anhydrous Aripiprazole Crystals B," which possesses "reduced hygroscopicity" (’302 Patent, col. 2:26-30). This more stable form is produced through a specific process of milling a conventional aripiprazole hydrate to create an intermediate ("Hydrate A") and then heating that intermediate under controlled conditions to produce the desired low-hygroscopicity anhydrous crystals (’302 Patent, col. 2:35-50).
  • Technical Importance: Developing a stable, low-hygroscopicity form of an active pharmaceutical ingredient is critical for ensuring manufacturing consistency, product stability, and reliable bioavailability for patients (’302 Patent, col. 2:5-12).
    No probative visual evidence provided in complaint.

Key Claims at a Glance

  • The complaint alleges infringement of "at least one claim of the '302 patent" but does not specify which claims are asserted (Compl. ¶21). Claim 1 is the first independent claim of the patent.
  • Essential elements of independent claim 1 include:
    • Anhydrous Aripiprazole Crystals B
    • having a powder x-ray diffraction spectrum which is substantially the same as the powder x-ray diffraction spectrum shown in FIG. 5
    • having low hygroscopicity
  • The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are "Zydus USA’s tablet generic products" containing 2, 5, 10, 15, 20, and 30 mg of aripiprazole, for which Zydus USA is seeking FDA approval via Abbreviated New Drug Application No. 90-472 (Compl. ¶18).

Functionality and Market Context

  • The accused products are generic versions of Otsuka’s branded drug, Abilify®, an antipsychotic medication (Compl. ¶17-18). The complaint is a pre-marketing infringement action filed under 35 U.S.C. § 271(e)(2), which defines the submission of an ANDA seeking approval to market a generic drug before a patent's expiration as a statutory act of infringement (Compl. ¶4, 22).

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart or detailed infringement allegations mapping specific claim elements to the accused products. The infringement theory is based on the statutory act of Zydus submitting ANDA No. 90-472 to the FDA, which seeks approval to manufacture and sell a generic aripiprazole product for the same approved uses as Otsuka's branded product (Compl. ¶4, 22). Plaintiff alleges that the product described in the ANDA, if approved and marketed, will infringe at least one claim of the ’302 Patent (Compl. ¶21). A representative analysis based on independent claim 1 is summarized below.

  • ’302 Patent Infringement Allegations
Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
Anhydrous Aripiprazole Crystals B... The active ingredient in Zydus's proposed generic product is alleged to be the specific crystalline form of aripiprazole claimed as "Anhydrous Aripiprazole Crystals B" (Compl. ¶18, 21). ¶18, 21 col. 2:30-33
...having a powder x-ray diffraction spectrum which is substantially the same as the powder x-ray diffraction spectrum shown in FIG. 5 By filing its ANDA, Zydus necessarily represents that its aripiprazole active ingredient possesses the physical and chemical characteristics that Otsuka alleges are defined by the patent's claims, including the specific powder X-ray diffraction pattern of the claimed polymorph (Compl. ¶22). ¶22 col. 6:50-53
...having low hygroscopicity. The aripiprazole active ingredient in Zydus's ANDA product is alleged to possess the claimed property of low hygroscopicity (Compl. ¶21). ¶21 col. 2:26-27
  • Identified Points of Contention:
    • Scope Questions: A central issue may be the interpretation of "substantially the same as the powder x-ray diffraction spectrum shown in FIG. 5." The court may need to determine whether this requires an exact match of the peaks shown in the figure or allows for minor variations typical in such analytical measurements.
    • Technical Questions: The factual dispute will likely center on a comparison of analytical data. What evidence does the data within Zydus's ANDA provide regarding the crystalline form of its aripiprazole drug substance, and does that data fall within the scope of the physical characteristics (e.g., specific PXRD peaks, IR absorption bands) defining "Anhydrous Aripiprazole Crystals B" as claimed in the ’302 Patent?

V. Key Claim Terms for Construction

  • The Term: "Anhydrous Aripiprazole Crystals B"
  • Context and Importance: This term is the central limitation of the asserted patent and defines the specific, novel crystalline form (polymorph) of aripiprazole alleged to be inventive. The entire infringement analysis will depend on whether the aripiprazole in Zydus's proposed generic product meets the definition of this term as construed by the court. Practitioners may focus on this term because polymorph patent litigation frequently turns on precise, data-driven definitions of crystal structures.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent's summary describes the invention as providing "a form of aripiprazole having reduced hygroscopicity," which could suggest a more functional definition (’302 Patent, col. 2:26-27).
    • Evidence for a Narrower Interpretation: The patent provides a highly specific definition for "Anhydrous Aripiprazole Crystals B" tied to objective, measurable data. The detailed description and claims explicitly reference the powder X-ray diffraction spectrum in FIG. 5 and list characteristic peaks at specific 2θ angles (e.g., 11.0°, 16.6°, 19.3°, 20.3°, and 22.1°) (’302 Patent, col. 6:50-53). This evidence may support a narrow construction limited to crystals exhibiting these precise physical properties.

VI. Other Allegations

  • Indirect Infringement: The complaint does not contain separate counts for indirect infringement. However, it alleges that Zydus USA's actions related to the ANDA were undertaken "with the cooperation, participation and assistance, and for the benefit, of Cadila Healthcare Limited" (Compl. ¶23). This allegation may form the basis for holding the parent company, Cadila, liable for Zydus USA's alleged infringement.
  • Willful Infringement: The complaint does not explicitly use the word "willful" but does request that the case be declared "exceptional" under 35 U.S.C. § 285, which is often associated with findings of willfulness (Prayer for Relief ¶5). The complaint alleges that Otsuka received a Notice of Certification letter from Zydus on March 9, 2017, establishing pre-suit knowledge of the ’302 Patent, a prerequisite for any willfulness claim (Compl. ¶19).

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

  • A core issue will be one of definitional scope: How will the court construe the term "Anhydrous Aripiprazole Crystals B"? The case will likely hinge on the precise physical and chemical parameters required to meet this definition, particularly the degree of similarity needed to be considered "substantially the same" as the powder X-ray diffraction pattern shown in the patent's FIG. 5.
  • A key evidentiary question will be one of factual identity: Does the aripiprazole drug substance as characterized in Zydus's ANDA possess the specific crystalline structure defined by the asserted claims of the ’302 Patent? This question will be resolved through a technical battle of analytical data and expert testimony comparing the accused product's properties to those required by the patent.