DCT

3:20-cv-20269

Otsuka Pharmaceutical Co Ltd v. Zydus Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:20-cv-20269, D.N.J., 12/23/2020
  • Venue Allegations: Venue is alleged to be proper as Defendant Zydus Cadila is a foreign entity that may be sued in any judicial district, Defendant Zydus Inc. is incorporated in New Jersey, and Defendant Zydus LLC's principal place of business is in New Jersey.
  • Core Dispute: Plaintiffs allege that Defendants' filing of an Abbreviated New Drug Application (ANDA) for generic brexpiprazole tablets constitutes an act of infringement of a reissued patent covering the brexpiprazole compound.
  • Technical Context: The technology involves a specific heterocyclic compound, brexpiprazole, which is the active pharmaceutical ingredient in an antipsychotic drug used for the adjunctive treatment of major depressive disorder and the treatment of schizophrenia.
  • Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Defendants' filing of ANDA No. 213660 and a corresponding Paragraph IV certification alleging non-infringement and/or invalidity of the patent-in-suit. The asserted patent, RE48,059, is a reissue of U.S. Patent No. 7,888,362. The original patent was the subject of prior litigation between the parties. The reissued patent was granted a Patent Term Extension of 986 days, extending its expiration date to December 23, 2028.

Case Timeline

Date Event
2005-04-14 RE'059 Patent Priority Date
2011-02-15 Original U.S. Patent No. 7,888,362 Issued
2015-07-10 FDA Approved NDA No. 205422 for REXULTI® (brexpiprazole)
2019-09-12 Zydus Sent First Notice Letter Regarding ANDA for '362 Patent
2020-06-23 U.S. Patent No. RE48,059 Reissued
2020-10-06 Patent Term Extension for RE'059 Patent Granted
2020-11-12 Zydus Sent Second Notice Letter Regarding ANDA for RE'059 Patent
2020-12-23 Complaint Filed

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

U.S. Patent No. RE48,059 - "Piperazine-Substituted Benzothiophenes for Treatment of Mental Disorders"

The Invention Explained

  • Problem Addressed: The patent's background section notes that because the causes of mental disorders like schizophrenia are varied, it is desirable for a single drug to have multiple pharmacological effects to provide a wide treatment spectrum (RE’059 Patent, col. 1:24-29). It also implicitly addresses the need for antipsychotic drugs with improved safety and tolerability compared to existing treatments (RE’059 Patent, col. 1:20-24).
  • The Patented Solution: The invention is a class of novel heterocyclic compounds that possess a unique combination of pharmacological activities: dopamine D2 receptor partial agonism, serotonin 5-HT2A receptor antagonism, and adrenalin α1 receptor antagonism, along with serotonin reuptake inhibition (RE’059 Patent, col. 1:25-34). This multi-faceted mechanism, embodied in the general chemical structure of formula (1), is intended to address the multifaceted nature of mental disorders (RE’059 Patent, col. 2:35-41).
  • Technical Importance: This approach allows the compound to act as a "dopamine system stabilizer," which can enhance dopaminergic neurotransmission when it is low and suppress it when it is high, a mechanism intended to improve both positive and negative symptoms of schizophrenia with fewer side effects (RE’059 Patent, col. 17:35-46).

Key Claims at a Glance

  • The complaint asserts "one or more claims" of the RE’059 patent (Compl. ¶39). Independent claim 1 is the broadest composition of matter claim.
  • Independent Claim 1 recites:
    • A heterocyclic compound represented by the formula (1) or a salt thereof.
    • Formula (1) defines a multi-part chemical structure comprising a bicyclic heterocyclic group (ring Q), a linker (A), a piperazine ring, and a benzothiophene ring.
    • The claim further defines the specific structures allowable for "ring Q" and the linker "A", as well as permissible substituents.

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are Defendants’ "brexpiprazole tablets, 0.25, 0.5, 1, 2, 3 and 4 mg," for which Zydus seeks FDA approval via ANDA No. 213660 (Compl. ¶27).

Functionality and Market Context

The complaint alleges that the Zydus products are generic versions of Plaintiffs’ REXULTI® tablets and that Zydus has represented to the FDA that its products are "pharmaceutically and therapeutically equivalent" to REXULTI® (Compl. ¶¶27, 37). REXULTI® is a prescription drug approved for the treatment of schizophrenia and as an adjunctive treatment for major depressive disorder (Compl. ¶20). The filing of the ANDA is an act to secure approval for commercial manufacture and sale of the generic product in the U.S. prior to the expiration of the RE’059 patent (Compl. ¶27).

IV. Analysis of Infringement Allegations

The complaint alleges infringement under 35 U.S.C. § 271(e)(2)(A), where the filing of an ANDA for a drug claimed in a patent is a technical act of infringement to create federal jurisdiction (Compl. ¶39). The core of the infringement allegation is that the brexpiprazole compound contained in Zydus's ANDA product falls within the scope of the claims of the RE’059 patent.

No probative visual evidence provided in complaint.

RE’059 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A heterocyclic compound represented by the formula (1) The Zydus ANDA product contains the active ingredient brexpiprazole, which is alleged to be a compound covered by formula (1). ¶27 col. 2:35-41
[wherein ring Q represented by...] The brexpiprazole compound, 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one, contains a 1H-quinolin-2-one moiety, which is a species of the "ring Q" structure. ¶27, ¶37 col. 2:42-59
[A represents -O-A₁- ... or a lower alkylene group] The brexpiprazole compound contains a butoxy group (-O-(CH₂)₄-) as the linker between the quinolinone ring and the piperazine ring, which is a species of the linker "A". ¶27, ¶37 col. 3:12-14
or a salt thereof The Zydus ANDA product is alleged to contain the brexpiprazole compound or a pharmaceutically acceptable salt thereof. ¶27 col. 3:15-16
  • Identified Points of Contention:
    • Scope Questions: As the case involves a reissued patent, a central question for the court may be whether the scope of the asserted claims was impermissibly broadened during the reissue prosecution relative to the original patent, potentially implicating the recapture rule. The complaint itself does not provide the file histories needed for this analysis.
    • Technical Questions: In typical ANDA litigation, the technical makeup of the generic product is not the primary dispute. The key question is not whether the generic product, if sold, would infringe, but rather whether the patent claims covering it are valid and enforceable. Zydus has asserted invalidity and/or unenforceability in its Paragraph IV certification (Compl. ¶31).

V. Key Claim Terms for Construction

  • The Term: "lower alkyl group"
  • Context and Importance: This term appears throughout the patent claims, defining the scope of various substituents that can be attached to the core chemical structure. Its precise definition is critical for determining the boundary between the claimed invention and potential prior art compounds, which is central to the validity analysis (e.g., anticipation and obviousness).
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party seeking a broader definition might argue that where the term is used without an explicit carbon-number limit, it should be given its plain and ordinary meaning as understood by a person of ordinary skill in the art, which could potentially extend beyond a specific range.
    • Evidence for a Narrower Interpretation: The specification provides a clear and explicit definition, stating: "As a lower alkyl group, a linear or branched alkyl group having 1 to 6 carbon atoms can be mentioned" (RE’059 Patent, col. 8:1-3). This passage provides strong intrinsic evidence that the patentee acted as its own lexicographer, defining the term as C1-C6 alkyl.

VI. Other Allegations

  • Indirect Infringement: The complaint pleads future active inducement and contributory infringement under 35 U.S.C. § 271(b) and (c) that would occur if the ANDA is approved and Zydus markets its generic product (Compl. ¶41). The factual basis for inducement would likely be Zydus's proposed product labeling, which would instruct physicians and patients to use the drug for its approved indications, thereby inducing infringement.
  • Willful Infringement: The complaint does not explicitly allege "willful infringement." However, it does allege that Zydus has "actual knowledge of Otsuka's RE'059 patent, as evidenced by Zydus' November 12, 2020, Second Notice Letter" (Compl. ¶38). This allegation establishes a basis for potential enhanced damages should Zydus launch its product "at risk" and later be found to infringe a valid patent. The prayer for relief also requests a finding that the case is "exceptional" for the purpose of awarding attorneys' fees (Compl. p. 9, ¶F).

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

  • A core issue will be one of patent validity: Can Zydus prove, by clear and convincing evidence, that the asserted claims of the RE'059 patent are invalid as either anticipated or rendered obvious by prior art chemical compounds or literature, as it has certified to the FDA?
  • A second dispositive question may be the scope of the reissue: Does an analysis of the prosecution histories of the original and reissued patents reveal that Plaintiffs impermissibly recaptured subject matter that was surrendered during the original prosecution, which would invalidate the reissued claims?