DCT

1:15-cv-00161

Otsuka Pharmaceutical Co Ltd v. Hetero Drugs Ltd

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:15-cv-00161, D.N.J., 01/08/2015
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey based on Defendant Hetero USA, Inc.’s principal place of business in Piscataway, New Jersey, its registration to do business in the state, and its continuous business activities within the district.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) for generic aripiprazole tablets constitutes an act of infringement of three patents related to low-hygroscopicity crystalline forms of aripiprazole and its use in combination therapies.
  • Technical Context: The technology concerns specific, stable crystalline forms of the atypical antipsychotic drug aripiprazole, which are designed to overcome manufacturing and bioavailability issues associated with moisture absorption.
  • Key Procedural History: The litigation was initiated under the Hatch-Waxman Act following a November 24, 2014 notification letter from Hetero to Otsuka. The letter informed Otsuka of Hetero's ANDA filing seeking FDA approval to market a generic version of Otsuka’s approved drug, Abilify®, prior to the expiration of patents listed in the FDA's Orange Book.

Case Timeline

Date Event
2001-09-25 ’796 & ’760 Patents Priority Date
2002-11-15 Otsuka's New Drug Application (NDA) for aripiprazole tablets approved
2002-12-27 ’350 Patent Priority Date
2013-11-12 ’796 Patent Issue Date
2014-02-04 ’760 Patent Issue Date
2014-06-24 ’350 Patent Issue Date
2014-11-24 Otsuka receives notice letter from Hetero regarding ANDA filing
2015-01-08 Complaint Filing Date

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

U.S. Patent No. 8,580,796 - "Low Hygroscopic Aripiprazole Drug Substance and Processes for the Preparation Thereof"

  • Patent Identification: U.S. Patent No. 8,580,796, "Low Hygroscopic Aripiprazole Drug Substance and Processes for the Preparation Thereof," issued November 12, 2013.

The Invention Explained

  • Problem Addressed: The patent’s background section states that conventional anhydrous aripiprazole crystals are "significantly hygroscopic," meaning they readily absorb moisture from the air (Compl. Ex. A, ’796 Patent, col. 2:42-45). This absorption can cause the drug to convert to a hydrous form, which is described as being less bioavailable and less dissoluble, creating challenges for consistent manufacturing, formulation, and storage stability (Compl. Ex. A, ’796 Patent, col. 2:50-57).
  • The Patented Solution: The invention claims to solve this problem by providing a specific, stable crystalline form of the drug, termed "Anhydrous Aripiprazole Crystals B," which possesses "reduced hygroscopicity" (Compl. Ex. A, ’796 Patent, col. 2:51-54, col. 3:25-31). This novel form is designed to resist moisture absorption and conversion to a hydrate, thereby preserving its solubility and bioavailability (Compl. Ex. A, ’796 Patent, col. 7:15-23).
  • Technical Importance: This technology aims to provide a more stable and reliable active pharmaceutical ingredient, which is critical for large-scale manufacturing, ensuring a longer product shelf-life, and delivering a consistent therapeutic dose to patients (Compl. Ex. A, ’796 Patent, col. 2:2-9).

Key Claims at a Glance

  • The complaint asserts infringement of at least one claim (Compl. ¶22). Independent claim 1 is representative.
  • The essential elements of independent claim 1 are:
    • Anhydrous Aripiprazole Crystals B
    • having low hygroscopicity
    • wherein said low hygroscopicity is defined as a moisture content of 0.40% or less
    • when said Crystals are placed for 24 hours in a dessicator maintained at a temperature of 60° C. and a humidity level of 100%.

U.S. Patent No. 8,642,760 - "Low Hygroscopic Aripiprazole Drug Substance and Processes for the Preparation Thereof"

  • Patent Identification: U.S. Patent No. 8,642,760, "Low Hygroscopic Aripiprazole Drug Substance and Processes for the Preparation Thereof," issued February 4, 2014.

The Invention Explained

  • Problem Addressed: Similar to the ’796 Patent, this patent addresses the technical challenge that known forms of anhydrous aripiprazole are hygroscopic, which complicates pharmaceutical processing and can negatively affect the drug's shelf-life and solubility (Compl. Ex. B, ’760 Patent, col. 2:42-50).
  • The Patented Solution: The invention provides an "aripiprazole drug substance of low hygroscopicity" that does not easily convert into a hydrate, even when stored for a long period (Compl. Ex. B, ’760 Patent, col. 2:50-58). This stability is intended to facilitate more reliable manufacturing and formulation of aripiprazole dosage units (Compl. Ex. B, ’760 Patent, col. 2:2-9).
  • Technical Importance: The development of a low-hygroscopicity drug substance provides a more robust active ingredient for pharmaceutical products, potentially reducing packaging costs and improving the consistency and reliability of the final medication (Compl. Ex. B, ’760 Patent, col. 2:2-6).

Key Claims at a Glance

  • The complaint asserts infringement of at least one claim (Compl. ¶33). Independent claim 1 is representative.
  • The essential elements of independent claim 1 are:
    • An aripiprazole drug substance
    • of low hygroscopicity
    • wherein said low hygroscopicity is defined as a moisture content of 0.40% or less
    • after placing said drug substance for 24 hours in a dessicator maintained at a temperature of 60° C. and a humidity level of 100%.

U.S. Patent No. 8,759,350 - "Carbostyril Derivatives and Serotonin Reuptake Inhibitors for Treatment of Mood Disorders"

  • Patent Identification: U.S. Patent No. 8,759,350, "Carbostyril Derivatives and Serotonin Reuptake Inhibitors for Treatment of Mood Disorders," issued June 24, 2014.
  • Technology Synopsis: This patent addresses the treatment of mood disorders, particularly refractory depression, that do not respond sufficiently to single-agent therapies (Compl. Ex. C, ’350 Patent, col. 2:15-24). The patented solution is a combination therapy comprising a carbostyril derivative (such as aripiprazole), which acts as a dopamine-serotonin system stabilizer, and a serotonin reuptake inhibitor (SRI), which are alleged to provide a more effective treatment (Compl. Ex. C, ’350 Patent, Abstract).
  • Asserted Claims: The complaint asserts infringement of "at least one claim" (Compl. ¶44). Independent claims include 1, 9, 10, 11, 17, and 18.
  • Accused Features: The complaint alleges that Hetero's "aripiprazole tablets" will infringe the patent (Compl. ¶43, ¶44). Since the patent claims a combination therapy, the infringement theory may be based on the potential use of the generic product in conjunction with an SRI.

III. The Accused Instrumentality

Product Identification

The accused instrumentality is the generic drug product described in Hetero USA, Inc.’s ANDA No. 205064, identified as "aripiprazole tablets (2mg, 5mg, 10mg, 15mg, 20mg and 30mg)" (Compl. ¶21, ¶32, ¶43).

Functionality and Market Context

The ANDA seeks FDA approval to manufacture, use, and sell a generic version of Otsuka’s Abilify® product, which is an approved atypical antipsychotic agent (Compl. ¶5, ¶18). Under 35 U.S.C. § 271(e)(2)(A), the act of infringement alleged in the complaint is the submission of the ANDA itself for the purpose of obtaining approval to engage in the commercial manufacture, use, or sale of a drug claimed in a patent before the expiration of such patent (Compl. ¶23, ¶34, ¶45). The complaint does not provide specific details on the physical or chemical properties of the drug substance contained within Hetero’s proposed generic product.

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 pleaded generally, stating that upon information and belief, Hetero's ANDA submission constitutes an act of infringement under 35 U.S.C. § 271(e)(2)(A) and that the future marketing of the generic product will infringe at least one claim of each asserted patent (Compl. ¶22, ¶23, ¶33, ¶34, ¶44, ¶45). No probative visual evidence provided in complaint.

The core infringement theory for the ’796 and ’760 Patents appears to be that the aripiprazole drug substance in Hetero's proposed generic product will necessarily possess the "low hygroscopicity" property recited in the claims. The infringement theory for the ’350 Patent appears to be that Hetero’s product will be used in a manner that infringes the patent's combination claims, which suggests a theory of indirect infringement.

Identified Points of Contention

  • Evidentiary Questions (’796 and ’760 Patents): A central factual dispute will be whether Hetero’s proposed generic aripiprazole product meets the specific quantitative "low hygroscopicity" limitation defined in the claims (i.e., a moisture content of ≤0.40% after being subjected to the test conditions of 60°C and 100% relative humidity for 24 hours). The outcome will depend on the physical and chemical properties of Hetero's actual drug substance.
  • Infringement Theory Question (’350 Patent): The complaint alleges that an ANDA for a single-ingredient aripiprazole tablet infringes claims directed to a combination of aripiprazole and a serotonin reuptake inhibitor. This raises the question of the specific legal basis for this allegation and whether the unstated theory is one of direct, induced, or contributory infringement.

V. Key Claim Terms for Construction

The Term: "Anhydrous Aripiprazole Crystals B" (’796 Patent, Claim 1)

Context and Importance

This term defines the patented crystalline form. The scope of this term is critical because the infringement analysis for the ’796 Patent will depend on whether Hetero's product is determined to be "Anhydrous Aripiprazole Crystals B." Practitioners may focus on this term to determine if it is limited to a specific crystal structure or if it broadly covers any crystal form meeting the functional properties described in the claim.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The body of claim 1 itself defines "Anhydrous Aripiprazole Crystals B" by its functional property: "having low hygroscopicity wherein said low hygroscopicity is defined as a moisture content of 0.40% or less..." (Compl. Ex. A, ’796 Patent, col. 63:25-32). This may support an argument that any crystal form meeting this test falls within the claim's scope, regardless of its specific polymorphic structure.
  • Evidence for a Narrower Interpretation: The specification provides extensive characterization data for "Anhydrous Aripiprazole Crystals B," including a specific powder X-ray diffraction spectrum with characteristic peaks (Compl. Ex. A, ’796 Patent, col. 9:45-50, Fig. 5) and distinct infrared absorption bands (Compl. Ex. A, ’796 Patent, col. 10:50-54). This may support an argument that the term is limited to the specific polymorph exhibiting these structural fingerprints, in addition to the functional hygroscopicity property.

VI. Other Allegations

Indirect Infringement

The complaint does not explicitly use the terms "inducement" or "contributory infringement." However, the allegation that Hetero’s single-ingredient aripiprazole tablets will infringe the ’350 patent, which claims a combination therapy, suggests that an indirect infringement theory may be central to that claim (Compl. ¶44). This theory would likely depend on the contents of the proposed product labeling for Hetero's generic drug.

Willful Infringement

The complaint does not contain a specific count for willful infringement or plead facts to support it. However, the prayer for relief requests that the court declare this to be an "exceptional case" under 35 U.S.C. §§ 285 and 271(e)(4) and award attorney fees (Compl., Prayer for Relief ¶13). The factual basis for this request is not specified in the body of the complaint.

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

  • A core issue will be one of product properties: Will testing of Hetero's proposed generic drug substance demonstrate that it possesses the specific "low hygroscopicity" characteristic as defined by the quantitative test protocol recited in the claims of the '796 and '760 patents?
  • A key legal question will be one of infringement theory: On what basis can Hetero's ANDA for a single-ingredient aripiprazole tablet be found to infringe the '350 patent, which claims a combination of aripiprazole and a serotonin reuptake inhibitor? This raises a fundamental question about the viability of the infringement claim against this specific patent.
  • A central question for claim construction will be one of definitional scope: Will the term "Anhydrous Aripiprazole Crystals B" in the '796 patent be construed broadly to cover any crystal form that meets the claim’s functional hygroscopicity test, or more narrowly to require the specific structural fingerprints detailed in the patent’s specification?