DCT

1:16-cv-01138

Orexo Ab v. Actavis Elizabeth LLC

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: Orexo AB et al. v. Actavis Elizabeth LLC, 1:16-cv-01138, D. Del., 12/07/2016
  • Venue Allegations: Venue is asserted on the basis that Defendant is a Delaware corporation that regularly conducts business in the state and has availed itself of the jurisdiction.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market generic versions of Plaintiff's Zubsolv® product constitutes an act of infringement of a patent related to abuse-resistant pharmaceutical compositions.
  • Technical Context: The technology concerns sublingual tablets for treating opioid dependence, a formulation designed to improve drug bioavailability and reduce the potential for intravenous abuse.
  • Key Procedural History: This action was filed under the Hatch-Waxman Act following a notification letter dated November 14, 2016, in which Defendant informed Plaintiff it had filed a Paragraph IV Certification with the FDA, asserting that its proposed generic product would not infringe the patent-in-suit or that the patent is invalid. The patent-in-suit is listed in the FDA's "Orange Book" as covering Plaintiff's commercial product, Zubsolv®.

Case Timeline

Date Event
2011-09-19 Priority Date for U.S. Patent No. 9,439,900
2016-09-13 U.S. Patent No. 9,439,900 Issued
2016-11-14 Defendant Notifies Plaintiff of ANDA Filing with Paragraph IV Certification
2016-12-07 Complaint Filed

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

U.S. Patent No. 9,439,900 - "Abuse-Resistant Pharmaceutical Composition for the Treatment of Opioid Dependence"

  • Patent Identification: U.S. Patent No. 9,439,900 (“the ’900 patent”), “Abuse-Resistant Pharmaceutical Composition for the Treatment of Opioid Dependence,” issued September 13, 2016.

The Invention Explained

  • Problem Addressed: The patent's background section describes limitations with existing sublingual tablets for opioid dependence, such as Suboxone®, including the potential for diversion and intravenous abuse, low bioavailability of the active ingredient (buprenorphine), slow tablet disintegration, and an unpleasant taste (’900 Patent, col. 2:35-58).
  • The Patented Solution: The invention is a pharmaceutical composition that combines microparticles of buprenorphine with separate particles of a weak acid or a weakly-acidic buffer. This combination is designed to create a temporary, localized drop in pH when the tablet dissolves under the tongue, which is intended to increase the dissolution rate and subsequent absorption of buprenorphine across the sublingual mucosa (’900 Patent, col. 3:25-31, col. 16:11-21). By increasing bioavailability, a smaller dose of buprenorphine can be used, thereby reducing the quantity of the opioid available for potential extraction and abuse (’900 Patent, col. 2:65-col. 3:4).
  • Technical Importance: This formulation approach seeks to provide a safer and more effective option for opioid substitution therapy by enhancing the delivery of the therapeutic agent while simultaneously mitigating its abuse potential (’900 Patent, col. 2:61-67).

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" without specifying particular claims (Compl. ¶26). Independent claim 1 is representative of the core composition.
  • Independent Claim 1: A pharmaceutical composition in the form of a tablet for sublingual administration comprising:
    • buprenorphine, or a pharmaceutically acceptable salt thereof, provided in the form of microparticles,
    • a weak acid, provided in the form of particles, which particles are separate from the microparticles of buprenorphine,
    • a disintegrant,
    • naloxone or a pharmaceutically acceptable salt thereof,
    • a specific per-tablet dosage of buprenorphine (1.4 mg, 2.9 mg, 5.7 mg, 8.6 mg, or 11.4 mg), and
    • a per-tablet dosage ratio of buprenorphine:naloxone of about 4:1.
  • The complaint does not explicitly reserve the right to assert dependent claims, but this is a standard aspect of patent litigation.

III. The Accused Instrumentality

Product Identification

  • Defendant's proposed "Buprenorphine Hydrochloride and Naloxone Hydrochloride Dihydrate Sublingual Tablets" in dosages of 8.6 mg/2.1 mg, 11.4 mg/2.9 mg, and 2.9 mg/0.71 mg (the "ANDA Products") (Compl. ¶11).

Functionality and Market Context

  • The complaint alleges that the ANDA Products are generic versions of Plaintiff's commercial Zubsolv® tablets and seek approval for the same indications: "maintenance treatment of opioid dependence and/or for the induction of buprenorphine maintenance therapy" (Compl. ¶21).
  • The functionality is further alleged to be identical to Zubsolv®, with the ANDA Products having the "same clinical instructions on use, be administered in the same manner, and achieve the same results" (Compl. ¶27). The filing of the ANDA is positioned as an attempt to enter the market for opioid dependence treatments with a generic equivalent to Plaintiff's branded product (Compl. ¶11, ¶16-18).
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

’900 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition in the form of a tablet suitable for sublingual administration The ANDA Products are described as "Sublingual Tablets" (Compl. ¶11). ¶11 col. 12:7-10
buprenorphine, or a pharmaceutically acceptable salt thereof, provided in the form of microparticles The ANDA Products contain "Buprenorphine Hydrochloride" (Compl. ¶11). The complaint does not provide sufficient detail for analysis of the particle size. ¶11 col. 3:25-28
a weak acid, provided in the form of particles, which particles are separate from the microparticles of buprenorphine... The complaint does not provide sufficient detail for analysis of this element. N/A col. 4:45-50
a disintegrant The complaint does not provide sufficient detail for analysis of this element. N/A col. 3:36-39
naloxone or a pharmaceutically acceptable salt thereof The ANDA Products contain "Naloxone Hydrochloride Dihydrate" (Compl. ¶11). ¶11 col. 4:50-54
wherein the per tablet dosage of buprenorphine...is 11.4 mg, 8.6 mg, 5.7 mg, 2.9 mg, or 1.4 mg The ANDA Products are identified as having dosages including "Eq. 8.6 mg...Base, Eq. 11.4 mg...Base, and Eq. 2.9 mg...Base" (Compl. ¶11). ¶11 col. 9:49-53
wherein the per tablet dosage ratio of buprenorphine:naloxone dose...is about 4:1 The alleged dosages (e.g., 8.6 mg/2.1 mg; 11.4 mg/2.9 mg; 2.9 mg/0.71 mg) correspond to ratios of approximately 4.1:1, 3.9:1, and 4.1:1 (Compl. ¶11). ¶11 col. 11:1-3
  • Identified Points of Contention:
    • Evidentiary Questions: The complaint does not allege that the ANDA product contains a "weak acid" or a "disintegrant." A primary factual question for the court will be whether the actual formulation described in the confidential ANDA filing includes components that meet these limitations. Without such components, there may be no literal infringement of claim 1.
    • Scope Questions: What is the scope of "microparticles" as used in the claim? The infringement analysis will depend on whether the particle size of the buprenorphine in the accused product falls within the construed definition of this term.

V. Key Claim Terms for Construction

  • The Term: "weak acid"

  • Context and Importance: This term is a cornerstone of the claimed invention, as the acid's purported function—creating a temporary pH drop to enhance dissolution—is a primary point of novelty described in the patent (’900 Patent, col. 16:11-21). Infringement of claim 1 hinges on the presence of a component meeting this definition in the accused product. Practitioners may focus on this term because the complaint is silent as to its presence in the accused formulation.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification provides a functional definition, stating the material should enable a pH of "between about 4.0 and about 6.5" for a period of time to facilitate dissolution (’900 Patent, col. 3:60-65). It also provides a non-exhaustive list of examples, including "malic acid, fumaric acid, adipic acid, succinic acid, lactic acid, acetic acid, oxalic acid, maleic acid, ammonium chloride, preferably tartaric acid, and more preferably citric acid" (’900 Patent, col. 5:14-18).
    • Evidence for a Narrower Interpretation: A party could argue that the term should be understood in the context of the preferred embodiments, which consistently use citric acid, sometimes in combination with sodium citrate (’900 Patent, col. 17:1-4; col. 22:29-33).

  • The Term: "separate from"

  • Context and Importance: Claim 1 requires the "weak acid" particles to be "separate from the microparticles of buprenorphine." The structural relationship between these two key components is a required claim limitation. The dispute will involve determining whether the physical arrangement of ingredients in the accused product meets this requirement.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification describes formulating the components in "associative admixture" or "simple mixture," which suggests that being distinct, un-granulated powders mixed together would satisfy the "separate" limitation (’900 Patent, col. 3:28-31; col. 4:47-50).
    • Evidence for a Narrower Interpretation: The patent also discusses "interactive mixtures" where smaller particles adhere to the surfaces of larger carrier particles (’900 Patent, col. 7:41-55). A party might argue this disclosure informs the meaning of "separate," potentially creating ambiguity if, for example, buprenorphine microparticles were found to be adhered to the surface of weak acid particles in an accused product.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges inducement to infringe, stating that the proposed label for the ANDA Products "will instruct doctors, caregivers, and/or patients to practice one or more of the methods claimed in the '900 patent" (Compl. ¶27). Contributory infringement is also pleaded (Compl. ¶26).
  • Willful Infringement: The complaint alleges that Defendant acted with pre-suit knowledge of the ’900 patent. It states that "Defendant was aware of the '900 patent at the time the Amendment to the ANDA was submitted and deliberately and intentionally submitted the Amendment...with knowledge that one or more claims of the '900 patent covered the ANDA Products" (Compl. ¶28). The Paragraph IV notice letter further serves as evidence of knowledge (Compl. ¶22-23).

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

  • A central issue will be one of evidentiary proof: does the formulation described in Defendant's confidential ANDA contain components corresponding to every limitation of the asserted claims, particularly the "weak acid" and "disintegrant" elements, which are not explicitly mentioned in the complaint's description of the accused product?
  • The outcome will also likely depend on claim construction: can the term "weak acid" be defined broadly enough to read on an excipient in the accused product, and what specific physical arrangement is required for the acid and buprenorphine particles to be considered "separate from" each other as mandated by the claim?