DCT
1:16-cv-01139
Orexo Ab v. Actavis Elizabeth LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Orexo AB (Sweden) and Orexo US, Inc. (Delaware)
- Defendant: Actavis Elizabeth LLC (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: 1:16-cv-01139, D. Del., 12/07/2016
- Venue Allegations: Venue is alleged to be proper as Defendant is a Delaware company that regularly conducts business in the state, holds relevant state licenses, and has availed itself of the forum in prior litigation.
- Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of Plaintiff's Zubsolv® product constitutes an act of infringement of a patent covering an abuse-resistant pharmaceutical composition for treating opioid dependence.
- Technical Context: The lawsuit concerns sublingual tablet formulations for opioid dependence therapy, a field focused on improving drug bioavailability while deterring misuse, such as intravenous injection by addicts.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act, triggered by Defendant’s filing of an ANDA (No. 206258) containing a Paragraph IV certification. This certification asserts that the patent-in-suit is invalid, unenforceable, or will not be infringed by Defendant’s proposed generic product. The patent-in-suit is listed in the FDA’s "Orange Book" for Plaintiff’s branded drug, Zubsolv®.
Case Timeline
| Date | Event |
|---|---|
| 2011-09-19 | '900 Patent Priority Date |
| 2016-09-13 | '900 Patent Issue Date |
| 2016-11-14 | Defendant Notifies Plaintiff of ANDA Filing with Paragraph IV Certification |
| 2016-12-07 | Complaint Filing Date |
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
The Invention Explained
- Problem Addressed: The patent describes existing sublingual treatments for opioid dependence, like Suboxone®, as having several drawbacks. These include poor bioavailability of the active ingredient (buprenorphine), requiring large and slow-dissolving tablets with an unpleasant taste, and a formulation that can still be diverted and abused by intravenous users (’900 Patent, col. 2:35-60).
- The Patented Solution: The invention is a pharmaceutical composition, typically a sublingual tablet, containing microparticles of buprenorphine in an "associative admixture" with separate particles of a weak acid. The weak acid is intended to temporarily lower the pH in the patient's mouth upon dissolution, which is theorized to increase the dissolution rate and subsequent absorption of the buprenorphine (’900 Patent, Abstract; col. 15:60-65).
- Technical Importance: By improving the bioavailability of buprenorphine, the invention purports to enable a lower effective dose, which reduces the total amount of opioid in the tablet and thereby diminishes its value for illicit extraction and abuse (’900 Patent, col. 2:65-col. 3:3).
Key Claims at a Glance
- The complaint asserts infringement of "one or more claims" without specifying them (Compl. ¶26). Independent claim 1 is representative of the core composition technology.
- Independent Claim 1:
- A pharmaceutical composition in the form of a tablet suitable 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, or a pharmaceutically acceptable salt thereof,
- a disintegrant, and
- naloxone or a pharmaceutically acceptable salt thereof,
- wherein the per tablet dosage of buprenorphine is one of several specified amounts (1.4 mg, 2.9 mg, 5.7 mg, 8.6 mg, or 11.4 mg), and
- wherein the per tablet dosage ratio of buprenorphine:naloxone is about 4:1.
- The complaint does not explicitly reserve the right to assert dependent claims but alleges infringement of method claims more generally (Compl. ¶27).
III. The Accused Instrumentality
Product Identification
- Defendant's Buprenorphine Hydrochloride and Naloxone Hydrochloride Dihydrate Sublingual Tablets, specifically the formulations described in ANDA No. 206258 (Compl. ¶11).
Functionality and Market Context
- The accused products are generic versions of Plaintiff's Zubsolv® tablets, intended for the same indications: "maintenance treatment of opioid dependence and/or for the induction of buprenorphine maintenance therapy" (Compl. ¶21). The complaint alleges the ANDA Products will have the "same clinical instructions on use, be administered in the same manner, and achieve the same results as Zubsolv®" (Compl. ¶27). The complaint identifies two dosage strengths for the ANDA products: Eq. 1.4 mg/0.36 mg Base and Eq. 5.7 mg/1.4 mg Base (Compl. ¶11).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint does not contain a detailed claim chart. The following table summarizes the infringement theory based on the complaint's allegation that the ANDA product is a generic equivalent of Plaintiff's Orange Book-listed drug.
'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 sublingual tablets intended for the treatment of opioid dependence. | ¶¶11, 21 | col. 25:7-8 |
| buprenorphine... provided in the form of microparticles... | The ANDA Products contain buprenorphine hydrochloride in a formulation that is alleged to be equivalent to Zubsolv® and to infringe the patent. | ¶¶11, 27 | col. 25:9-11 |
| a weak acid, provided in the form of particles, which particles are separate from the microparticles of buprenorphine... | The complaint does not provide specific details on the excipients of the ANDA product but alleges it will achieve the same results as Zubsolv®, which is covered by the '900 patent. | ¶¶25, 27 | col. 25:12-16 |
| a disintegrant, and | The ANDA Products are sublingual tablets alleged to be generic equivalents that necessarily contain a disintegrant. | ¶¶25, 27 | col. 25:17 |
| naloxone or a pharmaceutically acceptable salt thereof... | The ANDA Products contain naloxone hydrochloride dihydrate. | ¶11 | col. 25:18-19 |
| wherein the per tablet dosage of buprenorphine... is 1.4 mg, or 5.7 mg... | The complaint identifies two dosage strengths for the ANDA Products, 1.4 mg and 5.7 mg of buprenorphine base equivalent. | ¶11 | col. 25:20-22 |
| wherein the per tablet dosage ratio of buprenorphine:naloxone... is about 4:1 | The two identified dosage strengths in the ANDA (1.4 mg/0.36 mg and 5.7 mg/1.4 mg) correspond to a 3.89:1 and 4.07:1 ratio, respectively. | ¶11 | col. 25:23-25 |
Identified Points of Contention
- Scope Questions: The complaint's lack of technical detail on the accused formulation raises the question of whether infringement will be literal or under the doctrine of equivalents. The dispute may focus on whether the specific excipients and manufacturing process used by the Defendant result in a formulation that meets limitations such as "weak acid" and particles that are "separate from" the buprenorphine microparticles.
- Technical Questions: A central question for discovery will be the precise composition and morphology of the ANDA product. What specific acidic agent is used, and does it qualify as a "weak acid" as contemplated by the patent? Does the Defendant's manufacturing process (e.g., simple mixing vs. co-granulation) result in buprenorphine and weak acid particles that are "separate" as required by the claim?
V. Key Claim Terms for Construction
The Term: "separate from"
Context and Importance: This term is critical as it defines the physical relationship between the buprenorphine microparticles and the weak acid particles. The infringement analysis will depend on whether the defendant's formulation, which is not yet public, maintains this separation. Practitioners may focus on this term because different manufacturing techniques (e.g., dry blending vs. wet granulation) could place the components in varying degrees of proximity.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent's use of "associative admixture" and "interactive mixture" suggests the particles are intended to be mixed together, implying "separate" may simply mean the acid and the buprenorphine do not originate from the same co-formulated primary particle (’900 Patent, col. 7:21-24, col. 7:40-44).
- Evidence for a Narrower Interpretation: The claim language explicitly requires the weak acid to be in particles "which particles are separate from the microparticles of buprenorphine," which could be argued to require a more distinct physical separation than merely being different source powders in a blended mixture, potentially precluding certain granulation or coating methods (’900 Patent, col. 25:14-16).
The Term: "weak acid"
Context and Importance: The identity and properties of the acidic agent in the defendant's formulation will determine if it meets this limitation. This is a potentially dispositive issue if the defendant uses an excipient that it argues does not function as a "weak acid" in the manner described by the patent.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a functional definition related to achieving a certain pH range (between 4.0 and 6.5) and a chemical definition based on pKa (between about 1.5 and 10) (’900 Patent, col. 5:8-12, col. 5:60-63). This could be argued to cover any substance meeting those functional criteria.
- Evidence for a Narrower Interpretation: The patent provides a specific, though non-exhaustive, list of preferred weak acids, such as "citric acid, malic acid, tartaric acid," etc. (’900 Patent, col. 5:14-18, Claim 6). A party could argue that the term should be construed in light of these exemplary embodiments, potentially limiting its scope.
VI. Other Allegations
- Indirect Infringement: The complaint alleges inducement of infringement, stating that Defendant's proposed product label "will instruct doctors, caregivers, and/or patients to practice one or more of the methods claimed in the '900 patent" (Compl. ¶27).
- Willful Infringement: The complaint alleges that Defendant "was aware of the '900 patent at the time the Amendment to the ANDA was submitted" and acted "deliberately and intentionally" (Compl. ¶28). This allegation is based on Defendant’s November 14, 2016 notification letter and its Paragraph IV certification (Compl. ¶¶22-23).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of claim scope and construction: how broadly will the court interpret the terms "separate from" and "weak acid"? The definition of these terms will establish the boundaries of the patent's protection and will be critical in determining whether the undisclosed formulation in Defendant's ANDA infringes.
- A key evidentiary question will be one of factual infringement: Once the claim terms are construed, does the specific chemical composition and physical structure of Defendant’s proposed generic tablet, as detailed in its confidential ANDA, fall within the scope of the asserted claims? This will turn on detailed evidence regarding the excipients, particle characteristics, and manufacturing process of the accused product.