DCT
3:16-cv-00426
Horizon Pharma Inc v. Actavis Laboratories FL Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Horizon Pharma, Inc. (Delaware) and Pozen Inc. (Delaware)
- Defendant: Actavis Laboratories FL., Inc. (Florida); Actavis Pharma, Inc. (Delaware); and Actavis, Inc. (Nevada)
- Plaintiff’s Counsel: McCarter & English, LLP
- Case Identification: 3:16-cv-00426, D.N.J., 01/25/2016
- Venue Allegations: Venue is alleged to be proper in the District of New Jersey based on Defendants' business operations, including maintaining executive offices in the state, deriving substantial revenue from pharmaceutical sales in New Jersey, and being licensed to do business there.
- Core Dispute: Plaintiffs allege that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market a generic version of VIMOVO® constitutes an act of infringement of two patents covering coordinated-release pharmaceutical compositions.
- Technical Context: The technology concerns combination drug formulations that pair a non-steroidal anti-inflammatory drug (NSAID) with an acid inhibitor to reduce the risk of gastrointestinal side effects, such as ulcers, which are common with chronic NSAID use.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 204470 to the U.S. Food and Drug Administration (FDA). The complaint notes that Defendants sent a series of notice letters to Plaintiffs or their predecessors between March 2013 and December 2015, certifying that the patents listed in the FDA's Orange Book for VIMOVO®, including the patents-in-suit, are invalid, unenforceable, or will not be infringed by the proposed generic product. The complaint also certifies that the matter in controversy is the subject of numerous other related lawsuits against other generic manufacturers in the same district.
Case Timeline
| Date | Event |
|---|---|
| 2001-06-01 | Priority Date for ’920 and ’888 Patents |
| 2013-03-29 | ANDA Notice Letter sent regarding related ’907 patent |
| 2013-11-05 | ANDA Notice Letter sent regarding related ’285 patent |
| 2015-10-09 | ANDA Notice Letter sent regarding amended ANDA for new dosage strength |
| 2015-10-20 | Issue Date of U.S. Patent No. 9,161,920 |
| 2015-12-01 | Issue Date of U.S. Patent No. 9,198,888 |
| 2015-12-10 | ANDA Notice Letter sent regarding ’920 patent |
| 2016-01-25 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,161,920 - "Pharmaceutical Compositions for the Coordinated Delivery of NSAIDs"
- Patent Identification: U.S. Patent No. 9,161,920, "Pharmaceutical Compositions for the Coordinated Delivery of NSAIDs", issued October 20, 2015 (the "’920 Patent"). (Compl. ¶16).
The Invention Explained
- Problem Addressed: The patent addresses the well-known problem of gastroduodenal lesions (e.g., ulcers and erosions) caused by the administration of non-steroidal anti-inflammatory drugs (NSAIDs). The patent notes that while co-administering acid-inhibiting drugs can mitigate this, the timing of drug release is critical; if the NSAID is released while the stomach is still highly acidic, gastrointestinal damage can still occur. (’920 Patent, col. 1:40-53).
- The Patented Solution: The invention is a unit dosage form, such as a multi-layer tablet, that provides a coordinated release of two active agents. An acid inhibitor (esomeprazole) is formulated for immediate release to quickly raise the gastric pH. The NSAID (naproxen) is contained within a core that is surrounded by a pH-sensitive enteric coating. This coating is designed to prevent the release of the NSAID until the stomach's pH has been raised to a "safe level" (e.g., pH 3.5 or higher), thereby protecting the gastrointestinal mucosa from the NSAID's localized effects in a highly acidic environment. (’920 Patent, Abstract; col. 4:26-60; Fig. 1).
- Technical Importance: This formulation structure allows patients to receive the therapeutic pain-relief benefits of chronic NSAID therapy while proactively reducing the significant risk of associated gastrointestinal damage. (’920 Patent, col. 2:16-24).
Key Claims at a Glance
- The complaint alleges infringement of one or more claims of the ’920 Patent (Compl. ¶60). Independent claims 1 and 11 are directed to methods of reducing the incidence of NSAID-associated gastric ulcers.
- The essential elements of independent claim 1 include:
- Administering a tablet containing naproxen (200-600 mg) and esomeprazole (5-100 mg).
- The esomeprazole is formulated for release regardless of the surrounding pH.
- The release of naproxen is inhibited unless the surrounding medium's pH is 3.5 or higher.
U.S. Patent No. 9,198,888 - "Pharmaceutical Compositions for the Coordinated Delivery of NSAIDs"
- Patent Identification: U.S. Patent No. 9,198,888, "Pharmaceutical Compositions for the Coordinated Delivery of NSAIDs", issued December 1, 2015 (the "’888 Patent"). (Compl. ¶19).
The Invention Explained
- Problem Addressed: The ’888 Patent addresses the same technical problem as the ’920 Patent: the gastrointestinal toxicity of NSAIDs, which is exacerbated by the presence of stomach acid. (’888 Patent, col. 1:40-53).
- The Patented Solution: The solution is a unit dosage form that coordinates the release of an acid inhibitor and an NSAID. The composition is designed for the acid inhibitor (esomeprazole) to be released first to raise the gastric pH, followed by the delayed release of the NSAID (naproxen). This delay is achieved by a pH-sensitive coating on the naproxen component that dissolves only after the gastric pH has risen to a less damaging level. (’888 Patent, Abstract; col. 4:26-57; Fig. 1).
- Technical Importance: This approach aims to provide a safer therapeutic option for patients with conditions like osteoarthritis and rheumatoid arthritis who require long-term NSAID treatment. (’888 Patent, col. 2:16-24).
Key Claims at a Glance
- The complaint alleges infringement of one or more claims of the ’888 Patent (Compl. ¶84). Independent claim 1 is directed to a method of reducing the incidence of gastric ulcers.
- The essential elements of independent claim 1 include:
- Administering a unit dosage form comprising esomeprazole and naproxen.
- The esomeprazole is released regardless of the pH of the medium.
- The naproxen is surrounded by a coating that does not dissolve until the surrounding medium is at a pH of at least 3.5.
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is Defendants' proposed generic drug, identified as "naproxen and esomeprazole magnesium delayed-release tablets" in 500 mg/20 mg and 375 mg/20 mg strengths ("Actavis’ ANDA Product"). (Compl. ¶36).
Functionality and Market Context
- The complaint identifies the Actavis ANDA Product as a generic version of Plaintiffs' VIMOVO® Delayed-Release Tablets, for which Plaintiffs hold New Drug Application ("NDA") No. 022511. (Compl. ¶¶14, 36). The infringement allegation is based on Defendants' filing of ANDA No. 204470 seeking FDA approval to market this product. (Compl. ¶36). The complaint alleges that the patents-in-suit are listed in the FDA's Orange Book for VIMOVO®, and that Defendants seek to market their generic product prior to the patents' expiration. (Compl. ¶¶ 18, 21, 59, 82). The implied functionality of the accused product is therefore that of a bioequivalent, coordinated-release formulation as described in the asserted patents.
IV. Analysis of Infringement Allegations
The complaint alleges infringement under 35 U.S.C. § 271(e)(2), which makes the submission of an ANDA an act of infringement if the proposed generic product would infringe a valid patent. The complaint does not contain a detailed element-by-element infringement analysis. The infringement theory is based on the allegation that the Actavis ANDA Product is a generic copy of VIMOVO® and will therefore practice the methods claimed in the patents-in-suit listed in the Orange Book for VIMOVO®.
No probative visual evidence provided in complaint.
'920 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of reducing the incidence of NSAID-associated gastric ulcers... by administering... a pharmaceutical composition in unit dose form in the form of a tablet... | The Actavis ANDA product is a tablet intended to treat the same conditions as VIMOVO®, including reducing NSAID-associated ulcers. | ¶¶15, 36, 61 | col. 21:23-29 |
| said composition comprising: naproxen in an amount of 200-600 mg per unit dosage form; and esomeprazole in an amount of from 5 to 100 mg per unit dosage form... | The ANDA product is formulated in 375mg/20mg and 500mg/20mg strengths, which fall within the claimed dosage ranges. | ¶36 | col. 21:30-33 |
| wherein upon introduction... at least a portion of said esomeprazole is released regardless of the pH of the medium... | As a generic of VIMOVO®, the ANDA product is alleged to have an immediate-release esomeprazole component. | ¶¶36, 60 | col. 21:34-36 |
| and release of at least a portion of said naproxen is inhibited unless the pH of said medium is 3.5 or higher. | The ANDA product is identified as a "delayed-release" tablet, which is alleged to meet the pH-sensitive release limitation for the naproxen component. | ¶¶36, 61 | col. 21:37-39 |
'888 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of reducing the incidence of NSAID-associated gastric ulcers... comprising administering... a therapeutically effective amount of a pharmaceutical composition in unit dosage form... | The Actavis ANDA product is a unit dosage form intended to reduce the incidence of NSAID-associated ulcers. | ¶¶15, 36, 85 | col. 21:25-30 |
| (a) esomeprazole... wherein, upon introduction of said unit dosage form into a medium, said esomeprazole... is released regardless of the pH of the medium... | The ANDA product is alleged to contain an immediate-release formulation of esomeprazole, consistent with its characterization as a generic of VIMOVO®. | ¶¶36, 84 | col. 22:1-5 |
| (b) naproxen surrounded by coating that does not dissolve until the surrounding medium is at a pH of at least 3.5. | The ANDA product is alleged to be a "delayed-release" tablet, which implies a pH-sensitive coating on the naproxen component that meets this limitation. | ¶¶36, 85 | col. 22:6-8 |
- Identified Points of Contention:
- Scope Questions: The primary dispute will likely center on the proper construction of the claim language defining the release characteristics. A key question for the court will be whether the specific formulation described in Defendants' confidential ANDA submission falls within the scope of the claims as construed.
- Technical Questions: A factual question for discovery and expert testimony will be the precise dissolution profile of the coating on the naproxen component in the Actavis ANDA product. What evidence exists that the coating's dissolution is triggered at a pH of "at least 3.5," as required by the claims? Defendants may argue their formulation utilizes a different pH trigger to design around the patents.
V. Key Claim Terms for Construction
The complaint does not provide sufficient detail for analysis of specific disputed claim terms. However, based on the technology, certain terms are likely to be central to the dispute.
- The Term: "inhibited unless the pH of said medium is 3.5 or higher" (’920 Patent, Claim 1) / "coating that does not dissolve until the surrounding medium is at a pH of at least 3.5" (’888 Patent, Claim 1)
- Context and Importance: This limitation defines the core of the invention's coordinated-release mechanism. The determination of literal infringement will depend almost entirely on whether the accused product's coating meets this specific pH threshold. Practitioners may focus on this term because generic manufacturers often attempt to design around such specific numerical limitations.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification discusses the goal of preventing NSAID release at "very low pH" and describes various pH levels (e.g., "at least 4," "at least 5") as desirable targets, which may suggest the patent is not strictly limited to the precise 3.5 value. (’920 Patent, col. 5:1-5; col. 4:58-63).
- Evidence for a Narrower Interpretation: The claims explicitly recite the "3.5" pH value. The doctrine of claim differentiation and the choice of a specific numerical limit may be argued to confine the claim scope to that precise threshold. The specification's examples of specific polymers like Eudragit, which have known dissolution profiles, could be used to anchor the term's meaning to those specific embodiments. (’920 Patent, col. 10:21-28).
VI. Other Allegations
- Indirect Infringement: While the formal counts are for infringement under 35 U.S.C. § 271(e)(2) and declaratory judgment, the complaint includes language that tracks the statutes for indirect infringement. It alleges the Actavis ANDA product is a "material for use in practicing the methods patented," is "especially made or especially adapted for use in an infringement," and is not a "staple article or commodity of commerce suitable for substantial noninfringing use." (Compl. ¶¶ 62, 86).
- Willful Infringement: The complaint does not contain a formal allegation of willful infringement or a request for enhanced damages. However, it alleges that Defendants had pre-suit knowledge of the patents-in-suit and related patents through a series of ANDA notice letters dating back to 2013, which is a required predicate for any future willfulness claim. (Compl. ¶¶ 37-41, 58, 81).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of claim construction: how will the court define the precise pH-based functional limitations of the claims, specifically the phrase "at least 3.5"? The outcome of this legal determination will frame the entire infringement analysis.
- A key evidentiary question will be one of factual correspondence: does the specific formulation and dissolution profile of the accused generic product, as detailed in the confidential ANDA, meet every limitation of the asserted claims as construed by the court?
- A third central issue, inherent in any Hatch-Waxman litigation, will be patent validity. The case will likely involve a significant dispute over whether the asserted claims are invalid as obvious in light of prior art combining NSAIDs with acid-inhibiting agents, an argument that Defendants are required to make in their Paragraph IV certification to the FDA. (Compl. ¶¶ 74, 98).