DCT

2:16-cv-04920

Horizon Pharma Inc v. Lupin Ltd

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:16-cv-04920, D.N.J., 08/11/2016
  • Venue Allegations: Plaintiffs allege venue is proper in the District of New Jersey because Defendants conduct systematic and continuous business in the state, including the sale of generic drugs, and have a registered agent for service of process in New Jersey. The complaint also notes that Defendants have previously been sued in the district without challenging personal jurisdiction.
  • Core Dispute: Plaintiffs allege that Defendants’ filing of an Abbreviated New Drug Application (ANDA) with the FDA to market a generic version of VIMOVO® constitutes an act of patent infringement under 35 U.S.C. § 271(e)(2).
  • Technical Context: The technology relates to a combination pharmaceutical product designed to provide the therapeutic benefits of a non-steroidal anti-inflammatory drug (NSAID) while mitigating the known risk of NSAID-associated gastric ulcers via a co-formulated proton pump inhibitor (PPI).
  • Key Procedural History: The patents-in-suit are listed in the FDA’s Orange Book in connection with VIMOVO® (NDA No. 022511). Subsequent to the filing of this complaint, U.S. Patent No. 8,945,621 was subject to an Inter Partes Review (IPR2015-01718), which concluded with a certificate confirming the patentability of all original claims (1-16).

Case Timeline

Date Event
2001-06-01 Earliest Priority Date for '695 Patent
2008-09-09 Earliest Priority Date for '698 Patent
2009-06-25 Earliest Priority Date for '621 Patent
2015-02-03 U.S. Patent No. 8,945,621 Issues
2015-08-12 Inter Partes Review (IPR2015-01718) filed against '621 Patent
2015-12-29 U.S. Patent No. 9,220,698 Issues
2016-05-24 U.S. Patent No. 9,345,695 Issues
2016-08-11 Complaint Filed

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

  • Patent Identification: U.S. Patent No. 8,945,621, "Method for Treating a Patient at Risk for Developing an NSAID-Associated Ulcer," issued February 3, 2015.
  • The Invention Explained:
    • Problem Addressed: The patent addresses the substantial risk of upper gastrointestinal ulcerations and related complications, such as bleeding, that arises from chronic therapy with non-steroidal anti-inflammatory drugs (NSAIDs) ('621 Patent, col. 1:20-34).
    • The Patented Solution: The invention is a method of treatment using a unit dose pharmaceutical composition that combines an NSAID (naproxen) with a proton pump inhibitor (esomeprazole). The key innovation is a "coordinated release" mechanism: the esomeprazole is formulated for immediate release to raise the stomach's pH, while the naproxen is surrounded by a coating that prevents its release until the gastric pH reaches a less acidic level (3.5 or higher). This sequencing is designed to protect the gastric mucosa from the NSAID's damaging effects ('621 Patent, col. 2:1-10; Abstract).
    • Technical Importance: This coordinated-release formulation allows patients at risk for ulcers to receive the benefits of long-term NSAID therapy while proactively mitigating the drug's most common and dangerous gastrointestinal side effects ('621 Patent, col. 2:48-55).
  • Key Claims at a Glance:
    • The complaint alleges infringement of the patent generally, without identifying specific claims (Compl. ¶38, 53). Independent claim 1 is representative.
    • The essential elements of independent claim 1 include:
      • A method of reducing the incidence of NSAID-associated gastric ulcers in a specific patient population (those taking low dose aspirin).
      • Administering a unit dose form containing specific amounts of esomeprazole (20 mg) and naproxen (500 mg).
      • The composition provides for a "coordinated release," where esomeprazole is released independent of pH to raise the gastric pH to at least 3.5.
      • The naproxen release is delayed, with less than 10% being released after two hours in a highly acidic solution (0.1N HCl).
      • The method is more effective at reducing ulcer incidence in patients taking low dose aspirin (LDA) than in those not taking LDA.
    • The complaint does not explicitly reserve the right to assert dependent claims.
  • Patent Identification: U.S. Patent No. 9,220,698, "Method for Delivering a Pharmaceutical Composition to Patient in Need Thereof," issued December 29, 2015.
  • The Invention Explained:
    • Problem Addressed: The patent addresses the need for a clinically effective therapy that delivers both an NSAID and a PPI in a way that achieves specific, therapeutically desirable pharmacokinetic (drug concentration over time) and pharmacodynamic (drug effect on the body) profiles ('698 Patent, col. 1:41-47).
    • The Patented Solution: The invention is a method of treatment defined by the specific, measurable results achieved in the patient's body. It claims a method of administering a unit dose form of naproxen and esomeprazole twice daily (AM and PM doses) to achieve a particular pharmacodynamic outcome—maintaining the intragastric pH at a protective level (≥ 4.0) for at least 60% of a 24-hour period. The claims also recite specific pharmacokinetic parameters (Cmax and Tmax for naproxen; AUC for esomeprazole) that the formulation is designed to produce ('698 Patent, col. 2:1-22; Abstract).
    • Technical Importance: This patent defines the invention not just by its physical composition but by its functional performance in the body, providing a more precise and clinically relevant way to claim the therapeutic benefit of the coordinated-release formulation ('698 Patent, col. 1:33-40).
  • Key Claims at a Glance:
    • The complaint alleges infringement of the patent generally, without identifying specific claims (Compl. ¶61, 76). Independent claim 1 is representative.
    • The essential elements of independent claim 1 include:
      • A method of treating specific inflammatory conditions (e.g., osteoarthritis) by administering AM and PM doses.
      • Each dose comprises 500 mg naproxen and 20 mg esomeprazole.
      • The esomeprazole is released at a pH of about 0 or greater (i.e., immediately).
      • The naproxen is released only when the pH is about 3.5 or greater.
      • The method achieves specific pharmacokinetic profiles (Cmax, Tmax) for both the AM and PM doses of naproxen.
      • The method achieves a specific pharmacokinetic profile (AUC) for esomeprazole.
      • The method achieves a specific pharmacodynamic outcome: the mean percentage of time intragastric pH remains at or above 4.0 for a 24-hour period is at least about 60%.
    • The complaint does not explicitly reserve the right to assert dependent claims.
  • Multi-Patent Capsule: U.S. Patent No. 9,345,695
    • Patent Identification: U.S. Patent No. 9,345,695, "Pharmaceutical Compositions for the Coordinated Delivery of NSAIDs," issued May 24, 2016.
    • Technology Synopsis: This patent claims the pharmaceutical composition itself, rather than a method of use. The invention is a unit dosage form comprising an acid inhibitor and an NSAID, characterized by a specific structure: the NSAID is located in a core surrounded by a pH-sensitive coating that prevents its release until the pH is at least 3.5, while the acid inhibitor is located in one or more layers outside this coated core, allowing for its immediate release ('695 Patent, col. 2:28-44; Abstract).
    • Asserted Claims: The complaint does not specify which claims are asserted (Compl. ¶84, 98). The patent contains one independent claim (claim 1).
    • Accused Features: The complaint alleges that Lupin’s ANDA product, a generic version of VIMOVO®, is a pharmaceutical composition that embodies the claimed structure of a coated naproxen core and an outer esomeprazole layer (Compl. ¶¶ 83-85).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is Defendants' generic version of VIMOVO® Delayed-Release Tablets, for which Defendants filed Abbreviated New Drug Application (ANDA) No. 202654 with the FDA (Compl. ¶18). The product comprises naproxen and esomeprazole magnesium in 375 mg/20 mg and 500 mg/20 mg dosage strengths (Compl. ¶18).
  • Functionality and Market Context: The complaint alleges that the accused "Lupin's ANDA Product" is a generic copy of Plaintiffs' VIMOVO® tablets (Compl. ¶18). As such, its alleged function is to provide pain and inflammation relief for conditions like osteoarthritis while decreasing the risk of stomach ulcers associated with NSAID use (Compl. ¶8). The product is intended for commercial manufacture and sale in the United States upon FDA approval, positioning it as a direct competitor to VIMOVO® (Compl. ¶18). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed, element-by-element mapping of the asserted claims to the accused product. Instead, it advances an infringement theory under 35 U.S.C. § 271(e)(2), where the act of infringement is the submission of an ANDA seeking approval to market a generic drug before the expiration of patents covering the branded product.

  • Narrative Infringement Theory (’621 and ’698 Patents): For the method patents, the complaint's theory is that by filing an ANDA for a generic equivalent of VIMOVO®, Defendants are seeking approval to market a drug that will, upon approval, be used in a manner that directly infringes the claimed methods (Compl. ¶¶ 38, 61). This infringement would be carried out by patients and physicians following the instructions on the product's proposed label, which is expected to be substantially similar to the label for VIMOVO®. The complaint alleges that Defendants' product is "a material for use in practicing the methods patented" and is "especially made or especially adapted for use in an infringement" of the patents (Compl. ¶¶ 39, 62).
  • Narrative Infringement Theory (’695 Patent): For the composition patent, the infringement theory is more direct. The complaint alleges that the product described in ANDA No. 202654 itself embodies the claimed pharmaceutical composition (Compl. ¶¶ 83-84). The act of seeking approval to make, use, or sell this composition in the U.S. is alleged to be an act of infringement.
  • Identified Points of Contention:
    • Scope Questions: A central dispute may revolve around whether the specific formulation and release profiles of the product described in Lupin's ANDA fall within the scope of the patent claims. For the method claims, a question will be whether the proposed label for Lupin's generic product instructs or encourages the performance of all steps of the claimed methods.
    • Technical Questions: For the ’698 Patent, a key factual question will be whether Lupin’s product, upon administration, actually achieves the specific pharmacokinetic (e.g., Cmax, AUC) and pharmacodynamic (e.g., % time pH > 4.0) parameters required by the claims. For the composition-focused ’695 Patent, the question will be whether Lupin's formulation contains the specific structural elements claimed, such as the location and properties of the enteric coating relative to the NSAID and the acid inhibitor.

V. Key Claim Terms for Construction

  • The Term: "coordinated release" (’621 Patent, claim 1)
    • Context and Importance: This term is central to the inventive concept of the ’621 Patent. Its construction will determine the scope of protection for the sequential-release mechanism. Practitioners may focus on this term because the claim defines it functionally, which could lead to disputes over whether it is limited to the specific structures disclosed in the patent.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The claim itself provides a functional definition: "(i) at least a portion of said esomeprazole...is released independent of the pH...and (ii) the naproxen...is not released...until the pH of the surrounding medium is 3.5 or higher" ('621 Patent, col. 27:8-14). A party could argue that any formulation achieving this functional result, regardless of its specific structure, meets the limitation.
      • Evidence for a Narrower Interpretation: The specification describes a specific embodiment as a "multilayer tablet" where the naproxen is in a core surrounded by a pH-sensitive coating, and the esomeprazole is in an outer layer ('621 Patent, col. 3:3-14). A party could argue that the term "coordinated release" should be construed in light of these specific examples, potentially limiting its scope to similar layered tablet structures.
  • The Term: "mean % time at which intragastric pH remains at about 4.0 or greater for about a 24 hour period after reaching steady state is at least about 60%" (’698 Patent, claim 1)
    • Context and Importance: This pharmacodynamic limitation defines the required therapeutic effect of the claimed method with numerical precision. The construction of "at least about 60%" will be critical to the infringement analysis, as it sets the performance threshold that the accused method must meet.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The use of the term "about" suggests the patentee did not intend to be limited to a precise value of 60%. A party might argue it should encompass a range that accounts for normal clinical variability, consistent with the statistical data presented in the patent.
      • Evidence for a Narrower Interpretation: The patent specification includes extensive clinical trial data detailing the performance of specific formulations ('698 Patent, Tables 2-17). A party could argue that the term "about 60%" should be interpreted narrowly, in the context of the specific results and statistical confidence intervals disclosed for the embodiments that achieved this outcome (e.g., Table 5, showing a result of 71% for the PN 400/E20 formulation ('698 Patent, col. 31:40-50)).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges facts to support both induced and contributory infringement for the method patents. It asserts that Lupin's ANDA product is "especially made or especially adapted for use in an infringement" and not a staple article of commerce, supporting contributory infringement (Compl. ¶¶ 39, 62). For inducement, it alleges that Defendants are aware their product, if approved, "will be used in contravention of Plaintiffs' rights," implying knowledge and intent based on the proposed product label (Compl. ¶¶ 39, 62).
  • Willful Infringement: The complaint does not include a specific count for willful infringement. However, the prayer for relief includes a request for attorneys' fees pursuant to 35 U.S.C. § 285, which may be awarded in "exceptional cases" (Compl., Prayer for Relief ¶ G). This preserves the possibility of arguing for enhanced damages or fees based on conduct that could be deemed willful or otherwise exceptional.

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

  • Claim Construction and Scope: A core issue will be one of definitional scope: how will the court construe functional and numerical limitations such as "coordinated release" and "at least about 60%"? The outcome of claim construction will determine the technical and evidentiary threshold that Plaintiffs must meet to prove infringement.
  • Evidentiary Proof of Infringement: A key evidentiary question will be one of functional performance: what will discovery reveal about the actual characteristics of Lupin’s ANDA product? Specifically for the ’698 patent, does data from Lupin’s own bioequivalence studies demonstrate that its product achieves the claimed pharmacokinetic and pharmacodynamic profiles upon administration to a patient?
  • Induced Infringement and Labeling: For the asserted method claims, the analysis will likely focus on inducement via product labeling: does the proposed label for Lupin’s generic product—which is expected to mirror the VIMOVO® label—instruct or encourage physicians and patients to perform all of the steps recited in the asserted method claims, thereby establishing the requisite intent for induced infringement?