DCT

1:19-cv-01814

Horizon Medicines LLC v. Ajanta Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-01814, D. Del., 09/27/2019
  • Venue Allegations: Plaintiffs allege venue is proper based on Defendants' collaborative development, marketing, and distribution of generic pharmaceutical products throughout the United States, including purposefully conducting business in the District of Delaware, which is alleged to be a destination for Defendants' generic products.
  • 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 six patents related to pharmaceutical compositions that coordinate the delivery of a non-steroidal anti-inflammatory drug (NSAID) and an acid inhibitor.
  • Technical Context: The technology involves combining an NSAID (naproxen) with an acid inhibitor (esomeprazole) in a single tablet designed to release the acid inhibitor first, thereby raising stomach pH to protect against the gastrointestinal ulcers commonly caused by NSAIDs.
  • Key Procedural History: The lawsuit was triggered by Defendants' filing of ANDA No. 213699 with the U.S. Food and Drug Administration (FDA), seeking approval to market a generic version of Plaintiffs' VIMOVO® drug before the expiration of the patents-in-suit, which are listed in the FDA's Orange Book.

Case Timeline

Date Event
2001-06-01 Earliest Patent Priority Date ('695, '636, '996, '920, '888, '181 Patents)
2014-10-07 U.S. Patent No. 8,852,636 Issues
2014-10-14 U.S. Patent No. 8,858,996 Issues
2015-10-20 U.S. Patent No. 9,161,920 Issues
2015-12-01 U.S. Patent No. 9,198,888 Issues
2016-05-24 U.S. Patent No. 9,345,695 Issues
2017-07-18 U.S. Patent No. 9,707,181 Issues
2019-09-27 Complaint Filing Date

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

U.S. Patent No. 9,345,695 - “Pharmaceutical Compositions for the Coordinated Delivery of NSAIDs” (Issued May 24, 2016)

The Invention Explained

  • Problem Addressed: The patent describes the well-known problem that non-steroidal anti-inflammatory drugs (NSAIDs), while effective for pain, can cause gastroduodenal lesions like ulcers and erosions, particularly in the acidic environment of the stomach ('695 Patent, col. 1:31-39). The patent notes that co-administering acid inhibitors can be ineffective if the NSAID is released and causes local toxic effects before the stomach pH has been sufficiently raised ('695 Patent, col. 2:1-21).
  • The Patented Solution: The invention is a single, unit-dose pharmaceutical composition that coordinates the release of an acid inhibitor and an NSAID. The acid inhibitor (esomeprazole) is formulated for immediate release to quickly raise the stomach's pH. The NSAID (naproxen) is contained within a core that is surrounded by an enteric coating, which prevents the NSAID from being released until the gastric pH has been raised to a safer, less acidic level (e.g., pH 3.5 or higher) ('695 Patent, Abstract; col. 4:46-67). This sequential release is intended to protect the gastrointestinal mucosa from damage.
  • Technical Importance: This coordinated-release formulation aims to provide the therapeutic benefits of NSAIDs while mitigating their primary dose-limiting side effect, thereby improving patient compliance and safety during chronic treatment for conditions like arthritis (Compl. ¶7).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims of the '695 patent (Compl. ¶51, ¶66). Claim 1 is the first independent claim.
  • Essential Elements of Independent Claim 1:
    • A pharmaceutical composition in unit dosage form.
    • Comprising therapeutically effective amounts of (a) esomeprazole and (b) naproxen.
    • Wherein at least a portion of the esomeprazole is not surrounded by an enteric coating.
    • Wherein the naproxen is surrounded by a coating that inhibits its release unless the surrounding medium is at a pH of 3.5 or higher.
    • Wherein said coating comprises methacrylic acid copolymers.
  • The complaint reserves the right to assert infringement of other claims (Compl. p. 33).

U.S. Patent No. 8,852,636 - “Pharmaceutical Compositions for the Coordinated Delivery of NSAIDs” (Issued Oct. 7, 2014)

The Invention Explained

  • Problem Addressed: The '636 Patent addresses the same technical problem as the '695 Patent: NSAID-induced gastroduodenal damage caused by the combination of the drug's local toxicity and the highly acidic environment of the stomach ('636 Patent, col. 1:31-39).
  • The Patented Solution: The solution is a coordinated-release tablet with a specific physical structure. It consists of an inner core containing the NSAID (naproxen), which is surrounded by an enteric coating that prevents release at low pH. The acid inhibitor (esomeprazole) is located in one or more layers outside of this coated core, ensuring it is released first upon ingestion to raise the gastric pH before the NSAID is released ('636 Patent, Abstract; col. 4:46-67). Figure 1 of the patent illustrates a tablet with an outer acid inhibitor coat, an enteric film coat, and an inner naproxen core ('636 Patent, Fig. 1).
  • Technical Importance: This specific layered tablet structure provides a mechanism to enforce the sequential release of the two active ingredients, which is critical for protecting the gastrointestinal tract from the NSAID's damaging effects ('636 Patent, col. 2:1-21).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims of the '636 patent (Compl. ¶73, ¶88). Claim 1 is the first independent claim.
  • Essential Elements of Independent Claim 1:
    • A pharmaceutical composition in unit dose form, which is a tablet.
    • Comprising esomeprazole and naproxen.
    • Wherein the naproxen is present in a core.
    • The tablet comprises a coating that surrounds the core and does not release naproxen until the pH is 3.5 or higher.
    • The esomeprazole is in one or more layers outside the core.
    • These outer layer(s) do not include naproxen and are not surrounded by an enteric coating.
  • The complaint reserves the right to assert infringement of other claims (Compl. p. 33).

Multi-Patent Capsule: U.S. Patent No. 8,858,996

  • Patent Identification: U.S. Patent No. 8,858,996, “Pharmaceutical Compositions for the Coordinated Delivery of NSAIDs,” Issued Oct. 14, 2014 (Compl. ¶14).
  • Technology Synopsis: This patent claims a multilayer tablet containing esomeprazole and naproxen. The technology ensures the acid-inhibiting esomeprazole is released from an outer layer before the enterically-coated naproxen core is released, thereby protecting the stomach lining ('996 Patent, col. 21:18-42).
  • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶95).
  • Accused Features: The accused features are the formulation and composition of Defendants' ANDA Product, which is a generic version of VIMOVO® (Compl. ¶95, ¶102).

Multi-Patent Capsule: U.S. Patent No. 9,161,920

  • Patent Identification: U.S. Patent No. 9,161,920, “Pharmaceutical Compositions for the Coordinated Delivery of NSAIDs,” Issued Oct. 20, 2015 (Compl. ¶17).
  • Technology Synopsis: This patent claims a method of reducing the incidence of NSAID-associated gastric ulcers. The method involves administering a pharmaceutical composition comprising an immediate-release esomeprazole component and a delayed-release, enterically-coated naproxen component ('920 Patent, col. 21:18-41).
  • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶117).
  • Accused Features: Defendants' ANDA Product, if marketed, would be used according to the patented method, and its label would instruct such use, thereby infringing the patent (Compl. ¶117, ¶124).

Multi-Patent Capsule: U.S. Patent No. 9,198,888

  • Patent Identification: U.S. Patent No. 9,198,888, “Pharmaceutical Compositions for the Coordinated Delivery of NSAIDs,” Issued Dec. 1, 2015 (Compl. ¶20).
  • Technology Synopsis: This patent claims a pharmaceutical composition with esomeprazole and naproxen. The key feature is a coating surrounding the naproxen that does not dissolve until the surrounding pH is at least 4.0, a slightly different threshold than some of the other patents-in-suit ('888 Patent, col. 21:65-67).
  • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶139).
  • Accused Features: The formulation of Defendants' ANDA Product, specifically the release characteristics of its enterically-coated naproxen component, is accused of infringement (Compl. ¶139, ¶146).

Multi-Patent Capsule: U.S. Patent No. 9,707,181

  • Patent Identification: U.S. Patent No. 9,707,181, “Pharmaceutical Compositions for the Coordinated Delivery of NSAIDs,” Issued July 18, 2017 (Compl. ¶23).
  • Technology Synopsis: This patent claims a tablet composition with a single core containing naproxen. The core is surrounded by a coating that inhibits release below pH 3.5, and the esomeprazole is located in one or more layers outside this core, ensuring its prior release ('181 Patent, col. 21:35-58).
  • Asserted Claims: The complaint alleges infringement of one or more claims (Compl. ¶161).
  • Accused Features: The specific layered structure and pH-dependent release profile of Defendants' generic tablet formulation are the accused features (Compl. ¶161, ¶168).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendants' generic "naproxen and esomeprazole magnesium delayed-release tablets," referred to as the "ANDA Product" (Compl. ¶26).

Functionality and Market Context

  • The ANDA Product is a generic version of Plaintiffs' VIMOVO® Delayed-Release Tablets, intended for the same therapeutic uses: relieving symptoms of arthritis and decreasing the risk of gastric ulcers associated with NSAID treatment (Compl. ¶7, ¶26). The product is formulated in 375 mg/20 mg and 500 mg/20 mg strengths of naproxen and esomeprazole magnesium, respectively (Compl. ¶26). The filing of ANDA No. 213699 with the FDA represents Defendants' effort to obtain approval for commercial manufacture and sale in the United States (Compl. ¶26).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or sufficient technical detail regarding the formulation of the ANDA Product to construct a detailed claim chart. The infringement allegations are based on the act of filing the ANDA under 35 U.S.C. § 271(e)(2), which creates a statutory act of infringement for purposes of establishing jurisdiction in a Hatch-Waxman case (Compl. ¶52, ¶74). The central allegation is that the drug product that will be commercially manufactured and sold pursuant to the ANDA, if approved, will meet the limitations of one or more claims of the patents-in-suit (Compl. ¶51, ¶73).

  • Identified Points of Contention:
    • Structural Questions: A primary point of contention may be whether the physical structure of Defendants' proposed generic tablet, as described in its confidential ANDA submission, literally meets the structural limitations of the claims. This includes questions such as: "Does the ANDA product contain naproxen in a 'core' and esomeprazole in 'one or more layers outside said core' as required by claims like Claim 1 of the '636 Patent?"
    • Technical Questions: The infringement analysis will likely focus on the functional performance of the enteric coating on the naproxen component. A key question for the court will be: "What evidence does the ANDA provide that the coating on the accused product's naproxen component inhibits drug release below a pH of 3.5 but permits release at or above that specific pH threshold, as required by claims like Claim 1 of the '695 Patent?" This analysis will likely involve expert testimony interpreting dissolution testing data.

V. Key Claim Terms for Construction

  • The Term: "coating that... does not release said naproxen until the pH of the surrounding medium is 3.5 or higher" (from '695 Patent, Claim 1; '636 Patent, Claim 1).

  • Context and Importance: This term is critical because it defines the core functional element of the invention—the delayed-release mechanism that protects the stomach. The entire infringement case may turn on whether the coating in Defendants' ANDA Product meets this specific pH-dependent release profile. Practitioners may focus on this term because the outcome will depend on scientific evidence from dissolution studies and expert interpretation of that data.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification discloses that the pH at which the enteric coat dissolves "can be controlled by the polymer or combination of polymers selected" ('636 Patent, col. 8:39-44). This language could support an argument that any coating engineered to dissolve at or around this pH range falls within the claim scope, regardless of the precise chemical composition.
    • Evidence for a Narrower Interpretation: The claims themselves recite specific polymers, such as "methacrylic acid copolymers" ('695 Patent, Claim 1). The specification also provides detailed examples of specific coating formulations, such as those containing Eudragit® L-100-55 and Eudragit® L-100 ('636 Patent, col. 10:1-10). A defendant may argue that the claim should be limited to coatings similar to these specific examples, rather than any coating that happens to dissolve at the claimed pH.

  • The Term: "esomeprazole is in one or more layers outside said core" (from '636 Patent, Claim 1).

  • Context and Importance: This term defines the physical structure that ensures the acid inhibitor is released before the NSAID. A dispute over infringement could arise if the defendant's product achieves sequential release through a different physical arrangement that it argues does not meet this "layers outside said core" limitation.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification describes the tablet as having an "outer layer comprising the acid inhibitor" ('636 Patent, col. 4:52-54). This could support a reading that covers any formulation where the esomeprazole is physically exterior to the coated naproxen, regardless of the number or distinctness of the layers.
    • Evidence for a Narrower Interpretation: Figure 1 of the '636 Patent depicts a distinct "acid inhibitor coat" as a separate layer surrounding an "enteric film coat," which in turn surrounds the "naproxen sodium core tablet." A defendant could argue this figure defines the claimed term, requiring a physically distinct and separate layer, and that a formulation where the esomeprazole is, for example, mixed into a non-enteric barrier coat would not qualify as being in a "layer outside said core."

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Defendants' ANDA Product is "especially made or especially adapted for use in an infringement" of the patents and is not a "staple article or commodity of commerce suitable for substantial noninfringing use" (Compl. ¶53, ¶75). This language supports claims for contributory infringement. Allegations that Defendants are aware that the product will be used in contravention of Plaintiffs' rights could support claims for induced infringement, particularly for the asserted method patents.
  • Willful Infringement: The complaint does not use the word "willful" but does request attorneys' fees pursuant to 35 U.S.C. § 285, which is reserved for exceptional cases (Compl. p. 33, ¶G). The basis for knowledge is Defendants' legally required certification to the FDA that the patents-in-suit are either invalid or not infringed by the ANDA product, which presupposes knowledge of the patents (Compl. ¶48, ¶70).

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

This case appears to be a technically focused Hatch-Waxman dispute centered on pharmaceutical formulation. The outcome will likely depend on the confidential details of the Defendants' ANDA filing, interpreted through expert analysis. The central questions for the court will be:

  • A core issue will be one of structural and functional bioequivalence: Does the proposed generic tablet, as defined in its ANDA, possess the specific layered architecture and, more critically, the precise pH-dependent dissolution profile for the naproxen component that is explicitly recited in the asserted patent claims?
  • A key evidentiary question will be one of claim interpretation: Will the term "coating that... does not release... until the pH... is 3.5 or higher" be construed broadly to cover any formulation achieving a similar result, or will it be limited more narrowly to the specific types of methacrylic acid copolymer formulations disclosed in the patent's examples?