DCT

2:16-cv-04918

Horizon Pharma Inc v. DR Reddy's Laboratories Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:16-cv-04918, D.N.J., 08/11/2016
  • Venue Allegations: Venue is alleged based on Defendant Dr. Reddy's Inc. being a New Jersey corporation and both Defendants having substantial and continuous business contacts within the district, including the development and marketing of generic drugs.
  • Core Dispute: Plaintiffs allege that Defendants' filing of Abbreviated New Drug Applications (ANDAs) to market generic versions of Plaintiffs' VIMOVO® product constitutes an act of infringement of three U.S. patents directed to methods and compositions for the coordinated delivery of naproxen and esomeprazole.
  • Technical Context: The technology involves a combination pharmaceutical product designed to provide the therapeutic benefits of a non-steroidal anti-inflammatory drug (NSAID) while mitigating the common side effect of gastric ulcers by co-administering a proton pump inhibitor (PPI).
  • Key Procedural History: The complaint identifies this as a Hatch-Waxman action triggered by Defendants' submission of ANDA No. 202461 ("ANDA I") and ANDA No. 204206 ("ANDA II") to the FDA. The complaint notes that ANDA I received final FDA approval on September 27, 2013.

Case Timeline

Date Event
2001-06-01 U.S. Patent No. 9,345,695 Priority Date
2008-09-09 U.S. Patent No. 9,220,698 Priority Date
2009-06-25 U.S. Patent No. 8,945,621 Priority Date
2013-08-12 ANDA I receives tentative FDA approval
2013-09-27 ANDA I receives final FDA approval
2015-02-03 U.S. Patent No. 8,945,621 issues
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

U.S. Patent No. 8,945,621 - "Method for Treating a Patient at Risk for Developing an NSAID-Associated Ulcer"

The Invention Explained

  • Problem Addressed: The patent addresses the substantial risk of upper gastrointestinal (UGI) ulcers, bleedings, and perforations associated with chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) for pain and inflammation (’621 Patent, col. 1:19-29). The combination of gastric acid and the NSAID's reduction of protective mechanisms in the UGI mucosa contributes to this pathology (’621 Patent, col. 1:35-39).
  • The Patented Solution: The invention is a method of treatment using a pharmaceutical composition in a single unit dose form that provides for the "coordinated release" of esomeprazole (a proton pump inhibitor) and naproxen (an NSAID). The esomeprazole is formulated for immediate release to raise the patient's gastric pH to at least 3.5, while the naproxen is formulated for delayed release (e.g., via an enteric coating) until after the gastric pH has been raised, thereby protecting the stomach lining from the NSAID during its most acidic and vulnerable state (’621 Patent, col. 2:1-11).
  • Technical Importance: This coordinated-release strategy allows patients requiring long-term NSAID therapy to receive its anti-inflammatory benefits while actively mitigating the well-documented risk of serious gastrointestinal side effects (’621 Patent, col. 1:41-51).

Key Claims at a Glance

  • The complaint does not specify which claims are asserted, but Claim 1 is the principal independent method claim.
  • Essential elements of independent Claim 1 include:
    • A method of reducing the incidence of NSAID-associated gastric ulcers in patients taking low dose aspirin (LDA) who are at risk of developing such ulcers.
    • Administering a unit dose form comprising (a) 20 mg of esomeprazole and (b) 500 mg of naproxen.
    • The esomeprazole is in a form sufficient to raise the gastric pH to at least 3.5 and is released independent of the pH of the surrounding medium.
    • The unit dosage form releases less than 10% of the naproxen after 2 hours when tested under specified USP Paddle Method conditions.
    • The administration is more effective at reducing ulcer incidence in patients taking LDA than in patients not taking LDA.
  • The complaint reserves the right to assert additional claims (Compl. ¶62).

U.S. Patent No. 9,220,698 - "Method for Delivering a Pharmaceutical Composition to Patient in Need Thereof"

The Invention Explained

  • Problem Addressed: The patent addresses the need for a clinically effective therapy that delivers naproxen and esomeprazole to achieve a specific, desirable pharmacodynamic response (i.e., maintaining an intragastric pH of 4.0 or greater) and a specific, efficacious pharmacokinetic profile (i.e., plasma level of naproxen) (’698 Patent, col. 1:40-54).
  • The Patented Solution: The invention is a method of delivering the combination drug via a specific twice-daily dosing regimen (an AM dose and a PM dose approximately 10 hours later) that is designed to "target" and achieve specific numerical pharmacokinetic (PK) and pharmacodynamic (PD) outcomes. These targets include mean Cmax and Tmax values for naproxen, mean AUC (area under the curve) values for esomeprazole, and a mean percentage of time that the intragastric pH remains above 4.0 over a 24-hour period (’698 Patent, Abstract; col. 2:1-22).
  • Technical Importance: This method defines the treatment not just by the composition but by the specific, measurable PK/PD profile it achieves in the patient, providing a more precise and reliable therapeutic effect for managing pain while protecting the gastrointestinal tract.

Key Claims at a Glance

  • The complaint does not specify which claims are asserted, but Claim 1 is the principal independent method claim.
  • Essential elements of independent Claim 1 include:
    • A method for treating osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis.
    • Orally administering an AM unit dose form and, 10 hours (±20%) later, a PM unit dose form, each containing 500 mg of naproxen and 20 mg of esomeprazole.
    • The esomeprazole is released at a pH of 0 or greater.
    • The method targets a specific PK profile for naproxen, including defined mean Cmax and median Tmax values for both the AM and PM doses.
    • The method targets a specific PK profile for esomeprazole, including defined mean AUC values for the AM dose, PM dose, and total 24-hour exposure.
    • The method targets a pharmacodynamic profile where the mean percentage of time intragastric pH remains at or above 4.0 is at least 60%.
  • The complaint reserves the right to assert additional claims (Compl. ¶88).

U.S. Patent No. 9,345,695 - "Pharmaceutical Compositions for the Coordinated Delivery of NSAIDs"

Technology Synopsis

This patent is directed to the physical structure of a pharmaceutical dosage form for coordinated delivery of an acid inhibitor and an NSAID. The technical problem is ensuring the acid inhibitor is released to raise gastric pH before the NSAID is released. The patented solution is a unit dosage form with an NSAID-containing core surrounded by an enteric coating (which dissolves only at a higher pH), which is itself surrounded by an outer layer containing the acid inhibitor for immediate release (’695 Patent, col. 2:1-21; FIG. 1).

Asserted Claims

The complaint does not specify asserted claims; independent claim 1 is representative.

Accused Features

The complaint alleges that Defendants' ANDA products, being generic versions of VIMOVO®, are pharmaceutical compositions that will infringe the claims of the ’695 patent upon commercial manufacture and sale (Compl. ¶¶95-96).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are Defendants' "ANDA I Product" (filed under ANDA No. 202461) and "ANDA II Product" (filed under ANDA No. 204206) (Compl. ¶¶17, 19).

Functionality and Market Context

The complaint alleges that the ANDA products are generic versions of Plaintiffs' VIMOVO® Delayed-Release Tablets, containing naproxen and esomeprazole magnesium in strengths of 375 mg/20.71 mg and 500 mg/20.71 mg (Compl. ¶¶17, 19). The products are intended for the same therapeutic uses as VIMOVO®: to relieve symptoms of arthritis and to decrease the risk of stomach ulcers from NSAID treatment (Compl. ¶7). By seeking approval for generic versions, the complaint alleges Defendants intend to compete directly with Plaintiffs' branded product upon market entry (Compl. ¶¶58, 84).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart or detailed factual allegations mapping the accused products to the patent claims. The infringement theory is predicated on the allegation that Defendants' ANDA products are generic versions of VIMOVO® and that the products described in the ANDA filings, if manufactured and sold, would meet the limitations of the asserted claims (Compl. ¶¶43, 69, 95).

’8,945,621 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 pharmaceutical composition... Defendants' ANDA products are generic versions of VIMOVO®, a drug approved for this indication, and are intended for use in practicing the claimed method. ¶17, ¶19, ¶43-45 col. 8:58-62
comprising: (a) 20 mg of esomeprazole... wherein at least a portion of said esomeprazole... is released independent of the pH of the surrounding medium... The ANDA products contain 20.71 mg of esomeprazole magnesium and, as generic versions of VIMOVO®, allegedly possess an immediate-release component. ¶17, ¶19 col. 2:1-5
and (b) 500 mg of naproxen... wherein the unit dosage form releases less than 10% of the naproxen... after 2 hours when tested using the USP Paddle Method... The ANDA products contain 500 mg of naproxen and, as generic versions of VIMOVO®, allegedly possess a delayed-release component with the claimed dissolution profile. ¶17, ¶19 col. 3:28-35
wherein administration... is more effective at reducing the incidence of the NSAID-associated ulcers in patients taking LDA than in patients not taking LDA who are administered the unit dose form. As generic versions of VIMOVO®, the ANDA products are alleged to possess the same comparative efficacy profile described in the patent. ¶17, ¶19, ¶43 col. 27:14-20

’9,220,698 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating osteoarthritis... comprising orally administering... an AM unit dose form and, 10 hours (±20%) later, a PM unit dose form... The ANDA products, as generic versions of VIMOVO®, are intended for twice-daily administration to treat approved conditions. ¶7, ¶17, ¶19, ¶69 col. 2:1-4
...the AM and PM unit dose forms target: i) a pk profile for naproxen where: a) the AM dose has a mean Cmax of about 81 µg/mL... As bioequivalent generic products, the ANDA products are alleged to be formulated to achieve the same pharmacokinetic profile for naproxen as that claimed for VIMOVO®. ¶17, ¶19 col. 2:5-9
...ii) a pk profile for esomeprazole where: a) the AM dose has a mean area under the plasma concentration-time curve... is about 850 hr*ng/mL... As bioequivalent generic products, the ANDA products are alleged to be formulated to achieve the same pharmacokinetic profile for esomeprazole as that claimed for VIMOVO®. ¶17, ¶19 col. 2:12-18
...and the AM and PM unit dose forms further target a mean % time at which intragastric pH remains at about 4.0 or greater for about a 24 hour period after reaching steady state that is at least about 60%. As bioequivalent generic products, the ANDA products are alleged to be formulated to achieve the same pharmacodynamic effect on gastric pH as that claimed for VIMOVO®. ¶7, ¶17, ¶19 col. 52:41-44

Identified Points of Contention

  • Scope Questions: A potential point of contention for the ’621 Patent is the claim limitation requiring the method to be "more effective" in patients taking low-dose aspirin (LDA) than in those not taking it. The interpretation and evidentiary requirements for proving this comparative functional limitation based on an ANDA filing may be a central issue.
  • Technical Questions: For the ’698 Patent, a key question will be whether the product as described in the Defendants' ANDAs, which must be bioequivalent to VIMOVO®, necessarily "targets" and achieves the specific numerical pharmacokinetic and pharmacodynamic parameters required by the claims. The dispute may focus on whether bioequivalence data is sufficient to prove infringement of these precise PK/PD limitations.

V. Key Claim Terms for Construction

The Term: "coordinated release" (’621 Patent, Claim 1)

  • Context and Importance: This term defines the core functional relationship between the two active ingredients. The scope of this term is critical because it dictates what type of formulation infringes—specifically, whether any combination of an immediate-release PPI and a delayed-release NSAID meets the limitation, or if a more specific structural or functional relationship is required.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification provides a functional definition, stating the coordinated release is such that "(i) at least a portion of said esomeprazole... is released independent of the pH... and (ii) the naproxen... is not released... until the pH... is 3.5 or higher" (’621 Patent, col. 2:3-9). This language may support a construction covering any formulation that achieves this functional result.
    • Evidence for a Narrower Interpretation: The specification describes a specific embodiment as a "multilayer tablet" where the esomeprazole is in a layer surrounding an enteric-coated naproxen core (’621 Patent, col. 3:1-14). This could support an argument that "coordinated release" requires the specific physical structure disclosed in the embodiments.

The Term: "target" (’698 Patent, Claim 1)

  • Context and Importance: This term appears repeatedly in Claim 1 to introduce specific numerical PK and PD values (e.g., "the AM and PM unit dose forms target: i) a pk profile for naproxen..."). The construction of this term will determine the standard of proof for infringement: must the accused product be merely designed to achieve these values, or must it consistently achieve them in practice?
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The ordinary meaning of "target" suggests an aim or goal. This may support a construction where infringement is met if the accused product is formulated and intended to achieve the claimed PK/PD profile, even if individual results vary. The claims also use "about," suggesting some flexibility around the numerical values (’698 Patent, col. 52:41-47).
    • Evidence for a Narrower Interpretation: The specification provides extensive clinical trial data showing the achievement of these specific PK/PD values with the VIMOVO® product (’698 Patent, Tables 6-15). A defendant may argue that this data defines the scope of "target," requiring an accused product to demonstrate consistent achievement of these specific numerical outcomes.

VI. Other Allegations

Indirect Infringement

The complaint's declaratory judgment counts allege future infringement under 35 U.S.C. §§ 271(a), (b), and (c) (Compl. ¶¶52, 78, 104). The complaint alleges that Defendants are aware that their products are "especially made or especially adapted for use in an infringement" of the patents and will be used to practice the claimed methods, suggesting theories of contributory and induced infringement based on the product's nature and intended use (Compl. ¶¶45-46, 71-72, 97-98).

Willful Infringement

The complaint does not contain an explicit allegation of willful infringement.

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

  • A central issue will be one of evidentiary sufficiency in an ANDA context: Can Plaintiffs prove, by a preponderance of the evidence, that the product defined in Defendants’ ANDA filings will meet the specific functional and numerical limitations of the asserted claims—particularly the comparative efficacy limitation of the ’621 Patent and the precise PK/PD targets of the ’698 Patent—based primarily on the requirement that the generic product be bioequivalent to VIMOVO®?
  • A second core issue will be one of claim scope and construction: How will the court construe key functional terms like "coordinated release" in the ’621 Patent and "target" in the ’698 Patent? The outcome of claim construction will likely determine whether the Defendants' bioequivalent product falls within the scope of the claims.