DCT

2:11-cv-02317

Horizon Pharma Inc v. DR Reddy's Laboratories Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:11-cv-02317, D.N.J., 10/28/2011
  • Venue Allegations: Venue is alleged to be proper based on Defendant Dr. Reddy's Inc. being incorporated in New Jersey and both defendants conducting business in the district, including activities related to the development and commercialization of generic drug products.
  • Core Dispute: Plaintiffs allege that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the prescription drug VIMOVO® constitutes an act of infringement of six U.S. patents.
  • Technical Context: The technology involves combination pharmaceutical products designed to deliver a non-steroidal anti-inflammatory drug (NSAID) for pain relief while co-administering a gastric acid inhibitor to reduce the risk of gastrointestinal side effects like ulcers.
  • Key Procedural History: The action was initiated under the Hatch-Waxman Act following Defendants' notification to Plaintiffs via letters dated March 11, 2011, and September 19, 2011, of the filing of ANDA No. 202461. The complaint notes that the case is related to other litigation involving the same VIMOVO® product and has been consolidated for discovery purposes with a case against Lupin Ltd.

Case Timeline

Date Event
1993-05-28 Earliest Priority Date for ’504 and ’872 Patents
1997-05-30 Earliest Priority Date for ’085, ’070, and ’466 Patents
1998-02-03 Issue Date: U.S. Patent No. 5,714,504
2001-06-01 Earliest Priority Date for ’907 Patent
2002-04-09 Issue Date: U.S. Patent No. 6,369,085
2005-04-05 Issue Date: U.S. Patent No. 6,875,872
2005-08-09 Issue Date: U.S. Patent No. 6,926,907
2008-08-12 Issue Date: U.S. Patent No. 7,411,070
2010-06-29 Issue Date: U.S. Patent No. 7,745,466
2011-03-11 ANDA Notice Letter Sent to Plaintiffs
2011-09-19 Second ANDA Notice Letter Sent to Plaintiffs
2011-10-28 Complaint Filing Date

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

U.S. Patent No. 6,926,907 - “Pharmaceutical Compositions for the Coordinated Delivery of NSAIDs,” issued August 9, 2005

The Invention Explained

  • Problem Addressed: The patent describes the problem of gastrointestinal lesions (e.g., ulcers) caused by non-steroidal anti-inflammatory drugs (NSAIDs). It notes that even when co-administered with acid inhibitors, patients remain vulnerable to NSAID-induced damage, particularly during periods of low gastric pH that can occur between doses of short-acting inhibitors or before longer-acting inhibitors achieve their full effect (’907 Patent, col. 1:19-24; col. 2:1-17).
  • The Patented Solution: The invention is a single dosage form that coordinates the release of an acid inhibitor and an NSAID. The acid inhibitor is formulated for immediate release to raise the stomach's pH. The NSAID is contained in a core surrounded by a pH-sensitive enteric coating, which prevents its release until after the acid inhibitor has created a less acidic, and therefore less damaging, environment (’907 Patent, col. 3:5-13; col. 4:1-9). Figure 1 of the patent provides a schematic of a multi-layer tablet designed to achieve this sequential release (’907 Patent, Fig. 1).
  • Technical Importance: This coordinated-release strategy was designed to uncouple the timing of NSAID exposure from the highly acidic state of the stomach, offering a potential improvement in gastrointestinal safety over simple co-administration of the two drugs (’907 Patent, col. 1:12-18).

Key Claims at a Glance

  • The complaint asserts independent composition claim 1 and method of treatment claim 22, among others (Compl. ¶¶46-47).
  • Independent Claim 1 requires, in part:
    • A pharmaceutical composition in a unit dose form comprising an acid inhibitor and an NSAID.
    • The NSAID is surrounded by a coating that prevents its release unless the surrounding pH is 3.5 or higher.
    • At least a portion of the acid inhibitor is not surrounded by an enteric coating and is released immediately.
  • The complaint reserves the right to assert numerous dependent claims (Compl. ¶44).

U.S. Patent No. 5,714,504 - “Compositions,” issued February 3, 1998

The Invention Explained

  • Problem Addressed: The patent explains that omeprazole, a gastric acid secretion inhibitor, is a sulfoxide with an asymmetric center, meaning it exists as two distinct optical isomers (enantiomers). The patent notes the desirability of obtaining compounds with improved pharmacokinetic and metabolic properties, which can lead to a lower degree of interindividual variation in therapeutic response (’504 Patent, col. 2:49-54).
  • The Patented Solution: The invention provides novel, optically pure, and stable crystalline salts of single enantiomers of omeprazole. Specifically, it discloses salts of the (-)-enantiomer (esomeprazole), such as sodium or magnesium salts, which can be isolated in a pure, crystalline form (’504 Patent, Abstract; col. 2:54-63). This enables the creation of a drug product containing only the therapeutically desired enantiomer, free from its optical counterpart.
  • Technical Importance: By isolating a single, stable enantiomer, the invention allows for the development of a drug with potentially more predictable metabolism and consistent therapeutic effects across different patients compared to the racemic mixture (’504 Patent, col. 2:49-54).

Key Claims at a Glance

  • The complaint asserts independent composition claim 1 and method of treatment claim 6, among others (Compl. ¶¶53-55).
  • Independent Claim 1 requires, in part:
    • A pharmaceutical formulation for oral administration.
    • Comprising a pure solid state alkaline salt of the (-)-enantiomer of 5-methoxy-2[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole (esomeprazole).
    • A pharmaceutically acceptable carrier.
  • The complaint reserves the right to assert a number of other claims (Compl. ¶53).

Multi-Patent Capsule: U.S. Patent No. 6,875,872 - “Compounds,” issued April 5, 2005

  • Technology Synopsis: This patent, related to the ’504 patent, is directed specifically to magnesium salts of the (-)-enantiomer of omeprazole (esomeprazole). It claims these magnesium salts in high optical purity, addressing the need for stable, crystalline, single-enantiomer forms of the drug for use in pharmaceutical products (’872 Patent, Abstract; col. 2:49-54).
  • Asserted Claims: Claims 1-2, 4-5, 7-8, and 10-11 are asserted (’Compl. ¶62).
  • Accused Features: The accused product is alleged to contain esomeprazole magnesium, thereby infringing the claims to the magnesium salt of the (-)-enantiomer of omeprazole (Compl. ¶¶23, 66).

Multi-Patent Capsule: U.S. Patent No. 7,745,466 - “Form of S-omeprazole,” issued June 29, 2010

  • Technology Synopsis: This patent claims a specific crystalline form, or polymorph, of the magnesium salt of S-omeprazole (esomeprazole), identified as a trihydrate. The invention provides a stable and well-defined crystalline structure, which is advantageous for consistent manufacturing and formulation of the final drug product (’466 Patent, Abstract; col. 2:10-20).
  • Asserted Claims: Claims 1-16 are asserted (Compl. ¶17, ¶69).
  • Accused Features: The accused generic tablets are alleged to contain a magnesium salt of esomeprazole trihydrate, the specific polymorph claimed by the patent (Compl. ¶70).

Multi-Patent Capsule: U.S. Patent No. 7,411,070 - “Form of S-omeprazole,” issued August 12, 2008

  • Technology Synopsis: Part of the same family as the ’466 patent, this patent is also directed to the magnesium salt of S-omeprazole trihydrate. It claims the trihydrate compound as well as processes for its preparation, focusing on a reproducible and stable crystalline product (’070 Patent, Abstract; col. 2:10-20).
  • Asserted Claims: Claims 2 and 4 are asserted (Compl. ¶77).
  • Accused Features: The accused tablets are alleged to contain the claimed magnesium salt of esomeprazole trihydrate (Compl. ¶79) and to be manufactured by a process that infringes the preparation method claims (Compl. ¶80).

Multi-Patent Capsule: U.S. Patent No. 6,369,085 - “Form of S-omperazole,” issued April 9, 2002

  • Technology Synopsis: This patent is another member of the family directed to the magnesium salt of S-omeprazole trihydrate. The invention claims the specific trihydrate crystalline form, pharmaceutical compositions comprising it, and processes for its manufacture, all aimed at providing a stable and highly pure active ingredient (’085 Patent, Abstract; col. 2:10-20).
  • Asserted Claims: The complaint alleges infringement of "one or more claims" (Compl. ¶87).
  • Accused Features: The accused product is alleged to contain the claimed magnesium salt of esomeprazole trihydrate (Compl. ¶88).

III. The Accused Instrumentality

Product Identification

  • Dr. Reddy's Naproxen and Esomeprazole Magnesium Delayed Release Tablets, available in 375 mg naproxen/20.71 mg esomeprazole magnesium and 500 mg naproxen/20.71 mg esomeprazole magnesium strengths (Compl. ¶23).

Functionality and Market Context

  • The accused product is a generic version of Plaintiffs' VIMOVO® drug and is intended for the same therapeutic uses: relieving the signs and symptoms of arthritis and decreasing the risk of gastric ulcers associated with NSAID therapy (Compl. ¶¶10, 23). The product is the subject of ANDA No. 202461, the filing of which is the basis for this lawsuit under 35 U.S.C. § 271(e)(2) (Compl. ¶¶1, 23). The complaint does not contain specific visual evidence of the accused product. A diagram in the ’907 Patent, however, illustrates the layered tablet structure central to the infringement allegations (Compl. Ex. A, Fig. 1).

IV. Analysis of Infringement Allegations

'907 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition in unit dose form suitable for oral administration to a patient, comprising: (a) an acid inhibitor...; (b) a non-steroidal anti-inflammatory drug (NSAID)... The accused product is a tablet for oral administration containing naproxen (an NSAID) and esomeprazole magnesium (an acid inhibitor). ¶23 col. 20:10-18
wherein said unit dosage form provides for coordinated release such that: (i) said NSAID is surrounded by a coating that...prevents the release of essentially any NSAID...unless the pH...is 3.5 or higher; The complaint alleges the accused product is a "Delayed Release Tablet" that infringes the claims, implying it contains a pH-sensitive coating over the naproxen. ¶23, ¶46 col. 20:20-25
and (ii) at least a portion of said acid inhibitor is not surrounded by an enteric coating and...is released regardless of whether the pH of the surrounding medium is below 3.5 or above 3.5. The complaint alleges infringement, implying that the esomeprazole magnesium component is formulated for immediate release. ¶46 col. 20:25-29

'504 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical formulation for oral administration The accused product is a "Delayed Release Tablet" intended for oral use. ¶23 col. 14:1-2
comprising a pure solid state alkaline salt of the (-)-enantiomer of 5-methoxy-2[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole... The accused product contains "esomeprazole magnesium," which is an alkaline salt of the (-)-enantiomer of omeprazole. ¶23, ¶57 col. 14:2-7
and a pharmaceutically acceptable carrier. As a formulated tablet, the accused product necessarily contains pharmaceutically acceptable carriers. ¶23 col. 14:8-10

Identified Points of Contention

  • Scope Questions: For the ’907 patent, a central question will be whether the accused product's "delayed release" mechanism meets the specific "coordinated release" limitations of the claims. The court may need to determine if the alleged structure, with its pH-dependent release of naproxen, is functionally equivalent to the structure described and claimed.
  • Technical Questions: For the ’504, ’872, ’466, ’070, and ’085 patents, the infringement analysis will likely focus on the precise chemical and physical form of the esomeprazole magnesium in the accused product. Key questions will be whether it is the "pure solid state alkaline salt" required by the ’504 patent, the specific "magnesium salt" of the ’872 patent, and, most critically, the specific "trihydrate" polymorph claimed in the ’466, ’070, and ’085 patents. The use of 20.71 mg of esomeprazole magnesium in the generic, versus 20 mg in the branded product, may suggest an attempt to use a different salt or hydrate form to design around the patents.

V. Key Claim Terms for Construction

For the '907 Patent

  • The Term: "coordinated release"
  • Context and Importance: This term is central to the invention's purported novelty. The definition will determine whether any sequential release of an acid inhibitor and an NSAID infringes, or if a more specific, structurally-defined, pH-dependent interaction is required. Practitioners may focus on this term because it defines the core functional element of the patent.
  • Intrinsic Evidence for a Broader Interpretation: The patent summary describes the concept generally as providing for the "sequential release of acid inhibitor followed by analgesic" (’907 Patent, col. 5:20-22).
  • Intrinsic Evidence for a Narrower Interpretation: Claim 1 itself defines "coordinated release" with specific structural limitations, requiring an immediate-release acid inhibitor and an NSAID core with a coating that prevents release until the pH is 3.5 or higher, a mechanism depicted in Figure 1 (’907 Patent, col. 20:20-29; Fig. 1).

For the '504 Patent and its family

  • The Term: "pure solid state alkaline salt" (from ’504) and "magnesium salt of S-omeprazole trihydrate" (from ’466, ’070, ’085).
  • Context and Importance: The definition of these terms is critical for distinguishing the claimed inventions from the prior art racemic omeprazole and from other potential forms of esomeprazole. Infringement will depend entirely on whether the accused product contains these exact chemical and crystalline forms. Practitioners may focus on these terms because polymorphism and purity are common grounds for both infringement and non-infringement arguments in pharmaceutical patent cases.
  • Intrinsic Evidence for a Broader Interpretation: The term "pure" is not given a specific numerical value in the claims of the '504 patent, which could support an argument that it means only "substantially free" of the R-enantiomer.
  • Intrinsic Evidence for a Narrower Interpretation: The examples in the ’504 patent describe achieving optical purity of "≥99.8% e.e." (’504 Patent, col. 6:53-55). For the trihydrate patents, the claims are directed to a specific polymorph, and the specification provides detailed X-ray powder diffraction data that narrowly defines that crystalline form (’085 Patent, Fig. 1, Table 1).

VI. Other Allegations

Indirect Infringement

  • The complaint alleges that Defendants will induce infringement of the method of treatment claims. This is based on allegations that the accused product is "especially made or especially adapted" for the patented uses and that Defendants will, with knowledge, encourage and aid this infringing use through the product's marketing and labeling (Compl. ¶¶47-48, 55-56).

Willful Infringement

  • The complaint does not contain an explicit allegation of "willful infringement." However, it alleges that Defendants had knowledge of the patents-in-suit via the ANDA notice letters they sent (Compl. ¶¶24, 42, 51). Furthermore, the prayer for relief requests attorneys' fees under 35 U.S.C. § 285, which is reserved for exceptional cases, suggesting a potential basis for a willfulness claim based on post-suit conduct (Compl. p. 23, ¶E).

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

  • A core issue will be one of structural and functional correspondence: Does the "delayed release" formulation of the accused generic product meet the specific "coordinated release" limitations of the '907 patent, which require an immediate-release acid inhibitor and an NSAID core with a coating that is explicitly pH-sensitive?
  • A key evidentiary question will be one of polymorphic identity: Does the esomeprazole magnesium in the accused generic product exist in the specific crystalline "trihydrate" form required by the '466, '070, and '085 patents, or have the defendants used a different amorphous or polymorphic form to design around these claims?
  • A central dispute will likely be one of claim scope and non-infringement: Given the portfolio of patents covering the chemical compound, its specific salts, and its specific crystalline forms, have the defendants identified a "white space" in the patent protection that allows them to produce a bioequivalent but non-infringing product, for example, by using a different salt or hydrate form of esomeprazole?