DCT

2:11-cv-04275

Horizon Pharma Inc v. Lupin Ltd

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Key Events
Amended Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:11-cv-04275, D.N.J., 04/10/2014
  • Venue Allegations: Plaintiffs allege venue is proper in the District of New Jersey based on Defendants' business of developing, marketing, and selling generic drug products throughout the United States, including within the district. The complaint further alleges that Defendants have previously been sued in the district and have not challenged personal jurisdiction, thereby availing themselves of the jurisdiction.
  • Core Dispute: Plaintiffs allege that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market generic versions of Plaintiffs' VIMOVO® product constitutes an act of infringement of seven U.S. patents.
  • Technical Context: The technology relates to pharmaceutical compositions combining a non-steroidal anti-inflammatory drug (NSAID) with a gastric acid inhibitor to treat conditions like arthritis while mitigating gastrointestinal side effects.
  • Key Procedural History: The litigation was initiated under the Hatch-Waxman Act following Defendants' filing of ANDA No. 202654 with the U.S. Food and Drug Administration. Plaintiffs were notified of the ANDA and Defendants' certification that the patents-in-suit are invalid or not infringed via notice letters dated June 10, 2011, and March 12, 2014.

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 ’504 Patent Issued
2001-06-01 Earliest Priority Date for ’907 and ’285 Patents
2002-04-09 ’085 Patent Issued
2005-04-05 ’872 Patent Issued
2005-08-09 ’907 Patent Issued
2008-08-12 ’070 Patent Issued
2010-06-29 ’466 Patent Issued
2011-06-10 Defendants Serve 2011 ANDA Notice Letter
2013-10-15 ’285 Patent Issued
2014-03-12 Defendants Serve 2014 ANDA Notice Letter
2014-04-10 First Amended Complaint Filed

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

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

The Invention Explained

  • Problem Addressed: The patent’s background section describes the difficulty of separating the two optical isomers (enantiomers) of omeprazole, a gastric acid inhibitor. It notes that prior methods for preparing a single enantiomer required acidic conditions that could degrade the molecule, and that stable, crystalline forms of a single enantiomer had not been previously isolated (ʼ504 Patent, col. 1:26-44).
  • The Patented Solution: The invention provides novel, optically pure, and stable alkaline salts (e.g., sodium, magnesium) of the single enantiomers of omeprazole. These salt forms are crystalline, which makes them easier to handle, purify, and formulate into a pharmaceutical product compared to the non-crystalline (syrup) forms previously obtained (ʼ504 Patent, Abstract; col. 2:48-55; col. 3:35-40).
  • Technical Importance: Developing a stable, pure, single-enantiomer form of a drug can provide improved pharmacokinetic and metabolic properties, potentially leading to a better therapeutic profile with less variation in effect between individual patients (ʼ504 Patent, col. 2:48-52).

Key Claims at a Glance

  • The complaint asserts independent claims 1 and 6, as well as dependent claims 2-3, 5, and 10 (Compl. ¶46).
  • Independent Claim 1:
    • 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
    • and a pharmaceutically acceptable carrier.
  • Independent Claim 6:
    • A method of inhibiting gastric acid secretion
    • comprising the oral administration of a pharmaceutical formulation
    • comprising a therapeutically effective amount of a pure solid state alkaline salt of the (-)-enantiomer of 5-methoxy-2[[ (4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole
    • and a pharmaceutically acceptable carrier.

U.S. Patent No. 6,875,872 - "Compounds", issued April 5, 2005

The Invention Explained

  • Problem Addressed: Similar to the ʼ504 Patent, the background of the ʼ872 Patent addresses the challenge of creating therapeutically viable single enantiomers of omeprazole. The problem was obtaining compounds with high optical purity in a stable, crystalline form suitable for pharmaceutical manufacturing (ʼ872 Patent, col. 1:30-52).
  • The Patented Solution: The invention is directed specifically to magnesium salts of the (-)-enantiomer of omeprazole (esomeprazole) with a defined level of optical purity. The patent describes methods for preparing these salts in a crystalline form that is stable and resists racemization, making it suitable for therapeutic use (ʼ872 Patent, Abstract; col. 2:55-64).
  • Technical Importance: The creation of a specific, stable magnesium salt of a single enantiomer provides a reliable active pharmaceutical ingredient that can be manufactured consistently, leading to a drug product with a predictable therapeutic profile and improved pharmacokinetics (ʼ872 Patent, col. 2:55-60).

Key Claims at a Glance

  • The complaint asserts independent claim 1, as well as claims 2, 4-5, 7-8, and 10-11 (Compl. ¶55).
  • Independent Claim 1:
    • Magnesium salt of (-)-5-methoxy-2-[[(4-methoxy-3,5,dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole
    • in an optical purity of at least about 94% enantiomeric excess.

U.S. Patent No. 6,369,085 - "Form of S-omperazole", issued April 9, 2002

  • Technology Synopsis: This patent addresses the existence of different structural forms of the magnesium salt of S-omeprazole. The invention provides a novel, substantially pure, and highly crystalline trihydrate form, which is described as being more stable and easier to characterize and handle in full-scale production than previously known forms ('085 Patent, col. 2:10-29).
  • Asserted Claims: The complaint alleges infringement of "one or more claims" of the ʼ085 Patent (Compl. ¶65).
  • Accused Features: The complaint does not specify which features of the accused product infringe, but alleges infringement based on the filing of the ANDA (Compl. ¶65).

U.S. Patent No. 7,411,070 - "Form of S-omeprazole", issued August 12, 2008

  • Technology Synopsis: Like the ʼ085 Patent, this patent relates to a specific crystalline form of the magnesium salt of S-omeprazole trihydrate. The invention aims to provide a well-defined, stable form that is advantageous for pharmaceutical manufacturing due to its reproducibility and ease of handling ('070 Patent, col. 2:15-24).
  • Asserted Claims: The complaint alleges infringement of "one or more claims" of the ʼ070 Patent (Compl. ¶74).
  • Accused Features: The complaint alleges that the accused tablets contain a magnesium salt of esomeprazole trihydrate as claimed by the patent (Compl. ¶75).

U.S. Patent No. 7,745,466 - "Form of S-omeprazole", issued June 29, 2010

  • Technology Synopsis: This patent is directed to pharmaceutical compositions that combine two active ingredients. It claims a composition comprising a magnesium salt of S-omeprazole trihydrate as the first active ingredient, a second active ingredient, and a pharmaceutically acceptable carrier ('466 Patent, Abstract; col. 1:19-25).
  • Asserted Claims: The complaint alleges infringement of "one or more claims" of the ʼ466 Patent (Compl. ¶83).
  • Accused Features: The accused product is alleged to contain esomeprazole magnesium trihydrate and a second active ingredient (naproxen), thereby infringing the patent (Compl. ¶¶ 26, 84-85).

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

  • Technology Synopsis: This patent addresses the problem of gastrointestinal damage caused by NSAIDs. The invention is a unit dosage form designed for coordinated delivery, where an acid inhibitor is released first to raise the stomach's pH, followed by a delayed release of the NSAID once the gastric environment is less acidic and therefore less prone to damage ('907 Patent, col. 3:1-17).
  • Asserted Claims: The complaint alleges infringement of claims 1, 5, 9–17, 22–24, 28–29, 32–35, 37, 41–42, 45–48, and 50–55 (Compl. ¶91).
  • Accused Features: The accused generic VIMOVO® product is a delayed-release tablet containing both naproxen (an NSAID) and esomeprazole magnesium (an acid inhibitor), which Plaintiffs allege meets the limitations of the asserted claims (Compl. ¶¶ 26, 91).

U.S. Patent No. 8,557,285 - "Pharmaceutical Compositions for the Coordinated Delivery of NSAIDs", issued October 15, 2013

  • Technology Synopsis: As a continuation of the technology in the ʼ907 Patent, this patent is also directed to pharmaceutical compositions in a unit dosage form that coordinate the delivery of esomeprazole and naproxen. The formulation is designed to reduce the risk of NSAID-induced stomach ulcers ('285 Patent, Abstract; col. 3:5-20).
  • Asserted Claims: The complaint alleges infringement of claims 1–4 (Compl. ¶100).
  • Accused Features: The accused product is a unit dosage form tablet containing esomeprazole and naproxen, which Plaintiffs allege infringes the patent by admission via the 2014 ANDA Notice Letter (Compl. ¶¶ 26, 100).

III. The Accused Instrumentality

Product Identification

  • The accused products are "Lupin's Naproxen and Esomeprazole Magnesium Delayed-Release Tablets," which are generic versions of Plaintiffs' VIMOVO® product (Compl. ¶26).

Functionality and Market Context

  • The accused products are delayed-release oral tablets containing two active pharmaceutical ingredients: naproxen, a non-steroidal anti-inflammatory drug (NSAID), and esomeprazole magnesium, a proton pump inhibitor that reduces gastric acid (Compl. ¶26). The tablets are intended to treat the symptoms of conditions such as osteoarthritis and rheumatoid arthritis while simultaneously reducing the risk of developing stomach ulcers commonly associated with NSAID use (Compl. ¶11). Defendants have filed Abbreviated New Drug Application (ANDA) No. 202654 with the FDA seeking approval to manufacture and sell these generic versions in the United States (Compl. ¶26).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint’s infringement theory relies heavily on a legal argument of infringement by admission. For multiple patents, Plaintiffs allege that because Defendants' ANDA notice letters did not provide a detailed statement of non-infringement for certain claims, Defendants have admitted that their proposed generic product meets all limitations of those claims (Compl. ¶¶ 46, 55, 91, 100). The complaint does not present its own technical analysis, such as test results or compositional data, to map the accused product to the claim elements.

’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 an oral delayed-release tablet. ¶26 col. 8:7-11
...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 is alleged to contain esomeprazole magnesium, which is an alkaline salt of the (-)-enantiomer of omeprazole. Infringement is alleged by admission. ¶¶26, 46 col. 2:51-64
...and a pharmaceutically acceptable carrier. As a pharmaceutical tablet, the accused product necessarily contains pharmaceutically acceptable carriers. ¶26 col. 8:12-14

’872 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
Magnesium salt of (-)-5-methoxy-2-[[(4-methoxy-3,5,dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole... The accused product is identified as containing "esomeprazole magnesium," which is the claimed salt. ¶26 col. 2:59-64
...in an optical purity of at least about 94% enantiomeric excess. Plaintiffs allege that Defendants admitted this limitation was met by failing to address non-infringement of this claim in their 2011 ANDA Notice Letter. ¶55 col. 8:36-39

Identified Points of Contention

  • Legal Question: A primary issue for the court will be the legal weight of Defendants' alleged failure to provide non-infringement arguments for specific claims in their Paragraph IV notice letter. The case may turn on whether this omission legally constitutes an admission of infringement, thereby relieving Plaintiffs of their burden to prove this element with technical evidence.
  • Evidentiary Question: What evidence will be required to establish the precise characteristics of the accused product? The complaint relies on the ANDA filing itself rather than independent analysis. A dispute may arise over the actual enantiomeric purity and crystalline form of the esomeprazole magnesium in Lupin's proposed product and whether it meets the claimed limitations.

V. Key Claim Terms for Construction

  • The Term: "pure solid state alkaline salt" (from ʼ504 Patent, Claim 1)

    • Context and Importance: The definition of "pure" is central to the scope of Claim 1. The infringement analysis will depend on whether this term requires absolute enantiomeric purity or allows for trace amounts of the (+)-enantiomer. Practitioners may focus on this term because the feasibility and cost of achieving different purity levels in pharmaceutical manufacturing can be significant.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification uses the terms "optically pure" and "essentially free" seemingly interchangeably, which could support an interpretation that "pure" does not mean 100.00% purity but rather a level sufficient for therapeutic use and substantially free from the other enantiomer (ʼ504 Patent, col. 3:30-34).
      • Evidence for a Narrower Interpretation: The patent emphasizes the novelty of isolating the single enantiomers as crystalline products, distinct from prior art syrups. A party could argue that "pure" should be construed narrowly to mean a high degree of purity that enables this crystallization, such as the ≥99.8% enantiomeric excess (e.e.) achieved in an example (ʼ504 Patent, col. 3:45-48).

  • The Term: "at least about 94% enantiomeric excess" (from ʼ872 Patent, Claim 1)

    • Context and Importance: This term sets a numerical floor for infringement. The dispute will likely center on the meaning of "about" and the factual question of the actual e.e. of Lupin's product. The term provides a quantitative threshold that is not present in the earlier ʼ504 Patent.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: A party might argue that "about" should be interpreted to encompass normal manufacturing variances and measurement tolerances, consistent with the patent's overall goal of producing a therapeutically effective single-enantiomer drug, not a compound defined by a rigid numerical limit ('872 Patent, col. 1:15-17).
      • Evidence for a Narrower Interpretation: The patent discloses examples achieving much higher purities (e.g., 98.4% e.e. and 99.8% e.e.), which could be used to argue that the invention is directed to these higher-purity forms and that "about 94%" should not be read to cover a significantly broader range ('872 Patent, col. 8:46-47; col. 9:44-45).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon approval, the accused products will be prescribed and administered to patients for uses covered by the method claims of the patents-in-suit (e.g., inhibiting gastric acid secretion). Plaintiffs allege Defendants will actively induce this infringement with knowledge and specific intent, as the product's sole purpose is for these patented uses (Compl. ¶¶ 48, 57).

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

  • A central issue will be one of procedural law and evidence: Can infringement be established by an alleged admission-by-omission in a Paragraph IV notice letter, or will Plaintiffs be required to produce direct technical evidence analyzing the composition, purity, and performance of the accused generic product to meet their burden of proof?
  • A key question of claim construction will be the required level of purity: How will the court define the scope of "pure" in the ʼ504 Patent and "at least about 94% enantiomeric excess" in the ʼ872 Patent, and what factual evidence will determine whether the accused product falls within that scope?
  • The case also raises a strategic question of patent enforcement: With seven patents covering the active ingredient, its crystalline form, and its coordinated-delivery formulation, the litigation will likely test how these overlapping layers of intellectual property collectively define the scope of protection for the VIMOVO® product and determine the ultimate date of potential generic entry.