DCT

3:10-cv-00683

Lupin Ltd v. MERCK, Sharp & Dohme Corp

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:10-cv-00683, D.N.J., 02/01/2010
  • Venue Allegations: Venue is asserted based on Defendant Merck, Sharp & Dohme Corp.'s principal place of business being located within the District of New Jersey.
  • Core Dispute: Plaintiff seeks a declaratory judgment that its generic esomeprazole magnesium product, which is the subject of an Abbreviated New Drug Application (ANDA), will not infringe three of Defendant's patents related to processes for manufacturing and purifying omeprazole.
  • Technical Context: The technology concerns chemical processes designed to improve the purity and yield of omeprazole, a widely-used proton-pump inhibitor for treating acid-related gastrointestinal conditions.
  • Key Procedural History: The complaint states that the patents-in-suit are listed in the FDA's Orange Book for AstraZeneca's NEXIUM® product. In a prior litigation initiated by AstraZeneca against Lupin, Lupin filed counterclaims seeking a declaratory judgment of non-infringement and invalidity of the patents-in-suit. AstraZeneca moved to dismiss those counterclaims, arguing it did not own the patents. This separate action was subsequently filed by Lupin against Merck, the identified owner of the patents, to resolve the controversy over infringement.

Case Timeline

Date Event
1998-08-11 Priority Date for ’103, ’213, and ’148 Patents
2000-11-14 U.S. Patent No. 6,147,103 Issues
2000-12-26 U.S. Patent No. 6,166,213 Issues
2001-02-20 U.S. Patent No. 6,191,148 Issues
2009-10-21 Prior litigation filed by AstraZeneca against Lupin (No. 3:09-cv-05404)
2009-12-11 Lupin files counterclaims for DJ on patents-in-suit in prior litigation
2010-01-19 AstraZeneca moves to dismiss Lupin's counterclaims in prior litigation
2010-02-01 Complaint for Declaratory Judgment Filed

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

U.S. Patent No. 6,147,103 - "OMEPRAZOLE PROCESS AND COMPOSITIONS THEREOF," Issued November 14, 2000

The Invention Explained

  • Problem Addressed: The patent describes drawbacks in prior art processes for manufacturing the anti-ulcer drug omeprazole. These problems include incomplete or non-chemoselective oxidation of the precursor molecule, leading to yield loss and impurities, as well as the presence of residual organic solvents in the final drug product, which raises toxicity and safety concerns (’103 Patent, col. 1:45-col. 2:11).
  • The Patented Solution: The invention claims to solve these problems through an improved process for preparing and purifying omeprazole, resulting in a composition of high purity. The process involves careful control over the amount of oxidizing agent used, subsurface addition of reagents to avoid localized over-oxidation, and a multi-stage crystallization and purification protocol designed to remove specific residual solvents to "no chromatographically detectable levels" (’103 Patent, Abstract; col. 2:56-col. 3:52).
  • Technical Importance: This technology sought to improve the manufacturing efficiency, product purity, and safety profile for omeprazole, a significant commercial pharmaceutical (’103 Patent, col. 2:8-11).

Key Claims at a Glance

  • The complaint seeks a declaratory judgment of non-infringement of "any valid claim" (Compl. ¶16). Independent claim 1 is representative of the composition claims.
  • Claim 1 (as amended by the Certificate of Correction issued November 6, 2001):
    • A composition comprising 5-methoxy-2-[[4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole (omeprazole)
    • having less than three parts per million of residual aromatic hydrocarbon solvent
    • and 10-20 p.p.m. of residual methanol relative to omeprazole.

U.S. Patent No. 6,166,213 - "OMEPRAZOLE PROCESS AND COMPOSITIONS THEREOF," Issued December 26, 2000

The Invention Explained

  • Problem Addressed: This related patent addresses the same issues as the ’103 Patent: prior methods for synthesizing omeprazole were limited by low yields, incomplete reactions, and the creation of undesirable by-products and residual solvent impurities (’213 Patent, col. 1:50-col. 2:13).
  • The Patented Solution: The invention is an improved process for preparing omeprazole, with a focus on optimizing the key oxidation step. The claimed process involves treating a buffered solution of the precursor (pyrmetazole) with exactly one molar equivalent of an oxidizing agent at a controlled low temperature, followed by specific aging, phase separation, and solvent removal steps to isolate the desired product with high purity (’213 Patent, Abstract; col. 6:51-col. 7:2).
  • Technical Importance: The process aimed to provide a more controlled and efficient manufacturing method for omeprazole, overcoming the product purity and yield limitations of previous techniques (’213 Patent, col. 2:14-17).

Key Claims at a Glance

  • The complaint seeks a declaratory judgment of non-infringement of "any valid claim" (Compl. ¶19). Independent claim 1 is representative of the process claims.
  • Claim 1:
    • A process for the preparation of omeprazole, having the formula I, which comprises:
    • (a) treating, at about -5 to +5° C., a buffered solution of pyrmetazole... in a non-alcoholic organic reaction solvent, with one equivalent... of meta-chloroperoxybenzoic acid dissolved in the non-alcoholic organic reaction solvent in admixture with an alcoholic solvent... followed by aging in the presence of an aqueous base;
    • (b) separating the aqueous phase of the aged reaction mixture from the organic phase; and
    • (c) removing residual non-alcoholic organic reaction solvent from said aqueous phase followed by re-adjusting the alcoholic solvent concentration to about 15% v/v.

U.S. Patent No. 6,191,148 - "OMERAZOLE PROCESS AND COMPOSITIONS THEREOF," Issued February 20, 2001

  • Technology Synopsis: This patent, from the same family as the ’103 and ’213 patents, claims both highly purified compositions of omeprazole and the processes for making them. The invention addresses the formation of by-products like sulfone and sulfone-N-oxide during manufacturing by using precisely one molar equivalent of an oxidizing agent, thereby minimizing over-oxidation and yielding a final product of greater than 99.94% purity with diminished levels of residual solvents (’148 Patent, col. 1:54-col. 2:30; col. 13:1-4).
  • Asserted Claims: The complaint seeks a declaratory judgment of non-infringement for "any valid claim" of the patent (Compl. ¶22). The independent claims are 1, 11, and 14.
  • Accused Features: The complaint alleges that the manufacture, use, or sale of Lupin's esomeprazole magnesium products, which are the subject of ANDA 91-324, will not infringe the ’148 patent (Compl. ¶22).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are Plaintiff's "Esomeprazole Magnesium Delayed Release Capsules (20 mg Base and 40 mg)," which are the subject of Abbreviated New Drug Application ("ANDA") No. 91-324 (Compl. ¶7).

Functionality and Market Context

  • The product contains the active ingredient esomeprazole magnesium, a proton-pump inhibitor used for treating gastric acid-related disorders (’103 Patent, col. 1:15-25). The complaint identifies the product as a generic version of the formulation sold by AstraZeneca under the brand name NEXIUM® (Compl. ¶10). The act of alleged infringement giving rise to the controversy is the filing of the ANDA to seek FDA approval for marketing the generic drug (Compl. ¶7, ¶17).

IV. Analysis of Infringement Allegations

The complaint, which seeks a declaratory judgment, does not provide a detailed factual basis or claim chart for its non-infringement contentions. It asserts in a conclusory manner that the "manufacture, use, offer for sale, sale or importation" of its esomeprazole magnesium products will not infringe any valid claim of the patents-in-suit (Compl. ¶¶ 16, 19, 22). As such, a claim chart summary based on the complaint's allegations cannot be constructed.

No probative visual evidence provided in complaint.

  • Identified Points of Contention: Based on the technology and the nature of the dispute, the core questions for infringement will likely involve:
    • Scope Questions: The patents claim processes for making and compositions of "omeprazole," which is a racemic mixture. The accused product is "esomeprazole," the (S)-enantiomer of omeprazole. A threshold legal question is whether claims directed to "omeprazole" can be construed to read on a single enantiomer, esomeprazole.
    • Technical Questions (Composition): For composition claims like those in the ’103 and ’148 patents, the dispute will be factual. It will center on whether Lupin's final drug product contains the levels of specific "residual" solvents and impurities defined by the claim limitations. This will require chemical analysis of Lupin's product.
    • Technical Questions (Process): For process claims like those in the ’213 Patent, the analysis will focus on whether the manufacturing process used by Lupin practices every step of the claimed methods. Generic drug manufacturers often attempt to "design around" process patents, raising the question of whether Lupin’s process uses different reagents, reaction conditions, or purification steps than those recited in the claims.

V. Key Claim Terms for Construction

  • The Term: "omeprazole"

    • Context and Importance: This term is central to the entire dispute. The patents claim compositions of and processes for making "omeprazole." The accused product's active ingredient is "esomeprazole," a single stereoisomer. The construction of "omeprazole" may determine whether any of the patent claims can read on Lupin's product.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification provides the chemical name for omeprazole, "5-methoxy-2-[[4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole" (’103 Patent, col. 1:15-18). This name does not specify a particular stereoisomer, which may support a construction that encompasses the racemate as well as its individual enantiomers.
      • Evidence for a Narrower Interpretation: The patent background repeatedly refers to the commercial products LOSEC® and PRILOSEC® (’103 Patent, col. 1:19-20). At the time of the invention, these products were known to contain omeprazole as a racemic mixture. This context could support an argument that the inventors' disclosure and claims were directed specifically to the racemate.

  • The Term: "residual... solvent" (e.g., "residual aromatic hydrocarbon solvent")

    • Context and Importance: The composition claims in the ’103 and ’148 patents are defined by negative limitations on the quantity of specific residual solvents. Infringement of these claims will turn on whether Lupin's product meets these purity standards. Practitioners may focus on this term because its meaning could be outcome-determinative if Lupin's manufacturing process differs significantly from the one described in the patent.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: A party could argue the term simply means any amount of the specified solvent (e.g., toluene) found in the final product, regardless of its origin.
      • Evidence for a Narrower Interpretation: The specification discusses the removal of "entrained toluene or methylene chloride... from the oxidation step" (’103 Patent, col. 3:20-23) and "residual toluene or methylene chloride from the crude step" (’103 Patent, col. 6:45-48). This language may support an interpretation that a "residual" solvent must be one that was used in and remains from the specific process disclosed in the patent, potentially allowing a non-infringement argument if an accused infringer uses an entirely different process or different solvents.

VI. Other Allegations

The complaint does not contain sufficient detail for analysis of indirect or willful infringement.

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

  1. A core issue will be one of definitional scope: Can the term "omeprazole", which in the context of the patent often refers to a known racemic mixture, be construed to cover the single (S)-enantiomer "esomeprazole" that constitutes Lupin's accused product?
  2. A key evidentiary question for the composition claims will be one of factual compliance: Does Lupin's final drug product, as manufactured under its ANDA, actually contain the specific, low-level concentrations of residual solvents and impurities required by the negative limitations of claims in the ’103 and ’148 patents?
  3. For the process claims, the central question will be one of operational difference: Does the proprietary process Lupin uses to manufacture its esomeprazole fundamentally differ from the patented methods, thereby avoiding one or more essential steps of the process claimed in the ’213 Patent?