DCT

1:18-cv-00987

Teijin Ltd v. Torrent Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-00987, D. Del., 07/02/2018
  • Venue Allegations: Venue is asserted in the District of Delaware because Defendant Torrent Pharma Inc. is a Delaware corporation, and Defendant Torrent Pharmaceuticals Ltd. is a foreign corporation with no regular and established place of business in the United States.
  • Core Dispute: Plaintiffs allege that Defendants' Abbreviated New Drug Application (ANDA) to market generic febuxostat tablets constitutes an act of infringement of three patents covering a specific crystalline form of febuxostat and methods of its co-administration with the drug theophylline.
  • Technical Context: The technology concerns pharmaceutical formulations for treating hyperuricemia, a condition characterized by high levels of uric acid in the blood that is the primary cause of gout.
  • Key Procedural History: This is a Hatch-Waxman action triggered by Defendants' filing of ANDA No. 211837 with the U.S. Food and Drug Administration (FDA). The ANDA includes a "Paragraph IV" certification, asserting that the patents-in-suit, which are listed in the FDA's "Orange Book" as covering the brand-name drug Uloric®, are invalid, unenforceable, or will not be infringed by the proposed generic product. Plaintiffs received a notice letter regarding the ANDA filing on May 21, 2018.

Case Timeline

Date Event
2002-03-28 Earliest Priority Date for U.S. Patent No. 7,361,676
2008-04-22 U.S. Patent No. 7361676 Issues
2010-09-10 Earliest Priority Date for U.S. Patent Nos. 8,372,872 & 9,107,912
2013-02-12 U.S. Patent No. 8372872 Issues
2015-08-18 U.S. Patent No. 9107912 Issues
2018-05-21 Plaintiffs receive Defendants’ ANDA Notice Letter
2018-07-02 Complaint Filed

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

U.S. Patent No. 7,361,676 - "Solid Preparation Containing Single Crystal Form"

The Invention Explained

  • Problem Addressed: The patent describes that the active pharmaceutical ingredient febuxostat can exist in at least six different crystalline forms, or polymorphs (crystals A, B, C, D, E, G), as well as an amorphous form (’676 Patent, col. 1:23-50). This polymorphism presents a manufacturing challenge, as different crystal forms can have different physical properties, such as stability and dissolution rate, leading to potential "variation in the dissolution profiles of drugs" and inconsistent product performance (’676 Patent, col. 1:57-63).
  • The Patented Solution: The invention is a solid pharmaceutical preparation (e.g., a tablet) that uses a single, specific polymorph known as "crystal A." This crystal form is described as being physically stable over long-term storage, which ensures a uniform dissolution profile and consistent drug delivery (’676 Patent, col. 2:1-4, col. 4:46-55). The patent identifies crystal A by its characteristic X-ray powder diffraction pattern (’676 Patent, col. 1:26-30).
  • Technical Importance: Achieving a stable, single-polymorph formulation is a critical step in pharmaceutical development, as it ensures product consistency, predictable bioavailability, and compliance with regulatory standards for drug manufacturing (’676 Patent, col. 4:56-65).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" without specifying which ones (Compl. ¶38). Independent claim 1 is representative.
  • Essential elements of independent claim 1 include:
    • A tablet comprising "crystal A" of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid, defined by a specific X-ray powder diffraction pattern.
    • An excipient.
    • A disintegrating agent.
    • An average particle diameter of the crystal A that is from 12.9 µm to 26.2 µm.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 8,372,872 - "Methods For Concomitant Treatment of Theophylline and Febuxostat"

The Invention Explained

  • Problem Addressed: The patent explains that theophylline, a drug used to treat respiratory diseases like asthma, has a narrow therapeutic range, meaning small changes in its blood concentration can lead to either ineffectiveness or serious toxicity (’872 Patent, col. 1:30-39). Co-administration with xanthine oxidase inhibitors, such as allopurinol, was known to slow theophylline's metabolism and dangerously increase its concentration, leading to a contraindication against their combined use (’872 Patent, col. 2:40-54; Compl. ¶49-50).
  • The Patented Solution: The invention is a method of treatment based on the discovery that, contrary to expectations based on allopurinol, febuxostat can be co-administered with theophylline without causing a clinically significant change in theophylline's plasma concentration (’872 Patent, col. 2:55-65). This allows patients suffering from both hyperuricemia and a respiratory condition to be treated with both drugs safely and effectively, "without adjusting the amount of theophylline administered for adverse drug interactions" (’872 Patent, Claim 1).
  • Technical Importance: This discovery removed a significant treatment barrier for a population of patients with comorbidities, allowing a gout therapy to be used safely alongside a standard respiratory therapy without the need for complex dose adjustments or fear of toxicity (’872 Patent, col. 2:55-65).

Key Claims at a Glance

  • The complaint asserts infringement of the "sole claim" of the patent, which is independent claim 1 (Compl. ¶45, 60).
  • Essential elements of independent claim 1 include:
    • A method of co-administering febuxostat and theophylline to a hyperuricemic patient suffering from gout.
    • Administering a therapeutically effective amount of febuxostat in a dose of 80 mg.
    • Administering a therapeutically effective amount of theophylline subsequent to the administration of the febuxostat.
    • Performing the administration "without adjusting the amount of theophylline administered for adverse drug interactions."
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 9,107,912 - "Methods For Concomitant Treatment of Theophylline and Febuxostat"

Technology Synopsis

  • Like the related ’872 patent, this patent addresses the challenge of safely co-administering febuxostat and theophylline. The invention is a method of treating a patient suffering from hyperuricemia and a second disease state (e.g., asthma) by administering both drugs, based on the finding that febuxostat does not dangerously alter theophylline metabolism (’912 Patent, col. 1:24-col. 2:65).

Asserted Claims

  • The complaint asserts infringement of "one or more claims," and specifically calls out the "sole independent claim," which is claim 1 (Compl. ¶47, 64).

Accused Features

  • The accused act is Defendants' filing of an ANDA for a generic febuxostat product with proposed labeling that is expected to omit the prior contraindication against theophylline use, thereby allegedly inducing medical practitioners to co-administer the drugs as claimed (Compl. ¶53-54, 65).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are Defendants' proposed generic oral tablets containing 40 mg and 80 mg of the active ingredient febuxostat ("Torrent's Generic Products"), for which Defendants filed ANDA No. 211837 with the FDA (Compl. ¶14).

Functionality and Market Context

  • The proposed generic product is intended to be a therapeutic equivalent to Plaintiffs' brand-name drug, Uloric®, for the treatment of hyperuricemia (Compl. ¶27). The complaint alleges that Defendants' ANDA seeks approval for the commercial manufacture, use, and sale of this generic product before the expiration of the patents-in-suit (Compl. ¶29). The infringement allegations concern not only the physical composition of the tablets but also the prescribing information (product label) that will accompany them, which is alleged to induce infringement of the asserted method patents (Compl. ¶53-54).
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail for a claim-by-claim analysis of U.S. Patent No. 7,361,676. The infringement theory is based on the act of filing the ANDA under 35 U.S.C. § 271(e)(2)(A), with the allegation that the product Torrent seeks to market will infringe one or more claims (Compl. ¶38). The complaint notes that Torrent's notification letter contained "limited information about the crystal form or forms" of febuxostat in the proposed product, suggesting this will be a central point of discovery (Compl. ¶32).

’872 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of co-administering febuxostat and theophylline to a hyperuricemic patient suffering from gout, the method comprising the steps of: The proposed label for Torrent's Generic Products is expected to induce medical practitioners and patients to perform the claimed method of co-administration. ¶54, 57 col. 24:1-12
administering to the hyperuricemic patient suffering from gout a therapeutically effective amount of febuxostat in a dose of 80 mg; Torrent's proposed label is expected to contain dosage and administration instructions recommending an 80 mg dose of febuxostat, thereby inducing this step. ¶58-59, 60-61 col. 24:4-7
and administering to the patient a therapeutically effective amount of theophylline subsequent to the administration of the febuxostat without adjusting the amount of theophylline administered for adverse drug interactions. Torrent's proposed label is expected to remove the prior contraindication against theophylline and state that no dose adjustment is necessary, which allegedly encourages and instructs users to co-administer the drugs without dose adjustment. ¶53-57 col. 24:8-12

Identified Points of Contention

  • Scope Questions: A primary question for the ’676 Patent will be evidentiary: does the febuxostat in Torrent's Generic Products consist of "crystal A" as defined by the patent's specific X-ray diffraction peaks, and does it meet the claimed particle size range? The complaint suggests this information is not yet fully known (Compl. ¶32).
  • Technical Questions: For the ’872 and ’912 Patents, the dispute may center on the legal standard for inducement. The key question is whether Torrent's proposed label, by removing a contraindication and stating that "no dose adjustment is necessary," provides sufficient affirmative instruction to demonstrate the specific intent required to induce infringement, or whether it merely conveys factual clinical data without actively promoting the patented method (Compl. ¶54-57).

V. Key Claim Terms for Construction

"average particle diameter of the crystal A is from 12.9 µm to 26.2 µm" (’676 Patent, Claim 1)

  • Context and Importance: This limitation defines a specific, narrow range for the size of the active ingredient particles. Infringement of claim 1 depends on whether Torrent's product falls within these precise numerical boundaries. Practitioners may focus on this term because even if the correct crystal form is used, a product with a particle size outside this range would not literally infringe this claim.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party might argue that the range is merely exemplary of preferred embodiments that yield good results, although the claim language "is from" suggests a hard boundary. The specification does not appear to provide explicit language supporting a broader construction.
    • Evidence for a Narrower Interpretation: The patent specification explicitly ties this exact range to specific particles (Particles 2 and 3) produced by particular milling methods and links them to specific, favorable dissolution profiles shown in FIG. 7 (’676 Patent, Table 7, col. 11:1-12, col. 7:35-39). The patent also describes particles outside this range (e.g., Particle 1 at 3.5 µm and Particle 4 at 48.6 µm), reinforcing the specificity and potential criticality of the claimed range (’676 Patent, Table 7).

"without adjusting the amount of theophylline" (’872 Patent, Claim 1)

  • Context and Importance: This negative limitation is central to the claimed method, distinguishing it from prior art treatments (like allopurinol) where dose adjustment was required. The infringement analysis will likely turn on what actions (or non-actions) by a physician are covered by this phrase and whether Torrent's label induces them.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent repeatedly contrasts the invention with the known interaction with allopurinol, suggesting "without adjusting" means the absence of the significant dose modifications and close monitoring required when using allopurinol (’872 Patent, col. 2:40-54).
    • Evidence for a Narrower Interpretation: The clinical trial data in the patent shows that while co-administration is safe, the pharmacokinetic values are not identical; for example, the AUC for theophylline increased by 5% with febuxostat compared to placebo (’872 Patent, Table 6). A defendant could argue that "without adjusting" requires absolute non-interference, and that any label instruction to "use with caution" (as alleged in Compl. ¶55) acknowledges a potential interaction and thus falls outside the scope of the claim.

VI. Other Allegations

  • Indirect Infringement: The core of the allegations against the ’872 and ’912 Patents is induced infringement under 35 U.S.C. § 271(b). The complaint alleges that Defendants' proposed product labeling will induce infringement by medical professionals and patients. Specifically, it alleges the label will remove the prior contraindication against co-administration with theophylline and will contain affirmative statements that "no dose adjustment is necessary," thereby instructing and encouraging the practice of the claimed methods (Compl. ¶54, 56-57, 61-62).
  • Willful Infringement: The complaint alleges that Torrent was aware of the existence of all three patents-in-suit and knew that the filing of its ANDA constituted an act of infringement (Compl. ¶43, 68). This allegation of pre-suit knowledge provides a basis for a claim of willful infringement.

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

  • A central question for the '676 patent will be evidentiary and factual: does the proposed generic product, as described in its ANDA, actually use the "crystal A" polymorph of febuxostat, and does its "average particle diameter" fall within the narrowly claimed range of 12.9 µm to 26.2 µm? The resolution will depend on technical evidence from product testing and analysis.
  • The primary issue for the ’872 and ’912 method patents will be one of induced infringement: does the act of removing a prior contraindication and stating that "no dose adjustment is necessary" on a generic drug's label rise to the level of specific intent required to encourage infringement under § 271(b)? The court will have to determine whether this constitutes active instruction to perform the patented method or a permissible, factual statement about the drug's properties.