Teijin Ltd v. MSN Laboratories Private Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Teijin Limited (Japan), Teijin Pharma Limited (Japan), and Takeda Pharmaceuticals U.S.A., Inc. (Delaware)
  • Defendant: MSN Laboratories Private Ltd. (India) and MSN Pharmaceuticals, Inc. (Delaware)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
• Case Identification: 1:18-cv-00881, D. Del., 06/14/2018
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant MSN Pharmaceuticals Inc. is a Delaware corporation and Defendant MSN Laboratories Private Ltd. is a foreign corporation not resident in any U.S. district.
• Core Dispute: Plaintiffs allege that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the gout medication Uloric® (febuxostat) constitutes an act of infringement of three U.S. patents.
• Technical Context: The technology involves specific crystalline forms of the active ingredient febuxostat and methods for its safe co-administration with theophylline, a drug used to treat respiratory diseases.
• Key Procedural History: This is a Hatch-Waxman action initiated after Defendants filed ANDA No. 210461 with a Paragraph IV certification, asserting that Plaintiffs' patents covering Uloric® are invalid, unenforceable, or would not be infringed. The patents-in-suit are listed in the FDA's "Orange Book" for Uloric®. The complaint was filed within the 45-day period following receipt of Defendants' notice letter, triggering a statutory 30-month stay of FDA approval for the ANDA.

Case Timeline

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

U.S. Patent No. 7,361,676 - "Solid Preparation Containing Single Crystal Form" (Issued: Apr. 22, 2008)

The Invention Explained

• Problem Addressed: The patent's background describes the existence of at least six different crystalline forms (polymorphs) of febuxostat, the active pharmaceutical ingredient. It states that when formulating the drug, it was previously not possible to create solid preparations that maintained a consistent dissolution profile, even when using what was believed to be the most physically stable crystal form ('676 Patent, col. 1:57-65).
• The Patented Solution: The invention is a specific solid pharmaceutical preparation that solves the stability and consistency problem by using a single, defined crystal form of febuxostat, designated "crystal A," combined with an excipient and a disintegrating agent ('676 Patent, Abstract; col. 2:7-16). This specific combination is purported to result in a stable tablet with less variation in its dissolution profile and improved content uniformity over time, addressing the problems encountered with other polymorphs or mixtures ('676 Patent, col. 4:48-65).
• Technical Importance: For an orally administered drug, ensuring a consistent and stable crystalline structure is critical for achieving predictable bioavailability and shelf-life, which are fundamental requirements for regulatory approval and therapeutic reliability ('676 Patent, col.2:7-9).

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.
• Independent Claim 1 requires:
  • A tablet comprising "crystal A" of febuxostat, which is defined by a specific X-ray powder diffraction pattern.
  • An excipient.
  • A disintegrating agent.
  • An average particle diameter of the crystal A 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" (Issued: Feb. 12, 2013)

The Invention Explained

• Problem Addressed: Theophylline, a drug for respiratory conditions like asthma, has a narrow therapeutic range. The patent background notes that allopurinol, another drug for treating gout, is known to inhibit the metabolism of theophylline, dangerously increasing its concentration in the body ('872 Patent, col. 1:40-54). Because febuxostat also inhibits xanthine oxidase, it was expected to cause the same hazardous drug-drug interaction, leading to an initial contraindication against its use with theophylline (Compl. ¶¶49-50).
• The Patented Solution: The inventors discovered that, contrary to expectations, febuxostat can be co-administered with theophylline without causing a clinically significant alteration in theophylline's plasma concentration ('872 Patent, col. 2:21-31). The patent claims a method of treating a patient for both hyperuricemia (with febuxostat) and a respiratory condition (with theophylline) concurrently, without the need to adjust the theophylline dose that would otherwise be required to avoid toxicity ('872 Patent, col. 9:48-54).
• Technical Importance: This discovery removed a significant contraindication for febuxostat, making the drug a viable treatment option for a large population of gout patients who are also on theophylline for respiratory illnesses (Compl. ¶¶51-52).

Key Claims at a Glance

• The complaint asserts "the sole claim of the '872 patent," which is Claim 1 (Compl. ¶45).
• Independent Claim 1 requires:
  • 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 febuxostat.
  • The administration is performed without adjusting the amount of theophylline 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" (Issued: August 18, 2015)

Multi-Patent Capsule

• Patent Identification: U.S. Patent No. 9,107,912, "Methods For Concomitant Treatment of Theophylline and Febuxostat," Issued: August 18, 2015 (Compl. ¶25).
• Technology Synopsis: As a member of the same family as the ’872 Patent, this patent addresses the identical technical problem: the presumed drug-drug interaction between febuxostat and theophylline that would complicate treatment for patients with both gout and respiratory disease ('912 Patent, col. 1:25-54). The solution is a method of safely co-administering the two drugs based on the finding that, unlike with allopurinol, no clinically significant interaction occurs, thereby obviating the need for theophylline dose adjustment ('912 Patent, col. 2:4-31).
• Asserted Claims: The complaint asserts infringement of "one or more claims" (Compl. ¶47). Independent claim 1 is representative and is quoted in part in the complaint (Compl. ¶64).
• Accused Features: The allegations for the ’912 Patent are based on a theory of induced infringement. The complaint alleges that the prescribing information for MSN’s generic product will induce medical practitioners to co-administer febuxostat and theophylline by removing the prior contraindication and providing standard dosing instructions (Compl. ¶¶53-57, 65).

III. The Accused Instrumentality

Product Identification

• The accused instrumentalities are "MSN's Generic Products," which are proposed oral tablets containing 40 mg and 80 mg of the active ingredient febuxostat, as described in Abbreviated New Drug Application (ANDA) No. 210461 (Compl. ¶14).

Functionality and Market Context

• The products are generic versions of the branded drug Uloric®, designed to be therapeutically equivalent for the treatment of hyperuricemia (Compl. ¶¶27, 29). The infringement allegations center not only on the physical tablets but also on the proposed prescribing information that will accompany them. The complaint alleges this label will omit a prior contraindication against co-administration with theophylline and will contain dosing instructions expected to induce infringement of the asserted method patents (Compl. ¶¶53-59).
• No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

’676 Patent Infringement Allegations

• Identified Points of Contention:
  • Evidentiary Question: A central factual dispute will be one of composition. What is the actual polymorph or mixture of polymorphs of febuxostat in the product described in MSN's ANDA? The complaint itself suggests a lack of clear evidence on this point, making it a likely focus of discovery and expert testimony (Compl. ¶32).

’872 Patent Infringement Allegations

• Identified Points of Contention:
  • Legal Question: The primary legal question is one of inducement. Does a generic drug manufacturer's act of removing a contraindication from a product label, when combined with standard dosing instructions, rise to the level of specific intent and affirmative encouragement required to prove induced infringement of a method claim performed by third-party physicians and patients?

V. Key Claim Terms for Construction

For the ’676 Patent

• The Term: "crystal A"
• Context and Importance: The patent's entire premise is the use of a specific, stable polymorph of febuxostat. The definition of "crystal A" is therefore dispositive for infringement. A dispute may arise over how closely an accused product's crystalline structure must match the definition in the patent.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: A party might argue that substantial correspondence to the defining characteristics is sufficient. The specification describes crystal A using multiple techniques, including solid-state NMR, suggesting the definition is not limited to XRPD alone ('676 Patent, col. 2:40-58).
  • Evidence for a Narrower Interpretation: The claim recites a specific list of eleven X-ray powder diffraction (XRPD) peaks at particular reflection angles ('676 Patent, col. 12:5-8). A party would argue that "crystal A" must be a single polymorph that exhibits all or nearly all of these defining peaks, as any deviation would mean it is not the claimed crystal form.

For the ’872 Patent

• The Term: "without adjusting the amount of theophylline"
• Context and Importance: This negative limitation is central to the inventive concept of safe co-administration. The dispute will likely focus on what constitutes an "adjustment." Practitioners may focus on this term because the Uloric® label still advises "use with caution" (Compl. ¶55), and the meaning of "adjusting" in that clinical context is critical to determining whether the claimed method is practiced.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation (Plaintiff's View): The specification teaches that "co-administration of febuxostat and theophylline can be carried out without adjusting the amount of theophylline" ('912 Patent, col. 10:51-53, identical specification). This may support an interpretation where any administration of a standard therapeutic dose of theophylline, without a specific reduction made because of febuxostat, satisfies this limitation.
  • Evidence for a Narrower Interpretation (Defendant's View): A defendant could argue that the label's instruction to "use with caution" (Compl. ¶55) inherently implies that physicians should consider modifications, such as starting with a lower dose or monitoring levels more frequently. Such cautionary clinical practices could be framed as a form of "adjustment" that avoids direct infringement of the method claim, even if not a change from a pre-existing dose.

VI. Other Allegations

• Indirect Infringement: The primary theory for the ’872 and ’912 method patents is induced infringement. The complaint alleges that MSN's proposed product label, by removing the prior contraindication and providing dosing instructions, will encourage and instruct medical practitioners and patients to perform the patented methods of co-administration (Compl. ¶¶54-62, 65). For the ’676 patent, the complaint includes a general allegation that MSN will induce or contribute to infringement if it commercially sells its products (Compl. ¶41).
• Willful Infringement: The complaint alleges that MSN was "aware of the existence" of the patents-in-suit and knew that filing its ANDA constituted an act of infringement (Compl. ¶¶43, 68). These allegations of pre-suit knowledge form the basis for a potential claim of willful infringement.

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

1. An Evidentiary Question of Composition: For the ’676 patent, the case will depend on a core factual question: what is the precise polymorphic structure of the febuxostat in MSN's proposed generic product, and does the evidence show that it is the specific "crystal A" defined by the patent's claims? The complaint's own language suggests this evidence may be a point of significant contention.

2. A Legal Question of Inducement: For the ’872 and ’912 patents, a central legal issue will be one of intent and causation: does a generic drug label that omits a prior contraindication and includes standard dosing information constitute an affirmative act of encouraging infringement with the specific intent required by law, or is it merely providing neutral, factual information that does not rise to the level of inducement?