Teijin Ltd v. Sunshine Lake Pharma Co Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Teijin Limited, Teijin Pharma Limited (Japan), and Takeda Pharmaceuticals U.S.A., Inc. (Delaware)
  • Defendant: Sunshine Lake Pharma Co., Ltd. (China) and HEC Pharm USA Inc. (New Jersey)
  • Plaintiff’s Counsel: Saul Ewing Arnstein & Lehr LLP
• Case Identification: 3:19-cv-15448, D.N.J., 07/16/2019
• Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant HEC Pharm USA Inc. is a New Jersey corporation and Defendant Sunshine Lake Pharma Co., Ltd. is a foreign entity with no regular and established place of business in the United States.
• Core Dispute: Plaintiffs allege that Defendants' filing of an Abbreviated New Drug Application (ANDA) for generic febuxostat tablets constitutes an act of infringement of three patents related to Plaintiffs' branded drug, Uloric®.
• Technical Context: The technology concerns febuxostat, a xanthine oxidase inhibitor used for the chronic management of hyperuricemia in patients with gout, including patents on a specific crystal form and methods for its safe co-administration with other drugs.
• Key Procedural History: This is a Hatch-Waxman action filed within the 45-day window following Plaintiffs' receipt of Defendants' notice letter regarding its ANDA filing, which statutorily stays FDA approval of the generic product for up to 30 months pending litigation.

Case Timeline

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

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

• Patent Identification: U.S. Patent No. 7,361,676, titled "Solid Preparation Containing Single Crystal Form," issued April 22, 2008 (’676 Patent).

The Invention Explained

• Problem Addressed: The patent describes that the active pharmaceutical ingredient febuxostat can exist in multiple crystalline forms, or polymorphs, as well as an amorphous form (Compl., Ex. A, ’676 Patent, col. 1:23-52). Different forms can have varying physical stability and dissolution profiles, which could lead to inconsistent therapeutic effects in drug formulations (Compl., Ex. A, ’676 Patent, col. 1:61-2:6).
• The Patented Solution: The invention is a solid pharmaceutical preparation, such as a tablet, that contains febuxostat as a single, specific crystal form designated "Crystal A." This form is described as being stable in long-term storage, which allows for the production of drug preparations with uniform dissolution profiles and predictable performance (Compl., Ex. A, ’676 Patent, col. 2:7-12, col. 4:49-56). Crystal A is identified by a characteristic X-ray powder diffraction pattern with specific peaks (Compl., Ex. A, ’676 Patent, col. 2:54-58).
• Technical Importance: For orally administered drugs, controlling the crystal form of the active ingredient is critical for ensuring manufacturing consistency, product stability, and reliable bioavailability.

Key Claims at a Glance

• The complaint asserts infringement of one or more claims (Compl. ¶36). Independent claim 1 is representative.
• Essential elements of Independent Claim 1:
  • A tablet comprising crystal A of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid with an X-ray powder diffraction pattern having specific peaks at a reflection angle 2θ, of 6.62°, 7.18°, 12.80°, 13.26°, 16.48°, 19.58°, 21.92°, 22.68°, 25.84°, 26.70°, 29.16° and 36.70°,
  • an excipient,
  • and a disintegrating agent,
  • wherein the average particle diameter of the crystal A is from 12.9 µm to 26.2 µm.

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

• Patent Identification: U.S. Patent No. 8,372,872, titled "Methods For Concomitant Treatment of Theophylline and Febuxostat," issued February 12, 2013 (’872 Patent).

The Invention Explained

• Problem Addressed: Theophylline, a drug used for respiratory diseases, has a narrow therapeutic range, meaning the difference between effective and toxic blood concentrations is small (Compl., Ex. B, ’872 Patent, col. 1:24-38). Concomitant administration of other drugs that inhibit its metabolism, such as the gout medication allopurinol, can cause theophylline levels to rise to toxic levels, requiring dose adjustments (Compl., Ex. B, ’872 Patent, col. 2:40-52). Because febuxostat is also a xanthine oxidase inhibitor like allopurinol, there was a clinical expectation that it would cause a similar dangerous interaction.
• The Patented Solution: The invention is based on the discovery that, contrary to expectations, febuxostat can be co-administered with theophylline without causing a clinically significant alteration in theophylline plasma concentrations (Compl., Ex. B, ’872 Patent, col. 1:16-23). This allows for a method of treating a hyperuricemic patient who is also taking theophylline, where the febuxostat is administered "without adjusting the amount of theophylline administered for adverse drug interactions" (Compl., Ex. B, ’872 Patent, col. 23:21-24:20).
• Technical Importance: This method provides a treatment option for patients with gout who also suffer from respiratory conditions like asthma, avoiding a potentially dangerous drug-drug interaction and the need for complex dose adjustments.

Key Claims at a Glance

• The complaint asserts the sole claim of the patent (Compl. ¶43).
• Essential elements of Independent Claim 1:
  • A method of co-administering febuxostat and theophylline to a hyperuricemic patient suffering from gout,
  • comprising the step of administering to the patient a therapeutically effective amount of febuxostat in a dose of 80 mg;
  • 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.

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

• Patent Identification: U.S. Patent No. 9,107,912, titled "Methods For Concomitant Treatment of Theophylline and Febuxostat," issued August 18, 2015 (’912 Patent).

Technology Synopsis

• Similar to the ’872 Patent, this patent addresses the problem of potential drug-drug interactions between xanthine oxidase inhibitors and theophylline. It discloses a method for safely treating a patient suffering from hyperuricemia and a second disease state (e.g., asthma) by co-administering febuxostat and theophylline (Compl. ¶62; Compl., Ex. C, ’912 Patent, col. 1:16-23, col. 2:54-59).

Asserted Claims

• The complaint asserts infringement of one or more claims and quotes from independent Claim 1 (Compl. ¶¶45, 62).

Accused Features

• The accused feature is the proposed prescribing information for Defendants' generic products, which is expected to instruct or encourage medical practitioners to co-administer febuxostat and theophylline without adjusting the theophylline dose (Compl. ¶¶51-55, 63).

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 ("Sunshine Lake's Generic Products"), for which Defendants filed ANDA No. 213069 with the U.S. Food and Drug Administration (FDA) (Compl. ¶14).

Functionality and Market Context

• The accused products are intended to be generic versions of Plaintiffs' Uloric® brand febuxostat tablets, used for the chronic management of hyperuricemia in patients with gout (Compl. ¶¶27, 29). The complaint alleges that Defendants' ANDA seeks FDA approval to engage in the commercial manufacture, use, and sale of these generic products in the United States prior to the expiration of the patents-in-suit (Compl. ¶29). By filing an ANDA, Defendants are representing that their generic product is bioequivalent to the branded Uloric® product. The complaint alleges that the prescribing information for the accused generic products is expected to be the same or substantially the same as the current Uloric® label (Compl. ¶¶51, 54, 57).
• No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

’676 Patent Infringement Allegations

Identified Points of Contention

• Factual Question: The central dispute will be a factual one of composition: does the febuxostat active pharmaceutical ingredient in Defendants' proposed generic product consist of the claimed "Crystal A" polymorph, and does it meet the "average particle diameter" limitation of 12.9 µm to 26.2 µm? The complaint notes that Defendants' notice letter contained "limited information" on the crystal form, suggesting this will be a key area of discovery (Compl. ¶32).

’872 Patent Infringement Allegations

Identified Points of Contention

• Scope & Inducement Question: A primary issue will be whether the statements in Defendants' proposed product label rise to the level of active inducement under 35 U.S.C. § 271(b). The analysis may focus on whether the label's removal of a prior contraindication and its affirmative statement that "no dose adjustment is necessary" would lead a medical professional to directly infringe the method claim (Compl. ¶¶50-54).

V. Key Claim Terms for Construction

For the ’676 Patent

• The Term: "crystal A"
• Context and Importance: The definition of "crystal A" is dispositive for infringement of the asserted composition patent. The dispute will turn on whether Defendants' product contains this specific polymorph. Practitioners may focus on this term because the patent defines it by reference to a specific set of peaks in an X-ray powder diffraction pattern.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The claim language recites that the pattern has "specific peaks at a reflection angle 2θ, of [a list of angles]," which could be argued to mean the pattern must include these peaks but could also include others.
  • Evidence for a Narrower Interpretation: The specification repeatedly refers to "a single crystal form" and distinguishes Crystal A from other known polymorphs (Crystals B, C, D, G, and E), each with its own distinct peak pattern, suggesting Crystal A must be substantially pure and match the disclosed pattern without characteristics of other forms (Compl., Ex. A, ’676 Patent, col. 1:23-52).

For the ’872 Patent

• The Term: "without adjusting the amount of theophylline administered"
• Context and Importance: This negative limitation is the core of the claimed invention and the central point of the inducement allegation. Its meaning will determine whether the instructions on the accused label actually teach the patented method. Practitioners may focus on this term because infringement depends on whether the label's language encourages a specific lack of clinical action (i.e., not adjusting the dose).
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The claim language is absolute ("without adjusting"). This could be argued to cover any co-administration where the physician does not change the pre-existing theophylline dose specifically because of the addition of febuxostat. The specification contrasts this with allopurinol, where dose adjustment is required (Compl., Ex. B, ’872 Patent, col. 2:40-52).
  • Evidence for a Narrower Interpretation: A defendant might argue that this phrase requires a complete lack of consideration of dose adjustment, and that standard medical practice always involves monitoring, which could be construed as something other than administering "without adjusting." The patent itself discloses clinical trial data showing minor, non-statistically significant changes in theophylline concentration, which could be argued to leave room for some level of clinical judgment that falls outside the scope of "without adjusting" (Compl., Ex. B, ’872 Patent, col. 11:1-20).

VI. Other Allegations

• Indirect Infringement: The complaint alleges induced infringement of the ’872 and ’912 Patents. The basis for this allegation is that Defendants' proposed prescribing information for its generic products is expected to instruct and encourage medical practitioners and patients to co-administer febuxostat and theophylline without adjusting the theophylline dosage, thereby causing direct infringement by those third parties (Compl. ¶¶52-55, 60, 63).
• Willful Infringement: The complaint alleges that Defendants were aware of the existence of the ’676, ’872, and ’912 patents and that the filing of their ANDA and certification constituted an act of infringement of those patents, which may support a claim for willfulness (Compl. ¶¶41, 66).

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

• A central issue will be one of compositional identity: Can Plaintiffs produce evidence from Defendants' ANDA submission or through discovery to prove that the proposed generic product contains the specific "Crystal A" polymorph of febuxostat and meets the claimed particle size limitations of the '676 patent?
• A second core issue will be one of active inducement: Does the language on Defendants' proposed drug label—specifically, the removal of a prior contraindication for theophylline and an affirmative statement that no dose adjustment is necessary—constitute sufficient instruction and encouragement to a medical professional to satisfy the legal standard for inducing infringement of the method claims of the '872 and '912 patents?