Teijin Ltd v. Aurobindo Pharma 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: Aurobindo Pharma Ltd. (India) and Aurobindo Pharma USA Inc. (Delaware)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Paul Hastings LLP; Patterson Belknap Webb & Tyler LLP
• Case Identification: 1:17-cv-01314, D. Del., 09/15/2017
• Venue Allegations: Venue is asserted in Delaware because Defendant Aurobindo Pharma USA, Inc. is a Delaware corporation, and Defendant Aurobindo Pharma Ltd., a foreign corporation, may be sued in any judicial district.
• Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to market generic febuxostat tablets infringes four patents related to specific crystal forms, pharmaceutical formulations, and methods of using the drug.
• Technical Context: The technology concerns febuxostat (marketed as Uloric®), a xanthine oxidase inhibitor used for the chronic management of hyperuricemia in patients with gout.
• Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiffs' receipt of a Notice Letter on August 4, 2017, informing them of Aurobindo’s ANDA No. 210741 filing, which included a Paragraph IV certification challenging the asserted patents. The complaint notes that the patents-in-suit are listed in the FDA's "Orange Book" as covering Uloric®. A key allegation for two of the method patents is that their invention enabled the removal of a prior contraindication against co-administering febuxostat with theophylline, and that the generic drug's label will induce infringement by adopting this revised prescribing information.

Case Timeline

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

U.S. Patent No. 6,225,474 - “Polymorphs of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic Acid and Method of Producing the Same,” issued May 1, 2001

The Invention Explained

• Problem Addressed: The patent addresses the challenge that an active pharmaceutical ingredient can exist in multiple crystalline structures, known as polymorphs, which may have different physical properties such as stability and solubility, potentially affecting the quality and efficacy of the final drug product (U.S. Patent 6,225,474, col. 1:10-25).
• The Patented Solution: The invention identifies and characterizes several distinct polymorphs of febuxostat, designating them Crystals A, B, C, D, and G. The patent claims these specific crystal forms, defining them by their characteristic peaks in an X-ray powder diffraction pattern, and provides methods for producing them (U.S. Patent 6,225,474, col. 2:23-41; Abstract). Crystal A is identified as being particularly stable and suitable for pharmaceutical preparations (U.S. Patent 6,225,474, col. 8:1-5).
• Technical Importance: Isolating and claiming a single, stable polymorph of a drug substance is critical in pharmaceutical manufacturing to ensure batch-to-batch consistency, predictable dissolution rates, and stable shelf-life.

Key Claims at a Glance

• The complaint indicates that Defendant did not deny infringement of claims 5, 10, 17, and 25 apart from an invalidity assertion (Compl. ¶33). These claims depend from independent claim 1.
• Independent Claim 1:
  • A polymorph of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid,
  • which shows an X-ray powder diffraction pattern having specific peaks at reflection angles of about 6.62°, 13.26°, and 26.70°.

U.S. Patent No. 7,361,676 - “Solid Preparation Containing Single Crystal Form,” issued April 22, 2008

The Invention Explained

• Problem Addressed: The patent’s background section notes that even when using a physically stable crystal form of a drug, variations in dissolution profiles can still occur in the final solid preparation (e.g., tablets), which is undesirable for ensuring consistent therapeutic effect (’676 Patent, col. 1:56-64).
• The Patented Solution: The invention provides a solid pharmaceutical preparation that combines a single crystal form of febuxostat (specifically, Crystal A from the ’474 Patent) with particular excipients and disintegrating agents. The solution further involves controlling the average particle size of the drug substance within a specific range to achieve a uniform dissolution profile (’676 Patent, col. 4:49-55; Abstract).
• Technical Importance: This technology allows for the manufacture of oral solid dosage forms with highly consistent and predictable drug release characteristics, a key factor for regulatory approval and patient safety.

Key Claims at a Glance

• The complaint asserts one or more claims of the ’676 Patent (Compl. ¶42).
• Independent Claim 1:
  • A tablet comprising crystal A of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid with a specific X-ray powder diffraction pattern,
  • 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,” issued February 12, 2013

Technology Synopsis

The complaint explains that febuxostat was previously contraindicated for co-administration with theophylline due to concerns about increased theophylline plasma concentrations and potential toxicity (Compl. ¶¶ 53-54). The invention is based on the discovery that febuxostat can be safely co-administered with theophylline without requiring dose adjustment of theophylline, contrary to prior medical understanding (’872 Patent, Abstract; Compl. ¶55).

Asserted Claims

The complaint asserts the sole claim of the patent, Claim 1 (Compl. ¶¶ 49, 65).

Accused Features

The complaint alleges that Aurobindo's proposed product labeling will induce infringement by medical practitioners. The label allegedly removes the prior contraindication and includes dosage instructions that would lead doctors to prescribe 80 mg of febuxostat to patients also taking theophylline, thereby practicing the patented method (Compl. ¶¶ 58, 62, 66).

U.S. Patent No. 9,107,912 - “Methods For Concomitant Treatment of Theophylline and Febuxostat,” issued August 18, 2015

Technology Synopsis

Related to the ’872 Patent, this patent covers a method of administering febuxostat to a patient suffering from hyperuricemia and at least one other disease state, where the patient is also receiving theophylline to treat that other disease state (’912 Patent, Abstract). The core of the invention is the safe concomitant use of the two drugs.

Asserted Claims

The complaint asserts "one or more claims," including Claim 1 (Compl. ¶¶ 51, 69).

Accused Features

As with the ’872 Patent, the accusation is that Aurobindo's proposed labeling for its generic product will induce infringement by encouraging medical practitioners to co-administer febuxostat and theophylline without dose adjustment (Compl. ¶¶ 61-62, 70).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is "Aurobindo’s Generic Product," defined as oral tablets containing 40 mg and 80 mg of the active ingredient febuxostat, for which Aurobindo submitted Abbreviated New Drug Application (ANDA) No. 210741 to the FDA (Compl. ¶¶ 15, 29).

Functionality and Market Context

The product is a generic version of Plaintiffs' branded drug, Uloric®, and is intended for the treatment of hyperuricemia in patients with gout (Compl. ¶27). For the method patent claims, the instrumentality also includes the proposed prescribing information for Aurobindo's product, which is expected to contain instructions regarding dosage and administration that Plaintiffs allege will induce infringement (Compl. ¶¶ 57-64). The filing of the ANDA itself constitutes the act of infringement under 35 U.S.C. § 271(e)(2) (Compl. ¶38).

IV. Analysis of Infringement Allegations

The complaint alleges infringement under 35 U.S.C. § 271(e)(2)(A), which defines the submission of an ANDA seeking approval to market a drug claimed in a patent as an act of infringement (Compl. ¶38). The complaint states that Aurobindo's notice letter contained "limited information about the crystal form or forms of the febuxostat materials" and does not provide sufficient detail for a claim-by-claim analysis of the ’474 and ’676 patents (Compl. ¶32). Accordingly, a claim chart summary cannot be constructed.

No probative visual evidence provided in complaint.

• Narrative Infringement Theory (’474 and ’676 Patents): The complaint alleges that by seeking FDA approval to manufacture and sell a generic febuxostat product that is bioequivalent to Uloric®, Aurobindo's product will necessarily infringe one or more claims of the patents covering the specific stable crystal form of febuxostat and the solid preparation containing it (Compl. ¶¶ 38-39, 42-43).
• Narrative Infringement Theory (’872 and ’912 Patents): For the method patents, the complaint alleges induced infringement under 35 U.S.C. § 271(b). The theory is that Aurobindo's proposed product label will instruct and encourage medical professionals and patients to co-administer febuxostat and theophylline. This is based on the label allegedly removing a prior contraindication and including dosage recommendations that align with the patented methods (Compl. ¶¶ 58, 62, 66, 70).
• Identified Points of Contention:
  • Technical Questions: A primary technical question for the ’474 and ’676 patents will be factual: what is the precise crystalline structure and average particle size of the febuxostat active ingredient in Aurobindo's proposed generic product? The case may turn on whether Aurobindo has used the claimed Crystal A or has successfully designed a product with a different, non-infringing polymorph or an amorphous form.
  • Scope Questions: For the ’872 and ’912 method patents, the central question is one of inducement. Does the language in Aurobindo’s proposed prescribing information, taken as a whole, specifically encourage, recommend, or promote the administration of febuxostat in a manner that meets all the limitations of the asserted method claims?

V. Key Claim Terms for Construction

Term: "about" (from '474 Patent, Claim 1)

• Context and Importance: This term modifies the specific numerical values of the X-ray diffraction peaks that define the patented crystal form. The scope of the claims hinges on the degree of variability the court allows for this term. Practitioners may focus on this term because the infringement analysis will involve comparing the diffraction data of Aurobindo's product to the claimed peaks, and a dispute could arise if Aurobindo's peaks are close to, but not identical to, the recited values.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The repeated use of "about" for each peak in the claim language itself suggests the patentee did not intend the values to be absolute and acknowledged that minor experimental variations can occur.
  • Evidence for a Narrower Interpretation: The specification provides specific examples and figures showing the diffraction patterns. A party could argue that the scope of "about" should be limited to the range of variation observed within those disclosed examples (e.g., U.S. Patent 6,225,474, FIG. 1).

Term: "average particle diameter" (from '676 Patent, Claim 1)

• Context and Importance: Infringement of claim 1 of the ’676 patent requires the crystal A in the accused tablet to have an "average particle diameter" within the range of 12.9 µm to 26.2 µm. The definition of this term, including the method of measurement, is critical.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: A party might argue that unless a specific measurement technique is required by the claims, any standard industry method for determining average particle size is acceptable.
  • Evidence for a Narrower Interpretation: The specification states that the average particle size is "determined by an image analysis" (’676 Patent, col. 3:1-2). This explicit disclosure may support an argument that the claim term should be construed as being limited to the result obtained by that specific methodology.

VI. Other Allegations

Indirect Infringement

The complaint explicitly alleges that Aurobindo will induce infringement of the ’872 and ’912 patents. The basis for this allegation is that Aurobindo's proposed product label is expected to remove the prior contraindication against using febuxostat with theophylline and will contain affirmative statements and dosage instructions that encourage medical practitioners and patients to perform the claimed methods of co-administration (Compl. ¶¶ 58, 61-62, 66-67).

Willful Infringement

The complaint alleges that Aurobindo had pre-suit knowledge of all four patents-in-suit and was aware that filing its ANDA constituted an act of infringement (Compl. ¶¶ 47, 73). This forms the basis for a potential claim for enhanced damages should infringement be found.

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

This litigation presents two distinct types of infringement disputes common in Hatch-Waxman cases. The resolution of the case will likely depend on the answers to the following questions:

• A central factual question will be one of product composition: Does Aurobindo’s generic product utilize the specific "Crystal A" polymorph of febuxostat within the claimed particle size range, as required by the ’474 and ’676 patents, or has it successfully designed a product with a different, non-infringing crystal form?
• A key legal question will be one of induced infringement: Does the language in Aurobindo's proposed product label go beyond merely stating safety information and instead rise to the level of affirmatively instructing or encouraging medical professionals to perform the patented methods of co-administering febuxostat and theophylline, as claimed in the ’872 and ’912 patents?