IBSA Institut Biochimique SA v. Teva Pharmaceutical USA Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: IBSA Institut Biochimique SA (Switzerland), IBSA Pharma Inc. (Delaware), and Altergon SA (Switzerland)
  • Defendant: Teva Pharmaceuticals USA, Inc. (Delaware)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Fenwick & West LLP
• Case Identification: 1:19-cv-02115, D. Del., 11/08/2019
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because the defendant, Teva Pharmaceuticals USA, Inc., is a Delaware corporation.
• Core Dispute: Plaintiffs allege that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiffs' Tirosint® (levothyroxine sodium) capsules constitutes an act of infringement of two patents covering stable pharmaceutical formulations for thyroid hormones.
• Technical Context: The technology concerns soft gelatin capsule formulations for thyroid hormones, which are notoriously unstable and require precise dosing to treat conditions like hypothyroidism safely and effectively.
• Key Procedural History: This is a Hatch-Waxman patent infringement action initiated under 35 U.S.C. § 271(e)(2)(A). The action was triggered by Defendant Teva’s submission of an ANDA with a Paragraph IV certification, asserting that the patents-in-suit, which are listed in the FDA’s Orange Book for Tirosint®, are invalid, unenforceable, or will not be infringed by Teva’s proposed generic product.

Case Timeline

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

U.S. Patent No. 7,691,411 - "PHARMACEUTICAL FORMULAE FOR THYROID HORMONES AND PROCEDURES FOR OBTAINING THEM," issued April 6, 2010

The Invention Explained

• Problem Addressed: The patent describes the significant challenges in creating stable and reliable oral dosage forms for thyroid hormones (’411 Patent, col. 1:11-18). Due to a very narrow therapeutic index, even minor deviations in the dose of levothyroxine can lead to either ineffective treatment (hypothyroidism) or dangerous side effects like cardiac arrhythmia (hyperthyroidism) (’411 Patent, col. 2:3-10). The background notes that prior art solid tablet formulations suffered from poor stability and inconsistent active principle content, leading to product recalls and patient harm (’411 Patent, col. 2:21-46).
• The Patented Solution: The invention proposes a pharmaceutical composition in a "uniform matrix of soft-gel" designed for oral administration (’411 Patent, Abstract). Instead of a compacted tablet, the thyroid hormone is incorporated into a single-phase, homogenous soft gelatin matrix comprising specific ratios of gelatine, a solvent (such as glycerol or sorbitol), and water (’411 Patent, col. 3:9-36). This formulation is intended to provide superior stability and dosage uniformity compared to traditional tablets (’411 Patent, col. 3:49-54).
• Technical Importance: The development of a stable, soft-gel formulation provided a solution to the long-standing problem of dosage inconsistency for a class of drugs where precision is paramount for patient safety (’411 Patent, col. 2:50-54).

Key Claims at a Glance

• The complaint asserts independent claims 1 and 16, as well as dependent claims 2-15 and 17-32 (Compl. ¶19).
• Independent Claim 1 recites a pharmaceutical composition in a "single phase uniform matrix of soft-gel" comprising a thyroid hormone, 30%-68% gelatine, 31-60% glycerol, and 1-10% water.
• Independent Claim 16 recites a similar composition but requires 20-60% "sorbitol/sorbitans" instead of glycerol.
• The complaint reserves the right to assert all claims from 1-32 (’411 Patent, col. 27:1-col. 28:65; Compl. ¶19).

U.S. Patent No. 7,723,390 - "PHARMACEUTICAL FORMULATIONS FOR THYROID HORMONES," issued May 25, 2010

The Invention Explained

• Problem Addressed: Similar to the ’411 patent, the ’390 Patent addresses the instability and unreliable bioavailability of conventional thyroid hormone tablets (’390 Patent, col. 2:20-28). It notes that the active ingredient, levothyroxine, is sensitive to excipients and that the manufacturing process for tablets can itself contribute to degradation and dosage variability (’390 Patent, col. 3:1-4).
• The Patented Solution: The invention claims a pharmaceutical composition in one of two forms: either a soft elastic capsule containing a liquid or semi-liquid inner phase where the hormone is dissolved, or a "swallowable uniform soft-gel matrix" (’390 Patent, col. 14:31-44). Both approaches avoid the mechanical stress of tablet compaction and aim to protect the active ingredient in a stable vehicle, such as a solution of glycerol and/or gelatin (’390 Patent, Abstract; col. 6:20-39). The specification also highlights that these soft-gel matrices can be divided by the patient for dosage adjustments, a key advantage over conventional tablets (’390 Patent, col. 6:45-56).
• Technical Importance: This technology offered formulation platforms (liquid-filled capsules or uniform gel matrices) that circumvented the known degradation pathways associated with solid, compacted thyroid hormone tablets, thereby improving product reliability and safety (’390 Patent, col. 4:4-11).

Key Claims at a Glance

• The complaint asserts independent claim 1 and dependent claims 2-10 (Compl. ¶25).
• Independent Claim 1 recites a pharmaceutical composition for thyroid hormones in the form of either:
  • a) a soft elastic capsule with a shell and a "liquid or semi-liquid inner phase" containing the hormone dissolved in a vehicle of gelatin and/or glycerol; or
  • b) a "swallowable uniform soft-gel matrix" comprising glycerol and the hormone.
• The complaint reserves the right to assert all claims from 1-10 (’390 Patent, col. 14:30-col. 16:5).

III. The Accused Instrumentality

Product Identification

• The accused instrumentality is "Teva's Product," a generic version of levothyroxine sodium capsules for which Defendant submitted Abbreviated New Drug Application (ANDA) No. 213256 to the FDA (Compl. ¶10). The ANDA covers dosage strengths of 88 mcg, 100 mcg, and 125 mcg (Compl. ¶10).

Functionality and Market Context

• The complaint alleges that Teva's Product is a generic version of Plaintiffs' Tirosint® product and that Teva's ANDA relies on data demonstrating bioequivalence to Tirosint® (Compl. ¶11). This implies that Teva's Product is a soft gelatin capsule containing levothyroxine sodium, intended for oral administration to treat hypothyroidism. The complaint does not provide specific details on the excipients or manufacturing process of Teva's Product, as this information is contained within the confidential ANDA. No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint alleges that the submission of the ANDA is a statutory act of infringement under 35 U.S.C. § 271(e)(2)(A) and that future commercialization would constitute direct and indirect infringement (Compl. ¶¶18-19, 24-25). The infringement theory is based on the allegation that Teva's Product, by being a bioequivalent generic of the Tirosint® soft-gel capsule, necessarily possesses the features claimed by the patents-in-suit.

• ’411 Patent Infringement Allegations

• ’390 Patent Infringement Allegations

• Identified Points of Contention:
  • Compositional Questions: A primary point of contention will be factual: does the specific formulation disclosed in Teva's confidential ANDA actually meet the precise percentage-by-weight limitations for gelatine, glycerol, sorbitol/sorbitans, and water as required by the asserted claims of the ’411 Patent?
  • Structural Questions: A key legal and technical question for the ’390 Patent will be whether Teva's product is properly characterized as a two-part "soft elastic capsule" with a "liquid or semi-liquid inner phase" (claim 1(a)) or as a single-part "swallowable uniform soft-gel matrix" (claim 1(b)). The evidence distinguishing these two embodiments will be critical.

V. Key Claim Terms for Construction

• The Term: "single phase uniform matrix of soft-gel" (’411 Patent, claim 1)

  • Context and Importance: This term is foundational to the ’411 Patent's claims and distinguishes the invention from conventional capsules with a distinct shell and fill. Practitioners may focus on this term because its construction will determine whether the patent covers only novel, fully homogenous gel structures or could also read on more conventional soft-gel capsules where the fill and shell materials are similar.
  • Intrinsic Evidence for a Broader Interpretation: The specification describes the process as yielding "'full' capsules... that is uniform matrices of soft-gel which are perfectly single-phase," which could be argued to encompass any formulation where the active ingredient is homogeneously distributed, regardless of minor physical distinctions between a core and an outer layer (’411 Patent, col. 3:63-67).
  • Intrinsic Evidence for a Narrower Interpretation: The description of an injected material that "is spread uniformly in the gelatinous mixture, to give a uniform matrix" could support a narrower definition tied to a specific manufacturing process where the boundary between fill and shell is effectively eliminated (’411 Patent, col. 7:52-57).

• The Term: "liquid or semi-liquid inner phase" (’390 Patent, claim 1)

  • Context and Importance: This term defines the nature of the fill in the first embodiment of claim 1. Its definition is critical for determining whether Teva's formulation falls under part (a) of the claim. Practitioners may focus on this term because the line between a "semi-liquid," a viscous gel, and a paste can be a point of significant technical debate.
  • Evidence for a Broader Interpretation: The patent's overall objective of avoiding solid-state degradation could support a broad reading that includes any non-solid, flowable fill, including highly viscous gels or pastes (’390 Patent, col. 3:1-4).
  • Evidence for a Narrower Interpretation: The patent's Certificate of Correction, which systematically replaces "half-liquid" with "semi-liquid," suggests the term was deliberately chosen and has a specific technical meaning that may exclude compositions that are more solid-like or paste-like (’390 Patent, Certificate of Correction).

VI. Other Allegations

• Indirect Infringement: The complaint makes general allegations of induced and contributory infringement under 35 U.S.C. § 271(b) and (c) (Compl. ¶¶19, 25). The complaint implies that Teva, by marketing a generic drug with a label and instructions for an approved use, will actively encourage and enable physicians and patients to perform the infringing act of using the patented formulation.
• Willful Infringement: While not using the word "willful," the complaint requests a finding that the case is "exceptional" and an award of attorneys' fees under 35 U.S.C. § 285 (Compl. ¶¶22, 28). This request is predicated on Teva's pre-suit knowledge of the patents, evidenced by its submission of the Paragraph IV certifications to the FDA (Compl. ¶12).

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

• A central issue will be one of compositional identity: once Teva's ANDA formulation is revealed in discovery, will its specific components and their respective weight percentages fall within the numerical ranges required by the asserted claims of the ’411 patent, or will it have a distinct formulation that avoids infringement?
• A key question of claim construction will determine the scope of the patents: does the term "single phase uniform matrix" (’411 Patent) require a completely homogenous structure with no discernible boundary between shell and fill, and how does the accused product's architecture map to that definition?
• The case will also present a question of embodiment classification for the ’390 Patent: does the evidence show that Teva's product is a "soft elastic capsule" containing a "liquid or semi-liquid inner phase" per claim 1(a), or is it a "swallowable uniform soft-gel matrix" per claim 1(b)? The resolution of this question will dictate which claim language applies and may be dispositive of infringement for that patent.