DCT

1:17-cv-01772

Chiesi USA Inc v. Teva Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-01772, D. Del., 12/07/2017
  • Venue Allegations: Venue is alleged to be proper based on Defendant Teva USA, Inc. being a Delaware corporation and both defendants conducting business in Delaware, purposefully availing themselves of the jurisdiction, and intending to market the accused product in the state.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for a generic Tobramycin Inhalation Solution constitutes an act of infringement of three patents covering the formulation of Plaintiff's branded drug, BETHKIS®.
  • Technical Context: The technology concerns specific pharmaceutical formulations of tobramycin, an antibiotic, designed for aerosol delivery to treat chronic lung infections associated with cystic fibrosis.
  • Key Procedural History: The lawsuit was triggered by Defendant Teva's filing of ANDA No. 210915 with the U.S. FDA, which included a "paragraph IV" certification. This certification asserts that the patents-in-suit, which are listed in the FDA's "Orange Book" as covering the BETHKIS® drug product, are either invalid or will not be infringed by Teva's generic product. Under the Hatch-Waxman Act, the filing of such an ANDA is a statutory act of patent infringement.

Case Timeline

Date Event
2001-07-02 Earliest Priority Date for ’094, ’178, and ’502 Patents
2006-01-17 U.S. Patent No. 6,987,094 Issued
2010-04-13 U.S. Patent No. 7,696,178 Issued
2011-05-10 U.S. Patent No. 7,939,502 Issued
2012-10-12 Plaintiff's BETHKIS® (NDA No. 201820) Approved by FDA
2017-12-07 Complaint Filed

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

U.S. Patent No. 6,987,094 - "Optimized Formulation of Tobramycin for Aerosolization," issued January 17, 2006

The Invention Explained

  • Problem Addressed: The patent describes issues with prior methods of delivering the antibiotic tobramycin via aerosol for lung infections. Extemporaneously using commercially available injectable solutions was common, but these formulations often contained preservatives and antioxidants (e.g., phenol) that could cause adverse reactions like bronchospasm in sensitive patients, such as those with cystic fibrosis (CF) (’094 Patent, col. 2:5-9). Furthermore, these solutions often had suboptimal pH for stability and required large volumes, leading to long and inconvenient nebulization times that could reduce patient compliance (’094 Patent, col. 2:33-40; col. 3:5-24).
  • The Patented Solution: The invention is an "additive-free, isotonic solution" of tobramycin specifically optimized for aerosolization. It claims a precise formulation with a higher concentration of tobramycin (7.5% w/v) in a half-saline solution (0.45% sodium chloride) and a specific, slightly acidic pH range (4.0-5.5) (’094 Patent, col. 3:38-48). This combination is designed to be stable at room temperature without needing preservatives, to be isotonic to avoid irritating the airways, and to deliver an effective dose in a smaller volume, thereby shortening treatment time (’094 Patent, Abstract; col. 5:1-12).
  • Technical Importance: The invention provided a standardized, ready-to-use tobramycin formulation engineered for inhalation, aiming to improve safety, stability, and patient convenience compared to the off-label use of injectable preparations (’094 Patent, col. 2:10-25).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" without specifying which ones (Compl. ¶41). Independent claim 1 is a representative composition claim.
  • Independent Claim 1:
    • An aerosol formulation consisting of 75 mg/ml of tobramycin dissolved in an aqueous solution
    • containing 0.45% sodium chloride;
    • wherein the pH is between 4.0 and 5.5
    • and the osmolarity ranges between 250 and 450 mOsm/l.
  • The complaint reserves the right to assert other claims, including dependent claims (Compl. ¶41).

U.S. Patent No. 7,696,178 - "Optimised Formulation of Tobramycin for Aerosolization," issued April 13, 2010

The Invention Explained

  • Problem Addressed: As a continuation of the application leading to the ’094 Patent, this patent addresses the same technical problems: the need for a tobramycin inhalation solution that avoids preservatives known to cause bronchospasm and is optimized for stability, tolerability (isotonicity), and efficient delivery (’178 Patent, col. 2:5-24; col. 3:5-30).
  • The Patented Solution: The patented solution is a tobramycin formulation with the same core characteristics: a specific concentration, a specific saline content for isotonicity, and an optimized pH for stability (’178 Patent, col. 4:42-52). The claims of this patent, however, explicitly recite that the formulation is "free of preservatives and anti-oxidants," directly addressing the problem of additive-induced side effects described in the specification (’178 Patent, col. 8:53-54).
  • Technical Importance: This patent reinforces the technical contribution of a purpose-built, additive-free formulation for inhaled tobramycin therapy, seeking to enhance patient safety and compliance (’178 Patent, col. 2:25-33).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" (Compl. ¶53). Independent claim 1 is a representative composition claim.
  • Independent Claim 1:
    • An aerosol formulation, comprising:
    • 75 mg/ml of tobramycin dissolved in an aqueous solution containing 0.45% w/v of sodium chloride;
    • wherein the pH is between 4.5 and 5.5
    • and the osmolarity ranges between 250 and 450 mOsm/l,
    • and said formulation is free of preservatives and anti-oxidants.
  • The complaint reserves the right to assert other claims, including dependent claims (Compl. ¶53).

U.S. Patent No. 7,939,502 - "Optimised Formulation of Tobramycin for Aerosolization," issued May 10, 2011

  • Technology Synopsis: This patent is a divisional of the application that led to the ’178 Patent and claims a method of treatment. It protects the act of using the specifically formulated, additive-free, pH-optimized, and isotonic tobramycin solution to treat lung infections, particularly those caused by Pseudomonas aeruginosa (’502 Patent, Abstract; col. 8:45-62).
  • Asserted Claims: The complaint alleges infringement of "one or more claims" (Compl. ¶65). Independent claim 1 is a representative method claim.
  • Accused Features: The complaint alleges that the future use of Defendants' ANDA Product, as directed by its labeling, for the treatment of lung infections would infringe the claimed methods (Compl. ¶¶ 66, 72).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is "Defendants' ANDA Product," a generic "Tobramycin Inhalation Solution" for which Defendant Teva filed Abbreviated New Drug Application (ANDA) No. 210915 with the FDA (Compl. ¶¶ 15, 31).

Functionality and Market Context

  • The complaint alleges that Teva's ANDA Product is a generic version of Plaintiff's BETHKIS®, which is supplied as a 300 mg/4 mL (75 mg/mL) solution for inhalation (Compl. ¶¶ 25, 35). It is intended for the same therapeutic use: the management of cystic fibrosis in patients with Pseudomonas aeruginosa lung infections (Compl. ¶26). The complaint does not contain specific details of the ANDA product's formulation, as this is confidential. The infringement theory is premised on the allegation that for Teva's product to be approved as a generic equivalent of BETHKIS®, it must necessarily have the same characteristics as those protected by the patents-in-suit (Compl. ¶¶ 36, 42, 54).
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart or specific factual allegations detailing how the accused product meets each claim limitation. The infringement theory is based on the allegation that Teva's ANDA seeks approval for a generic version of BETHKIS®, and therefore the ANDA Product will possess the properties claimed in the patents covering BETHKIS®.

’094 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
An aerosol formulation consisting of 75 mg/ml of tobramycin... The complaint alleges the ANDA Product is a generic version of BETHKIS®, which is a 300 mg/4 mL solution (i.e., 75 mg/mL), and that its manufacture and sale will infringe the patent. ¶¶25, 35, 42 col. 8:60-61
...dissolved in an aqueous solution containing 0.45% sodium chloride; The complaint alleges the ANDA Product infringes claims covering BETHKIS®; the patent identifies this specific saline concentration as a key feature for achieving an isotonic formulation. ¶¶36, 42 col. 8:62-63
wherein the pH is between 4.0 and 5.5 The complaint's infringement allegation suggests the ANDA product will have a pH within this range, which the patent describes as optimal for stability without requiring preservatives. ¶¶36, 42 col. 8:63-64
and the osmolarity ranges between 250 and 450 mOsm/l. The complaint's infringement allegation suggests the ANDA product will have an osmolarity within this range, which the patent teaches is a feature of an isotonic and well-tolerated solution. ¶¶36, 42 col. 8:64-65

’178 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
An aerosol formulation, comprising: 75 mg/ml of tobramycin... The complaint alleges the ANDA Product is a generic version of BETHKIS®, a 75 mg/mL solution, and that its manufacture and sale will infringe the patent. ¶¶25, 35, 54 col. 8:47-48
...dissolved in an aqueous solution containing 0.45% w/v of sodium chloride; The complaint alleges the ANDA Product infringes claims covering BETHKIS®; the patent identifies this saline concentration as a key feature. ¶¶36, 54 col. 8:48-49
wherein the pH is between 4.5 and 5.5 The complaint's infringement allegation suggests the ANDA product will have a pH within this more specific range claimed in the patent. ¶¶36, 54 col. 8:50-51
and the osmolarity ranges between 250 and 450 mOsm/l, The complaint's infringement allegation suggests the ANDA product will have an osmolarity within this range. ¶¶36, 54 col. 8:51-52
and said formulation is free of preservatives and anti-oxidants. The complaint's infringement allegation suggests the ANDA Product is free of such additives, consistent with the BETHKIS® product and the problem the patent purports to solve. ¶¶36, 54 col. 8:53-54
  • Identified Points of Contention:
    • Technical Questions: A primary question will be factual: does the formulation described in Teva's confidential ANDA actually meet every numerical and compositional limitation of the asserted claims? Any deviation in tobramycin concentration, sodium chloride concentration, pH, or osmolarity from the claimed ranges could form the basis of a non-infringement defense.
    • Scope Questions: For the ’094 Patent, a key dispute may arise over the term "consisting of." This term strictly limits the invention to the listed components. The case raises the question of whether Teva's ANDA product contains any additional, unrecited ingredients (e.g., other excipients or buffers) that would place it outside the scope of claims using this restrictive language.

V. Key Claim Terms for Construction

  • The Term: "consisting of" (’094 Patent, Claim 1)

    • Context and Importance: This is a transition phrase with a well-established, narrow legal meaning. Practitioners may focus on this term because it closes the claim to any elements not explicitly recited. If Teva's formulation contains any other ingredient beyond tobramycin, sodium chloride, and water, it would have a strong argument for non-infringement of this claim.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: A broader interpretation is legally disfavored. A party might argue that trace impurities should not be considered "ingredients" that would negate infringement, but the patent provides little support for this.
      • Evidence for a Narrower Interpretation: The specification's repeated emphasis on creating an "additive-free" solution to avoid the problems of prior art preservatives and antioxidants strongly supports the strict, closed meaning of "consisting of" (’094 Patent, Abstract; col. 2:5-9).

  • The Term: "free of preservatives and anti-oxidants" (’178 Patent, Claim 1)

    • Context and Importance: This explicit negative limitation is central to the ’178 Patent's scope. Practitioners may focus on this term because its boundaries could be debated. The dispute could center on whether an ingredient with a secondary or incidental preservative or anti-oxidant effect, but used for another primary purpose (e.g., as a tonicity agent or buffer), would render the formulation not "free of" such agents.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent background explains that the problem with preservatives and anti-oxidants is the potential to cause "paradoxical reactions such as bronchospasm and cough" (’178 Patent, col. 2:15-17). A party could argue the term should be broadly construed to exclude any substance known to cause such effects, regardless of its formal classification.
      • Evidence for a Narrower Interpretation: The specification explicitly mentions substances like "phenol or other preservatives and anti-oxidants" found in intravenous solutions, and later discusses avoiding "sodium EDTA and/or sodium metabisulphite and preservatives such as phenol" (’178 Patent, col. 2:2-9; col. 3:55-58). A party could argue the term is limited to these conventional classes of additives and does not extend to multi-functional excipients not primarily intended as preservatives or anti-oxidants.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Defendant Teva Ltd. will induce and/or contribute to infringement by Defendant Teva USA (Compl. ¶¶ 48, 60). For the ’502 method patent, the complaint alleges Teva will induce infringement by physicians and patients through the product's labeling and instructions for use (Compl. ¶72). It also alleges contributory infringement, stating the ANDA product is a material part of the claimed method, is not a staple article of commerce suitable for substantial noninfringing uses, and that Teva knows it will be used to infringe (Compl. ¶73).
  • Willful Infringement: The complaint does not use the word "willful." However, it alleges that Defendants knew of the patents-in-suit, citing as evidence the filing of the ANDA with a Paragraph IV certification that specifically references the patents (Compl. ¶¶ 47, 59, 71). This allegation of knowledge could be used to support a later claim for enhanced damages.

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

  • A central issue will be one of factual correspondence: does the specific chemical formulation detailed in Teva's confidential ANDA—including its precise pH, osmolarity, and concentration of all components—fall squarely within the numerical boundaries of every limitation in the asserted claims, or did Teva successfully "design around" one or more of these parameters?
  • A key legal issue will be the definitional scope of "consisting of" in the ’094 patent. The case will question whether Teva's formulation includes any unrecited excipients and, if so, whether those additions are sufficient to place the product outside the scope of this strictly closed claim language.
  • A third major question will involve patent validity. Teva's Paragraph IV notice inherently asserts that the patents are invalid or not infringed. The case will therefore likely involve a challenge to the patents' validity, potentially arguing that the claimed formulation was obvious in light of prior art tobramycin solutions and general knowledge in pharmaceutical formulation at the time of the invention.