DCT

1:24-cv-00417

UroGen Pharma Ltd v. Teva Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-00417, D. Del., 04/02/2024
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware based on Defendant entities Teva Inc. and Teva USA being incorporated in Delaware, maintaining registered agents in the state, and conducting business within the district.
  • Core Dispute: Plaintiff alleges that Defendant’s Abbreviated New Drug Application (ANDA) for a generic version of JELMYTO® infringes two patents related to thermoreversible hydrogel compositions for sustained-release drug delivery.
  • Technical Context: The technology involves pharmaceutical compositions that are liquid at or below room temperature for ease of administration into a body cavity and transform into a viscous gel at body temperature to adhere to tissue for prolonged, localized drug delivery.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant’s submission of ANDA No. 218215 to the FDA. The complaint states that on February 20, 2024, Defendant sent a notice letter with a Paragraph IV certification, asserting that the patents-in-suit, which are listed in the FDA’s Orange Book for JELMYTO®, are invalid, unenforceable, and/or will not be infringed by its proposed generic product.

Case Timeline

Date Event
2010-01-20 Earliest Priority Date for ’074 and ’069 Patents
2015-05-26 U.S. Patent No. 9,040,074 Issued
2018-04-24 U.S. Patent No. 9,950,069 Issued
2020-04-15 FDA Approved Plaintiff’s JELMYTO® Product
2024-02-20 Defendant Sent Paragraph IV Certification Notice Letter
2024-04-02 Complaint Filed

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

No probative visual evidence provided in complaint.

U.S. Patent No. 9,040,074 - Material and Method for Treating Internal Cavities

  • Issued: May 26, 2015

The Invention Explained

  • Problem Addressed: The patent describes the difficulty of administering topical treatments to internal body cavities, such as the urinary bladder. These environments are wet, lined with non-adherent mucosal tissue, and subject to constant changes in shape and volume, which causes traditional liquid drug formulations to be expelled quickly, limiting their therapeutic efficacy due to short exposure time (’074 Patent, col. 5:51-65; col. 7:36-44).
  • The Patented Solution: The invention is a "thermoreversible hydrogel composition" that is liquid at low temperatures, allowing it to be easily injected into a body cavity, but transitions into a viscous, adhesive gel at body temperature. This property allows the material to coat the internal tissue, conform to its shape, and provide a sustained release of an embedded therapeutic agent over a prolonged period before naturally degrading and being expelled from the body (’074 Patent, Abstract; col. 8:51-64).
  • Technical Importance: This approach aims to enhance the effectiveness of topical treatments for conditions like superficial bladder cancer by maintaining a higher drug concentration at the target tissue for a longer duration than is possible with standard intravesical instillations (’074 Patent, col. 5:1-3).

Key Claims at a Glance

  • The complaint asserts infringement of at least one claim without specifying which; independent claim 15 is a representative composition claim.
  • Independent Claim 15:
    • A thermoreversible hydrogel, comprising:
    • between 20% and 30% (w/w) of an ethylene oxide/propylene oxide triblock copolymer characterized by an average molar mass of 13000 and a general formula E101 P56 E101;
    • between 0.05% and 0.3% HPMC;
    • between 0.4% and 2.5% PEG-400;
    • an effective amount of a therapeutic agent selected from a group including, inter alia, Mitomycin C, Deoxrubicin, Valrubicin, and Gemcitabine; and
    • the balance water.
  • The complaint implicitly reserves the right to assert other claims of the patent.

U.S. Patent No. 9,950,069 - Material and Method for Treating Internal Cavities

  • Issued: April 24, 2018

The Invention Explained

  • Problem Addressed: The ’069 Patent, a continuation of the application that led to the ’074 Patent, addresses the same technical challenge: the short residence time and resulting limited efficacy of conventional liquid drugs administered topically inside dynamic internal body cavities (’069 Patent, col. 5:51-65).
  • The Patented Solution: The patent discloses further thermoreversible hydrogel formulations that are liquid when cool for administration and become an adhesive gel at body temperature. This gel is designed to adhere to mucosal surfaces, providing a platform for the sustained topical release of a therapeutic agent directly to the affected tissue (’069 Patent, Abstract; col. 9:1-17).
  • Technical Importance: The invention provides specific, alternative formulations for the sustained-release hydrogel platform, thereby protecting a refined compositional space for treating conditions in internal cavities like upper tract urothelial cancer (’069 Patent, col. 4:5-17).

Key Claims at a Glance

  • The complaint asserts infringement of at least one claim without specifying which; independent claim 1 is a representative composition claim.
  • Independent Claim 1:
    • A thermoreversible hydrogel, comprising:
    • between 23% and 27% (w/w) of an ethylene oxide/propylene oxide triblock copolymer having a general formula E101 P56 E101;
    • between 0.1% and 0.2% hydroxypropylmethylcellulose (HPMC);
    • between 0.5% and 1% polyethylene glycol 400 (PEG-400);
    • an effective amount of a therapeutic agent; and
    • the balance water.
  • The complaint implicitly reserves the right to assert other claims of the patent.

III. The Accused Instrumentality

Product Identification

Defendant’s proposed generic version of JELMYTO® (mitomycin) for pyelocalyceal solution, 40 mg/vial, which is the subject of ANDA No. 218215 submitted to the FDA (Compl. ¶1, ¶12).

Functionality and Market Context

The accused product is alleged to be a powder containing 40 mg/vial of mitomycin C, intended to be sold with a sterile thermoreversible hydrogel for reconstitution (Compl. ¶37, ¶60). The complaint alleges, upon information and belief, that this hydrogel composition will contain specific weight percentages of poloxamer, hydroxypropylmethylcellulose (HPMC), and polyethylene glycol (PEG-400) (Compl. ¶37, ¶60). Following reconstitution and instillation into a patient's pyelocalyceal system, the product is intended to form a gel that conforms to the cavity and delivers mitomycin to the surrounding tissue over a prolonged period (Compl. ¶39, ¶62). The product is intended to be a generic equivalent to Plaintiff's JELMYTO® and seeks market entry prior to the expiration of the patents-in-suit (Compl. ¶1, ¶13).

IV. Analysis of Infringement Allegations

U.S. Patent No. 9,040,074 Infringement Allegations

Claim Element (from Independent Claim 15) Alleged Infringing Functionality Complaint Citation Patent Citation
A thermoreversible hydrogel, comprising: The accused product is a powder sold with a sterile thermoreversible hydrogel composition for reconstitution. ¶37 col. 9:4-12
between 20% and 30% (w/w) of an ethylene oxide/propylene oxide triblock copolymer... The hydrogel allegedly comprises between 23% and 27% (w/w) poloxamer. ¶37 col. 37:63-65
between 0.05% and 0.3% HPMC; The hydrogel allegedly comprises between 0.1% and 0.2% HPMC. ¶37 col. 9:18-23
between 0.4% and 2.5% PEG-400; The hydrogel allegedly comprises between 0.5% and 1% PEG-400. ¶37 col. 9:18-23
an effective amount of a therapeutic agent selected from the group consisting of Mitomycin C...; and The accused product consists of a powder that contains mitomycin in an amount of 40 mg/vial. ¶37 col. 12:17-20
the balance water. The complaint does not explicitly allege the presence of water but it is an inherent component of a hydrogel for reconstitution. ¶37 col. 9:18-23
  • Identified Points of Contention:
    • Factual Question: The complaint alleges that the composition of the accused product falls squarely within the ranges recited in claim 15 of the ’074 Patent (Compl. ¶37). The primary point of contention will likely be factual: does the formulation described in Defendant’s ANDA contain these components in these exact concentrations? Discovery into the ANDA's contents will be central to resolving this question.

U.S. Patent No. 9,950,069 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A thermoreversible hydrogel, comprising: The accused product is a powder sold with a sterile thermoreversible hydrogel composition for reconstitution. ¶60 col. 9:1-17
between 23% and 27% (w/w) of an ethylene oxide/propylene oxide triblock copolymer... The hydrogel allegedly comprises between 23% and 27% (w/w) poloxamer. ¶60 col. 62:21-25
between 0.1% and 0.2% hydroxypropylmethylcellulose (HPMC); The hydrogel allegedly comprises between 0.1% and 0.2% HPMC. ¶60 col. 62:26-28
between 0.5% and 1% polyethylene glycol 400 (PEG-400); The hydrogel allegedly comprises between 0.5% and 1% PEG-400. ¶60 col. 62:29-30
an effective amount of a therapeutic agent; and The accused product consists of a powder that contains mitomycin C in an amount of 40 mg/vial. ¶60 col. 64:8-15
the balance water. The complaint does not explicitly allege the presence of water but it is an inherent component of a hydrogel for reconstitution. ¶60 col. 62:31-31
  • Identified Points of Contention:
    • Factual Question: The infringement theory for the ’069 Patent is based on an allegation that the accused product’s composition matches the claimed ranges of claim 1 exactly (Compl. ¶60). As with the ’074 Patent, the central dispute will be factual, hinging on whether the evidence from the ANDA confirms these specific compositional details. If the allegations are proven true, a finding of literal infringement may be difficult for the Defendant to overcome, shifting the focus of the case to the patent's validity.

V. Key Claim Terms for Construction

  • The Term: "thermoreversible hydrogel"
  • Context and Importance: This term appears in the preamble of the asserted independent claims and defines the invention's fundamental character. Its construction is critical because if Defendant’s product, even with matching chemical components, does not meet the functional definition of a "thermoreversible hydrogel" as understood in the patent, it may not infringe. Practitioners may focus on this term to determine if functional properties, beyond the mere list of ingredients, are required to fall within the claim scope.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification provides a broad, functional description, stating the material is "of sufficiently low viscosity at room temperature to be injectable" and "at body temperature... exhibits a much higher viscosity and will stably adhere to the internal surface of a body cavity" (’074 Patent, Abstract). This could support a construction based on the general property of transitioning from a liquid to a gel with an increase in temperature.
    • Evidence for a Narrower Interpretation: The specification also discloses specific physical parameters, such as "a viscosity of less than 200 Pa's over a temperature range of 4° C.-12° C.; a viscosity of greater than 10³ Pa's at 37° C." (’074 Patent, col. 9:6-9). A party could argue that these specific, quantified properties are essential characteristics of the claimed "thermoreversible hydrogel," thereby narrowing the claim's scope to compositions that exhibit these precise rheological behaviors.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement. Inducement is based on the allegation that Defendant’s proposed product label will instruct and encourage healthcare professionals to reconstitute and administer the product in a manner that directly infringes the patents (Compl. ¶38, ¶61). Contributory infringement is alleged on the basis that Defendant's product is a material component of the invention, is not a staple article of commerce, and is especially adapted for an infringing use (Compl. ¶41, ¶64).
  • Willful Infringement: While the complaint does not use the term "willful," it alleges that Defendant's positions on non-infringement and invalidity, as stated in its notice letter, are "devoid of an objective good faith basis in either the facts or the law" and that the "case is exceptional" (Compl. ¶43, ¶66). These allegations form the basis for a potential claim for enhanced damages and attorney fees, predicated on Defendant's alleged pre-suit knowledge of the patents from their Orange Book listing and the notice letter itself (Compl. ¶40, ¶63).

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

  • A core issue will be one of evidentiary fact: does the chemical composition of Defendant’s proposed generic product, as detailed in its confidential ANDA submission to the FDA, contain the specific poloxamer, HPMC, and PEG-400 components in the precise weight-percentage ranges alleged by the Plaintiff, which directly map onto the asserted claims?
  • A second key question will be one of patent validity: assuming the accused product's formulation is found to fall within the scope of the claims, the case will likely turn on Defendant’s ability to prove by clear and convincing evidence its assertion that the patents are invalid, for instance, on grounds of obviousness over prior art pharmaceutical formulations.