DCT

1:24-cv-00391

Arcutis BioTherap Inc v. Padagis Israel Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-00391, D. Del., 07/19/2024
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendants Padagis US LLC and Padagis LLC are incorporated and reside in Delaware. Venue over Defendant Padagis Israel Pharmaceuticals Ltd. is based on its status as a foreign corporation subject to personal jurisdiction in the district.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's ZORYVE® (roflumilast) cream, 0.3%, constitutes an act of infringement of eleven U.S. patents related to topical roflumilast formulations and methods of use.
  • Technical Context: The technology concerns pharmaceutical cream formulations of roflumilast, a phosphodiesterase-4 (PDE-4) inhibitor used for the topical treatment of plaque psoriasis.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 219158 and service of two Paragraph IV certification letters to the Plaintiff, the first received on February 14, 2024, and the second on July 17, 2024, asserting that the patents-in-suit are invalid and/or not infringed.

Case Timeline

Date Event
2017-06-07 Earliest Patent Priority Date (’050, ’788, ’142, ’818, ’796, ’496, ’051, ’052 Patents)
2018-02-06 U.S. Patent No. 9,884,050 Issued
2018-03-06 U.S. Patent No. 9,907,788 Issued
2018-11-16 Earliest Patent Priority Date (’480, ’437, ’848 Patents)
2021-03-09 U.S. Patent No. 10,940,142 Issued
2021-09-28 U.S. Patent No. 11,129,818 Issued
2023-10-24 U.S. Patent No. 11,793,796 Issued
2023-11-21 U.S. Patent No. 11,819,496 Issued
2024-02-13 Defendant sends first Paragraph IV Letter
2024-02-14 Plaintiff receives first Paragraph IV Letter
2024-05-28 U.S. Patent No. 11,992,480 Issued
2024-06-11 U.S. Patent No. 12,005,051 Issued
2024-06-11 U.S. Patent No. 12,005,052 Issued
2024-06-18 U.S. Patent No. 12,011,437 Issued
2024-06-25 U.S. Patent No. 12,016,848 Issued
2024-07-16 Defendant sends second Paragraph IV Letter
2024-07-17 Plaintiff receives second Paragraph IV Letter
2024-07-19 Complaint Filing Date

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

U.S. Patent No. 9,884,050 - "Inhibition of Crystal Growth of Roflumilast," Issued February 6, 2018

The Invention Explained

  • Problem Addressed: The patent describes the technical challenge that roflumilast, the active pharmaceutical ingredient (API), has very low water solubility, which complicates its use in water-containing topical formulations like creams ('050 Patent, col. 1:47-54). When formulated near its saturation limit, the dissolved roflumilast can precipitate out of solution during storage, particularly due to temperature fluctuations during shipping, forming crystals that grow larger over time—a phenomenon known as Ostwald ripening ('050 Patent, col. 2:1-7; col. 3:53-64). This change in crystal size can negatively impact the product's bioavailability and therapeutic efficacy, as only dissolved API can effectively penetrate the skin ('050 Patent, col. 3:4-12).
  • The Patented Solution: The invention addresses this stability issue by including hexylene glycol as an excipient in the roflumilast formulation ('050 Patent, Abstract). The patent asserts that hexylene glycol inhibits the crystalline growth of suspended or precipitated roflumilast particles, thereby maintaining a stable particle size distribution over the product's shelf life and ensuring consistent bioavailability ('050 Patent, col. 4:21-26; col. 5:55-62).
  • Technical Importance: Maintaining a consistent particle size distribution is critical for ensuring that a topical drug delivers a predictable and reliable therapeutic dose from the first use to the last ('050 Patent, col. 3:46-53).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 ('050 Patent; Compl. ¶90).
  • Claim 1 requires:
    • A pharmaceutical composition
    • comprising roflumilast
    • comprising hexylene glycol
    • comprising cetearyl alcohol
    • comprising dicetyl phosphate
    • comprising ceteth-10 phosphate
  • The complaint reserves the right to assert additional claims (Compl. ¶90, fn 1).

U.S. Patent No. 9,907,788 - "Inhibition of Crystal Growth of Roflumilast," Issued March 6, 2018

The Invention Explained

  • Problem Addressed: This patent, which shares a specification with the '050 Patent, addresses the same technical challenge of roflumilast's low aqueous solubility and its tendency to form unstable crystals in topical formulations ('788 Patent, col. 1:47-54; col. 2:1-7).
  • The Patented Solution: The patent claims a method of treatment that uses a composition containing hexylene glycol to inhibit roflumilast crystal growth, thereby ensuring stable and consistent drug delivery ('788 Patent, Abstract; col. 4:21-26).
  • Technical Importance: The claimed method provides a way to use roflumilast for treating skin conditions by ensuring the pharmaceutical composition remains stable and effective over time ('788 Patent, col. 3:46-53).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 ('788 Patent; Compl. ¶109).
  • Claim 1 requires:
    • A method of inhibiting phosphodiesterase 4 in a patient
    • comprising administering a composition to a patient in need thereof
    • wherein the composition comprises roflumilast
    • wherein the composition comprises hexylene glycol
  • The complaint reserves the right to assert additional claims (Compl. ¶109, fn 3).

U.S. Patent No. 10,940,142 - "Inhibition of Crystal Growth of Roflumilast," Issued March 9, 2021

  • Technology Synopsis: This patent relates to the same technology family as the '050 and '788 patents. It addresses the problem of roflumilast crystal growth in topical formulations by including hexylene glycol as a stabilizing agent to ensure consistent bioavailability ('142 Patent, Abstract; col. 1:15-22).
  • Asserted Claims: At least independent claim 1 (Compl. ¶144).
  • Accused Features: The accused features are the composition of Padagis's Proposed ANDA Product and its intended use for treating plaque psoriasis (Compl. ¶¶141, 144).

U.S. Patent No. 11,129,818 - "Topical Roflumilast Formulation Having Improved Delivery and Plasma Half Life," Issued September 28, 2021

  • Technology Synopsis: This patent addresses the problem of patient adherence to treatment regimens, which can be negatively impacted by formulations that require frequent dosing. The patented solution is a topical roflumilast formulation that provides improved delivery and a longer plasma half-life, making the treatment more "forgiving" if a patient misses a dose ('818 Patent, col. 1:11-23; col. 2:6-10).
  • Asserted Claims: At least independent claim 1 (Compl. ¶163).
  • Accused Features: The accused features are the composition of Padagis's Proposed ANDA Product and its intended use, which allegedly improves treatment adherence by extending the plasma half-life of roflumilast (Compl. ¶¶160, 181).

U.S. Patent No. 11,793,796 - "Inhibition of Crystal Growth of Roflumilast," Issued October 24, 2023

  • Technology Synopsis: This patent is from the same family as the '050, '788, and '142 patents. It is directed to solving the technical problem of roflumilast's low aqueous solubility and tendency for crystal growth in topical formulations by using hexylene glycol as a stabilizing excipient ('796 Patent, Abstract; col. 1:17-24).
  • Asserted Claims: At least independent claim 1 (Compl. ¶198).
  • Accused Features: The accused features are the formulation of Padagis's Proposed ANDA Product and its intended therapeutic use (Compl. ¶¶195, 198).

U.S. Patent No. 11,819,496 - "Topical Roflumilast Formulation Having Improved Delivery and Plasma Half Life," Issued November 21, 2023

  • Technology Synopsis: This patent belongs to the same family as the '818 patent. The invention is a topical roflumilast formulation designed to improve the therapeutic outcome by providing consistent delivery and a longer plasma half-life, which enhances patient adherence to the treatment schedule ('496 Patent, col. 1:11-23; Abstract).
  • Asserted Claims: At least independent claim 1 (Compl. ¶217).
  • Accused Features: The accused features are the formulation of Padagis's Proposed ANDA Product and its intended use to treat psoriasis (Compl. ¶¶214, 235).

U.S. Patent No. 11,992,480 - "Method for reducing side effects from administration of phosphodiesterase-4 inhibitors," Issued May 28, 2024

  • Technology Synopsis: This patent addresses the problem that oral administration of PDE-4 inhibitors like roflumilast can cause a sharp spike in plasma concentration (Cmax), leading to gastrointestinal side effects. The invention is a method using a topical formulation that provides a flattened plasma concentration curve and reduced Cmax relative to oral administration, thereby reducing side effects while maintaining therapeutic efficacy ('480 Patent, Abstract; col. 1:15-24).
  • Asserted Claims: At least independent claim 1 (Compl. ¶252).
  • Accused Features: The accused features are the composition of Padagis's Proposed ANDA Product and its method of use, which allegedly improves therapeutic outcomes (Compl. ¶¶249, 270).

U.S. Patent No. 12,005,051 - "Topical Roflumilast Formulation Having Improved Delivery and Plasma Half Life," Issued June 11, 2024

  • Technology Synopsis: This patent is from the same family as the '818 and '496 patents. It describes a topical roflumilast formulation intended to improve therapeutic outcomes by ensuring consistent delivery and extending the drug's plasma half-life, thus improving patient adherence ('051 Patent, Abstract).
  • Asserted Claims: At least independent claim 1 (Compl. ¶287).
  • Accused Features: The accused features are the formulation of Padagis's Proposed ANDA Product and its intended therapeutic use (Compl. ¶¶284, 287).

U.S. Patent No. 12,005,052 - "Topical Roflumilast Formulation Having Improved Delivery and Plasma Half Life," Issued June 11, 2024

  • Technology Synopsis: This patent is also from the same family as the '818, '496, and '051 patents. It is directed to a topical roflumilast formulation that improves delivery and lengthens plasma half-life to enhance patient adherence and therapeutic outcomes ('052 Patent, Abstract).
  • Asserted Claims: At least independent claim 1 (Compl. ¶306).
  • Accused Features: The accused features are the formulation of Padagis's Proposed ANDA Product and its intended therapeutic use (Compl. ¶¶303, 306).

U.S. Patent No. 12,011,437 - "Roflumilast Formulations With An Improved Pharmacokinetic Profile," Issued June 18, 2024

  • Technology Synopsis: This patent is from the same family as the '480 patent. It is directed to a topical roflumilast formulation that produces a flattened plasma concentration curve and a reduced Cmax compared to oral administration. This pharmacokinetic profile is intended to reduce gastrointestinal side effects and improve patient compliance ('437 Patent, Abstract).
  • Asserted Claims: At least independent claim 1 (Compl. ¶325).
  • Accused Features: The accused features are the formulation of Padagis's Proposed ANDA Product and its intended therapeutic use (Compl. ¶¶322, 325).

U.S. Patent No. 12,016,848 - "Roflumilast formulations with an improved pharmacokinetic profile," Issued June 25, 2024

  • Technology Synopsis: This patent is also from the same family as the '480 and '437 patents. It describes a topical roflumilast formulation with an improved pharmacokinetic profile characterized by a flattened plasma concentration curve and reduced Cmax, which aims to minimize side effects associated with oral PDE-4 inhibitors ('848 Patent, Abstract).
  • Asserted Claims: At least independent claim 1 (Compl. ¶344).
  • Accused Features: The accused features are the formulation of Padagis's Proposed ANDA Product and its intended therapeutic use (Compl. ¶¶341, 344).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is "Padagis's Proposed ANDA Product," a generic version of Arcutis's ZORYVE® (roflumilast) cream, 0.3%, for which Padagis seeks FDA approval via ANDA No. 219158 (Compl. ¶¶1, 8).

Functionality and Market Context

  • The complaint alleges that by filing its ANDA, Padagis has represented to the FDA that its proposed generic product has the same active ingredient (roflumilast), dosage form (cream), and strength (0.3%) as ZORYVE®, and that it is bioequivalent (Compl. ¶71). The proposed product is intended for the topical treatment of plaque psoriasis in patients six years of age and older, the same indication as ZORYVE® (Compl. ¶¶72, 74). As a generic drug, it is designed to be a lower-cost, substitutable alternative to the branded product upon receiving FDA approval (Compl. ¶¶2, 76).
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart, as Plaintiff alleges it has not yet received a complete copy of Defendants' ANDA (Compl. ¶85). The infringement allegations are based on the premise that to gain FDA approval, the Proposed ANDA Product must be a bioequivalent copy of the ZORYVE® product, which is covered by the patents-in-suit, and that its proposed label will instruct for an infringing use (Compl. ¶¶63, 71, 75).

'050 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition comprising roflumilast, The Proposed ANDA Product is a pharmaceutical composition that must contain roflumilast to be a generic equivalent of ZORYVE®. ¶¶71, 90 col. 5:40-41
hexylene glycol, The Proposed ANDA Product is alleged to contain hexylene glycol as part of a formulation that is bioequivalent to the ZORYVE® cream. ¶¶71, 90 col. 5:40-41
cetearyl alcohol, The Proposed ANDA Product is alleged to contain cetearyl alcohol as part of a formulation that is bioequivalent to the ZORYVE® cream. ¶¶71, 90 col. 5:40-41
dicetyl phosphate, and The Proposed ANDA Product is alleged to contain dicetyl phosphate as part of a formulation that is bioequivalent to the ZORYVE® cream. ¶¶71, 90 col. 5:40-41
ceteth-10 phosphate. The Proposed ANDA Product is alleged to contain ceteth-10 phosphate as part of a formulation that is bioequivalent to the ZORYVE® cream. ¶¶71, 90 col. 5:40-41

'788 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of inhibiting phosphodiesterase 4 in a patient, The proposed label will allegedly instruct physicians and patients to use the product to treat plaque psoriasis, a condition mediated by PDE-4. Roflumilast is a known PDE-4 inhibitor. ¶¶74, 127-128 col. 1:36-41
comprising administering a composition comprising roflumilast and hexylene glycol The Proposed ANDA Product is a composition that contains roflumilast and is alleged to contain hexylene glycol to match the ZORYVE® formulation. ¶¶71, 109 col. 5:40-41
to a patient in need thereof. The proposed label will direct administration to patients with plaque psoriasis. ¶¶74-75 col. 9:43-51

Identified Points of Contention

  • Evidentiary Questions: The central point of contention will be factual and dependent on discovery of the ANDA's contents. The primary question is whether Padagis's proposed generic formulation contains every ingredient recited in the asserted composition claims, such as claim 1 of the '050 Patent. Padagis's Paragraph IV letter asserts non-infringement, suggesting it may have designed its formulation to omit one or more of the claimed excipients (Compl. ¶78).
  • Scope Questions: For the method claims, a potential dispute may arise over whether the instructions on the proposed product label for treating plaque psoriasis constitute instruction to perform the claimed method of "inhibiting phosphodiesterase 4." This raises the question of whether treating the symptom (psoriasis) with a known PDE-4 inhibitor is legally equivalent to performing the claimed method directed to the underlying biological mechanism.

V. Key Claim Terms for Construction

  • The Term: "comprising" (from claim 1 of the '050 Patent and other patents)

    • Context and Importance: This transitional phrase is fundamental to the scope of all composition claims. Its construction determines whether the presence of additional, unlisted ingredients in Padagis's product could avoid infringement. Practitioners may focus on this term because if Padagis has added other excipients, the "open" nature of "comprising" would mean infringement is still possible.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: "Comprising" is a standard patent law term of art meaning "including but not limited to." This well-established, broad interpretation allows a claim to read on a product that contains the listed elements plus additional, unrecited elements. The patent specifications do not contain language that suggests a departure from this standard meaning.
      • Evidence for a Narrower Interpretation: The complaint does not provide a basis for analysis of a narrower interpretation. A defendant typically faces a significant challenge in arguing that "comprising" should be interpreted as a closed-ended term like "consisting of."

  • The Term: "inhibiting phosphodiesterase 4" (from claim 1 of the '788 Patent and other method patents)

    • Context and Importance: This phrase defines the functional result of the claimed method. The infringement analysis for method claims will depend on whether the actions instructed by the accused product's label meet this limitation. The dispute will likely center on the intent element required for induced infringement.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent specification explicitly links the treatment of dermatoses like psoriasis to the PDE-inhibiting properties of roflumilast ('788 Patent, col. 1:36-41). This may support an argument that instructing a physician to treat psoriasis with a known PDE-4 inhibitor is inherently an instruction to inhibit PDE-4.
      • Evidence for a Narrower Interpretation: A defendant could argue that a product label instructing the "topical treatment of plaque psoriasis" (Compl. ¶74) only describes treating an observable condition and does not require a user to understand or intend to affect the underlying biological mechanism of PDE-4 inhibition. This could raise questions about whether such a label is sufficient evidence of the specific intent to induce infringement of the claimed method.

VI. Other Allegations

  • Indirect Infringement: Plaintiff alleges induced infringement for the asserted method claims. The complaint asserts that Defendants' proposed product label will instruct and encourage physicians and healthcare providers to administer the product to patients in a manner that directly infringes the patented methods (e.g., Compl. ¶¶127-131, 181-185). Knowledge is alleged based on the patents' listing in the FDA Orange Book and Defendants' Paragraph IV letters certifying non-infringement and invalidity (Compl. ¶¶62, 110).
  • Willful Infringement: The complaint does not contain a specific count for willful infringement. However, in its requests for declaratory judgment of infringement upon FDA approval, it alleges that Defendants' actions "have been made and will be made with full knowledge of the ['###] Patent and without a reasonable basis for believing that it would not be liable for infringing," which mirrors the standard for willfulness (e.g., Compl. ¶¶124, 178).

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

  • A central issue will be one of factual correspondence: Does the confidential formulation disclosed in Padagis's ANDA contain every excipient recited in Arcutis's composition claims, such as hexylene glycol, cetearyl alcohol, dicetyl phosphate, and ceteth-10 phosphate in claim 1 of the '050 patent? The outcome of the infringement analysis for numerous patents will depend entirely on the results of this factual discovery.
  • A key legal question will be one of induced infringement: Assuming the accused product is used as directed, will Padagis's proposed label, by instructing the treatment of a medical condition (plaque psoriasis), be found to actively and intentionally encourage infringement of method claims directed at an underlying biological mechanism ("inhibiting phosphodiesterase 4") or an improved pharmacokinetic profile?
  • A third question will concern claim scope and validity: Given the assertion of eleven patents across several families with overlapping subject matter, the case may involve significant disputes over claim differentiation, potential double patenting issues, and the validity of later-issued claims in view of the earlier patents and other prior art, as asserted in Defendants' Paragraph IV letters (Compl. ¶¶77-80).