DCT

2:23-cv-21826

Incyte Corp v. Padagis Israel Pharma Ltd

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:23-cv-21826, D.N.J., 11/02/2023
  • Venue Allegations: Plaintiff alleges venue is proper because Defendant is a foreign corporation that may be sued in any judicial district and has sufficient contacts with the United States as a whole to satisfy due process. The complaint also asserts that the District of New Jersey is a likely destination for the accused product.
  • Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of Plaintiff's Opzelura® (ruxolitinib) cream constitutes an act of infringement of nine U.S. patents covering the drug's formulation and methods of use.
  • Technical Context: The technology relates to topical formulations of ruxolitinib, a Janus kinase (JAK) inhibitor, used for treating skin disorders such as atopic dermatitis and nonsegmental vitiligo.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant's submission of ANDA No. 218657 with a Paragraph IV certification, alleging that the patents-in-suit are invalid and/or will not be infringed. Plaintiff received a notice letter regarding this certification on or after September 21, 2023. The patents-in-suit are listed in the FDA's "Orange Book" with respect to Opzelura®.

Case Timeline

Date Event
2010-05-21 Earliest Priority Date for ’543, ’870, ’624, ’425, ’136 Patents
2019-09-06 Earliest Priority Date for ’138, ’536 Patents
2019-09-11 Earliest Priority Date for ’923, ’137 Patents
2020-09-01 U.S. Patent No. 10,758,543 Issues
2020-12-22 U.S. Patent No. 10,869,870 Issues
2022-01-11 U.S. Patent No. 11,219,624 Issues
2022-11-29 U.S. Patent No. 11,510,923 Issues
2023-02-07 U.S. Patent No. 11,571,425 Issues
2023-02-28 U.S. Patent No. 11,590,136 Issues
2023-02-28 U.S. Patent No. 11,590,137 Issues
2023-02-28 U.S. Patent No. 11,590,138 Issues
2023-03-14 U.S. Patent No. 11,602,536 Issues
2023-09-21 Date on or after which Defendant sent Paragraph IV Notice Letter
2023-11-02 Complaint Filed

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

U.S. Patent No. 10,758,543 - "Topical Formulation for a JAK Inhibitor," issued September 1, 2020 (’543 Patent)

The Invention Explained

  • Problem Addressed: The patent describes a need for improved topical formulations of Janus kinase (JAK) inhibitors for treating skin disorders. The technical challenges identified include creating a formulation that is stable, easily applicable, and provides good skin permeation characteristics (’543 Patent, col. 2:31-35).
  • The Patented Solution: The invention is an oil-in-water emulsion containing the JAK inhibitor ruxolitinib. This formulation is described as having a "thick, creamy appearance" that allows for good spreadability on the skin, which in turn leads to better skin permeation compared to anhydrous formulations (’543 Patent, Abstract; col. 4:29-34). The patent suggests this specific formulation provides advantages in stability and therapeutic delivery for skin disorders (’543 Patent, col. 2:12-30).
  • Technical Importance: The formulation provided a method for topical delivery of a JAK inhibitor, a class of drugs recognized for its therapeutic potential in treating skin immune disorders like psoriasis by blocking inflammatory cytokine signaling (’543 Patent, col. 2:12-30).

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims without specifying which ones (Compl. ¶35). Independent claim 1 is a representative composition claim.
  • Claim 1 Elements:
    • A pharmaceutical composition suitable for topical skin application, comprising:
    • an oil-in-water emulsion, comprising: water, an oil component, an emulsifier component, a solvent component, and
    • from about 0.5% to about 1.5% by weight of the emulsion on a free base basis of 1:1 (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl-]propanenitrile phosphoric acid salt,
    • wherein the oil-in-water emulsion in the composition is a solubilized cream for topical skin application and further wherein the oil-in-water emulsion has a pH of not greater than 3.6.

U.S. Patent No. 10,869,870 - "Topical Formulation for a JAK Inhibitor," issued December 22, 2020 (’870 Patent)

The Invention Explained

  • Problem Addressed: Similar to the ’543 Patent, this patent addresses the need for stable and effective topical formulations of JAK inhibitors to treat skin disorders (’870 Patent, col. 2:34-38).
  • The Patented Solution: The ’870 Patent also discloses an oil-in-water emulsion of ruxolitinib. The solution is presented as a stable cream with good spreadability and skin permeation, suitable for treating skin immune disorders (’870 Patent, Abstract; col. 4:30-34). The key distinction from the ’543 patent family appears to be the claimed concentration of the active ingredient.
  • Technical Importance: This patent further protects specific concentrations of the ruxolitinib topical formulation, aiming to secure a particular dosage form shown to be effective for skin disorders (’870 Patent, col. 2:12-30).

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims without specification (Compl. ¶44). Independent claim 1 is a representative composition claim.
  • Claim 1 Elements:
    • A pharmaceutical composition suitable for topical skin application, comprising:
    • an oil-in-water emulsion, comprising: water, an oil component, an emulsifier component, a solvent component, and
    • about 1.5% by weight of the emulsion on a free base basis of 1:1 (R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl-]propanenitrile phosphoric acid salt,
    • wherein the oil-in-water emulsion in the composition is a solubilized cream for topical skin application and further wherein the oil-in-water emulsion has a pH of not greater than 3.6.

U.S. Patent No. 11,219,624 - "Topical Formulation for a JAK Inhibitor," issued January 11, 2022 (’624 Patent)

  • Technology Synopsis: This patent claims methods of treating atopic dermatitis by topically applying a pharmaceutical composition comprising an oil-in-water emulsion of ruxolitinib (’624 Patent, Abstract). The problem and solution are substantially the same as described for the ’543 Patent.
  • Asserted Claims: The complaint does not specify claims, but a representative independent claim is Claim 1, a method of use claim (Compl. ¶53).
  • Accused Features: Defendant’s submission of an ANDA for a generic version of Opzelura® cream, which is approved for the treatment of atopic dermatitis, is the alleged act of infringement (Compl. ¶¶ 17, 51, 54).

U.S. Patent No. 11,510,923 - "Ruxolitinib Formulation for Reduction of Itch in Atopic Dermatitis," issued November 29, 2022 (’923 Patent)

  • Technology Synopsis: This patent is directed to methods of reducing itch associated with atopic dermatitis by administering a topical ruxolitinib cream (’923 Patent, Abstract). The formulation technology is consistent with that of the other asserted patents.
  • Asserted Claims: The complaint does not specify claims, but a representative independent claim is Claim 1, a method of use claim (Compl. ¶62).
  • Accused Features: The accused act is the filing of an ANDA for a product to treat atopic dermatitis, a condition for which itch is a primary symptom (Compl. ¶¶ 17, 60, 63).

U.S. Patent No. 11,571,425 - "Topical Formulation for a JAK Inhibitor," issued February 7, 2023 (’425 Patent)

  • Technology Synopsis: This patent claims methods of treating skin disorders by applying a topical oil-in-water ruxolitinib emulsion having specific formulation parameters, including a concentration of about 0.5% to about 1.5% by weight and a pH not greater than 3.6 (’425 Patent, Abstract; Claim 1).
  • Asserted Claims: The complaint does not specify claims, but a representative independent claim is Claim 1 (Compl. ¶71).
  • Accused Features: Defendant’s ANDA submission for a generic ruxolitinib cream is the basis for the infringement allegation (Compl. ¶¶ 69, 72).

U.S. Patent No. 11,590,136 - "Topical Formulation for a JAK Inhibitor," issued February 28, 2023 (’136 Patent)

  • Technology Synopsis: This patent claims methods of treating vitiligo by applying a topical oil-in-water ruxolitinib emulsion, building on the same core formulation technology as the other asserted patents (’136 Patent, Abstract).
  • Asserted Claims: The complaint does not specify claims; representative independent claims cover methods of treating vitiligo (Compl. ¶80).
  • Accused Features: Defendant's ANDA submission is for a generic version of Opzelura®, which is approved for the topical treatment of nonsegmental vitiligo (Compl. ¶¶ 18, 78, 81).

U.S. Patent No. 11,590,137 - "Ruxolitinib Formulation for Reduction of Itch in Atopic Dermatitis," issued February 28, 2023 (’137 Patent)

  • Technology Synopsis: This patent is directed to methods of reducing itch in atopic dermatitis by twice-daily application of a topical ruxolitinib cream, claiming specific clinical outcomes such as a ≥4-point improvement in itch score (’137 Patent, Abstract).
  • Asserted Claims: The complaint does not specify claims; representative independent claims cover methods for reducing itch with specific clinical endpoints (Compl. ¶89).
  • Accused Features: The accused act is the filing of an ANDA for a product to treat atopic dermatitis, for which reduction of itch is a key therapeutic goal (Compl. ¶¶ 17, 87, 90).

U.S. Patent No. 11,590,138 - "Topical Treatment of Vitiligo by a JAK Inhibitor," issued February 28, 2023 (’138 Patent)

  • Technology Synopsis: This patent claims methods for treating vitiligo by applying a 1.5% ruxolitinib cream twice per day, specifying treatment durations and patient populations (’138 Patent, Abstract).
  • Asserted Claims: The complaint does not specify claims; representative independent claims cover methods of treating vitiligo (Compl. ¶98).
  • Accused Features: Defendant's ANDA submission is for a generic version of Opzelura®, which is approved for topical treatment of nonsegmental vitiligo (Compl. ¶¶ 18, 96, 99).

U.S. Patent No. 11,602,536 - "Topical Treatment of Vitiligo by a JAK Inhibitor," issued March 14, 2023 (’536 Patent)

  • Technology Synopsis: This patent is also directed to methods of treating vitiligo by applying a 1.5% ruxolitinib cream, focusing on specific patient populations and treatment outcomes over time (’536 Patent, Abstract).
  • Asserted Claims: The complaint does not specify claims; representative independent claims cover methods of treating vitiligo (Compl. ¶107).
  • Accused Features: Defendant's ANDA submission is for a generic version of Opzelura®, which is approved for the topical treatment of nonsegmental vitiligo (Compl. ¶¶ 18, 105, 108).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is "Padagis's Proposed Product," a generic ruxolitinib cream that is the subject of ANDA No. 218657 submitted to the FDA (Compl. ¶¶ 1, 23).
  • Functionality and Market Context: The complaint alleges that the Proposed Product is a generic version of Incyte’s Opzelura® (ruxolitinib) cream (Compl. ¶1). It further alleges, on information and belief, that Defendant seeks approval to manufacture and sell this product for the same indications as Opzelura®, namely the topical treatment of atopic dermatitis and nonsegmental vitiligo (Compl. ¶¶ 17-18, 23). The lawsuit is predicated on the statutory act of infringement under 35 U.S.C. § 271(e)(2)(A), which arises from the submission of an ANDA seeking approval to market a generic drug prior to the expiration of patents listed in the FDA's Orange Book (Compl. ¶¶ 16, 33). The complaint does not provide specific details on the formulation of the accused product itself, as such information is contained within the confidential ANDA submission. No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail for a claim chart analysis. The central allegation is that Defendant’s submission of ANDA No. 218657 constitutes a statutory act of infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶33, 42, 51, 60, 69, 78, 87, 96, 105). The complaint alleges that upon FDA approval, the manufacture, use, sale, or importation of Padagis's Proposed Product will directly infringe one or more claims of the patents-in-suit (Compl. ¶35, 44, 53, 62, 71, 80, 89, 98, 107). The narrative theory is that because the Proposed Product is a generic version of Opzelura®, it will necessarily be a topical cream containing ruxolitinib that meets the composition limitations of the asserted patents, and its proposed labeling will instruct users to perform the patented methods of use.

  • Identified Points of Contention:
    • Scope Questions: Based on the claims of the lead patents, a central point of contention may be whether Defendant's formulation meets the specific definitions of a "solubilized cream" and a pH "not greater than 3.6" as required by claim 1 of both the ’543 and ’870 Patents. Defendant's non-infringement position, asserted in its Paragraph IV certification, could be based on a formulation designed to fall outside these parameters (Compl. ¶30).
    • Technical Questions: For the ’870 Patent, a key question will be the technical scope of the term "about 1.5% by weight." The factual evidence regarding the concentration of ruxolitinib in Defendant's product and the accepted variance implied by "about" in the pharmaceutical formulation art will be critical.

V. Key Claim Terms for Construction

  • The Term: "solubilized cream"

    • Context and Importance: This term appears in the independent claims of the lead composition patents (’543 Patent, Claim 1; ’870 Patent, Claim 1). Its construction is critical because infringement will depend on whether Defendant’s ANDA product, as formulated, qualifies as a "solubilized cream." Defendant could argue its formulation is a different type, such as a dispersion or suspension, to avoid infringement.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent specification uses the term in the context of describing the invention generally as an "oil-in-water formulation" suitable for topical administration (’543 Patent, col. 2:47-51). This may support an interpretation that covers a range of stable oil-in-water cream emulsions.
      • Evidence for a Narrower Interpretation: The specification contrasts the "solubilized cream" with "water-in-oil formulations," which "displayed syneresis" (separation), and notes the trend of increased permeability for the "solubilized cream" (’543 Patent, col. 4:54-64). This could support a narrower definition tied to specific stability and permeability characteristics demonstrated by the oil-in-water examples provided.

  • The Term: "about 1.5% by weight"

    • Context and Importance: This limitation is central to claim 1 of the ’870 Patent. The determination of infringement may hinge on how much variability the term "about" permits. A narrow construction would allow a generic manufacturer to design a product with a concentration just outside the literal range (e.g., 1.44%) and argue non-infringement.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The term "about" is generally understood in patent law to afford some degree of numerical flexibility to account for measurement error and equivalents. A party could argue it encompasses a range that is functionally equivalent to 1.5%.
      • Evidence for a Narrower Interpretation: The patent specification and figures disclose formulations tested at discrete concentrations of 0.5%, 1.0%, and 1.5% (’543 Patent, Fig. 2; col. 4:36-37). This explicit recitation of distinct values may be used to argue that "about 1.5%" does not extend to encompass values closer to 1.0% and should be construed narrowly around the 1.5% point.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon approval of its ANDA, Defendant will induce infringement by encouraging and instructing physicians, pharmacists, and patients to use the proposed generic product in accordance with its labeling, which will allegedly describe the patented methods of treating atopic dermatitis and vitiligo (Compl. ¶¶ 17-19, 36, 45). The complaint also alleges contributory infringement, stating the Proposed Product is especially adapted for an infringing use and has no substantial non-infringing use (Compl. ¶¶ 37, 46).
  • Willful Infringement: The complaint does not explicitly use the word "willful." However, it alleges that Defendant has knowledge of the patents-in-suit, at least as of its Paragraph IV certification, and requests that the case be found "exceptional" and that attorneys' fees be awarded under 35 U.S.C. § 285, which are remedies associated with findings of egregious infringement (Compl. ¶¶ 40, 49; Prayer for Relief ¶J).

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

  • A core issue will be one of formulation equivalence: Will the specific formulation detailed in Padagis's confidential ANDA submission be found to meet the claimed requirements of a "solubilized cream" with a pH "not greater than 3.6," or has Padagis successfully designed around these claim limitations?
  • A central question of claim construction will be the scope of "about 1.5%" in the ’870 Patent. The court's interpretation will determine whether a generic product with a concentration numerically close but not identical to 1.5% infringes.
  • A determinative issue will be validity: As this is an ANDA case, a significant portion of the litigation will focus on Padagis's asserted defense that the patents are invalid, likely on grounds of obviousness based on the state of the art of topical pharmaceutical formulations at the time of the inventions.