DCT

3:24-cv-10734

Cassiopea Spa v. Aurobindo Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:24-cv-10734, D.N.J., 11/25/2024
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Aurobindo Pharma USA, Inc. has a regular and established place of business in the state and committed alleged acts of infringement, including filing its Abbreviated New Drug Application (ANDA), from New Jersey.
  • Core Dispute: Plaintiffs allege that Defendants’ filing of an ANDA to market a generic version of Plaintiffs' WINLEVI® topical cream constitutes an act of infringement of six U.S. patents directed to specific crystalline forms of the active ingredient clascoterone, pharmaceutical compositions containing them, and methods of their use for treating acne.
  • Technical Context: The technology relates to pharmaceutical formulations for dermatology, specifically the identification and use of distinct crystalline polymorphs of a steroid-based topical androgen receptor inhibitor for the treatment of acne vulgaris.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants’ submission of an ANDA with a Paragraph IV certification, asserting that the patents covering the reference listed drug, WINLEVI®, are invalid, unenforceable, or will not be infringed by the proposed generic product. The complaint notes that Defendants have a history of utilizing the Hatch-Waxman process to challenge patents on branded pharmaceuticals.

Case Timeline

Date Event
2007-08-03 Priority Date for all Patents-in-Suit
2014-07-22 U.S. Patent No. 8,785,427 Issues
2016-09-06 U.S. Patent No. 9,433,628 Issues
2016-11-08 U.S. Patent No. 9,486,458 Issues
2018-12-25 U.S. Patent No. 10,159,682 Issues
2020-08-26 FDA approves WINLEVI® for topical treatment of acne vulgaris
2021-12-28 U.S. Patent No. 11,207,332 Issues
2024-03-26 U.S. Patent No. 11,938,141 Issues
2024-10-11 Date of Aurobindo's Notice Letter regarding its ANDA submission
2024-11-25 Complaint for Patent Infringement Filed

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

U.S. Patent No. 8,785,427 - “Enzymatic process for obtaining 17 alpha-monoesters of cortexolone and/or its 9,11-dehydroderivatives”

  • Patent Identification: U.S. Patent No. 8,785,427, entitled “Enzymatic process for obtaining 17 alpha-monoesters of cortexolone and/or its 9,11-dehydroderivatives,” issued July 22, 2014 (“’427 Patent”).

The Invention Explained

  • Problem Addressed: The patent family addresses the technical challenge of preparing and isolating stable, pure forms of cortexolone derivatives for pharmaceutical use, as these compounds can be unstable and difficult to purify using conventional chemical methods (’682 Patent, col. 2:1-9).
  • The Patented Solution: While the patent title suggests a process, the asserted claims are directed to a specific crystalline polymorph of cortexolone-17α-propionate, designated “form III” (Compl. ¶87). This form is defined by its unique analytical characteristics, including its Diffractive X-ray (DRX), Differential Scanning Calorimetry (DSC), and Infrared (IR) spectra, which distinguish it from other forms of the same compound (Compl. ¶¶53, 87; ’682 Patent, FIGS. 7-15). The invention provides a stable and identifiable solid form of the active pharmaceutical ingredient.
  • Technical Importance: Isolating distinct and stable polymorphs is critical in pharmaceutical development, as different crystalline forms can affect a drug's solubility, bioavailability, and stability, thereby influencing its efficacy and safety (Compl. ¶73).

Key Claims at a Glance

  • The complaint asserts independent claim 20 and dependent claims 24 and 25 (Compl. ¶87).
  • Independent Claim 20:
    • A crystalline form III of cortexolone-17α-propionate
    • having a DRX spectrum as represented in FIG. 7 or 10 or 13
    • and a DSC spectrum as represented in FIG. 8 or 11 or 14
    • and an IR spectrum as represented in FIG. 9 or 12 or 15.

U.S. Patent No. 9,433,628 - “Enzymatic process for obtaining 17a-monoesters of cortexolone and/or its 9,11-dehydroderivatives”

  • Patent Identification: U.S. Patent No. 9,433,628, entitled “Enzymatic process for obtaining 17a-monoesters of cortexolone and/or its 9,11-dehydroderivatives,” issued September 6, 2016 (“’628 Patent”).

The Invention Explained

  • Problem Addressed: As with the related ’427 Patent, this invention addresses the need for stable, well-characterized forms of cortexolone-17α-propionate suitable for pharmaceutical formulation (’682 Patent, col. 2:1-9).
  • The Patented Solution: The asserted claims cover a different crystalline polymorph designated “form IV,” compositions containing it, and a process for its preparation (Compl. ¶110). Crystalline form IV is described as a hydrated or "solvate" form of the active ingredient, meaning it incorporates water molecules into its crystal structure (Compl. ¶54; ’682 Patent, col. 9:22-26). The patent claims this specific polymorph, identifiable by its characteristic X-ray Powder Diffraction (XRPD) peaks, and pharmaceutical creams containing it.
  • Technical Importance: The discovery of a stable hydrated polymorph provides an alternative solid form for formulation which can arise during aqueous-based manufacturing processes, and its characterization allows for control over the final drug product's composition (Compl. ¶57; ’682 Patent, col. 9:32-40).

Key Claims at a Glance

  • The complaint asserts independent claims 2, 3, and 14, as well as dependent claims 17 and 18 (Compl. ¶110).
  • Independent Claim 14 (Composition):
    • A pharmaceutical composition
    • comprising crystalline form IV of cortexolone-17α-propionate,
    • water, and
    • at least one physiologically acceptable excipient.
  • Independent Claim 3 (Process):
    • A process for preparing crystalline form IV of cortexolone-17α-propionate,
    • the process comprising crystallizing cortexolone-17α-propionate from a propylene glycol/water or polyethylene glycol/water mixture.

Multi-Patent Capsule: U.S. Patent No. 9,486,458

  • Patent Identification: U.S. Patent No. 9,486,458 (“’458 Patent”), entitled “Enzymatic process for obtaining 17 alpha-monoesters of cortexolone and/or its 9,11-dehydroderivatives,” issued November 8, 2016 (Compl. ¶34).
  • Technology Synopsis: The patent claims methods for treating skin pathologies, including acne, by administering an effective amount of a composition containing crystalline form IV of cortexolone-17α-propionate (Compl. ¶135). The invention is directed to the therapeutic application of this specific polymorph.
  • Asserted Claims: Independent claim 14 and its dependents are asserted (Compl. ¶135).
  • Accused Features: The administration of Aurobindo’s product according to its proposed label for the treatment of acne is alleged to constitute infringement of the claimed methods (Compl. ¶139).

Multi-Patent Capsule: U.S. Patent No. 10,159,682

  • Patent Identification: U.S. Patent No. 10,159,682 (“’682 Patent”), entitled “Enzymatic process for obtaining 17 alpha-monoesters of cortexolone and/or its 9,11-dehydroderivatives,” issued December 25, 2018 (Compl. ¶36).
  • Technology Synopsis: The patent claims methods of treating skin conditions by administering a composition that contains crystalline form III of cortexolone-17α-propionate (Compl. ¶159). Some claims further require the composition to contain other crystalline forms (I, II, or IV) and solubilized drug substance.
  • Asserted Claims: Independent claim 7 and its dependents are asserted (Compl. ¶159).
  • Accused Features: The administration of Aurobindo's product according to its proposed label is alleged to infringe the claimed methods, based on Plaintiffs' belief that the product contains crystalline form III and other forms (Compl. ¶¶75, 162).

Multi-Patent Capsule: U.S. Patent No. 11,207,332

  • Patent Identification: U.S. Patent No. 11,207,332 (“’332 Patent”), entitled “Enzymatic process for obtaining 17 α-monoesters of cortexolone and/or its 9,11-dehydroderivatives,” issued December 28, 2021 (Compl. ¶38).
  • Technology Synopsis: This patent claims pharmaceutical compositions that comprise a combination of both crystalline form III and crystalline form IV of cortexolone-17α-propionate (Compl. ¶182). It also claims methods of treating skin conditions using such combination compositions.
  • Asserted Claims: Independent claims 1 (composition) and 17 (method) and their dependents are asserted (Compl. ¶182).
  • Accused Features: Aurobindo's product is alleged to contain both crystalline forms III and IV, thereby infringing the composition claims, and its proposed label is alleged to induce infringement of the method claims (Compl. ¶¶185, 186).

Multi-Patent Capsule: U.S. Patent No. 11,938,141

  • Patent Identification: U.S. Patent No. 11,938,141 (“’141 Patent”), entitled “Enzymatic process for obtaining 17 alpha-monoesters of cortexolone and/or its 9,11-dehydroderivatives,” issued March 26, 2024 (Compl. ¶40).
  • Technology Synopsis: This patent is directed to topical compositions that comprise at least two different crystalline forms of cortexolone-17α-propionate, selected from a group consisting of Forms I, II, III, and IV (Compl. ¶206).
  • Asserted Claims: Independent claim 1 and its dependents are asserted (Compl. ¶206).
  • Accused Features: Aurobindo’s product is alleged to infringe by containing a combination of crystalline forms III and IV, thereby meeting the requirement of comprising "at least two crystalline forms" (Compl. ¶209).

III. The Accused Instrumentality

Product Identification

  • Defendants' proposed generic 1% clascoterone topical cream product, for which Aurobindo submitted ANDA No. 219862 to the FDA for approval (Compl. ¶¶2, 69).

Functionality and Market Context

  • The accused product is a topical cream intended for the treatment of acne vulgaris in patients 12 years of age and older (Compl. ¶76). The complaint includes a diagram of the chemical structure of clascoterone, the active ingredient (Compl. ¶50). The product is designed to be a generic equivalent of Plaintiffs' WINLEVI® product and, according to the complaint, relies on WINLEVI®'s safety and efficacy data and purports to be bioequivalent (Compl. ¶¶67, 74).

IV. Analysis of Infringement Allegations

'427 Patent Infringement Allegations

Claim Element (from Independent Claim 20) Alleged Infringing Functionality Complaint Citation Patent Citation
Crystalline form III of cortexolone-17α-propionate Based on the accused product's purported bioequivalence to WINLEVI®, which contains Form III, the complaint alleges on information and belief that the Aurobindo product comprises crystalline clascoterone form III. ¶75, ¶90 ’682 Patent, col. 8:5-15
having a DRX spectrum as represented in FIG. 7 or 10 or 13 The complaint alleges the Form III in Aurobindo's product has the claimed spectral characteristics. ¶90 ’682 Patent, FIGS. 7, 10, 13
and a DSC spectrum as represented in FIG. 8 or 11 or 14 The complaint alleges the Form III in Aurobindo's product has the claimed spectral characteristics. ¶90 ’682 Patent, FIGS. 8, 11, 14
and an IR spectrum as represented in FIG. 9 or 12 or 15. The complaint alleges the Form III in Aurobindo's product has the claimed spectral characteristics. ¶90 ’682 Patent, FIGS. 9, 12, 15
  • Identified Points of Contention:
    • Evidentiary Question: The complaint's allegation that Aurobindo's product contains crystalline Form III is made on "information and belief," predicated on the product's purported bioequivalence to WINLEVI® (Compl. ¶75). A central question for the court will be what direct evidence, such as analytical testing data, Plaintiffs can produce to demonstrate the actual presence of this specific polymorph in Defendants' product.
    • Scope Question: The claim defines Form III by reference to specific figures in the patent. A potential dispute may arise over how closely an accused product's spectral data must match the representative spectra in the patent figures to constitute literal infringement.

'628 Patent Infringement Allegations

Claim Element (from Independent Claim 14) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition Aurobindo's ANDA Product is a 1% clascoterone cream formulation, which is a pharmaceutical composition. ¶69, ¶113 ’682 Patent, col. 9:32-40
comprising crystalline form IV of cortexolone-17α-propionate, The complaint alleges, based on Aurobindo's Notice Letter, that the ANDA Product comprises clascoterone crystalline form IV. ¶70, ¶113 ’682 Patent, col. 9:22-31
water, As an aqueous cream formulation, the product contains water. ¶75, ¶113 ’682 Patent, col. 9:37-38
and at least one physiologically acceptable excipient. As a cream formulation, the product necessarily contains one or more excipients to form the cream base. ¶71, ¶113 ’682 Patent, col. 9:43-46
  • Identified Points of Contention:
    • Technical Question: The complaint alleges that Aurobindo's Notice Letter does not contest the presence of Form IV (Compl. ¶70). The primary technical question will be the confirmation of this polymorph's presence and whether its characteristics meet the definition in other asserted claims (e.g., claim 2, which defines Form IV by specific XRPD peaks).
    • Process vs. Product: Plaintiffs also assert process claim 3. This raises the question of whether Plaintiffs can establish that Defendants' manufacturing process involves the claimed step of "crystallizing...from a propylene glycol/water...mixture" (Compl. ¶115). Infringement of this claim will depend on evidence of the manufacturing process itself, not just the final product composition.

V. Key Claim Terms for Construction

  • The Term: "crystalline form IV of cortexolone-17α-propionate" (’628 Patent, claim 14) and similar terms for Form III (’427 Patent, claim 20).
  • Context and Importance: The entire case hinges on the presence of specific, claimed crystalline polymorphs in the accused product. The definition of these forms, which are distinguished from each other only by their crystal structure and corresponding analytical data, is therefore central to the infringement analysis for every asserted patent.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: Practitioners may cite the term "about" used in claim 2 of the ’628 Patent to define the XRPD peaks for Form IV (e.g., "peaks at about 4.8, 12.9...") (Compl. ¶110). This term explicitly introduces a degree of variability and could support a construction that does not require exact correspondence to the recited numerical values.
    • Evidence for a Narrower Interpretation: Practitioners may point to the patent's specific examples and figures (e.g., ’682 Patent, FIG. 28) as defining the quintessential embodiment of Form IV. This could support a narrower construction where "about" allows for only minor instrumental or experimental variance, and where the overall pattern must closely match the representative spectrum depicted in the patent.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement for all six patents. The primary basis is that Aurobindo’s proposed product labeling will instruct medical professionals and patients to administer the cream topically for the treatment of acne, which allegedly constitutes direct infringement of the asserted method claims (e.g., Compl. ¶¶93, 118, 142). The complaint also pleads contributory infringement, alleging the product is especially made for an infringing use and is not a staple article of commerce (e.g., Compl. ¶¶94, 119, 143).
  • Willful Infringement: Willfulness is alleged based on Defendants' pre-suit knowledge of the patents, evidenced by their filing of an ANDA containing a Paragraph IV certification against each of the patents-in-suit (Compl. ¶¶96, 121). The complaint alleges that Defendants proceeded "without a reasonable basis for believing" they would not be liable for infringement, making the case "exceptional" under 35 U.S.C. § 285.

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

  • A core issue will be one of evidentiary proof: Can Plaintiffs produce direct analytical evidence (e.g., XRPD, DSC) demonstrating that Aurobindo’s ANDA product, as manufactured, contains the specific crystalline polymorphs (Form III and Form IV) required by the asserted claims, or must the case rely on inferences drawn from the product's bioequivalence to WINLEVI®?
  • A key question of claim construction will be the interpretation of spectral data: For claims that define polymorphs by specific analytical peaks preceded by the word "about," what is the permissible scope of deviation from the recited values that still falls within the claim, and how does that scope relate to the representative spectra depicted in the patents' figures?
  • The viability of the process claim infringement theory will present a discovery question: What evidence can Plaintiffs obtain regarding Aurobindo's confidential manufacturing process to determine if it meets the specific crystallization steps recited in claim 3 of the ’628 patent?