DCT

1:23-cv-01221

Orion Corp v. Hetero USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-01221, D. Del., 10/28/2024
  • Venue Allegations: Venue is alleged to be proper as to Defendant Hetero USA Inc. because it is a Delaware corporation. Venue is alleged to be proper as to the foreign defendants because they are subject to personal jurisdiction in the district.
  • Core Dispute: Plaintiffs allege that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the prostate cancer drug Nubeqa® (darolutamide) constitutes an act of infringement of five U.S. patents.
  • Technical Context: The patents-in-suit relate to specific crystalline forms, formulations, and particles of the active pharmaceutical ingredient darolutamide, an androgen receptor antagonist.
  • Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act following Defendants’ submission of ANDA No. 218787 to the FDA. Plaintiffs were notified of the ANDA filing via a Notice Letter dated September 11, 2023, which included a Paragraph IV certification asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed by the proposed generic product. Four of the five patents are listed in the FDA's Orange Book for Nubeqa®.

Case Timeline

Date Event
2015-01-30 Earliest Priority Date ('530, '853, '515 Patents)
2016-08-26 Earliest Priority Date ('221 Patent)
2017-03-07 Earliest Priority Date ('058 Patent)
2018-07-03 Issue Date: U.S. Patent No. 10,010,530
2019-08-20 Issue Date: U.S. Patent No. 10,383,853
2020-10-27 Issue Date: U.S. Patent No. 10,815,221
2020-11-17 Issue Date: U.S. Patent No. 10,835,515
2021-11-09 Issue Date: U.S. Patent No. 11,168,058
2023-09-11 Date of Hetero's Notice Letter
2024-10-28 First Amended Complaint Filing Date

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

U.S. Patent No. 10,010,530 - "Carboxamide Derivative and Its Diastereomers in Stable Crystalline Form," issued July 3, 2018

The Invention Explained

  • Problem Addressed: The patent discloses the chemical compound darolutamide and its diastereomers, which are potent androgen receptor (AR) modulators for treating diseases like prostate cancer (’530 Patent, col. 1:24-38). The implicit technical challenge is isolating this compound in a form with consistent physical properties suitable for large-scale pharmaceutical manufacturing and formulation.
  • The Patented Solution: The invention is a specific solid crystalline form of darolutamide, designated "crystalline form I." This form is created through a defined crystallization process and is identified by a unique X-ray powder diffraction (XRPD) pattern, which acts as a structural fingerprint (’530 Patent, col. 2:40-47; col. 3:27-34). The patent notes that this form is stable during pharmaceutical processing and storage (’530 Patent, col. 3:7-11).
  • Technical Importance: Obtaining a specific, stable polymorph (crystalline form) of an active pharmaceutical ingredient is critical for ensuring consistent product quality, dissolution, bioavailability, and shelf life.

Key Claims at a Glance

  • The complaint asserts independent Claim 1 (Compl. ¶30, ¶62).
  • The essential elements of Claim 1 are:
    • Crystalline form I of N—((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl) propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide (I)
    • having an X-ray powder diffraction pattern comprising characteristic peaks at about 8.5, 10.4, 16.6, 16.9, and 24.3 degrees 2-theta.
  • The complaint alleges infringement literally and/or under the doctrine of equivalents but does not specify other claims (Compl. ¶62).

U.S. Patent No. 10,383,853 - "Carboxamide Derivative and Its Diastereomers in Stable Crystalline Form," issued August 20, 2019

The Invention Explained

  • Problem Addressed: As a continuation of the application leading to the ’530 Patent, the ’853 Patent addresses the same challenge: producing a stable, manufacturable form of darolutamide (’853 Patent, (63); col. 1:27-38). This patent, however, focuses on the purity of the crystalline form.
  • The Patented Solution: The invention is the same "crystalline form I" of darolutamide but adds a negative limitation, claiming the form as being "substantially free of any other crystalline form" of the same compound (’853 Patent, col. 2:60-65). This aims to protect a polymorphically pure version of the drug substance.
  • Technical Importance: Polymorphic purity is crucial in pharmaceuticals because the presence of other, less stable or less soluble crystalline forms can negatively impact a drug's performance and safety profile.

Key Claims at a Glance

  • The complaint asserts independent Claim 1 (Compl. ¶35, ¶71).
  • The essential elements of Claim 1 are:
    • Crystalline form I of N—((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide (I) having an X-ray powder diffraction pattern comprising characteristic peaks at about 8.5, 10.4, 16.6, and 24.3 degrees 2-theta,
    • wherein the crystalline form I is substantially free of any other crystalline form of N-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide (I).
  • The complaint reserves rights under the doctrine of equivalents but does not specify other claims (Compl. ¶71).

U.S. Patent No. 10,835,515 - "Carboxamide Derivative and Its Diastereomers in Stable Crystalline Form," issued November 17, 2020

  • Patent Identification: "Carboxamide Derivative and Its Diastereomers in Stable Crystalline Form," issued November 17, 2020 (Compl. ¶37).
  • Technology Synopsis: This patent claims a pharmaceutical dosage form, specifically a tablet or capsule, that contains the "crystalline form I" of darolutamide together with a pharmaceutical excipient (’515 Patent, Abstract; col. 16:47-56). The invention moves beyond the drug substance itself to cover its formulation into a final product for oral administration (Compl. ¶40).
  • Asserted Claims: Independent Claim 1 (Compl. ¶40, ¶80).
  • Accused Features: Hetero's ANDA Product is described as an oral tablet, which Plaintiffs allege comprises crystalline form I of darolutamide and an excipient (Compl. ¶54, ¶80).

U.S. Patent No. 11,168,058 - "Manufacture of a Crystalline Pharmaceutical Product," issued November 9, 2021

  • Patent Identification: "Manufacture of a Crystalline Pharmaceutical Product," issued November 9, 2021 (Compl. ¶42).
  • Technology Synopsis: This patent is directed to crystalline particles of darolutamide defined by specific physical characteristics rather than only the internal crystal structure. The claims cover particles having a specific surface area (SSA) within a defined range or a combination of rounded particle shape and a particular volume median diameter (’058 Patent, Abstract; col. 4:32-52). These properties are important for manufacturing processes like powder flow and tablet compression.
  • Asserted Claims: Independent Claims 1 and 10 (Compl. ¶45, ¶46, ¶89).
  • Accused Features: Plaintiffs allege on information and belief that the particles in Hetero's ANDA Product will possess the claimed SSA, rounded shape, and/or particle size distribution (Compl. ¶89).

U.S. Patent No. 10,815,221 - "Crystal Forms of an Androgen Receptor Antagonist, Preparation Method and Use Thereof," issued October 27, 2020

  • Patent Identification: "Crystal Forms of an Androgen Receptor Antagonist, Preparation Method and Use Thereof," issued October 27, 2020 (Compl. ¶48).
  • Technology Synopsis: This patent claims a different crystalline form of darolutamide (referred to as ODM-201), designated "crystalline form B" (’221 Patent, Abstract; col. 4:5-9). This form is also identified by a unique XRPD pattern, distinct from that of "crystalline form I" asserted in the other patents. The patent presents this as a novel form with advantageous properties such as low hygroscopicity and high stability (’221 Patent, col. 3:20-43).
  • Asserted Claims: Independent Claim 1 (Compl. ¶50, ¶142).
  • Accused Features: Plaintiffs allege that Hetero's ANDA product "contains form B of darolutamide in accordance with the requirements of at least claim 1 of the '221 patent" (Compl. ¶142). The complaint provides a structural diagram of the darolutamide molecule from this patent (Compl. ¶50).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is "Hetero's ANDA Product," a proposed generic version of Plaintiffs' Nubeqa® (darolutamide) tablets for which Defendants seek FDA approval via ANDA No. 218787 (Compl. ¶1, ¶53).

Functionality and Market Context

  • According to information from Hetero's Notice Letter, the product is an oral tablet with a proposed dosage strength of 300 mg (Compl. ¶54, ¶55). As a generic version of Nubeqa®, its function is to act as an androgen receptor antagonist for the treatment of prostate cancer. The filing represents a direct commercial challenge to Plaintiffs' branded product, seeking to enter the market prior to the expiration of the patents-in-suit (Compl. ¶1). The complaint notes that the ANDA itself and samples of the product are not publicly available (Compl. ¶56, ¶57).

IV. Analysis of Infringement Allegations

The complaint’s infringement theory is based on the act of filing the ANDA, which under 35 U.S.C. § 271(e)(2) constitutes a technical act of infringement, and the future infringement that would occur if the product were commercially launched. The complaint includes a chemical structure of darolutamide, which is the active ingredient in both the branded and accused generic products (Compl. ¶50).

'530 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
Crystalline form I of N—((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl) propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide (I) On information and belief, Hetero's ANDA Product is an oral tablet containing the active ingredient darolutamide in a crystalline form. ¶53, ¶54, ¶62 col. 3:27-31
having an X-ray powder diffraction pattern comprising characteristic peaks at about 8.5, 10.4, 16.6, 16.9, and 24.3 degrees 2-theta. On information and belief, the crystalline form of darolutamide in Hetero's ANDA Product will have an XRPD pattern with the characteristic peaks recited in the claim. ¶62 col. 3:31-34

'853 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
Crystalline form I of N—((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide (I) having an X-ray powder diffraction pattern comprising characteristic peaks at about 8.5, 10.4, 16.6, and 24.3 degrees 2-theta... On information and belief, Hetero's ANDA Product is an oral tablet containing crystalline form I of the active ingredient darolutamide, which will exhibit the claimed XRPD pattern. ¶53, ¶54, ¶71 col. 16:50-54
...wherein the crystalline form I is substantially free of any other crystalline form of N-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide (I). On information and belief, the crystalline form I in Hetero's ANDA Product will be polymorphically pure and thus substantially free of other crystalline forms. ¶71 col. 16:54-60

Identified Points of Contention

  • Evidentiary Question: The primary dispute for all asserted patents will be factual and will depend on discovery of Hetero's confidential ANDA. The key question is: What are the actual physical and chemical properties of the proposed generic product? The complaint's allegations are made "on information and belief," and their verification will require access to Hetero's manufacturing specifications and product characterization data (e.g., XRPD, SSA, particle analysis) (Compl. ¶56, ¶62, ¶71, ¶89, ¶142).
  • Technical Question: The complaint asserts infringement of patents claiming two different, mutually exclusive crystalline forms: "form I" (’530 and ’853 Patents) and "form B" (’221 Patent). This raises the question of whether Hetero's product can infringe both, or if these allegations represent alternative pleading theories pending discovery. The determination of which crystalline form, if any, is present in the accused product will be a dispositive technical issue.

V. Key Claim Terms for Construction

The Term: "about"

  • Context and Importance: This term modifies the numerical XRPD peak values in the claims of the ’530, ’853, and ’515 patents. The scope of "about" is critical because it determines the permissible range of deviation from the recited values for a finding of infringement. Practitioners may focus on this term because even slight shifts in measured peak positions are common, and the breadth of this term could decide the outcome of the infringement analysis.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The use of the word "about" itself suggests the patentee did not intend the values to be precise and absolute.
    • Evidence for a Narrower Interpretation: The specifications of the ’530 and ’853 patents state that XRPD peak positions "can be subject to variations of +/-0.15 degrees 2-theta" (’530 Patent, col. 4:21-25). A court may view this as an explicit definition that cabins the scope of "about" to that specific numerical range.

The Term: "substantially free"

  • Context and Importance: This term from Claim 1 of the ’853 Patent is central to distinguishing it from the ’530 Patent. The definition of the required level of polymorphic purity will be a primary focus of claim construction. If Hetero’s product contains even a small amount of another crystalline form, the meaning of "substantially free" will determine whether it infringes.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent does not provide a specific numerical percentage (e.g., >95% pure). This lack of a bright-line rule could support an argument that the term allows for more than a de minimis amount of other forms.
    • Evidence for a Narrower Interpretation: The patent’s "Summary of the Invention" emphasizes that it was a discovery to obtain the compound in a "stable and substantially pure crystalline form" (’853 Patent, col. 2:42-43). This context may support a narrower construction requiring a high degree of purity that is meaningful from a pharmaceutical standpoint.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement and contributory infringement for all patents-in-suit. The stated basis for inducement is that Defendants' proposed product labeling will instruct physicians and patients to administer the drug, which allegedly contains the claimed crystalline forms and particles, thereby causing direct infringement (Compl. ¶64, ¶65). The basis for contributory infringement is that the product is "especially made or adapted" for this infringing use and is "not suitable for substantial non-infringing use" (Compl. ¶66).
  • Willful Infringement: While the complaint does not contain a separate count for willful infringement, it alleges that Defendants have knowledge of the patents-in-suit, at least as of the date of their Paragraph IV certification and Notice Letter (Compl. ¶51, ¶52, ¶97, ¶108, etc.). The prayer for relief requests a declaration that the case is exceptional and an award of attorneys' fees under 35 U.S.C. § 285, which is often predicated on a finding of willful infringement or other litigation misconduct (Compl. p. 26).

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

  • A central issue will be one of factual evidence: What are the precise physical characteristics of the generic product described in Hetero's confidential ANDA? The case will turn on whether characterization data (XRPD, SSA, etc.) shows the product meets the limitations of "crystalline form I," "crystalline form B," or neither.
  • A second core issue will be one of claim construction: How will the court define the term "substantially free" in the '853 patent? The outcome of this legal determination will set the threshold for polymorphic purity required to prove infringement of that patent.
  • Finally, a key strategic question arises from the pleading of alternative theories: By asserting patents for two distinct crystalline forms ("Form I" and "Form B"), Plaintiffs have created a tension that must be resolved through discovery. The case will likely focus on determining if Hetero designed its product to fall within one of these patented forms or successfully designed around both.