DCT

2:24-cv-06784

Aragon Pharma Inc v. Hetero Labs Ltd Unit V

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:24-cv-06784, D.N.J., 06/06/2024
  • Venue Allegations: Venue is alleged in the District of New Jersey based on Defendant Hetero USA, Inc. having a regular and established place of business in the district and having committed acts of infringement there, including the submission of the Abbreviated New Drug Application (ANDA) that precipitated this lawsuit.
  • Core Dispute: Plaintiffs allege that Defendants' filing of an ANDA to market a generic version of the prostate cancer drug Erleada® (apalutamide) constitutes an act of infringement of three U.S. patents covering the apalutamide compound, pharmaceutical compositions containing it, and methods of its use.
  • Technical Context: The patents relate to a class of chemical compounds known as androgen receptor modulators, which are designed to treat hormone-sensitive and hormone-refractory prostate cancer by inhibiting the activity of the androgen receptor.
  • Key Procedural History: This action is a Hatch-Waxman lawsuit filed in response to Defendants' April 26, 2024, notification letter, which included a Paragraph IV certification challenging the patents-in-suit. The complaint notes that other patents covering Erleada® are the subject of separate, ongoing litigation between certain of the parties.

Case Timeline

Date Event
2006-03-27 Earliest Priority Date for ’689, ’159, and ’261 Patents
2014-08-12 U.S. Patent No. 8,802,689 Issued
2016-07-12 U.S. Patent No. 9,388,159 Issued
2018-06-05 U.S. Patent No. 9,987,261 Issued
2022-02-14 Defendants allegedly submitted ANDA No. 217185 to the FDA
2024-04-26 Defendants allegedly amended the ANDA with Paragraph IV certification for the Patents-in-Suit
2024-06-06 Complaint Filed

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

U.S. Patent No. 8,802,689 - "Androgen Receptor Modulator for the Treatment of Prostate Cancer and Androgen Receptor-Associated Diseases"

The Invention Explained

  • Problem Addressed: The patent’s background section describes the challenge of treating prostate cancer that has become "hormone refractory." In this state, the Androgen Receptor (AR) is often overexpressed, which can cause existing anti-androgen drugs to paradoxically begin stimulating cancer growth (acting as agonists) rather than inhibiting it. (’689 Patent, col. 1:41-54; col. 2:1-16).
  • The Patented Solution: The invention claims a method of treating prostate cancer by administering compounds from a class of non-steroidal AR modulators, specifically including thiohydantoins. These compounds are designed to be potent AR antagonists with minimal agonistic activity, thereby remaining effective even in the hormone-refractory setting where the AR is overexpressed. (’689 Patent, Abstract; col. 2:26-32).
  • Technical Importance: The technology provided a therapeutic approach designed to overcome a key mechanism of resistance in advanced prostate cancer, where AR overexpression converts prior-generation antagonists into agonists. (’689 Patent, col. 2:12-16).

Key Claims at a Glance

  • The complaint asserts at least claim 2, which depends on independent claim 1. (Compl. ¶64).
  • The essential elements of independent claim 1 are:
    • A method for treating prostate cancer in a subject.
    • The method comprises administering a compound of a specific chemical structure (Formula II).
    • The structural formula requires a six-membered heterocyclic unit ("Het").
    • A core ring structure where substituent "A" is sulfur and "B" is oxygen.
    • Substituent "R1" is an aryl or substituted aryl group.
    • Substituents "R2" and "R3" can, together with their attached carbon, form a cycloalkyl ring.
  • Claim 2 further specifies that the ring formed by R2 and R3 is a cyclobutyl ring. (’689 Patent, col. 32:3-5).

U.S. Patent No. 9,388,159 - "Substituted Diazaspiroalkanes as Androgen Receptor Modulators"

The Invention Explained

  • Problem Addressed: The patent addresses the same problem as the ’689 Patent: the failure of common anti-androgens to effectively treat hormone-refractory prostate cancer due to weak antagonism and conversion to agonists upon Androgen Receptor (AR) overexpression. (’159 Patent, col. 1:53-col. 2:16).
  • The Patented Solution: The invention discloses and claims a genus of compounds, defined by a core diazaspiroalkane chemical structure, that function as AR modulators. The solution is the compound itself, which is designed to potently antagonize the AR without stimulating it, making it suitable for treating advanced prostate cancer. (’159 Patent, Abstract; col. 2:26-32).
  • Technical Importance: This patent claims specific chemical matter within the broader therapeutic concept, identifying a diazaspiroalkane scaffold as a basis for potent, non-steroidal AR antagonists designed for hormone-refractory disease. (’159 Patent, col. 2:12-16).

Key Claims at a Glance

  • The complaint asserts at least claims 1, 12, and 17. (Compl. ¶81).
  • The essential elements of independent claim 1 are:
    • A compound having a specific chemical structure (Formula II).
    • The formula requires a five or six-membered heterocyclic unit ("Het").
    • A core ring structure where substituent "A" is sulfur and "B" is oxygen.
    • Substituents "R2" and "R3" can, together with their attached carbon, form a cycle.
  • Independent claim 12 claims a pharmaceutical composition comprising a therapeutically effective amount of a compound from claim 1 and a pharmaceutically acceptable carrier, diluent, or adjuvant. (’159 Patent, col. 34:25-29).
  • Independent claim 17 claims a pharmaceutical composition of claim 12 that is formulated in an oral dosage form. (’159 Patent, col. 34:42-44).

U.S. Patent No. 9,987,261 - "Substituted Diazaspiroalkanes as Androgen Receptor Modulators"

Technology Synopsis

This patent is directed to specific pharmaceutical formulations containing the diazaspiroalkane androgen receptor modulators. It claims tablets comprising a specified range of the active compound (from 0.0005 to 500 mg) along with a pharmaceutically acceptable carrier, providing a concrete dosage form for the therapeutic agents. (’261 Patent, Abstract; Claim 10).

Asserted Claims

At least claims 10 and 12. (Compl. ¶98). Claim 10 is an independent claim.

Accused Features

The complaint alleges that Defendants' Proposed ANDA Product is a tablet containing apalutamide in a quantity that falls within the claimed dosage range and includes a pharmaceutically acceptable carrier. (Compl. ¶100).

III. The Accused Instrumentality

Product Identification

Defendants' "Proposed ANDA Product" is a generic version of Erleada®, identified as "Apalutamide Tablets; Oral 60 mg" (Compl. ¶2, ¶56).

Functionality and Market Context

  • The product's active pharmaceutical ingredient is apalutamide, an androgen receptor modulator. (Compl. ¶37). The complaint provides the chemical structure of apalutamide. (Compl. ¶65). The product is indicated for the treatment of non-metastatic castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer. (Compl. ¶37). A visual of the accused apalutamide compound's chemical structure is provided in the complaint, showing a thiohydantoin core with a spirocyclic cyclobutane ring. (Compl. ¶65).
  • The complaint alleges that Defendants submitted ANDA No. 217185 seeking FDA approval to manufacture and sell this generic product in the United States prior to the expiration of the patents-in-suit. (Compl. ¶2, ¶30).

IV. Analysis of Infringement Allegations

U.S. Patent No. 8,802,689 Infringement Allegations

Claim Element (from Independent Claim 1, as limited by Claim 2) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating prostate cancer in a subject The Proposed ANDA Product is indicated for treating prostate cancer, and its product label will instruct physicians and patients on this use. ¶66, ¶67 col. 31:15-16
said method comprising administering... a compound having the formula [Formula II]... The Proposed ANDA Product contains the active ingredient apalutamide, which is alleged to be a compound falling within the scope of Formula II. ¶65 col. 31:17-30
wherein A is sulfur and B is oxygen The chemical structure of apalutamide contains a thiohydantoin ring, which includes a sulfur atom and an oxygen atom double-bonded to the heterocyclic core. ¶65 col. 31:39
wherein R2 and R3 together with the carbon to which they are linked, form a cyclobutyl The chemical structure of apalutamide contains a spirocyclic cyclobutane ring attached to the core, which allegedly satisfies this limitation. ¶65 col. 32:3-5
  • Identified Points of Contention:
    • Scope Questions: While the infringement allegation appears to map the apalutamide structure directly onto the claim limitations, a potential dispute may arise over whether the patent's specification provides sufficient written description and enablement to support the full scope of the genus claimed in Formula II as it reads on the specific apalutamide compound.
    • Technical Questions: A central question for the method claim will be whether Defendants’ proposed product label will instruct users to perform the claimed method, thereby inducing infringement. This will depend on the final, FDA-approved label for the generic product.

U.S. Patent No. 9,388,159 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound having the formula [Formula II]... The Proposed ANDA Product contains apalutamide, a compound whose chemical structure is alleged to be a species within the genus defined by Formula II. ¶83 col. 32:1-25
wherein A is sulfur and B is oxygen Apalutamide's chemical structure includes a thiohydantoin core, which contains the required sulfur and oxygen atoms. ¶83 col. 32:33-34
wherein R2 and R3... together with the carbon to which they are linked, form a cycle... The spirocyclic cyclobutane ring in apalutamide's structure allegedly satisfies the requirement that R2 and R3 together form a cycle. ¶83 col. 32:41-47
Claim 17: A pharmaceutical composition... formulated in an oral dosage form The Proposed ANDA Product is described as an oral tablet containing apalutamide along with a pharmaceutically acceptable carrier, diluent, or adjuvant. ¶84 col. 34:42-44
  • Identified Points of Contention:
    • Scope Questions: As with the ’689 Patent, the primary question is one of definitional scope: does the specific structure of apalutamide fall within the genus claimed in Formula II?
    • Technical Questions: For the composition claims (12 and 17), the infringement analysis will depend on the specific formulation disclosed in the confidential ANDA. A question for the court may be whether the excipients and other components of the generic drug meet the definition of a "pharmaceutically acceptable carrier, diluent, or adjuvant" as understood in the context of the patent.

V. Key Claim Terms for Construction

  • The Term: "a compound having the formula..."
  • Context and Importance: This phrase introduces the chemical genus that is the subject of the compound claims in the ’159 Patent and the method claims in the ’689 Patent. The entire infringement dispute hinges on whether the accused compound, apalutamide, is a species encompassed by this claimed genus. Practitioners may focus on this term because validity challenges in pharmaceutical cases often allege that a broad genus claim lacks sufficient written description or enablement for a specific, commercially valuable species.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification provides broad definitions for the various "R" group substituents in Formula II, suggesting an intent to cover a wide class of compounds. For instance, R1 is defined to include a long list of possibilities, including "aryl, substituted aryl, alkyl, substituted alkyl," and more. (’159 Patent, col. 32:35-41). The patent also provides numerous specific examples of compounds falling within the formula, which may suggest the formula is intended to be read broadly. (’159 Patent, col. 11-14).
    • Evidence for a Narrower Interpretation: The specification highlights certain compounds, such as "A51" and "A52," in its examples and figures. (’159 Patent, col. 3:25-42; FIG. 1-6). A defendant could argue that these specific embodiments represent the core of the invention and that the genus should be construed more narrowly to cover only compounds that are structurally and functionally similar to these disclosed examples.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement of the ’689 method patent. Inducement is alleged based on Defendants' intent to sell the Proposed ANDA Product with a label that will instruct physicians and patients to administer it for treating prostate cancer. (Compl. ¶67, ¶76). Contributory infringement is alleged on the basis that the product is a material part of the claimed invention and is not a staple article of commerce suitable for substantial non-infringing use. (Compl. ¶68, ¶77).
  • Willful Infringement: While the complaint does not contain a formal count for "willful infringement," it alleges that Defendants have had "actual knowledge" of the Patents-in-Suit since at least April 2022 via their Orange Book listings and multiple notice letters sent by Defendants themselves. (Compl. ¶43, ¶60, ¶70, ¶87, ¶103). The prayer for relief also requests a finding that the case is "exceptional" under 35 U.S.C. § 285, a remedy often associated with findings of willfulness or litigation misconduct. (Compl. p. 21).

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

  • A central issue will be one of chemical scope and validity: does the accused compound apalutamide fall within the structural genus defined by the patents' claims, and if so, does the patent specification provide sufficient written description and enablement to support a claim scope that is broad enough to cover that specific compound?
  • A key evidentiary question will be one of formulation equivalence: for the asserted composition and tablet claims, does the precise formulation of the Proposed ANDA Product, as confidentially disclosed to the Plaintiffs, meet every limitation regarding dosage amounts and the nature of the "pharmaceutically acceptable carrier, diluent, or adjuvant" as set forth in the claims?