DCT

2:25-cv-11924

Aragon Pharma Inc v. Hetero Labs Ltd Unit V

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:25-cv-11924, D.N.J., 06/18/2025
  • Venue Allegations: Plaintiffs allege venue is proper in the District of New Jersey because Hetero Labs is a foreign corporation and Hetero USA has a regular and established place of business in Piscataway, New Jersey.
  • Core Dispute: Plaintiffs allege that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the prostate cancer drug Erleada® (apalutamide) constitutes an act of infringement of ten U.S. patents covering the compound, its crystalline forms, and methods of use.
  • Technical Context: The dispute concerns second-generation anti-androgen modulators used to treat castration-resistant prostate cancer, a field where therapies aim to overcome resistance to earlier hormonal treatments.
  • Key Procedural History: The complaint notes prior patent litigation between the parties in the same district concerning Defendants' proposed generic version of a 60 mg tablet of Erleada®, which involved several of the same patents-in-suit. This history may be relevant to Defendants’ knowledge of the patents for the purposes of indirect and willful infringement allegations.

Case Timeline

Date Event
2006-03-27 Earliest Priority Date for ’507, ’689, ’159, and ’261 Patents
2012-06-07 Earliest Priority Date for ’663 Patent
2012-09-26 Earliest Priority Date for ’054, RE353, and ’888 Patents
2013-05-21 U.S. Patent No. 8,445,507 Issues
2014-08-12 U.S. Patent No. 8,802,689 Issues
2016-07-12 U.S. Patent No. 9,388,159 Issues
2016-11-01 U.S. Patent No. 9,481,663 Issues
2017-10-16 Earliest Priority Date for ’508 Patent
2018-02-06 U.S. Patent No. 9,884,054 Issues
2018-06-05 U.S. Patent No. 9,987,261 Issues
2019-01-30 Earliest Priority Date for ’952 Patent
2020-07-07 U.S. Patent No. 10,702,508 Issues
2020-12-01 U.S. Patent No. 10,849,888 Issues
2023-01-03 U.S. Patent No. RE49,353 Issues
2024-04-23 U.S. Patent No. 11,963,952 Issues
2025-03-20 Defendants allegedly submit ANDA No. 220525 to the FDA
2025-05-08 Defendants allegedly send Paragraph IV Notice Letter to Plaintiffs
2025-06-18 Complaint filed

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

U.S. Patent No. 8,445,507 - “Androgen Receptor Modulator for the Treatment of Prostate Cancer and Androgen Receptor-Associated Diseases”

Issued May 21, 2013

The Invention Explained

  • Problem Addressed: The patent describes a critical problem in prostate cancer treatment where the cancer becomes "hormone refractory." In this stage, the Androgen Receptor (AR) is often overexpressed, which causes first-generation anti-androgen drugs (like bicalutamide) to paradoxically start acting as agonists, stimulating rather than inhibiting cancer growth (ʼ507 Patent, col. 1:21-50).
  • The Patented Solution: The invention discloses a new class of thiohydantoin compounds that function as potent AR antagonists with minimal agonist activity. These compounds are designed to effectively inhibit AR signaling even when the receptor is overexpressed, thereby overcoming the resistance mechanism that limits older therapies (’507 Patent, col. 2:5-13; Abstract).
  • Technical Importance: This approach provided a second-generation anti-androgen therapy intended to be effective in patients whose prostate cancer had progressed despite castration and treatment with first-generation anti-androgens (’507 Patent, col. 1:43-50).

Key Claims at a Glance

  • The complaint asserts independent claims 1, 3, 19, and 22 (Compl. ¶ 60).
  • Claim 1: A compound according to a specified chemical genus (Formula II).
  • Claim 3: A method of treating a hyperproliferative disorder in a subject, comprising administering a compound of Formula II.
  • Claim 19: A method of treating prostate cancer in a subject, comprising administering the specific compound apalutamide.
  • Claim 22: The specific compound 4-[7-(6-Cyano-5-trifluoromethyl-pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methyl-benzamide (apalutamide).
  • The complaint also asserts dependent claims 2 and 11 (Compl. ¶ 60).

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

Issued August 12, 2014

The Invention Explained

  • Problem Addressed: As a continuation of the ʼ507 Patent, this patent addresses the same technical problem of hormone-refractory prostate cancer, where existing anti-androgens fail due to Androgen Receptor overexpression and a switch from antagonistic to agonistic activity (’689 Patent, col. 1:24-52).
  • The Patented Solution: The patent claims methods of using the previously disclosed class of thiohydantoin compounds to treat prostate cancer. By administering these compounds, the invention provides a way to inhibit AR activity in patients whose cancer has become resistant to other therapies (’689 Patent, Abstract; col. 2:6-14).
  • Technical Importance: This patent secures protection not just for the chemical compounds themselves, but for the specific methods of using them to treat prostate cancer, a key aspect of pharmaceutical patenting (’689 Patent, col. 1:45-52).

Key Claims at a Glance

  • The complaint asserts at least claim 2 (Compl. ¶ 79). Claim 1 is the independent claim from which claim 2 depends.
  • Claim 1: A compound according to a specified chemical genus (Formula II).
  • Claim 2: A method for treating prostate cancer in a subject, comprising administering a compound of claim 1 to a subject in need of such treatment.

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

Issued July 12, 2016

Technology Synopsis

  • Belonging to the same family as the lead patents, the ’159 Patent claims a specific genus of diazaspiroalkane compounds that act as androgen receptor modulators. The technology addresses the need for potent AR antagonists to treat hormone-refractory prostate cancer (Compl. ¶ 42; ’159 Patent, col. 1:17-50).

Asserted Claims

  • Claims 1, 12, and 17 are asserted (Compl. ¶ 96). Claim 1 is an independent claim to a genus of compounds.

Accused Features

  • The complaint alleges that the apalutamide contained in the Proposed ANDA Product falls within the scope of the claims (Compl. ¶¶ 97-98).

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

Issued June 5, 2018

Technology Synopsis

  • This patent, also from the same family, claims pharmaceutical compositions comprising the diazaspiroalkane compounds. It specifically claims tablet formulations containing a defined amount of the active compound and a pharmaceutically acceptable carrier, intended for treating androgen receptor-associated diseases (Compl. ¶ 43; ’261 Patent, Abstract).

Asserted Claims

  • Claims 10 and 12 are asserted (Compl. ¶ 113). Claim 10 is an independent claim.

Accused Features

  • The infringement allegation targets the tablet formulation of the Proposed ANDA Product, which is alleged to comprise apalutamide in a claimed dosage range along with a carrier (Compl. ¶ 115).

U.S. Patent No. 9,481,663 - “Crystalline Forms of an Androgen Receptor Modulator”

Issued November 1, 2016

Technology Synopsis

  • This patent shifts focus from the chemical compound itself to its solid-state form. It claims specific crystalline forms of apalutamide, identified as "Form B," characterized by specific X-Ray powder diffraction (XRPD) patterns. Different crystalline forms (polymorphs) of a drug can have different properties affecting manufacturing, stability, and bioavailability (Compl. ¶ 44; ’663 Patent, Abstract).

Asserted Claims

  • Claims 1, 13, and 17 are asserted (Compl. ¶ 129). Claim 1 is an independent claim to crystalline Form B.

Accused Features

  • The complaint alleges that the drug substance in the Proposed ANDA Product contains crystalline Form B of apalutamide, identified by its characteristic XRPD peaks (Compl. ¶¶ 130-131).

U.S. Patent No. 9,884,054 - “Anti-androgens for the Treatment of Non-metastatic Castrate-resistant Prostate Cancer”

Issued February 6, 2018

Technology Synopsis

  • This patent claims methods of treating a specific patient population: those with non-metastatic castration-resistant prostate cancer. The claimed method involves administering apalutamide orally at a specific dose of about 240 mg per day (Compl. ¶ 45; ’054 Patent, Abstract).

Asserted Claims

  • Claims 6 and 15 are asserted (Compl. ¶ 148). Claim 6 is an independent claim.

Accused Features

  • The complaint alleges that the Proposed ANDA Product, being a 240 mg tablet, will be used by physicians and patients according to its label to practice the claimed method of treatment (Compl. ¶ 149).

U.S. Patent No. RE49,353 - “Anti-androgens for the Treatment of Non-metastatic Castrate-resistant Prostate Cancer”

Issued January 3, 2023

Technology Synopsis

  • As a reissue of the ’054 Patent, this patent covers a method of treating non-metastatic castration-resistant prostate cancer with apalutamide, further specifying that the treatment includes co-administration of a gonadotropin releasing hormone (GnRH) agonist (Compl. ¶ 46; RE353 Patent, Abstract).

Asserted Claims

  • Claims 1 and 19 are asserted (Compl. ¶ 163). Claim 1 is an independent claim.

Accused Features

  • The complaint alleges that the proposed use of the generic product will infringe because treatment guidelines for apalutamide require concurrent androgen deprivation therapy, which often involves a GnRH agonist (Compl. ¶ 164).

U.S. Patent No. 10,849,888 - “Anti-androgens for the Treatment of Non-metastatic Castrate-resistant Prostate Cancer”

Issued December 1, 2020

Technology Synopsis

  • This patent claims another specific method of treatment for non-metastatic castration-resistant prostate cancer. The claimed method involves administering apalutamide at a dose of about 240 mg per day where the treatment method further comprises orchiectomy (surgical castration) (Compl. ¶ 47; ’888 Patent, Abstract).

Asserted Claims

  • Claims 1 and 8 are asserted (Compl. ¶ 178). Claim 1 is an independent claim.

Accused Features

  • Infringement is alleged on the basis that orchiectomy is an alternative form of androgen deprivation therapy used in conjunction with apalutamide treatment (Compl. ¶ 179).

U.S. Patent No. 10,702,508 - “Anti-androgens for the Treatment of Non-metastatic Castrate-resistant Prostate Cancer”

Issued July 7, 2020

Technology Synopsis

  • This patent claims a method of improving a specific clinical outcome—metastasis-free survival—in male humans with nonmetastatic castration-resistant prostate cancer. The method comprises administering an approved drug product comprising apalutamide in combination with androgen deprivation therapy, wherein the median metastasis-free survival is about 40.5 months (Compl. ¶ 48; ’508 Patent, Abstract).

Asserted Claims

  • Claims 1, 2, 5, and 7 are asserted (Compl. ¶ 193). Claim 1 is an independent claim.

Accused Features

  • The complaint alleges that the proposed label for the generic product will instruct its use in a manner that improves metastasis-free survival, thereby inducing infringement of the claimed method (Compl. ¶¶ 194, 196).

U.S. Patent No. 11,963,952 - “Anti-Androgens for the Treatment of Metastatic Castration-Sensitive Prostate Cancer”

Issued April 23, 2024

Technology Synopsis

  • This patent claims a method for treating metastatic castration-sensitive prostate cancer by administering apalutamide. A key feature of the claimed method is a dose reduction protocol: the dosage is decreased to 180 mg/day or 120 mg/day if the patient experiences Grade 3 or greater toxicity (Compl. ¶ 49; ’952 Patent, Abstract).

Asserted Claims

  • Claims 6, 7, and 8 are asserted (Compl. ¶ 210). Claim 6 is an independent claim.

Accused Features

  • The complaint alleges that the proposed label for the generic product will include instructions for dose reduction in response to toxicity, thereby inducing physicians to practice the claimed method (Compl. ¶¶ 211-212).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendants’ "Proposed ANDA Product," identified as a generic version of Erleada® to be marketed as "Apalutamide Tablets; Oral, 240 mg" (Compl. ¶¶ 2, 52).

Functionality and Market Context

  • The Proposed ANDA Product contains the active pharmaceutical ingredient apalutamide, a second-generation anti-androgen (Compl. ¶¶ 38-39). The complaint provides a chemical structure diagram of apalutamide, which is accused of infringing the compound patents (Compl. ¶ 80).
  • It is intended for the treatment of patients with specific forms of prostate cancer, such as non-metastatic castration-resistant prostate cancer (Compl. ¶ 38). The complaint alleges that the Defendants' submission of ANDA No. 220525 to the FDA is an act of infringement under 35 U.S.C. § 271(e)(2), as it seeks approval to market this generic product before the expiration of the patents-in-suit (Compl. ¶ 2).

IV. Analysis of Infringement Allegations

8,445,507 Patent Infringement Allegations

Claim Element (from Independent Claim 22) Alleged Infringing Functionality Complaint Citation Patent Citation
The compound 4-[7-(6-Cyano-5-trifluoromethyl-pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methyl-benzamide. The complaint alleges that the Proposed ANDA Product contains the compound apalutamide, which is the chemical entity recited in the claim and depicted in a chemical structure diagram. (Compl. ¶ 80) ¶62, ¶80 col. 31:4-9

Identified Points of Contention

  • Scope Questions: For a compound claim like claim 22, the primary dispute is typically not one of literal infringement scope, as the generic product is formulated to be bioequivalent to the branded drug and contains the same active ingredient. The central dispute will likely concern the validity of the patent claim itself.
  • Technical Questions: A potential technical question, though more relevant to validity than infringement, could be whether the synthesis process used by the Defendants results in the exact compound claimed, free from impurities or isomers that might place it outside the claim's scope, but this is not a focus of the complaint's infringement theory.

8,802,689 Patent Infringement Allegations

Claim Element (from Independent Claim 2) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating prostate cancer in a subject, comprising administering a compound of claim 1, or a pharmaceutically acceptable salt thereof, to a subject in need of such treatment... The complaint alleges that upon FDA approval, Defendants will induce infringement by selling the Proposed ANDA Product with a label that instructs physicians and patients to administer the apalutamide-containing tablets for the treatment of prostate cancer. (Compl. ¶ 81, ¶ 83) ¶81-83 col. 32:4-10

Identified Points of Contention

  • Scope Questions: A central issue for this method claim will be one of inducement. The question for the court will be whether the language of the Defendants' final, FDA-approved label will specifically instruct or encourage physicians and patients to use the generic drug in a manner that meets all the limitations of the claimed method.
  • Technical Questions: An evidentiary question will be what facts demonstrate Defendants' specific intent to induce infringement. Plaintiffs point to the ANDA filing itself and the proposed labeling as evidence of this intent (Compl. ¶¶ 82-83).

V. Key Claim Terms for Construction

The Term: "therapeutically effective amount"

(from, e.g., ʼ507 Patent, claim 2)

  • Context and Importance: This term is central to both composition and method claims in pharmaceutical patents. Its definition determines the dosage required to infringe. Practitioners may focus on this term because its meaning is often tied to achieving a specific clinical outcome, which can be a point of factual dispute.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification does not provide a single numeric definition, stating that the "actual amount required for treatment ... will depend on the judgment of the practitioner" (’507 Patent, col. 28:5-10), which may support a broader construction covering any amount that a physician deems effective.
    • Evidence for a Narrower Interpretation: The specification provides exemplary dosages, such as "about 10 mg per kg body weight per day" (’507 Patent, col. 27:4-7). A party might argue that these specific examples limit the scope of what constitutes a "therapeutically effective amount."

The Term: "hyperproliferative disorder"

(from, e.g., ʼ507 Patent, claim 3)

  • Context and Importance: The scope of this term defines the types of diseases covered by the method of treatment claim. While the complaint equates this with prostate cancer, a defendant could challenge the claim's validity by arguing the term is indefinite or overly broad.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent lists "prostate cancer" as an example of a hyperproliferative disorder, but the use of "for example" suggests the term is not limited to just prostate cancer (’507 Patent, col. 27:32-34).
    • Evidence for a Narrower Interpretation: The patent's title, abstract, and background are heavily focused on prostate cancer. A party could argue that the context of the invention limits the scope of "hyperproliferative disorder" to androgen receptor-associated cancers, particularly prostate cancer (’507 Patent, Title; Abstract).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for the method claims. Inducement is primarily based on allegations that Defendants will sell the Proposed ANDA Product with instructions and labeling that will encourage and direct physicians and patients to perform the patented methods of treatment (e.g., Compl. ¶ 65, ¶ 82). Contributory infringement is based on allegations that the product is not a staple article of commerce and is specifically designed for an infringing use (e.g., Compl. ¶ 66, ¶ 83).
  • Willful Infringement: The complaint does not contain a separate count for willful infringement, but it lays a factual basis for it. It alleges that Defendants have had "actual knowledge of each of the Patents-In-Suit" based on both the Paragraph IV notice letter and prior litigation involving many of the same patents, which may support an allegation of post-suit willfulness if infringement is found (Compl. ¶ 56, ¶ 68).

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

  • A central issue will be one of patent validity: With ten patents covering the same drug, including its chemical structure, crystalline forms, and various methods of use and dosing regimens, Defendants will likely mount a substantial challenge to the validity of the claims on grounds such as obviousness, obviousness-type double patenting, anticipation, and lack of written description or enablement.
  • A key question of inducement will apply to the numerous method-of-treatment patents: Will the final, FDA-approved label for Defendants' generic apalutamide product contain specific instructions that direct physicians and patients to perform all the steps of the claimed methods, particularly those related to specific patient populations (e.g., non-metastatic), dosages (e.g., 240 mg/day), and combination therapies (e.g., with a GnRH agonist)? The outcome may depend on the precise language of the final label.