DCT

2:23-cv-01685

Aragon Pharma Inc v. Zydus Worldwide DMCC

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:23-cv-01685, D.N.J., 03/24/2023
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Zydus Pharmaceuticals (USA) Inc. is incorporated in and maintains a regular and established place of business in New Jersey. The foreign defendants are alleged to be subject to venue as foreign corporations.
  • Core Dispute: Plaintiffs allege that Defendants' submission of Abbreviated New Drug Application (ANDA) No. 217113 to the U.S. Food and Drug Administration, seeking approval to market a generic version of the prostate cancer drug Erleada® (apalutamide), constitutes an act of infringement of five U.S. patents.
  • Technical Context: The patents-in-suit relate to androgen receptor modulators, specifically the compound apalutamide and methods of its use, for treating androgen receptor-associated diseases like prostate cancer, particularly forms that become resistant to conventional hormone therapies.
  • Key Procedural History: The complaint notes that U.S. Reissued Patent No. RE49,353 is a reissue of U.S. Patent No. 10,052,314, which was previously asserted against the Defendants. Following the reissue, Plaintiffs requested the FDA withdraw the original patent and list the reissue patent in the FDA's "Orange Book" as covering Erleada®.

Case Timeline

Date Event
2006-03-27 Earliest Priority Date for ’507 and ’689 Patents
2007-03-27 Earliest Priority Date for ’159 and ’261 Patents
2013-05-21 Issue Date for U.S. Patent No. 8,445,507
2013-03-06 Earliest Priority Date for RE353 Patent
2014-08-12 Issue Date for U.S. Patent No. 8,802,689
2016-07-12 Issue Date for U.S. Patent No. 9,388,159
2018-06-05 Issue Date for U.S. Patent No. 9,987,261
2022-04-11 Date of Defendants' first Notice Letter regarding ANDA filing
2023-01-03 Issue Date for U.S. Reissued Patent No. RE49,353
2023-02-10 Date of Defendants' second Notice Letter regarding ANDA filing
2023-03-24 Complaint Filing Date

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

No probative visual evidence provided in complaint.

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

  • Patent Identification: U.S. Patent No. 8,445,507, issued May 21, 2013.

The Invention Explained

  • Problem Addressed: The patent background describes how advanced prostate cancer is typically treated with androgen deprivation therapy, but these treatments often fail as the cancer becomes "hormone refractory" (’507 Patent, col. 1:20-31). A cause for this resistance is the overexpression of the androgen receptor (AR), which can convert existing anti-androgen drugs from inhibitors (antagonists) into activators (agonists), thereby promoting cancer growth (’507 Patent, col. 1:32-49).
  • The Patented Solution: The invention provides a class of non-steroidal compounds, including thiohydantoins, that modulate the function of the androgen receptor (’507 Patent, Abstract). These compounds are designed to be better AR inhibitors that retain potent antagonistic activity and have minimal agonistic activity, even when the AR is overexpressed, thereby providing a treatment for both hormone-sensitive and hormone-refractory prostate cancer (’507 Patent, col. 2:5-13; col. 1:49-62).
  • Technical Importance: This technology provided a potential solution to the critical clinical problem of hormone-refractory prostate cancer by creating AR inhibitors that were less likely to be converted into agonists when the cancer evolved (’507 Patent, col. 2:5-13).

Key Claims at a Glance

  • The complaint asserts independent claims 1, 2, and 3, as well as dependent claims 11, 19, and 22 (Compl. ¶67).
  • Independent Claim 1 (Compound Claim):
    • A compound having a specified chemical core structure (Formula I).
    • Or a pharmaceutically acceptable salt thereof.
  • Independent Claim 2 (Composition Claim):
    • A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1.
    • And a pharmaceutically acceptable carrier, diluent, or adjuvant.
  • Independent Claim 3 (Method of Treatment Claim):
    • A method for treating a hyperproliferative disorder.
    • Comprising administering a compound of claim 1 or its salt to a subject in need of such treatment.
    • Thereby treating the hyperproliferative disorder.

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

  • Patent Identification: U.S. Patent No. 8,802,689, issued August 12, 2014.

The Invention Explained

  • Problem Addressed: The ’689 Patent, which shares a specification with the ’507 Patent, addresses the same technical problem of prostate cancer becoming resistant to conventional anti-androgen therapies due to overexpression of the androgen receptor (’689 Patent, col. 1:20-49).
  • The Patented Solution: The invention claims specific methods of using the non-steroidal AR modulators disclosed in the specification to treat prostate cancer. By administering these compounds, the method aims to inhibit AR activity even in a hormone-refractory state, thereby treating the disease (’689 Patent, col. 2:40-61).
  • Technical Importance: The claimed methods provide a specific therapeutic application for the novel compounds, targeting the unmet clinical need for effective treatments for advanced and hormone-refractory prostate cancer (’689 Patent, col. 2:5-13).

Key Claims at a Glance

  • The complaint asserts independent claim 2 (Compl. ¶86).
  • Independent Claim 2 (Method of Treatment Claim):
    • A method for treating prostate cancer in a subject.
    • The method comprises administering a specific compound, 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide, or a pharmaceutically acceptable salt thereof, to the subject.

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

  • Patent Identification: U.S. Patent No. 9,388,159, issued July 12, 2016.
  • Technology Synopsis: This patent discloses a specific genus of compounds characterized by a diazaspiroalkane core structure that function as androgen receptor modulators. The invention addresses the same problem of hormone-refractory prostate cancer by providing compounds designed to be potent AR antagonists with minimal agonist activity (’159 Patent, col. 2:1-15).
  • Asserted Claims: The complaint asserts independent claims 1 and 12 (Compl. ¶103).
  • Accused Features: The complaint alleges that the Proposed ANDA Product, which contains the compound apalutamide, infringes claims to the compound itself (claim 1) and pharmaceutical compositions containing it in an oral dosage form (claim 12) (Compl. ¶105-106).

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

  • Patent Identification: U.S. Patent No. 9,987,261, issued June 5, 2018.
  • Technology Synopsis: This patent, related to the ’159 Patent, also claims substituted diazaspiroalkanes as AR modulators for treating prostate cancer. The claims are directed to pharmaceutical compositions comprising these compounds within specific dosage ranges.
  • Asserted Claims: The complaint asserts independent claim 8 (Compl. ¶120).
  • Accused Features: The complaint alleges infringement based on the Proposed ANDA Product being a tablet that comprises apalutamide in a dosage range of 0.0005 to 500 mg, along with a pharmaceutically acceptable carrier (Compl. ¶122).

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

  • Patent Identification: U.S. Reissued Patent No. RE49,353, issued January 3, 2023.
  • Technology Synopsis: This reissue patent claims methods of treating a specific subtype of prostate cancer (non-metastatic castration-resistant) by administering an anti-androgen, specifically identified as apalutamide, at a particular daily dose, in combination with a gonadotropin releasing hormone (GnRH) agonist.
  • Asserted Claims: The complaint asserts independent claims 1 and 19 (Compl. ¶136).
  • Accused Features: Infringement is alleged because physicians and patients will purportedly practice the claimed method by administering the Proposed ANDA Product (containing apalutamide) at a dose of about 240 mg per day to treat non-metastatic castration-resistant prostate cancer, in conjunction with a GnRH agonist (Compl. ¶137).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is Defendants' "Proposed ANDA Product," identified as a generic version of the drug Erleada® (Compl. ¶2). The product is described as "apalutamide tablets, 60 mg" (Compl. ¶57, ¶61).
  • Functionality and Market Context: The Proposed ANDA Product contains the active pharmaceutical ingredient (API) apalutamide (Compl. ¶49, ¶68). Apalutamide is an androgen receptor modulator indicated for the treatment of non-metastatic castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer (Compl. ¶48). By filing an ANDA, Defendants seek FDA approval to market this product as a generic equivalent to the brand-name drug Erleada® before the expiration of the patents-in-suit (Compl. ¶2, ¶57).

IV. Analysis of Infringement Allegations

’507 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound having the formula [Formula I] or a pharmaceutically acceptable salt thereof The Proposed ANDA Product is alleged to contain the compound apalutamide, which Plaintiffs allege falls within the scope of the claimed formula. ¶69 col. 12:15-40

’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, The Proposed ANDA Product is intended for and will be used to treat prostate cancer in patients. ¶88 col. 1:14-17
said method comprising administering... the compound 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide The Proposed ANDA Product contains apalutamide, which is the compound specified in the claim, and will be administered to patients. ¶87, ¶88 col. 12:46-55
  • Identified Points of Contention:
    • Scope Questions: For the compound and composition claims (e.g., in the ’507, ’159, and ’261 Patents), a primary question is whether the apalutamide in Defendants' product falls within the scope of the claimed chemical structures and formulations. The complaint’s direct identification of the API as "apalutamide" suggests this may not be a central point of dispute, but it remains a formal element of proof for the Plaintiffs (Compl. ¶69, ¶105, ¶122).
    • Technical Questions: For the method of treatment claims (e.g., in the ’689 and RE353 Patents), a key question is one of induced infringement: does the complaint provide sufficient factual basis to suggest that the proposed label for Defendants’ generic product will instruct or encourage physicians and patients to perform the specific steps of the claimed methods? The complaint alleges the product will be "specifically labeled for use in practicing the claims" (Compl. ¶90, ¶139).

V. Key Claim Terms for Construction

  • The Term: "therapeutically effective amount" (from ’507 Patent, claim 2)

  • Context and Importance: This term is central to the infringement analysis of the composition claims. The definition will determine whether the 60 mg dosage of the Proposed ANDA Product constitutes an infringing "amount." Practitioners may focus on this term because its scope could either broadly cover any effective dose or be limited to specific ranges disclosed in the patent.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification provides a very broad dosage range, stating that a compound can be administered "at a dosage in the range of from about 1 mg per kg body weight per day to about 50 mg per kg body weight per day," which suggests flexibility in what constitutes an effective amount (’507 Patent, col. 13:45-49).
    • Evidence for a Narrower Interpretation: While not providing a restrictive definition, the specification's discussion of specific in vivo assays using a 10 mg/kg dose could be cited in an attempt to link the term to dosages proven effective in the patent's own examples (’507 Patent, col. 24:18-20).

  • The Term: "treating" (from ’689 Patent, claim 2)

  • Context and Importance: The construction of "treating" is critical for the method claims, as it defines the required outcome of the administration. Whether "treating" requires a complete cure, symptom management, or merely slowing disease progression will directly impact the scope of infringement.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent frequently uses the phrase "preventing or treating," suggesting "treating" is part of a broad continuum of therapeutic interventions (’689 Patent, col. 13:37-38). The patent's goal of slowing the progression of hormone-refractory cancer also supports a broad reading that does not require a complete cure (’689 Patent, col. 1:49-55).
    • Evidence for a Narrower Interpretation: A defendant could argue that the term should be limited by the examples in the specification, which demonstrate specific outcomes like retarding tumor growth in animal models, potentially narrowing the term to actions that produce a measurable anti-tumor effect rather than just palliative care (’689 Patent, col. 24:18-24).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement for all asserted method claims, stating that Defendants will actively induce infringement by labeling the Proposed ANDA Product for use in practicing the claimed methods (Compl. ¶72, ¶89, ¶138). The complaint also pleads contributory infringement, alleging the product is a material part of the claimed inventions and is not a staple article of commerce suitable for substantial non-infringing use (Compl. ¶73, ¶90, ¶107, ¶123, ¶139).
  • Willful Infringement: The complaint does not explicitly use the word "willful." However, it alleges that Defendants have "actual knowledge" of each patent-in-suit, citing the notice letters sent as part of the ANDA process (Compl. ¶75, ¶92, ¶109, ¶125, ¶141). These allegations of pre-suit knowledge form the factual basis for a potential claim of willfulness and the request for an exceptional case finding in the prayer for relief.

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

  • A core issue will be one of induced infringement: will the evidence, particularly the proposed product labeling for Defendants' generic apalutamide, be sufficient to establish that Defendants will actively encourage and instruct physicians and patients to administer the drug in a manner that directly infringes the specific methods of treatment claimed in the ’689 and RE353 patents?
  • Given the Hatch-Waxman context, a central question will be the validity of the asserted claims. The case will likely focus on whether the patents-in-suit can withstand Defendants' anticipated challenges that the claims are invalid as obvious over or anticipated by prior art, or fail to meet statutory requirements for written description and enablement.
  • A key procedural question will concern the enforceability and scope of the reissue patent: can Plaintiffs demonstrate that the RE353 Patent corrected a genuine "error" in the original ’314 patent without impermissibly recapturing subject matter that was surrendered during the original prosecution, a common and complex issue in litigation involving reissue patents?