DCT

3:24-cv-08217

Astellas Pharma Inc v. Qilu Pharmaceutical Hainan Co Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:24-cv-08217, D.N.J., 08/01/2024
  • Venue Allegations: Plaintiff alleges venue is proper because Defendant Qilu Ltd. is a foreign corporation not residing in any U.S. district, and Defendant Qilu Inc. has a regular and established place of business in the District of New Jersey.
  • Core Dispute: Plaintiffs allege that Defendants' filing of an Abbreviated New Drug Application (ANDA) seeking to market generic versions of the prostate cancer drug Xtandi® (enzalutamide) constitutes an act of infringement of two U.S. patents.
  • Technical Context: The patents relate to the chemical compound enzalutamide, an androgen receptor inhibitor, and pharmaceutical formulations designed to improve its delivery and bioavailability for treating prostate cancer.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiffs' receipt of a "Notice Letter" from Qilu, dated June 24, 2024, which advised that Qilu had filed ANDA No. 219140 containing a Paragraph IV certification. The certification alleges that certain claims of the patents-in-suit are invalid, unenforceable, and/or not infringed. Both patents are listed in the FDA’s "Orange Book" for Xtandi® tablets.

Case Timeline

Date Event
2005-05-13 ’517 Patent Priority Date
2010-05-04 ’517 Patent Issue Date
2012-09-11 ’689 Patent Priority Date
2020-08-04 FDA approved Xtandi® 40 mg and 80 mg tablets
2023-12-12 ’689 Patent Issue Date
2024-06-24 Date of Qilu Notice Letter to Plaintiffs
2024-08-01 Complaint Filing Date

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

U.S. Patent No. 7,709,517 - "Diarylhydantoin Compounds"

The Invention Explained

  • Problem Addressed: The patent describes a critical challenge in prostate cancer treatment where the disease becomes "hormone refractory" (Compl. ¶14; ’517 Patent, col. 1:45-53). In this advanced stage, the androgen receptor (AR) is often overexpressed, which can cause existing anti-androgen drugs, like bicalutamide, to paradoxically act as agonists, thereby promoting rather than inhibiting cancer growth (’517 Patent, col. 2:40-53).
  • The Patented Solution: The invention provides a new class of diarylhydantoin compounds that are potent AR antagonists with minimal agonistic activity, even in the presence of overexpressed AR (’517 Patent, Abstract). These compounds, including the specific compound enzalutamide, are designed to inhibit hormone refractory prostate cancer growth where prior treatments have failed (’517 Patent, col. 2:50-58).
  • Technical Importance: This technology offered a new therapeutic mechanism for treating late-stage prostate cancer that had developed resistance to standard androgen deprivation therapies.

Key Claims at a Glance

  • The complaint asserts infringement of at least Claim 1 of the ’517 Patent (Compl. ¶54).
  • Independent Claim 1 recites:
    • A compound selected from a Markush group of specific chemical structures.
    • One of the enumerated compounds in this group is enzalutamide (4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl}-2-fluoro-N-methylbenzamide) (’517 Patent, col. 115:1-116:15).

U.S. Patent No. 11,839,689 - "Formulations of Enzalutamide"

The Invention Explained

  • Problem Addressed: While the patent does not explicitly detail a problem in its background, pharmaceutical formulation patents for compounds like enzalutamide typically address challenges of low aqueous solubility, which can lead to poor or inconsistent absorption and bioavailability when administered orally (’689 Patent, col. 2:20-24).
  • The Patented Solution: The invention is a pharmaceutical composition comprising a "solid dispersion" of enzalutamide in its amorphous (non-crystalline) state with a specific "concentration-enhancing polymer," hydroxypropyl methylcellulose acetate succinate (HPMCAS) (’689 Patent, Abstract). This formulation is designed to improve the solubility and absorption of enzalutamide, which can enhance its oral bioavailability and provide for more stable and effective dosing (’689 Patent, col. 2:20-35).
  • Technical Importance: Amorphous solid dispersions represent a key formulation strategy for improving the delivery of poorly water-soluble drugs, enabling them to be administered effectively in a solid oral dosage form like a tablet.

Key Claims at a Glance

  • The complaint asserts infringement of at least one claim, including Claim 1 of the ’689 Patent (Compl. ¶62, ¶67).
  • Independent Claim 1 recites:
    • A pharmaceutical composition
    • comprising a solid dispersion
    • consisting essentially of amorphous enzalutamide and hydroxypropyl methylcellulose acetate succinate (“HPMCAS”).

III. The Accused Instrumentality

Product Identification

  • The accused products are Qilu’s generic enzalutamide tablets in 40 mg and 80 mg dosages, for which Qilu has filed ANDA No. 219140 with the FDA (Compl. ¶39).

Functionality and Market Context

  • The complaint alleges that Qilu's generic products are versions of Plaintiffs' Xtandi® tablets and seek approval for the same indications, including the treatment of castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer (Compl. ¶41). The complaint describes enzalutamide, the active ingredient, using its chemical name and structure. The complaint includes a diagram of the chemical structure of enzalutamide (Compl. ¶27).

IV. Analysis of Infringement Allegations

’517 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound selected from the group consisting of... [a list of compounds including enzalutamide] Qilu's Generic Products will contain the compound enzalutamide. ¶54 col. 35:55-67
  • Identified Points of Contention:
    • Technical Questions: The primary factual question will be whether Qilu's ANDA product contains the specific diarylhydantoin compound known as enzalutamide, as claimed. Given the nature of a generic drug application, which seeks to prove bioequivalence, this is a central allegation.
    • Scope Questions: While infringement of this compound claim appears to be a direct factual question, disputes may arise over validity, which the complaint notes Qilu has raised in its Paragraph IV certification (Compl. ¶42).

’689 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
a pharmaceutical composition Qilu's Generic Products will contain a pharmaceutical composition. ¶67 col. 3:5-7
comprising a solid dispersion The accused composition comprises a solid dispersion. ¶67 col. 4:47-53
consisting essentially of amorphous enzalutamide and hydroxypropyl methylcellulose acetate succinate (“HPMCAS”) The solid dispersion consists essentially of amorphous enzalutamide and HPMCAS. The complaint alleges Qilu copied the claimed formulation. ¶65, ¶67 col. 1:55-65
  • Identified Points of Contention:
    • Technical Questions: A key factual question for the court will be whether the enzalutamide in Qilu’s product is in the "amorphous" state and combined with HPMCAS to form a "solid dispersion," as those terms are understood in the patent. The complaint alleges that Qilu copied the Xtandi® formulation, which is covered by the patent (Compl. ¶63, ¶65).
    • Scope Questions: The transitional phrase "consisting essentially of" will be a central point of claim construction. The analysis will raise the question of whether any additional excipients in Qilu's formulation materially alter the basic and novel characteristics of the claimed invention (i.e., the enhanced solubility and bioavailability provided by the specific two-component dispersion).

V. Key Claim Terms for Construction

  • The Term: "consisting essentially of" (’689 Patent, Claim 1)
  • Context and Importance: This transitional phrase defines the scope of the claimed two-part "solid dispersion." Its construction is critical because Qilu's generic formulation may contain additional ingredients (excipients) not listed in the claim. The infringement analysis will depend on whether these unlisted ingredients are permissible under this phrase or if their presence places the accused product outside the claim's scope.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent does not appear to provide an explicit special definition for this term. A party could argue that it should be given its ordinary legal meaning, which permits the presence of unlisted components so long as they do not "materially affect the basic and novel characteristics of the invention" (’689 Patent, col. 4:1-5), which are described as improved solubility and absorption.
    • Evidence for a Narrower Interpretation: A party could argue that the patent’s focus on the specific combination of amorphous enzalutamide and HPMCAS as the solution for bioavailability suggests that the "basic and novel characteristics" are derived solely from this two-part system (’689 Patent, col. 2:20-29). Therefore, any additional component that affects formulation stability, dissolution rate, or absorption could be argued to be a "material" alteration.

VI. Other Allegations

  • Indirect Infringement: The complaint does not plead separate counts for indirect infringement. However, it alleges facts that could support such a claim, stating that Qilu "knows or should know" that its future commercial activities will infringe (Compl. ¶57, ¶70). The primary allegation is the statutory act of infringement under 35 U.S.C. § 271(e)(2)(A) based on the ANDA filing (Compl. ¶50, ¶61).
  • Willful Infringement: The complaint alleges that Qilu had knowledge of the patents-in-suit, at the latest, by virtue of their listing in the FDA's Orange Book and Qilu’s reference to them in its Notice Letter (Compl. ¶55, ¶69). Plaintiffs further allege that Qilu's non-infringement and invalidity positions are "devoid of an objective good faith basis in either the facts or the law," and request a finding that the case is "exceptional" (Compl. ¶58, ¶71).

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

  • A central issue for the ’689 patent will be one of claim scope: can the phrase "consisting essentially of amorphous enzalutamide and hydroxypropyl methylcellulose acetate succinate" be construed to read on Qilu's proposed generic formulation, which may contain other excipients? The outcome will depend on whether those additional components are found to materially affect the claimed invention's properties.
  • A key legal and factual question will be the viability of Defendants' invalidity defenses. The complaint alleges Qilu's Paragraph IV certification foreshadows such defenses but provides no detail, which Plaintiffs characterize as an admission of validity. The ultimate resolution of the case will likely depend on whether Qilu can present sufficient evidence to invalidate the asserted claims of either the compound patent (’517) or the formulation patent (’689).