DCT

3:24-cv-09403

Astellas Pharma Inc v. Haimen Pharma Inc

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:24-cv-09403, D.N.J., 09/24/2024
  • Venue Allegations: Venue is alleged to be proper because Defendants are foreign corporations not residing in any U.S. judicial district and because the alleged acts of infringement will cause foreseeable harm and injury to Plaintiffs within New Jersey.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to market generic versions of the prostate cancer drug Xtandi® (enzalutamide) constitutes an act of infringement of two U.S. patents covering the active pharmaceutical ingredient and its tablet formulation.
  • Technical Context: The dispute involves a second-generation anti-androgen compound and an advanced pharmaceutical formulation technology known as an amorphous solid dispersion, which is used to improve the oral bioavailability of poorly soluble drugs.
  • Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act following Plaintiffs' receipt of a Notice Letter dated August 15, 2024, in which Defendants provided a Paragraph IV certification against the patents-in-suit. The asserted patents are listed in the U.S. Food and Drug Administration's "Orange Book" for Xtandi® tablets. The complaint alleges that Defendants' Notice Letter did not assert non-infringement or invalidity of the '517 patent, nor invalidity of the '689 patent.

Case Timeline

Date Event
2005-05-13 U.S. Patent No. 7,709,517 Priority Date
2010-05-04 U.S. Patent No. 7,709,517 Issued
2012-09-11 U.S. Patent No. 11,839,689 Priority Date
2020-08-04 FDA approved NDA for Xtandi® tablets
2023-11-16 FDA approved expanded indication for Xtandi® tablets
2023-12-12 U.S. Patent No. 11,839,689 Issued
2024-08-15 Defendants' Notice Letter sent to Plaintiffs
2024-09-24 Complaint Filed

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

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

Patent Identification

  • U.S. Patent No. 7,709,517, "Diarylhydantoin Compounds," issued May 4, 2010.

The Invention Explained

  • Problem Addressed: The patent addresses the challenge of "hormone refractory prostate cancer," a stage of the disease where cancer progresses despite androgen deprivation therapies like castration and first-generation anti-androgens (e.g., bicalutamide) (’517 Patent, col. 1:21-41). A key mechanism for this resistance is the overexpression of the androgen receptor (AR), which can convert traditional AR inhibitors from antagonists (blockers) into agonists (activators), thereby promoting rather than inhibiting cancer growth (’517 Patent, col. 2:37-50).
  • The Patented Solution: The patent discloses a class of diarylhydantoin compounds designed to be potent AR antagonists with minimal agonistic activity, even in cancer cells that overexpress the AR (’517 Patent, col. 2:51-59). The claimed chemical structures, including the compound enzalutamide, are designed to bind to the AR and inhibit its function without being converted into an agonist, thus providing a way to treat hormone-refractory prostate cancer (’517 Patent, col. 34:1-13).
  • Technical Importance: This technology provided a second-generation anti-androgen therapy specifically engineered to overcome a known clinical mechanism of resistance to earlier treatments.

Key Claims at a Glance

  • The complaint asserts infringement of at least independent Claim 1 (Compl. ¶54).
  • Claim 1 claims a compound selected from a Markush group of specifically enumerated chemical structures. The key element relevant to this dispute is the inclusion of the compound enzalutamide, which is depicted as follows:
    • A compound having the chemical structure for 4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl}-2-fluoro-N-methylbenzamide (enzalutamide).

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

Patent Identification

  • U.S. Patent No. 11,839,689, "Formulations of Enzalutamide," issued December 12, 2023.

The Invention Explained

  • Problem Addressed: The patent notes that enzalutamide is a poorly soluble drug, which presents challenges for oral administration, potentially leading to low or variable bioavailability (’689 Patent, col. 2:19-23).
  • The Patented Solution: The invention is a pharmaceutical formulation that improves enzalutamide's solubility and absorption by creating a "solid dispersion" (’689 Patent, Abstract). This is achieved by dissolving enzalutamide with a specific concentration-enhancing polymer—hydroxypropyl methylcellulose acetate succinate (HPMCAS)—and rapidly removing the solvent (e.g., via spray-drying) to trap the drug in a stable, high-energy "amorphous" (non-crystalline) state (’689 Patent, col. 21:46-51, Fig. 1). This amorphous form dissolves more readily in the body than the crystalline form, enhancing absorption (’689 Patent, col. 21:46-54).
  • Technical Importance: Amorphous solid dispersions are a critical formulation strategy in modern pharmaceutics for enabling the effective oral delivery of promising but poorly water-soluble drug compounds.

Key Claims at a Glance

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

III. The Accused Instrumentality

Product Identification

  • Defendants' generic enzalutamide tablets in 40 mg and 80 mg dosage strengths, for which Defendants seek marketing approval via Abbreviated New Drug Application (ANDA) No. 219675 (Compl. ¶37).

Functionality and Market Context

  • The accused products are generic versions of Plaintiffs' Xtandi® tablets and are intended for the same therapeutic indications, which include the treatment of castration-resistant prostate cancer, metastatic castration-sensitive prostate cancer, and non-metastatic castration-sensitive prostate cancer (Compl. ¶38-39). The complaint provides the chemical structure of enzalutamide, the active ingredient in both the branded and accused generic products (Compl. ¶25). This visual, a standard 2D chemical structure diagram, identifies the specific molecule at issue in the '517 Patent infringement claim (Compl. ¶25). As generic products submitted under an ANDA, they are intended to be pharmaceutically and therapeutically equivalent to the branded reference product.

IV. Analysis of Infringement Allegations

U.S. Patent No. 7,709,517 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] Defendants' Generic Products, if approved by the FDA, will contain the compound enzalutamide. ¶52, ¶54 col. 35:55-65

U.S. Patent No. 11,839,689 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
a pharmaceutical composition comprising a solid dispersion Defendants' Generic Products will contain a pharmaceutical composition comprising a solid dispersion of enzalutamide. ¶67 col. 2:19-23
consisting essentially of amorphous enzalutamide The solid dispersion in Defendants' Generic Products will consist essentially of amorphous enzalutamide. ¶67 col. 2:24-28
and hydroxypropyl methylcellulose acetate succinate (“HPMCAS”) The solid dispersion in Defendants' Generic Products will also consist essentially of HPMCAS. ¶67 col. 2:24-28

Identified Points of Contention

  • Scope Questions: For the ’689 Patent, a primary question for the court will be the scope of the phrase "consisting essentially of." The dispute may focus on whether Defendants' formulation includes any unlisted excipients within the solid dispersion itself that materially alter the "basic and novel properties" of the claimed invention, namely the enhanced dissolution and stability of amorphous enzalutamide.
  • Technical Questions: A key evidentiary question for the ’689 Patent will be factual: what is the physical form of the enzalutamide in Defendants' proposed generic product? Plaintiffs' infringement theory relies on the allegation that the enzalutamide is "amorphous," a technical point that will likely require resolution through competing analytical data and expert testimony.

V. Key Claim Terms for Construction

The Term for Construction

  • "consisting essentially of" (’689 Patent, Claim 1)

Context and Importance

  • This transitional phrase defines the scope of the claimed "solid dispersion." Its construction is critical because it will determine whether Defendants can avoid infringement by including additional, unlisted substances in their solid dispersion. Practitioners may focus on this term because the dispute will turn on whether any such additional ingredients materially affect the invention's core characteristics of solubility enhancement and stability.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The patent specification describes the claimed "solid dispersion" as part of a larger "pharmaceutical composition" that may include other additives like fillers, binders, and lubricants (’689 Patent, col. 19:20-22). A party might argue this suggests the "solid dispersion" itself can tolerate minor, non-interfering components without departing from the claim's scope.
  • Evidence for a Narrower Interpretation: The patent's abstract and detailed description repeatedly emphasize the combination of amorphous enzalutamide and HPMCAS as the solution to the bioavailability problem (’689 Patent, col. 2:19-28; Abstract). A party could argue that this focus implies that the "basic and novel properties" of the solid dispersion are derived specifically from the interaction of these two components, and the introduction of any other substance into the dispersion would materially alter those properties.

VI. Other Allegations

Indirect Infringement

  • The complaint does not plead specific facts to support claims of induced or contributory infringement, focusing instead on direct infringement under 35 U.S.C. § 271(a) and the artificial act of infringement arising from the ANDA submission under § 271(e)(2)(A) (Compl. ¶50, ¶53, ¶61, ¶68).

Willful Infringement

  • The complaint alleges that Defendants knew of the patents-in-suit, citing their listing in the FDA's Orange Book and their inclusion in Defendants' Notice Letter (Compl. ¶55, ¶69). Plaintiffs further allege that Defendants "copied the claimed invention" of both patents (Compl. ¶56, ¶65). Based on these allegations, the complaint asserts that the case is "exceptional" and requests an award of attorney fees under 35 U.S.C. § 285 (Compl., Prayer for Relief ¶E).

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

  • A central issue for the ’689 Patent will be one of definitional scope: can the term "solid dispersion consisting essentially of" be construed to read on a generic formulation that may contain additional, unrecited excipients within the dispersion? The outcome will depend on whether those excipients are found to materially alter the fundamental solubility and stability characteristics of the claimed enzalutamide-HPMCAS combination.
  • A key evidentiary question for the ’689 Patent will be one of physical state: does the enzalutamide in the Defendants' proposed product exist in the "amorphous" state as claimed? This is a technical question of fact that will likely be resolved through a battle of competing analytical chemistry data and expert testimony.
  • A notable procedural question is raised by the complaint's allegation that Defendants have admitted the validity of the asserted patents by not challenging it in their Notice Letter (Compl. ¶44, ¶46). The extent to which this pleading constitutes a binding admission or limits Defendants' ability to later contest validity will be an early point of contention for the court.