DCT
3:25-cv-15434
Astellas Pharma Inc v. Hetero USA Inc
I. Executive Summary and Procedural Information
Parties & Counsel:
- Plaintiff: Astellas Pharma Inc. (Japan); Astellas US LLC (Delaware); Astellas Pharma US, Inc. (Delaware); Medivation LLC (Delaware); Medivation Prostate Therapeutics LLC (Delaware)
- Defendant: Hetero USA, Inc. (Delaware); Hetero Labs Limited (India); Hetero Labs Limited Unit-V (India)
- Plaintiff’s Counsel: Walsh Pizzi O'Reilly Falanga LLP
Case Identification: 3:25-cv-15434, D.N.J., 09/10/2025
Venue Allegations: Venue is based on Defendant Hetero USA having a principal place of business in Piscataway, New Jersey, and on Defendants Hetero Labs and Hetero Unit-V being foreign corporations subject to suit in any judicial district.
Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market generic versions of Plaintiff's prostate cancer drug Xtandi® (enzalutamide) constitutes an act of infringement of patents covering specific formulations and methods of using the drug.
Technical Context: The dispute centers on enzalutamide, an androgen receptor signaling inhibitor used to treat prostate cancer, and patented technologies for improving its bioavailability and managing drug interactions.
Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant's notification to Plaintiff of its ANDA filing, which included a certification that Plaintiff's patents are invalid, unenforceable, and/or not infringed. The complaint notes that the patents-in-suit are listed in the FDA's "Orange Book" for Xtandi® tablets.
Case Timeline
| Date | Event |
|---|---|
| 2012-09-11 | U.S. Patent No. 11,839,689 Priority Date |
| 2015-08-12 | U.S. Patent No. 12,161,628 Priority Date |
| 2020-08-04 | FDA approves NDA for Xtandi® (enzalutamide) tablets |
| 2023-12-12 | U.S. Patent No. 11,839,689 Issues |
| 2024-12-10 | U.S. Patent No. 12,161,628 Issues |
| 2025-07-28 | Hetero sends notice letter regarding ANDA No. 220481 |
| 2025-09-10 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,839,689 - "Formulations of Enzalutamide," issued December 12, 2023
The Invention Explained
- Problem Addressed: The patent describes formulations intended to improve the solubility and absorption of enzalutamide, a drug compound used for treating prostate cancer (’689 Patent, col. 2:20-24). Poor solubility can limit a drug's oral bioavailability, meaning less of the active ingredient reaches the bloodstream to exert its therapeutic effect.
- The Patented Solution: The invention is a "solid dispersion" that combines enzalutamide with a specific polymer, hydroxypropyl methylcellulose acetate succinate (HPMCAS), to create a stable, non-crystalline (amorphous) form of the drug ('689 Patent, col. 3:47-50, Claim 1). This amorphous form is described as dissolving more quickly and to a greater extent than the drug's crystalline form, resulting in higher oral bioavailability ('689 Patent, col. 2:46-56).
- Technical Importance: Developing stable amorphous solid dispersions is a key strategy in pharmaceutical science for formulating poorly water-soluble drugs, enabling effective oral delivery that might otherwise be unachievable.
Key Claims at a Glance
- Independent claim 1 is asserted in the complaint (Compl. ¶52).
- Claim 1 Elements:
- A pharmaceutical composition
- comprising a solid dispersion
- consisting essentially of amorphous enzalutamide and hydroxypropyl methylcellulose acetate succinate.
U.S. Patent No. 12,161,628 - "Combination Therapy," issued December 10, 2024
The Invention Explained
- Problem Addressed: The patent addresses a drug-drug interaction that occurs when enzalutamide is co-administered with a "strong CYP3A4 inducer" such as rifampin (’628 Patent, col. 2:1-5). Such inducers accelerate the metabolism of enzalutamide, which can decrease its concentration in the blood and potentially reduce its therapeutic efficacy.
- The Patented Solution: The patent claims a method to counteract this effect by increasing the daily dose of enzalutamide to 240 mg when it is co-administered with rifampin ('628 Patent, col. 2:6-14, Claim 1). This dose adjustment is intended to maintain a therapeutically effective concentration of enzalutamide despite the accelerated metabolism.
- Technical Importance: Managing drug-drug interactions through specific dosage adjustments is critical for ensuring patient safety and treatment efficacy, particularly in oncology where patients often take multiple medications concurrently.
Key Claims at a Glance
- Independent claim 1 is asserted in the complaint (Compl. ¶67).
- Claim 1 Elements:
- A method of treating prostate cancer in a patient to whom rifampin is administered,
- comprising co-administering to the patient a daily dose of 240 mg of enzalutamide.
III. The Accused Instrumentality
Product Identification
Defendant’s proposed generic enzalutamide tablets, 40 mg and 80 mg, which are the subject of ANDA No. 220481 ("Hetero's Generic Products") (Compl. ¶40).
Functionality and Market Context
- The accused products are generic versions of Plaintiffs' Xtandi® tablets, intended to contain the same active pharmaceutical ingredient, enzalutamide (Compl. ¶41). The complaint provides the chemical structure of enzalutamide (Compl. p. 8, Figure). The proposed generic is intended for the same indications as the branded product, including the treatment of various forms of prostate cancer (Compl. ¶42).
- By filing an ANDA, Defendant seeks to market a bioequivalent version of the branded drug, which Plaintiffs allege is covered by the patents-in-suit (Compl. ¶16).
IV. Analysis of Infringement Allegations
11,839,689 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a pharmaceutical composition | Hetero's Generic Products are alleged to be tablets, which are a type of pharmaceutical composition. | ¶54 | col. 3:5-6 |
| comprising a solid dispersion | The accused products are alleged to contain a solid dispersion. | ¶55 | col. 2:20-23 |
| consisting essentially of amorphous enzalutamide and hydroxypropyl methylcellulose acetate succinate | The complaint alleges on information and belief that Hetero's Generic Products will contain a solid dispersion of amorphous enzalutamide and HPMCAS. | ¶55 | col. 3:47-50 |
- Identified Points of Contention:
- Scope Questions: The central dispute may involve the term "consisting essentially of." This term permits the presence of unlisted ingredients that do not materially alter the basic and novel characteristics of the claimed solid dispersion. The question for the court will be whether any additional components in Hetero's generic formulation materially alter the solubility and dissolution stability properties of the claimed amorphous enzalutamide and HPMCAS dispersion.
- Technical Questions: A key evidentiary question will be the precise composition and physical state of the enzalutamide in Defendant's ANDA product. Discovery will focus on whether the enzalutamide is indeed amorphous and whether the formulation constitutes a "solid dispersion" with HPMCAS as defined by the patent.
12,161,628 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating prostate cancer in a patient to whom rifampin is administered | The complaint alleges Hetero's proposed product labeling will instruct physicians to prescribe Hetero's Generic Products to prostate cancer patients who are also receiving rifampin. | ¶¶69-70 | col. 2:6-14 |
| comprising co-administering to the patient a daily dose of 240 mg of enzalutamide. | The complaint alleges the proposed labeling will direct the co-administration of Hetero's product at a daily dose of 240 mg for patients receiving rifampin. | ¶69 | col. 2:6-14 |
- Identified Points of Contention:
- Scope Questions: The term "co-administering" is unlikely to be a major point of construction dispute, as its meaning is generally understood in the pharmaceutical context. The dispute is less about claim scope and more about induced conduct.
- Technical Questions: The primary question is factual: what will Defendant's final, FDA-approved product label actually instruct? The infringement allegation hinges on the specific language of the proposed label encouraging or directing physicians to increase the enzalutamide dose to 240 mg/day when taken with rifampin, thereby inducing infringement of the patented method.
V. Key Claim Terms for Construction
- The Term: "consisting essentially of" (from Claim 1 of the ’689 Patent)
- Context and Importance: This term's construction will be critical to determining the scope of the claim for the ’689 Patent. If Defendant’s product includes additional excipients, the case may turn on whether those excipients "materially affect the basic and novel properties" of the claimed solid dispersion. Practitioners may focus on this term because it is a well-established legal standard that is highly fact-dependent.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent does not appear to explicitly define the term. A party arguing for a broader scope might contend that only ingredients that fundamentally defeat the purpose of the solid dispersion—improved solubility and stability—are material.
- Evidence for a Narrower Interpretation: A party arguing for a narrower scope could point to the specification's emphasis on the specific combination of amorphous enzalutamide and HPMCAS as being the key to the invention ('689 Patent, col. 3:47-50). They may argue that any additional polymer or agent that affects the dissolution profile, even if not destroying the amorphous character, is a material alteration.
VI. Other Allegations
- Indirect Infringement:
- ’689 Patent: The primary allegation is direct infringement.
- ’628 Patent: The complaint alleges active inducement of infringement under 35 U.S.C. § 271(b) (Compl. ¶68). The basis is the allegation that Defendant’s proposed product labeling will instruct and encourage physicians to prescribe the generic product in a manner that directly infringes the patented method of use (Compl. ¶¶69-71).
- Willful Infringement: The complaint alleges willful infringement of both patents. The basis for this allegation is Defendant's alleged knowledge of the patents, as evidenced by their listing in the Orange Book and their citation in Defendant's notice letter, and the assertion that Defendant's non-infringement positions lack an objective good faith basis (Compl. ¶¶59, 61, 65, 75).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of compositional scope: for the ’689 patent, does the term "consisting essentially of" permit the inclusion of other excipients found in Hetero's ANDA product, or do those components materially alter the claimed invention's properties related to solubility and dissolution?
- A key evidentiary question will be one of induced conduct: for the ’628 patent, will the final, FDA-approved label for Hetero's generic product contain specific instructions that direct or encourage physicians to co-administer a 240 mg daily dose of enzalutamide with rifampin, thereby inducing infringement of the patented method?
- A third question concerns the validity and enforceability of the patents-in-suit. While the complaint asserts that Hetero's notice letter admits the validity of the claims by not raising certain invalidity defenses (Compl. ¶¶45, 47), Hetero's ANDA certification states an opinion that the claims are invalid, unenforceable, and/or not infringed, preserving these defenses for litigation (Compl. ¶43).