DCT
2:24-cv-03747
Astellas Pharma Inc v. Qilu Pharmaceutical Co Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Astellas Pharma Inc.; Astellas US LLC; Astellas Pharma US, Inc.; Medivation LLC; Medivation Prostate Therapeutics LLC; The Regents of the University of California (collectively "Astellas") (Japan, Delaware, California)
- Defendant: Qilu Pharmaceutical (Hainan) Co., Ltd.; Qilu Pharma, Inc. (collectively "Qilu") (China, Pennsylvania)
- Plaintiff’s Counsel: McCarter & English, LLP (Venable LLP, Of Counsel)
- Case Identification: 2:24-cv-03747, E.D. Pa., 08/02/2024
- Venue Allegations: Venue is alleged to be proper in the Eastern District of Pennsylvania because Defendant Qilu Pharma, Inc. is incorporated in and resides in Pennsylvania, and Defendant Qilu Pharmaceutical (Hainan) Co., Ltd. is a foreign corporation that may be sued in any judicial district.
- Core Dispute: Plaintiffs allege that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the prostate cancer drug Xtandi® constitutes an act of infringement of two U.S. patents covering the active ingredient and its pharmaceutical formulation.
- Technical Context: The technology relates to diarylhydantoin compounds for treating prostate cancer and specific solid dispersion formulations designed to improve the bioavailability of the active pharmaceutical ingredient, enzalutamide.
- Key Procedural History: The litigation was initiated under the Hatch-Waxman Act following Plaintiffs' receipt of a "Qilu Notice Letter" dated June 24, 2024, which advised of Qilu's ANDA submission seeking FDA approval to market generic enzalutamide tablets. The complaint states that the patents-in-suit are listed in the FDA's "Orange Book" for Xtandi® tablets, putting potential generic manufacturers on notice.
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 Issue Date |
| 2012-09-11 | U.S. Patent No. 11,839,689 Priority Date |
| 2020-08-04 | FDA approved NDA for Xtandi® tablets |
| 2023-12-12 | U.S. Patent No. 11,839,689 Issue Date |
| 2024-06-24 | Date of Qilu's Notice Letter to Plaintiffs |
| 2024-08-02 | Complaint Filing Date |
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 ("’517 Patent").
The Invention Explained
- Problem Addressed: The patent describes a need for new treatments for hormone-refractory prostate cancer, noting that existing anti-androgen therapies often fail as the cancer progresses and the androgen receptor (AR) becomes overexpressed (’517 Patent, col. 2:20-46). Overexpression of AR can convert existing anti-androgen drugs from antagonists (inhibitors) into agonists (stimulators), promoting cancer growth (’517 Patent, col. 2:47-51).
- The Patented Solution: The invention provides a class of diarylhydantoin compounds that act as AR antagonists with minimal agonist activity, even in cancer cells that overexpress the androgen receptor (’517 Patent, col. 2:50-57). The compound enzalutamide, which is the subject of this litigation, is one such compound disclosed and claimed by the patent. The complaint provides the chemical structure of enzalutamide (Compl. p. 6).
- Technical Importance: The claimed compounds offered a potential therapeutic solution for advanced prostate cancer that had become resistant to standard hormone deprivation therapies (’517 Patent, col. 2:62-65).
Key Claims at a Glance
- The complaint asserts at least independent Claim 1 (Compl. ¶52).
- Claim 1 recites:
- A compound selected from a large group of specified chemical structures (a Markush group).
- One of the enumerated compounds in this group is enzalutamide, identified in the patent as compound RD162 (’517 Patent, col. 36:1-15).
- The complaint does not explicitly reserve the right to assert dependent claims but alleges infringement of "one or more claims" (Compl. ¶51).
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 ("’689 Patent").
The Invention Explained
- Problem Addressed: While not explicitly stated in a background section, the patent addresses the technical challenge that enzalutamide has poor aqueous solubility, which can limit its absorption and bioavailability when administered orally (’689 Patent, col. 2:20-24).
- The Patented Solution: The patent discloses a specific formulation to overcome this solubility issue. The solution is a "solid dispersion" where amorphous enzalutamide is dispersed within a concentration-enhancing polymer, specifically hydroxypropyl methylcellulose acetate succinate (HPMCAS) (’689 Patent, Abstract; col. 2:20-24). This approach is designed to improve the solubility, absorption, and dissolution stability of enzalutamide, allowing for an effective solid oral dosage form like a tablet (’689 Patent, col. 2:20-35).
- Technical Importance: This formulation technology provides a method to create a stable, solid oral dosage form for a poorly soluble but therapeutically important compound, potentially enhancing its clinical efficacy (’689 Patent, col. 2:36-41).
Key Claims at a Glance
- The complaint asserts at least independent Claim 1 (Compl. ¶60, 65).
- Claim 1 recites:
- A pharmaceutical composition comprising a solid dispersion
- consisting essentially of amorphous enzalutamide and hydroxypropyl methylcellulose acetate succinate.
- The complaint notes that certain dependent claims specify that the formulation is a tablet (Compl. ¶60).
III. The Accused Instrumentality
Product Identification
- The accused instrumentalities are Qilu's generic enzalutamide tablets in 40 mg and 80 mg dosages, which are the subject of ANDA No. 219140 filed with the FDA (Compl. ¶37).
Functionality and Market Context
- The complaint alleges that Qilu's generic products are versions of Plaintiffs' Xtandi® tablets (Compl. ¶38). Qilu is seeking approval for the same indications as Xtandi®, including the treatment of various forms of prostate cancer (Compl. ¶39). The core functionality alleged to be infringing is that the tablets contain the compound enzalutamide and are formulated as a solid dispersion of amorphous enzalutamide and HPMCAS, allegedly copying the formulation of Xtandi® tablets (Compl. ¶52, 61, 63, 65).
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 group of compounds including enzalutamide] | The complaint alleges on information and belief that Qilu's Generic Products will contain the compound enzalutamide. | ¶52 | col. 36:1-15 |
- Identified Points of Contention:
- Technical Questions: The primary factual question is whether Qilu’s ANDA product does, in fact, contain the chemical compound enzalutamide as claimed in the ’517 Patent. The complaint alleges that Qilu's notice letter does not allege non-infringement of certain claims, which may suggest this point is not in substantial dispute (Compl. ¶41-42).
’689 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a pharmaceutical composition comprising a solid dispersion | The complaint alleges on information and belief that Qilu's Generic Products will contain a pharmaceutical composition comprising a solid dispersion. | ¶65 | col. 2:20-24 |
| consisting essentially of amorphous enzalutamide and hydroxypropyl methylcellulose acetate succinate (“HPMCAS”) | The complaint alleges the solid dispersion in Qilu's Generic Products will consist essentially of amorphous enzalutamide and HPMCAS. | ¶60, ¶65 | col. 2:20-24 |
- Identified Points of Contention:
- Scope Questions: A central issue may be the interpretation of the phrase "consisting essentially of." This raises the question of whether Qilu's generic formulation contains other unlisted ingredients that materially affect the basic and novel properties of the claimed solid dispersion, such as its dissolution stability or ability to enhance bioavailability.
- Technical Questions: The complaint alleges that Qilu copied the claimed invention of the ’689 Patent and the Xtandi® tablet formulation (Compl. ¶63). A key factual question will be what evidence supports the allegation that Qilu’s product is in fact a "solid dispersion" containing "amorphous" enzalutamide as those terms are understood in the patent. The complaint alleges that Qilu's notice letter does not dispute infringement of any claim of the '689 patent, which may indicate Qilu does not contest that its product meets these limitations (Compl. ¶62).
V. Key Claim Terms for Construction
The Term: "solid dispersion" (’689 Patent, Claim 1)
Context and Importance: The entire inventive concept of the ’689 patent rests on creating a "solid dispersion" to improve enzalutamide's properties. The definition of this term will be critical to determine if Qilu's formulation method and resulting product fall within the claim scope. Practitioners may focus on whether the term implies a specific degree of molecular mixing or homogeneity between the drug and the polymer.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent states that a solid dispersion can exist as "a pure phase, as a solid solution of enzalutamide homogeneously distributed throughout the polymer, or any combination of these states" (’689 Patent, col. 4:11-15), which could support a broader definition that does not require perfect homogeneity.
- Evidence for a Narrower Interpretation: The patent repeatedly emphasizes the benefits of a "substantially homogeneous" dispersion, which is characterized by a single glass transition temperature (Tg) (’689 Patent, col. 4:17-34). This could be used to argue that only formulations achieving this high level of homogeneity meet the definition of "solid dispersion" as used in the patent.
The Term: "consisting essentially of" (’689 Patent, Claim 1)
Context and Importance: This transitional phrase opens the claim to include unlisted ingredients that do not materially affect the "basic and novel properties" of the invention. The dispute will likely focus on what those properties are and whether any additional excipients in Qilu’s product materially affect them.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent does not explicitly list the "basic and novel properties." An argument could be made that only properties directly tied to the core function (e.g., being a solid oral dosage form) are covered, allowing for a wide range of other formulation aids.
- Evidence for a Narrower Interpretation: The patent describes the invention's properties as including "improvement solubility and absorption of enzalutamide" and "dissolution stability" (’689 Patent, col. 2:21-24). This language could support a narrower reading where any unlisted ingredient that affects these specific characteristics would place a formulation outside the claim scope.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Qilu "knows or should know" that its commercial activities will infringe the asserted patents (Compl. ¶55, ¶68). This knowledge is predicated on the patents' listing in the FDA Orange Book and Qilu's reference to the patents in its notice letter (Compl. ¶53, ¶67).
- Willful Infringement: The complaint alleges willfulness based on Qilu's pre-suit knowledge of the patents from the Orange Book (Compl. ¶53, ¶67). The willfulness claim is further supported by allegations that Qilu copied the claimed inventions (Compl. ¶54, ¶63) and that Qilu's opinions on non-infringement and invalidity are "devoid of an objective good faith basis" (Compl. ¶56, ¶69). The complaint seeks a declaration that the case is "exceptional" 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 claim scope: can the phrase "consisting essentially of amorphous enzalutamide and HPMCAS" be construed to read on Qilu's generic formulation, or does the generic product contain additional excipients that materially alter the basic and novel properties of the claimed solid dispersion, such as its dissolution stability and bioavailability enhancement?
- A key evidentiary question will be the degree of similarity between the accused product and the patented invention. Given the complaint's allegations that Qilu's notice letter does not dispute infringement of any claim of the '689 patent and that Qilu copied the Xtandi® formulation, the case may turn on evidence demonstrating the precise composition and physical characteristics of Qilu's product compared to the claim limitations.
- While the complaint focuses on infringement, the allegations that Qilu's non-infringement and invalidity assertions lack a good faith basis suggest that a primary legal battleground, particularly for the '517 compound patent, will likely be the validity of the patents-in-suit, an issue to be developed during subsequent stages of litigation.