DCT

1:19-cv-19081

AstraZeneca Pharma LP v. Xiromed LLC

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-19081, D.N.J., 10/17/2019
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey as it is the judicial district where multiple defendants maintain their principal places of business and conduct substantial business.
  • Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) for a generic version of Plaintiff’s FASLODEX® (fulvestrant) injection constitutes an act of infringement of four patents directed to pharmaceutical formulations.
  • Technical Context: The technology concerns long-acting, injectable formulations for fulvestrant, an estrogen receptor antagonist used to treat hormone receptor-positive breast cancer, which is difficult to formulate due to its poor solubility.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' notification to Plaintiff of their ANDA filing containing a Paragraph IV certification, asserting that the patents-in-suit are invalid and/or not infringed. The complaint notes an extensive history of prior litigation involving the same patents against numerous other generic drug manufacturers in the same district, with many of those cases having been terminated.

Case Timeline

Date Event
2000-01-10 Priority Date for '122, '160, '680, and '139 Patents
2004-08-10 U.S. Patent No. 6,774,122 Issues
2008-11-25 U.S. Patent No. 7,456,160 Issues
2012-12-11 U.S. Patent No. 8,329,680 Issues
2013-06-18 U.S. Patent No. 8,466,139 Issues
2019-09-10 Date of Defendants' ANDA Notice Letter to AstraZeneca
2019-10-17 Complaint Filing Date
2020-08-25 Expiration of FDA Data Exclusivity for FASLODEX®

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

U.S. Patent No. 6,774,122 - "Formulation"

  • Issued: August 10, 2004

The Invention Explained

  • Problem Addressed: The patent addresses the difficulty of formulating the active pharmaceutical ingredient fulvestrant, a highly lipophilic (poorly water-soluble) compound, for parenteral administration ('122 Patent, col. 4:46-54). A high concentration of the drug is needed to deliver a therapeutically effective dose in a small, injectable volume (e.g., 5 mL or less), which is not achievable with conventional oil-based solvents alone ('122 Patent, col. 6:26-41).
  • The Patented Solution: The invention is a pharmaceutical formulation that dissolves fulvestrant in a specific combination of excipients: a ricinoleate vehicle (specifically castor oil), at least one alcohol (such as ethanol and benzyl alcohol), and a non-aqueous ester solvent (such as benzyl benzoate) ('122 Patent, Abstract; col. 6:49-58). This ternary solvent system was found to surprisingly increase the solubility of fulvestrant to a level sufficient for a low-volume, long-acting intramuscular depot injection ('122 Patent, col. 6:51-54).
  • Technical Importance: This formulation provided a commercially viable way to administer fulvestrant, a "pure" antiestrogen with therapeutic benefits over prior treatments like tamoxifen, as a long-acting monthly injection for hormone-dependent breast cancer ('122 Patent, col. 4:11-18).

Key Claims at a Glance

  • The complaint alleges infringement of "one or more Claims" ('122 Patent, ¶35). Independent claims 1 and 5 are directed to methods of treatment using the formulation.
  • Independent Claim 1:
    • A method of treating a hormonal dependent benign or malignant disease of the breast or reproductive tract.
    • By administering to a human an intramuscular injection of a pharmaceutical formulation comprising fulvestrant, a mixture of 10% weight of ethanol per volume of formulation, 10% weight of benzyl alcohol per volume of formulation, and 15% weight of benzyl benzoate per volume of formulation.
    • The formulation includes a sufficient amount of a castor oil vehicle.
    • The method results in a therapeutically significant blood plasma fulvestrant concentration of at least 2.5 ngml⁻¹ for at least 2 weeks after injection.
  • The complaint does not explicitly reserve the right to assert dependent claims but makes broad allegations covering the patents.

U.S. Patent No. 7,456,160 - "Formulation"

  • Issued: November 25, 2008

The Invention Explained

  • Problem Addressed: As a continuation of the application leading to the '122 Patent, the '160 Patent addresses the same technical problem of creating a high-concentration, stable, injectable formulation for the poorly soluble compound fulvestrant ('160 Patent, col. 4:47-55).
  • The Patented Solution: The patented solution is the same three-part solvent system comprising a ricinoleate vehicle, an alcohol component, and a non-aqueous ester solvent to achieve high solubility and enable a low-volume, long-acting depot injection ('160 Patent, Abstract; col. 6:51-59).
  • Technical Importance: The invention's importance is identical to that described for the '122 Patent, enabling the practical administration of fulvestrant as a long-acting injection for breast cancer patients ('160 Patent, col. 4:11-19).

Key Claims at a Glance

  • The complaint alleges infringement of "one or more Claims" ('160 Patent, ¶49). Independent claims 1 and 2 are directed to methods of treatment.
  • Independent Claim 1:
    • A method of treating a hormonal dependent benign or malignant disease of the breast or reproductive tract.
    • By administering an intramuscular injection of a pharmaceutical formulation comprising fulvestrant, a mixture of from 10 to 30% weight of ethanol and benzyl alcohol per volume of formulation, and 10 to 25% weight of benzyl benzoate per volume of formulation.
    • The formulation includes a sufficient amount of a castor oil vehicle.
    • The method results in a therapeutically significant blood plasma fulvestrant concentration of at least 2.5 ngml⁻¹ for at least 2 weeks after injection.
  • The complaint's general allegations may encompass dependent claims.

U.S. Patent No. 8,329,680 - "Formulation"

  • Issued: December 11, 2012

Technology Synopsis

This patent, part of the same family, addresses the challenge of creating a stable, long-acting injectable formulation for the poorly soluble drug fulvestrant. It discloses a solution using a specific combination of a ricinoleate vehicle (castor oil), alcohols (ethanol, benzyl alcohol), and a non-aqueous ester solvent (benzyl benzoate) to achieve a high drug concentration suitable for a low-volume, once-monthly injection (Compl. ¶¶63-67; '680 Patent, Abstract).

Key Claims and Accused Features

  • Asserted Claims: Independent claims 1 and 9.
  • Accused Features: The accused generic product is a pharmaceutical formulation containing fulvestrant, ethanol, benzyl alcohol, benzyl benzoate, and a castor oil vehicle, which allegedly meets the specific component concentrations and achieves the therapeutic effect described in the claims (Compl. ¶¶30, 63-67).

U.S. Patent No. 8,466,139 - "Formulation"

  • Issued: June 18, 2013

Technology Synopsis

As another member of the same patent family, this patent also describes a solution to the problem of formulating poorly soluble fulvestrant for intramuscular injection. The invention combines a ricinoleate vehicle, specific alcohols, and a non-aqueous ester solvent to create a stable, high-concentration, long-acting formulation for treating breast cancer (Compl. ¶¶77-81; '139 Patent, Abstract).

Key Claims and Accused Features

  • Asserted Claims: Independent claims 1 and 11.
  • Accused Features: The complaint alleges that the formulation of Defendants' proposed generic product, containing fulvestrant, ethanol, benzyl alcohol, benzyl benzoate, and castor oil, infringes the patent by matching the claimed composition and achieving the claimed therapeutic profile (Compl. ¶¶30, 77-81).

III. The Accused Instrumentality

Product Identification

  • Defendants' proposed generic Fulvestrant Injection, 250 mg/5 mL (50 mg/mL), which is the subject of Abbreviated New Drug Application (ANDA) No. 213553 (the "Proposed ANDA Product") (Compl. ¶¶9, 11).

Functionality and Market Context

  • The Proposed ANDA Product is a pharmaceutical formulation intended for intramuscular injection to treat hormone-dependent breast cancer (Compl. ¶32). The complaint alleges a specific composition: fulvestrant (50 mg/mL), 10% weight/volume ethanol, 10% weight/volume benzyl alcohol, 15% weight/volume benzyl benzoate, and a sufficient amount of a castor oil vehicle (Compl. ¶30). The complaint further alleges that the Defendants' ANDA contains data demonstrating the bioequivalence of the Proposed ANDA Product to AstraZeneca's FASLODEX®, including its ability to achieve a blood plasma concentration of at least 8.5 mg/ml⁻¹ for at least 4 weeks after injection (Compl. ¶31).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

'122 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating a hormonal dependent benign or malignant disease of the breast or reproductive tract by administration to a human in need of such treatment an intra-muscular injection of a pharmaceutical formulation The Proposed ANDA Product is a generic version of FASLODEX® for which Defendants seek FDA approval; the proposed product label will allegedly instruct for its use by intramuscular injection to treat hormone-dependent breast cancer. ¶¶9, 11, 32, 37 col. 12:56-62
comprising fulvestrant, a mixture of 10% weight of ethanol per volume of formulation, 10% weight of benzyl alcohol per volume of formulation and 15% weight of benzyl benzoate per volume of formulation The complaint alleges that the Proposed ANDA Product is a pharmaceutical formulation containing these exact components at these exact concentrations. ¶30 col. 6:49-58
and a sufficient amount of a castor oil vehicle The complaint alleges the Proposed ANDA Product contains a castor oil vehicle. ¶30 col. 7:25-29
whereby a therapeutically significant blood plasma fulvestrant concentration of at least 2.5 ngml⁻¹ is attained for at least 2 weeks after injection. The complaint alleges the ANDA demonstrates bioequivalence with FASLODEX®, including achieving a blood plasma fulvestrant concentration of at least 8.5 mg/ml⁻¹ for at least 4 weeks, which meets the claimed pharmacokinetic profile. (Note: Unit mg/ml⁻¹ in complaint is likely a typo for ng/ml⁻¹). ¶31 col. 9:1-5

'160 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating a hormonal dependent benign or malignant disease of the breast or reproductive tract by... an intra-muscular injection of a pharmaceutical formulation The Proposed ANDA Product label will allegedly instruct for use by intramuscular injection to treat hormone-dependent breast cancer. ¶¶9, 32, 51 col. 12:4-8
comprising fulvestrant, a mixture of from 10 to 30% weight of ethanol and benzyl alcohol per volume of formulation The alleged formulation contains 10% ethanol and 10% benzyl alcohol, for a total of 20% alcohol w/v, which falls within the claimed range of 10-30%. ¶30 col. 7:6-12
and 10 to 25% weight of benzyl benzoate per volume of formulation The alleged formulation contains 15% benzyl benzoate w/v, which falls within the claimed range of 10-25%. ¶30 col. 7:52-62
and a sufficient amount of a castor oil vehicle The alleged formulation contains a sufficient amount of a castor oil vehicle. ¶30 col. 7:25-29
whereby a therapeutically significant blood plasma fulvestrant concentration of at least 2.5 ngml⁻¹ is attained for at least 2 weeks after injection. The ANDA allegedly demonstrates bioequivalence, including achieving a blood plasma concentration that meets or exceeds the claimed threshold. ¶31 col. 9:1-5

Identified Points of Contention

  • Scope Questions: The complaint alleges a formulation that appears to fall squarely within the scope of the asserted claims, particularly for the '122 Patent, where the alleged concentrations are identical to those claimed. For the '160 Patent, a question may arise as to whether the term "a mixture of... ethanol and benzyl alcohol" requires both to be present, and whether the percentage applies to their sum, as the complaint's theory assumes.
  • Technical Questions: A key question for the court will be whether Defendants' primary defense strategy will be non-infringement or a challenge to patent validity. The complaint's specific allegations regarding the ANDA product's composition (Compl. ¶30) suggest that a literal infringement argument is strong on its face, potentially shifting the focus of the dispute to the patents' validity (e.g., obviousness) in view of prior art pharmaceutical formulations.

V. Key Claim Terms for Construction

The Term: "a sufficient amount of a castor oil vehicle" ('122 Patent, Claim 1)

  • Context and Importance: This term defines the primary solvent vehicle and is open-ended. Its construction is critical because if defined too narrowly, it could provide a path for a non-infringement defense; if found indefinite, the claim could be invalid. Practitioners may focus on this term to determine if its scope is limited by the specification's examples or if it simply means a quantity sufficient to make up the remaining volume of the formulation.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim language itself does not impose an upper or lower limit, suggesting any amount that serves the purpose of a vehicle is "sufficient."
    • Evidence for a Narrower Interpretation: The specification provides preferred embodiments, stating the ricinoleate vehicle "should preferably be present in the formulation in a proportion of at least 30% weight per volume" ('122 Patent, col. 7:28-30). A party could argue that "sufficient" should be interpreted in light of these more specific disclosures.

The Term: "a therapeutically significant blood plasma fulvestrant concentration" ('122 Patent, Claim 1)

  • Context and Importance: This is a functional limitation that defines the required outcome of the administration. The claim itself sets a quantitative floor ("at least 2.5 ngml⁻¹ for at least 2 weeks"), but the term's meaning is central to proving infringement, as the accused product must be shown to achieve this result.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim explicitly defines the minimum threshold (≥2.5 ngml⁻¹ for ≥2 weeks). A plain reading suggests any formulation meeting this floor satisfies the limitation. The complaint alleges the accused product achieves a concentration well above this floor (Compl. ¶31).
    • Evidence for a Narrower Interpretation: The specification describes achieving blood plasma concentrations of "at least 8.5 ngml⁻¹" ('122 Patent, col. 9:2-3). A defendant could argue that "therapeutically significant" should be construed to require this higher concentration, although this may be a difficult argument given the explicit language in the claim itself.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement, stating that Defendants' proposed product label will "substantially copy the instructions for FASLODEX®" and will direct and instruct physicians and patients to administer the Proposed ANDA Product in an infringing manner (Compl. ¶¶32, 37, 51).
  • Willful Infringement: Willfulness is alleged based on pre-suit knowledge. The complaint asserts that Defendants were aware of the patents-in-suit at the time they filed their ANDA with a Paragraph IV certification and that they received a notice letter from AstraZeneca, but proceeded with their intent to market the product regardless (Compl. ¶¶28, 29, 40, 42).

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

  • A core issue will be one of litigation strategy: will the case primarily turn on questions of infringement or validity? The complaint alleges a product composition that appears to map directly onto the patent claims, which may compel the Defendants to focus their defense on challenging the validity of the patents as being obvious over prior art pharmaceutical formulation techniques rather than arguing non-infringement.
  • A key evidentiary and constructional question will be the scope of the formulation's components. Can terms like "a sufficient amount of a castor oil vehicle" be limited by preferred embodiments in the specification, or does their plain meaning control? The resolution of such terms will determine the ultimate boundaries of the claims and whether the accused product, as formulated, falls within them.