DCT

1:18-cv-11238

AstraZeneca Pharma LP v. Apotex Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-11238, D.N.J., 06/29/2018
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendants conduct substantial business in the state, and the filing of an Abbreviated New Drug Application (ANDA) with the intent to market the accused product nationwide subjects them to specific personal jurisdiction.
  • Core Dispute: Plaintiff alleges that Defendant’s submission of an ANDA for a generic version of the breast cancer drug FASLODEX® constitutes an act of infringement of four patents directed to the drug's long-acting injectable formulation.
  • Technical Context: The technology concerns pharmaceutical formulations designed to achieve sustained release of fulvestrant, a poorly water-soluble anti-estrogen compound, via intramuscular injection.
  • Key Procedural History: The complaint certifies that this case is related to more than a dozen prior lawsuits filed by AstraZeneca against other generic drug manufacturers over the same FASLODEX® patents. The complaint notes that those cases were assigned to Judge Renée M. Bumb, and many have since been terminated, suggesting a history of prior claim construction, discovery, and potential settlements or rulings that may be relevant to this proceeding.

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
2018-05-30 Defendant Notifies Plaintiff of ANDA No. 211730 Filing
2018-06-29 Complaint Filed

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

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

  • Patent Identification: 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 anti-cancer drug fulvestrant for injection ('122 Patent, col. 4:46-54). Because fulvestrant has extremely low water solubility, it requires an oil-based vehicle. However, using oil alone would necessitate an impractically large injection volume to deliver a therapeutic dose ('122 Patent, col. 6:36-41). While adding a co-solvent like alcohol helps dissolve the drug, high concentrations of alcohol create manufacturing challenges ('122 Patent, col. 5:60-65).
  • The Patented Solution: The invention is a specific three-part solvent system that enables a concentrated, low-volume, sustained-release formulation. The solution combines a "ricinoleate vehicle" (specifically castor oil), a pharmaceutically acceptable alcohol, and a non-aqueous ester solvent (such as benzyl benzoate) ('122 Patent, Abstract). The patent asserts the surprising discovery that this combination eases the solubilization of fulvestrant beyond what would be expected, allowing a high drug concentration in a small volume suitable for intramuscular injection ('122 Patent, col. 6:48-58).
  • Technical Importance: This formulation technology made it feasible to administer a long-acting, 30-day dose of fulvestrant in a clinically acceptable volume (e.g., 5 ml), which was a significant advancement for patient treatment ('122 Patent, col. 6:36-41).

Key Claims at a Glance

  • The complaint asserts infringement of one or more unspecified claims ('Compl. ¶35). Independent claims 1 and 5 are method of treatment claims.
  • Independent Claim 1 requires:
    • A method of treating a hormonal dependent disease of the breast or reproductive tract.
    • Administering by intra-muscular injection a pharmaceutical formulation.
    • The formulation comprises fulvestrant, a mixture of 10% w/v ethanol, 10% w/v benzyl alcohol, and 15% w/v benzyl benzoate.
    • The formulation also comprises a sufficient amount of a castor oil vehicle.
    • The method results in a blood plasma concentration of at least 2.5 ng/ml for at least 2 weeks.

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

  • Patent Identification: U.S. Patent No. 7,456,160, "Formulation," issued November 25, 2008.

The Invention Explained

  • Problem Addressed: As a continuation of the application for the ’122 Patent, this patent addresses the same technical challenge: creating a concentrated, stable, and sustained-release injectable formulation for the poorly soluble drug fulvestrant (’160 Patent, col. 4:49-57).
  • The Patented Solution: The patent describes the same solution as the ’122 Patent: a formulation vehicle comprising a ricinoleate vehicle, an alcohol, and a non-aqueous ester solvent to effectively solubilize fulvestrant at a high concentration (’160 Patent, col. 6:51-61).
  • Technical Importance: This formulation enables the delivery of a therapeutically effective dose of fulvestrant in a single, low-volume injection that provides sustained drug release, improving patient convenience and compliance (’160 Patent, col. 6:39-44).

Key Claims at a Glance

  • The complaint asserts infringement of one or more unspecified claims (Compl. ¶49). Independent claims 1 and 2 are method of treatment claims.
  • Independent Claim 1 requires:
    • A method of treating a hormonal dependent disease of the breast or reproductive tract.
    • Administering by intra-muscular injection a pharmaceutical formulation.
    • The formulation comprises fulvestrant, a mixture of from 10 to 30% w/v of ethanol and benzyl alcohol.
    • The formulation further comprises from 10 to 25% w/v of benzyl benzoate.
    • The formulation also comprises a sufficient amount of a castor oil vehicle.
    • The method results in a blood plasma concentration of at least 2.5 ng/ml for at least 2 weeks.

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

  • Patent Identification: U.S. Patent No. 8,329,680, "Formulation," issued December 11, 2012.
  • Technology Synopsis: This patent, part of the same family, also claims a long-acting injectable formulation for fulvestrant using a castor oil, alcohol, and benzyl benzoate solvent system. The claims of the ’680 Patent differ from the ’122 Patent by reciting the component concentrations with the word "about," suggesting a broader scope, and by requiring the therapeutic effect to last for "at least four weeks," a longer duration than specified in the lead patents.
  • Asserted Claims: One or more unspecified claims (Compl. ¶63). Independent claims 1 and 9 are identified.
  • Accused Features: The formulation of the Proposed ANDA Product is alleged to infringe (Compl. ¶63-64).

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

  • Patent Identification: U.S. Patent No. 8,466,139, "Formulation," issued June 18, 2013.
  • Technology Synopsis: This patent also claims the three-component solvent system for delivering fulvestrant. The claims of the ’139 Patent are distinguished by reciting specific, narrower ranges for the alcohol (17-23% w/v) and benzyl benzoate (12-18% w/v) components compared to the ranges in the '160 Patent.
  • Asserted Claims: One or more unspecified claims (Compl. ¶77). Independent claims 1 and 11 are identified.
  • Accused Features: The formulation of the Proposed ANDA Product is alleged to infringe (Compl. ¶77-78).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendants' "Proposed ANDA Product," a generic Fulvestrant Injectable at a 50 mg/ml concentration, for which Defendants submitted ANDA No. 211730 to the FDA for approval (Compl. ¶8, ¶11).

Functionality and Market Context

  • The complaint alleges the Proposed ANDA Product is a generic copy intended for the same use as AstraZeneca's branded drug, FASLODEX® (Compl. ¶32-33). It is designed to be bioequivalent to FASLODEX® and, upon approval, would be marketed as a lower-cost alternative for treating hormone-dependent breast cancer (Compl. ¶11, ¶32). The infringement action was triggered by the Defendants' notice letter and Paragraph IV certification, which seek to clear a path for marketing the generic product prior to the expiration of the patents-in-suit (Compl. ¶30).
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint alleges that the filing of ANDA No. 211730 is a technical act of infringement under 35 U.S.C. § 271(e)(2) and that the future manufacture and sale of the Proposed ANDA Product will directly and indirectly infringe the patents-in-suit (Compl. ¶36, ¶39).

'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 The proposed product label for the ANDA product will instruct for intramuscular injection to treat hormone-dependent breast cancer, thereby inducing infringement of this method step. ¶33, ¶37 col. 12:55-59
of a pharmaceutical formulation comprising fulvestrant, The Proposed ANDA Product is a fulvestrant injectable containing 50 mg/ml of the active ingredient. ¶8, ¶11 col. 12:60
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 on information and belief that the formulation of the Proposed ANDA Product is covered by this claim, implying it contains these specific excipients at these exact concentrations. ¶35 col. 12:60-64
and a sufficient amount of a castor oil vehicle, The Proposed ANDA Product is alleged to contain castor oil as the vehicle. ¶35 col. 13:1
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 Proposed ANDA Product is alleged to be bioequivalent to the branded FASLODEX® product, which exhibits this pharmacokinetic profile. ¶32 col. 13:1-3

'160 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
a mixture of from 10 to 30% weight of ethanol and benzyl alcohol per volume of formulation The complaint alleges that the concentration of alcohols in the Proposed ANDA Product falls within this claimed range. ¶49 col. 13:12-14
and from 10 to 25% weight of benzyl benzoate per volume of formulation The complaint alleges that the concentration of benzyl benzoate in the Proposed ANDA Product falls within this claimed range. ¶49 col. 13:15-17
and a sufficient amount of a castor oil vehicle, whereby a therapeutically significant blood plasma fulvestrant concentration of at least 2.5 ngml⁻¹ is attained for at least 2 weeks after injection. As described above, the Proposed ANDA Product is alleged to contain a castor oil vehicle and to be bioequivalent to FASLODEX®, thereby meeting the pharmacokinetic limitations. ¶32, ¶49 col. 13:17-21
  • Identified Points of Contention:
    • Scope Questions: A primary point of dispute may be the scope of the recited excipient concentrations. For the ’122 Patent, does Apotex's formulation contain exactly 10% ethanol, 10% benzyl alcohol, and 15% benzyl benzoate? For the ’160, ’680, and ’139 patents, does the formulation fall within the literal scope of the claimed ranges or the term "about"? The differences in claim language across the patent family suggest these specific values and ranges were deliberately chosen and may become focal points of the infringement and validity analyses.
    • Technical Questions: The core of a Hatch-Waxman defense is typically a challenge to the patents' validity. While not detailed in the complaint, Apotex’s Paragraph IV certification states the patents are invalid and/or not infringed (Compl. ¶30). The case will therefore raise the question of whether the claimed formulations were obvious in light of prior art knowledge regarding injectable drug delivery systems for poorly soluble compounds.

V. Key Claim Terms for Construction

  • The Term: "ricinoleate vehicle" ('122 Patent, cl. 1)

    • Context and Importance: This term defines the primary oil component of the formulation. Its construction is critical because if Apotex uses an oil that is not a "ricinoleate vehicle," it may not infringe. Practitioners may focus on this term to determine if it is limited to castor oil or if it can encompass other synthetic or natural oils.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification states that the "ricinoleate vehicle may be a synthetic oil or conveniently is castor oil" ('122 Patent, col. 7:27-29), which may support an interpretation that is not strictly limited to natural castor oil.
      • Evidence for a Narrower Interpretation: The specification repeatedly highlights the unique properties of castor oil, attributing its solvating ability to the high proportion of ricinoleic acid triglycerides ('122 Patent, col. 6:20-24). The preferred embodiment is castor oil, which could be used to argue the invention is centered on and limited to oils with the specific chemical properties of castor oil.

  • The Term: "a mixture of 10% weight of ethanol..., 10% weight of benzyl alcohol... and 15% weight of benzyl benzoate" ('122 Patent, cl. 1)

    • Context and Importance: The precision of these values will be central to the literal infringement analysis for the ’122 Patent. Apotex will likely argue that any deviation, however minor, places its product outside the claim's scope.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation (or Doctrine of Equivalents): AstraZeneca may point to other claims in the patent family (e.g., in the ’160 Patent) that recite ranges, arguing that the purpose of the invention—solubilizing fulvestrant—is achieved by concentrations around these values, not just these exact numbers. The specification itself discusses various ranges of components ('122 Patent, col. 7:6-22).
      • Evidence for a Narrower Interpretation: Apotex may argue that the patentee's choice to claim specific percentages, rather than using ranges or the word "about" as seen in other family members (e.g., the '680 patent), was a deliberate surrender of broader scope. This choice implies that the claim is precisely limited to a formulation containing these exact concentrations.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Defendants will induce infringement by providing a product label that instructs medical professionals and patients to administer the Proposed ANDA Product in a manner that directly infringes the asserted method claims (Compl. ¶33, ¶37). The allegation is that the proposed label will substantially copy the label for FASLODEX® (Compl. ¶33).
  • Willful Infringement: The complaint alleges that Defendants had knowledge of the patents-in-suit at the time of their ANDA submission, as evidenced by their Paragraph IV certification, and that any subsequent infringement upon commercial launch will be willful (Compl. ¶40, ¶42).

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

  • A core issue will be one of infringement and claim scope: Does Apotex's confidential ANDA formulation fall within the literal scope of the asserted claims? The dispute may focus on whether the precise percentages recited in the ’122 Patent or the ranges and "about" language in the other patents read on the accused product, raising questions of both literal infringement and the doctrine of equivalents.
  • A second key issue will be patent validity: Apotex has certified that the patents-in-suit are invalid or not infringed. The case will likely depend heavily on whether Apotex can prove by clear and convincing evidence that the claimed formulations were obvious over the prior art, particularly given the common use of oils, alcohols, and co-solvents in formulating poorly soluble drugs.
  • A final procedural and strategic question will be the impact of prior litigation: Given the extensive litigation history involving these same patents against other generic manufacturers before the same court, a central question is how prior claim construction orders, expert testimony, and other rulings from those related cases will influence the proceedings and legal strategies in this matter.