DCT

1:10-cv-00018

AstraZeneca Pharma LP v. Teva Parenteral Medicines Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:10-cv-00018, D. Del., 01/07/2010
  • Venue Allegations: Venue is asserted in the District of Delaware based on Defendant entities Teva Parenteral Medicines, Inc. and Teva Pharmaceuticals USA, Inc. being incorporated under Delaware law, and Defendant Teva Pharmaceutical Industries Ltd. conducting business in the state.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for a generic version of Plaintiff's antioestrogen breast cancer drug, FASLODEX®, constitutes an act of infringement of two patents covering the drug's formulation.
  • Technical Context: The patents relate to injectable, sustained-release pharmaceutical formulations for poorly-soluble active ingredients, a critical technology for delivering certain drugs that cannot be effectively administered orally.
  • Key Procedural History: The action was triggered by a notice letter, dated November 25, 2009, in which Teva informed AstraZeneca of its ANDA filing. The complaint notes that this letter included allegations of patent invalidity but contained no allegations that Teva's proposed generic product would not infringe the asserted patents.

Case Timeline

Date Event
2000-01-10 Earliest Priority Date for ’122 and ’160 Patents
2004-08-10 U.S. Patent No. 6,774,122 Issued
2008-11-25 U.S. Patent No. 7,456,160 Issued
2009-11-25 Teva sends ANDA Notice Letter to AstraZeneca
2009-11-27 AstraZeneca receives Teva's Notice Letter (approximate date)
2010-01-07 Complaint Filed
2021-01-09 Patent Expiration Date (as alleged in complaint)

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 drug fulvestrant for injection. Fulvestrant is described as a highly lipophilic (oil-soluble) molecule with extremely low aqueous solubility, making it challenging to create a solution that is concentrated enough to be administered in a small, patient-tolerable volume (e.g., 5 ml) for sustained-release therapy (’122 Patent, col. 4:46-58). A previously disclosed formulation required a high concentration of alcohol, which the patent notes would complicate commercial-scale manufacturing (’122 Patent, col. 5:58-65).
  • The Patented Solution: The invention is a pharmaceutical formulation that dissolves fulvestrant in a "ricinoleate vehicle," specifically castor oil, which has a better solvating ability for steroids than other oils (’122 Patent, col. 6:20-24). To achieve the necessary high drug concentration, the formulation adds both an alcohol (e.g., ethanol, benzyl alcohol) and, critically, a non-aqueous ester solvent (e.g., benzyl benzoate). The inventors state it was "surprisingly found" that the addition of the ester solvent, in which fulvestrant is less soluble than in alcohol, nevertheless "eases the solubilisation" and allows for a high drug concentration in a small volume suitable for intramuscular injection (’122 Patent, col. 6:48-58).
  • Technical Importance: This three-part solvent system (ricinoleate vehicle, alcohol, ester solvent) provided a method to formulate a high dose of a poorly soluble drug into a small-volume, injectable, sustained-release product, overcoming a significant pharmaceutical delivery challenge (’122 Patent, col. 6:5-6).

Key Claims at a Glance

  • The complaint asserts infringement of one or more unspecified claims (Compl. ¶22). Independent claim 5 is representative of the specific formulations claimed.
  • Independent Claim 5 (Method of Treating):
    • A method of treating a hormonal dependent benign or malignant disease of the breast or reproductive tract by administering an intra-muscular injection to a human;
    • of a pharmaceutical formulation comprising fulvestrant;
    • a mixture of 10% weight of ethanol per volume of formulation and 10% weight of benzyl alcohol per volume of formulation;
    • 15% weight of benzyl benzoate per volume of formulation;
    • a sufficient amount of a castor oil vehicle;
    • whereby the formulation comprises at least 45 mg/ml of fulvestrant.

U.S. Patent No. 7,456,160 - "Formulation," issued November 25, 2008

The Invention Explained

  • Problem Addressed: The ’160 Patent, a continuation of the application that led to the ’122 Patent, addresses the same formulation challenges related to fulvestrant's low solubility and the need for a concentrated, injectable, sustained-release product (’160 Patent, col. 4:49-54).
  • The Patented Solution: The solution is the same three-component solvent system described in the ’122 Patent, combining a ricinoleate vehicle, an alcohol, and a non-aqueous ester solvent to effectively dissolve fulvestrant (’160 Patent, Abstract; col. 6:43-53).
  • Technical Importance: Like its parent, this patent provides a technical solution for formulating a challenging, poorly soluble drug for effective clinical use as a long-acting injection (’160 Patent, col. 6:5-6).

Key Claims at a Glance

  • The complaint asserts infringement of one or more unspecified claims (Compl. ¶35). Independent claim 2 is representative of the broader, ranged formulations claimed.
  • Independent Claim 2 (Method of Treating):
    • A method of treating a hormonal dependent benign or malignant disease of the breast or reproductive tract by administering an intra-muscular injection to a human;
    • of a pharmaceutical formulation comprising fulvestrant;
    • a mixture of from 10% to 30% weight of a mixture of ethanol and benzyl alcohol per volume of formulation;
    • from 10% to 25% weight of benzyl benzoate per volume of formulation;
    • a sufficient amount of a castor oil vehicle;
    • whereby the formulation comprises at least 45 mg/ml of fulvestrant.

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Teva’s proposed generic "Fulvestrant Injection, 50 mg/ml," as described in Abbreviated New Drug Application (ANDA) No. 200479 submitted to the FDA (Compl. ¶19). The act of infringement alleged is the submission of this ANDA to obtain approval for commercial manufacture and sale prior to the expiration of the patents-in-suit (Compl. ¶¶23, 36).

Functionality and Market Context

The complaint alleges that Teva’s ANDA Product is a generic version of AstraZeneca’s FASLODEX®, an antioestrogen drug used for treating hormone receptor positive metastatic breast cancer (Compl. ¶¶12-13). The complaint further alleges that upon approval, Teva intends to sell its ANDA product for this use, directly competing with FASLODEX® (Compl. ¶¶25, 38). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart or specific factual allegations mapping elements of Teva's proposed product to the patent claims, which is common in ANDA litigation prior to discovery of the confidential ANDA filing. The infringement theory is that the product described in the ANDA will, if approved and sold, meet the limitations of the asserted claims.

’122 Patent Infringement Allegations

Claim Element (from Independent Claim 5) Alleged Infringing Functionality Complaint Citation Patent Citation
a pharmaceutical formulation comprising fulvestrant The complaint alleges that Teva's ANDA Product is a formulation that contains the active ingredient fulvestrant. ¶¶19, 22 col. 4:63-65
a mixture of 10% weight of ethanol per volume of formulation, [and] 10% weight of benzyl alcohol The complaint alleges that the use of Teva's ANDA Product is covered by the claims, suggesting it contains these specific alcohol excipients. ¶¶22, 26 col. 7:18-20
15% weight of benzyl benzoate per volume of formulation The complaint alleges that the use of Teva's ANDA Product is covered by the claims, suggesting it contains this specific ester solvent. ¶¶22, 26 col. 7:61-62
a sufficient amount of a castor oil vehicle The complaint alleges that the use of Teva's ANDA Product is covered by the claims, suggesting it contains a castor oil vehicle. ¶¶22, 26 col. 7:26-28
whereby the formulation comprises at least 45 mgml⁻¹ of fulvestrant The complaint identifies Teva's ANDA Product as a "50 mg/ml" injection, which meets this limitation. ¶19 col. 6:25-26

’160 Patent Infringement Allegations

Claim Element (from Independent Claim 2) Alleged Infringing Functionality Complaint Citation Patent Citation
a pharmaceutical formulation comprising fulvestrant The complaint alleges that Teva's ANDA Product is a formulation that contains the active ingredient fulvestrant. ¶¶19, 35 col. 4:51-55
a mixture of from 10 to 30% weight of a mixture of ethanol and benzyl alcohol per volume of formulation The complaint alleges that the use of Teva's ANDA Product is covered by the claims, suggesting its alcohol content falls within this claimed range. ¶¶35, 39 col. 7:10-14
and from 10 to 25% weight of benzyl benzoate per volume of formulation The complaint alleges that the use of Teva's ANDA Product is covered by the claims, suggesting its ester solvent content falls within this claimed range. ¶¶35, 39 col. 7:56-62
a sufficient amount of a castor oil vehicle The complaint alleges that the use of Teva's ANDA Product is covered by the claims, suggesting it contains a castor oil vehicle. ¶¶35, 39 col. 7:26-28
whereby the formulation comprises at least 45 mgml⁻¹ of fulvestrant The complaint identifies Teva's ANDA Product as a "50 mg/ml" injection, which meets this limitation. ¶19 col. 6:39-40
  • Identified Points of Contention:
    • Factual Question: The central dispute will be factual: Does the precise composition of the formulation described in Teva's confidential ANDA meet all the percentage or ranged limitations of the asserted claims? The claims of the ’122 Patent require exact percentages (e.g., 10% ethanol, 15% benzyl benzoate), creating a potentially narrow scope for literal infringement.
    • Scope Question: A key difference is the use of ranged values in the ’160 Patent claims (e.g., "from 10 to 30%"). This raises the question of whether Teva’s formulation, if not infringing the specific percentages of the ’122 Patent, still falls within the broader ranges of the ’160 Patent.
    • Equivalents Question: The complaint pleads infringement under the doctrine of equivalents in the alternative (Compl. ¶¶26, 39). This raises the question of whether any excipient in Teva's formulation that differs from the claimed excipients nevertheless performs substantially the same function in substantially the same way to achieve the same result.

V. Key Claim Terms for Construction

  • The Term: "castor oil vehicle"
  • Context and Importance: This term defines the primary solvent and delivery medium. While seemingly straightforward, its construction is important because a defendant could argue its formulation uses a mixed-oil vehicle that is not properly characterized as a "castor oil vehicle," even if castor oil is a component. Practitioners may focus on whether this term requires castor oil to be the sole or predominant oil component.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification introduces the concept of a "ricinoleate vehicle," which it defines as an oil having a high proportion of triglycerides of ricinoleic acid, and then states it "may be a synthetic oil or conveniently is castor oil" (’122 Patent, col. 7:22-28). This language may support an interpretation that is not strictly limited to pure castor oil.
    • Evidence for a Narrower Interpretation: The specific claim language uses "castor oil vehicle," not the broader term "ricinoleate vehicle" used elsewhere in the specification. An argument could be made that the patentees deliberately chose a narrower term in the claims, restricting the scope to vehicles where castor oil is the defining component.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges inducement of infringement of the method claims, asserting that upon approval, Teva "will direct physicians and patients on the use of Teva's ANDA Product through product labeling" (Compl. ¶¶25, 38). Contributory infringement is also alleged (Compl. ¶¶27, 40).
  • Willful Infringement: Willfulness is alleged based on Teva having knowledge of the patents at the time it filed its ANDA (Compl. ¶¶29, 42). The complaint further alleges that Teva's notice letter "lacks any legal or factual basis for non-infringement," which may be used to argue that any subsequent infringement would be willful (Compl. ¶¶31, 44).

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

  1. A central question will be one of factual correspondence: Does the specific formulation detailed in Teva's confidential ANDA literally meet the compositional requirements of the asserted claims, particularly the exact percentages of the ’122 Patent versus the broader ranges of the ’160 Patent?
  2. A primary defense will be one of patent validity: As foreshadowed by Teva's notice letter (Compl. ¶20), the case will likely involve a significant dispute over whether the asserted claims are invalid in light of prior art, a standard defense strategy in ANDA litigation.
  3. A key alternative infringement theory will be the doctrine of equivalents: If Teva’s formulation does not literally infringe, the court will have to consider whether any different components in Teva's product are insubstantially different from the claimed components, a complex and fact-intensive inquiry.