DCT

1:17-cv-02448

AstraZeneca Pharma LP v. Teva Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Case Name: AstraZeneca Pharmaceuticals LP v. Teva Pharmaceuticals USA, Inc.
  • Parties & Counsel:
  • Case Identification: 1:17-cv-02448, D.N.J., 04/10/2017
  • Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendant maintains a place of business, is registered to conduct business, and derives substantial revenue from the district.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of a New Drug Application for a generic fulvestrant injection product constitutes an act of infringement of four patents covering the formulation of Plaintiff's branded drug, FASLODEX®.
  • Technical Context: The technology concerns pharmaceutical formulations designed to dissolve a poorly water-soluble, anti-cancer steroid (fulvestrant) in a non-aqueous vehicle for sustained-release intramuscular injection.
  • Key Procedural History: This is a Hatch-Waxman action triggered by Defendant’s February 27, 2017 notice letter, which included a Paragraph IV certification of non-infringement. The patents-in-suit are listed in the FDA’s Orange Book for Plaintiff's FASLODEX® product. The complaint references numerous other parallel litigations filed by AstraZeneca against other generic manufacturers over the same patents and product, requesting this case be assigned to the same judge for efficiency.

Case Timeline

Date Event
2000-01-10 Earliest Priority Date for '122, '160, '680, '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
2017-02-27 Teva Notifies AstraZeneca of NDA Filing with Paragraph IV Certification
2017-04-10 Complaint Filed

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 drug, fulvestrant, which is a "particularly lipophilic molecule" with "extremely low" aqueous solubility (’122 Patent, col. 4:49-52). This property makes it challenging to create a solution with a high enough drug concentration to be administered in a small, clinically acceptable volume for intramuscular injection (e.g., 5 ml or less) (’122 Patent, col. 5:35-40).
  • The Patented Solution: The patent discloses a formulation that solves this problem by dissolving fulvestrant in a specific three-part solvent system: a ricinoleate vehicle (castor oil), a pharmaceutically acceptable alcohol (such as ethanol and/or benzyl alcohol), and a non-aqueous ester solvent (such as benzyl benzoate) (’122 Patent, Abstract; col. 6:7-17). The patent asserts the surprising discovery that including the non-aqueous ester solvent, in which fulvestrant is less soluble than in alcohol, "eases the solubilisation" of the drug into the castor oil vehicle, enabling a high-concentration, sustained-release formulation (’122 Patent, col. 5:47-54).
  • Technical Importance: This formulation provided a means to deliver a long-acting, injectable version of fulvestrant, a "pure" antiestrogen, for the treatment of hormone-dependent conditions like breast cancer, which would otherwise be difficult to administer effectively due to its physical properties (’122 Patent, col. 4:26-45).

Key Claims at a Glance

  • The complaint asserts infringement of one or more unspecified claims of the ’122 Patent (Compl. ¶33). Independent claim 1 is representative.
  • Independent Claim 1 requires:
    • A method of treating a hormonal dependent disease of the breast or reproductive tract.
    • Administering via intra-muscular injection a formulation comprising fulvestrant.
    • The formulation includes a specific mixture of excipients: 10% weight of ethanol, 10% weight of benzyl alcohol, 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 two weeks.
  • The complaint does not explicitly reserve the right to assert dependent claims.

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 technical problem of dissolving the highly lipophilic fulvestrant for injection (’160 Patent, col. 4:50-53).
  • The Patented Solution: The solution is identical to that of the ’122 Patent: a formulation using a ricinoleate vehicle, an alcohol, and a non-aqueous ester solvent to achieve a stable, high-concentration solution suitable for sustained-release intramuscular injection (’160 Patent, col. 6:5-17).
  • Technical Importance: As with the parent patent, this formulation technology enabled the development of a clinically viable long-acting injectable treatment for hormone-sensitive breast cancer (’160 Patent, col. 4:25-46).

Key Claims at a Glance

  • The complaint asserts infringement of one or more unspecified claims of the ’160 Patent (Compl. ¶47). Independent claim 1 is representative.
  • Independent Claim 1 requires:
    • A method of treating a hormonal dependent disease of the breast or reproductive tract.
    • Administering via intra-muscular injection a formulation comprising fulvestrant.
    • The formulation includes a mixture of excipients within defined ranges: from 10 to 30% weight of ethanol and benzyl alcohol, and from 10 to 25% weight of benzyl benzoate.
    • 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 two weeks.
  • The complaint does not explicitly reserve the right to assert dependent claims.

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

  • Issued: December 11, 2012

  • Technology Synopsis: Belonging to the same patent family, the ’680 Patent addresses the technical challenge of creating a high-concentration, injectable formulation for the poorly soluble drug fulvestrant. The disclosed solution is a formulation comprising fulvestrant, a ricinoleate vehicle (castor oil), one or more alcohols, and a non-aqueous ester solvent to enable a stable, sustained-release product suitable for intramuscular injection (’680 Patent, Abstract; col. 2:1-4).

  • Asserted Claims: The complaint alleges infringement of one or more unspecified claims (Compl. ¶61). Independent claim 1 is a representative method of treatment claim.

  • Accused Features: Teva's proposed generic Fulvestrant Injection, 250 mg/5ml, is alleged to be formulated in a way that will infringe when used as directed (Compl. ¶¶61, 64).

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

  • Issued: June 18, 2013

  • Technology Synopsis: As a member of the same patent family, the ’139 Patent is also directed to solving the poor solubility of fulvestrant to create a viable clinical product. It discloses a sustained-release formulation for intramuscular injection using a combination of a ricinoleate vehicle, alcohol co-solvents, and a non-aqueous ester solvent (’139 Patent, Abstract; col. 2:1-4).

  • Asserted Claims: The complaint alleges infringement of one or more unspecified claims (Compl. ¶75). Independent claim 1 is a representative method of treatment claim.

  • Accused Features: The accused instrumentality is Teva’s proposed generic fulvestrant injection, which the complaint alleges will meet the limitations of the claims when used according to its label (Compl. ¶¶75, 78).

III. The Accused Instrumentality

Product Identification

  • Defendant’s "Proposed NDA Product," identified as "Fulvestrant Injection, 250 mg/5ml (50 mg/ml)" (Compl. ¶¶ 6, 8).

Functionality and Market Context

  • The accused product is a generic version of AstraZeneca’s FASLODEX®, an injectable drug for treating hormone-dependent breast cancer (Compl. ¶¶ 8, 19). The complaint alleges that the product is designed for intramuscular injection and that its labeling will "substantially copy the instructions for FASLODEX®," thereby directing physicians and patients to use it in an infringing manner (Compl. ¶¶ 30, 35). This action arises under the Hatch-Waxman Act, where the filing of the New Drug Application (NDA) itself is the statutory act of infringement (Compl. ¶7). 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 comprising fulvestrant... Defendant's product is a Fulvestrant Injection intended for treating hormone-dependent breast cancer, and its label will direct administration via intramuscular injection. ¶¶ 8, 30 col. 9:56-61
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 Defendant’s product formulation meets every claim limitation, implying it contains this specific mixture of excipients. ¶31 col. 9:61-64
and a sufficient amount of a castor oil vehicle... The complaint alleges that Defendant's product contains a castor oil vehicle as required by the claim. ¶31 col. 9:64-65
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 a generic equivalent to FASLODEX®, the Defendant's product is alleged to produce the same results, including achieving the claimed pharmacokinetic profile. ¶31 col. 10:1-2

’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 administration to a human in need of such treatment an intra-muscular injection of a pharmaceutical formulation comprising fulvestrant... Defendant's product is a Fulvestrant Injection intended for treating hormone-dependent breast cancer, and its label will direct administration via intramuscular injection. ¶¶ 8, 49-50 col. 13:5-11
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 complaint alleges that Defendant’s product formulation meets every claim limitation, implying its excipient concentrations fall within these claimed ranges. ¶50 col. 13:11-15
and a sufficient amount of a castor oil vehicle... The complaint alleges that Defendant's product contains a castor oil vehicle as required by the claim. ¶50 col. 13:15-16
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 a generic equivalent to FASLODEX®, the Defendant's product is alleged to produce the same results, including achieving the claimed pharmacokinetic profile. ¶50 col. 13:16-19
  • Identified Points of Contention:
    • Technical Questions: The complaint does not provide the specific formulation of Teva's product. A primary factual question for the court will be whether the accused product's formulation literally contains the claimed excipients (ethanol, benzyl alcohol, benzyl benzoate, castor oil) in the amounts specified by the claims of the ’122 and ’160 patents, or is equivalent thereto.
    • Scope Questions: The asserted independent claims are for methods of treatment. Infringement will depend on a theory of inducement. A key legal question will be whether the instructions on Teva's proposed product label direct medical professionals to perform all steps of the claimed methods, thereby inducing infringement.

V. Key Claim Terms for Construction

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

  • Context and Importance: Practitioners may focus on this term because its interpretation determines the precision required to infringe. The absence of the word "about" could be a focal point for a non-infringement argument if Defendant’s formulation deviates even slightly from these exact percentages. This term is critical for the ’122 Patent, which recites exact values, but less so for the ’160 Patent, which claims ranges.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: A patentee might argue that a person of ordinary skill in the art would understand these values to include standard, acceptable manufacturing tolerances.
    • Evidence for a Narrower Interpretation: The claim language recites specific numerical percentages without qualification. The patent specification’s "Formulation Example" also recites these exact percentages, which could support a narrow construction limited to the precise values claimed (’122 Patent, col. 9:7-12).

  • The Term: "ricinoleate vehicle" (’122 Patent, Claim 1).

  • Context and Importance: The scope of this term defines the type of oil required. While the claim itself later specifies a "castor oil vehicle," clarity on the scope of "ricinoleate vehicle" is relevant, as it is used throughout the specification. Practitioners may focus on whether this term is limited to natural castor oil or could encompass other oils with similar chemical properties.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification explicitly states that the "ricinoleate vehicle may be a synthetic oil or conveniently is castor oil" (’122 Patent, col. 7:26-29), suggesting the term is not limited to naturally derived castor oil.
    • Evidence for a Narrower Interpretation: The primary embodiment described is castor oil, and the specification consistently refers to castor oil in its examples and discussion of prior art formulations (’122 Patent, col. 5:25-40; Tables 3-4).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement of infringement under 35 U.S.C. § 271(b). The factual basis is the allegation that Defendant's product will be sold with a label that directs and instructs physicians and patients to administer the drug in a manner that performs the steps of the patented methods (Compl. ¶¶ 30, 35, 37).
  • Willful Infringement: Willfulness is alleged based on Defendant’s knowledge of the patents-in-suit at the time it filed its NDA with a Paragraph IV certification (Compl. ¶¶ 38, 40). The complaint claims Defendant "knowingly and willfully" infringes and that its Paragraph IV certification was "wholly unjustified" (Compl. ¶¶ 40, 42).

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

  • A central issue will be one of factual composition: Does the formulation of Teva’s proposed generic product, which was not disclosed in the complaint, contain the same combination of a ricinoleate vehicle, specific alcohols, and a non-aqueous ester solvent in the concentrations recited in AstraZeneca's patents? Discovery of Teva's formulation will be critical to resolving this question of literal infringement or infringement under the doctrine of equivalents.
  • A key legal question will be one of induced infringement: Assuming the formulation is found to be infringing, does Teva's proposed product labeling contain instructions that are sufficiently detailed and direct to lead a fact-finder to conclude that Teva intended for, and would cause, medical professionals to perform every step of the asserted method-of-treatment claims?