DCT
1:17-cv-13075
AstraZeneca Pharma LP v. Fresenius Kabi USA LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: AstraZeneca Pharmaceuticals LP (Delaware), AstraZeneca UK Limited (England and Wales), and AstraZeneca AB (Sweden)
- Defendant: Fresenius Kabi USA, LLC (Delaware)
- Plaintiff’s Counsel: McCarter & English LLP; O’Melveny & Myers LLP
- Case Identification: 1:17-cv-13075, D.N.J., 12/14/2017
- Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant conducts substantial business in the state, is registered as a drug manufacturer there, and intends to market and sell the accused product within the district.
- Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's FASLODEX® (fulvestrant) product constitutes an act of infringement of four patents covering the drug's formulation and method of use.
- Technical Context: The technology concerns a long-acting, injectable pharmaceutical formulation designed to solubilize fulvestrant, a highly water-insoluble anti-estrogen compound used to treat hormone receptor-positive breast cancer.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant’s submission of ANDA No. 210326 with a Paragraph IV certification, asserting that the patents-in-suit are invalid and/or will not be infringed by its proposed generic product. The complaint notes that AstraZeneca has been involved in extensive, similar litigation against numerous other generic drug manufacturers over the same patents and FASLODEX® product.
Case Timeline
| Date | Event |
|---|---|
| 2000-01-10 | Earliest Priority Date for all Patents-in-Suit |
| 2004-08-10 | U.S. Patent No. 6,774,122 Issued |
| 2008-11-25 | U.S. Patent No. 7,456,160 Issued |
| 2012-12-11 | U.S. Patent No. 8,329,680 Issued |
| 2013-06-18 | U.S. Patent No. 8,466,139 Issued |
| 2017-10-31 | Fresenius Kabi sends Paragraph IV Notice Letter to AstraZeneca |
| 2017-12-08 | AstraZeneca gains limited access to Fresenius's ANDA materials |
| 2017-12-14 | 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 describes the therapeutic agent fulvestrant as a highly effective "pure" antiestrogen, but one that is extremely difficult to formulate for injection due to its very low aqueous solubility (’122 Patent, col. 4:50-54). Standard oil-based solvents alone cannot dissolve a sufficient amount of the drug to allow for a therapeutic dose to be administered in a clinically practical, low-volume injection (e.g., under 5 ml) (’122 Patent, col. 6:36-41).
- The Patented Solution: The invention is a pharmaceutical formulation that overcomes this solubility problem by dissolving fulvestrant in a specific combination of excipients: a ricinoleate vehicle (such as castor oil), a pharmaceutically acceptable alcohol (such as ethanol and/or benzyl alcohol), and a pharmaceutically acceptable non-aqueous ester solvent (such as benzyl benzoate) (’122 Patent, Abstract; col. 6:50-58). This combination of solvents unexpectedly allows for a much higher concentration of fulvestrant to be dissolved, enabling a sustained-release formulation that can be delivered in a small injection volume (’122 Patent, col. 6:46-52).
- Technical Importance: This formulation provided a vehicle for the long-term, intramuscular delivery of fulvestrant, enabling its use as a therapeutic agent for hormone-dependent conditions like breast cancer (’122 Patent, col. 4:59-64).
Key Claims at a Glance
- The complaint asserts infringement of "one or more Claims" of the ’122 Patent (Compl. ¶33). Independent claim 1 is representative.
- Independent Claim 1 is a method of treatment claim comprising the following essential elements:
- A method of treating a hormonal dependent benign or malignant disease of the breast or reproductive tract;
- By administering to a human an intra-muscular injection of a pharmaceutical formulation;
- Wherein the formulation comprises fulvestrant, a mixture of 10% weight of ethanol, 10% weight of benzyl alcohol, 15% weight of benzyl benzoate (all per volume of formulation), and a sufficient amount of a castor oil vehicle;
- Whereby a therapeutically significant blood plasma concentration of at least 2.5 ngml⁻¹ is attained for at least 2 weeks.
- The complaint implicitly reserves the right to assert other claims.
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 challenge: formulating the highly lipophilic and poorly soluble compound fulvestrant into a stable, high-concentration solution suitable for sustained-release intramuscular injection (’160 Patent, col. 5:1-11).
- The Patented Solution: The patented solution is the same formulation concept as in the ’122 Patent, comprising fulvestrant dissolved in a vehicle containing a ricinoleate vehicle (castor oil), at least one alcohol, and a non-aqueous ester solvent (’160 Patent, Abstract; col. 6:5-13). The claims of this patent, however, define the excipients using ranges rather than the fixed percentages of the ’122 Patent's lead claim.
- Technical Importance: The invention provides a viable pharmaceutical product for a potent anti-estrogen agent, addressing a significant formulation hurdle that could have otherwise limited its clinical utility (’160 Patent, col. 2:11-18).
Key Claims at a Glance
- The complaint asserts infringement of "one or more Claims" of the ’160 Patent (Compl. ¶47). Independent claim 1 is representative.
- Independent Claim 1 is a method of treatment claim comprising the following essential elements:
- A method of treating a hormonal dependent benign or malignant disease of the breast or reproductive tract;
- By administering to a human an intra-muscular injection of a pharmaceutical formulation;
- Wherein the formulation comprises fulvestrant, a mixture of from 10 to 30% weight of ethanol and benzyl alcohol, and from 10 to 25% weight of benzyl benzoate (all per volume of formulation), and a sufficient amount of a castor oil vehicle;
- Whereby a therapeutically significant blood plasma concentration of at least 2.5 ngml⁻¹ is attained for at least 2 weeks.
- The complaint implicitly reserves the right to assert other claims.
U.S. Patent No. 8,329,680 - “Formulation”
Issued December 11, 2012
- Patent Identification: U.S. Patent No. 8,329,680, “Formulation,” issued December 11, 2012 (Compl. ¶17).
- Technology Synopsis: This patent continues the same inventive theme, addressing the problem of formulating the poorly soluble drug fulvestrant for injection. The patent claims a specific method of treating hormone-dependent diseases by administering a formulation containing about 50 mg/ml of fulvestrant dissolved in a vehicle comprising specific amounts of ethanol, benzyl alcohol, benzyl benzoate, and castor oil to achieve a sustained therapeutic effect for at least four weeks (’680 Patent, Abstract; cl. 1).
- Asserted Claims: The complaint is general; independent claims 1 and 9 are representative (Compl. ¶61).
- Accused Features: The accused feature is Fresenius’s proposed generic fulvestrant injection, which the complaint alleges is intended to be used in a manner that infringes the patented method (Compl. ¶¶ 61-62).
U.S. Patent No. 8,466,139 - “Formulation”
Issued June 18, 2013
- Patent Identification: U.S. Patent No. 8,466,139, “Formulation,” issued June 18, 2013 (Compl. ¶18).
- Technology Synopsis: This patent also covers methods of treating hormone-dependent breast cancer by administering a sustained-release fulvestrant formulation. The invention solves the drug’s low solubility by using a specific combination of a ricinoleate vehicle, alcohols, and a non-aqueous ester solvent, with claims directed to specific compositional ranges and resulting therapeutic profiles (’139 Patent, Abstract; cl. 1).
- Asserted Claims: The complaint is general; independent claims 1 and 11 are representative (Compl. ¶75).
- Accused Features: The complaint alleges that Fresenius's proposed generic fulvestrant injection, including its formulation and intended use as described in its ANDA, infringes the patented method (Compl. ¶¶ 75-76).
III. The Accused Instrumentality
- Product Identification: The accused instrumentality is Defendant Fresenius’s proposed generic Fulvestrant Injection, 250 mg/5ml (50 mg/ml), for which it seeks FDA approval via ANDA No. 210326 (Compl. ¶¶ 6, 8).
- Functionality and Market Context: The complaint alleges that the accused product is a generic copy of AstraZeneca’s branded FASLODEX® product and relies upon it as the reference product (Compl. ¶29). The product is an intramuscular injection intended for the treatment of hormone-dependent breast cancer (Compl. ¶¶ 19, 30). As a generic submitted under an ANDA, the proposed product is intended to be therapeutically equivalent to the branded drug. The complaint alleges that Fresenius's proposed product label will substantially copy the instructions for FASLODEX®, directing its use for the patented indications (Compl. ¶30). The filing of the ANDA is the act of infringement giving rise to the lawsuit under 35 U.S.C. § 271(e)(2) (Compl. ¶34).
IV. Analysis of Infringement Allegations
The complaint alleges that because the accused product is a generic version of FASLODEX®, its composition and intended method of use will infringe the patents-in-suit (Compl. ¶¶ 29, 31). The specific details of the accused formulation are contained in the confidential ANDA and are not yet public record (Compl. ¶27). The allegations are therefore made on information and belief. No probative visual evidence provided in complaint.
’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... | Fresenius seeks approval to market its product for treating hormone-dependent breast cancer, and its proposed label will instruct users to perform this method of treatment. | ¶30 | col. 11:4-8 |
| by administration to a human in need of such treatment an intra-muscular injection of a pharmaceutical formulation... | The proposed product is an intramuscular injection designed for human use. | ¶30 | col. 6:42-45 |
| 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 and a sufficient amount of a castor oil vehicle,... | The complaint alleges on information and belief that the proposed product contains a formulation that meets every limitation of the claims, as it is a generic copy of the patented FASLODEX® product. | ¶31 | col. 11:55-61 |
| 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 required to be bioequivalent to FASLODEX®, the proposed product, when administered as directed, will allegedly produce the claimed pharmacokinetic profile. | ¶31 | col. 11:62-65 |
’160 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| ...comprising fulvestrant, a mixture of from 10 to 30% weight of ethanol and benzyl alcohol per volume of formulation and from 10 to 25% weight of benzyl benzoate per volume of formulation and a sufficient amount of a castor oil vehicle,... | The complaint alleges on information and belief that the proposed product's formulation, being a copy of FASLODEX®, will have excipient concentrations that fall within these claimed ranges. | ¶50 | col. 7:7-21 |
| [Other elements are substantially identical to those in claim 1 of the ’122 Patent and are alleged to be met on the same bases described above] | [The infringement theory is the same as for the corresponding elements of the ’122 Patent, based on the product being a generic copy intended for the same use] | ¶¶ 49-50 | col. 7:1-6, 22-24 |
- Identified Points of Contention:
- Factual Question: The primary factual dispute will concern the precise composition of Fresenius’s proposed generic product. The case will depend on whether discovery reveals that the formulation, as specified in the confidential ANDA, literally meets the compositional elements of the asserted claims.
- Scope Questions: The dispute may center on the scope of the claimed compositions. For the ’122 Patent, with its precise percentages, any deviation in Fresenius’s formulation could support a non-infringement defense. For the patents with ranges, the dispute may focus on whether Fresenius has designed a formulation that falls outside those ranges, or whether the ranges themselves are validly claimed.
V. Key Claim Terms for Construction
The Term: "a mixture of [X]% weight of... per volume of formulation" (and its variants with ranges).
- Context and Importance: This term is the core of the invention. Infringement will be determined by whether Fresenius's product formulation, as detailed in its ANDA, contains the claimed excipients at the specified concentrations. Practitioners may focus on this term because even minor deviations in the accused formulation from the claimed percentages could form the basis of a non-infringement argument, especially for the claims reciting exact percentages.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specifications of the patents disclose broader ranges for the components than what is recited in some of the narrowest claims (e.g., alcohol from 3-35% w/v) (’122 Patent, col. 7:6-12). A patentee might argue this context supports a less rigid interpretation, particularly for the doctrine of equivalents.
- Evidence for a Narrower Interpretation: The "Formulation Example" in the patents explicitly discloses a formulation with 10% ethanol, 10% benzyl alcohol, and 15% benzyl benzoate, which directly corresponds to the limitations in claim 1 of the ’122 Patent (’122 Patent, col. 11:55-12:18). A defendant could argue this ties the claim scope strictly to that specific, successful embodiment.
The Term: "ricinoleate vehicle"
- Context and Importance: This term defines the primary solvent system. The patents' success is attributed to this specific vehicle in combination with the other excipients. If Fresenius uses a different primary oil, it could argue non-infringement.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification defines the term as an oil having a certain proportion of its composition as triglycerides of ricinoleic acid and states it "may be a synthetic oil or conveniently is castor oil" (’122 Patent, col. 7:23-28). This language suggests the term is not limited exclusively to naturally derived castor oil.
- Evidence for a Narrower Interpretation: The specification consistently uses "castor oil" in all working examples and comparative data (e.g., FIG. 1), and attributes the formulation's unique solvating ability to castor oil specifically (’122 Patent, col. 6:20-25). A defendant may argue that the invention is functionally and factually limited to castor oil itself.
VI. Other Allegations
- Indirect Infringement: The complaint pleads induced infringement, alleging that Fresenius, through its proposed product labeling, will actively and intentionally instruct physicians and patients to administer the generic drug in a manner that directly infringes the patented methods of treatment (Compl. ¶¶ 30, 37, 51).
- Willful Infringement: Willfulness is alleged based on Fresenius having pre-suit knowledge of the patents-in-suit, as evidenced by its filing of a Paragraph IV certification, and proceeding to seek approval for its product nonetheless (Compl. ¶¶ 40, 54). The complaint further alleges that Fresenius lacked a good faith basis for its non-infringement and invalidity positions (Compl. ¶¶ 42, 56).
VII. Analyst’s Conclusion: Key Questions for the Case
- A primary issue will be one of compositional fact: does the precise formulation of excipients and their concentrations, as confidentially detailed in Fresenius’s ANDA, fall within the literal scope of any of AstraZeneca’s asserted patent claims?
- A central legal and factual dispute will be the question of validity: as required by its Paragraph IV certification, Fresenius will have to prove by clear and convincing evidence that the claimed formulation, which solved a known and difficult solubility problem, was nonetheless obvious or anticipated by the prior art at the time of the invention.
- The case may also present a question of claim scope and estoppel: should literal infringement fail, a key issue will be how the court construes the claim terms, and whether statements made during patent prosecution limit AstraZeneca's ability to recapture any surrendered subject matter through the doctrine of equivalents.