DCT
1:17-cv-01968
AstraZeneca Pharma LP v. Amneal Pharma LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: AstraZeneca Pharmaceuticals LP (Delaware), AstraZeneca UK Limited (United Kingdom), and AstraZeneca AB (Sweden)
- Defendant: Amneal Pharmaceuticals LLC (Delaware)
- Plaintiff’s Counsel: McCarter & English LLP; O'Melveny & Myers LLP (Of Counsel)
- Case Identification: 1:17-cv-01968, D.N.J., 03/24/2017
- Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant maintains its principal place of business in the state.
- Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of Plaintiffs’ FASLODEX® (fulvestrant) injection constitutes an act of infringement of four patents covering pharmaceutical formulations.
- Technical Context: The technology concerns injectable, oil-based formulations designed to provide sustained release of fulvestrant, an anti-estrogen compound with very low water solubility used to treat hormone-receptor-positive breast cancer.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant’s ANDA filing and Paragraph IV certification notice. The complaint notes that numerous similar infringement actions concerning the same FASLODEX® product and patents have been filed against other generic manufacturers and have been assigned to or consolidated before the same judge, indicating a significant history of litigation over this patent portfolio.
Case Timeline
| Date | Event |
|---|---|
| 2000-01-10 | Earliest Priority Date (’122, ’160, ’680, ’139 Patents) |
| 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 |
| 2017-03-07 | Date of Defendant's Notice Letter |
| 2017-03-24 | Complaint Filing Date |
| 2019-02-19 | FASLODEX® New Indication Exclusivity Expiration |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 6,774,122 - “Formulation”
- Patent Identification: U.S. Patent No. 6774122, “Formulation,” issued August 10, 2004.
The Invention Explained
- Problem Addressed: The patent addresses the difficulty of formulating the drug fulvestrant for injection (’122 Patent, col. 4:46-54). Fulvestrant is a potent anti-estrogen agent, but it is "particularly lipophilic" and has "extremely low" aqueous solubility, making it difficult to prepare in a concentration high enough to be administered in a small, clinically acceptable injection volume (e.g., less than 5 ml) (’122 Patent, col. 4:49-54; col. 6:35-41).
- The Patented Solution: The invention is a pharmaceutical formulation that dissolves fulvestrant at a high concentration in a non-aqueous, oil-based vehicle suitable for sustained release after intramuscular injection (’122 Patent, Abstract). The solution uses a specific three-part solvent system: (1) a "ricinoleate vehicle" (such as castor oil), which is a better solvent for fulvestrant than other oils; (2) at least one alcohol (e.g., ethanol, benzyl alcohol); and (3) a non-aqueous ester solvent (e.g., benzyl benzoate) (’122 Patent, col. 1:7-15). The patent asserts the surprising discovery that this combination of excipients "eases the solubilisation of fulvestrant" to a high concentration, which could not be achieved with the oil alone or just the oil and alcohol (’122 Patent, col. 6:49-58).
- Technical Importance: This formulation technology enabled the development of a commercially viable, long-acting depot injection for fulvestrant, providing sustained therapeutic drug levels for weeks from a single injection and improving patient convenience and compliance (’122 Patent, col. 6:1-6).
Key Claims at a Glance
- The complaint asserts infringement of "one or more Claims" without specifying them (Compl. ¶23). Independent claim 1 is a representative method of treatment claim.
- Essential elements of independent claim 1:
- A method of treating a hormonal dependent benign or malignant disease of the breast or reproductive tract.
- By administering an intra-muscular injection of a pharmaceutical formulation comprising fulvestrant.
- The formulation includes 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.
- It includes 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.
- The complaint does not explicitly reserve the right to assert dependent claims.
U.S. Patent No. 7,456,160 - “Formulation”
- Patent Identification: U.S. Patent No. 7456160, “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: the difficulty of creating a highly concentrated, stable, injectable formulation for the poorly soluble drug fulvestrant (’160 Patent, col. 5:1-5).
- The Patented Solution: The patented solution is materially the same as in the ’122 Patent, centering on a formulation containing fulvestrant, a ricinoleate vehicle, a pharmaceutically acceptable alcohol, and a non-aqueous ester solvent (’160 Patent, col. 6:5-12). The claims of the ’160 Patent recite different and broader concentration ranges for the excipients.
- Technical Importance: The invention provides an alternative, potentially broader scope of protection for the core formulation technology, covering a wider range of excipient concentrations that achieve the desired sustained-release profile (’160 Patent, col. 7:2-11).
Key Claims at a Glance
- The complaint asserts infringement of "one or more Claims" without specifying them (Compl. ¶37). Independent claim 1 is a representative method of treatment claim.
- Essential elements of independent claim 1:
- A method of treating a hormonal dependent benign or malignant disease of the breast or reproductive tract.
- By administering an intra-muscular injection of a pharmaceutical formulation comprising fulvestrant.
- The formulation includes a mixture of from 10 to 30% weight of ethanol and benzyl alcohol per volume of formulation.
- It includes from 10 to 25% weight of benzyl benzoate per volume of formulation.
- It includes 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.
- The complaint does not explicitly reserve the right to assert dependent claims.
U.S. Patent No. 8,329,680 - “Formulation”
- Patent Identification: U.S. Patent No. 8329680, "Formulation," issued December 11, 2012.
- Technology Synopsis: The ’680 Patent is also in the same family and addresses the same problem of creating a stable, long-acting injectable formulation for fulvestrant. The solution is the same three-part solvent system (ricinoleate vehicle, alcohol(s), and a non-aqueous ester solvent) but claims a specific embodiment of that formulation (’680 Patent, col. 11:41-51).
- Asserted Claims: The complaint asserts "one or more Claims" (Compl. ¶51). Independent claim 1 is a representative method of treatment claim.
- Accused Features: The accused feature is the formulation of Defendant's Proposed ANDA Product, which is alleged to contain the claimed combination of fulvestrant, ethanol, benzyl alcohol, benzyl benzoate, and castor oil vehicle (Compl. ¶¶6, 51, 54).
U.S. Patent No. 8,466,139 - “Formulation”
- Patent Identification: U.S. Patent No. 8466139, "Formulation," issued June 18, 2013.
- Technology Synopsis: The ’139 Patent continues the same patent family and technology, directed to specific methods of using the fulvestrant formulation. It claims specific concentration ranges for the excipients that differ from the parent patents, aiming to protect particular optimized versions of the formulation (’139 Patent, col. 11:10-23).
- Asserted Claims: The complaint asserts "one or more Claims" (Compl. ¶65). Independent claim 1 is a representative method of treatment claim.
- Accused Features: The accused feature is the formulation of Defendant's Proposed ANDA Product and its method of use, which are alleged to meet the specific composition and concentration parameters of the claims (Compl. ¶¶6, 65, 68).
III. The Accused Instrumentality
Product Identification
- Defendant Amneal's "Proposed ANDA Product," identified as Fulvestrant Injection, 250 mg/5 mL (50 mg/mL) prefilled syringes, submitted for FDA approval under ANDA No. 210044 (Compl. ¶6).
Functionality and Market Context
- The Proposed ANDA Product is a generic version of AstraZeneca's branded drug, FASLODEX® (Compl. ¶6). The complaint alleges it is intended for the same use: treatment of hormone receptor (HR)-positive metastatic breast cancer in postmenopausal women (Compl. ¶21). The ANDA filing relies on the clinical data for FASLODEX® and contains data intended to demonstrate bioequivalence (Compl. ¶20). The commercial context is that of a generic drug seeking to enter the market upon the expiration of regulatory exclusivities and patents covering the branded reference product (Compl. ¶18). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint does not provide a claim chart or specific details of the accused formulation. The infringement allegations are based on the submission of ANDA No. 210044, which itself constitutes a technical act of infringement under 35 U.S.C. § 271(e)(2). The following tables summarize the infringement theory based on the allegation that the Proposed ANDA Product is a generic copy of FASLODEX®, which is covered by the patents-in-suit.
'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 | The Proposed ANDA Product will have instructions for use to treat HR-positive metastatic breast cancer. | ¶21 | col. 9:4-6 |
| by administration...an intra-muscular injection of a pharmaceutical formulation comprising fulvestrant... | The Proposed ANDA Product is a fulvestrant formulation in a prefilled syringe for intramuscular injection. | ¶6, ¶21 | col. 9:7-9 |
| 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 the Proposed ANDA Product is covered by the claims, implying its formulation contains these excipients at these concentrations. | ¶23, ¶26 | col. 9:59-62 |
| and a sufficient amount of a castor oil vehicle... | The complaint alleges the Proposed ANDA Product is covered by the claims, implying its formulation contains a castor oil vehicle. | ¶23, ¶26 | col. 9:62-63 |
'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 | The Proposed ANDA Product will have instructions for use to treat HR-positive metastatic breast cancer. | ¶21 | col. 12:7-10 |
| by administration...an intra-muscular injection of a pharmaceutical formulation comprising fulvestrant... | The Proposed ANDA Product is a fulvestrant formulation in a prefilled syringe for intramuscular injection. | ¶6, ¶21 | col. 12:7-13 |
| a mixture of from 10 to 30% weight of ethanol and benzyl alcohol per volume of formulation | The complaint alleges the Proposed ANDA Product is covered by the claims, implying its formulation contains this mixture within this range. | ¶37, ¶40 | col. 13:9-11 |
| and from 10 to 25% weight of benzyl benzoate per volume of formulation... | The complaint alleges the Proposed ANDA Product is covered by the claims, implying its formulation contains this excipient within this range. | ¶37, ¶40 | col. 13:11-13 |
| and a sufficient amount of a castor oil vehicle... | The complaint alleges the Proposed ANDA Product is covered by the claims, implying its formulation contains a castor oil vehicle. | ¶37, ¶40 | col. 13:13-14 |
Identified Points of Contention
- Factual Scope: The central question will be factual: does the specific formulation detailed in Amneal's confidential ANDA contain the claimed excipients within the claimed concentration ranges? As the complaint does not disclose Amneal's formulation, this will be a primary focus of discovery.
- Technical Questions: A key technical question is whether Defendant’s formulation, if it differs slightly from the claims, can be considered equivalent. For instance, does a different non-aqueous ester solvent perform the same function in the same way to achieve the same result as the claimed benzyl benzoate? The complaint does not provide sufficient detail for analysis of this point.
V. Key Claim Terms for Construction
The Term: "ricinoleate vehicle" (’122 Patent, col. 9:63)
Context and Importance
This term defines the primary oil solvent and is the foundation of the formulation. The defendant may argue for a narrow construction limited to specific grades or types of castor oil, while the plaintiff will likely argue for a broader meaning covering any oil that functions as a ricinoleate vehicle. Practitioners may focus on this term because its scope determines whether formulations using synthetic or modified oils with similar chemical properties could be captured by the claims.
Intrinsic Evidence for Interpretation
- Evidence for a Broader Interpretation: The specification defines the term functionally: "an oil which has as a proportion (at least 20%...) of its composition as triglycerides of ricinoleic acid" (’122 Patent, col. 7:23-26). This language suggests that any oil meeting this functional definition, not just natural castor oil, would fall within the scope.
- Evidence for a Narrower Interpretation: The specification consistently uses "castor oil" as the primary and ideal example, stating "The ricinoleate vehicle may be a synthetic oil or conveniently is castor oil, ideally of pharmacopoeial standards" (’122 Patent, col. 7:26-28). A defendant could argue this emphasis, combined with the examples, limits the term's practical scope to castor oil itself.
The Term: "a mixture of ... ethanol and benzyl alcohol" (’160 Patent, col. 13:9-11)
Context and Importance
This term describes the alcohol co-solvent component. The construction of "mixture" and the associated concentration ranges is critical. The patents-in-suit have claims with varying degrees of specificity for the alcohol components, and a dispute may arise over whether simply having both alcohols present is sufficient, or if a particular ratio or functional interaction is implicitly required.
Intrinsic Evidence for Interpretation
- Evidence for a Broader Interpretation: The claims in the ’160 Patent provide a broad range for the combined alcohols (10-30% w/v), suggesting flexibility in the composition. The specification discusses them as "pharmaceutically-acceptable alcohols" that may consist of "one alcohol or a mixture of two or more alcohols" (’160 Patent, col. 7:26-29).
- Evidence for a Narrower Interpretation: The preferred embodiment described in the specification uses equal amounts (10% w/v each) of ethanol and benzyl alcohol (’160 Patent, col. 7:32-34). A defendant might argue that this specific combination is what enables the invention and that the term "mixture" should be construed in light of this optimal, disclosed ratio.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that upon approval, Amneal will actively induce infringement by providing product labeling that "will direct physicians and patients on the use of the Proposed ANDA Product" in a manner that directly infringes the method claims (Compl. ¶25, ¶27, ¶39). This is a standard allegation in Hatch-Waxman litigation.
- Willful Infringement: Willfulness is alleged based on Defendant’s knowledge of the patents-in-suit at the time it filed its ANDA, as evidenced by its Paragraph IV certification (Compl. ¶¶18-19, 30, 44). The complaint further alleges that the Defendant’s notice letter "lacks any legal or factual basis for non-infringement" and that its invalidity certification was not made in good faith, which could support a finding of willful infringement and an exceptional case under 35 U.S.C. § 285 (Compl. ¶29, ¶32).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central question will be one of factual infringement: Does the confidential formulation disclosed in Amneal’s ANDA No. 210044 fall within the literal scope of any asserted claim, particularly with respect to the identity and concentration of the claimed excipients (castor oil, specific alcohols, and benzyl benzoate)?
- The case will also involve a significant battle over patent validity. While not detailed in the complaint, Amneal’s Paragraph IV certification asserts that the patents are invalid. The court will need to adjudicate whether the claimed formulations were obvious in light of prior art knowledge regarding the use of co-solvents for poorly soluble steroids.
- Finally, a key legal issue will be one of claim scope: How broadly will the court construe dispositive terms like "ricinoleate vehicle"? The outcome of claim construction will determine whether minor variations in the generic formulation—should they exist—are sufficient to place the Proposed ANDA Product outside the reach of AstraZeneca's patents.