AstraZeneca Pharma LP v. Chia Tai Tianqing Pharmaceutical Group Co Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: AstraZeneca Pharmaceuticals LP (Delaware), et al.
  • Defendant: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. (China), et al.
  • Plaintiff’s Counsel: McCarter & English LLP
• Case Identification: 1:18-cv-17194, D.N.J., 12/13/2018
• Venue Allegations: Venue is alleged to be proper based on Defendants' business activities in New Jersey and, for the foreign defendant, the act of filing an Abbreviated New Drug Application (ANDA) with intent to market the product nationwide, including in the district.
• Core Dispute: Plaintiff alleges that Defendants' filing of an ANDA for a generic version of Plaintiff's FASLODEX® product constitutes an act of infringement of four patents covering the drug's long-acting injectable formulation.
• Technical Context: The technology concerns a pharmaceutical formulation designed to dissolve a poorly soluble anti-cancer drug, fulvestrant, in a non-aqueous vehicle for sustained intramuscular release.
• Key Procedural History: The complaint notes that the asserted patents have been the subject of numerous prior infringement suits against other generic drug manufacturers in the same district, and requests the case be assigned to the same judge, Hon. Renée M. Bumb, due to her familiarity with the technology and patents.

Case Timeline

Date	Event
2000-01-10	Priority Date for '122', '160', '680', '139' Patents
2004-08-10	'122 Patent Issued
2008-11-25	'160 Patent Issued
2012-12-11	'680 Patent Issued
2013-06-18	'139 Patent Issued
2018-11-02	Defendants' ANDA Notice Letter Sent
2018-12-13	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 difficulty of formulating the anti-estrogen drug fulvestrant, which is highly lipophilic and has extremely low aqueous solubility ('122 Patent, col. 4:50-55). This property makes it challenging to create a sustained-release injectable formulation that is concentrated enough to deliver a therapeutic dose in a small, clinically acceptable volume without the drug precipitating out of solution at the injection site ('122 Patent, col. 5:26-42).
• The Patented Solution: The invention is a non-aqueous, oil-based formulation that dissolves fulvestrant by using a specific combination of three components: a ricinoleate vehicle (castor oil), at least one alcohol co-solvent (such as ethanol and benzyl alcohol), and a non-aqueous ester co-solvent (such as benzyl benzoate) ('122 Patent, Abstract; col. 6:49-55). The patent asserts that the surprising discovery is that the addition of the non-aqueous ester solvent significantly improves the solubility of fulvestrant in the castor oil vehicle, enabling a high-concentration, low-volume, sustained-release product ('122 Patent, col. 6:49-60).
• Technical Importance: This formulation technology enabled the practical delivery of fulvestrant as a long-acting depot injection, providing a therapeutic option for hormone-dependent breast cancer that is a "pure" antiestrogen, unlike older drugs that had partial estrogen-like effects ('122 Patent, col. 4:5-19).

Key Claims at a Glance

• The complaint asserts infringement of one or more claims, with independent claims 1 and 5 being central to the method of use.
• Independent claim 1 requires, in essence:
  • A method of treating hormone-dependent breast or reproductive tract disease.
  • By intramuscular injection of a formulation comprising fulvestrant.
  • The formulation contains a mixture of 10% w/v ethanol, 10% w/v benzyl alcohol, and 15% w/v benzyl benzoate.
  • It also contains a sufficient amount of a castor oil vehicle.
  • The method results in a blood plasma concentration of at least 2.5 ngml⁻¹ for at least 2 weeks.
• The complaint reserves the right to assert other claims, including dependent claims (Compl. ¶35).

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 identical technical problem: creating a stable, long-acting, and sufficiently concentrated injectable formulation for the poorly soluble drug fulvestrant ('160 Patent, col. 4:52-58).
• The Patented Solution: The solution is the same combination of a ricinoleate vehicle (castor oil), alcohol co-solvents, and a non-aqueous ester solvent ('160 Patent, Abstract). The claims in this patent, however, recite broader ranges for the excipients, rather than the precise percentages found in claim 1 of the '122 Patent.
• Technical Importance: This patent broadens the protection around the core formulation concept, aiming to cover variations of the specific commercial embodiment.

Key Claims at a Glance

• The complaint asserts infringement of one or more claims, with independent claims 1 and 2 being central to the method of use.
• Independent claim 1 requires, in essence:
  • A method of treating hormone-dependent breast or reproductive tract disease.
  • By intramuscular injection of a formulation comprising fulvestrant.
  • The formulation contains a mixture of 10% to 30% w/v ethanol and benzyl alcohol.
  • It also contains 10% to 25% w/v of benzyl benzoate.
  • It also contains a sufficient amount of a castor oil vehicle.
  • The method results in a blood plasma concentration of at least 2.5 ngml⁻¹ for at least 2 weeks.
• The complaint reserves the right to assert other claims (Compl. ¶49).

U.S. Patent No. 8,329,680 - "Formulation", Issued December 11, 2012

• Technology Synopsis: This patent, a further continuation in the same family, addresses the challenge of creating a stable, long-acting injectable formulation for the highly insoluble anti-cancer drug fulvestrant ('680 Patent, col. 2:20-30). It discloses a specific combination of a castor oil vehicle, alcohol co-solvents (ethanol and benzyl alcohol), and a non-aqueous ester solvent (benzyl benzoate) to achieve a high drug concentration in a low, injectable volume, thereby enabling a once-monthly dosing regimen ('680 Patent, col. 11:40-45).
• Asserted Claims: Independent claims 1 and 9 are asserted ('680 Patent, col. 11:36-12:14; Compl. ¶63).
• Accused Features: The Proposed ANDA Product is accused of infringing by comprising the claimed formulation of fulvestrant, ethanol, benzyl alcohol, benzyl benzoate, and castor oil for the treatment of breast cancer (Compl. ¶¶30, 63).

U.S. Patent No. 8,466,139 - "Formulation", Issued June 18, 2013

• Technology Synopsis: As a later continuation in this patent family, this patent also addresses the problem of formulating the poorly soluble drug fulvestrant for intramuscular injection ('139 Patent, col. 2:23-33). The patented solution is a formulation comprising fulvestrant dissolved in a castor oil vehicle with a specific mixture of co-solvents—ethanol, benzyl alcohol, and benzyl benzoate—which enables a sustained-release, high-concentration product suitable for a defined dosing schedule ('139 Patent, Abstract; col. 11:8-23).
• Asserted Claims: Independent claims 1 and 11 are asserted ('139 Patent, col. 11:9-12:12; Compl. ¶77).
• Accused Features: The Proposed ANDA Product is accused of infringing by containing the claimed combination of active drug and excipients for use in treating breast cancer (Compl. ¶¶30, 77).

III. The Accused Instrumentality

Product Identification

• Defendants' Proposed ANDA Product is a generic Fulvestrant Injection, 250 mg/5 mL (50 mg/mL), submitted to the FDA under ANDA No. 211422 (Compl. ¶¶8, 10).

Functionality and Market Context

• The product is an injectable drug formulation intended to be a generic equivalent to AstraZeneca's branded FASLODEX® product (Compl. ¶10). The complaint alleges, on information and belief, that the product's formulation consists of fulvestrant, 10% w/v ethanol, 10% w/v benzyl alcohol, 15% w/v benzyl benzoate, and a sufficient amount of castor oil to achieve a final concentration of about 50 mg/ml fulvestrant (Compl. ¶30). The product is intended for the treatment of hormone-dependent breast cancer and is alleged to be bioequivalent to FASLODEX®, achieving a sustained blood plasma concentration (Compl. ¶¶31-32).
• No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

U.S. Patent No. 6,774,122 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	Defendants filed ANDA No. 211422 seeking approval to market and sell their product for the treatment of hormone-dependent breast cancer. The proposed product label is alleged to instruct physicians and patients to administer the drug for this purpose.	¶¶8, 32, 36	col. 4:5-19
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 ANDA Product is a pharmaceutical formulation containing these exact components in these exact proportions.	¶30	col. 9:11-16
whereby a therapeutically significant blood plasma fulvestrant concentration of at least 2.5 ngml⁻¹ is attained for at least 2 weeks after injection.	The ANDA is alleged to contain data demonstrating bioequivalence with FASLODEX®, including the achievement of a blood plasma fulvestrant concentration of at least 2.5 ng/ml⁻¹ for at least 4 weeks after injection.	¶31	col. 9:1-5

U.S. Patent No. 7,456,160 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	Defendants filed ANDA No. 211422 seeking approval to market their generic product with a label that will allegedly direct its use for treating hormone-dependent breast cancer.	¶¶8, 32, 50	col. 4:5-20
comprising fulvestrant, 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 and a sufficient amount of a castor oil vehicle	The alleged formulation of the Proposed ANDA Product (10% ethanol, 10% benzyl alcohol, 15% benzyl benzoate) falls within the claimed ranges for each excipient.	¶30	col. 7:1-21
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 FASLODEX® and to achieve the claimed pharmacokinetic profile.	¶31	col. 9:1-5

Identified Points of Contention

• Factual Question: The complaint's allegations regarding the precise formulation of the Proposed ANDA Product are made "on information and belief" (Compl. ¶30). The primary factual question for the court will be whether discovery of the confidential ANDA documents confirms that the generic formulation is identical to the one recited in the '122 Patent's claims and falls within the ranges of the '160 Patent's claims.
• Legal Question: Given that the infringement allegations map directly onto the alleged product composition, the central legal dispute will foreseeably focus on the validity of the asserted patents. Defendants' Paragraph IV certification alleges invalidity, suggesting they will likely argue that the claimed combination of known pharmaceutical excipients was obvious to a person of ordinary skill in the art at the time of the invention (Compl. ¶28).

V. Key Claim Terms for Construction

The Term: "a sufficient amount of a castor oil vehicle" ('122 Patent, Claim 1)

• Context and Importance: This term defines the quantity of the primary solvent in the formulation. Its construction is critical for definiteness under 35 U.S.C. § 112. Practitioners may focus on this term because open-ended quantity limitations can be vulnerable to indefiniteness challenges if the claim and specification fail to provide objective boundaries.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: Plaintiff may argue the term is clear in context, meaning the amount of castor oil needed to bring the total volume to 100% after adding the specified weight/volume percentages of the other components. The patent specification itself discusses making the solution to a final weight with castor oil, supporting this interpretation ('122 Patent, col. 9:57-60).
  • Evidence for a Narrower Interpretation: A defendant may argue the term is indefinite because it lacks an explicit lower or upper limit. They could point to the specification's disclosure that the ricinoleate vehicle should "preferably be present in the formulation in a proportion of at least 30% weight per volume" to argue that this essential characteristic is missing from the claim, rendering its scope unclear ('122 Patent, col. 7:28-31).

The Term: "therapeutically significant blood plasma fulvestrant concentration" ('122 Patent, Claim 1)

• Context and Importance: This term sets the functional pharmacokinetic requirement of the claimed method. Its definition is key to determining both infringement and whether the patent provides an enabling disclosure.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: Plaintiff will argue the patent provides its own definition. The specification states, "By use of the term 'therapeutically significant levels' we mean that blood plasma concentrations of at least 2.5 ngml⁻¹ ... are achieved in the patient" ('122 Patent, col. 9:1-5). This language suggests the term is explicitly defined and bounded.
  • Evidence for a Narrower Interpretation: A defendant might argue that the term is nonetheless indefinite if extrinsic evidence suggests a 2.5 ngml⁻¹ level is not, in fact, "therapeutically significant." They may also point to the patent's immediate follow-on sentence mentioning "ideally at least 3 ngml⁻¹, at least 8.5 ngml⁻¹" to suggest ambiguity in what level is truly required ('122 Patent, col. 9:3-4).

VI. Other Allegations

Indirect Infringement

• The complaint alleges induced infringement under 35 U.S.C. § 271(b). The factual basis is that Defendants' submission of an ANDA with a proposed product label that allegedly "substantially copy the instructions for FASLODEX®" demonstrates an affirmative intent to encourage and instruct physicians and patients to perform the patented method of treatment (Compl. ¶¶32, 37, 39).

Willful Infringement

• The complaint alleges that Defendants had knowledge of the patents-in-suit at the time of their ANDA filing, as evidenced by their Paragraph IV certification (Compl. ¶¶28-29). It further alleges that Defendants "lacked a good faith basis" for their assertions of invalidity and non-infringement, and therefore "knowingly and willfully" infringed (Compl. ¶¶42, 44).

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

• A central factual question will be one of compositional identity: Does the Defendants' proposed generic product, as detailed in their confidential ANDA, contain the exact formulation recited in the asserted claims? The case for infringement is premised on the complaint's "information and belief" allegations about the product's composition, which must be confirmed in discovery.
• A core legal issue will be one of patent validity: Can the Defendants establish by clear and convincing evidence that the claimed formulation—a specific combination of known excipients (castor oil, alcohols, benzyl benzoate) to solve the known problem of poor drug solubility—would have been obvious to a skilled formulator at the time of the invention? The extensive history of litigation involving these same patents against other generic challengers suggests this obviousness question has been and will continue to be the primary battleground.