DCT

1:17-cv-02652

AstraZeneca Pharma LP v. HBT Labs Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-02652, D.N.J., 04/18/2017
  • Venue Allegations: Venue is asserted based on Defendant's marketing and sale of generic pharmaceuticals in the District of New Jersey, from which it allegedly derives substantial revenue, and its maintenance of continuous and systematic contacts with the state.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for a generic version of Plaintiff's FASLODEX® breast cancer treatment constitutes an act of infringement of four patents covering the drug's injectable formulation.
  • Technical Context: The technology concerns sustained-release pharmaceutical formulations designed to overcome the poor solubility of fulvestrant, an antiestrogen drug used to treat hormone receptor-positive breast cancer.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant’s notification to Plaintiff of its ANDA filing (No. 209714), which included a Paragraph IV certification alleging the patents-in-suit are invalid or not infringed. The complaint notes that numerous related litigations against other generic manufacturers for the same product have been filed in the District of New Jersey.

Case Timeline

Date Event
2000-01-10 Priority Date for ’122, ’160, ’680, and ’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
2017-03-27 Date of Defendant's ANDA Notice Letter to Plaintiff
2017-04-18 Complaint Filing Date

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 6,774,122 - Formulation

  • Patent Identification: U.S. Patent No. 6,774,122 ("the ’122 Patent"), Formulation, issued August 10, 2004.

The Invention Explained

  • Problem Addressed: The patent addresses the difficulty of formulating the anti-estrogen drug fulvestrant for injection (Compl. ¶15; ’122 Patent, col. 4:47-53). Fulvestrant is highly lipophilic (oil-soluble) and has extremely low aqueous solubility, making it challenging to create a solution that is concentrated enough to be administered in a small, patient-acceptable volume while also providing a sustained therapeutic effect (’122 Patent, col. 4:47-53). A simple oil-based solvent would require an "excessively large volume" of at least 10 ml for a single dose (’122 Patent, col. 6:36-41).
  • The Patented Solution: The invention is a pharmaceutical formulation that uses a three-part solvent system to overcome fulvestrant's solubility issues. The formulation combines a ricinoleate vehicle (specifically, 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). The patent teaches that this specific combination of excipients "surprisingly eases the solubilisation of fulvestrant," enabling a high-concentration (e.g., 50 mg/ml) solution that can be administered in a low volume (e.g., 5 ml) for sustained release (’122 Patent, col. 6:47-58).
  • Technical Importance: This formulation technology was critical for the development of fulvestrant as a long-acting intramuscular injection, providing a practical way to deliver a therapeutic dose that remains effective for weeks (’122 Patent, col. 6:26-34).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims of the ’122 Patent (Compl. ¶25). The patent’s broadest independent claim is method of treatment claim 1.
  • Essential elements of independent claim 1 include:
    • A method of treating a hormonal dependent disease of the breast or reproductive tract.
    • Administering via intra-muscular injection a pharmaceutical formulation comprising fulvestrant.
    • The formulation contains a mixture of "10% weight of ethanol," "10% weight of benzyl alcohol," and "15% weight of benzyl benzoate" per volume of formulation.
    • The formulation also contains "a sufficient amount of a castor oil vehicle."
    • The method results in a blood plasma fulvestrant concentration of "at least 2.5 ngml⁻¹" for "at least 2 weeks after injection."

U.S. Patent No. 7,456,160 - Formulation

  • Patent Identification: U.S. Patent No. 7,456,160 ("the ’160 Patent"), Formulation, issued November 25, 2008.

The Invention Explained

  • Problem Addressed: The ’160 Patent, which is a continuation of the application that led to the ’122 Patent, addresses the same technical challenge of fulvestrant's poor solubility hampering the development of a practical, low-volume, sustained-release injectable (’160 Patent, col. 4:51-58).
  • The Patented Solution: The solution is the same three-part solvent system comprising a ricinoleate vehicle, an alcohol, and a non-aqueous ester solvent (’160 Patent, Abstract). The specification is substantively identical to that of the ’122 Patent, but the claims are structured differently, claiming ranges of excipients rather than fixed percentages.
  • Technical Importance: The technology provides a viable platform for delivering the therapeutically important but difficult-to-formulate fulvestrant drug via intramuscular injection (’160 Patent, col. 6:8-14).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims of the ’160 Patent (Compl. ¶39). The patent’s broadest independent claim is method of treatment claim 1.
  • Essential elements of independent claim 1 include:
    • A method of treating a hormonal dependent disease of the breast or reproductive tract.
    • Administering via intra-muscular injection a pharmaceutical formulation comprising fulvestrant.
    • The formulation contains a mixture of "from 10 to 30% weight of ethanol and benzyl alcohol" per volume of formulation.
    • The formulation contains "from 10 to 25% weight of benzyl benzoate" per volume of formulation.
    • The formulation also contains "a sufficient amount of a castor oil vehicle."
    • The method results in a blood plasma fulvestrant concentration of "at least 2.5 ngml⁻¹" for "at least 2 weeks after injection."

Multi-Patent Capsule: U.S. Patent No. 8,329,680

  • Patent Identification: U.S. Patent No. 8,329,680 ("the ’680 Patent"), Formulation, issued December 11, 2012.
  • Technology Synopsis: As a continuation in the same patent family, the ’680 Patent addresses the identical problem of fulvestrant's poor solubility (’680 Patent, col. 6:45-50). It claims a method of treating hormone-dependent diseases by administering a specific formulation of fulvestrant in a castor oil vehicle with alcohol and benzyl benzoate co-solvents, where the formulation provides a therapeutic effect for at least four weeks (’680 Patent, col. 11:41-59).
  • Asserted Claims: The complaint does not specify claims (Compl. ¶53); independent claims 1 and 9 are the broadest.
  • Accused Features: Defendant's Proposed ANDA Product is alleged to be a formulation containing the same ingredients as claimed, with a proposed label that instructs its use for treating breast cancer in a manner that allegedly infringes the claimed method (Compl. ¶¶21-23, 53).

Multi-Patent Capsule: U.S. Patent No. 8,466,139

  • Patent Identification: U.S. Patent No. 8,466,139 ("the ’139 Patent"), Formulation, issued June 18, 2013.
  • Technology Synopsis: The ’139 Patent is also part of the same patent family and addresses the same technical problem (’139 Patent, col. 6:50-55). It claims methods of treating hormone-dependent diseases by administering a fulvestrant formulation containing specific ranges of alcohol and benzyl benzoate in a castor oil vehicle (’139 Patent, col. 11:10-24).
  • Asserted Claims: The complaint does not specify claims (Compl. ¶67); independent claims 1 and 11 are the broadest.
  • Accused Features: The composition of Defendant's Proposed ANDA Product and the instructions for its use on the proposed label are alleged to meet the limitations of the asserted claims (Compl. ¶¶21-23, 67).

III. The Accused Instrumentality

Product Identification

  • Defendant HBT Labs, Inc.’s "Proposed ANDA Product," identified as Fulvestrant Injection, 250 mg/5 mL, for which it seeks FDA approval under ANDA No. 209714 (Compl. ¶6).

Functionality and Market Context

  • The Proposed ANDA Product is a generic version of AstraZeneca’s FASLODEX® and is intended for intramuscular injection to treat hormone receptor (HR)-positive metastatic breast cancer (Compl. ¶6, ¶23).
  • The complaint alleges the product is a pharmaceutical formulation comprising the active ingredient fulvestrant at a concentration of about 50 mg/ml, along with the following excipients: "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" (Compl. ¶21).
  • The complaint further alleges that the ANDA contains data demonstrating the product's bioequivalence to FASLODEX®, including its ability to achieve a blood plasma fulvestrant concentration of at least 2.5 ngml⁻¹ for at least 4 weeks after injection (Compl. ¶22).
  • 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... The Defendant's Proposed ANDA Product will have instructions for use that direct physicians to administer the product via intramuscular injection for the treatment of hormone receptor (HR)-positive metastatic breast cancer in humans. ¶23 col. 9:4-11
comprising fulvestrant... The Proposed ANDA Product is a pharmaceutical formulation that contains fulvestrant as its active ingredient. ¶21 col. 4:63-65
...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 the Proposed ANDA Product contains the exact mixture of excipients specified in the claim: 10% w/v ethanol, 10% w/v benzyl alcohol, and 15% w/v benzyl benzoate. ¶21 col. 9:58-63
...and a sufficient amount of a castor oil vehicle... The Proposed ANDA Product contains a castor oil vehicle. ¶21 col. 9:63-64
...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 Defendant’s ANDA filing allegedly contains data demonstrating that its product is bioequivalent to FASLODEX® and achieves a plasma concentration of at least 2.5 ngml⁻¹ for at least 4 weeks, thereby meeting this limitation. ¶22 col. 9:1-5

’160 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
...a mixture of from 10 to 30% weight of ethanol and benzyl alcohol per volume of formulation... The Proposed ANDA Product allegedly contains 10% w/v ethanol and 10% w/v benzyl alcohol, for a total alcohol content of 20% w/v. This amount falls squarely within the claimed range of 10% to 30%. ¶21 col. 7:1-12
...and from 10 to 25% weight of benzyl benzoate per volume of formulation... The Proposed ANDA Product allegedly contains 15% w/v of benzyl benzoate, which falls within the claimed range of 10% to 25%. ¶21 col. 7:42-50
Other elements are substantially similar to those analyzed for the ’122 Patent. The alleged infringing functionalities for the method of use, presence of fulvestrant, castor oil vehicle, and resulting plasma concentration are identical to those described for the ’122 Patent. ¶21-23 col. 9:1-11
  • Identified Points of Contention:
    • Scope Questions: The infringement allegation for the ’122 Patent appears to rely on the defendant's formulation having the exact percentages recited in claim 1 (e.g., "10%," "15%"). A central question for the court may be whether these terms must be interpreted as precise values or if they permit standard manufacturing tolerances. Any deviation in the composition specified in the ANDA could be the basis for a non-infringement defense against this specific patent, though the ranges in the ’160 Patent provide a wider scope of protection for the plaintiff.
    • Technical Questions: The case will depend on a factual comparison between the specific formulation detailed in HBT’s confidential ANDA submission and the claim limitations. While the complaint makes direct allegations about the ANDA product's composition (Compl. ¶21), discovery will be required to confirm whether this composition is what the ANDA actually specifies.

V. Key Claim Terms for Construction

  • The Term: "10% weight of ethanol per volume of formulation" (and similar terms for other excipients in claim 1 of the ’122 Patent).
  • Context and Importance: The construction of this term is critical for the infringement analysis of the ’122 Patent. Practitioners may focus on this term because the patentee chose to claim a specific percentage without using modifiers like "about," while later patents in the same family (e.g., the ’160 Patent) explicitly claim ranges. The defendant may argue that this demonstrates an intent to limit the claim to the exact percentage, providing a potential non-infringement defense if its product's specification deviates even slightly.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification describes preferred ranges for the formulation components, for example, stating that the alcohol may be present in a range of 3-35% w/v (’122 Patent, col. 7:6-12). A party could argue that the specific "10%" value in the claim is an exemplary embodiment and should be interpreted in light of the broader disclosure, thus encompassing minor variations.
    • Evidence for a Narrower Interpretation: The claim language itself is precise. The fact that other patents in the family, and even other claims within the extended prosecution history, use ranges could be used to argue that the patentee deliberately chose a narrow, specific value here. This contrast between the use of ranges elsewhere and a specific number in claim 1 of the ’122 Patent may support a construction that does not allow for variation beyond the exact number.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement, stating that Defendant's proposed product labeling will instruct physicians and patients to administer the drug for treating HR-positive breast cancer (Compl. ¶23). This act of providing instructions for a use covered by the method claims is alleged to demonstrate HBT's intent to encourage infringement by others (Compl. ¶27-29, ¶41-43).
  • Willful Infringement: Willfulness is alleged based on Defendant’s pre-suit knowledge of the patents. The complaint asserts that HBT was "necessarily aware" of the patents when it filed its ANDA and the associated Paragraph IV Certification, and that it received a formal Notice Letter, thereby establishing knowledge (Compl. ¶19-20, ¶32). The complaint further alleges that HBT's certification of non-infringement or invalidity was "wholly unjustified" and lacked a good faith basis (Compl. ¶34).

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

  • A central issue will be one of claim construction versus factual identity: Will the court construe the term "10%" in the ’122 Patent to mean precisely 10.0%, or will it allow for standard manufacturing variations? The outcome of this question, when compared against the specific formulation disclosed in HBT's ANDA, will likely be dispositive of infringement for the earliest patent in the family.
  • A key legal and factual battleground will likely be obviousness: Given that the defendant certified the patents as invalid, the litigation may focus on whether combining a castor oil vehicle with alcohol and benzyl benzoate co-solvents to increase the solubility of a lipophilic steroid like fulvestrant would have been obvious to a person of ordinary skill in the art at the time of the invention.
  • An underlying question is one of induced infringement: As the patents-in-suit primarily contain method of treatment claims, the plaintiff's case relies on showing that the defendant's proposed product label will actively encourage or instruct physicians to perform the patented method, thereby inducing infringement.