DCT
2:23-cv-00123
Fennec Pharma Inc v. Cipla Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Fennec Pharmaceuticals Inc. (North Carolina)
- Defendant: Cipla Limited (India) and Cipla USA, Inc. (Delaware)
- Plaintiff’s Counsel: Marino, Tortorella & Boyle, P.C.; Groombridge, Wu, Baughman & Stone LLP
- Case Identification: 2:23-cv-00123, D.N.J., 07/27/2023
- Venue Allegations: Venue is alleged to be proper based on Cipla Ltd. being a foreign corporation subject to personal jurisdiction in the district, and Cipla USA, Inc. having a regular and established place of business in Warren, New Jersey.
- Core Dispute: Plaintiff alleges that Defendant’s Abbreviated New Drug Application (ANDA) for a generic sodium thiosulfate injection infringes patents covering formulations of Plaintiff's branded drug, PEDMARK®, used to prevent chemotherapy-induced hearing loss in pediatric patients.
- Technical Context: The technology concerns stable, injectable pharmaceutical formulations of sodium thiosulfate designed to mitigate ototoxicity (hearing damage) associated with cisplatin chemotherapy.
- Key Procedural History: This Hatch-Waxman action was initiated after Defendant filed an ANDA seeking FDA approval for a generic version of Plaintiff's PEDMARK®. Defendant provided Plaintiff with Paragraph IV Certifications asserting that the patents-in-suit are invalid, unenforceable, and/or will not be infringed by the proposed generic product. Plaintiff's PEDMARK® product is listed in the FDA's Orange Book and has been granted orphan-drug exclusivity until September 2029.
Case Timeline
| Date | Event |
|---|---|
| 2018-07-03 | Priority Date for ’728, ’984, and ’793 Patents |
| 2022-04-05 | U.S. Patent No. 11,291,728 Issues |
| 2022-09-20 | FDA Approves Fennec’s PEDMARK® |
| 2022-10-06 | ’728 Patent Listed in FDA Orange Book |
| 2022-11-29 | U.S. Patent No. 11,510,984 Issues |
| 2022-12-01 | Fennec Receives Paragraph IV Notice Letter for ’728 Patent |
| 2022-12-14 | ’984 Patent Listed in FDA Orange Book |
| 2023-01-06 | Fennec Receives Paragraph IV Notice Letter for ’984 Patent |
| 2023-01-25 | FDA Grants PEDMARK® Orphan Drug Exclusivity |
| 2023-04-04 | U.S. Patent No. 11,617,793 Issues |
| 2023-04-17 | ’793 Patent Listed in FDA Orange Book |
| 2023-05-11 | Fennec Receives Paragraph IV Notice Letter for ’793 Patent |
| 2023-07-27 | Second Amended Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,291,728 - "Anhydrous Sodium Thiosulfate and Formulations Thereof"
- Patent Identification: U.S. Patent No. 11,291,728, "Anhydrous Sodium Thiosulfate and Formulations Thereof," issued April 5, 2022.
The Invention Explained
- Problem Addressed: The patent background describes the significant clinical problem of ototoxicity—progressive and irreversible hearing loss—caused by platinum-based chemotherapeutics such as cisplatin, particularly in pediatric cancer patients who depend on normal hearing for development (ʼ728 Patent, col. 1:26-45).
- The Patented Solution: The invention provides a pharmaceutical composition of anhydrous sodium thiosulfate in a specific aqueous formulation with a buffer. The detailed description explains that such compositions are designed to be stable and suitable for administration to reduce ototoxicity without compromising the efficacy of the chemotherapy (ʼ728 Patent, col. 1:46-51, Abstract).
- Technical Importance: The development of a stable, approved formulation for sodium thiosulfate addressed a long-standing need for a therapy to prevent a severe side effect of a common pediatric cancer treatment (Compl. ¶1).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶40).
- Claim 1 requires:
- A pharmaceutical composition comprising aqueous anhydrous sodium thiosulfate,
- wherein the aqueous anhydrous sodium thiosulfate is at a concentration of about 0.5 M,
- and further comprising about 0.004 M boric acid.
- The complaint seeks relief for infringement of "one or more claims," suggesting the right to assert additional claims is preserved (Compl. ¶59).
U.S. Patent No. 11,510,984 - "Anhydrous Sodium Thiosulfate and Formulations Thereof"
- Patent Identification: U.S. Patent No. 11,510,984, "Anhydrous Sodium Thiosulfate and Formulations Thereof," issued November 29, 2022.
The Invention Explained
- Problem Addressed: The patent addresses the same technical problem as the related ’728 Patent: cisplatin-induced ototoxicity in pediatric patients and the need for a safe and effective otoprotective formulation (ʼ984 Patent, col. 1:26-51).
- The Patented Solution: This patent also discloses a pharmaceutical composition based on aqueous anhydrous sodium thiosulfate. It distinguishes itself from the ’728 Patent by claiming the composition based on the concentration of "borate ions" rather than the molarity of boric acid, offering a different way to define the formulation's buffering system (ʼ984 Patent, Claim 1).
- Technical Importance: As part of the same patent family covering Fennec's PEDMARK® product, this patent helps protect the commercial formulation that was the first FDA-approved therapy for this indication (Compl. ¶1, ¶2).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶43).
- Claim 1 requires:
- A pharmaceutical composition comprising aqueous anhydrous sodium thiosulfate,
- wherein the aqueous anhydrous sodium thiosulfate is at a concentration of about 0.5 M,
- and further comprising borate ions wherein the concentration of borate ions is less than 0.05%.
- The complaint preserves the right to assert additional claims (Compl. ¶80).
U.S. Patent No. 11,617,793 - "Anhydrous Sodium Thiosulfate and Formulations Thereof"
- Patent Identification: U.S. Patent No. 11,617,793, "Anhydrous Sodium Thiosulfate and Formulations Thereof," issued April 4, 2023.
Technology Synopsis
This patent addresses the problem of cisplatin-induced hearing loss by claiming a specific sodium thiosulfate formulation (’793 Patent, col. 1:26-51). The patented solution is an aqueous composition defined by the concentrations of sodium thiosulfate and boric acid, as well as a specific pH range, intended to provide a stable and effective otoprotective agent (’793 Patent, Abstract; Claim 1).
Asserted Claims
Independent claim 1 is asserted (Compl. ¶46).
Accused Features
The complaint alleges that Defendant’s proposed generic product, by seeking to be a generic equivalent of PEDMARK®, will necessarily have the composition claimed by the patent, including its active ingredient concentrations and pH (Compl. ¶93-94, ¶98).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is "Cipla's ANDA Product," a generic single-use vial of sodium thiosulfate for injection, for which Defendant filed Abbreviated New Drug Application (ANDA) No. 218028 (Compl. ¶12).
Functionality and Market Context
The product is a proposed generic version of Fennec's PEDMARK® and is intended to be used for reducing the risk of ototoxicity induced by cisplatin chemotherapy in pediatric patients (Compl. ¶12). As an ANDA product, it must have the same active ingredient, route of administration, dosage form, and strength as the reference listed drug, PEDMARK® (Compl. ¶56). The complaint alleges that the formulation of PEDMARK® contains about 0.5 M aqueous sodium thiosulfate anhydrous, about 0.004 M boric acid, a pH between 7 and 9, and less than 0.05% borate ions (Compl. ¶51, ¶72). The lawsuit is based on the act of filing the ANDA, which constitutes a statutory act of infringement under the Hatch-Waxman Act (Compl. ¶59). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
11,291,728 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical composition comprising aqueous anhydrous sodium thiosulfate... | Defendant’s ANDA Product is a single-use vial of sodium thiosulfate for injection, which is an aqueous solution (Compl. ¶12). | ¶12, ¶51 | col. 11:3-4 |
| ...wherein the aqueous anhydrous sodium thiosulfate is at a concentration of about 0.5 M | The complaint alleges that the reference product, PEDMARK®, contains 8 grams of sodium thiosulfate anhydrous in 100 mL, which calculates to about 0.5 M, and that the ANDA Product will copy this. | ¶51, ¶56 | col. 11:4-6 |
| ...and further comprising about 0.004 M boric acid. | The complaint alleges that PEDMARK® contains 0.025 grams of boric acid in 100 mL, which calculates to about 0.004 M, and that the ANDA Product will copy this formulation. | ¶51, ¶56 | col. 11:6-7 |
11,510,984 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical composition comprising aqueous anhydrous sodium thiosulfate... | Defendant’s ANDA Product is an aqueous solution of sodium thiosulfate (Compl. ¶12). | ¶12, ¶72 | col. 11:3-4 |
| ...wherein the aqueous anhydrous sodium thiosulfate is at a concentration of about 0.5 M | The complaint alleges that the reference product, PEDMARK®, contains a concentration of about 0.5 M sodium thiosulfate anhydrous, a formulation that the ANDA Product is alleged to copy. | ¶72, ¶77 | col. 11:4-6 |
| ...and further comprising borate ions wherein the concentration of borate ions is less than 0.05%. | The complaint alleges that the PEDMARK® formulation, containing specific amounts of boric acid and having a pH between 7 and 9, results in a borate ion concentration of less than 0.05%. | ¶72, ¶77 | col. 11:6-8 |
Identified Points of Contention
- Scope Questions: A central issue may be the interpretation of the term "about" in relation to the claimed molar concentrations. The infringement analysis could turn on whether the precise formulation disclosed in Defendant's ANDA falls within the scope afforded by "about," even if it is not identical to the target values of 0.5 M and 0.004 M.
- Technical Questions: The primary factual question for the court will be the exact composition of the product described in Defendant's ANDA filing. The complaint proceeds on the basis that a generic drug must copy the reference drug's formulation, but the actual infringement determination will depend on a comparison of the ANDA's specifications to the patent claims (Compl. ¶56). The complaint does not provide the specific formulation from the ANDA itself.
V. Key Claim Terms for Construction
The Term: "about"
Context and Importance: This term qualifies the concentration of both the active ingredient ("about 0.5 M") and the buffering agent ("about 0.004 M boric acid") in the asserted claim of the ’728 Patent. The scope of "about" will be critical for determining the literal infringement boundary and could be dispositive if Defendant's ANDA formulation deviates even slightly from the stated values.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patents use the term "about" in the claims, which typically signals that the inventors did not intend for the numerical values to be exact and that some degree of variability is permitted (’728 Patent, Claim 1). The specification does not provide an explicit numerical definition for "about," which may suggest reliance on its ordinary meaning in the context of pharmaceutical formulation.
- Evidence for a Narrower Interpretation: The exemplary formulations provided in the patents’ specifications consistently recite exact concentrations (e.g., 0.5 M sodium thiosulfate, 0.004 M boric acid), which could be used to argue that "about" should be construed narrowly around these specific examples (’728 Patent, Table 2).
The Term: "anhydrous sodium thiosulfate"
Context and Importance: The claims specify the "anhydrous" form of the active ingredient. This could become a point of contention if Defendant's manufacturing process or ANDA specification involves a hydrated form (e.g., sodium thiosulfate pentahydrate) as a starting material. Practitioners may focus on this term because the dispute could center on whether the claim refers to the solid form used to make the solution or the state of the solute once dissolved in the final aqueous composition.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party could argue that once dissolved in an aqueous solution, the distinction between starting with an anhydrous versus a hydrated salt becomes moot, and the claim term "aqueous anhydrous sodium thiosulfate" simply describes the solute in its dissolved state.
- Evidence for a Narrower Interpretation: The patent titles, abstracts, and claims consistently and explicitly recite "anhydrous" sodium thiosulfate, suggesting the inventors considered this form to be a key feature of the invention, potentially to distinguish it from prior art or for reasons of manufacturing stability (’728 Patent, Title; Abstract; Claim 1).
VI. Other Allegations
- Indirect Infringement: The complaint alleges inducement to infringe on the basis that Defendant's proposed product label will necessarily instruct physicians and patients to use the infringing composition for the patented indication (Compl. ¶56, ¶77, ¶98). It alleges contributory infringement on the basis that the accused product is not a staple article of commerce and has no substantial non-infringing uses (Compl. ¶58, ¶79, ¶100).
- Willful Infringement: The complaint alleges that Defendant has actual knowledge of the asserted patents through the Paragraph IV notice letters (Compl. ¶50, ¶71, ¶92). While not explicitly pleading willfulness, it alleges that Defendant’s assertions of non-infringement and invalidity in its notice letters are "devoid of an objective good faith basis," which forms the predicate for a request for attorneys' fees under 35 U.S.C. § 285 for an "exceptional" case (Compl. ¶66, ¶87, ¶108).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of definitional scope: how broadly will the court construe the term "about" when applied to the specific chemical concentrations recited in the claims? The outcome of the literal infringement analysis may depend entirely on whether the formulation specified in Defendant's ANDA falls within the range of variability permitted by this term.
- A key evidentiary question will be one of compositional identity: what is the precise formulation of the accused generic product as defined in its ANDA filing? As this is a Hatch-Waxman case based on the filing itself, the infringement analysis will turn on a direct comparison of the ANDA's technical specifications to the claim language, rather than on analysis of a physical product.