DCT
1:24-cv-03990
Actelion Pharma Ltd v. Torrent Pharma Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Actelion Pharmaceuticals Ltd (Switzerland) and Actelion Pharmaceuticals US, Inc. (Delaware)
- Defendant: Torrent Pharmaceuticals Ltd. (India) and Torrent Pharma Inc. (Delaware)
- Plaintiff’s Counsel: ROBINSON MILLER LLC
- Case Identification: 1:24-cv-03990, D.N.J., 03/19/2024
- Venue Allegations: Venue is alleged to be proper as to the foreign defendant, Torrent Ltd., because it is subject to personal jurisdiction in the district, and as to the domestic defendant, Torrent Inc., because it maintains its principal place of business in New Jersey.
- Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for generic macitentan tablets constitutes an act of infringement of two patents covering the active compound and its pharmaceutical formulation.
- Technical Context: The technology relates to macitentan, the active ingredient in the drug OPSUMIT®, which is used for the treatment of pulmonary arterial hypertension (PAH).
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant’s notice to Plaintiff that it had filed an ANDA with a Paragraph IV certification, seeking to market a generic version of OPSUMIT® prior to the expiration of Plaintiff's patents. The complaint states it was filed within the 45-day period provided by statute, which triggers an automatic 30-month stay on FDA approval of the ANDA. The patents-in-suit are listed in the FDA’s Orange Book for OPSUMIT®. The complaint's certification of prior litigation indicates U.S. Patent No. 7,094,781 has been the subject of numerous other ANDA lawsuits against different generic manufacturers.
Case Timeline
| Date | Event |
|---|---|
| 2000-12-18 | '781 Patent Priority Date |
| 2005-09-12 | '015 Patent Priority Date |
| 2006-08-22 | '781 Patent Issue Date |
| 2013-10-18 | FDA Approval for OPSUMIT® |
| 2021-03-16 | '015 Patent Issue Date |
| 2024-03-19 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,094,781 - "Sulfamides and Their Use as Endothelin Receptor Antagonists"
- Patent Identification: U.S. Patent No. 7094781, titled “Sulfamides and Their Use as Endothelin Receptor Antagonists,” issued on August 22, 2006 (Compl. ¶26).
The Invention Explained
- Problem Addressed: The patent describes endothelin peptides as potent vasoconstrictors involved in various diseases, including hypertension and heart failure. It notes that previously developed endothelin receptor antagonists suffered from weaknesses such as "complex synthesis, low solubility, high molecular weight, poor pharmacokinetics, or safety problems" ('781 Patent, col. 1:55-62).
- The Patented Solution: The invention provides a new class of pyrimidine-sulfamide compounds that act as endothelin receptor antagonists. These novel compounds, defined by a general chemical structure (Formula I), are intended to have improved properties for therapeutic use ('781 Patent, col. 2:1-5, Abstract). The specific compound macitentan is explicitly claimed ('781 Patent, col. 12:8-21, claim 11).
- Technical Importance: This class of compounds provided a new chemical scaffold for developing treatments for endothelin-mediated diseases, potentially offering better safety and pharmacokinetic profiles than existing options ('781 Patent, col. 5:26-47).
Key Claims at a Glance
- The complaint asserts independent claim 1 and dependent claims 5-9 and 11 (Compl. ¶32).
- Independent Claim 1 defines a broad genus of chemical compounds of Formula I, characterized by:
- A central pyrimidine core structure
- Substituted with a sulfamide group ("-NH-SO2-NH-")
- Various substituent groups ("R¹" through "R⁶", "X") defined by Markush groups, allowing for a wide range of specific chemical entities.
- Dependent claim 11 specifically recites the chemical structure for propylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-yl]-amide, which is the active ingredient macitentan.
U.S. Patent No. 10,946,015 - "Stable Pharmaceutical Compositions Comprising a Pyrimidine-Sulfamide"
- Patent Identification: U.S. Patent No. 10,946,015, titled “Stable Pharmaceutical Compositions Comprising a Pyrimidine-Sulfamide,” issued on March 16, 2021 (Compl. ¶27).
The Invention Explained
- Problem Addressed: The patent explains that for the compound of formula I (macitentan), which was being evaluated in clinical trials, a "stable formulation had to be developed" ('015 Patent, col. 1:55-58). This indicates a technical challenge in creating a reliable and durable oral dosage form for the active pharmaceutical ingredient (API).
- The Patented Solution: The patent discloses specific pharmaceutical compositions that render the macitentan API stable for oral administration. The solution involves combining the API with a particular set of excipients—a filler, a disintegrant, a surfactant, and a lubricant—within specified weight percentage ranges to ensure stability and proper dissolution ('015 Patent, col. 2:56-col. 3:54; Fig. 1).
- Technical Importance: Creating a stable oral formulation is a critical step in drug development, necessary to ensure consistent dosing, bioavailability, and a commercially viable shelf-life, all of which are required for regulatory approval and patient safety ('015 Patent, col. 9:51-56).
Key Claims at a Glance
- The complaint asserts independent claim 1 and a large number of dependent claims (2, 4, 9, 10, 12-14, 16-18, 21-42) (Compl. ¶33).
- Independent Claim 1 claims a pharmaceutical composition comprising:
- The compound of formula I (macitentan) in an amount of 1% to 50% by weight.
- A filler in an amount of 10% to 95% by weight.
- A disintegrant in an amount of 1% to 20% by weight.
- A surfactant in an amount of 0.1% to 1% by weight, where the surfactant comprises a polysorbate.
- A lubricant in an amount of 0.05% to 10% by weight.
- The asserted dependent claims further narrow the invention, for example by specifying the polysorbate as "polysorbate 80" (claim 16) or the lubricant as "magnesium stearate" (claim 18).
III. The Accused Instrumentality
- Product Identification: The accused instrumentality is Defendant's generic macitentan 10 mg oral tablets, for which it submitted Abbreviated New Drug Application (ANDA) No. 211107 to the FDA (Compl. ¶15, ¶29).
- Functionality and Market Context: The "ANDA Product" is a generic version of Plaintiff's OPSUMIT® drug and is intended for the same therapeutic use: the treatment of pulmonary arterial hypertension (PAH) (Compl. ¶15, ¶24). The complaint alleges that by filing the ANDA, Defendant seeks approval to commercially manufacture, use, and sell this product in the United States before the expiration of the patents-in-suit (Compl. ¶30).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint alleges that the filing of ANDA No. 211107 is a statutory act of infringement under 35 U.S.C. § 271(e)(2)(A), as the product described therein is covered by the patents-in-suit (Compl. ¶36). The complaint does not contain specific factual details or test results comparing the ANDA product to the claims.
'781 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A compound of general formula I...or an optically pure enantiomer or diastereomer...or a meso-form or a pharmaceutically acceptable salt thereof | The complaint alleges that the ANDA Product contains propylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-yl]-amide (macitentan), which is a compound falling within the scope of Formula I (Compl. ¶36). | ¶36 | col. 5:4-14 |
- Identified Points of Contention:
- Technical Questions: A foundational question is whether the active pharmaceutical ingredient in Torrent's ANDA Product is, in fact, the precise chemical compound recited in claim 11 of the ’781 Patent. The analysis will depend on chemical characterization of the ANDA product, which is not detailed in the complaint.
'015 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a) the compound of the formula I...in a total amount of 1 to 50% in weight based on the total weight of the pharmaceutical composition | The complaint alleges that the ANDA Product contains macitentan within the claimed weight percentage range (Compl. ¶36). | ¶36 | col. 29:20-23 |
| b) filler, in an amount of 10 to 95% in weight... | The complaint alleges that the ANDA Product's formulation contains one or more fillers within the claimed weight percentage range (Compl. ¶36). | ¶36 | col. 29:24-26 |
| c) disintegrant, in an amount of 1 to 20% in weight... | The complaint alleges that the ANDA Product's formulation contains a disintegrant within the claimed weight percentage range (Compl. ¶36). | ¶36 | col. 29:27-29 |
| d) surfactant, in an amount from 0.1 to 1% in weight... wherein the surfactant comprises a polysorbate | The complaint alleges that the ANDA Product's formulation contains a surfactant comprising a polysorbate within the claimed weight percentage range (Compl. ¶36). | ¶36 | col. 29:30-33 |
| e) lubricant, in an amount from 0.05 to 10% in weight... | The complaint alleges that the ANDA Product's formulation contains a lubricant within the claimed weight percentage range (Compl. ¶36). | ¶36 | col. 29:34-36 |
- Identified Points of Contention:
- Scope Questions: Do the specific excipients used in the ANDA Product fall within the definitions of "filler," "disintegrant," "surfactant," and "lubricant" as used in the patent? The complaint does not disclose the specific excipients in Defendant's formulation.
- Technical Questions: Does the ANDA Product's formulation meet the specific weight percentage limitations for each category of ingredient as required by the claims? This will be a central factual dispute requiring analysis of Defendant's confidential ANDA filing.
V. Key Claim Terms for Construction
The complaint does not provide sufficient detail for analysis of most claim terms. However, based on the technology of the '015 patent, the following term may be central to the dispute.
- The Term: 'stable' ('015 Patent, e.g., Title, Abstract, col. 1:55-63)
- Context and Importance: The '015 patent is directed to "stable" pharmaceutical compositions. The definition of this term is critical because it sets the standard that the accused product must meet to infringe. Practitioners may focus on this term because if Torrent's formulation can be shown to achieve its own form of stability without meeting the patent's definition, it could support a non-infringement defense.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a general definition, stating a composition is considered "stable" if "70%, preferably 80% and most preferably 95% of the initial content of compound of formula I...is maintained over said period of time" ('015 Patent, col. 9:51-56). Plaintiff may argue this broad definition should apply.
- Evidence for a Narrower Interpretation: The patent includes detailed stability test data showing very high levels of purity (e.g., total related substances of only 0.14% after 3 months at 40° C/75% RH for one embodiment) ('015 Patent, col. 24:65). Defendant may argue that these examples implicitly define "stable" as requiring this high degree of purity under accelerated aging conditions, a standard its own product might not meet.
VI. Other Allegations
- Indirect Infringement: The complaint includes a request for a declaration that if Defendant commercially manufactures or sells the ANDA Product, it will induce or contribute to infringement by others (e.g., doctors and patients) (Compl. ¶43). This allegation is predicated on the future marketing and labeling of the product for its intended, patented use.
- Willful Infringement: While the complaint does not use the term "willful," it alleges that Defendant was "aware" that its submission of the ANDA constituted an act of infringement and that future commercialization would also infringe (Compl. ¶38, ¶42). These allegations of pre-suit and post-suit knowledge of the patents could form the basis for a later claim of willful infringement.
VII. Analyst’s Conclusion: Key Questions for the Case
- A key evidentiary question will be one of formulation identity: does the precise mixture of active ingredient and excipients in Defendant's ANDA Product, including their respective weight percentages, fall within the literal scope of the composition claims of the '015 patent? The resolution will depend on the confidential details of Defendant's formulation.
- The infringement analysis for the '015 patent will likely turn on a question of definitional scope: will the term "stable" be construed according to the patent’s broad written definition (e.g., maintaining 70% of the API), or will it be narrowed by the high-purity results shown in the patent's specific examples? The outcome will set the technical bar for infringement.
- For the '781 patent, the infringement question appears straightforward, centering on compound identity: is the API in the ANDA product the same chemical entity recited in claim 11? While infringement seems likely if the ANDA is for macitentan, the core of the dispute for this patent will likely shift to questions of validity, such as obviousness, as the case develops.