DCT

3:24-cv-03990

Actelion Pharma Ltd v. Torrent Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:24-cv-03990, D.N.J., 03/19/2024
  • Venue Allegations: Venue is alleged to be proper as to Torrent Ltd. as it is a foreign entity subject to personal jurisdiction in the district. Venue is alleged to be proper as to Torrent Inc. because it has a principal place of business in New Jersey and has committed acts of infringement in the district.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the U.S. Food and Drug Administration (FDA) for a generic version of the drug macitentan constitutes an act of patent infringement under the Hatch-Waxman Act.
  • Technical Context: The patents relate to a chemical compound, macitentan, used as an endothelin receptor antagonist for treating pulmonary arterial hypertension (PAH), and to stable pharmaceutical formulations of that compound.
  • Key Procedural History: The complaint certifies that U.S. Patent 7094781 has been the subject of numerous prior lawsuits against other generic manufacturers, several of which were dismissed. The complaint also notes that both patents-in-suit are at issue in an ongoing case against Mylan Pharmaceuticals Inc. in the Northern District of West Virginia.

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 grants approval for Plaintiff's NDA No. 204410 (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,” issued August 22, 2006

The Invention Explained

  • Problem Addressed: The patent addresses the need for effective endothelin receptor antagonists to treat various diseases associated with vasoconstriction, proliferation, or inflammation, such as pulmonary hypertension (’781 Patent, col. 1:13-14, 42-48). Existing molecules had weaknesses including complex synthesis, low solubility, and poor pharmacokinetics (’781 Patent, col. 1:59-63).
  • The Patented Solution: The invention provides a new class of pyrimidine-sulfamides, which are chemical compounds designed to inhibit endothelin receptors. The patent describes the synthesis and activity of these novel compounds, including the compound that would become known as macitentan (’781 Patent, col. 2:1-9; col. 8:5-20). The core of the invention is the specific chemical structure that provides the desired therapeutic effect.
  • Technical Importance: The development of novel, potent, and safe endothelin receptor antagonists represented a significant therapeutic advance for treating life-threatening conditions like PAH (’781 Patent, col. 5:28-45).

Key Claims at a Glance

  • The complaint asserts Claims 1, 5-9, and 11 (Compl. ¶32).
  • Independent Claim 1 is a composition of matter claim directed to a compound of a specific chemical structure (Formula I) or its pharmaceutically acceptable salt, covering a range of related molecules including macitentan. Key elements include:
    • A central pyrimidine ring.
    • A sulfamide group attached to the pyrimidine ring.
    • A substituted phenyl group (R3) attached to the pyrimidine ring.
    • An ether linkage (X=oxygen) connecting a side chain (R2) to the pyrimidine ring.

U.S. Patent No. 10,946,015 - “Stable Pharmaceutical Compositions Comprising a Pyrimidine-Sulfamide,” issued March 16, 2021

The Invention Explained

  • Problem Addressed: The patent addresses the challenge of creating a chemically stable oral dosage form for the specific pyrimidine-sulfamide compound (macitentan) from the ’781 patent, which was under evaluation in clinical trials (’015 Patent, col. 1:55-62).
  • The Patented Solution: The invention is a specific pharmaceutical formulation that ensures the stability of the active ingredient. The solution is not the drug itself, but the combination of the drug with a particular set of inactive ingredients (excipients) in specific proportions, including a filler, a disintegrant, a surfactant, and a lubricant (’015 Patent, col. 2:12-18, Abstract). The detailed description provides specific examples of suitable excipients and manufacturing processes that yield a stable product (’015 Patent, col. 2:48-65; Fig. 3).
  • Technical Importance: Developing a stable, manufacturable solid oral dosage form is a critical step in transforming a promising chemical compound into a viable commercial drug product.

Key Claims at a Glance

  • The complaint asserts Claims 1, 2, 4, 9, 10, 12-14, 16-18, and 21-42 (Compl. ¶33).
  • Independent Claim 1 is a composition claim for a pharmaceutical product. Its essential elements are:
    • The active compound of Formula I (macitentan).
    • 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 from 0.1 to 1% by weight, wherein the surfactant comprises a polysorbate.
    • A lubricant, in an amount from 0.05 to 10% by weight.

III. The Accused Instrumentality

Product Identification

  • Defendants' generic macitentan 10 mg oral tablets, for which Abbreviated New Drug Application (ANDA) No. 211107 was submitted to the FDA (Compl. ¶¶15, 29).

Functionality and Market Context

  • The complaint alleges that the "ANDA Product" is a generic version of Plaintiffs’ branded drug, OPSUMIT®, which is approved for the treatment of pulmonary arterial hypertension (PAH) (Compl. ¶¶23-24).
  • By filing an ANDA, Defendants are representing to the FDA that their product has the same active ingredient, dosage form, strength, and route of administration as OPSUMIT®, and is bioequivalent to it.
  • The complaint alleges that Defendants seek FDA approval to commercially manufacture and sell the ANDA Product prior to the expiration of the patents-in-suit, based on a Paragraph IV certification that the patents are invalid, unenforceable, or will not be infringed (Compl. ¶¶30-31).

IV. Analysis of Infringement Allegations

The complaint is a formulaic filing typical in Hatch-Waxman litigation, providing notice of the suit without detailing a specific infringement theory. Infringement under 35 U.S.C. § 271(e)(2) is a statutorily defined, "artificial" act based on the submission of the ANDA itself. The analysis below is based on the necessary inference that for Defendants' product to be an approved generic, it must practice the inventions claimed in the patents covering the branded drug.

No probative visual evidence provided in complaint.

’781 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound of formula I...or a pharmaceutically acceptable salt...thereof The complaint alleges that by seeking approval for its ANDA, Defendant has infringed. It is a necessary inference that the ANDA Product contains macitentan, a compound falling within the scope of Formula I. ¶36 col. 5:2-14
  • Identified Points of Contention:
    • Factual Question: The primary question is one of fact: does the active pharmaceutical ingredient in Torrent's ANDA Product meet the structural limitations of the asserted claims? This will depend on the chemical analysis of the product defined in the ANDA.
    • Scope Question: A potential dispute could arise over whether any specific crystalline form or salt of macitentan used by Torrent falls outside the scope of the asserted claims as construed by the court.

’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... The complaint alleges the ANDA Product is a 10 mg oral tablet that infringes, from which it can be inferred that the active ingredient (macitentan) is present within the claimed weight percentage. ¶¶15, 36 col. 29:13-23
b) filler, in an amount of 10 to 95% in weight... The complaint's allegations imply that Torrent's formulation contains a filler within the claimed range to achieve bioequivalence with the branded product. ¶36 col. 29:24-26
c) disintegrant, in an amount of 1 to 20% in weight... The complaint's allegations imply that Torrent's formulation contains a disintegrant within the claimed range. ¶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's allegations imply that Torrent's formulation contains a polysorbate surfactant within the narrow claimed range. ¶36 col. 29:30-34
e) lubricant, in an amount from 0.05 to 10% in weight... The complaint's allegations imply that Torrent's formulation contains a lubricant within the claimed range. ¶36 col. 29:35-38
  • Identified Points of Contention:
    • Technical Question: A central issue will be whether the specific formulation detailed in Torrent’s confidential ANDA filing meets both the qualitative (e.g., "polysorbate") and quantitative (% by weight) limitations of the ’015 Patent’s composition claims. Even minor deviations in excipient identity or percentage could form the basis of a non-infringement argument.
    • Scope Question: How will the court construe the functional terms "filler," "disintegrant," and "lubricant"? Does Torrent use an excipient that arguably performs a different or dual function, raising a question about whether it meets a specific claim limitation?

V. Key Claim Terms for Construction

The complaint does not provide sufficient detail to identify specific claim construction disputes. However, based on the patent claims, the following terms may be central.

For the ’015 Patent:

  • The Term: "stable" (from the title and preamble)

  • Context and Importance: Although appearing in the preamble, the term "stable" is central to the patent's purpose of solving the problem of formulating macitentan. Practitioners may focus on this term because if it is found to be a limiting part of the claim, Defendants could argue their product does not meet the patent's specific definition of stability, even if the composition is otherwise identical.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: A party might argue "stable" should be given its plain and ordinary meaning in the pharmaceutical arts, referring generally to a product that maintains its physical and chemical integrity over its shelf life.
    • Evidence for a Narrower Interpretation: The specification provides an explicit definition: "A pharmaceutical composition... is considered 'stable', if during a certain period of time 70%, preferably 80% and most preferably 95% of the initial content of compound of formula I... is maintained..." (’015 Patent, col. 10:50-56). A party could argue this specific, quantitative definition must be imported into the claims.

  • The Term: "surfactant" (from Claim 1)

  • Context and Importance: Claim 1 requires a surfactant comprising a polysorbate in a very narrow weight range (0.1 to 1%). The identity and function of this component will be critical. Practitioners may focus on this term because Torrent could argue its formulation uses an excipient that does not function as a surfactant or uses a different class of surfactant not covered by the term "polysorbate."

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification lists "polysorbates (commercially available as Tween®)" as one of several types of surfactants, which may support an interpretation covering the entire class of polysorbates (’015 Patent, col. 5:19-28).
    • Evidence for a Narrower Interpretation: Claim 16 of the patent narrows the term to "polysorbate 80." A party could argue that the broader term in claim 1 should be interpreted in light of this more specific dependent claim, although this is generally disfavored under the doctrine of claim differentiation. The specification also states that a polysorbate "may for example be polysorbate 80" (’015 Patent, col. 5:32-33), which could be used to argue either for or against a narrow construction.

VI. Other Allegations

  • Indirect Infringement: The complaint includes a request for a declaration of future infringement, including inducement and contributory infringement, should Torrent commercially launch its product (Compl. ¶43). This allegation is based on the presumed instructions for use in the ANDA Product's labeling, which would direct medical professionals and patients to use the drug in an infringing manner.
  • Willful Infringement: The complaint alleges that Torrent was aware of the patents-in-suit, as evidenced by its sending of Notice Letters that included Paragraph IV certifications for those patents (Compl. ¶¶30-31, 38, 42). This alleged pre-suit knowledge forms the basis for the willfulness claim.

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

This case presents a classic Hatch-Waxman dispute where the key evidence resides in the defendant's confidential FDA filing. The central questions for the court will likely be:

  1. A question of factual infringement under § 271(e)(2): Does the specific compound and formulation described in Torrent's confidential ANDA fall within the scope of the asserted claims of the ’781 and ’015 patents, respectively? Resolution will depend entirely on a comparison of the ANDA's contents to the claim language.
  2. A question of patent validity: Although not an issue raised by the plaintiff, Torrent's Paragraph IV certification signals an intent to challenge the validity of the patents-in-suit. A key issue will be whether Torrent can present invalidity arguments for the heavily-litigated ’781 patent that have not been overcome in prior cases, and whether it can successfully challenge the more recent ’015 formulation patent.
  3. A question of claim scope for the formulation patent: Will the court construe the term "stable" as a substantive limitation of the ’015 patent claims, and if so, does Torrent's product meet the patent's specific quantitative definition? The interpretation of this term could be dispositive for the infringement analysis of the ’015 patent.