DCT

1:23-cv-00734

Actelion Pharma Ltd v. Apotex Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00734, D. Del., 07/06/2023
  • Venue Allegations: Venue is alleged to be proper as Defendant Apotex Corp. is a Delaware corporation and Defendant Apotex Inc. is a foreign entity subject to personal jurisdiction in the district.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for a generic version of the drug OPSUMIT® (macitentan) constitutes an act of infringement of a patent covering the active ingredient.
  • Technical Context: The technology involves sulfamide-based chemical compounds that act as endothelin receptor antagonists, used for the treatment of pulmonary arterial hypertension.
  • Key Procedural History: This action was filed under the Hatch-Waxman Act following Plaintiff’s receipt of a notice letter from Defendant regarding its ANDA and Paragraph IV certification. The complaint alleges that Defendant was aware of multiple prior litigations involving the same patent, which concluded in consent judgments where other generic drug manufacturers admitted the patent’s claims were valid and enforceable. The complaint also notes that Defendant initially filed a Paragraph III certification in 2017 before later converting it to the Paragraph IV certification that triggered this lawsuit.

Case Timeline

Date Event
2000-12-18 ’781 Patent Priority Date
2006-08-22 ’781 Patent Issue Date
2013-10-18 FDA Approval for branded drug OPSUMIT®
2017-10-18 Apotex files ANDA No. 211195 with Paragraph III Certification
2023-05-26 Apotex sends Paragraph IV Certification Notice Letter to Actelion
2023-07-06 Complaint Filed

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. 7,094,781, "Sulfamides and Their Use as Endothelin Receptor Antagonists," issued August 22, 2006 (’781 Patent).

The Invention Explained

  • Problem Addressed: The patent background describes a need for new endothelin receptor antagonists. It notes that while such therapeutic agents existed, they often suffered from weaknesses including "complex synthesis, low solubility, high molecular weight, poor pharmacokinetics, or safety problems (e.g. liver enzyme increases)" (’781 Patent, col. 3:56-62).
  • The Patented Solution: The invention discloses a "new class of substituted pyrimidines" featuring a sulfamide core structure that function as endothelin receptor antagonists (’781 Patent, col. 3:2-5). This new class of compounds is intended to provide effective therapeutic agents for diseases associated with endothelins, such as pulmonary hypertension, while allowing for the "specific tailoring" of physicochemical and pharmacokinetic properties (’781 Patent, col. 3:45-49, 3:62-65).
  • Technical Importance: Endothelins are peptides that act as potent vasoconstrictors and are implicated in various cardiovascular disease states; developing orally active, safe, and effective antagonists was a significant area of pharmaceutical research (’781 Patent, col. 3:14-24).

Key Claims at a Glance

  • The complaint asserts infringement of claims 1, 5-9, and 11 of the ’781 Patent (Compl. ¶44).
  • Independent claim 1 recites a compound of a general Markush formula (Formula I) defining a class of pyrimidine-sulfamides by their core structure and permissible chemical substituents (’781 Patent, col. 137:1-65).
  • Dependent claim 11 further narrows claim 1 to a specific list of named chemical compounds (’781 Patent, col. 141:55-144:65).
  • The complaint does not explicitly reserve the right to assert other dependent claims.

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Defendant's generic macitentan 10 mg oral tablets, for which Apotex filed ANDA No. 211195 with the U.S. Food and Drug Administration (FDA) (Compl. ¶13).

Functionality and Market Context

The ANDA Product contains macitentan as its active pharmaceutical ingredient and is a generic version of Plaintiff's branded drug, OPSUMIT® (Compl. ¶13, ¶45). OPSUMIT® is approved for the treatment of pulmonary arterial hypertension (PAH) (Compl. ¶26). The ’781 Patent is listed in the FDA's "Orange Book" as covering OPSUMIT®, and Apotex seeks approval to market its generic version prior to the expiration of the ’781 Patent (Compl. ¶13, ¶29).

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail for a formal claim chart. The infringement theory is a narrative of literal infringement based on chemical identity. The filing of ANDA No. 211195 seeking approval for a generic drug is the statutorily defined act of infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶50).

The complaint alleges that the active ingredient in the ANDA Product, macitentan, is a compound covered by the asserted claims of the ’781 Patent (Compl. ¶45, ¶50). The central factual allegation for infringement is that "The chemical name of the compound macitentan is one of the chemical names recited in Claim 11 of the ’781 patent" (Compl. ¶46). The complaint further alleges that Apotex’s Paragraph IV notice letter failed to provide any factual basis or opinion for noninfringement of claims 1, 5-9, and 11, suggesting that Apotex's challenge to the patent is based on validity rather than noninfringement (Compl. ¶44).

No probative visual evidence provided in complaint.

Identified Points of Contention

  • Scope Questions: A primary question for the court will be whether the chemical compound macitentan is within the scope of the asserted claims. The infringement analysis may focus on the complaint's direct allegation that macitentan is one of the specific compounds enumerated in dependent claim 11 (Compl. ¶46). Should that allegation be contested, the focus could shift to whether macitentan's structure falls within the Markush group definitions of the broader independent claim 1.
  • Technical Questions: The key technical question is one of direct comparison: does the chemical structure of macitentan, as specified in ANDA No. 211195, literally match a chemical structure claimed in the ’781 Patent?

V. Key Claim Terms for Construction

The complaint, which relies on a theory of literal infringement of a specific chemical compound, does not provide a basis to identify specific claim terms that are likely to be in dispute for construction. The case appears to turn on a direct comparison of the accused product's chemical structure to the claimed compounds, rather than on the interpretation of disputed terminology.

VI. Other Allegations

Indirect Infringement

The complaint includes a request for a declaration that if Apotex commercially manufactures and sells the ANDA Product post-approval, it will induce infringement under 35 U.S.C. § 271(b) (Compl. ¶57). This allegation is based on the future intent to market the drug for its approved indication.

Willful Infringement

The complaint alleges that Apotex's infringement has been and continues to be willful. The allegations supporting willfulness include Apotex's alleged pre-suit knowledge of the ’781 Patent since at least October 2017 (Compl. ¶31-32) and its alleged awareness of multiple consent judgments from prior lawsuits in which other companies admitted that the claims of the ’781 Patent are valid and enforceable (Compl. ¶36-43). The complaint further alleges that Apotex failed to comply with its affirmative duty of care and lacked an objective good-faith basis for its invalidity defenses (Compl. ¶47, ¶59).

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

  • A central issue will be one of validity and objective baselessness: in light of the ’781 Patent's history of being upheld in multiple prior litigations (Compl. ¶36-43), what novel and objectively reasonable invalidity argument can Apotex present? The court's determination on this point will be critical not only for the patent's survival but also for the associated claim of willful infringement.
  • A threshold question will be one of factual identity: does the active ingredient in Apotex's ANDA product, macitentan, fall within the literal scope of an asserted patent claim? This will require a direct comparison of chemical structures and will test the accuracy of the complaint’s specific allegation tying macitentan to the list of compounds in Claim 11 (Compl. ¶46).