DCT

1:25-cv-01488

Actelion Pharmaceuticals US Inc v. Apotex Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:25-cv-01488, D. Del., 12/10/2025
  • Venue Allegations: Plaintiffs allege venue is proper in the District of Delaware because Defendant Apotex Corp. is a Delaware corporation and Defendant Apotex Inc. conducts substantial business in the state and, as a foreign entity, may be sued in any judicial district where it is subject to personal jurisdiction.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the pulmonary arterial hypertension drug UPTRAVI® (selexipag) constitutes an act of infringement of two patents covering a specific crystalline form of the active ingredient and methods of its therapeutic use.
  • Technical Context: The technology concerns pharmaceutical polymorphism, where a specific, stable crystalline structure of an active pharmaceutical ingredient is developed to ensure consistent manufacturing, stability, and bioavailability.
  • Key Procedural History: The complaint notes that the patents-in-suit are listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (the "Orange Book") as covering UPTRAVI®. It also references several prior lawsuits against other generic drug manufacturers which concluded with consent judgments where those parties admitted the validity and enforceability of the patents-in-suit.

Case Timeline

Date Event
2009-06-26 Priority Date for ’122 and ’280 Patents
2014-07-29 ’122 Patent Issue Date
2015-12-21 FDA Approval for UPTRAVI® (NDA No. 207947)
2016-03-15 ’280 Patent Issue Date
2017-09-15 ’122 Patent Reexamination Certificate Issued
2025-10-30 Apotex Paragraph IV Certification Notice Letter Sent
2025-12-10 Complaint Filing Date

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

U.S. Patent No. 8,791,122 - Form-I Crystal of 2-{4-[N-(5,6-Diphenylpyrazin-2-yl)-N-Isopropylamino]Butyloxy}-N-(Methylsulfonyl)Acetamide and Method for Producing the Same

The Invention Explained

  • Problem Addressed: The patent background discloses the therapeutic utility of the chemical compound selexipag (referred to as "compound A") but notes that, prior to the invention, "no reference describes or suggests the possibility of existence of crystals of compound A" (’122 Patent, col. 2:45-48). In pharmaceutical science, developing a specific, stable, and reproducible crystalline form of a drug is a critical and non-obvious step to enable consistent, large-scale manufacturing and ensure predictable drug performance.
  • The Patented Solution: The invention provides a specific crystalline polymorph of selexipag, designated "Form-I" (’122 Patent, col. 2:64-65). This novel crystal is not defined by its chemical structure alone, but by its unique physical properties, specifically the characteristic peaks it produces in a powder X-ray diffraction (PXRD) spectrum, as illustrated in Figure 1 (’122 Patent, Fig. 1; col. 3:33-37).
  • Technical Importance: The creation of a stable crystalline form with defined physical characteristics is essential for formulating a safe and effective pharmaceutical product with reliable dosage, dissolution, and bioavailability.

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims (Compl. ¶45). Independent Claim 1 is representative of the patent’s core subject matter.
  • Claim 1 of the ’122 Patent requires:
    • A crystal of the compound 2-{-4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl)acetamide (selexipag).
    • The crystal must show diffraction peaks in its X-ray powder diffraction spectrum at least at the specific 2θ angles of 9.4°, 9.8°, 17.2°, and 19.4°.
    • The spectrum must be obtained using Cu Kα radiation.
  • The complaint does not specify assertion of dependent claims but makes a general allegation of infringement of the patents-in-suit (Compl. ¶45).

U.S. Patent No. 9,284,280 - Use of Form-I Crystal of 2-{4-[N-(5,6-Diphenylpyrazin-2-yl)-N-Isopropyl-Amino]Butyloxy}-N-(Methyl-Sulfonyl)Acetamide

The Invention Explained

  • Problem Addressed: As with the ’122 patent, the ’280 Patent is predicated on the creation of the novel Form-I crystal of selexipag (’280 Patent, col. 1:49-54). The problem addressed is how to effectively use this specific, stable polymorph for therapeutic purposes.
  • The Patented Solution: The patent claims methods of treating a list of specific medical conditions by administering the Form-I crystal of selexipag (’280 Patent, Abstract). This ties the medical treatment method directly to the use of the specific, physically-defined crystalline form identified in the ’122 Patent. The background section lists numerous diseases for which compound A has therapeutic utility, including pulmonary hypertension and thrombosis (’280 Patent, col. 1:55 - col. 2:43).
  • Technical Importance: This patent extends protection from the composition of matter (the crystal itself) to its specific application in medicine, thereby protecting the innovator's market for treating diseases with its proprietary crystal form.

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims (Compl. ¶45). Independent Claim 1 is representative.
  • Claim 1 of the ’280 Patent requires:
    • A method for treating a specified list of diseases, which includes pulmonary hypertension and thrombosis.
    • The method comprises the step of administering the Form-I crystal of selexipag to a subject.
    • The Form-I crystal is defined, as in the ’122 Patent, as showing PXRD peaks at least at 2θ angles of 9.4°, 9.8°, 17.2°, and 19.4° when using Cu Kα radiation.
  • The complaint does not specify assertion of dependent claims but makes a general allegation of infringement of the patents-in-suit (Compl. ¶45).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are Defendants' generic selexipag oral tablets in strengths of 200 mcg, 400 mcg, 600 mcg, 800 mcg, 1000 mcg, 1200 mcg, 1400 mcg, and 1600 mcg ("Apotex's ANDA Products") (Compl. ¶13).

Functionality and Market Context

The complaint alleges that Apotex has filed ANDA No. 220457 with the FDA seeking approval to market these products as generic equivalents to Plaintiffs’ UPTRAVI® brand selexipag tablets (Compl. ¶¶13, 32). UPTRAVI® is approved for the treatment of pulmonary arterial hypertension (PAH) (Compl. ¶27). The complaint alleges that Apotex seeks to manufacture and sell its generic products in the United States before the expiration of the patents-in-suit (Compl. ¶13). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint, characteristic of initial pleadings in ANDA litigation, does not provide a detailed, element-by-element infringement analysis or a claim chart. Instead, it alleges that the submission of ANDA No. 220457 constitutes a statutory act of infringement under 35 U.S.C. § 271(e)(2)(A) because the product for which approval is sought, if commercially manufactured and sold, would infringe one or more claims of the patents-in-suit (Compl. ¶¶ 45-46). The core of the infringement allegation is that the generic selexipag tablets described in Apotex's ANDA necessarily contain the Form-I crystal claimed in the ’122 Patent and are intended for the uses claimed in the ’280 Patent.

  • Identified Points of Contention:
    • Factual/Technical Question: The central dispute for the ’122 Patent will be a factual one: does the active ingredient in Apotex's proposed generic product exist in the specific "Form-I crystal" structure? This will likely be resolved through competing expert analysis of scientific data, such as PXRD spectra, of Apotex's product.
    • Scope Question: For the ’280 Patent, infringement depends first on a finding of infringement of the ’122 Patent. If Apotex's product contains the Form-I crystal, the question becomes whether Apotex’s proposed product label will instruct physicians and patients to use the drug for one of the conditions recited in the claims, such as pulmonary hypertension (Compl. ¶27).

V. Key Claim Terms for Construction

  • The Term: "A crystal ... showing diffraction peaks in its X-ray powder diffraction spectrum at least at the following angles of diffraction 2θ: 9.4 degrees, 9.8 degrees, 17.2 degrees and 19.4 degrees" (’122 Patent, Claim 1).
  • Context and Importance: This phrase is not a conventional term but the primary structural definition of the patented invention. The entire infringement analysis for both patents hinges on whether Apotex's product meets this physical description. Practitioners may focus on the precision required to match these peak values and the significance of the phrase "at least."
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification provides a margin of error for the peak values, stating that an angle of diffraction "is to be understood as an interval from said value minus 0.2° to said value plus 0.2°" (’122 Patent, col. 3:25-30). The use of "at least" in the claim suggests that the presence of additional PXRD peaks in an accused product does not avoid infringement, so long as the four recited peaks are present.
    • Evidence for a Narrower Interpretation: A party might argue that the characterization of the crystal requires more than just the presence of four peaks within a certain tolerance. They could point to the representative PXRD spectrum in Figure 1 of the patents as defining the invention with more specificity, potentially including the relative intensities of the peaks, even though intensities are not explicitly recited in the claim language (’122 Patent, Fig. 1).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that if Apotex's ANDA is approved, its commercial activities will induce infringement of the patents-in-suit (Compl. ¶53). This allegation, particularly as it relates to the ’280 method-of-use patent, would be based on Apotex’s proposed product labeling instructing users to take the generic drug for the patented therapeutic indications.
  • Willful Infringement: The complaint does not use the word "willful" but lays a foundation for such a claim. It alleges Apotex had "actual and constructive notice of the patents-in-suit prior to the filing" of its ANDA (Compl. ¶51). It further alleges that Apotex was aware of multiple prior litigations where other companies admitted the patents were valid and enforceable (Compl. ¶¶ 34-38). Plaintiffs also request a declaration that the case is "exceptional" to recover attorneys' fees (Compl., Request for Relief ¶E).

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

  • A core issue will be one of structural identity: Does the selexipag active ingredient in Apotex's proposed generic product, as described in its ANDA, exhibit the specific four-peak powder X-ray diffraction signature that defines the "Form-I crystal" claimed in the ’122 Patent? This is a purely factual question that will likely be resolved by competing scientific evidence.
  • A secondary issue, contingent on the first, will be one of induced infringement: Assuming Apotex's product contains the patented Form-I crystal, will its FDA-approved labeling direct medical professionals and patients to use the drug for treating pulmonary arterial hypertension or another indication claimed in the ’280 Patent?