DCT
1:23-cv-00088
Actelion Pharma Ltd v. Mylan Pharma Inc
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Actelion Pharmaceuticals Ltd (Switzerland) and Actelion Pharmaceuticals US, Inc. (Delaware)
- Defendant: Mylan Pharmaceuticals Inc. (West Virginia)
- Plaintiff’s Counsel: Simmerman Law Office, PLLC; Paul Hastings LLP (Of Counsel)
- Case Identification: 1:23-cv-00088, N.D. W. Va., 11/07/2023
- Venue Allegations: Venue is based on Defendant being incorporated in West Virginia and having its principal place of business within the judicial district.
- Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the drug Opsumit® (macitentan) constitutes an act of infringement of patents covering the compound itself and its pharmaceutical formulation.
- Technical Context: The technology relates to endothelin receptor antagonists, specifically the compound macitentan, used for the treatment of pulmonary arterial hypertension (PAH), a serious condition involving high blood pressure in the arteries of the lungs.
- Key Procedural History: This is a Hatch-Waxman action triggered by Defendant’s submission of ANDA No. 211161 with a Paragraph IV certification, asserting that its generic product would not infringe the patents-in-suit or that the patents are invalid. The patents-in-suit are listed in the FDA’s “Orange Book” as covering Plaintiff’s Opsumit® product.
Case Timeline
| Date | Event |
|---|---|
| 2000-12-18 | Priority Date for U.S. Patent No. 7,094,781 |
| 2005-09-12 | Priority Date for U.S. Patent No. 10,946,015 |
| 2006-08-22 | U.S. Patent No. 7,094,781 Issued |
| 2013-10-18 | FDA grants approval for Opsumit® (macitentan) under NDA No. 204410 |
| 2021-03-16 | U.S. Patent No. 10,946,015 Issued |
| 2023-11-07 | 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"
The Invention Explained
- Problem Addressed: The patent background describes the role of endothelins—potent vasoconstrictors—in various diseases such as hypertension and pulmonary hypertension, and notes that existing endothelin receptor antagonist molecules possess weaknesses including complex synthesis, low solubility, and potential safety problems (e.g., liver enzyme increases) (’781 Patent, col. 1:12-62).
- The Patented Solution: The invention discloses a new class of pyrimidine-sulfamide compounds that act as endothelin receptor antagonists (’781 Patent, col. 2:1-5). These compounds, defined by a general chemical structure, are designed to treat diseases associated with increased vasoconstriction, such as pulmonary arterial hypertension (’781 Patent, col. 5:26-47).
- Technical Importance: The patent introduced a novel chemical scaffold for creating endothelin receptor antagonists, leading to the development of the therapeutic compound macitentan.
Key Claims at a Glance
- The complaint asserts independent claims 1 and 11, along with dependent claims 5-9 (Compl. ¶23).
- Independent Claim 11 is a compound claim directed to: Propylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-yl]-amide, also known as macitentan.
- The complaint also asserts method of treatment claims but focuses its factual allegations on the compound itself.
U.S. Patent No. 10,946,015 - "Stable Pharmaceutical Compositions Comprising a Pyrimidine-Sulfamide"
The Invention Explained
- Problem Addressed: The patent explains that the subject compound (macitentan) was being evaluated in clinical trials, creating a need for a "stable formulation" suitable for a commercial drug product (’015 Patent, col. 1:55-58). Developing a stable oral dosage form is a common challenge in pharmaceutical development.
- The Patented Solution: The invention provides a stable pharmaceutical composition comprising the active compound along with a specific combination of excipients. The claimed solution involves formulating the compound with a filler, a disintegrant, a specific type of surfactant (a polysorbate), and a lubricant, all within defined weight percentage ranges, to ensure product stability and proper dissolution (’015 Patent, col. 2:60 - col. 3:13, Claim 1).
- Technical Importance: This technology enabled the creation of a stable, manufacturable, and orally administrable tablet form of macitentan, which is essential for its use as a commercial therapeutic.
Key Claims at a Glance
- The complaint asserts independent claims 1 and 34, among numerous other claims (Compl. ¶26).
- Independent Claim 1 is a composition claim comprising:
- a) the compound of formula I (macitentan) in an amount of 1 to 50% by weight;
- b) a filler, in an amount of 10 to 95% by weight;
- c) a disintegrant, in an amount of 1 to 20% by weight;
- d) a surfactant, in an amount from 0.1 to 1% by weight, wherein the surfactant comprises a polysorbate; and
- e) a lubricant, in an amount from 0.05 to 10% by weight.
III. The Accused Instrumentality
Product Identification
- Defendant’s generic macitentan 10 mg oral tablets, which are the subject of Abbreviated New Drug Application (ANDA) No. 211161 (“the ANDA Product”) (Compl. ¶19).
Functionality and Market Context
- The ANDA Product is a generic pharmaceutical intended for the treatment of pulmonary arterial hypertension (PAH) to reduce the risks of disease progression and hospitalization (Compl. ¶14, ¶19). As a generic, it is designed to be therapeutically equivalent to Plaintiff’s branded drug, Opsumit®, and will be marketed as a lower-cost alternative upon receiving FDA approval (Compl. ¶6, ¶19). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint’s infringement theory rests on 35 U.S.C. § 271(e)(2)(A), which defines the submission of an ANDA seeking approval to market a generic drug before the expiration of a relevant patent as a statutory act of infringement (Compl. ¶29).
’781 Patent Infringement Allegations
| Claim Element (from Independent Claim 11) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| Propylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-yl]-amide, or a salt thereof. | The complaint alleges that the chemical name of the compound macitentan is one of the chemical names recited in Claim 11. The ANDA Product for which Mylan seeks FDA approval is alleged to include macitentan 10 mg as the active ingredient, thereby literally infringing the claim. | ¶24, ¶25 | col. 142:50-55 |
’015 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a) the compound of formula I... in a total amount of 1 to 50% in weight | The ANDA Product is alleged to contain macitentan 10 mg as the active ingredient, which is expected to fall within the claimed weight percentage for a pharmaceutical tablet. | ¶19, ¶24 | col. 29:20-23 |
| b) filler, in an amount of 10 to 95% in weight | As a generic equivalent to Opsumit®, the ANDA Product is alleged to be a composition that necessarily includes a filler within the claimed range to achieve the appropriate dosage form and size. | ¶19 | col. 29:24-26 |
| c) disintegrant, in an amount of 1 to 20% in weight | The ANDA Product is alleged to be a composition that necessarily includes a disintegrant within the claimed range to ensure proper breakdown and release of the active ingredient upon ingestion. | ¶19 | col. 29:27-29 |
| d) surfactant, in an amount from 0.1 to 1% in weight... wherein the surfactant comprises a polysorbate | The ANDA Product is alleged to be a composition that necessarily includes a surfactant comprising a polysorbate within the claimed range to achieve bioequivalence with the branded Opsumit® product. | ¶19 | col. 29:30-33 |
| e) lubricant, in an amount from 0.05 to 10% in weight | The ANDA Product is alleged to be a composition that necessarily includes a lubricant within the claimed range to facilitate the manufacturing of the tablets. | ¶19 | col. 29:34-36 |
- Identified Points of Contention:
- Scope Questions: For the ’015 Patent, a central question will be whether the specific excipients and their relative amounts in Mylan's ANDA Product fall within the scope of the asserted claims. For example, if Mylan's formulation uses a surfactant that is not a "polysorbate," it may have a viable non-infringement defense against claims requiring that specific component.
- Technical Questions: While infringement of the ’781 compound patent appears straightforward, the primary defense is likely to be a challenge to the patent's validity. For the ’015 Patent, the key technical question is one of composition: what are the actual ingredients and their weight percentages in Mylan's ANDA product? This information, currently unavailable in the complaint, will be central to the infringement analysis.
V. Key Claim Terms for Construction
’015 Patent
- The Term: "wherein the surfactant comprises a polysorbate" (Claim 1)
- Context and Importance: This term is critical because it defines a specific chemical class required for the surfactant component. The infringement analysis for the ’015 patent will likely hinge on whether Mylan’s formulation includes a polysorbate. Practitioners may focus on this term because designing around such specific formulation elements is a common strategy for generic drug manufacturers.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification discloses a broad class of potential surfactants, including "sodium lauryl sulphate, polysorbates, polyethylene polyoxypropylene polymers," among others (’015 Patent, col. 2:58-63). A party might argue that "polysorbate" should be viewed in this wider context, though the claim language "comprises a polysorbate" appears limiting.
- Evidence for a Narrower Interpretation: The claim language itself explicitly narrows the broad class of surfactants disclosed in the specification to only those that include a "polysorbate." Furthermore, the patent’s preferred embodiments and examples specify using a polysorbate, such as "Tween 80V" (’015 Patent, col. 15, Example RE3), reinforcing that this specific class of surfactant was considered important to the invention.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that if Mylan commercially manufactures and sells its ANDA Product, it will induce and contribute to infringement by third parties (e.g., doctors and patients) (Compl. ¶34). This is based on the expectation that Mylan's product label will instruct users to take the drug for the patented indication of treating PAH.
- Willful Infringement: Willfulness is alleged based on Mylan’s awareness of the patents-in-suit, which are listed in the FDA’s Orange Book (Compl. ¶18, ¶30, ¶33). The act of filing a Paragraph IV certification itself demonstrates knowledge of the patents, which could support a finding of willfulness for any post-suit infringement.
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of validity: Can Mylan successfully challenge the validity of the ’781 compound patent, which appears to be literally infringed by a generic macitentan product? The outcome of this question is fundamental to the entire case.
- A key evidentiary question will be one of compositional fact: Does Mylan's generic formulation fall within the literal scope of the ’015 patent's claims? Specifically, the case may turn on whether Mylan’s product contains the precise excipients, such as a "polysorbate" surfactant, required by the asserted claims, or if Mylan has successfully designed around the formulation patent.