DCT
1:24-cv-00434
Actelion Pharma Ltd v. Gland Pharma Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Actelion Pharmaceuticals Ltd (Switzerland)
- Defendant: Gland Pharma Limited (India)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: 1:24-cv-00434, D. Del., 04/05/2024
- Venue Allegations: Venue is alleged to be proper because the Defendant is a foreign corporation not resident in the United States.
- Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) for a generic version of Plaintiff's VELETRI® product constitutes an act of infringement of a patent covering a stable formulation of epoprostenol and its method of manufacture.
- Technical Context: The technology concerns pharmaceutical formulations of epoprostenol, a drug for treating pulmonary arterial hypertension (PAH), that are chemically stabilized by using a high-pH environment to improve shelf-life and ease of use for patients.
- Key Procedural History: This is a Hatch-Waxman litigation initiated after Defendant filed an ANDA with a Paragraph IV certification, asserting that U.S. Patent No. 8,598,227, which is listed in the FDA's Orange Book for VELETRI®, is invalid or will not be infringed by its proposed generic product. The complaint was filed within the 45-day statutory window, which typically triggers a 30-month stay of FDA approval for the generic.
Case Timeline
| Date | Event |
|---|---|
| 2006-02-03 | '227 Patent Priority Date |
| 2008-06-27 | FDA approval for VELETRI® (1.5 mg/vial) |
| 2012-06-28 | FDA approval for VELETRI® (0.5 mg/vial) |
| 2013-12-03 | '227 Patent Issue Date |
| 2024-04-05 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,598,227 - Epoprostenol Formulation and Method of Making Thereof (Issued Dec. 3, 2013)
The Invention Explained
- Problem Addressed: The patent’s background section describes the chemical instability of epoprostenol, a prostacyclin used to treat cardiovascular diseases ('227 Patent, col. 1:15-19). Epoprostenol degrades rapidly in solution, particularly at lower pH levels, which complicates its administration via continuous intravenous infusion and requires burdensome procedures like refrigeration and frequent replacement of the drug solution ('227 Patent, col. 3:35-40, Table 1).
- The Patented Solution: The invention is based on the discovery that formulating epoprostenol at a very high pH (greater than 11) in the presence of an alkalinizing agent dramatically improves its stability ('227 Patent, col. 3:16-23). This allows the reconstituted drug to be stored and administered at ambient temperatures for extended periods (e.g., 24-48 hours), simplifying patient use ('227 Patent, col. 3:25-27). The patent describes both the stable composition and a method for producing a lyophilized (freeze-dried) version by adjusting the pH of a bulk solution to above 13 prior to lyophilization ('227 Patent, col. 4:49-53).
- Technical Importance: This enhanced stability addresses a significant practical challenge for patients with PAH who rely on continuous epoprostenol infusion, reducing the logistical burden and potential for error associated with the prior art formulation ('227 Patent, col. 4:8-12).
Key Claims at a Glance
- The complaint alleges infringement of "one or more claims" ('227 Patent, ¶20). The factual allegations most closely map to independent method of making claim 1.
- Independent Claim 1:
- A method for making an epoprostenol composition comprising the steps of:
- (a) providing a bulk solution comprising (i) epoprostenol or a salt thereof, and (ii) an alkalinizing agent; and
- (b) adjusting the pH of the bulk solution to greater than 13.
- The general nature of the allegations suggests Plaintiff reserves the right to assert additional claims, including dependent claims and method of treatment claims (e.g., claim 16, claim 22).
III. The Accused Instrumentality
- Product Identification: The accused instrumentalities are "Gland's ANDA Products," specifically generic epoprostenol sodium for injection in 1.5 mg/vial and 0.5 mg/vial dosage forms, for which Gland seeks FDA approval via ANDA No. 219237 (Compl. ¶2, ¶15).
- Functionality and Market Context: The ANDA Products are lyophilized powders intended to be reconstituted into a solution for injection for the treatment of PAH (Compl. ¶2, ¶12). The complaint alleges, on information and belief, that the manufacturing process specified in Gland's ANDA involves preparing a bulk solution of epoprostenol with an alkaline agent, adjusting the pH of that solution to a level greater than 13, and then lyophilizing the solution (Compl. ¶24-25, ¶29-30). These products are intended to be generic equivalents to Actelion’s branded drug, VELETRI® (Compl. ¶2, ¶14).
IV. Analysis of Infringement Allegations
The complaint does not contain claim charts. The following table summarizes the infringement theory for claim 1 based on the narrative allegations.
No probative visual evidence provided in complaint.
'227 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| (a) providing a bulk solution comprising (i) epoprostenol or a salt thereof, and (ii) an alkalinizing agent; | Defendant's manufacturing process allegedly includes providing a bulk solution containing epoprostenol and an agent that creates an alkaline environment (pH > 7). | ¶24, ¶29 | col. 10:30-33 |
| (b) adjusting the pH of the bulk solution to greater than 13. | Defendant's manufacturing process allegedly includes adjusting the pH of the bulk solution to a value greater than 13 before lyophilizing it. | ¶25, ¶30 | col. 10:33-34 |
- Identified Points of Contention:
- Evidentiary Question: The complaint's allegations regarding Defendant's manufacturing process are made "on information and belief" (Compl. ¶24). The central question for the court will be a factual one: does the process detailed in Gland's confidential ANDA actually include the step of "adjusting the pH of the bulk solution to greater than 13," as required by claim 1?
- Scope Question: A dispute may arise over the claim term "alkalinizing agent." The court may need to determine if the specific excipient used in Gland's formulation falls within the patent's definition of this term, which could be construed narrowly to mean specific types of non-hydroxide bases.
V. Key Claim Terms for Construction
- The Term: "alkalinizing agent"
- Context and Importance: This term appears in the first step of independent claim 1 and is fundamental to defining the scope of the invention. Whether Gland’s product infringes will depend on whether the agent it uses to achieve an alkaline pH meets the definition of this term as construed by the court.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent provides a definition: "An alkalinizing agent, as used herein, means an agent that provides alkaline environment (pH>7) when epoprostenol is dissolved in water along with the alkalinizing agent" ('227 Patent, col. 5:3-5). This language could support a broad reading covering any substance that achieves this result.
- Evidence for a Narrower Interpretation: The specification adds a qualifier: "it does not contain a basic hydroxide group, but may contain at least one functional group that accepts a proton from water" and then lists examples such as arginine, lysine, and sodium carbonates ('227 Patent, col. 5:6-18). This language could support an argument that the term is limited to non-hydroxide bases or to the specific classes of compounds disclosed.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that upon FDA approval, Gland will induce infringement of the patent's method of treatment claims (Compl. ¶31-33). The basis for this allegation is that Gland will market its generic product with a label instructing physicians and patients to reconstitute and administer the drug for its approved indication, which will cause them to perform the steps of the patented methods.
VII. Analyst’s Conclusion: Key Questions for the Case
- A primary issue in this case will be one of evidentiary proof: does Gland's confidential ANDA submission describe a manufacturing process that explicitly requires adjusting the pH of the pre-lyophilized bulk solution to "greater than 13"? The resolution of this factual question, based on evidence from the ANDA itself, will be determinative for the infringement analysis of the asserted method claim.
- A secondary issue will be one of definitional scope: does the specific excipient used in Gland's proposed generic product meet the patent's definition of an "alkalinizing agent," particularly in light of specification language that may be argued to limit the term to non-hydroxide bases capable of accepting a proton?