DCT
1:23-cv-00731
Actelion Pharma US Inc v. MSN Laboratories Private Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Actelion Pharmaceuticals US, Inc. (Delaware), Actelion Pharmaceuticals Ltd (Switzerland), and Nippon Shinyaku Co., Ltd. (Japan)
- Defendant: MSN Laboratories Private Ltd. (India) and MSN Pharmaceuticals Inc. (Delaware)
- Plaintiff’s Counsel: Ashby & Geddes; Paul Hastings LLP
- Case Identification: 1:23-cv-00731, D. Del., 07/06/2023
- Venue Allegations: Venue is alleged to be proper as to Defendant MSN Pharmaceuticals Inc. because it is a Delaware corporation. Venue is alleged to be proper as to foreign Defendant MSN Laboratories Private Ltd. because it is subject to personal jurisdiction in the district, based on its control over its Delaware-based subsidiary and its business contacts with the state.
- Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) for a generic version of UPTRAVI® (selexipag) constitutes an act of infringement of patents covering a specific crystalline form of the drug and its use in treating pulmonary arterial hypertension.
- Technical Context: The dispute concerns a specific crystalline polymorph (Form-I) of selexipag, an active pharmaceutical ingredient, where distinct crystal structures can affect a drug's stability, bioavailability, and therapeutic performance.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' Paragraph IV certification notice, which asserted that the patents-in-suit are invalid, unenforceable, or will not be infringed by the proposed generic product. U.S. Patent No. 8,791,122 was reissued on September 15, 2017. The complaint notes that Defendants have not produced requested samples of their ANDA product.
Case Timeline
| Date | Event |
|---|---|
| 2009-06-26 | Priority Date for ’122 and ’280 Patents |
| 2014-07-29 | U.S. Patent No. 8,791,122 Issue Date |
| 2016-03-15 | U.S. Patent No. 9,284,280 Issue Date |
| 2017-09-15 | U.S. Patent No. 8,791,122 Reissue Date |
| 2021-07-29 | FDA Approval for UPTRAVI® (intravenous use) |
| 2023-05-24 | Date of Defendant's Paragraph IV Certification Notice Letter |
| 2023-07-06 | 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 explains that while the therapeutic usefulness of the chemical compound selexipag (referred to as "compound A") was known, "no reference describes or suggests the possibility of existence of crystals of compound A" (’122 Patent, col. 2:46-49). The development of a drug product requires a stable, high-quality solid form that can be handled industrially and provides a consistent therapeutic effect (’122 Patent, col. 2:57-60).
- The Patented Solution: The patent discloses the discovery and characterization of novel crystalline forms (polymorphs) of selexipag. Specifically, it claims a "Form-I crystal," which is a unique solid-state arrangement of the selexipag molecules. This form is identified by a characteristic signature in its powder X-ray diffraction (PXRD) spectrum, which serves as a fingerprint for its specific crystal structure (’122 Patent, col. 2:64 - col. 3:3; Fig. 1).
- Technical Importance: Identifying a stable, pure crystalline polymorph is critical in pharmaceutical development, as different forms can have varying solubility, stability, and bioavailability, directly impacting the drug's safety and efficacy.
Key Claims at a Glance
- The complaint asserts infringement of one or more unspecified claims (Compl. ¶36). Independent claim 1 recites:
- A crystal of 2-{-4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl)acetamide;
- 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;
- wherein the X-ray powder diffraction diagram is obtained by using Cu Kα radiation.
U.S. Patent No. 9,284,280 - “Use of Form-I Crystal of 2-{4-[N-(5,6-Diphenylpyrazin-2-yl)-N-Isopropylamino]Butyloxy}-N-(Methylsulfonyl)Acetamide”
The Invention Explained
- Problem Addressed: Similar to its parent patent, the ’280 Patent notes the prior absence of a known crystalline form of selexipag suitable for consistent therapeutic use (’280 Patent, col. 2:45-49). The technical challenge is applying this compound in a reliable form to treat specific medical conditions.
- The Patented Solution: The patent claims methods of treating a list of specific diseases by administering the specific "Form-I crystal" of selexipag. By linking the stable crystalline form to a therapeutic use, the invention claims a method for achieving a reliable medical outcome for conditions including pulmonary hypertension (’280 Patent, cl. 1).
- Technical Importance: Method-of-use patents protect the specific application of a known or novel compound for treating particular diseases, providing a distinct layer of intellectual property beyond the composition of matter itself.
Key Claims at a Glance
- The complaint asserts infringement of one or more unspecified claims (Compl. ¶36). Independent claim 1 recites:
- A method for treating a condition selected from a list including, among others, pulmonary hypertension and peripheral circulatory disturbance;
- comprising the step of administering to a subject a crystal of selexipag;
- where the crystal shows the characteristic Form-I diffraction peaks at 9.4, 9.8, 17.2, and 19.4 degrees 2θ.
III. The Accused Instrumentality
Product Identification
The accused instrumentality is Defendant's generic "Selexipag for Injection, 1.8 mg/vial," for which it submitted Abbreviated New Drug Application (ANDA) No. 218430 to the FDA for approval (Compl. ¶13).
Functionality and Market Context
The ANDA product is a generic version of Plaintiffs' brand-name drug, UPTRAVI® (Compl. ¶¶13, 24). The complaint alleges that UPTRAVI® is used for the treatment of pulmonary arterial hypertension (PAH) (Compl. ¶25). As a generic, the ANDA product is intended to be a bioequivalent and substitutable version of UPTRAVI®, and the act of filing the ANDA to seek approval for this generic version before patent expiry is the statutory basis for the infringement action (Compl. ¶36).
IV. Analysis of Infringement Allegations
The complaint does not provide claim charts or detailed, element-by-element infringement allegations. The infringement theory is based on the statutory act of filing an ANDA for a generic version of a branded drug that is allegedly covered by the patents-in-suit.
’122 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A crystal of 2-{-4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl)acetamide... | The complaint alleges on information and belief that MSN's ANDA Product contains or embodies the claimed crystal of selexipag. This is predicated on the ANDA product being a generic copy of UPTRAVI®, which is listed in the FDA's Orange Book as being covered by the '122 patent. | ¶¶29, 37 | col. 2:51-63 |
| ...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... | The complaint alleges that MSN's ANDA product meets all elements of one or more claims. To be an equivalent generic, the product's active ingredient must be the same as that in UPTRAVI®, which Plaintiffs allege is the claimed Form-I crystal characterized by these specific peaks. | ¶37 | col. 3:1-3 |
’280 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for treating...pulmonary hypertension...comprising the step of administering, as an active ingredient to a subject, a crystal of...[selexipag] showing [Form-I peaks]... | The complaint alleges that MSN's filing of its ANDA constitutes infringement. This suggests an anticipation that Defendants will seek approval to market their generic product with a label that instructs physicians and patients to use it for treating pulmonary arterial hypertension—an indication for which UPTRAVI® is approved and an indication explicitly recited in the claim. This would form the basis for an inducement allegation. | ¶¶25, 36, 44 | cl. 1 |
No probative visual evidence provided in complaint.
- Identified Points of Contention:
- Technical Question: A central factual question is whether MSN's ANDA product actually contains the claimed "Form-I crystal" of selexipag. The infringement case hinges on proving that the active ingredient in MSN's product exhibits the specific PXRD peaks recited in the claims. The complaint notes Plaintiffs' inability to confirm this due to MSN's alleged failure to provide samples (Compl. ¶32).
- Scope Question: For the ’280 patent, a key issue will be the contents of MSN's proposed product label. The dispute may turn on whether the label will explicitly instruct for the treatment of pulmonary hypertension or another claimed indication, which would support a claim of induced infringement.
V. Key Claim Terms for Construction
The Term: "a crystal of"
- Context and Importance: This term is foundational, as the patents claim a specific polymorphic form, not amorphous selexipag or other potential crystal forms. The definition of "crystal" and what properties are required to meet that definition (e.g., degree of crystallinity, purity of the polymorphic form) will be critical to the infringement analysis.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent does not provide a special definition for "crystal," which may support giving the term its plain and ordinary meaning to one of skill in the art of pharmaceutical chemistry.
- Evidence for a Narrower Interpretation: The specification distinguishes between Form-I, Form-II, and Form-III crystals, each with unique PXRD patterns (’122 Patent, Abstract; col. 3:4-19). A party could argue that "a crystal" must be read in this context to mean a substantially pure polymorphic form that is clearly identifiable and distinct from other forms or amorphous material.
The Term: "showing diffraction peaks...at least at the following angles..."
- Context and Importance: This phrase defines the claimed Form-I crystal. Practitioners may focus on this term because the core of the infringement case will involve comparing the PXRD data of MSN's product against these claimed peak locations. The interpretation of "showing" and "at least" will determine how exact the match must be.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification explicitly contemplates variability, stating that a peak value "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" suggests the list of four peaks is the minimum required fingerprint, not an exhaustive list.
- Evidence for a Narrower Interpretation: A party could argue that the claimed peaks must be the prominent, defining peaks of the crystal's diffraction pattern, not merely minor or incidental peaks. They might also argue that the ±0.2° range is a strict boundary for what constitutes a match.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that if MSN commercially manufactures and sells its ANDA Product, it will induce infringement of the ’280 method patent (Compl. ¶44). The factual basis for this future-looking claim is the expected use of a product label that will instruct medical professionals and patients to administer the drug for the patented purpose of treating pulmonary arterial hypertension.
- Willful Infringement: Willfulness is predicated on the allegation that MSN had "actual and constructive notice of the ’122 and ’280 patents prior to the filing of MSN’s ANDA" (Compl. ¶42). The act of filing a Paragraph IV certification itself demonstrates knowledge of the patents, which Plaintiffs will likely argue supports the claim of willfulness if infringement is found.
VII. Analyst’s Conclusion: Key Questions for the Case
The resolution of this case will likely depend on the answers to two central questions:
- A central evidentiary question will be one of composition: does the selexipag in MSN’s ANDA product exist in the specific "Form-I crystal" structure, as defined by the characteristic X-ray diffraction peaks required by the asserted claims, or is it a different polymorph, an amorphous solid, or a mixture of forms?
- For the method-of-use patent, a key issue will be inducement: will the proposed label for MSN's generic product direct or encourage its administration for treating pulmonary arterial hypertension, an indication explicitly recited in claim 1 of the ’280 patent, thereby establishing the requisite intent for induced infringement?