DCT
1:24-cv-01162
Actelion Pharma US Inc v. Lannett Co Inc
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: Lannett Company, Inc. (Delaware)
- Plaintiff’s Counsel: Ashby & Geddes; Paul Hastings LLP
- Case Identification: 1:24-cv-01162, D. Del., 10/17/2024
- Venue Allegations: Venue is asserted as proper in the District of Delaware on the basis that Defendant is a Delaware corporation and conducts business within the state.
- Core Dispute: Plaintiffs allege that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for generic selexipag tablets constitutes an act of infringement of two patents covering a specific crystalline form of the selexipag compound and its method of use.
- Technical Context: The dispute centers on a specific polymorphic form (Form-I) of selexipag, the active ingredient in the drug UPTRAVI®, which is used to treat pulmonary arterial hypertension.
- Key Procedural History: The patents-in-suit are listed in the FDA’s "Orange Book" as covering UPTRAVI®. Defendant submitted a Paragraph IV certification with its ANDA, asserting non-infringement or invalidity of the patents. U.S. Patent No. 8,791,122 underwent an ex parte reexamination, with a certificate issuing on September 15, 2017, which resulted in the cancellation of claim 3. This lawsuit was filed within the 45-day statutory window following receipt of Defendant's Paragraph IV notice, triggering a 30-month stay on FDA approval of the generic 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 Issued |
| 2015-12-21 | FDA Approval for UPTRAVI® (NDA No. 207947) |
| 2016-03-15 | U.S. Patent No. 9,284,280 Issued |
| 2017-09-15 | Reexamination Certificate Issued for '122 Patent |
| 2024-09-06 | Lannett Sends Paragraph IV Notice Letter to Plaintiffs |
| 2024-10-17 | Complaint Filed |
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”
- Patent Identification: 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,” issued July 29, 2014.
The Invention Explained
- Problem Addressed: The patent’s background section notes the therapeutic usefulness of the active compound (selexipag, or "compound A") but states 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). For pharmaceutical manufacturing, an active ingredient should be a "thing of a high quality for which constant effect can be always shown and of a form which is handled easily industrially" ('122 Patent, col. 2:56-59). The absence of a defined, stable crystalline form presents challenges for consistent manufacturing and drug product performance.
- The Patented Solution: The invention provides a specific, novel crystalline polymorph of selexipag, designated "Form-I" ('122 Patent, col. 2:64-65). This crystalline form is not defined by its chemical structure alone, but by its unique physical properties, specifically a characteristic set of diffraction peaks observed in a powder X-ray diffraction (PXRD) spectrum ('122 Patent, col. 3:1-3). This provides a stable and reproducible solid form of the drug suitable for pharmaceutical development.
- Technical Importance: Identifying and characterizing a specific, stable crystalline form of an active pharmaceutical ingredient is critical for ensuring product consistency, stability, and predictable bioavailability in a final drug product.
Key Claims at a Glance
- The complaint generally asserts infringement of one or more claims (Compl. ¶27). The independent claims are:
- Independent Claim 1:
- 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.
- Independent Claim 2:
- A pharmaceutical composition comprising the crystal of claim 1 as an active ingredient.
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”
- Patent Identification: 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,” issued March 15, 2016.
The Invention Explained
- Problem Addressed: The patent describes a need for preventive or therapeutic agents for a wide range of conditions, including peripheral circulatory disturbances, thrombosis, and pulmonary hypertension ('280 Patent, col. 2:49-61).
- The Patented Solution: The invention claims a method of treating these specified medical conditions by administering the specific "Form-I" crystal of selexipag, which is identified by the same characteristic PXRD peaks as in the ’122 Patent ('280 Patent, col. 17:58-65). The patent thereby protects the therapeutic application of this specific crystalline form.
- Technical Importance: This patent extends protection beyond the composition of matter to the specific medical use of the defined crystalline form, a common strategy to secure comprehensive patent coverage for a new drug product.
Key Claims at a Glance
- The complaint generally asserts infringement of one or more claims (Compl. ¶27). The sole independent claim is:
- Independent Claim 1:
- A method for treating a condition selected from a group including, among others, diabetic neuropathy, peripheral circulatory disturbance, pulmonary hypertension, and chronic renal failure,
- comprising the step of administering to a subject an active ingredient,
- wherein the active ingredient is the Form-I crystal of selexipag as defined by the characteristic PXRD peaks of 9.4, 9.8, 17.2, and 19.4 degrees.
III. The Accused Instrumentality
Product Identification
Defendant's proposed generic selexipag tablets, for which it seeks FDA approval under ANDA No. 219117 ("Lannett's ANDA Products") (Compl. ¶8).
Functionality and Market Context
The complaint alleges that Lannett's ANDA Products are generic versions of Plaintiffs' UPTRAVI® tablets, available in multiple strengths (Compl. ¶¶8, 16). The function of the accused products is to deliver selexipag for the treatment of pulmonary arterial hypertension (PAH) (Compl. ¶17). The filing of the ANDA itself implies that Lannett's product is bioequivalent to UPTRAVI® and will be marketed as a lower-cost alternative upon receiving FDA approval. The complaint notes that Plaintiffs requested samples of Defendant's active pharmaceutical ingredient and exhibit batches to evaluate infringement, but as of the filing date, Defendant had not provided them (Compl. ¶24).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint does not contain a claim chart or specific, element-by-element infringement allegations. It makes a general allegation that Lannett's ANDA Products meet all elements of one or more claims of the patents-in-suit (Compl. ¶28). The analysis below is based on the implied infringement theories for this type of ANDA litigation.
'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 active pharmaceutical ingredient (API) in Lannett's ANDA Products is alleged to be a crystalline form of selexipag. | ¶28 | col. 15:47-51 |
| ...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 selexipag API in Lannett's ANDA Products is alleged to possess the specific "Form-I" crystal structure, which would exhibit these characteristic PXRD peaks. | ¶28 | col. 15:52-56 |
'280 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for treating... pulmonary hypertension... | Lannett seeks approval to market its generic selexipag for the treatment of pulmonary arterial hypertension, the same indication as the brand-name drug UPTRAVI®. | ¶¶8, 17 | col. 17:50-54 |
| ...comprising the step of administering... a crystal of [selexipag] showing diffraction peaks [at the specified angles]... | Lannett’s proposed product labeling will allegedly instruct physicians and patients to administer its generic product, which is alleged to contain the claimed Form-I crystal, for the treatment of PAH. | ¶¶28, 35 | col. 17:58-65 |
- Identified Points of Contention:
- Technical Question: A central factual question for the '122 Patent is whether the selexipag API in Lannett's ANDA Products is, in fact, the claimed Form-I crystal. The resolution of this issue will depend on scientific evidence, such as PXRD analysis of Lannett's product, which the complaint notes has not yet been provided to Plaintiffs (Compl. ¶24).
- Scope Question: For both patents, a potential dispute could arise over the interpretation of the PXRD peak data. The analysis will question whether the diffraction peaks from Lannett’s product fall within the scope of the claims, especially considering instrumental variability and the patent's explicit definition of a peak as the stated value +/- 0.2 degrees ('122 Patent, col. 3:24-29).
V. Key Claim Terms for Construction
- The Term: "showing diffraction peaks... at least at the following angles of diffraction 2θ: 9.4 degrees, 9.8 degrees, 17.2 degrees and 19.4 degrees"
- Context and Importance: This phrase is the defining limitation of the claimed "Form-I" crystal and is at the heart of the infringement analysis for both patents. The determination of whether Lannett's product infringes will depend on whether its PXRD spectrum meets this limitation. Practitioners may focus on this term because disputes over PXRD data in polymorph cases often involve arguments about measurement precision and the scope of such defining peak lists.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification explicitly states: "When specifying an angle of diffraction 2 theta (2θ) for a peak...it should be understood that the value given is to be understood as an interval from said value minus 0.2° to said value plus 0.2°" ('122 Patent, col. 3:24-29). This language may support an argument that any product whose peaks fall within this defined range infringes.
- Evidence for a Narrower Interpretation: A party could argue that the provided tolerance accounts for minor experimental shifts but does not cover a fundamentally different crystalline form that happens to have peaks nearby. They may point to the specific PXRD chart in Figure 1 of the patent as the quintessential example of the invention, potentially arguing that significant deviation from that pattern, even if within the +/- 0.2° range, indicates a different, non-infringing form.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that if Lannett commercially manufactures and sells its ANDA Products, it will induce infringement of the '122 and '280 patents (Compl. ¶35). For the '280 Patent (a method of treatment claim), the primary theory is induced infringement under 35 U.S.C. § 271(b). The alleged inducement is based on the instructions for use in Lannett's proposed product labeling, which will direct medical professionals and patients to administer the drug for the treatment of PAH.
- Willful Infringement: The complaint alleges that Lannett had "actual and constructive notice" of the patents-in-suit prior to filing its ANDA (Compl. ¶33). This allegation of pre-suit knowledge, likely based on the patents' listing in the FDA Orange Book, forms the basis for a potential claim of willful infringement.
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of factual identity: As a matter of scientific evidence, does the crystalline structure of the selexipag active ingredient in Defendant’s proposed generic product meet the specific powder X-ray diffraction peak limitations defining the "Form-I" crystal in the patents-in-suit? The case will likely turn on expert analysis and testing of Defendant's product samples.
- A second key question will be one of induced infringement: Will the final, FDA-approved product label for Defendant's generic drug contain instructions that actively encourage or direct medical professionals to administer the product for treating pulmonary hypertension or another condition explicitly recited in the '280 Patent's method claims?