DCT
1:22-cv-01450
Actelion Pharma US Inc v. Cipla 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: Alembic Pharmaceuticals Limited (India) and Alembic Pharmaceuticals, Inc. (Delaware)
- Plaintiff’s Counsel: Ashby & Geddes; Paul Hastings LLP
- Case Identification: 1:22-cv-01450, D. Del., 11/03/2022
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Alembic Inc. is a Delaware corporation and Defendant Alembic Ltd. is a foreign corporation subject to personal jurisdiction in the district through its U.S. subsidiary and its own business contacts and prior litigation conduct in Delaware.
- Core Dispute: Plaintiffs allege that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of UPTRAVI® (selexipag) constitutes an act of infringement of two patents covering a specific crystalline form of selexipag and its therapeutic use.
- Technical Context: The technology concerns a specific crystalline polymorph (Form-I) of selexipag, a pharmaceutical compound used for treating pulmonary arterial hypertension (PAH).
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of a Paragraph IV certification notice letter, asserting that their proposed generic product would not infringe the patents-in-suit, which are listed in the FDA's "Orange Book" as covering the branded drug UPTRAVI®. The complaint notes that U.S. Patent No. 8,791,122 was the subject of a reexamination proceeding that concluded on September 15, 2017.
Case Timeline
| Date | Event |
|---|---|
| 2009-06-26 | Priority Date for '122 and '280 Patents |
| 2014-07-29 | U.S. Patent No. 8,791,122 Issues |
| 2016-03-15 | U.S. Patent No. 9,284,280 Issues |
| 2017-09-15 | '122 Patent Reexamination Certificate Issued |
| 2021-07-29 | FDA Approves UPTRAVI® for Intravenous Use |
| 2022-09-23 | Date of Alembic's Paragraph IV Certification Notice Letter |
| 2022-11-03 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,791,122
- 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. (Compl. ¶29; '122 Patent).
The Invention Explained
- Problem Addressed: The patent's background section notes the therapeutic utility of the chemical compound selexipag (referred to as "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. 2:46-49). This implies a need for a physically stable and pure form of the compound suitable for pharmaceutical manufacturing.
- The Patented Solution: The invention provides a novel, specific crystalline form of selexipag, designated "Form-I." This crystalline form is distinguished from other potential solid forms (such as amorphous solids or other polymorphs) by a unique and reproducible pattern of peaks when analyzed by powder X-ray diffraction (PXRD), a standard analytical technique. ('122 Patent, Abstract; col. 2:63-col. 3:4).
- Technical Importance: The patent notes the goal is to create a "medicament bulk" of "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). Discovering a stable crystalline form is a critical step in drug development, as it ensures consistent physical properties like solubility, stability, and dissolution rate, which directly impact a drug's safety and efficacy.
Key Claims at a Glance
- The complaint asserts infringement of "one or more claims" of the '122 patent (Compl. ¶38). Independent claim 1 is the sole independent composition of matter claim.
- 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.
U.S. Patent No. 9,284,280
- 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. (Compl. ¶30; '280 Patent).
The Invention Explained
- Problem Addressed: The patent identifies a wide range of diseases, including pulmonary hypertension, that can be treated with selexipag ('280 Patent, col. 1:50-col. 2:43). The technical problem is the effective therapeutic treatment of these specific medical conditions.
- The Patented Solution: The invention is a method of treating the specified diseases by administering the specific "Form-I crystal" of selexipag, which is identified by the same characteristic PXRD peaks as claimed in the '122 patent ('280 Patent, col. 16:50-65).
- Technical Importance: This patent provides method-of-use protection, linking the specific, stable crystalline form of the drug substance to its approved therapeutic application. This allows the patent holder to assert infringement against those who use or encourage others to use a generic product for the patented medical indication.
Key Claims at a Glance
- The complaint asserts infringement of "one or more claims" of the '280 patent (Compl. ¶38). Independent claim 1 is the lead independent method claim.
- Independent Claim 1:
- A method for treating a list of diseases including "pulmonary hypertension,"
- comprising the step of administering, as an active ingredient to a subject, 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.
III. The Accused Instrumentality
Product Identification
Defendant's "generic Selexipag for Injection, 1.8 mg/vial," referred to as "Alembic's ANDA Product" (Compl. ¶13).
Functionality and Market Context
The accused product is a generic version of Plaintiffs' UPTRAVI®, which is approved for the treatment of pulmonary arterial hypertension (PAH) (Compl. ¶27, ¶31). The product is a lyophilized powder intended for reconstitution and injection (Compl. ¶26). By filing its ANDA, Alembic seeks FDA approval to manufacture and sell this generic version in the U.S. before the expiration of the patents-in-suit (Compl. ¶13). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint alleges infringement under 35 U.S.C. § 271(e)(2)(A), which defines the submission of an ANDA for a patented drug as a technical act of infringement to create federal court jurisdiction. The complaint makes a general allegation that the ANDA product "meets or embodies all elements of one or more claims" (Compl. ¶39), without providing a detailed, element-by-element analysis.
'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, | Alembic's ANDA Product is identified as "generic Selexipag for Injection," containing the specified chemical compound. | ¶13 | col. 1:24-30 |
| 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 on information and belief that the active ingredient in Alembic's ANDA Product is the claimed Form-I crystal. | ¶39 | col. 3:1-4 |
'280 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for treating... pulmonary hypertension... | Alembic's ANDA seeks approval for a generic version of UPTRAVI®, which is indicated for treating pulmonary arterial hypertension (PAH). | ¶27 | col. 8:40-41 |
| comprising the step of administering... a crystal of [selexipag] showing [the specific Form-I PXRD peaks]... | The complaint alleges that Alembic will induce and contribute to infringement by marketing its ANDA product, which contains the claimed Form-I crystal, with a label instructing its administration for the patented use. | ¶39, ¶41, ¶46 | col. 16:59-65 |
- Identified Points of Contention:
- Technical Question: The central dispute will likely be one of polymorphic identity. The case may turn on whether the active pharmaceutical ingredient in Alembic's ANDA product is, in fact, the specific "Form-I crystal" defined by the patents' PXRD peak limitations. The complaint notes that Alembic has not provided samples for testing, which "has impaired Plaintiffs' ability to evaluate the veracity of the statements made by Alembic Ltd. in its Paragraph IV Certification Notice Letter" (Compl. ¶34). This frames the core issue as a factual and evidentiary one to be resolved through discovery.
- Legal Question: For the '280 Patent, a key question will be whether Alembic's proposed product label will induce infringement. If the label includes PAH as an indication, and the drug product is found to contain the Form-I crystal, this would support a finding of induced infringement of the method-of-use claims.
V. Key Claim Terms for Construction
- The Term: "showing diffraction peaks... at... 9.4 degrees, 9.8 degrees, 17.2 degrees and 19.4 degrees" ('122 Patent, Claim 1).
- Context and Importance: This phrase is the structural fingerprint that defines the patented invention. The infringement analysis for both patents will depend entirely on whether Alembic's product exhibits this specific set of PXRD peaks. Practitioners may focus on this term because experimental data from analytical instruments like PXRD machines has inherent variability, and disputes often arise over how much deviation from the claimed peak values is permissible before a product is considered non-infringing.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification explicitly states that a peak value should be understood as an interval: "from said value minus 0.2° to said value plus 0.2°, and preferably from said value minus 0.1° to said value plus 0.1°" ('122 Patent, col. 3:24-29). A party could argue this language builds a specific degree of flexibility directly into the claim's scope.
- Evidence for a Narrower Interpretation: The patent provides a detailed example for producing the Form-I crystal and includes Figure 1, a representative PXRD spectrum ('122 Patent, Example 1; Fig. 1). A party could argue that the claims should be construed in light of this specific embodiment and its corresponding spectrum, potentially cabining the acceptable range of deviation from the recited values.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that if Alembic's ANDA is approved, it will induce infringement under 35 U.S.C. § 271(b) (Compl. ¶41, ¶46). The basis for this allegation is that Alembic's marketing of its product with a label instructing its use for the treatment of PAH will cause physicians and patients to directly infringe the method claims of the '280 patent.
- Willful Infringement: While the complaint does not explicitly use the word "willful," it lays a foundation for such a claim by alleging that Alembic had "actual and constructive notice" of the patents before filing its ANDA (Compl. ¶44) and sent a Paragraph IV notice letter on September 23, 2022 (Compl. ¶33). The prayer for relief requests a declaration of an "exceptional case" and an award of attorneys' fees, which is consistent with an assertion of egregious infringement (Compl. p. 11, ¶E).
VII. Analyst’s Conclusion: Key Questions for the Case
A central evidentiary question will be one of polymorphic identity: Does the selexipag active ingredient in Alembic’s proposed generic product, when analyzed, exhibit the specific X-ray diffraction pattern of the claimed "Form-I crystal"? The outcome of this factual determination, which will depend on expert analysis and discovery, will be dispositive for the infringement of the '122 patent's composition claims.
A key legal question will be one of inducement: Assuming the product contains the infringing crystal form, will Alembic’s proposed product labeling, by including an indication for pulmonary arterial hypertension, be found to actively encourage and instruct physicians and patients to infringe the method-of-treatment claims of the '280 patent?