DCT

1:20-cv-01617

Adverio Pharma GmbH v. MSN Laboratories Pvt Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:20-cv-01617, D. Del., 11/25/2020
  • Venue Allegations: Venue is alleged to be proper in Delaware because Defendant MSN Pharmaceuticals Inc. is incorporated in Delaware, is registered to do business there, and has consented to suit. Plaintiffs also allege both defendants have continuous contacts with the district and have previously consented to jurisdiction in a related patent case.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market generic versions of Plaintiff's Adempas® (riociguat) tablets constitutes an act of infringement of a patent covering specific crystalline forms of the active ingredient.
  • Technical Context: The lawsuit concerns specific solid-state forms (polymorphs and solvates) of the active pharmaceutical ingredient riociguat, which are crucial for ensuring the stability, purity, and manufacturing consistency of a drug product.
  • Key Procedural History: The action was initiated under the Hatch-Waxman Act following Defendants' submission of a Paragraph IV certification asserting that U.S. Patent No. 10,662,188 is invalid, unenforceable, or will not be infringed by their proposed generic product. The complaint notes a prior related patent case between the parties in the same district.

Case Timeline

Date Event
2013-02-21 Earliest Priority Date for '188 Patent
2020-05-26 U.S. Patent No. 10,662,188 Issued
2020-10-16 Plaintiffs allegedly received Defendants' Paragraph IV Letter regarding the '188 Patent
2020-11-25 Complaint Filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 10,662,188 - Forms of Methyl {4,6-Diamino-2-[1(2-Fluorobenzyl)-1H-Pyrazolo[3-4-B]Pyridino-3-Yl]Pyrimidino-5-Yl} Methyl Carbamate, Issued May 26, 2020

The Invention Explained

  • Problem Addressed: The patent describes prior art methods for preparing the chemical compound riociguat—the active ingredient in Adempas®—as having a "number of disadvantages" ('188 Patent, col. 2:40-42). In pharmaceutical development, producing a pure and stable form of an active ingredient is a critical challenge, as different physical forms can affect a drug's performance and shelf-life.
  • The Patented Solution: The invention claims to have discovered and characterized several distinct, stable solid forms of riociguat, including two crystalline modifications (polymorphs) and several solvates (crystals incorporating solvent molecules) ('188 Patent, col. 4:56-66). By isolating and defining these specific forms using analytical techniques like X-ray powder diffraction, the patent provides a basis for producing a consistent and stable drug substance for use in pharmaceutical compositions ('188 Patent, col. 5:5-12).
  • Technical Importance: Identifying and controlling the specific crystalline form of an active pharmaceutical ingredient is essential for large-scale manufacturing, ensuring predictable dissolution rates, bioavailability, and regulatory approval.

Key Claims at a Glance

  • The complaint asserts claims 15-18, 21-22, and 26-30 (Compl. ¶37). The independent claims in this set are 15 and 21.
  • Independent Claim 15: A compound claim covering:
    • The compound of formula (I) (riociguat);
    • in the form of "Modification I," as "1/4-ethyl acetate solvate," or a mixture thereof.
  • Independent Claim 21: A pharmaceutical composition claim comprising:
    • "only one" of the forms selected from "Modification I" and "1/4-ethyl acetate solvate" of the compound of formula (I);
    • and a pharmaceutically acceptable carrier.
  • The complaint reserves the right to assert other claims, including dependent claims which further define the forms by specific analytical data (Compl. ¶37).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Defendants' generic riociguat tablet in 0.5 mg, 1 mg, 1.5 mg, 2 mg, and 2.5 mg dosage strengths, for which they seek FDA approval via Abbreviated New Drug Application (ANDA) No. 211135 (Compl. ¶1, ¶9).

Functionality and Market Context

The defendants' product is a generic version of Bayer's Adempas®, a soluble guanylate cyclase (sGC) stimulator (Compl. ¶26, ¶28). It is intended for the treatment of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension (Compl. ¶26). The complaint alleges that MSN intends to manufacture, use, sell, and import this product into the U.S. market upon receiving FDA approval, prior to the expiration of the ’188 Patent (Compl. ¶1, ¶29).

IV. Analysis of Infringement Allegations

The complaint alleges that the submission of ANDA No. 211135 is an act of infringement under 35 U.S.C. § 271(e)(2) and that the future commercialization of the ANDA product would infringe claims 15-18, 21-22, and 26-30 of the ’188 Patent (Compl. ¶36, ¶37). The complaint does not provide a claim chart or specific factual allegations mapping the characteristics of the defendants' proposed generic product to the elements of the asserted claims. Instead, it asserts that MSN’s Paragraph IV letter "does not contend that Defendants' ANDA Product, or its use, will not infringe" the asserted claims, suggesting the dispute may center on patent validity rather than infringement (Compl. ¶38). Figure 1 of the '188 patent is an X-ray powder diffractogram showing the characteristic peaks for the crystalline form designated "Modification I" ('188 Patent, Fig. 1). Dependent claim 18 explicitly characterizes "Modification I" by reference to this figure, making it central to the infringement analysis of that claim ('188 Patent, col. 30:1-3).

Given the lack of detailed allegations, a claim-chart analysis is not possible based on the complaint alone. The core infringement theory is that the active pharmaceutical ingredient in MSN's ANDA product is, or is contained within, one of the specific crystalline forms claimed in the '188 Patent.

  • Identified Points of Contention:
    • Evidentiary Question: A primary question for the court will be whether the crystalline form of riociguat in MSN's ANDA product is, in fact, one of the forms claimed by the ’188 Patent. This will depend on a comparison of analytical data (e.g., X-ray powder diffraction, infrared spectroscopy) from MSN's product with the characterization data defining the claimed forms in the patent.
    • Scope Questions: The interpretation of terms defining the claimed forms will be critical. For example, dependent claim 18 defines "Modification I" as having an X-ray powder diffractogram "substantially as shown in FIGS. 1, 4" ('188 Patent, col. 30:1-3). The scope of "substantially" will be a key issue in determining the breadth of the claim and whether it reads on MSN's product, which may exhibit minor, instrument-related variations in its diffraction pattern.

V. Key Claim Terms for Construction

  • The Term: "Modification I"

  • Context and Importance: This term defines one of the core crystalline forms of riociguat claimed in the patent and is recited in asserted independent claim 15. Its construction is critical because infringement will depend on whether MSN's product contains this specific polymorph. Practitioners may focus on this term because polymorph claims are defined by their physical characteristics, and the patent provides multiple, potentially conflicting, definitions.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent specification describes "Modification I" as the "thermodynamically stable form between 0° C. and 80° C." ('188 Patent, col. 5:13-14). A party could argue this functional language should inform the term's scope beyond strict adherence to the analytical data.
    • Evidence for a Narrower Interpretation: The patent provides highly specific analytical data to define "Modification I," including X-ray powder diffraction peaks listed to one decimal place (e.g., "6.7, 9.1, 14.3, 14.4...") and a reference to the diffractogram in Figure 1 ('188 Patent, col. 8:18-23; col. 30:1-3). A party could argue that the claim is limited to forms that precisely match this detailed "fingerprint."

  • The Term: "comprising only one of the forms" (from Claim 21)

  • Context and Importance: This phrasing in independent claim 21 creates a negative limitation. The claim covers a composition that includes "Modification I" or the "1/4-ethyl acetate solvate," but not other forms. This is important because pharmaceutical manufacturing processes can sometimes result in mixtures of polymorphs.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation (i.e., allowing trace amounts of other forms): A party might argue that "only one" should be interpreted in the context of pharmaceutical purity, where trace, undetectable, or insignificant amounts of other forms do not negate the essential character of the composition as containing "only one" form. The patent's use of "no significant fractions" elsewhere could be used to support this view ('188 Patent, col. 5:31-32).
    • Evidence for a Narrower Interpretation (i.e., requiring absolute absence of other forms): The plain language "only one" is restrictive. A party could argue that the presence of any detectable amount of another crystalline form (e.g., Modification II, an amorphous form, or another solvate) would place the composition outside the literal scope of the claim.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon approval and commercialization, MSN's actions will induce and contribute to the infringement of the ’188 Patent by others, such as physicians and patients using the product (Compl. ¶37; Prayer for Relief ¶C).
  • Willful Infringement: The complaint alleges that MSN had actual knowledge of the ’188 Patent at least as of its Paragraph IV notice letter, dated October 16, 2020 (Compl. ¶30, ¶39). It further alleges that MSN "has no reasonable basis to conclude that it has not infringed" and that the case is "exceptional," forming the basis for a claim of willfulness and a request for enhanced damages and attorneys' fees (Compl. ¶43; Prayer for Relief ¶F, ¶G).

VII. Analyst’s Conclusion: Key Questions for the Case

  • A central issue will be one of characterization and equivalence: Does the riociguat in MSN's proposed generic product exhibit the specific physical and chemical "fingerprint" (e.g., X-ray diffraction peaks, melting point) required by the asserted claims? This is a technical, evidence-intensive question that will likely require expert testimony on analytical chemistry.
  • A key legal question will be the scope of patentability for polymorphs: Assuming MSN contests validity, the case will test whether the specific crystalline forms claimed in the ’188 Patent were novel and non-obvious over prior art disclosures of the riociguat compound itself.
  • A determinative strategic question will be whether the dispute focuses on infringement or validity. The complaint's allegation that MSN's pre-suit notice did not contest infringement raises the possibility that MSN may concede that its product falls within the claim scope and focus its entire defense on proving the patent is invalid.