DCT

1:18-cv-00073

Adverio Pharma GmbH v. MSN Laboratories Pvt Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-00073, D. Del., 01/09/2018
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because two defendant entities are incorporated in Delaware, have registered agents in the state, and have allegedly consented to suit. Plaintiffs further allege that Defendants intend to market and sell the accused product in Delaware.
  • Core Dispute: Plaintiffs allege that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the drug Adempas® (riociguat) constitutes an act of infringement of a patent covering the riociguat compound.
  • Technical Context: The technology relates to a class of pharmaceutical compounds known as soluble guanylate cyclase (sGC) stimulators, used for the treatment of cardiovascular disorders such as pulmonary hypertension.
  • Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 211127 and a subsequent Paragraph IV notification letter. The letter asserted that U.S. Patent No. 6,743,798 is invalid and that the proposed generic product would not infringe claims 3-6. The complaint notes that the letter does not contest infringement of claims 1, 2, 7, and 8, apart from the assertion of invalidity. This suit, filed within 45 days of receipt of the letter, triggers a statutory 30-month stay on FDA approval of the ANDA.

Case Timeline

Date Event
1998-07-29 ’798 Patent Priority Date
2004-06-01 ’798 Patent Issue Date
2017-12-01 Date of Alembic's Paragraph IV Letter
2018-01-09 Complaint Filing Date

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

U.S. Patent No. 6,743,798 - "Substituted Pyrazole Derivatives Condensed with Six-Membered Heterocyclic Rings"

  • Patent Identification: U.S. Patent No. 6,743,798, “Substituted Pyrazole Derivatives Condensed with Six-Membered Heterocyclic Rings,” issued June 1, 2004.

The Invention Explained

  • Problem Addressed: The patent seeks to provide novel compounds for the treatment of cardiovascular disorders ('798 Patent, col. 1:8-10). The background section notes prior art related to similar compounds for inhibiting platelet aggregation and treating cardiovascular and central nervous system disorders, implying a need for new or improved therapeutic agents in this area ('798 Patent, col. 1:11-23).
  • The Patented Solution: The invention provides a class of chemical compounds, defined by a general structural formula, that act as direct stimulators of the enzyme soluble guanylate cyclase (sGC) ('798 Patent, Abstract; col. 27:36-39). This stimulation leads to vasorelaxation and an inhibition of platelet aggregation, which can be used to treat conditions like high blood pressure and angina pectoris ('798 Patent, col. 27:36-49). The specific compound riociguat is disclosed as Example 16 in the patent's detailed description ('798 Patent, col. 47:11-28).
  • Technical Importance: The development of direct sGC stimulators provided a novel therapeutic mechanism for managing cardiovascular diseases, particularly those where nitric oxide (NO) bioavailability is impaired ('798 Patent, col. 27:36-42).

Key Claims at a Glance

  • The complaint asserts infringement of claims 1-8 ('798 Patent, col. 82:14–col. 92:50; Compl. ¶46). The independent claims are 1 (compound), 6 (process), 7 (composition), and 8 (method of use).
  • Independent claim 1, a composition of matter claim, recites:
    • A compound of the formula (I)
    • wherein R¹ is a pyrimidinyl group, with specified optional substitutions;
    • wherein R² and R³, together with a double bond, form a fused pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl ring, with specified optional substitutions;
    • wherein A is one of several specified chemical groups (including phenyl), with specified optional substitutions;
    • or a stereoisomeric form or salt thereof.
  • The complaint reserves the right to assert infringement of dependent claims, which narrow the scope of the independent claims ('798 Patent, col. 85:40–col. 91:53).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is the generic drug product described in Defendants' ANDA No. 211127, intended to be a generic equivalent of Bayer's Adempas® tablets (Compl. ¶1).

Functionality and Market Context

  • The active pharmaceutical ingredient (API) in the ANDA product is riociguat (Compl. ¶¶ 1, 29). The product is formulated as tablets in various dosages (0.5 mg, 1 mg, 1.5 mg, 2 mg, and 2.5 mg) for the treatment of pulmonary hypertension (Compl. ¶¶ 1, 32). The filing of the ANDA signifies a commercial intent to market a lower-cost, generic version of the branded Adempas® drug upon receiving FDA approval (Compl. ¶34). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

'798 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound of the formula (I) ... or a stereoisomeric form or salt thereof. The complaint alleges that Defendants' ANDA product contains the active ingredient riociguat, which is a compound claimed by the '798 Patent. The filing of the ANDA seeking approval to market this product is alleged to be an act of infringement. ¶29, ¶45, ¶46 col. 1:36-44
  • Identified Points of Contention:
    • Validity: The complaint states that Defendants’ Paragraph IV letter asserts the '798 Patent is invalid (Compl. ¶38). As the complaint does not provide the specific invalidity grounds, the central technical and legal question for the court will be whether the asserted claims, particularly those covering the riociguat compound, are valid over the prior art.
    • Scope Questions: The complaint notes that Defendants' letter contends non-infringement of claims 3-6 but does not contest infringement of claims 1, 2, 7, and 8 on grounds other than invalidity (Compl. ¶¶ 38-39). This raises the question of what specific claim construction or factual distinction forms the basis for this partial non-infringement argument, and whether it represents a material dispute over claim scope.

V. Key Claim Terms for Construction

  • The Term: "a fused pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl ring"
  • Context and Importance: This term, part of the definition of R² and R³ in independent claim 1, defines the core heterocyclic scaffold of the claimed chemical compounds. The construction of this Markush group will be critical for determining the overall scope of the genus claimed by the patent. Practitioners may focus on this term because its breadth could be a focal point of Defendants' invalidity arguments, which may attempt to read prior art compounds onto a broad interpretation of the claim.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The plain language of the claim uses the disjunctive "or," suggesting that any compound with one of these four specified ring systems, and which meets the other limitations, falls within the claim's scope ('798 Patent, col. 85:50-51). The specification describes the invention as relating broadly to "substituted pyrazole derivatives condensed with six-membered heterocyclic rings," which could support a construction covering a wide range of such structures ('798 Patent, Title; col. 1:6-8).
    • Evidence for a Narrower Interpretation: A party could argue that the term should be interpreted in light of the specific embodiments disclosed. For instance, the patent’s primary example, riociguat (Example 16), is a "pyrazolo[3,4-b]pyridine" derivative ('798 Patent, col. 6:27-31). This specific embodiment could be used to argue that the functional properties of the invention are tied to this particular scaffold, potentially narrowing the effective scope of the claim.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that the eventual commercial manufacture, use, and sale of the ANDA product would induce and contribute to the infringement of the asserted claims, including method-of-use claim 8 (Compl. ¶¶ 46, 50). The basis for this allegation is the intent to market the generic drug for the same FDA-approved indications as the branded product, Adempas® (Compl. ¶¶ 32, 34).
  • Willful Infringement: Willfulness is alleged based on Defendants' "actual and constructive notice" of the '798 Patent prior to filing the ANDA, allegedly evidenced by the patent's listing in the FDA's Orange Book and the sending of the Paragraph IV letter (Compl. ¶¶ 40, 48, 52). The complaint asserts that Defendants proceeded with "no reasonable basis to conclude that it has not infringed," seeking a declaration that the case is "exceptional" for the purpose of awarding attorneys' fees (Compl. ¶52; Prayer ¶F).

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

  • A central issue will be one of validity: are the claims of the '798 Patent that cover the riociguat compound valid, or can Defendants demonstrate that they are anticipated or rendered obvious by the prior art? This question is fundamental to nearly all ANDA litigation.
  • A key secondary issue will be one of claim scope and infringement: what is the specific technical or legal basis for Defendants’ assertion of non-infringement for claims 3-6, and does this argument raise a substantive claim construction dispute that could allow the accused product to avoid infringement of this subset of claims?