DCT

1:18-cv-00111

Adverio Pharma GmbH v. MSN Laboratories Pvt Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: Adverio Pharma GmbH et al. v. MSN Laboratories Private Limited et al., 1:18-cv-00111, D. Del., 01/19/2018
  • Venue Allegations: Venue is alleged to be proper in Delaware because Defendant MSN Pharmaceuticals Inc. is a Delaware corporation and thus "at home" in the district, is registered to do business in the state, has appointed a registered agent for service of process, and has engaged in Delaware-related activities, including sending a notice letter regarding its drug application to Plaintiff Bayer HealthCare, a Delaware corporation.
  • Core Dispute: Plaintiffs allege that Defendants' filing of an Abbreviated New Drug Application (ANDA) seeking approval 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 chemical compounds known as carbamate-substituted pyrazolopyridines, which act as soluble guanylate cyclase (sGC) stimulators for the treatment of cardiovascular disorders like pulmonary hypertension.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiffs' receipt of a "Paragraph IV Letter" from Defendants on or about December 15, 2017. The letter notified Plaintiffs that Defendants had filed an ANDA seeking to market a generic version of Adempas® prior to the expiration of the patent-in-suit. The letter reportedly asserted invalidity of the patent and non-infringement of claims 8, 9, and 11-13, but did not contest infringement of claims 1-7 and 10 if the patent is held valid. The patent-in-suit is listed in the FDA's "Orange Book" in connection with Adempas® and was granted a patent term extension of 1,319 days.

Case Timeline

Date Event
2002-05-08 '037 Patent Priority Date
2007-02-06 '037 Patent Issue Date
2017-12-14 MSN sends Paragraph IV certification letter
2018-01-19 Complaint Filing Date

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

U.S. Patent No. 7,173,037 - "Carbamate-Substituted Pyrazolopyridines"

  • Patent Identification: U.S. Patent No. 7,173,037, “Carbamate-Substituted Pyrazolopyridines,” issued February 6, 2007 (’037 Patent). (Compl. ¶22).

The Invention Explained

  • Problem Addressed: The patent describes the cellular NO/cGMP signaling system as crucial for regulating physiological processes like smooth muscle relaxation. It notes that under pathological conditions such as high blood pressure or heart failure, this system may be suppressed. Existing therapies, such as organic nitrates, rely on the release of nitric oxide (NO) and suffer from disadvantages including the development of patient tolerance. ('037 Patent, col. 1:8-col. 2:4).
  • The Patented Solution: The invention claims to provide a new class of pyrazolopyridine compounds that directly stimulate the soluble guanylate cyclase (sGC) enzyme, thereby increasing cGMP levels without requiring the prior release of NO. This new class of compounds is distinguished by a specific carbamate residue on a pyrimidine ring, a structural feature intended to provide effective sGC stimulation while avoiding the drawbacks of prior art compounds. ('037 Patent, Abstract; col. 2:16-24).
  • Technical Importance: This approach offers a therapeutic pathway for treating cardiovascular disorders that is independent of the NO-generation mechanism, suggesting a potential to circumvent the tolerance issues associated with traditional nitrate-based therapies. ('037 Patent, col. 2:42-54).

Key Claims at a Glance

  • The complaint asserts infringement of claims 1-13 of the ’037 Patent (Compl. ¶40). The key independent claim is Claim 1.
  • Independent Claim 1:
    • A compound of the formula (I) [a core pyrazolopyridine structure], in which
    • R¹ is -NR³C(=O)OR⁴,
    • R² is hydrogen or NH₂,
    • R³ is hydrogen or (C₁-C₄)-alkyl,
    • R⁴ is (C₁-C₆)-alkyl,
    • or a salt or hydrate thereof. ('037 Patent, col. 26:1-26).
  • The complaint notes that the Defendants' Paragraph IV letter did not contend non-infringement of claims 1-7 and 10 if the patent were held valid (Compl. ¶33).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is the generic drug product described in Defendants’ Abbreviated New Drug Application (ANDA) No. 211135 (Compl. ¶1).

Functionality and Market Context

The ANDA seeks FDA approval to market generic riociguat tablets in 0.5 mg, 1 mg, 1.5 mg, 2 mg, and 2.5 mg dosages (Compl. ¶1). This product is a generic version of Bayer's branded drug Adempas®, which is a soluble guanylate cyclase (sGC) stimulator used for treating certain forms of pulmonary hypertension (Compl. ¶26). The complaint alleges that riociguat is a compound that is specifically claimed by the ’037 Patent (Compl. ¶23).

IV. Analysis of Infringement Allegations

The infringement allegation is based on 35 U.S.C. § 271(e)(2), which defines the submission of an ANDA seeking to market a patented drug before patent expiration as an act of infringement (Compl. ¶39). The complaint’s theory is that the proposed generic product, if approved, would infringe because its active pharmaceutical ingredient, riociguat, is a compound covered by the asserted claims.

'037 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound of the formula (I) or a salt or hydrate thereof, where formula (I) specifies a pyrazolopyridine core with substituents including R¹, a carbamate group [-NR³C(=O)OR⁴], and R², an amino group [NH₂] or hydrogen, where R³ is a hydrogen or small alkyl group and R⁴ is a small alkyl group. The complaint alleges that Defendants submitted an ANDA for a generic version of Adempas®, whose active pharmaceutical ingredient is riociguat (Compl. ¶1, ¶28). The complaint further alleges that "Riociguat is one of the compounds claimed in the '037 Patent" (Compl. ¶23). The chemical structure of riociguat, Methyl {4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}(methyl)carbamate, is an embodiment of formula (I) and is specifically recited in dependent claim 4 of the patent. The submission of the ANDA is therefore alleged to be a direct act of infringement under § 271(e)(2) (Compl. ¶39). ¶¶1, 23, 39, 40 col. 26:1-26

Identified Points of Contention

  • Scope Questions: The complaint suggests that the primary dispute will concern patent validity rather than the scope of the claims. It explicitly states that the Defendants' Paragraph IV letter did not assert non-infringement of claims 1-7 and 10 on the condition that the patent is valid (Compl. ¶33). This raises the question of whether Defendants will focus their defense entirely on invalidity arguments (e.g., obviousness, lack of enablement) for these claims.
  • Technical Questions: A potential, though unstated, question for the court could be whether the specific crystalline form (polymorph), salt, or hydrate of riociguat used in the Defendants' ANDA product falls outside the scope of the asserted claims. However, the language "or a salt or hydrate thereof" in Claim 1 provides broad coverage that may preempt such an argument.

No probative visual evidence provided in complaint.

V. Key Claim Terms for Construction

Because the infringement allegation rests on the identity between the accused compound (riociguat) and a specifically claimed compound (claim 4), claim construction may be less of a focal point than validity. However, the breadth of certain terms could become relevant in the context of an invalidity challenge.

  • The Term: "compound"
  • Context and Importance: Practitioners may focus on this term because the Defendants could argue that the specific form of riociguat in their ANDA product (e.g., a particular salt or polymorph) is not the "compound" covered by the claims. The construction of this term, and the associated phrase "or a salt or hydrate thereof," will define the precise boundary of the patent's coverage over different physical forms of the active ingredient.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification discloses a generic formula (I) representing a class of compounds, not just a single entity ('037 Patent, col. 2:25-44). The explicit inclusion of "or a salt or hydrate thereof" in Claim 1 supports a construction that covers various pharmaceutically acceptable forms beyond the base molecule. ('037 Patent, col. 26:26).
    • Evidence for a Narrower Interpretation: An argument could be made that the term should be interpreted in light of the specific embodiments synthesized and described in the patent's examples, potentially limiting the scope to those exact forms. ('037 Patent, col. 19-25).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that the eventual commercialization of the ANDA product would induce and contribute to infringement by others (Compl. ¶40; Prayer for Relief ¶C). This allegation is likely predicated on the fact that the product's FDA-approved label would instruct physicians and patients to use the drug for treating pulmonary hypertension, a method of use protected by claims of the ’037 Patent (e.g., Claim 10).
  • Willful Infringement: The complaint alleges that Defendants had "actual and constructive notice" of the ’037 Patent prior to filing the ANDA and proceeded with knowledge of the patent (Compl. ¶¶ 34, 46). The allegation is supported by Defendants' submission of the Paragraph IV letter, which demonstrates awareness of the patent.

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

  • A core issue will be one of patent validity: Given that the accused product's active ingredient, riociguat, is expressly recited in claim 4 of the patent, the central dispute will likely concern the defendants' affirmative defenses that the asserted claims are invalid, for reasons such as obviousness over prior art or failure to meet the written description and enablement requirements of 35 U.S.C. § 112.
  • A key question for the indirect infringement claim will be evidentiary: Does the proposed product labeling submitted with the Defendants' ANDA contain instructions that would inevitably lead medical professionals and patients to use the generic drug in a manner that practices the methods of treatment recited in the patent's asserted method claims?