DCT

2:23-cv-01285

Adverio Pharma GmbH v. Alembic Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:23-cv-01285, D.N.J., 03/07/2023
  • Venue Allegations: Venue is asserted based on Defendant Alembic Pharmaceuticals, Inc. maintaining regular and established physical places of business in New Jersey.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the drug ADEMPAS® constitutes an act of infringement of a patent claiming the active compound, riociguat.
  • Technical Context: The technology concerns a specific class of chemical compounds, pyrazolopyridines, which act as stimulators of soluble guanylate cyclase for the treatment of cardiovascular disorders like pulmonary hypertension.
  • Key Procedural History: This Hatch-Waxman litigation was initiated after Defendants notified Plaintiffs of their ANDA filing containing a Paragraph IV certification, asserting that U.S. Patent No. 7,173,037 is invalid, unenforceable, or will not be infringed by the proposed generic product. The patent is listed in the U.S. Food and Drug Administration's "Approved Drug Products with Therapeutic Equivalence Evaluations" (the Orange Book) for Plaintiffs' ADEMPAS® product.

Case Timeline

Date Event
2002-05-08 '037 Patent Priority Date
2007-02-06 '037 Patent Issue Date
2023-01-23 Date of Alembic's ANDA Notice Letter to Plaintiffs
2023-03-07 Complaint Filing Date

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

  • Patent Identification: U.S. Patent No. 7,173,037, "Carbamate-Substituted Pyrazolopyridines," issued February 6, 2007.

The Invention Explained

  • Problem Addressed: The patent's background section notes that while prior pyrazolopyridine derivatives were known to stimulate soluble guanylate cyclase, they suffered from disadvantages regarding their in vivo properties, such as their pharmacokinetic behavior, metabolic pathway, or dose-response relationship (’037 Patent, col. 2:7-12).
  • The Patented Solution: The invention claims to solve this problem by providing a new class of pyrazolopyridine derivatives distinguished by a specific substitution pattern. The core of the invention is a compound having "a pyrimidine residue which has a particular subsitution [sic] pattern, namely a carbamate residue in position 5 of the pyrimidine ring, and an amino group in position 4 of the pyrimidine ring" (’037 Patent, col. 2:18-24). This specific chemical architecture is asserted to provide improved properties over the prior art.
  • Technical Importance: The patented compounds offer a therapeutic approach for cardiovascular disorders by directly stimulating soluble guanylate cyclase, a mechanism that is independent of nitric oxide (NO) and thus may avoid the development of tolerance associated with traditional organic nitrate therapies (’037 Patent, col. 2:42-54).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claim 4 (’037 Patent, ¶34).
  • Independent Claim 1 recites:
    • A compound of the formula (I)
    • 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.
  • The complaint does not explicitly reserve the right to assert other dependent claims.

III. The Accused Instrumentality

Product Identification

  • Defendants' generic riociguat tablets in 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg dosage strengths, for which Alembic submitted ANDA No. 211127 to the FDA (Compl. ¶12).

Functionality and Market Context

  • The accused products are proposed generic versions of Plaintiffs' ADEMPAS® tablets (Compl. ¶32). The complaint alleges that these products contain the active pharmaceutical ingredient riociguat, which is a compound having a specific chemical formula (Compl. ¶33). Riociguat functions as a stimulator of soluble guanylate cyclase, a mechanism used in the treatment of certain types of pulmonary hypertension (’037 Patent, col. 9:1-4).

IV. Analysis of Infringement Allegations

The complaint’s infringement theory is one of literal infringement, alleging that the chemical compound in the accused product is identical to the compound recited in claim 4 of the ’037 patent. The complaint includes a chemical structure diagram of riociguat that Defendants allegedly provided in their notice letter (Compl. ¶33, p. 9). This diagram depicts the specific compound that is the subject of the infringement allegation.

’037 Patent Infringement Allegations

Claim Element (from Dependent Claim 4) Alleged Infringing Functionality Complaint Citation Patent Citation
The compound of claim 1 having the following structure: methyl 4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl(methyl)carbamate or a salt or hydrate thereof. The complaint alleges that in Defendants' notice letter, they stated their ANDA Products contain the compound riociguat, and provides a chemical structure for riociguat that corresponds to the structure recited in claim 4. ¶33 col. 26:41-68

Identified Points of Contention

  • Technical Questions: The complaint's infringement theory relies on the factual assertion that Alembic's product contains the specific chemical compound, riociguat (Compl. ¶33). A central evidentiary question will be whether the active pharmaceutical ingredient in Alembic's ANDA Products is, in fact, the precise chemical structure recited in claim 4.
  • Scope Questions: Since the infringement allegation is based on a direct structural identity between the accused compound and a specific species claim, the dispute may turn less on claim scope and more on patent validity. The complaint notes that "Alembic did not assert non-infringement of any claim of the ’037 patent" in its notice letter (Compl. ¶35), which suggests the primary legal battle may concern whether the patent is valid over the prior art rather than whether the accused product infringes.

V. Key Claim Terms for Construction

  • The Term: "or a salt or hydrate thereof"
  • Context and Importance: This term appears in both asserted claims 1 and 4. While the core of the dispute appears to be over the riociguat molecule itself, the construction of this term could become critical if Alembic's proposed product is formulated as a specific salt or hydrate. Practitioners may focus on this term because a dispute could arise over whether a particular salt or crystalline form of riociguat falls within the scope of the claims as understood by a person of ordinary skill in the art at the time of the invention.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification provides a broad definition, stating that salts can be formed with "organic or inorganic bases or acids" and lists numerous examples, including "hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid," as well as "sodium, potassium, magnesium or calcium salts" (’037 Patent, col. 3:32-44). This language could support a construction that covers a wide range of conventional pharmaceutically acceptable salts and hydrates.
    • Evidence for a Narrower Interpretation: The specification states that "Physiologically acceptable salts are preferred" (’037 Patent, col. 3:31-32). A party could argue this preference implies a limitation, potentially excluding non-physiologically-acceptable intermediates or forms. Furthermore, an argument could be made that novel or unconventional salt or hydrate forms, not contemplated by the specification, fall outside the claim scope.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Alembic will actively induce infringement upon FDA approval by providing proposed labeling that directs the use of its products in an infringing manner (Compl. ¶41, ¶43). It also alleges contributory infringement, stating that Alembic's products "are especially made or adapted for use in infringing the ’037 patent" and are "not suitable for substantial noninfringing use" (Compl. ¶42).
  • Willful Infringement: The complaint alleges that "Alembic has knowledge of the claims of the ’037 patent" and "specifically intends infringement of the ’037 patent" (Compl. ¶40). While the term "willful" is not used, the prayer for relief requests a declaration that this is an "exceptional case" and an award of attorneys' fees pursuant to 35 U.S.C. § 285 (Compl. p. 13, ¶(e)).

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

  • A foundational issue for the court will be one of chemical identity. The infringement case hinges on the factual question of whether the active ingredient in Alembic's proposed generic product is the specific riociguat compound recited in claim 4 of the '037 patent, a fact the complaint alleges was confirmed in Alembic's own notice letter.
  • Given the allegation of direct structural correspondence, a central question for the litigation will likely be the validity of the patent claims. As the complaint suggests Alembic did not contest infringement in its notice letter, the dispute will likely shift to Alembic's asserted defenses that the '037 patent's claims are invalid as anticipated or obvious in view of the prior art.