DCT

1:25-cv-00479

Adverio Pharma GmbH v. Changzhou Pharmaceutical Factory

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I. Executive Summary and Procedural Information

Case Timeline

Date Event
2010-05-26 Earliest Priority Date for all Asserted Patents
2013-04-16 U.S. Patent No. 8,420,656 Issued
2014-12-30 U.S. Patent No. 8,921,377 Issued
2017-03-28 U.S. Patent No. 9,604,948 Issued
2018-06-12 U.S. Patent No. 9,993,476 Issued
2020-08-11 U.S. Patent No. 10,736,896 Issued
2022-09-13 U.S. Patent No. 11,439,642 Issued
2025-03-05 Torrent Notice Letter Date
2025-03-06 Teva Notice Letter Date
2025-03-17 Changzhou Notice Letter Date
2025-03-19 MSN Notice Letter Date
2025-03-21 Annora Notice Letter Date
2025-04-18 Complaint Filing Date

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

U.S. Patent No. 8,420,656 - “Substituted 5-fluoro-1H-pyrazolopyridines and their use”

  • Patent Identification: U.S. Patent No. 8420656, titled “Substituted 5-fluoro-1H-pyrazolopyridines and their use,” issued on April 16, 2013 (Compl. ¶74).

The Invention Explained

  • Problem Addressed: The patent describes that conventional treatments for cardiovascular disorders, such as organic nitrates, stimulate the production of cyclic guanosine monophosphate (cGMP) by releasing nitrogen monoxide (NO). However, this approach can lead to the development of tolerance and other side effects, creating a need for novel substances that can stimulate the enzyme soluble guanylate cyclase (sGC) directly and independently of NO (’896 Patent, col. 3:67-4:24).
  • The Patented Solution: The invention provides a new class of compounds, substituted 5-fluoro-1H-pyrazolopyridines, that act as direct stimulators of sGC. By directly activating this enzyme, the compounds increase intracellular levels of cGMP, which mediates key physiological processes such as vasorelaxation and inhibition of platelet aggregation, offering a therapeutic benefit for cardiovascular disorders (’896 Patent, col. 4:18-58; Abstract). The patent specifically claims the compound vericiguat.
  • Technical Importance: This technology provided a therapeutic pathway for treating cardiovascular diseases that is independent of NO, suggesting a potential to circumvent the tolerance issues associated with traditional nitrate-based therapies (’896 Patent, col. 4:59-63).

Key Claims at a Glance

  • The complaint asserts at least independent claim 7 (Compl. ¶97, ¶117, ¶138, ¶159, ¶179).
  • Claim 7 is a composition of matter claim directed to a single chemical entity:
    • The compound methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate.

U.S. Patent No. 8,921,377 - “Substituted 5-fluoro-1H-pyrazolopyridines and their use”

  • Patent Identification: U.S. Patent No. 8921377, titled “Substituted 5-fluoro-1H-pyrazolopyridines and their use,” issued on December 30, 2014 (Compl. ¶77).

The Invention Explained

  • Problem Addressed: As with the related ’656 Patent, the technology addresses the limitations of existing NO-dependent cardiovascular therapies, such as the development of tolerance (’896 Patent, col. 3:67-4:2).
  • The Patented Solution: The patent claims methods of using the previously identified 5-fluoro-1H-pyrazolopyridine compounds, specifically vericiguat, to treat cardiovascular disorders. By administering a therapeutically effective amount of the compound, the claimed method stimulates sGC to achieve therapeutic effects such as vasorelaxation for the treatment of conditions like heart failure (’896 Patent, col. 4:18-58, col. 18:25-30).
  • Technical Importance: The claimed methods of use establish a specific therapeutic application for the novel sGC-stimulating compounds, translating the chemical invention into a direct clinical intervention for heart failure (’896 Patent, col. 4:59-63).

Key Claims at a Glance

  • The complaint asserts at least independent claim 8 (Compl. ¶98, ¶118, ¶139, ¶160, ¶180).
  • Claim 8 is a method of treatment claim with the following essential elements:
    • A method of treating heart failure in a patient in need thereof;
    • comprising administering to said patient a therapeutically effective amount of the compound methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate (i.e., vericiguat);
    • or a salt, solvate, or solvate of a salt thereof.

U.S. Patent No. 9,604,948 - “Process for preparing substituted 5-fluoro-1H-pyrazolopyridines”

  • Patent Identification: U.S. Patent No. 9604948, “Process for preparing substituted 5-fluoro-1H-pyrazolopyridines,” issued March 28, 2017 (Compl. ¶80).
  • Technology Synopsis: This patent is directed to a specific solid-state form of vericiguat. It claims the compound in a specific crystalline structure, Polymorph I, which may offer advantages in stability, manufacturing, or bioavailability over other forms (Compl. ¶81).
  • Asserted Claims: At least claim 1 is asserted (Compl. ¶99, ¶119, ¶140, ¶161, ¶181).
  • Accused Features: The complaint alleges that the vericiguat in Defendants’ proposed generic products is in the crystalline form of Polymorph I (Compl. ¶96, ¶116, ¶137, ¶158, ¶178).

U.S. Patent No. 9,993,476 - “Substituted 5-flouro-1H-pyrazolopyridines and their use”

  • Patent Identification: U.S. Patent No. 9993476, “Substituted 5-flouro-1H-pyrazolopyridines and their use,” issued June 12, 2018 (Compl. ¶83).
  • Technology Synopsis: This patent claims methods for treating or preventing a range of cardiovascular disorders. The claimed methods involve administering a therapeutically effective amount of vericiguat to a patient (Compl. ¶84).
  • Asserted Claims: At least claim 4 is asserted (Compl. ¶100, ¶120, ¶141, ¶162, ¶182).
  • Accused Features: The proposed labeling for Defendants’ ANDA products allegedly directs the use of vericiguat for indications, such as reducing the risk of heart failure hospitalization, that are covered by the patent's method claims (Compl. ¶95).

U.S. Patent No. 10,736,896 - “Substituted 5-flouro-1H-pyrazolopyridines and their use”

  • Patent Identification: U.S. Patent No. 10736896, “Substituted 5-flouro-1H-pyrazolopyridines and their use,” issued August 11, 2020 (Compl. ¶86).
  • Technology Synopsis: This patent is directed to vericiguat itself and pharmaceutical formulations containing it. The claims cover the specific active pharmaceutical ingredient and compositions suitable for administration to patients (Compl. ¶87).
  • Asserted Claims: At least claim 4 is asserted (Compl. ¶101, ¶121, ¶142, ¶163, ¶183).
  • Accused Features: Defendants’ ANDA products are described as oral tablets containing vericiguat, which are alleged to be pharmaceutical formulations covered by the patent (Compl. ¶93, ¶94).

U.S. Patent No. 11,439,642 - “Substituted 5-flouro-1H-pyrazolopyridines and their use”

  • Patent Identification: U.S. Patent No. 11439642, “Substituted 5-flouro-1H-pyrazolopyridines and their use,” issued September 13, 2022 (Compl. ¶89).
  • Technology Synopsis: Similar to the ’476 patent, this patent claims methods of treating or preventing various cardiovascular and related disorders. The invention is the use of a therapeutically effective amount of vericiguat for these specified medical conditions (Compl. ¶90).
  • Asserted Claims: At least claim 1 is asserted (Compl. ¶102, ¶122, ¶143, ¶164, ¶184).
  • Accused Features: The proposed labels for the generic products allegedly instruct use for treating heart failure, an indication Plaintiffs contend is covered by the claims (Compl. ¶95).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are the generic vericiguat tablets for which the various Defendants have filed ANDAs seeking FDA approval (Compl. ¶1). Specific ANDA numbers are identified for Changzhou (No. 220264), Teva (No. 220286), Torrent (No. 220221), MSN (No. 220354), and Annora (No. 220244) (Compl. ¶8, ¶14, ¶22, ¶30, ¶38).

Functionality and Market Context

  • The products are oral tablets containing the active pharmaceutical ingredient vericiguat (Compl. ¶93, ¶94). The complaint provides a chemical structure diagram of vericiguat to identify the compound in the accused products (Compl. ¶93). The complaint alleges the vericiguat is in a specific crystalline form, Polymorph I (Compl. ¶96). The proposed labeling for these generic products directs their use to "reduce the risk of cardiovascular death and heart failure (HF) hospitalization" in certain adults (Compl. ¶95). The products are positioned as generic equivalents to Plaintiffs' VERQUVO® brand drug, intended for commercial manufacture, use, and sale in the United States upon FDA approval (Compl. ¶1, ¶9).

IV. Analysis of Infringement Allegations

U.S. Patent No. 8,420,656 Infringement Allegations

Claim Element (from Independent Claim 7) Alleged Infringing Functionality Complaint Citation Patent Citation
The compound methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate. The Defendants’ ANDA products are alleged to contain the specific active ingredient vericiguat, which is the compound identified in the claim (Compl. ¶93). ¶93 ’896 Patent, col. 33:5-34:49

U.S. Patent No. 8,921,377 Infringement Allegations

Claim Element (from Independent Claim 8) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating heart failure in a patient in need thereof The proposed labeling for the Defendants' ANDA products directs their use to "reduce the risk of cardiovascular death and heart failure (HF) hospitalization" in certain adults (Compl. ¶95). ¶95 ’896 Patent, col. 18:25-30
comprising administering to said patient a therapeutically effective amount of the compound [vericiguat] The Defendants’ ANDA products are oral tablets containing the active ingredient vericiguat (Compl. ¶93, ¶94). ¶93; ¶94 ’896 Patent, col. 33:5-34:49
or a salt, solvate, or solvate of a salt thereof. The complaint alleges the products contain the base compound vericiguat (Compl. ¶93). ¶93 ’896 Patent, col. 5:5-10

Identified Points of Contention

  • Scope Questions: For the method claims (e.g., in the ’377 Patent), a potential question for the court is whether the indication specified on the defendants’ proposed labels—"to reduce the risk of cardiovascular death and heart failure (HF) hospitalization"—falls within the scope of the patented method of "treating heart failure."
  • Technical Questions: A central evidentiary question will concern the claims to a specific crystalline form in the ’948 patent. The analysis will likely focus on scientific evidence, such as X-ray powder diffraction data, to determine if the vericiguat in the defendants’ products is, in fact, "Polymorph I" as defined and characterized within the patent specification. The complaint alleges this is the case but notes that some defendants did not set forth a theory of noninfringement for this patent in their notice letters (Compl. ¶96, ¶116, ¶178).

V. Key Claim Terms for Construction

The Term: "crystalline form of Polymorph I"

(from U.S. Patent No. 9,604,948, claim 1)

  • Context and Importance: Infringement of the ’948 patent hinges entirely on whether the defendants' generic active ingredient exists in this specific solid-state form. The definition of this polymorph, which is distinguished from other potential crystalline or amorphous forms, will be critical. Practitioners may focus on this term because solid-state chemistry disputes in ANDA litigation often turn on precise interpretations of characterization data.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party could argue that the term should not be limited to a perfect match of every data point, but should cover any crystalline form that possesses the essential structural characteristics of Polymorph I as disclosed in the specification.
    • Evidence for a Narrower Interpretation: The patent specification provides detailed characterization data to define Polymorph I, including specific peak maxima in an X-ray powder diffractogram (e.g., peaks at 2 theta angles of 5.9, 6.9, and 22.7) and specific bands in an IR spectrum (’948 Patent, FIG. 1, FIG. 5, Claim 2). A party would likely argue that the claim term is precisely and exclusively defined by these objective data points.

The Term: "treating heart failure"

(from U.S. Patent No. 8,921,377, claim 8)

  • Context and Importance: The infringement analysis for the method-of-use patents depends on whether the indication on the defendants’ proposed labels constitutes "treating heart failure." Defendants may argue that their label's indication for "reducing the risk" of certain outcomes is distinct from "treating" the underlying condition itself.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification describes the invention as useful for the "treatment and/or prophylaxis" of a wide range of cardiovascular disorders, including "acute and chronic heart failure" (’896 Patent, col. 18:25-30). This may support a construction where "treating" includes preventative or risk-reduction measures.
    • Evidence for a Narrower Interpretation: A party could argue that "treating" should be construed to mean managing or reversing the symptoms of existing, diagnosed heart failure, potentially distinct from prophylactic use or risk reduction in a population of patients. The specification's separate mention of "treatment and/or prophylaxis" may suggest the patentee viewed these as distinct concepts.

VI. Other Allegations

Indirect Infringement

  • The complaint alleges active inducement of infringement for the asserted method-of-use patents. This allegation is based on the contents of the defendants’ proposed product labeling, which will allegedly instruct physicians and patients to administer the generic drugs for the patented methods of treating heart failure (Compl. ¶107, ¶127, ¶148, ¶169, ¶189). The complaint also pleads contributory infringement, alleging the ANDA products are especially made or adapted for this infringing use and have no substantial non-infringing use (Compl. ¶108, ¶128, ¶149, ¶170, ¶190).

Willful Infringement

  • The complaint does not use the term "willful," but it alleges facts that could support such a claim. It states that defendants have "knowledge of the claims of the Asserted Patents" and, notwithstanding this knowledge, have continued to seek approval to market their products, thereby "specifically intend[ing] infringement" (Compl. ¶106, ¶126, ¶147, ¶168, ¶188). These allegations of pre-suit knowledge and intent to infringe upon approval form a basis for a potential willfulness argument.

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

  • A core issue will be one of technical identity: what is the precise crystalline form of the vericiguat active ingredient in each Defendant’s proposed generic product, and does the evidence (likely from competing expert analyses) demonstrate that it meets the specific structural definition of "Polymorph I" as claimed in the ’948 patent?
  • A key infringement question for the method patents will be one of definitional scope: can Plaintiffs prove that the indication for "reduc[ing] the risk of cardiovascular death and heart failure (HF) hospitalization" on the Defendants’ proposed labels instructs users to perform the patented method of "treating heart failure" as that term is construed by the court?
  • A central question underlying the entire dispute will be the validity of the asserted claims: Defendants have filed Paragraph IV certifications, asserting that the patents are invalid and/or not infringed. The litigation will therefore likely involve significant disputes over whether the claimed inventions—the vericiguat compound, its specific polymorphic form, and its methods of use—were obvious or anticipated by the prior art at the time of the invention.