DCT
2:22-cv-06104
Adverio Pharma GmbH v. Alembic Pharmaceutical Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Adverio Pharma GmbH (Germany), Bayer AG (Germany), and Bayer HealthCare Pharmaceuticals Inc. (Delaware)
- Defendant: Alembic Pharmaceuticals Limited (India), Alembic Global Holding SA (Switzerland), and Alembic Pharmaceuticals, Inc. (Delaware)
- Plaintiff’s Counsel: Gibbons P.C.
- Case Identification: 2:22-cv-06104, D.N.J., 10/17/2022
- Venue Allegations: Venue is alleged to be proper based on Defendant Alembic Pharmaceuticals, Inc.'s maintenance of regular and established places of business in New Jersey and its registration with state agencies.
- Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) for generic riociguat tablets (ADEMPAS®) constitutes an act of infringement of two patents covering specific crystalline forms of the active pharmaceutical ingredient.
- Technical Context: The technology concerns polymorphs and solvates—distinct solid-state forms of a chemical compound—which can have different physical properties impacting a drug's stability, manufacturability, and bioavailability.
- Key Procedural History: The lawsuit is a Hatch-Waxman action triggered by Defendants’ submission of ANDA No. 216967 to the FDA, which included Paragraph IV certifications asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed by the proposed generic product.
Case Timeline
| Date | Event |
|---|---|
| 2013-02-21 | Earliest Priority Date for ’188 and ’593 Patents |
| 2020-05-26 | U.S. Patent No. 10,662,188 Issues |
| 2021-12-21 | U.S. Patent No. 11,203,593 Issues |
| 2022-09-02 | Alembic sends Notice Letter of ANDA filing to Plaintiffs |
| 2022-10-17 | 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 background discusses the compound riociguat (formula I), a stimulator of soluble guanylate cyclase, and notes that prior art processes for its preparation are associated with certain disadvantages (U.S. Patent No. 10662188, col. 2:39-44). The implicit problem is the need for a pure, stable, and consistently characterizable form of the active pharmaceutical ingredient suitable for commercial drug manufacturing.
- The Patented Solution: The invention is the discovery and characterization of several distinct crystalline forms (polymorphs and solvates) of the riociguat compound (’188 Patent, col. 4:58-66). By isolating specific forms, such as the claimed "sesqui-DMSO solvate" and "¼-ethyl acetate solvate," the inventors created versions of the active ingredient with defined, reproducible physical properties, particularly their X-Ray Powder Diffractogram (XRPD) patterns, which are essential for consistent pharmaceutical production.
- Technical Importance: Identifying and claiming specific polymorphs of an active pharmaceutical ingredient is critical for ensuring product consistency, stability, and bioavailability, and can provide a basis for extending the market exclusivity of a drug.
Key Claims at a Glance
- The complaint asserts independent claims 1, 8, and 15 (Compl. ¶40).
- Claim 1 is directed to a pharmaceutical composition comprising:
- a sesqui-DMSO solvate of a compound of formula (I);
- which is characterized by an X-Ray powder diffractogram comprising peak maxima at 2-Theta angles of 8.3, 13.7, and 15.7; and
- wherein the composition contains more than 90 percent by weight of the sesqui-DMSO solvate.
- Claim 8 is directed to a pharmaceutical composition comprising a ¼-ethyl acetate solvate of a compound of formula (I), characterized by a specific XRPD pattern.
- Claim 15 is directed to a compound of formula (I) in the form of Modification I, as a ¼-ethyl acetate solvate, or a mixture thereof.
U.S. Patent No. 11,203,593 - Forms of Methyl {4,6-diamino-2-[1(2-fluorobenzyl)-1H-pyrazolo[3-4-b]pyridino-3-yl]pyrimidino-5-yl} Methyl Carbamate, issued December 21, 2021
The Invention Explained
- Problem Addressed: As with the parent ’188 Patent, the invention addresses the need for well-characterized, stable solid forms of the riociguat compound for pharmaceutical use (U.S. Patent No. 11203593, col. 2:39-44).
- The Patented Solution: This patent claims a specific crystalline polymorph of riociguat known as "Modification I" (’593 Patent, col. 4:58-62). The specification notes that this particular form is the thermodynamically stable form of the compound between 0° C. and 80° C., which may suggest advantages in stability during storage and formulation (’593 Patent, col. 5:13-15).
- Technical Importance: Claiming a thermodynamically stable polymorph can be particularly valuable, as it is less likely to convert to other forms over time, ensuring the long-term consistency and performance of the final drug product.
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶41).
- Claim 1 is directed to:
- a compound of the formula (I);
- in crystalline form;
- having an X-Ray powder diffractogram comprising at least three peak maxima selected from a list including 6.7, 9.1, 14.3, 14.4, 17.8, 19.8, 20.2, 24.8, 25.6, and 27.3.
III. The Accused Instrumentality
Product Identification
- The accused instrumentalities are Defendants' proposed generic riociguat tablets in 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg dosage strengths ("Alembic's ANDA Products") (Compl. ¶12).
Functionality and Market Context
- The products are generic versions of Plaintiffs' ADEMPAS® tablets, for which Defendants have filed ANDA No. 216967 seeking FDA approval for commercial sale prior to the expiration of the patents-in-suit (Compl. ¶¶1, 38). In their notice letter to Plaintiffs, Defendants stated that the accused products contain a "crystalline form of riociguat," which is the active pharmaceutical ingredient (Compl. ¶39).
IV. Analysis of Infringement Allegations
The complaint provides a chemical diagram of the compound of formula (I), riociguat, which is the active ingredient in both the patented and accused products (Compl. ¶27, p. 7).
’188 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical composition comprising a sesqui-DMSO solvate of a compound of formula (I) | On information and belief, Alembic’s ANDA Products are pharmaceutical compositions that contain a form of riociguat which Plaintiffs allege is the claimed sesqui-DMSO solvate. | ¶40 | col. 8:34-40 |
| wherein the sesqui-DMSO solvate of the compound of formula (I) is characterized by an X-Ray powder diffractogram comprising peak maxima of the 2 Theta angel [sic] of 8.3, 13.7, 15.7, | On information and belief, the crystalline form of riociguat in Alembic’s ANDA Products exhibits an XRPD pattern with the requisite peak maxima. | ¶40 | col. 8:34-40 |
| and further wherein the pharmaceutical composition contains more than 90 percent by weight of the sesqui-DMSO solvate... | On information and belief, Alembic’s ANDA Products contain the alleged infringing solvate at a purity level of more than 90 percent by weight. | ¶40 | col. 28:5-10 |
’593 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A compound of the formula (I) ... in crystalline form | Alembic’s notice letter stated its ANDA Products contain a "crystalline form of riociguat." | ¶39 | col. 8:18-24 |
| having an X-Ray powder diffractogram comprising at least three peak maxima of the 2 Theta angle selected from 6.7, 9.1, 14.3, 14.4, 17.8, 19.8, 20.2, 24.8, 25.6 and 27.3. | On information and belief, the crystalline form of riociguat in Alembic’s ANDA Products exhibits an XRPD pattern with at least three peaks matching the recited list, corresponding to "Modification I." | ¶41 | col. 8:18-24 |
Identified Points of Contention
- Technical Question: The primary dispute will likely be factual and technical: does the specific crystalline form of riociguat used in Alembic's ANDA product actually exhibit the XRPD peak maxima required by the asserted claims? The outcome will depend on expert analysis of the accused product samples.
- Scope Question: For the composition claims of the ’188 Patent, a potential point of contention could be the purity limitation (e.g., "more than 90 percent by weight"). The litigation may explore not only the identity of the crystalline form but also its concentration in the final drug product.
V. Key Claim Terms for Construction
- The Term: "characterized by an X-Ray powder diffractogram comprising peak maxima of the 2 Theta angle of..." followed by a list of numbers (e.g., '188 Patent, Claim 1).
- Context and Importance: This phrase is the central limitation defining the patented crystalline forms. The entire infringement analysis hinges on whether the accused product's XRPD data falls within the scope of this language. Practitioners may focus on this term because the precision of the numerical values and the meaning of "comprising peak maxima" will determine whether minor variations in an accused product's measured XRPD pattern are sufficient to avoid infringement.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The use of the open-ended word "comprising" suggests that the claimed form must have the recited peaks but may also have additional, unlisted peaks. A party could argue this supports finding infringement even if the accused product's full diffractogram is not identical to the examples in the patent.
- Evidence for a Narrower Interpretation: The patents explicitly state that the forms can be "characterized unambiguously" by these peaks and provide specific figures (e.g., ’188 Patent, FIG. 10) and detailed tables (e.g., ’188 Patent, Table 3) showing the XRPD patterns. A party could argue this supports a construction requiring a close correspondence between the accused product's peak positions and the recited values, allowing for only minimal, standard experimental error.
VI. Other Allegations
- Indirect Infringement: The complaint alleges active inducement, stating that Alembic plans and intends for its product to be used in an infringing manner upon approval, and that this intent is demonstrated by the filing of the ANDA itself and the product's proposed labeling (Compl. ¶¶51, 53). The complaint also alleges contributory infringement, asserting that Alembic's product is especially made for an infringing use and is not suitable for a substantial non-infringing use (Compl. ¶52).
- Willful Infringement: The complaint does not use the word "willful" but alleges that Alembic has "knowledge of the claims of the '188 and '593 patents" and "specifically intends infringement" (Compl. ¶50). It further requests a declaration that the case is "exceptional" and an award of attorneys' fees pursuant to 35 U.S.C. § 285, which is the statutory basis often associated with findings of willful infringement or litigation misconduct (Compl. ¶(i), p. 17).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of evidentiary proof: Will forensic analysis of Alembic's proposed generic product reveal a crystalline form of riociguat that exhibits the specific X-ray powder diffraction peak patterns recited in the asserted claims of the '188 and '593 patents?
- A key legal question will be one of claim scope: How much deviation from the precise numerical values of the XRPD peaks listed in the claims is permissible? The court's construction of terms like "comprising peak maxima of..." will be critical in determining whether minor variations due to measurement techniques or manufacturing differences fall inside or outside the scope of the patents.