DCT
3:25-cv-05696
Ascendis Pharma AS v. BioMarin Pharmaceutical Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Ascendis Pharma A/S (Denmark)
- Defendant: BioMarin Pharmaceutical Inc. (Delaware)
- Plaintiff’s Counsel: Latham & Watkins LLP
- Case Identification: 3:25-cv-05696, N.D. Cal., 07/07/2025
- Venue Allegations: Venue is asserted as proper in the Northern District of California because Defendant BioMarin is subject to personal jurisdiction, resides, does business, and maintains its principal place of business and corporate headquarters in the District.
- Core Dispute: Plaintiff seeks a declaratory judgment that its TransCon CNP investigational drug product does not infringe Defendant's patent related to modified C-type natriuretic peptide (CNP) variants.
- Technical Context: The technology involves chemically modified peptides designed to treat skeletal growth disorders, such as achondroplasia, by extending the therapeutic effect of the naturally occurring CNP hormone.
- Key Procedural History: This declaratory judgment action was filed by Ascendis in response to an International Trade Commission (ITC) complaint (Inv. No. 337-TA-1447) filed by BioMarin on April 1, 2025. The ITC action alleges that Ascendis's importation of its investigational drug for clinical trials constitutes infringement of the patent-in-suit.
Case Timeline
| Date | Event |
|---|---|
| 2009-05-20 | RE'267 Patent Priority Date |
| 2020-10-20 | RE'267 Patent Issue Date |
| 2025-03-31 | Ascendis submits New Drug Application (NDA) for TransCon CNP |
| 2025-04-01 | BioMarin files ITC complaint against Ascendis |
| 2025-06-02 | FDA accepts Ascendis's NDA for priority review |
| 2025-07-07 | Complaint for Declaratory Judgment filed |
| 2025-11-30 | PDUFA goal date for FDA review of TransCon CNP |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Reissue Patent No. RE48,267 - "VARIANTS OF C-TYPE NATRIURETIC PEPTIDE"
The Invention Explained
- Problem Addressed: The patent's background section explains that while the naturally occurring C-type natriuretic peptide (CNP) shows promise for treating skeletal disorders like achondroplasia, its therapeutic use is severely limited by its extremely short half-life in the body (approximately 2-3 minutes) (RE'267 Patent, col. 3:24-34).
- The Patented Solution: The invention claims to solve this problem by creating modified "CNP variants." These variants are coupled to other molecules, such as a synthetic polymer like polyethylene glycol (PEG), to increase their size and stability (RE'267 Patent, Abstract). This modification is designed to protect the CNP variant from rapid degradation, thereby extending its therapeutic activity and allowing for less frequent dosing (RE'267 Patent, col. 4:28-35).
- Technical Importance: Developing long-acting versions of peptide-based drugs was a critical step in making them clinically and commercially viable, as it can transform a therapy requiring constant infusion into one that can be administered with periodic injections (RE'267 Patent, col. 3:24-34; Compl. ¶ 18).
Key Claims at a Glance
- The complaint identifies independent claims 15 and 18 as having been asserted by BioMarin in the related ITC action (Compl. ¶ 25).
- Independent Claim 15:
- A macromolecule capable of releasing a CNP variant,
- comprising a synthetic polymeric group coupled to the CNP variant through a hydrolysable linkage,
- wherein hydrolysis of the hydrolysable linkage releases the CNP variant.
- Independent Claim 18:
- A sustained release CNP variant formulation
- comprising a synthetic polymeric group coupled to the CNP variant through a hydrolysable linkage.
- The complaint notes that BioMarin also asserted dependent claims 16–17, 19–20, and 31–48 in the ITC proceeding (Compl. ¶ 25).
III. The Accused Instrumentality
Product Identification
The accused product is Ascendis’s "TransCon CNP (navepegritide) investigational prodrug product" (Compl. ¶ 16).
Functionality and Market Context
- TransCon CNP is described as a once-weekly, investigational prodrug designed for the treatment of achondroplasia (Compl. ¶ 18). The complaint alleges the product is specifically engineered to be an inactive conjugate in its administered form (Compl. ¶ 27). Upon administration, it is designed to allow for "continuous exposure of active CNP" over time (Compl. ¶ 18).
- The product is currently investigational and not commercially available, having been imported into the U.S. solely for clinical trial purposes to support a New Drug Application (NDA) submitted to the FDA (Compl. ¶¶ 16, 19, 23). The complaint emphasizes that all imported quantities are labeled for investigational use only and are not stockpiled (Compl. ¶¶ 22, 24). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint seeks a declaratory judgment of non-infringement. The table below summarizes Ascendis's arguments for why its product does not meet the limitations of the asserted claims.
RE'267 Patent Infringement Allegations
| Claim Element (from Independent Claim 15) | Alleged Non-Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A macromolecule capable of releasing a CNP variant... | The TransCon CNP product is described as a prodrug that is inactive in its PEGylated form. | ¶27 | col. 269:64-65 |
| ...comprising a synthetic polymeric group coupled to the CNP variant through a hydrolysable linkage... | The complaint states that the TransCon CNP product does not release the CNP variant through hydrolysis of its linkage. | ¶27 | col. 270:1-2 |
| ...wherein hydrolysis of the hydrolysable linkage releases the CNP variant. | The complaint alleges that the accused product "does not release CNP through hydrolysis." | ¶27 | col. 270:2-3 |
- Identified Points of Contention:
- Scope Questions: A central dispute concerns the meaning of "hydrolysis of the hydrolysable linkage releases the CNP variant." The complaint suggests that the release mechanism of the TransCon CNP prodrug is chemically distinct from the "hydrolysis" described and enabled in the patent (Compl. ¶ 27). The case may turn on whether the court construes "hydrolysis" broadly to cover any water-involved cleavage or narrowly to specific mechanisms disclosed in the patent.
- Technical Questions: The complaint draws a distinction between the patent's alleged disclosure of active PEGylated conjugates and its own inactive prodrug (Compl. ¶ 27). This raises the question of whether the claims, particularly the "sustained release... formulation" language of claim 18, can be interpreted to cover a prodrug that is not itself active but is later converted into an active form in vivo.
V. Key Claim Terms for Construction
The Term: "hydrolysis of the hydrolysable linkage"
- Context and Importance: This term is the crux of Ascendis's non-infringement argument. Ascendis explicitly alleges its product "does not release CNP through hydrolysis" (Compl. ¶ 27). The viability of the infringement case will depend heavily on whether the release mechanism of the TransCon CNP product falls within the scope of this term.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A defendant might argue that "hydrolysis" should be given its ordinary chemical meaning, which could potentially encompass a wide range of cleavage reactions involving water. The patent’s summary of the invention broadly discusses providing variants with increased half-life, which may support an intent to claim various solutions to that problem (RE’267 Patent, col. 4:28-35).
- Evidence for a Narrower Interpretation: Ascendis's position suggests that the patent's specification may define "hydrolysable linkage" by referencing specific chemical structures or embodiments whose cleavage mechanism is distinct from that of its TransCon technology (Compl. ¶ 27). Practitioners may argue that if the specification only provides examples of certain types of hydrolytic bonds, the claims should be limited to those examples.
The Term: "sustained release... formulation" (in Claim 18)
- Context and Importance: Ascendis argues its product is not "formulated" for sustained release in the manner described by the patent, which it contends involves active PEGylated molecules (Compl. ¶ 27). The distinction between a "sustained release formulation" and a "prodrug" will likely be a key issue for claim construction.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party could argue "sustained release formulation" is a functional term meaning any composition that provides the active ingredient over an extended time. The patent's disclosure of using "polymeric systems" for "slow controlled release and sustained release" could be argued to cover any method achieving that result (RE’267 Patent, col. 88:63-89:7).
- Evidence for a Narrower Interpretation: The complaint suggests that the patent's description of "sustained release" is tied to specific embodiments where the conjugate itself is active (Compl. ¶ 27). Ascendis may argue that the term "formulation" implies a mixture of components designed for a specific release profile, rather than a single prodrug molecule that undergoes a chemical transformation in vivo.
VI. Other Allegations
The complaint does not provide sufficient detail for analysis of indirect or willful infringement, as it is a declaratory judgment action focused on denying the infringement allegations made by the defendant in a separate ITC proceeding.
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of mechanistic scope: Can the claim term "hydrolysis of the hydrolysable linkage," as defined by the patent, be construed to read on the specific in vivo activation and release mechanism of Ascendis's TransCon CNP prodrug, which Ascendis alleges is not hydrolytic?
- A second key question will be one of technical definition: Does the patent's disclosure and claims, particularly the "sustained release... formulation" of claim 18, encompass an inactive prodrug that is later activated in the body, or are they limited to formulations where the modified CNP molecule is itself therapeutically active, as Ascendis contends?