DCT

3:25-cv-03302

Ascendis Pharma AS v. BioMarin Pharmaceutical Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 5:25-cv-03302, N.D. Cal., 04/11/2025
  • Venue Allegations: Venue is alleged to be proper in the Northern District of California because Defendant BioMarin is subject to personal jurisdiction, resides in, does business in, and maintains its principal place of business and corporate headquarters in the district.
  • Core Dispute: Plaintiff seeks a declaratory judgment of non-infringement of Defendant's patent related to C-type natriuretic peptide variants, arguing its activities concerning an investigational drug product are protected by the statutory "safe harbor" for acts related to seeking FDA approval.
  • Technical Context: The technology involves chemically modified protein variants designed to treat skeletal disorders like achondroplasia, a common form of dwarfism, by overcoming the short biological half-life of the naturally occurring protein.
  • Key Procedural History: This declaratory judgment action was filed in response to a complaint filed by BioMarin against Ascendis at the U.S. International Trade Commission (ITC) on April 1, 2025. In the ITC action, BioMarin alleges that Ascendis's importation of its drug product infringes the patent-in-suit. The existence of the ITC action forms the basis for the "actual controversy" required for this district court case.

Case Timeline

Date Event
2009-05-20 RE’267 Patent Earliest Priority Date
2020-10-20 U.S. Reissue Patent No. RE48,267 Issues
2025-03-31 Ascendis submits New Drug Application (NDA) to the FDA
2025-04-01 BioMarin files ITC complaint against Ascendis
2025-04-11 Ascendis files this Complaint for Declaratory Judgment

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

U.S. Reissue Patent No. RE48,267 - VARIANTS OF C-TYPE NATRIURETIC PEPTIDE

  • Patent Identification: U.S. Reissue Patent No. RE48,267, "VARIANTS OF C-TYPE NATRIURETIC PEPTIDE," issued October 20, 2020.

The Invention Explained

  • Problem Addressed: The patent's background section explains that while C-type natriuretic peptide (CNP) has therapeutic potential for treating skeletal disorders like achondroplasia, its clinical use is hindered by a very short plasma half-life of approximately 2.6 minutes, which makes it difficult to maintain effective concentrations in the body (RE’267 Patent, col. 3:24-30).
  • The Patented Solution: The invention describes modified variants of CNP designed to have an increased half-life and greater resistance to degradation by enzymes in the body (RE’267 Patent, Abstract). These variants are created through methods including amino acid substitutions or by attaching other molecules, such as polyethylene glycol (PEG), to the peptide, thereby improving its stability and therapeutic potential for treating chronic conditions (RE’267 Patent, col. 4:3-23; col. 9:1-5).
  • Technical Importance: By engineering a longer-acting version of CNP, the invention sought to create a viable therapeutic agent for chronic skeletal dysplasias that require sustained drug activity, something unachievable with the natural, rapidly degrading form of the peptide (RE’267 Patent, col. 3:31-38).

Key Claims at a Glance

  • The complaint states that BioMarin's ITC action alleges infringement of "one or more claims" of the RE’267 patent (Compl. ¶31). The complaint does not specify which claims. Independent claim 1 is a representative composition claim.
  • Independent Claim 1:
    • A variant of C-type natriuretic peptide (CNP)
    • selected from the group consisting of four specific amino acid sequences identified as SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 185, and SEQ ID NO: 186.

III. The Accused Instrumentality

Product Identification

The accused product is Ascendis's "TransCon CNP (navepegritide)" (Compl. ¶9).

Functionality and Market Context

  • TransCon CNP is described as an investigational "prodrug" of CNP designed for once-weekly administration to treat achondroplasia by providing "continuous exposure of active CNP" to relevant tissues (Compl. ¶¶7-8).
  • The product is not yet FDA-approved, but Ascendis submitted a New Drug Application on March 31, 2025 (Compl. ¶16). The complaint states that TransCon CNP has been imported into the United States "solely for use in clinical trials and testing to obtain regulatory approval" (Compl. ¶¶20-21). It is alleged that 22,244 vials have been imported for use in six clinical trials (Compl. ¶22).
  • The complaint notes that BioMarin markets Voxzogo®, currently the "only FDA-approved treatment for achondroplasia for children," positioning TransCon CNP as a potential future competitor (Compl. ¶28, citing Ex. 2, ¶66).

IV. Analysis of Infringement Allegations

The complaint, being for a declaratory judgment of non-infringement premised on the § 271(e)(1) safe harbor, does not contain a detailed, element-by-element infringement analysis or a claim chart. The central legal argument is that Ascendis's activities are statutorily exempt from infringement, regardless of whether the accused product otherwise meets the patent's claim limitations (Compl. ¶¶ 33-34).

No probative visual evidence provided in complaint.

Identified Points of Contention

  • Legal Question (Safe Harbor Scope): The primary dispute presented is whether Ascendis's importation and use of TransCon CNP in clinical trials qualifies as an activity "solely for uses reasonably related to the development and submission of information under a Federal law which regulates the...use...of drugs" (Compl. ¶¶ 33-34). This raises the question of whether the scale and nature of Ascendis's activities fall within the bounds of the § 271(e)(1) safe harbor.
  • Factual Question (Purpose of Importation): The complaint directly contests allegations from BioMarin's ITC action that Ascendis imported quantities of TransCon CNP that "exceeds any quantity that would be solely for uses reasonably related" to FDA submission (Compl. ¶26). Ascendis counters that the imported amounts correspond to clinical trial needs and do not represent stockpiling for commercial sale (Compl. ¶¶ 24, 26). Resolution of this factual dispute over the purpose and quantity of the imported product may be determinative of the safe harbor defense.

V. Key Claim Terms for Construction

While the complaint focuses on the safe harbor defense, any underlying infringement analysis would depend on the construction of key claim terms.

The Term: "variant of C-type natriuretic peptide (CNP)"

Context and Importance

This term is the preamble and subject of the independent claims. Determining whether Ascendis's "TransCon CNP," which it describes as a "prodrug" (Compl. ¶7), falls within the scope of a claimed "variant" is a threshold infringement question. Practitioners may focus on this term because the distinction between a "prodrug" (an inactive precursor) and a "variant" (an active, modified molecule) could be a basis for a non-infringement argument.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The specification describes "CNP variants" broadly, including those with "additions, deletions, or substitutions" as well as conjugations to other moieties like polymers or proteins (RE’267 Patent, col. 4:3-23; col. 21:1-10). This language could be used to argue that the term encompasses a wide array of modified CNP molecules, including prodrug formulations that release a CNP variant.
  • Evidence for a Narrower Interpretation: Independent claim 1 is highly specific, claiming a "variant...selected from the group consisting of" four exact amino acid sequences (RE’267 Patent, col. 268:44-62). An argument could be made that the claim scope is limited to these precise sequences and does not cover other modifications or prodrug forms not explicitly recited. The patent also describes methods for creating fusion proteins and cleaving them to yield the final product, which could be used to distinguish the claimed "variant" from a precursor "prodrug" form (RE’267 Patent, col. 27:29-68).

VI. Other Allegations

  • Indirect Infringement: The complaint seeks a declaration of non-infringement "directly or indirectly" (Compl. ¶32). However, it does not plead specific facts regarding allegations of inducement or contributory infringement, as its focus is on its own direct acts of importation and use for clinical trials.
  • Willful Infringement: As a declaratory judgment plaintiff, Ascendis does not allege willfulness against itself. Instead, it makes an affirmative claim for attorneys' fees under 35 U.S.C. § 285, alleging that BioMarin's ITC complaint is "objectively baseless" (Compl. ¶¶ 35-36). This claim is founded on the allegation that BioMarin filed its action with knowledge that Ascendis's conduct was protected by the § 271(e)(1) safe harbor (Compl. ¶35).

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

This case appears to present a preemptive challenge to an unfolding patent dispute initiated at the ITC, with the core issues framed as follows:

  • A primary question of statutory exemption: Do Ascendis's pre-approval activities, including the importation of its TransCon CNP product for U.S. clinical trials, fall entirely within the § 271(e)(1) "safe harbor," which would provide a complete defense to infringement?
  • A key evidentiary question of commercial intent: Does the evidence surrounding the quantity and handling of the imported TransCon CNP support Ascendis's position that its use is solely for FDA data generation, or does it suggest a commercial purpose, such as stockpiling, that would fall outside the safe harbor's protection?
  • A secondary question of infringement scope: If the safe harbor defense were to fail, the case would turn to a technical infringement analysis, centered on whether Ascendis's "prodrug" formulation constitutes a "variant of C-type natriuretic peptide" as defined by the specific sequences recited in the RE’267 patent's claims.