DCT

4:25-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 Pharmaceutical Inc. maintains its corporate headquarters and principal place of business in the district, resides there, and is subject to personal jurisdiction.
  • Core Dispute: Plaintiff Ascendis seeks a declaratory judgment that its pre-approval manufacture, use, and importation of an investigational drug product does not infringe Defendant BioMarin's patent covering variants of that drug, based on the statutory "safe harbor" of 35 U.S.C. § 271(e)(1).
  • Technical Context: The technology involves modified C-type natriuretic peptides (CNPs), which are used to treat skeletal growth disorders such as achondroplasia, the most common form of skeletal dysplasia.
  • Key Procedural History: This declaratory judgment action was filed in response to an underlying complaint filed by BioMarin against Ascendis at the U.S. International Trade Commission (ITC) on April 1, 2025. That ITC action alleges that Ascendis's importation of its investigational drug infringes the patent-in-suit. The existence of the ITC complaint is the basis for Ascendis's claim of a justiciable case or controversy, giving it a reasonable apprehension of being sued for patent infringement in district court.

Case Timeline

Date Event
2009-05-20 Earliest Priority Date for RE’267 Patent
2013-12-03 Issue Date of Original U.S. Patent No. 8,598,121
2020-10-20 Issue Date of U.S. Reissue Patent No. RE48,267
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 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 describes C-type natriuretic peptide (CNP) as a promising therapeutic for skeletal disorders like achondroplasia, but notes its clinical utility is severely limited by its very short plasma half-life of 2.6 minutes, which requires continuous infusion (RE’267 Patent, col. 3:25-36). The underlying condition, achondroplasia, is an autosomal dominant disorder caused by a mutation in the fibroblast growth factor receptor 3 (FGFR-3) gene, which results in disproportionate short stature (RE’267 Patent, col. 2:56-65).
  • The Patented Solution: The patent discloses modified variants of CNP designed to have increased resistance to degradation and a longer half-life, making them more suitable for therapeutic use (RE’267 Patent, col. 4:1-12). The invention covers compositions of these variants, including those modified with polymers like polyethylene glycol (PEG) or other moieties, and methods for using them to treat bone-related disorders (RE’267 Patent, Abstract; col. 4:13-23). The goal is to create a CNP-based drug that can be administered less frequently while maintaining therapeutic effect.
  • Technical Importance: Creating long-acting versions of naturally occurring peptides is a significant challenge in biopharmaceutical development, and a successful approach could enable effective treatments for chronic conditions that would otherwise be impractical to manage.

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" but does not identify specific claims (Compl. ¶31). Independent Claim 1, a composition of matter claim, is representative of the core invention.
  • Essential elements of Independent Claim 1 include:
    • A variant of C-type natriuretic peptide (CNP)
    • Wherein the variant is selected from a group of five specific amino acid sequences identified by SEQ ID NOs: 179, 180, 185, 181, or 186.
  • The complaint does not explicitly reserve the right to assert dependent claims but seeks a declaration of non-infringement of "any claims of the RE’267 patent" (Compl. p. 10).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Ascendis’s investigational prodrug "TransCon CNP (navepegritide)" (Compl. ¶¶ 1, 7).

Functionality and Market Context

  • TransCon CNP is described as a once-weekly administered prodrug specifically designed to treat achondroplasia (Compl. ¶7). It is engineered to allow for "continuous exposure of active CNP to receptors on tissues throughout the body," thereby addressing the short half-life problem of natural CNP (Compl. ¶¶ 7-8).
  • The complaint states the product is currently investigational, has not received FDA approval, and is not commercially available in the U.S. other than for use in clinical trials (Compl. ¶¶ 19-20, 28). Ascendis submitted a New Drug Application (NDA) for TransCon CNP to the FDA on March 31, 2025, for the treatment of achondroplasia in children (Compl. ¶16).

IV. Analysis of Infringement Allegations

The complaint, being an action for declaratory judgment of non-infringement, does not contain detailed infringement allegations or a claim chart. Instead, its central argument is that all of its activities related to TransCon CNP are protected from infringement liability by the Bolar exemption, or "safe harbor," under 35 U.S.C. § 271(e)(1) (Compl. ¶¶ 1, 33-34).

The core of the dispute, as framed by Ascendis, centers on the scope of this safe harbor. Ascendis asserts that its importation of TransCon CNP into the United States has been "solely for use in clinical trials and testing to obtain regulatory approval" (Compl. ¶20). It alleges that the data from all clinical trials will be reported to the FDA to obtain this approval (Compl. ¶21).

The complaint directly addresses what it characterizes as BioMarin’s central allegation in the parallel ITC proceeding: that Ascendis imported a quantity of the drug substance that "exceeds any quantity that would be solely for uses reasonably related to the development and submission of information to the FDA" (Compl. ¶26). Ascendis counters this by arguing that BioMarin misunderstands the importation data, claiming that the cited 24 kg quantity refers to an aqueous solution of the drug substance, not the actual amount of active TransCon CNP (Compl. ¶26).

No probative visual evidence provided in complaint.

  • Identified Points of Contention:
    • Factual Question: The primary factual dispute will be whether Ascendis's importation activities were, as it claims, "solely for uses reasonably related to" its FDA submission. This will likely involve a quantitative and qualitative analysis of the imported product to determine if the amounts and uses are consistent with clinical trial needs or suggest commercial stockpiling.
    • Legal Question: The central legal question is whether Ascendis's conduct falls within the scope of the § 271(e)(1) safe harbor. Even if the imported product embodies the patented invention, there is no infringement if the safe harbor applies.
    • Scope Question: Should the safe harbor defense fail, a secondary question would be whether Ascendis's TransCon CNP molecule is a "variant of C-type natriuretic peptide (CNP)" as defined by the claims of the RE’267 patent.

V. Key Claim Terms for Construction

While the primary dispute centers on the safe harbor, claim construction would become critical if that defense were to fail.

  • The Term: "A variant of C-type natriuretic peptide (CNP)"
  • Context and Importance: This term appears in the preamble of numerous independent claims (e.g., Claim 1) and defines the entire class of molecules covered by the patent. The outcome of the infringement analysis would depend on whether Ascendis's TransCon CNP product falls within the scope of this term. Practitioners may focus on this term because its breadth will determine whether the patent covers only the specific embodiments disclosed or a wider range of modified CNP molecules.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification provides a general chemical formula for CNP variants, suggesting the invention is not limited to a few specific examples: (x)-(y)-Cys-Phe-Gly-Leu-Lys-Leu-Asp-Arg-Ile-Gly-Ser-(y)-(z) (SEQ ID NO. 48) (RE’267 Patent, col. 15:23-27). The detailed description also discloses numerous types of modifications, including conjugation to polymers, substitutions with unnatural amino acids, and the creation of chimeras, which may support a broad definition of "variant" (RE’267 Patent, col. 5:1-12; col. 21:1-12).
    • Evidence for a Narrower Interpretation: The patent's abstract and summary explicitly focus on variants with "increased half-life" and "resistance to proteolysis" (RE’267 Patent, Abstract; col. 4:1-5). A party might argue that to be a "variant" under the patent, a molecule must possess these specific functional properties. Furthermore, Claim 1 itself recites a closed Markush group of five specific sequences, which could be argued to limit the scope of that particular claim to only those five molecules.

VI. Other Allegations

  • Indirect Infringement: The complaint does not contain allegations of indirect infringement against Ascendis.
  • Willful Infringement: The complaint does not allege willful infringement by Ascendis. However, it makes allegations regarding BioMarin's state of mind in bringing the ITC action. Ascendis alleges that "BioMarin knew or should have known that Ascendis's accused conduct fell within the § 271(e)(1) safe harbor" and that its ITC complaint is "objectively baseless" (Compl. ¶35). These allegations form the basis for Ascendis’s prayer for a declaration that the case is "exceptional" under 35 U.S.C. § 285, which would entitle it to an award of attorneys' fees (Compl. p. 10).

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

This declaratory judgment action appears poised to turn on two primary questions, one statutory and one factual, with claim construction held in reserve.

  • A central threshold issue will be one of statutory scope: Do Ascendis's activities, including the importation of its TransCon CNP investigational prodrug, fall entirely within the § 271(e)(1) safe harbor? The court's analysis will focus on whether these activities were "solely for uses reasonably related to the development and submission of information" to the FDA.
  • A key evidentiary question will be one of commercial purpose: Does the quantity of drug substance imported by Ascendis, as alleged by BioMarin in the underlying ITC action, exceed what would be necessary for clinical trials and suggest a commercial purpose, such as stockpiling, that would place its conduct outside the safe harbor?
  • Should the safe harbor defense be unsuccessful, the case would then turn to a question of technical scope: Does Ascendis's TransCon CNP molecule meet the specific structural or functional limitations of a "variant of C-type natriuretic peptide (CNP)" as that term is defined in the asserted claims of the RE’267 patent?