Will an upcoming Markman hearing reveal if Ascendis’ TransCon CNP infringes Biomarin’s patent?
Zachary Silbersher
Biomarin’s bid to block Ascendis from launching a competing drug for treating achondroplasia is nearing the merits. Biomarin started its campaign in the International Trade Commission (ITC), and in response, Ascendis filed two district court declaratory judgment actions. Ascendis withdrew the first DJ action, and the second one has been stayed. The ITC case is now scheduled to hear the parties’ claim construction disputes later this month. The outcome of that hearing, which will finally touch upon the merits of Biomarin’s infringement allegations, could prove to be a major inflection point in this dispute. What’s at stake in the upcoming Markman hearing?
In the ITC case, Biomarin alleges that Ascendis’ TransCon CNP drug infringes Biomarin’s RE267 patent. Interestingly, when Ascendis filed its second declaratory judgment action, its complaint alleged multiple reasons why its TransCon CNP will not infringe Biomarin’s patent. To understand Ascendis’ non-infringement arguments, we have to look at the “claims” from Biomarin’s patent.
(By way of brief background, the “claims” of a patent are the short, numbered paragraphs that appear at the end of a patent. Those paragraphs, technically, are the “inventions” protected by the patent. During the claim constructionhearing, otherwise known as the Markman hearing, the court will determine the scope of the claims. By way of analogy, that’s much like a surveyor determining the boundary line for a piece of real property. Where the boundary lines for a patent are drawn can dictate whether or not a given drug infringes that patent.)
Claim 15 from Biomarin’s RE267 patent recites:
15. A macromolecule capable of releasing a CNP variant comprising a synthetic polymeric group coupled to the CNP variant through a hydrolysable linkage, wherein the CNP variant is selected from the group consisting of: [sequences omitted]
and wherein hydrolysis of the hydrolysable linkage releases the CNP variant.
As recited above, claim 15 requires a “CNP variant.” Ascendis claimed in its declaratory judgment complaint that its “TransCon CNP investigational prodrug product is inactive (not functional) in the PEGylated form.” (See 4:25-cv-05696-YGR, N.D. Cal., ECF 1 at 7). Ascendis argued that although the RE267 patent teaches that “CNP Variants” can include PEGylated conjugates, the patent “only describes and supports PEGylated conjugates that are active in PEGylated form.” Id. Ascendis claimed that it cannot infringe the RE467 patent because its TransCon CNP product includes a CNP variant with a PEGylated conjugate that is purportedly inactive in the PEGylated form.
On September 22, 2025, the parties to the ITC case filed a joint statement indicating their positions in the upcoming Markman hearing. (See ITC Investigation No. 337-TA-1447, Sep. 22, 2025, Appendix A). The statement shows that the parties are disputing the meaning of the term, “CNP variant.” Ascendis is arguing that the term means, “C-type natriuretic peptide comprising the amino acid sequence that is Cys6 to Cys22 of CNP-22 along with any modifications, substitutions, deletions and conjugations, and that is capable of binding and activating NRP-B, and thereby inducing cGMP production.” Ascendis therefore appears to be attempting to construe the meaning of “CNP variant” to be limited to one that is active in its conjugated, or PEGlyated, form. By contrast, Biomain is arguing the term is self-explanatory and needs no specific definition. If Ascendis prevails on this dispute, that could be a basis to show non-infringement.
Interestingly, the Staff recommendation is that “CNP variant” must have “substantially similar or better functionality than wild-type CNP22.” That proposed construction appears to be somewhere in between Ascendis’ and Biomarin’s proposed constructions, though probably closer to Biomarin’s. It’s not clear if Ascendis will be able to show infringement if the Staff’s proposed construction is adopted.
Claim 15 also requires that “hydrolysis of the hydrolysable linkage releases the CNP variant.” Ascendis argues that this limitation of claim 15 “requires hydrolysis through the incorporation of a water molecule.” (See 4:25-cv-05696-YGR, N.D. Cal., ECF 1 at 7). Ascendis previously argued in its declaratory judgment complaint that its drug does not meet this limitation because the “TransCon CNP investigational prodrug product does not release CNP through hydrolysis.” Id.
The claim construction statement filed in the ITC action again shows the parties are disputing the meaning of the term, “hydrolysis.” Biomarin argues that the term means a “chemical reaction in which water reacts with another substance to form two or more substances.” Ascendis, by contrast, argues hydrolosis means, “reaction between a compound and water in which a bond in the compound is cleaved and the water components (H+ and OH-) are added where the bond was broken.” Ascendis again appears to be narrowing the meaning of “hydrolysis” to mean something that can be distinguished from how its drug works. If it prevails, that may again set up a non-infringement defense. The Staff’s recommendation for this term again leans closer to Biomarin’s, suggesting Ascendis’ argument may be a stretch.
Claim 18 from Biomarin’s RE267 patent recites:
18. A sustained release CNP variant formulation comprising a synthetic polymeric group coupled to the CNP variant through a hydrolysable linkage, wherein the CNP variant is selected from the group consisting of: [sequences omitted].
Claim 18 requires a “sustained release CNP variant formulation.” Ascendis argues that the RE267 patent teaches that this requires the CNP variant is formulated using polymeric systems. Id. By contrast, Ascendis claims that its TransCon CNP product is not formulated for sustained release using polymeric systems. Id.
Once again, the parties are disputing the meaning of the term “sustained release CNP variant formulation.” Biomarin argues this term should have its ordinary meaning, i.e., “a mixture containing a system for maintaining a relatively constant level of CNP variant over a desired time period.” The Staff’s proposal is similar. Ascendis, by contrast, argues the CNP variant must be “coupled to [a] synthetic polymeric group through hydrolysable linkage.” By doing so, Asendis again appears to be attempting to narrow the boundary line of Biomarin’s patent so that its drug falls doesn’t infringe.
In its declaratory judgment complaint, Ascendis pointed to a paragraph from the specification for the RE267 patent located at column 88, line 63 through column 89, line 7. The paragraph is set forth below.
In addition, pharmaceutical compositions comprising a CNP variant can be formulated as a slow release, controlled release or sustained release system for maintaining a relatively constant level of dosage over a desired time period, such as 1 week, 2 weeks, 3 weeks, 1 month, 2 months, or 3 months. Slow release, controlled release and sustained release formulations can be prepared using, e.g., biodegradable polymeric systems {which can comprise, e.g., hydrophilic polymers [e.g., polylactide, polyglycolide, poly(lactide-glycolide)]}, and can take the form of, e.g., microparticles, microspheres or liposomes, as is known in the art.
(emphasis added).
The foregoing excerpt from the patent’s specification clearly teaches that “sustained release formulations can be prepared using . . . polymeric systems.” The paragraph further explains that the polymeric systems can be biodegradeable, and it goes further to provide specific examples of such biodegradeable polymeric systems, such as hydrophilic polymers, including polyactide and polyglycolide, among others.
Yet, one of the cornerstones of patent law provides that patent claims are not limited to their preferred embodiments. That’s another way of saying, just because a patent’s specification provides examples of how to formulate for sustained release, those examples are not presumed to be exhaustive. On the contrary, if examples are taught as the just that, namely, “examples,” then the presumption is that they are not exhaustive. Indeed, here, the paragraph from the paten specifically teaches that biodegradable polymers are just “e.g.,” examples, of how to formulate for sustained release.
The foregoing terms in dispute may be ones to watch at the upcoming Markman hearing. If Ascendis prevails on just one or two terms, that could easily set up a clean non-infringement defense that will take Ascendis’ drug outside the scope of Biomarin’s patent. Yet, by trying to narrow the claims beyond what the actual words say, Ascendis is already fighting a battle where the odds, and the law, may be slightly stacked against it.