PTAB

PGR2026-00013

Ascendis Pharma AS v. BioMarin Pharmaceutical Inc

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Treatment of Skeletal Dysplasia with C-type Natriuretic Peptide (CNP) Variants
  • Brief Description: The ’106 patent is directed to methods for treating skeletal dysplasia, such as achondroplasia, in very young subjects. The claimed method involves administering a CNP variant to a subject aged from about 0 months to about 2 years old.

3. Grounds for Unpatentability

Ground 1: Obviousness over Högler and Savarirayan - Claims 1-10 and 13-14 are obvious over Högler in view of Savarirayan.

  • Prior Art Relied Upon: Högler (a 2020 journal article) and Savarirayan (a 2019 journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination teaches all limitations of the challenged claims. Högler taught that achondroplasia (a form of skeletal dysplasia) involves serious complications like foramen magnum stenosis and significant height loss occurring within "the first 2 years of life," necessitating intervention "very early in life." Savarirayan disclosed successfully treating achondroplasia in children (5-14 years old) with vosoritide, a CNP variant explicitly recited in claim 1 (as Pro-Gly-CNP37). Critically, Savarirayan also disclosed an ongoing clinical trial of vosoritide for "infants and younger children (age range, 0 to <60 months)," which overlaps with the claimed age range of "about 0 month to about 2 years old."
    • Motivation to Combine: A POSITA would combine these teachings to address the known, severe complications of achondroplasia that manifest in early infancy. Högler established the urgent clinical need for treatment in the first two years of life, while Savarirayan identified vosoritide as a promising and safe therapeutic already being tested in that precise patient population. The primary motivations were to prevent life-threatening conditions like foramen magnum stenosis and to mitigate the most significant period of height loss.
    • Expectation of Success: A POSITA would have a reasonable expectation of success because the underlying pathophysiology of achondroplasia—constitutively active FGFR3 signaling—is the same in infants as in the older children successfully treated in Savarirayan. Vosoritide was known to counteract this specific mechanism. The fact that an advanced clinical trial for infants was already underway, as disclosed by Savarirayan, would have strongly supported the expectation that the treatment would be successful in the claimed age group.

Ground 2: Anticipation by Wendt-242 - Claims 1-7 and 9-14 are anticipated by Wendt-242.

  • Prior Art Relied Upon: Wendt-242 (Patent 8,198,242).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner asserted that Wendt-242 expressly discloses every element of the challenged claims. Example 13 of Wendt-242 teaches a method of treating achondroplasia in a mouse model by administering a CNP variant (CNP-37) starting at 3 weeks of age, which falls within the claimed age range of 0-2 years. More directly, Example 19 discloses therapeutic methods for treating achondroplasia in human subjects including "infant[s] (<1 year of age) to pre-adolescent (<13 years of age)." This disclosure explicitly covers the claimed patient population. Wendt-242 also discloses administering Pro-Gly-CNP37 (vosoritide), the primary variant recited in the ’106 patent claims, and describes administration routes (subcutaneous), frequencies (once daily), and pharmaceutical compositions that anticipate the dependent claims.

Ground 3: Lack of Enablement under §112 - Claims 1-14 are not enabled.

  • Prior Art Relied Upon: N/A.

  • Core Argument for this Ground:

    • Prior Art Mapping: Petitioner argued the claims are not enabled because practicing their full scope would require undue experimentation. The claims are exceptionally broad, encompassing three massive and diverse genera:
      • "Subject": Defined in the patent to include all mammals and non-mammals, covering tens of thousands of different species.
      • "Skeletal dysplasia": A genus of hundreds of distinct conditions with varying pathologies, including some (like those caused by NPR-B receptor mutations or bone overgrowth syndromes) for which CNP therapy is known to be ineffective or even harmful.
      • "CNP variant": A 65-member Markush group with widely varying pharmacokinetic properties and half-lives, including at least two PEGylated variants that prior art showed were inoperative.
    • Key Aspects: The specification provides only a single working example—treating achondroplasia in human children with vosoritide. Petitioner contended this provides no guidance for determining effective amounts for the thousands of other combinations of subjects, diseases, and CNP variants, forcing a POSITA into a process of "random trial-and-error discovery" to practice the full, broad scope of the claims.

  • Additional Grounds: Petitioner asserted additional obviousness challenges over Pauli and Savarirayan; Högler, Savarirayan, and Bullens; and Pauli, Savarirayan, and Bullens. Petitioner also challenged claim 8 as unpatentable under §112(d) for failing to further limit claim 5.

4. Key Claim Construction Positions

  • "Subject": Petitioner argued this term should be construed broadly as defined in the ’106 patent specification: "encompasses mammals and non-mammals," including humans, primates, farm animals, domestic animals, rodents, birds, fish, and the like. This broad construction is central to the non-enablement argument.
  • "Amount effective to treat": Based on the specification’s definitions of "effective amount" and "treatment," Petitioner argued this term should be construed as "a dosage sufficient to produce a desired result in a health condition, pathology, or disease of a subject...comprising a subjective or objective improvement."

5. Relief Requested

  • Petitioner requests institution of post-grant review (PGR) and cancellation of claims 1-14 of the ’106 patent as unpatentable under 35 U.S.C. §§ 102, 103, and 112.