PTAB

IPR2021-01134

Sarepta Therapeutics Inc v. National Center Of Neurology Psychiatry

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Antisense Nucleic Acids
  • Brief Description: The ’361 patent relates to an antisense oligomer (AO) for treating Duchenne muscular dystrophy (DMD). The AO is designed to cause skipping of exon 53 in the human dystrophin gene, thereby restoring a functional dystrophin protein.

3. Grounds for Unpatentability

Ground 1: Claims 1-7 are obvious over Popplewell and Sazani

  • Prior Art Relied Upon: Popplewell et al., Neuromuscul. Disord. (2010) (“Popplewell”) and Sazani et al., Int’l J. of Toxicology (2010) (“Sazani”).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination of Popplewell and Sazani discloses all limitations of claims 1-7. Independent claim 1 recites an AO consisting of SEQ ID NO: 57, which targets nucleotides +36 to +60 of exon 53. Popplewell taught that the region of nucleotides +30 to +65 of exon 53 was a "hotspot" for effective AOs and identified a 25-mer phosphorodiamidate morpholino oligomer (PMO) called PMO-A, targeting nucleotides +35 to +59, as a "viable alternative" for clinical development. Petitioner contended the claimed AO is merely a one-nucleotide shift from Popplewell's highly effective PMO-A and falls squarely within the disclosed hotspot.
    • Dependent claims 2-5 recite various chemical modifications, including 2'-OMePS (claim 2) and PMO backbones (claims 3-5). Petitioner asserted these were two prominent, well-known, and interchangeable AO chemistries used for exon skipping therapy at the time. Popplewell itself tested PMOs and invited investigation into 2'-OMePS as an alternative.
    • Dependent claim 6 recites conjugation of a triethylene glycol (TEG) moiety to the 5' end. Petitioner argued Sazani explicitly disclosed this structure in its analysis of AVI-4658, a clinically studied PMO, and that adding a TEG moiety to improve solubility was a routine modification.
    • Dependent claim 7, directed to a pharmaceutical composition for treating muscular dystrophy, was allegedly rendered obvious by Popplewell's stated goal of identifying AOs for clinical trials in DMD patients and Sazani's safety and efficacy data for a related PMO.
    • Motivation to Combine: A POSITA would combine the teachings because Popplewell established a promising target region and identified a lead candidate (PMO-A) for exon 53 skipping. A POSITA would have been motivated by the "normal desire of scientists" to optimize this known lead candidate through routine, well-established techniques, such as the "stepped base-by-base screening" that Popplewell itself described. This optimization would have led directly to the claimed sequence. The motivation to incorporate the modifications taught by Sazani (e.g., the TEG moiety) was to improve known properties like solubility, a common and predictable goal in drug development.
    • Expectation of Success: Petitioner argued a POSITA would have had a high expectation of success because Popplewell demonstrated that every AO tested within the broader +29 to +74 region, and particularly those in the +30 to +65 hotspot, successfully induced exon skipping. The high success rate of numerous overlapping AOs in this specific region would make it highly predictable that a slight, one-nucleotide shift of a top-performing candidate like PMO-A would also be effective. Sazani’s favorable safety data for a similar PMO structure would further bolster the expectation of creating a viable pharmaceutical composition.

4. Key Claim Construction Positions

  • “consisting of the nucleotide sequence of SEQ ID NO: 57”: Petitioner proposed that this transitional phrase closes the claim to AOs having the exact sequence of SEQ ID NO: 57, which contains uracil bases. Under this construction, AOs with thymine bases or any other nucleobase additions, substitutions, or modifications would be excluded from the scope of the claims. This construction was central to defining the precise target for the prior art analysis.

5. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial under 35 U.S.C. § 325(d) would be inappropriate because the petition raised new arguments and evidence not previously before the Examiner.
  • The primary reference relied upon during prosecution was a preliminary publication of the Popplewell study (the ’212 Publication), which lacked critical disclosures found in the final Popplewell reference, such as the identification of the 25-mer PMO-A as a "viable alternative."
  • Sazani was an entirely new reference not of record, providing crucial, non-cumulative disclosures regarding the chemical structure and safety of a clinically relevant PMO (AVI-4658), which directly mapped to the limitations of dependent claim 6.
  • Petitioner also contended the Examiner committed a material error by accepting the Patent Owner's flawed "unexpected results" argument, which was based on an improper indirect comparison of experiments. Petitioner pointed to direct comparison data within the ’361 patent’s own specification that contradicted the Patent Owner's argument and was overlooked by the Examiner.

6. Relief Requested

  • Petitioner requested the institution of an inter partes review and cancellation of claims 1-7 of the ’361 patent as unpatentable under 35 U.S.C. § 103.