PTAB

IPR2021-01139

Sarepta Therapeutics Inc v. National Center Of Neurology Psychiatry

Log In
Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Antisense Nucleic Acids
  • Brief Description: The ’217 patent relates to methods for treating Duchenne Muscular Dystrophy (DMD). The methods involve intravenously administering a specific antisense oligomer (AO)—a phosphorodiamidate morpholino oligomer (PMO)—that is 100% complementary to nucleotides +36 to +60 of exon 53 in the human dystrophin pre-mRNA, which causes skipping of that exon.

3. Grounds for Unpatentability

Ground 1: Obviousness over Popplewell and Sazani - Claims 1-4 are obvious over Popplewell in view of Sazani.

  • Prior Art Relied Upon: Popplewell (a 2010 article in Neuromuscul. Disord.) and Sazani (a 2010 article in Int'l J. of Toxicology).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination of Popplewell and Sazani discloses all elements of the challenged claims. Popplewell identified a "hotspot" target region (+30 to +65) on exon 53 for effective exon skipping and specifically disclosed a 25-mer PMO, named PMO-A, targeting the +35 to +59 sequence as a "viable alternative" for clinical development. The claimed invention targets the adjacent +36 to +60 sequence, a single nucleotide shift from Popplewell’s PMO-A. Sazani described the precise chemical structure of a clinically advanced PMO (AVI-4658), which included the exact phosphorodiamidate morpholino monomer subunit and 5' triethylene glycol (TEG) moiety recited in the claims of the ’217 patent. Sazani also provided safety data supporting intravenous administration.
    • Motivation to Combine: Petitioner contended that a person of ordinary skill in the art (POSITA) would combine these references. A POSITA, starting with Popplewell’s promising PMO-A, would have been motivated to perform routine optimization using a well-known "oligonucleotide walk"—a stepwise, one-nucleotide screen across the known hotspot region—to identify the most effective sequence. This routine process would have led directly to the claimed +36 to +60 target sequence. The POSITA would then incorporate the successful chemical features from Sazani, such as the PMO backbone and the 5' TEG moiety for improved solubility, to create a drug candidate with a higher probability of success.
    • Expectation of Success: A POSITA would have had a high expectation of success. Popplewell demonstrated that every PMO tested within the +30 to +65 hotspot region successfully induced exon skipping, making the outcome of a minor, one-nucleotide shift highly predictable. Furthermore, Sazani’s data on the clinically successful, structurally analogous AVI-4658 provided strong evidence of the safety and efficacy of this class of PMOs when administered intravenously, reinforcing the expectation that an exon 53-targeting PMO with the same chemistry would also be successful.

4. Key Claim Construction Positions

  • "A method of treating a DMD patient": Petitioner argued this preamble phrase is non-limiting and serves only to identify the intended patient population. It does not impose a requirement that the method achieve any particular clinical outcome or therapeutic effect.
  • "causes skipping of the 53rd exon...": Petitioner asserted that a POSITA would understand this phrase to be satisfied by any measurable level of exon skipping demonstrated in standard in vitro tests using human cells, as described in the ’217 patent’s own examples. This construction does not require a specific threshold of skipping efficiency or proof of skipping in a human patient.

5. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial under 35 U.S.C. § 325(d) would be inappropriate because the petition raises new arguments and relies on prior art not previously considered by the USPTO. Specifically, Sazani was not before the examiner, and while Popplewell was cited in the patent’s background, its most relevant teachings—particularly the disclosure of PMO-A as a viable 25-mer clinical candidate and the closest prior art—were never substantively analyzed or applied in a rejection. Petitioner contended the examiner made a material error in allowing the claims by overlooking these key disclosures and by relying on the Patent Owner's flawed "unexpected results" arguments during prosecution of a related application.

6. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-4 of the ’217 patent as unpatentable.