PTAB

IPR2021-01138

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 ’741 patent relates to methods of administering an antisense phosphorodiamidate morpholino oligomer (PMO) to a patient with Duchenne Muscular Dystrophy (DMD). The PMO is designed to be complementary to a specific sequence within exon 53 of the human dystrophin pre-mRNA to induce skipping of that exon.

3. Grounds for Unpatentability

Ground 1: Claims 1-12 are obvious over Popplewell in view of Sazani.

  • Prior Art Relied Upon: Popplewell et al., “Comparative Analysis of Antisense Oligonucleotide Sequences Targeting Exon 53 of the Human DMD Gene: Implications for Future Clinical Trials,” Neuromuscul. Disord. (2010) (“Popplewell”); and Sazani et al., “Safety Pharmacology and Genotoxicity Evaluation of AVI-4658,” Int. J. Toxicol. (2010) (“Sazani”).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination of Popplewell and Sazani disclosed all elements of the challenged claims. Independent claims 1, 4, 7, and 10 recite administering a 25-mer PMO that is 100% complementary to the +36 to +60 nucleotide sequence of exon 53 to a DMD patient to induce exon skipping. Popplewell was argued to disclose the use of PMOs to induce exon 53 skipping in DMD and identified a “hotspot” target region from nucleotides +30 to +65. Within this hotspot, Popplewell taught that a 25-mer PMO, designated PMO-A, targeting the +35 to +59 sequence (a sequence shifted by only one nucleotide from the claimed sequence) was highly effective and a “viable alternative” for clinical development.
    • Dependent claims 2, 5, 8, and 11 add limitations specifying the chemical structure of the PMO monomer, and claims 3, 6, 9, and 12 further add a 5' end group selected from a triethylene glycol (TEG) moiety, an amide moiety, or a hydroxyl group. Petitioner asserted Sazani disclosed the precise PMO monomer structure and the TEG moiety at the 5' end in its description of AVI-4658, a clinically studied PMO for DMD targeting a different exon. These chemical features were described as well-known and routinely used in the art to improve the properties of PMOs.
    • Motivation to Combine: Petitioner contended a person of ordinary skill in the art (POSA) would combine these references to arrive at the claimed invention. Popplewell’s identification of a highly effective PMO (PMO-A) targeting a sequence nearly identical to the claimed one within a proven hotspot would have motivated a POSA to conduct routine optimization. This optimization, such as performing a standard "oligonucleotide walk" or stepped-array screening (a technique acknowledged by Popplewell), would have inevitably led to testing the adjacent +36 to +60 sequence. A POSA would then be motivated to construct this optimized PMO using the well-characterized, safe, and effective monomer and 5' TEG moiety structures for clinical PMOs as taught by Sazani and known in the art.
    • Expectation of Success: A POSA 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, and several, including the 25-mer PMO-A, were highly effective. The claimed sequence falls squarely within this active region and is only minimally different from PMO-A. Furthermore, the chemical structures described in Sazani were already part of a PMO (AVI-4658) in clinical trials for DMD, confirming their suitability and safety for use in human patients and providing a strong expectation that incorporating them into an exon 53-targeting PMO would be successful.

4. Arguments Regarding Discretionary Denial

  • Petitioner argued that the Board should not exercise its discretion to deny institution under 35 U.S.C. § 325(d). The petition asserted that the arguments and evidence presented were materially different from those before the examiner during prosecution. Specifically, Sazani was a new reference not of record, and while Popplewell was cited on the face of the patent, its most critical teachings—including the high efficacy of the 25-mer PMO-A as a "viable alternative"—were overlooked by the examiner. Petitioner contended the examiner erred by allowing the claims of a related patent based on flawed and indirect "unexpected results" arguments made by the patent owner, which this petition directly rebutted with data from the patent’s own specification.

5. Relief Requested

  • Petitioner requested the institution of an inter partes review and the cancellation of claims 1-12 of the ’741 patent as unpatentable under 35 U.S.C. § 103.