PTAB

IPR2021-01137

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 ’106 patent relates to a specific phosphorodiamidate morpholino oligomer (PMO), which is a type of antisense oligomer (AO), designed to cause the skipping of exon 53 in the human dystrophin gene. This therapeutic approach is intended for the treatment of Duchenne muscular dystrophy (DMD).

3. Grounds for Unpatentability

Ground 1: Claims 1-2 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 or suggests every element of the challenged claims. Popplewell taught using PMOs to induce exon 53 skipping for DMD treatment and identified a "hotspot" target region from nucleotide +30 to +65. Critically, Popplewell disclosed PMO-A, a 25-mer PMO targeting the +35 to +59 sequence, as a "viable alternative" for clinical development. The claimed invention is a 25-mer PMO targeting the nearly identical +36 to +60 sequence. Sazani disclosed the exact chemical structure of a different clinical-stage PMO (AVI-4658), which included the specific phosphorodiamidate morpholino monomer and the 5’ triethylene glycol (TEG) moiety recited in the challenged claims. Petitioner contended that creating the claimed PMO amounted to making a minor, one-nucleotide shift to Popplewell’s promising PMO-A sequence and applying the standard, clinically-validated chemistry taught by Sazani. Claim 2, which adds uracil as a possible nucleobase, was also obvious as a POSITA would have understood that thymine and uracil are functionally equivalent for base pairing in this context.
    • Motivation to Combine: A POSITA would combine these references out of a desire to optimize the most promising known compounds for treating DMD. Popplewell identified the 25-mer PMO-A as a highly effective clinical candidate. A POSITA would be motivated to conduct routine "oligonucleotide walks"—a standard optimization technique involving stepped base-by-base screening—starting with Popplewell's PMO-A to identify an even more effective sequence. This routine process would have led directly to the claimed +36 to +60 target sequence. The motivation to incorporate the monomer and TEG moiety from Sazani was strong, as Sazani taught this specific chemistry was part of a PMO (AVI-4658) already in clinical trials, demonstrating a favorable safety and solubility profile suitable for human use.
    • Expectation of Success: Petitioner asserted a high expectation of success. Popplewell demonstrated that numerous PMOs targeting the +30 to +65 hotspot were effective at inducing exon skipping, indicating that small modifications within this region, such as a one-nucleotide shift from the highly effective PMO-A, would predictably retain function. The synthesis of PMOs with a TEG moiety was a well-known, routine procedure, and the methods for testing their exon-skipping efficacy were well-established, further ensuring a successful outcome.

4. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial under 35 U.S.C. § 325(d) would be inappropriate because the grounds relied upon were not substantially the same as those previously presented to the Office.
  • The primary combination of Popplewell and Sazani was not considered during prosecution. Sazani is a new reference that is not cumulative, as it provides the complete chemical structure, including the specific 5' TEG moiety, and critical safety data for a clinical-stage PMO.
  • Petitioner further contended that while Popplewell was cited on the face of the ’106 patent, the Examiner did not rely on it in any rejection and overlooked its most persuasive teachings. Specifically, the Examiner missed Popplewell's disclosure of the 25-mer PMO-A as a "viable alternative," which is the closest prior art to the claimed invention.
  • The petition also highlighted alleged flaws in the Patent Owner's "unexpected results" arguments made during prosecution of the grandparent ’361 patent, arguing the Examiner improperly relied on a flawed, indirect comparison of data from different experiments. Petitioner pointed to a direct comparison within the patent’s own specification that contradicted these arguments, an error Petitioner asserted warrants review.

5. Relief Requested

  • Petitioner requests institution of inter partes review (IPR) and cancellation of claims 1 and 2 of the ’106 patent as unpatentable.