PTAB

IPR2021-01135

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 ’092 patent relates to an antisense oligomer (AO) that causes skipping of exon 53 in the human dystrophin gene. The claims are directed to a specific 25-mer phosphorodiamidate morpholino oligomer (PMO) sequence for treating Duchenne muscular dystrophy (DMD).

3. Grounds for Unpatentability

Ground 1: Obviousness over Popplewell and Sazani - Claims 1-3 are obvious over Popplewell in view of Sazani.

  • Prior Art Relied Upon: Popplewell (a 2010 journal article describing tests of PMOs for exon 53 skipping) and Sazani (a 2010 journal article detailing the structure and safety of a clinical-stage PMO).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination of Popplewell and Sazani disclosed all elements of the challenged claims. Claim 1 recites a 25-mer PMO that is 100% complementary to the 36th to 60th nucleotides (+36+60) of exon 53 for inducing exon skipping. Popplewell identified a highly effective "hotspot" target region for exon 53 skipping at nucleotides +30 to +65. Within this hotspot, Popplewell disclosed "PMO-A," a 25-mer PMO targeting the +35+59 sequence, which demonstrated high efficacy and was described as a "viable alternative" for clinical development. This prior art PMO is the same length and targets a sequence shifted by only one nucleotide from the claimed oligomer. For claims 2 and 3, Sazani disclosed the precise chemical structure of a clinically advanced PMO, AVI-4658, which included the specific N,N-dimethyl phosphorodiamidate monomer recited in claim 2 and the 5' triethylene glycol (TEG) moiety recited in claim 3.
    • Motivation to Combine: A person of ordinary skill in the art (POSITA) as of August 31, 2011, would combine these teachings. The established success of Popplewell's PMO-A within a known active region would have motivated a POSITA to perform routine optimization to identify an even better candidate. A standard and well-known method for such optimization was "oligonucleotide walking," or a stepped, base-by-base screening of adjacent sequences. Applying this routine technique to Popplewell’s promising +35+59 sequence would have led directly to making and testing the claimed +36+60 sequence. A POSITA would then construct this optimized PMO using the well-known and clinically-validated chemical components described in Sazani—the specific monomer and 5' TEG modification—to ensure favorable characteristics like safety and solubility, which were known benefits for PMO-based therapeutics.
    • Expectation of Success: A POSITA would have had a high expectation of success. Popplewell demonstrated that every PMO tested within the +30+65 hotspot region successfully induced exon 53 skipping. The claimed sequence is not only minimally different (a one-nucleotide shift) from the highly effective PMO-A but is also fully encompassed within the target sequences of other effective PMOs disclosed by Popplewell (e.g., PMO-I, targeting +36+65). This predictability, combined with the use of standard, proven chemistry from Sazani, would have provided a strong reason to believe the resulting oligomer would work as intended.
    • Key Aspects: Petitioner contended that any arguments for non-obviousness based on secondary considerations were unfounded. It argued that the Patent Owner’s "unexpected results" presented during prosecution of a related patent were based on flawed, indirect comparisons. In contrast, Petitioner pointed to a direct comparison within the ’092 patent specification which allegedly showed the claimed AO performed no better than an AO targeting the sequence of the closest prior art (PMO-A). Additionally, Petitioner cited the near-simultaneous invention of the claimed AO sequence by an unrelated research group (Prosensa) as objective evidence of obviousness.

4. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial under 35 U.S.C. § 325(d) would be inappropriate because the petition raised new issues and prior art that were not before the Examiner during prosecution. The primary reference, Popplewell, while cited in the patent, was never applied in a rejection, and its most critical teachings—the high efficacy and clinical viability of the 25-mer PMO-A, the closest prior art—were overlooked. The secondary reference, Sazani, was not of record and presented non-cumulative disclosures, including the complete chemical structure and crucial safety data for a clinical-stage PMO. Petitioner asserted that these references and the arguments based upon them are materially different from what the Examiner considered and are necessary to correct a material error in allowing the claims, particularly regarding the flawed "unexpected results" arguments made by the Patent Owner.

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-3 of Patent 10,385,092 as unpatentable under 35 U.S.C. §103.