PTAB

PGR2021-00059

Triplet Therapeutics Inc v. Board Of Supervisors Of Louisiana State University Agricultural Mechanical College

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Compositions and Uses for Treatment Thereof
  • Brief Description: The ’542 patent discloses isolated, nuclease-resistant oligonucleotides, known as splice-switching oligonucleotides (SSOs), designed to modulate the expression of the human mismatch repair gene MLH3. The SSOs are intended to hybridize to the pre-mRNA of the MLH3 gene to induce the skipping of exon 7, thereby producing a specific MLH3 protein isoform that lacks the domain encoded by that exon.

3. Grounds for Unpatentability

Ground 1: Lack of Written Description - Claims 1-15 are unpatentable under 35 U.S.C. § 112.

  • Prior Art Relied Upon: N/A
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the claims are directed to vast, functionally-defined genera of oligonucleotides, encompassing trillions of potential structures with variations in sequence, length, and nuclease-resistant chemical modifications. In contrast, the specification only disclosed and demonstrated the function of four specific SSOs. These exemplified SSOs were argued to be structurally homogenous (all 25-mer morpholinos targeting the same donor/acceptor regions of exon 7) and thus not representative of the massive claimed genera. Petitioner contended this limited disclosure failed to demonstrate that the inventors were in possession of the full scope of the claims and did not provide a reliable structure-function correlation to guide a person of ordinary skill in the art (POSITA) in identifying other functional SSOs within the claimed scope.

Ground 2: Obviousness over Fuselier, Morcos, and Santucci-Darmanin - Claims 1-4, 6, and 9-12 are obvious over Fuselier in view of Morcos and Santucci-Darmanin.

  • Prior Art Relied Upon: Fuselier (a 2015 conference abstract), Morcos (a 2007 journal article), and Santucci-Darmanin (a 2002 journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Morcos taught using nuclease-resistant morpholino SSOs as a "powerful technique" for targeted exon skipping to modulate gene expression. Santucci-Darmanin established that the MLH3 gene is expressed as two primary isoforms, with one isoform lacking exon 7 as a result of alternative splicing. Fuselier, investigating trinucleotide repeat expansion disorders, taught that MLH3 isoform 1 (containing exon 7) plays a "pivotal role" in disease pathology and expressly suggested "switching isoforms of MLH3" as a therapeutic strategy.
    • Motivation to Combine: A POSITA would combine these references because Fuselier provided the explicit motivation to switch MLH3 isoforms for therapeutic purposes. Santucci-Darmanin identified that this isoform switch is achieved by skipping exon 7, and Morcos provided the well-known tool (morpholino SSOs) and a detailed methodology for achieving this specific outcome.
    • Expectation of Success: A POSITA would have a reasonable expectation of success because Morcos provided a detailed "guide" for designing effective SSOs, including targeting splice junctions and using a typical 25-mer length. Morcos stated that for internal exons, exon skipping is the "likely outcome" of applying this established technology.

Ground 3: Obviousness over Pinto, Morcos, and Santucci-Darmanin - Claims 1-4, 6, and 9-12 are obvious over Pinto in view of Morcos and Santucci-Darmanin.

  • Prior Art Relied Upon: Pinto (a 2013 journal article), Morcos (a 2007 journal article), and Santucci-Darmanin (a 2002 journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground presented an alternative motivation, substituting Pinto for Fuselier. Pinto (2013) identified the MLH3 protein as a key driver of CAG repeat expansion in a Huntington's disease mouse model. Crucially, Pinto proposed a clear direction for future research: determining whether MLH3's putative endonuclease domain is required for this expansion. A POSITA would have known from Santucci-Darmanin that this specific domain is encoded by exon 7.
    • Motivation to Combine: Pinto provided a clear scientific question and motivation to investigate the function of the exon 7-encoded domain. A POSITA would have been motivated to use Morcos's well-established SSO technology for exon skipping as the direct and logical method to functionally remove the exon 7 domain and answer the question posed by Pinto.
    • Expectation of Success: The expectation of success was argued to be high for the same reasons as in Ground 2, based on the detailed and predictable nature of the SSO methodology described in Morcos.
  • Additional Grounds: Petitioner asserted further obviousness challenges for claims directed to pharmaceutical compositions (7, 8, 14, 15) by adding Wheeler, which taught formulating morpholino SSOs in a pharmaceutically acceptable carrier (e.g., PBS) for administration to mice to study their in vivo effects.

4. Key Claim Construction Positions

  • "[W]herein the isolated nuclease resistant oligonucleotide does not impact the total cellular ratios of MLH1 and its binding partners": Petitioner argued this clause, present in claims 1 and 7, is a non-limiting statement of intended result rather than an additional functional requirement. The petition asserted this outcome is a necessary and inherent consequence of skipping exon 7 (which leaves the other MLH3 isoform intact) and therefore does not impart a separate patentable limitation on the claims.

5. Key Technical Contentions (Beyond Claim Construction)

  • Priority Date Entitlement: A central contention was that the ’542 patent is not entitled to its claimed 2014 or 2015 priority dates because the priority applications allegedly suffer from the same, if not worse, lack of written description support as the issued patent. Petitioner argued this establishes a later effective filing date of November 7, 2016, which is critical for ensuring that references like Fuselier (2015) are available as prior art for the obviousness challenges.

6. Relief Requested

  • Petitioner requested institution of Post-Grant Review and cancellation of claims 1-15 of Patent 10,669,542 as unpatentable.