Curio Bioscience Inc v. Prognosys Biosciences Inc

1. Case Identification

• Case #: IPR2025-00192
• Patent #: 11,549,138
• Filed: November 15, 2024
• Petitioner(s): Curio Bioscience, Inc.
• Patent Owner(s): Prognosys Biosciences Inc. and 10x Genomics, Inc.
• Challenged Claims: 1, 5, 17, 20, 23, 28-29

2. Patent Overview

• Title: Spatially Encoded Biological Assays
• Brief Description: The ’138 patent relates to compositions comprising an array of capture probes immobilized on a substrate. These arrays are used for spatially resolved analysis of nucleic acids (e.g., mRNA) from a biological sample, such as a tissue section placed on the array.

3. Grounds for Unpatentability

Ground 1: Obviousness over Cantor - Claims 1, 5, 17, 20, 23, 28-29 are obvious over Cantor in view of the knowledge of a Person of Ordinary Skill in the Art (POSA).

• Prior Art Relied Upon: Cantor (WO 2009/091934).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Cantor disclosed all key elements of independent claim 1. Cantor taught arrays comprising a substrate with a plurality of beads, where each bead acts as a solid support for capture probes. These probes were described as single-stranded nucleic acids comprising: (i) a "probe sequence" serving as a target-binding domain; (ii) a unique "identifier sequence" (or barcode) that corresponds to the bead's location on the array; and (iii) a "primer sequence" serving as a primer binding site. Petitioner contended that the final limitation of claim 1, immobilizing the probes in a "random pattern," was one of only two obvious choices for arranging the beads (the other being an ordered pattern). A POSA would have been motivated to use a random distribution to simplify array fabrication, followed by a known decoding step to map the barcodes to their locations.
  • Motivation to Combine: The motivation to combine Cantor's teachings with general POSA knowledge stemmed from the desire for simpler, more scalable array manufacturing. Petitioner asserted that for high-density arrays, random placement of barcoded beads followed by sequencing-based decoding was a known and obvious alternative to the more complex process of ordered, site-specific placement. For claim 17, which adds a tissue section, Petitioner argued Cantor expressly disclosed that the sample nucleic acid could originate from a "tissue...or a biopsy." A POSA would have been motivated to place a tissue section directly onto Cantor's array to preserve the spatial information of nucleic acids, a well-understood goal in the art.
  • Expectation of Success: A POSA would have had a high expectation of success, as all constituent steps—creating barcoded bead arrays, randomizing them on a substrate, decoding their positions, and applying tissue samples for spatial analysis—were well-established techniques in the field before 2010.

Ground 2: Obviousness over Cantor and Armani - Claims 1, 5, 17, 20, 23, 28-29 are obvious over Cantor in view of Armani.

• Prior Art Relied Upon: Cantor (WO 2009/091934), Armani (a 2009 article on 2D-PCR in Lab on a Chip).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground incorporated the analysis of Cantor from Ground 1. Armani was introduced to provide an explicit teaching and motivation for applying a tissue section to a substrate for spatial nucleic acid analysis, particularly as recited in claim 17. Armani described a "2D-PCR" method where a tissue section (including a fresh-frozen section) is pressed onto a multi-well array to isolate tissue subregions, followed by lysis and amplification to create a molecular map correlated with histology.
  • Motivation to Combine: A POSA would combine Cantor's barcoded sequencing arrays with Armani's tissue-on-array methodology to improve spatial analysis. Armani expressed a need for mapping RNA from tissue, which its PCR-based method could not do with high sensitivity. Cantor’s sequencing-based detection would overcome this limitation, allowing for the detection of low-abundance mRNAs. Combining the two would replace Armani's cumbersome fluorescent imaging steps with a more powerful and streamlined sequencing readout, using Cantor's barcodes to spatially map the results.
  • Expectation of Success: Success was expected because the combination involved applying Cantor's well-described array in a manner explicitly detailed by Armani for the shared purpose of spatially resolved nucleic acid analysis from tissue.

Ground 3: Anticipation by Frisen - Claims 1, 5, 17, 20, 23, 28-29 are anticipated by Frisen.

• Prior Art Relied Upon: Frisen (WO 2014/060483).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner first argued that the ’138 patent is not entitled to its claimed priority date of April 5, 2010. The petition contended that the priority documents lack written description for the claimed invention (placing a tissue sample onto a pre-made array of probes). Instead, those documents allegedly described a fundamentally different method: delivering reagents in a defined pattern onto a pre-affixed tissue sample. Petitioner asserted the effective priority date is no earlier than February 14, 2019, making the 2014 Frisen publication prior art.
  • Frisen was alleged to anticipate every limitation of the challenged claims. Frisen disclosed a composition for spatial analysis of RNA by placing a tissue section onto a substrate (e.g., a slide) comprising a plurality of immobilized capture probes. Frisen’s probes were described as having (i) a "capture domain" (target-binding domain), (ii) a "positional domain" with a unique barcode sequence to identify location, and (iii) a "universal domain" that functions as an "amplification domain" (primer binding site). Frisen explicitly taught that the probes could be immobilized on beads, which could then be randomly distributed on the substrate. Frisen also disclosed using various tissue types, including fresh-frozen and formalin-fixed paraffin-embedded (FFPE) sections.

4. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under Fintiv is not warranted. The parallel district court litigation was in its early stages with limited investment from the court and parties. A trial was scheduled for May 2026, which would coincide with the Board’s Final Written Decision (FWD), and Petitioner intended to file for a stay.
• Petitioner also contended that denial under §325(d) would be inappropriate. For Grounds 1 and 2, the Cantor reference was cited in a large Information Disclosure Statement (IDS) but was never substantively evaluated by the Examiner. For Ground 3, the Examiner did not have the benefit of Petitioner's detailed analysis showing a lack of written description support in the priority documents, which is essential to establishing Frisen as anticipatory prior art.

5. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 1, 5, 17, 20, 23, 28, and 29 of the ’138 patent as unpatentable.