Prior art

V. Prior Art Analysis

This section analyzes the most relevant prior art references cited during the prosecution of U.S. Patent 11,566,277. The analysis focuses on how each reference relates to the independent claims of the '277 patent and its potential to anticipate those claims under 35 U.S.C. § 102. The key inventive concept in the '277 patent is the use of a "temporally-sequential" detection of subsequences on a nucleic acid label to generate a "temporal order of the signal signatures," which acts as a unique identifier for a probe.

---

1. U.S. Patent Application Publication No. 2007/0231824 ("the '824 application")

• Full Citation: US 2007/0231824 A1; Gunderson, et al.; "Methods for Decoding a Sensor Array"; Published Oct. 4, 2007; Filed Jan. 12, 2007.
• Brief Description: The '824 application describes methods for decoding sensor arrays, such as bead arrays, where each bead has a unique identifier. The decoding process involves sequentially applying different decoding probes to the array. In one embodiment, a first set of probes is hybridized, an image is taken, the probes are stripped, and then a second set of probes is hybridized, and a second image is taken. This cycle is repeated several times. The sequence of signals (e.g., colors) observed at a specific bead's location across the series of images reveals its unique code.
• Potential Anticipation Analysis:
  • This reference is highly relevant as it explicitly discloses a multi-step, sequential decoding process. The method of hybridizing, imaging, stripping, and re-hybridizing is a clear example of "detecting in a temporally-sequential manner" to generate a "temporal order of the signal signatures," as claimed in Claim 1.
  • The '824 application describes probes attached to beads, where the beads act as the substrate for the identifier nucleic acids. This maps closely to the "detection reagent" of Claim 14, which comprises a probe and a nucleic acid label with subsequences forming an identifier. The '824 disclosure of a decoding process over several cycles directly teaches using subsequences to be "detected in a temporally-sequential manner."
  • The '824 application also discloses kits containing the necessary reagents, such as the beads and the decoding probes, which is relevant to Claim 21.
  • Conclusion: The '824 application appears to disclose many key elements of the independent claims. The '277 patent itself attempts to distinguish this reference by stating the '824 application's methods are for immobilized microspheres on an array and "cannot be used and detected directly on a sample (e.g., on a tissue sample) or in situ" (Col. 14, ll. 5-11). However, whether this distinction is sufficient to overcome an anticipation rejection could be a central point of dispute. From a technical standpoint, the core concept of temporal decoding is present.

---

2. U.S. Patent No. 7,473,767 ("the '767 patent")

• Full Citation: US 7,473,767 B2; Geiss, et al.; "Methods for Detection and Quantification of Analytes in Complex Mixtures"; Issued Jan. 6, 2009; Filed Jul. 3, 2001.
• Brief Description: The '767 patent, related to NanoString Technologies' core platform, describes using "nanoreporters" which consist of a target-specific probe attached to a nucleic acid backbone. This backbone contains a series of label attachment regions, where different fluorescent labels can bind to create a unique color code, or "barcode." The patent describes immobilizing and elongating these nanoreporters and then imaging the spatial pattern of the colors along the backbone to identify the analyte.
• Potential Anticipation Analysis:
  • This reference teaches the use of a probe conjugated to a nucleic acid label with multiple distinct regions that produce a signal to identify the probe, which is a core element of Claim 14.
  • However, the method of detection in the '767 patent is fundamentally different from that in the '277 patent. The '767 patent's method is based on reading the spatial arrangement of different colors along a single molecule at a single point in time. The '277 patent, in contrast, claims reading signals from the same location over a sequence of time steps.
  • Conclusion: The '767 patent does not appear to anticipate Claim 1 because it fails to teach the "temporally-sequential" detection and the generation of a "temporal order of signal signatures." It teaches a spatial order of signals. While it discloses a similar composition (probe + barcoded nucleic acid label), the method of using that composition is distinct. Therefore, anticipation under § 102 is unlikely.

---

3. U.S. Patent No. 9,677,143 ("the '143 patent")

• Full Citation: US 9,677,143 B2; Church, et al.; "Compositions and Methods for Analyte Detection"; Issued Jun. 13, 2017; Filed Feb. 15, 2017.
• Brief Description: The '143 patent is an earlier patent from the same inventors and assignee as the '277 patent and shares a priority claim. It describes similar compositions and methods for detecting analytes using detection reagents with nucleic acid labels. It explicitly describes detecting subsequences in a "temporally-sequential manner" through repeated cycles of hybridization, imaging, and signal removal.
• Potential Anticipation Analysis:
  • This patent is part of the same patent family as the '277 patent and contains a very similar disclosure. However, as prior art, it must be analyzed for what it teaches. It discloses all the key features of the independent claims of the '277 patent: the detection reagent composition, the method of temporal-sequential detection, and kits for performing the method.
  • Conclusion: This reference would likely anticipate the claims of the '277 patent if it were not for their shared priority claim. Because they are related applications, the '143 patent is not prior art to the '277 patent under § 102. This reference is primarily of interest for understanding the prosecution history and the scope of the broader invention claimed by the applicants.

---

4. U.S. Patent No. 9,447,468 ("the '468 patent")

• Full Citation: US 9,447,468 B2; Emily M. Leproust, et al.; "Multiplexed Selection and Detection of Nucleic Acids"; Issued Sep. 20, 2016; Filed Aug. 24, 2012.
• Brief Description: The '468 patent discloses methods for enriching and detecting target nucleic acids. The method involves using probes with unique barcode sequences. After hybridization and enrichment, the barcodes are typically identified by amplification and sequencing (e.g., next-generation sequencing).
• Potential Anticipation Analysis:
  • This reference describes a composition of a probe linked to a nucleic acid barcode for analyte identification, which is relevant to Claim 14.
  • The primary detection method disclosed is high-throughput sequencing. While sequencing is inherently a step-wise process, it is typically understood in the art as a method for determining a complete sequence, not for generating a "temporal order of signal signatures" in situ for probe identification in the manner of the '277 patent (i.e., multiple rounds of imaging). The '468 patent's method involves physically sequencing the barcode to read the code, not optically detecting a series of transient signals over time.
  • Conclusion: The '468 patent does not appear to anticipate Claim 1. It does not teach the repeated cycles of hybridization/imaging/stripping to generate a temporal code. The detection mechanism is fundamentally different. Therefore, anticipation under § 102 is unlikely.