Prior art — US Patent 11021737

Analysis of Cited Prior Art

This analysis focuses on the prior art references cited by the USPTO examiner during the prosecution of U.S. Patent 11,021,737. The patent's priority date is December 22, 2011. The following references were published before this critical date and were considered material to the patentability of the invention.

Key Prior Art References and Potential Anticipation

1. U.S. Patent Application Publication No. US 2007/0231824 A1 ("Gunderson")

Full Citation: US 2007/0231824 A1
Title: Methods for decoding sensor arrays
Filing Date: March 27, 2007
Publication Date: October 4, 2007
Brief Description: Gunderson discloses a method for identifying analytes using a sensor array, such as a fiber optic array with beads in wells. Each bead has a specific probe and is associated with a unique "address" sequence. The method involves sequentially hybridizing and stripping labeled "decoder probes" to these address sequences to identify the location of each bead type. After decoding the array, the sample is introduced, and analyte binding is detected.
Potential Anticipation of Claims:
- Claim 1 & 12 (Method Claims): Gunderson teaches a form of sequential detection using decoder probes to identify unique nucleic acid sequences, which generates a temporal series of signals. However, a key distinction exists. Gunderson's method first decodes the spatial positions of the probes on a fixed array before the sample is introduced. The detection of the analyte is a separate, subsequent step. In contrast, the '737 patent claims a method where the detection reagent (e.g., antibody + nucleic acid label) first binds to the analyte in the sample, and then the temporal decoding of the nucleic acid label reveals the identity of the bound analyte, preserving its location within the sample itself. The '737 patent is designed for in-situ analysis where the analyte's position is unknown beforehand, whereas Gunderson decodes a pre-fabricated sensor array. Therefore, Gunderson likely does not anticipate claims 1 or 12 because it does not teach detecting the temporal order of signals from a detection reagent already bound to an analyte within a biological sample.
- Claim 20 (Composition Claim): Gunderson describes probes attached to beads, where the beads are associated with nucleic acid tags (address sequences). This is structurally similar to the "probe reagent" and "nucleic acid label" of claim 20. However, the '737 patent specifies that the detection reagent is designed for use in a solution phase to contact a sample, whereas Gunderson's probes are part of a fixed, solid-support array. The '737 patent itself explicitly argues this distinction, stating the '824 application's microspheres are "immobilized on a solid support ... rather than designed to be in a solution phase" and "cannot be used and detected directly on a sample (e.g., on a tissue sample) or in situ as described herein." This distinction likely prevents a finding of direct anticipation.

2. U.S. Patent No. 7,473,767 B2 ("Dimitrov")

Full Citation: US 7,473,767 B2
Title: Polynucleotide probes for detecting and identifying analytes and methods of using the same
Filing Date: May 19, 2005
Publication Date: January 6, 2009
Brief Description: This patent, foundational to NanoString's technology, describes a method using "nanoreporters" or "nanostrings." These are probes with a nucleic acid backbone containing a series of repeating units, each labeled with a different colored fluorescent molecule. A unique target is identified by the specific spatial order of these colors along the nucleic acid backbone, creating a "barcode." The probes are imaged after binding, and the sequence of colors along the probe's length identifies the analyte.
Potential Anticipation of Claims:
- Claim 1 & 12 (Method Claims): Dimitrov does not anticipate these claims because its detection method is fundamentally different. It relies on detecting a spatial code—the ordered sequence of different colors along a single probe, captured in a single image. The '737 patent claims a temporal code, where a series of signals is generated over time from the same location through sequential hybridization/detection/removal steps. The '737 patent's specification highlights this, stating that NanoString's technology is "based on determination of the 'spatial location of signals' ... rather than temporal detection of signals as described herein."
- Claim 20 (Composition Claim): Dimitrov discloses a probe reagent linked to a nucleic acid label that acts as an identifier. However, the label described in Dimitrov is structured to present a spatially-ordered code of optical labels. The '737 patent's claim 20 requires a nucleic acid label comprising subsequences "to be detected in a temporally-sequential manner." Because Dimitrov's label is designed for spatial, not temporal, decoding, it would not anticipate this claim element.

3. U.S. Patent No. 7,785,790 B1 ("Church")

Full Citation: US 7,785,790 B1
Title: In-situ sequencing
Filing Date: January 24, 2007
Publication Date: August 31, 2010
Brief Description: This patent, which includes one of the same inventors (George M. Church), describes methods for determining nucleic acid sequences directly within a fixed sample (in situ). The core method involves amplifying nucleic acids (like mRNA) within a cell to create localized clusters of amplicons ("rolonies"). These rolony clusters are then sequenced in place, for example, by sequencing-by-ligation or sequencing-by-synthesis. This provides the sequence of the nucleic acid while preserving its original location in the cell or tissue.
Potential Anticipation of Claims:
- Claim 1 & 12 (Method Claims): Church '790 teaches in-situ analysis and sequential detection (as part of the sequencing process). However, it is focused on directly sequencing endogenous nucleic acids (like RNA) or synthetic DNA. It does not describe the key step of the '737 invention: using a pre-made detection reagent (e.g., an antibody) conjugated to a synthetic nucleic acid barcode to first target a non-nucleic acid analyte (like a protein), and then decoding that barcode to identify the protein. Church '790 is about identifying the nucleic acids that are already there, not using nucleic acids as labels to identify other types of molecules. This difference in purpose and method means it would not anticipate claims 1 or 12.
- Claim 20 (Composition Claim): This patent does not describe or suggest the claimed detection reagent—a probe reagent like an antibody conjugated to a nucleic acid label with subsequences that form an identifier. The subject matter is the in-situ analysis of nucleic acids themselves, not a composition for detecting other analytes via a nucleic acid barcode. Therefore, it does not anticipate claim 20.