Prior art

Analysis of Prior Art for US Patent 12,168,797: Signal Encoding and Decoding in Multiplexed Biochemical Assays

Washington D.C. - A detailed analysis of the prior art cited against U.S. Patent No. 12,168,797, titled "Signal encoding and decoding in multiplexed biochemical assays," reveals a landscape of foundational technologies in multiplexed assays and signal processing. The patent, assigned to the California Institute of Technology, describes methods for detecting multiple analytes in a single sample by encoding each analyte's presence as a unique signal signature, which is then decoded from a cumulative measurement. This approach aims to overcome limitations in the number of analytes that can be simultaneously detected due to spectral overlap of fluorescent labels.

The most relevant prior art has been identified and examined for its potential to anticipate the claims of the '797 patent under 35 U.S.C. § 102. The analysis focuses on the core inventive concepts of the '797 patent, namely the non-degenerate encoding schemes and the methods for decoding cumulative signals to identify the presence or absence of specific analytes.

Key Prior Art and Potential Anticipation of Claims:

The following U.S. patents and patent application publications are considered the most relevant prior art cited in the prosecution history of US Patent 12,168,797.

1. U.S. Patent No. 8,951,733 (Published February 10, 2015; Filed August 3, 2012)

• Full Citation: US Patent 8,951,733, "Methods and compositions for multiplexed analysis of nucleic acids," assigned to The Trustees of Columbia University in the City of New York.
• Brief Description: This patent discloses methods for high-order multiplexed analysis of nucleic acids using a limited number of detection labels. It describes a "barcoding" strategy where combinations of labels are used to uniquely identify a larger number of target molecules. The method involves assigning a unique combination of probes, each with a specific fluorescent label, to each target nucleic acid.
• Potential Anticipation: This reference is highly relevant and could potentially anticipate the independent claims of the '797 patent, particularly those related to encoding analytes with a combination of signals (e.g., different fluorophores). The core concept of using a limited set of labels to create a larger set of unique identifiers for multiplexed detection is a central theme in both the '733 patent and the '797 patent. The anticipation would depend on the specific limitations of the claims in the '797 patent regarding the "non-degenerate" nature of the encoding and the specific decoding algorithms, and whether the '733 patent discloses or renders obvious these specific features.

2. U.S. Patent No. 9,914,981 (Published March 13, 2018; Filed June 24, 2015)

• Full Citation: US Patent 9,914,981, "Methods for multiplexed nucleic acid detection," assigned to Bio-Rad Laboratories, Inc.
• Brief Description: This patent describes methods for performing multiplexed nucleic acid amplification and detection in a single reaction vessel. It focuses on using probes with different melting temperatures (Tm) to distinguish between different target nucleic acids. The detection is based on changes in fluorescence as the temperature is varied.
• Potential Anticipation: While this patent deals with multiplexed detection, its primary mode of differentiation (melting temperature) is distinct from the signal intensity and wavelength encoding described in the '797 patent. Therefore, it is less likely to directly anticipate the core claims of the '797 patent under § 102. However, it could be considered relevant for obviousness arguments (§ 103) when combined with other prior art that teaches signal intensity-based encoding.

3. U.S. Patent No. 10,662,468 (Published May 26, 2020; Filed July 13, 2018)

• Full Citation: US Patent 10,662,468, "Multiplexed analysis of analytes," assigned to Luminex Corporation.
• Brief Description: This patent discloses methods and systems for multiplexed analysis using encoded microspheres. Each microsphere is encoded with a unique spectral signature, and each microsphere is associated with a specific analyte. The presence and quantity of analytes are determined by analyzing the signals from the microspheres.
• Potential Anticipation: This reference is less likely to anticipate the claims of the '797 patent because it relies on a solid-phase-based encoding (encoded microspheres), whereas the '797 patent describes a solution-phase assay where the encoding is inherent in the signaling molecules themselves, not on a separate solid support. This fundamental difference in the assay format likely distinguishes the '797 patent's claims.

4. U.S. Patent No. 11,208,683 (Published December 28, 2021; Filed May 20, 2020)

• Full Citation: US Patent 11,208,683, "Methods and compositions for highly multiplexed nucleic acid detection," assigned to 10X Genomics, Inc.
• Brief Description: This patent describes methods for barcoding nucleic acids in a highly multiplexed manner, often in the context of single-cell analysis. It involves partitioning nucleic acids into droplets and attaching unique barcode sequences to them.
• Potential Anticipation: Similar to the '733 patent, this reference teaches a form of molecular barcoding. However, the '683 patent's focus is on sequence-based barcoding for downstream sequencing applications, which is different from the real-time or end-point fluorescence signal encoding and decoding described in the '797 patent. Therefore, direct anticipation is unlikely.

5. U.S. Patent No. 10,337,049 (Published July 2, 2019; Filed October 26, 2016)

• Full Citation: US Patent 10,337,049, "Methods and systems for multiplexed analysis of single cells and cell populations," assigned to The Board of Trustees of the Leland Stanford Junior University.
• Brief Description: This patent relates to methods for analyzing multiple parameters of single cells using a combination of fluorescent probes. It describes techniques for spectral deconvolution to distinguish between overlapping fluorescent signals.
• Potential Anticipation: This reference's disclosure of spectral deconvolution techniques is relevant to the decoding aspect of the '797 patent. However, the '049 patent is focused on cellular analysis and the deconvolution of existing overlapping signals, rather than the a priori design of a non-degenerate encoding scheme to avoid ambiguity in the first place, which is a key inventive concept of the '797 patent.

6. U.S. Patent Application Publication No. 2013/0203616 (Published August 8, 2013; Filed February 4, 2013)

• Full Citation: US Patent Application Publication 2013/0203616, "Methods for high-throughput, multiplexed detection of analytes."
• Brief Description: This application describes methods for detecting a plurality of analytes in a sample using a set of probes, where each probe has a unique identifying characteristic. It mentions the use of combinations of fluorescent labels to increase the number of identifiable probes.
• Potential Anticipation: This application, similar to the '733 patent, teaches the concept of using combinations of labels for multiplexing. Its potential to anticipate the '797 patent would hinge on the level of detail it provides regarding the creation of non-degenerate codes and the methods for decoding the resulting cumulative signals.

7. U.S. Patent Application Publication No. 2017/0253920 (Published September 7, 2017; Filed March 3, 2017)

• Full Citation: US Patent Application Publication 2017/0253920, "Compositions and methods for multiplexed detection of nucleic acids."
• Brief Description: This application discloses methods for multiplexed detection of nucleic acids using sets of probes that can be distinguished by their signal properties. It discusses using combinations of fluorophores to create unique spectral barcodes.
• Potential Anticipation: This application is highly relevant as it explicitly discusses spectral barcoding. The analysis of anticipation would require a close comparison of the specific encoding strategies and decoding methods described in this application with the claims of the '797 patent.

8. U.S. Patent Application Publication No. 2020/0040388 (Published February 6, 2020; Filed August 1, 2019)

• Full Citation: US Patent Application Publication 2020/0040388, "Methods for multiplexed digital PCR."
• Brief Description: This application focuses on methods for increasing the multiplexing capacity of digital PCR (dPCR). It describes strategies for assigning different fluorescent labels or combinations of labels to different targets within a dPCR experiment.
• Potential Anticipation: While focused on dPCR, the principles of using combinations of fluorescent signals to increase multiplexing are applicable to the broader field of the '797 patent. The anticipation analysis would need to consider whether the specific encoding and decoding schemes claimed in the '797 patent are disclosed within the context of dPCR in this application.

In conclusion, while several prior art references disclose the general concept of using combinations of fluorescent labels to increase the multiplexing capacity of biochemical assays, the patentability of the claims of US Patent 12,168,797 likely rests on the specific details of its "non-degenerate" encoding schemes and the corresponding decoding algorithms. A thorough examination of the file history and a detailed claim construction would be necessary to definitively determine the extent to which these prior art references anticipate the claims of the '797 patent. The most significant challenges to the patent's validity under § 102 appear to come from references that teach combinatorial labeling or "barcoding" strategies.