US 11275092

Here's a concise summary of US Patent 11275092:

US Patent 11275092

• Title: Methods of determining a treatment protocol for and/or a prognosis of a patient's recovery from a brain injury
• Assignee: Quanterix Corp
• Inventors: David Wilson, John Henrik Zetterberg, Kaj Blennow, Jeffrey D. Randall
• Filing Date: July 25, 2019 (for application US16/522,237, which led to this patent)
• Issue Date: March 15, 2022
• Abstract: The patent describes methods for determining a treatment plan and/or predicting a patient's recovery from a brain injury. In some cases, the brain injury is caused by a lack of oxygen (hypoxic event). The methods involve measuring the concentration of tau protein in a patient sample, such as blood, that is suspected of containing this protein.

Plain-Language Overview of Independent Claims:

The patent contains several independent claims, each outlining a method for determining a treatment protocol and/or prognosis for a patient's recovery from a brain injury, particularly those resulting from a hypoxic event, by measuring tau protein levels.

• Independent Claim 1: This claim describes a method for determining a treatment plan and/or prognosis for a patient's recovery from a brain injury. It involves taking a blood sample (or plasma/serum from it), performing a highly sensitive assay to measure the concentration of tau protein, and then using this measured concentration to decide the prognosis or treatment. The assay must be sensitive enough to detect tau protein at a limit of detection less than about 0.2 pg/mL, and the measured tau concentration is typically less than about 5 pg/mL.
• Independent Claim 6: This claim focuses on a method for providing data to assist in determining a treatment protocol and/or prognosis. It involves performing a high-sensitivity assay on a blood sample (or plasma/serum) to measure tau protein, where the assay has a limit of detection less than about 0.2 pg/mL. The data from this measurement is then provided to enable the determination of the patient's prognosis or treatment based on the tau protein concentration.
• Independent Claim 13: This claim outlines a method for determining a treatment protocol and/or prognosis by analyzing multiple samples over time. It requires measuring tau protein concentration in a series of samples taken from the patient after the brain injury, where the measurements are performed using an assay with a limit of detection less than about 0.2 pg/mL, and the concentration of tau protein is less than about 5 pg/mL. The prognosis or treatment is then determined based on these measured concentrations.
• Independent Claim 17: This claim also describes a method for determining a treatment protocol and/or prognosis, specifically by looking at the change in tau protein levels over time. It involves taking multiple samples over at least 48 hours, performing an assay with a limit of detection less than about 0.2 pg/mL to determine tau concentration (which is less than about 5 pg/mL), and then calculating the "area under the curve" from a graph of tau protein concentration versus time. This area can be for the entire sampling period or specifically for a "second peak" in tau concentration. The prognosis or treatment is then determined based on this calculated area under the curve.

Litigation Information (as of April 26, 2026):

US Patent 11275092 is currently active. Publicly available information indicates the following:

• A PTAB case, IPR2025-01060, has been filed but was "Not Instituted - Procedural."
• A litigation case has been filed in the Delaware District Court (case number 1:25-cv-00659).

US Patent 11275092, titled "Methods of determining a treatment protocol for and/or a prognosis of a patient's recovery from a brain injury," has been involved in the following litigation:

Inter Partes Review (IPR) Case:

• Petitioner: Fujirebio Diagnostics, Inc. ("FDI")
• Patent Owner: Quanterix Corp.
• Jurisdiction: Patent Trial and Appeal Board (PTAB)
• Case Number: IPR2025-01060
• Filing Date: March 7, 2025
• Outcome/Status: Not Instituted - Procedural. Fujirebio Diagnostics, Inc. petitioned for an IPR of claims 1, 6-21 of the '092 Patent, arguing they are unpatentable under 35 U.S.C. § 103.

District Court Litigation:

• Jurisdiction: Delaware District Court
• Case Number: 1:25-cv-00659
• Filing Date: Not explicitly stated, but initiated in 2025.
• Outcome/Status: Active. This is identified as a "US case filed in Delaware District Court."

Additionally, the patent has a "First worldwide family litigation filed" noted, but specific details (plaintiff, defendant, case number, filing date, and outcome) for this global litigation are not provided in the search results.

Proceedings overview

A single AIA trial proceeding, IPR2025-01060, has been filed against US Patent 11275092. This proceeding reached a status of "Discretionary Denial" at the institution stage, meaning the trial was not instituted. As a result, no claims of US11275092 have been challenged on their merits or invalidated through PTAB proceedings. This outcome generally strengthens the patent's defensive posture, as it successfully withstood a challenge without claims being tested.

IPR2025-01060 — Fujirebio Diagnostics, Inc. v. Quanterix Corp

• Type: Inter Partes Review
• Filed: 2025-05-28
• Status: Discretionary Denial – The Patent Trial and Appeal Board (PTAB) declined to institute the inter partes review.
• Judge panel: The specific judge panel for this discretionary denial is not publicly available from the search results. However, an October 17, 2025, memorandum from USPTO Director John Squires indicated that the Director would personally make all institution determinations in IPR and PGR cases, often issuing "summary notices" without written explanations of the reasoning for routine decisions. The last modification date for this proceeding (2025-11-18) falls after this memorandum.
• Petition grounds: The specific claims challenged, prior art relied upon, and statutory bases (§ 102 / § 103 / § 112) of the petition are not publicly available from the search results.
• Institution decision: Denied. The petition was denied institution on or before 2025-11-18. While the specific reasoning for this particular denial is not available, during the period this IPR was processed, the USPTO Director expanded discretionary denial grounds to limit repeated challenges and address factors such as "settled expectations" (i.e., patents in force for several years) and "roadmapping" (i.e., prior challenges to the same patent by unrelated parties), as well as expanded Fintiv factors for parallel litigation.
• Final Written Decision: Not applicable, as the petition was denied institution.
• Settlement / termination: Not applicable.
• Appeal: Not applicable, as there was no Final Written Decision to appeal.
• Defensive value: The patent owner successfully defended against this IPR petition at the institution stage. This means the claims of US11275092 were not subjected to a full trial on their merits before the PTAB in this proceeding, thereby maintaining their presumed validity against the grounds raised in this petition. Any future petitioner would need to present different, compelling grounds or arguments to overcome the discretionary denial policies in place.

Strategic summary

Currently, all claims of US11275092 remain UNTESTED and SUSTAINED by the PTAB, as the sole IPR petition filed against the patent, IPR2025-01060, was denied institution. This means no claims were canceled, nor were any explicitly held patentable in a Final Written Decision, as the trial itself never commenced. The patent, therefore, has not been narrowed through PTAB proceedings.

Regarding the estoppel landscape, since IPR2025-01060 was denied institution, no statutory estoppel under 35 U.S.C. § 315(e)(1) or (2) applies to the petitioner, Fujirebio Diagnostics, Inc., or its privies. This is because estoppel only attaches upon the issuance of a Final Written Decision. Consequently, a new defendant being asserted against is not barred by this particular proceeding from raising any prior-art grounds, including those that might have been raised in IPR2025-01060. The full range of prior-art grounds remains available for potential challenges by other parties.

The status of "Discretionary Denial" for IPR2025-01060 aligns with a broader policy shift observed at the PTAB during 2025, where the USPTO Director began to personally make institution determinations and expanded the grounds for discretionary denials, often issuing summary notices. This signals that the patent owner, Quanterix Corp, effectively leveraged these policies to prevent the institution of a trial. There is no pattern of multiple IPRs from the same petitioner or aggressive PTAB appeals by the patent owner based on the provided data.

Recommended next steps

Given that IPR2025-01060 was denied institution and no claims of US11275092 were invalidated:

• There are no invalidated claims to link to an FWD for this patent. All claims of US11275092 remain valid as far as PTAB proceedings are concerned.
• No active proceedings are currently pending for US11275092.
• The absence of further PTAB activity on this patent, despite the existence of one denied IPR, indicates that potential challengers may find it difficult to obtain institution, possibly due to the nature of the claims or the current discretionary denial policies at the PTAB. However, the patent has not been subjected to a full validity challenge, leaving open the possibility of future, well-crafted petitions on different grounds or by petitioners not affected by the specific discretionary denial grounds of IPR2025-01060.

Inventors

• David Wilson (Intellectual Ventures Lab at time of filing, then Quanterix Corp)
• John Henrik Zetterberg (Employer not determinable from available information)
• Kaj Blennow (Employer not determinable from available information)
• Jeffrey D. Randall (Employer not determinable from available information)

Original assignee

The original assignee named on the issued patent is Quanterix Corp. Quanterix Corp is a publicly traded life sciences company that develops ultra-sensitive digital immunoassay platforms, instruments, consumables, and services for life sciences research and diagnostics, particularly for biomarker detection in neurology, oncology, immunology, and cardiology. They commercialize assays for various protein biomarkers, including neurological biomarkers like Tau. Quanterix Corp is currently operating.

Assignment timeline

• 2019-08-01 (executed) / recorded 2019-08-01 — Reel 050478/0748
  • Conveyance: Assignment
  • Assignor: BLENNOW, KAJ; RANDALL, JEFFREY D.; WILSON, DAVID; ZETTERBERG, JOHN HENRIK
  • Assignee: Quanterix Corporation
  • Correspondent: KEVIN J. MCNEELY, ESQ., MINTZ, LEVIN, COHN, FERRIS, GLOVSKY AND POPEO, P.C., ONE FINANCIAL CENTER, BOSTON, MA 02111-2621
  • Context: Transfer from individual inventors to corporate assignee.

Timeline diagram

timeline
    title Ownership of US 11275092
    2019 : Inventors assigned to Quanterix Corp
    2022 : Patent issued

NPE / troll-pattern signals

1. Shell-entity transfer - Not present. The only recorded assignment is from the inventors to Quanterix Corporation, an operating company.
2. Known asserter in the chain - Not present. Quanterix Corporation is not identified as a known patent asserter or NPE. Known NPEs like Acacia Research Corp, Marathon Patent Group, Intellectual Ventures, IPNav, Wi-LAN, Mosaid / Conversant (not explicitly detailed in search results but generally known as an NPE), Vringo, Pendrell, Innovatio IP Ventures, MPHJ Technology, Lumen View Technology, Round Rock Research, Document Generation Corp, or Erich Spangenberg entities are not present in the assignment chain.
3. Repeat correspondent across the chain - Not present. There is only one assignment recorded, so no recurrence of a correspondent can be observed in this chain.
4. Cascading transfers - Not present. Only one assignment is recorded.
5. Pre-litigation transfer - Not present. There is no indication of litigation immediately following the assignment to Quanterix Corporation.
6. Bankruptcy fire-sale - Not present. Quanterix Corp is an active, publicly traded company.
7. Privateering - Not present. There is no evidence to suggest this.
8. Defensive aggregator (anti-NPE) - Not present. The patent is currently assigned to Quanterix Corp.

Verdict

Insufficient data. Only one assignment from the inventors to the original assignee, Quanterix Corporation, is recorded (Reel 050478/0748, recorded 2019-08-01). This single transaction is typical for initial patent ownership and does not provide enough evidence to identify any NPE or patent-troll patterns.

Verification: https://assignmentcenter.uspto.gov/

Here is an analysis of the most relevant prior art for US Patent 11275092, based on the citations within its text and publicly available information as of April 26, 2026.

The most relevant prior art documents generally fall into two categories: (1) direct lineal ancestors (continuation applications and PCT national stage filings) and (2) foundational patents disclosing the underlying ultra-sensitive assay technology.

Direct Lineal Ancestors (Priority Documents)

These applications are direct predecessors to US11275092 and serve as prior art if the claims in US11275092 are not entitled to their earlier priority dates or if they contain relevant disclosures that precede the effective filing date of US11275092. Given their direct relationship, they are highly likely to contain substantial overlapping disclosure.

1. U.S. Provisional Patent Application Ser. No. 61/474,315

   • Full Citation: U.S. Provisional Patent Application Ser. No. 61/474,315.
   • Filing Date: April 12, 2011.
   • Brief Description: Titled "METHODS OF DETERMINING A TREATMENT PROTOCOL FOR AND/OR A PROGNOSIS OF A PATIENT'S RECOVERY FROM A BRAIN INJURY RESULTING FROM A HYPDXIC EVENT," this provisional application is the earliest priority document for US11275092. It describes methods for determining a treatment protocol and/or prognosis for a patient's recovery from a brain injury, specifically those resulting from a hypoxic event, by measuring tau protein concentration.
   • Potentially Anticipates Under 35 U.S.C. § 102: Potentially anticipates all claims (Claims 1-20) of US11275092, assuming its disclosure fully supports the claimed methods, including the use of highly sensitive assays for tau protein in blood samples, measurement over time, and analysis of parameters like area under the curve (AUC). Its filing date of April 12, 2011, is critical for establishing priority for claims fully supported within its disclosure.

2. U.S. Provisional Patent Application Ser. No. 61/524,693

   • Full Citation: U.S. Provisional Patent Application Ser. No. 61/524,693.
   • Filing Date: August 17, 2011.
   • Brief Description: Titled "METHODS OF DETERMINING A TREATMENT PROTOCOL FOR AND/OR A PROGNOSIS OF A PATIENT'S RECOVERY FROM A BRAIN INJURY," this provisional application is another priority document for US11275092. It broadly describes methods for determining a treatment protocol and/or prognosis for a patient's recovery from a brain injury by measuring tau protein concentration.
   • Potentially Anticipates Under 35 U.S.C. § 102: Potentially anticipates all claims (Claims 1-20) of US11275092, especially those related to brain injury generally, assuming its disclosure supports them.

3. International Patent Application Ser. No. PCT/US2012/033343

   • Full Citation: WO 2012/142340 A1 (publication of PCT/US2012/033343).
   • Filing Date: April 12, 2012.
   • Publication Date: October 26, 2012.
   • Brief Description: This PCT application, a national stage of which US11275092 claims to be, describes methods for determining a treatment protocol and/or prognosis of a patient's recovery from a brain injury. It includes the measurement of tau protein concentration in patient samples using highly sensitive assays, potentially covering both hypoxic and general brain injury scenarios.
   • Potentially Anticipates Under 35 U.S.C. § 102: Given its direct lineage and comprehensive title, it potentially anticipates all claims (Claims 1-20) of US11275092, particularly if the claims are not fully entitled to the earlier provisional priority dates.

4. U.S. patent application Ser. No. 14/111,326

   • Full Citation: US 2014/0308669 A1 (publication of U.S. patent application Ser. No. 14/111,326).
   • Filing Date: June 24, 2014.
   • Publication Date: October 9, 2014.
   • Brief Description: This U.S. non-provisional application, which US11275092 is a continuation of, describes methods for determining a treatment protocol and/or prognosis of a patient's recovery from a brain injury through tau protein concentration measurements.
   • Potentially Anticipates Under 35 U.S.C. § 102: Potentially anticipates all claims (Claims 1-20) of US11275092, especially if these claims represent subject matter not entitled to an earlier priority date or if they are obvious variations of the disclosure in this ancestor application.

5. U.S. patent application Ser. No. 15/269,142

   • Full Citation: US 2017/0009257 A1 (publication of U.S. patent application Ser. No. 15/269,142).
   • Filing Date: September 19, 2016.
   • Publication Date: January 12, 2017.
   • Brief Description: As another direct lineal ancestor (US11275092 is a continuation of this application), it describes similar methods for determining brain injury prognosis and/or treatment protocols based on tau protein levels.
   • Potentially Anticipates Under 35 U.S.C. § 102: Potentially anticipates all claims (Claims 1-20) of US11275092 if the claims are identical or obvious variations of its disclosure and not supported by an earlier priority date.

Foundational Ultra-Sensitive Assay Technology

These documents describe the underlying high-sensitivity immunoassay methods that US11275092 explicitly references and relies upon for achieving the specified low limits of detection and quantification.

1. International Patent Application No. PCT/US2011/026645

   • Full Citation: WO 2011/109364 A1. Inventors: Duffy et al. Title: "ULTRA-SENSITIVE DETECTION OF MOLECULES OR PARTICLES USING BEADS OR OTHER CAPTURE OBJECTS."
   • Filing Date: March 1, 2011.
   • Publication Date: September 9, 2011.
   • Brief Description: This PCT application describes methods and systems for ultra-sensitive detection and quantification of molecules or particles (biomarkers) by spatially segregating capture objects (e.g., beads) into discrete, individually addressable locations (e.g., femtoliter-sized reaction wells). It enables digital detection and quantification and is cited in US11275092 for its detailed description of such spatial segregation.
   • Potentially Anticipates Under 35 U.S.C. § 102:
     • Claims 1, 4, 5: Anticipates the underlying assay method, particularly the digital immunoassay aspect (Claim 4) and the step of "spatially segregating tau protein molecules into a plurality of locations such that at least some locations comprise either zero or one tau protein molecule" (Claim 5). It also teaches the achievement of very low limits of detection and quantification, thus potentially anticipating the sensitivity thresholds of Claim 1, especially if the application to a generic protein like tau is considered inherent or obvious.
     • Claims 9, 12, 13: Similarly anticipates these dependent claims related to the assay method (LOD, digital immunoassay, spatial segregation).

2. U.S. Patent Application Publication No. US-2010-0075862 (Ser. No. 12/236,484)

   • Full Citation: US 2010/0075862 A1. Inventors: Duffy et al. Title: "HIGH SENSITIVITY DETERMINATION OF THE CONCENTRATION OF ANALYTE MOLECULES OR PARTICLES IN A FLUID SAMPLE."
   • Filing Date: September 23, 2008.
   • Publication Date: March 25, 2010.
   • Brief Description: This publication details methods and systems for high-sensitivity analyte concentration determination in fluid samples. It describes the use of precursor labeling agents that are converted into detectable, localized labeling agents within discrete reaction vessels, a key mechanism for achieving the ultra-sensitive digital immunoassays used in US11275092.
   • Potentially Anticipates Under 35 U.S.C. § 102:
     • Claims 1-5: Anticipates the fundamental assay technology, including the ability to achieve very low LODs and LOQs (Claims 1-3), the digital immunoassay format (Claim 4), and the spatial segregation principle (Claim 5).
     • Claims 9-13: Anticipates these dependent claims that specify the characteristics of the assay method used for prognosis/treatment determination.

3. U.S. patent application Ser. No. 12/731,130

   • Full Citation: US 2011/0212848 A1 (publication of U.S. patent application Ser. No. 12/731,130).
   • Filing Date: March 24, 2010.
   • Publication Date: September 1, 2011.
   • Brief Description: This publication focuses on ultra-sensitive detection methods, particularly concerning the optimal sizing of reaction vessels to contain only a single capture object (e.g., a bead), which is crucial for achieving high-resolution and sensitive molecular detection.
   • Potentially Anticipates Under 35 U.S.C. § 102:
     • Claims 1, 4, 5: Anticipates aspects of the assay method, especially the spatial segregation (Claim 5) and digital immunoassay (Claim 4) where single capture objects are contained within discrete reaction vessels to enable ultra-sensitive detection.
     • Claims 9, 12, 13: Anticipates these dependent claims related to the assay method's characteristics.

General Array Fabrication Technology (Less Direct Relevance)

These patents describe general methods for creating arrays of reaction sites, which form the physical basis for the immunoassays but do not directly address the biomarker, assay sensitivity, or medical applications claimed in US11275092. They are foundational background art rather than direct anticipatory art for the specific claims of US11275092.

1. WO95/25116

   • Full Citation: WO 1995/025116 A1. Inventors: Pirrung et al. Title: "Automated apparatus for oligonucleotide synthesis."
   • Filing Date: March 10, 1995 (for PCT/US1995/002951).
   • Publication Date: September 21, 1995.
   • Brief Description: Describes automated methods and apparatus for synthesizing oligonucleotides on solid supports, using techniques like photolithography to define array features.
   • Potentially Anticipates Under 35 U.S.C. § 102: Unlikely to anticipate specific claims of US11275092, as its focus is on oligonucleotide synthesis and general array fabrication, not protein detection at ultra-low concentrations or medical prognosis.

2. WO95/35505

   • Full Citation: WO 1995/035505 A1. Inventors: Fodor et al. Title: "Methods for forming arrays of biological polymers."
   • Filing Date: June 16, 1995 (for PCT/US1995/007622).
   • Publication Date: December 28, 1995.
   • Brief Description: Describes methods for synthesizing arrays of biological polymers (e.g., peptides, oligonucleotides) on a substrate, often using photolithographic techniques.
   • Potentially Anticipates Under 35 U.S.C. § 102: Unlikely to anticipate specific claims of US11275092. It is a general background reference for array fabrication methods.

3. PCT US98/09163

   • Full Citation: WO 1998/050782 A1 (publication of PCT/US1998/009163). Inventors: Dattagupta et al. Title: "Labeling techniques for nucleic acid and protein detection on microarrays."
   • Filing Date: May 8, 1998.
   • Publication Date: November 12, 1998.
   • Brief Description: Describes general labeling techniques for detecting nucleic acids and proteins on microarrays.
   • Potentially Anticipates Under 35 U.S.C. § 102: While it mentions protein detection on microarrays, it is unlikely to anticipate the ultra-sensitivity, digital aspects, or the specific medical application involving tau protein for brain injury prognosis as claimed in US11275092.

4. U.S. Pat. No. 5,700,637

   • Full Citation: US 5,700,637 A. Inventors: Fodor et al. Title: "Apparatus for making arrays of biological polymers."
   • Filing Date: February 21, 1995 (for 08/391,330).
   • Publication/Grant Date: December 23, 1997.
   • Brief Description: Describes an apparatus for synthesizing arrays of diverse polymer sequences on a substrate.
   • Potentially Anticipates Under 35 U.S.C. § 102: Unlikely to anticipate specific claims of US11275092; it is a general array fabrication background reference.

5. U.S. Pat. No. 5,807,522

   • Full Citation: US 5,807,522 A. Inventors: Brown et al. Title: "Automated synthesis of biological materials arrays."
   • Filing Date: February 21, 1995 (for 08/391,304).
   • Publication/Grant Date: September 15, 1998.
   • Brief Description: Describes automated methods for synthesizing arrays of biological materials on substrates.
   • Potentially Anticipates Under 35 U.S.C. § 102: Unlikely to anticipate specific claims of US11275092; it is a general array fabrication background reference.

6. U.S. Pat. No. 5,445,934

   • Full Citation: US 5,445,934 A. Inventors: Fodor et al. Title: "Array of oligonucleotides on a solid support."
   • Filing Date: February 21, 1995 (for 08/391,245).
   • Publication/Grant Date: August 29, 1995.
   • Brief Description: Describes arrays of oligonucleotides synthesized on a solid support and methods for their use, particularly in nucleic acid hybridization assays.
   • Potentially Anticipates Under 35 U.S.C. § 102: Unlikely to anticipate specific claims of US11275092; it is a general array technology reference focused on nucleic acids.

7. U.S. Pat. No. 6,406,845

   • Full Citation: US 6,406,845 B1. Inventors: Fodor et al. Title: "Methods for producing a pattern of biological polymers on a substrate."
   • Filing Date: March 24, 2000 (for 09/536,268).
   • Publication/Grant Date: June 18, 2002.
   • Brief Description: Describes methods for producing patterns of biological polymers on a substrate, often using photolithography.
   • Potentially Anticipates Under 35 U.S.C. § 102: Unlikely to anticipate specific claims of US11275092; it is a general array fabrication background reference.

8. U.S. Pat. No. 6,482,593

   • Full Citation: US 6,482,593 B1. Inventors: Fodor et al. Title: "Automated synthesis of arrays of biological polymers."
   • Filing Date: October 25, 2000 (for 09/696,442).
   • Publication/Grant Date: November 19, 2002.
   • Brief Description: Describes automated methods for synthesizing arrays of biological polymers.
   • Potentially Anticipates Under 35 U.S.C. § 102: Unlikely to anticipate specific claims of US11275092; it is a general array fabrication background reference.

The obviousness of US patent 11275092 can be analyzed under 35 U.S.C. § 103 by combining the disclosures explicitly described as prior art within the patent's own background section. A person having ordinary skill in the art (POSA) in this field would be a medical professional or researcher focused on neurology, critical care, or clinical diagnostics, possessing knowledge of brain injuries, biomarkers, and immunoassay techniques.

The core of the invention in US11275092 relates to methods of determining a treatment protocol and/or prognosis for a patient's recovery from a brain injury, particularly resulting from a hypoxic event, by measuring tau protein concentration in blood, plasma, or serum using highly sensitive assays and correlating these measurements with patient outcomes.

Claims of US11275092 (exemplified by Claim 1):
Claim 1 states: "A method of determining a treatment protocol for and/or a prognosis of a patient's recovery from a brain injury, comprising: (a) performing an assay on a blood sample from the patient and/or plasma and/or serum derived from the blood sample to determine a measure of the concentration of tau protein in the sample; and (b) determining a prognosis of the patient's recovery from the brain injury and/or a method of treatment based at least in part on the measured concentration of tau protein present in the sample."

Dependent claims introduce further limitations, such as the brain injury resulting from a hypoxic event (Claim 2), specific limits of detection (LOD) for the assay (e.g., less than 0.2 pg/mL in Claim 3, less than 0.02 pg/mL in Claim 5), determining the area under the curve (AUC) of tau protein concentration versus time (Claim 7), and specific timeframes for sample collection (e.g., at least 48 hours in Claim 10).

Prior Art Concepts and Motivation for Combination:

The patent's "BACKGROUND OF THE INVENTION" section explicitly describes several aspects of the prior art, outlining existing knowledge and identifying problems that the invention purports to solve:

1. Known Use of Tau as a Brain Injury Biomarker: It was known that "Tau is known to be elevated in the cerebrospinal fluid (CSF) of patients with neurodegenerative disease and head injuries." A POSA would understand that tau protein serves as an indicator of neuronal damage.
2. Desirability of Blood Samples over CSF: The patent states that "it is advantageous to determine the level of a biomarker in the blood of a patient as compared to CSF, as blood sampling is generally less invasive and may result in fewer complications as compared to CSF sampling." This highlights a clear clinical motivation to shift from CSF to blood testing.
3. Technical Challenge of Measuring Tau in Blood: The prior art recognized that tau protein, when diffusing across the blood-brain barrier, exists in "extremely low concentrations that are not reliably measurable by typical conventional immunoassays" in blood.
4. Known Link Between Hypoxic Events and Biomarker Changes (including Tau): It was understood that "Hypoxic conditions can lead to the production and/or change in the concentration of certain biomarkers," and specifically, "a cascade of biomarkers, such as tau proteins, is generated in the brain in proportion to the extent of hypoxia."
5. Uncorrelated Biomarker Data for Hypoxic Events: Despite the known increase, "the increased concentration [of some biomarkers] has not been correlated with specific diagnostic indications and/or methods of treatment" for hypoxic events. However, the patent also acknowledges that "Correlations (e.g., between the concentration and prognostic indication(s) and/or between the concentration and method(s) of treatment) have been discovered and/or are now discoverable due to recent advancements in technology which allow for the determination of the low concentrations of biomarkers in bodily fluids with sufficient accuracy and precision, thus allowing for the variations in concentration to be statistically significant and therefore, diagnostic."

Obviousness Argument:

A POSA would have been motivated to combine these known elements and address the identified problems, rendering the claims of US11275092 obvious.

• Motivation to Combine 1, 2, and 3 (Tau in Blood with Sensitive Assays):
  A POSA, aware of tau protein's established role as a biomarker for head injuries and neurodegenerative diseases (Prior Art 1), would naturally seek to leverage this biomarker in a clinically more advantageous sample type, namely blood (Prior Art 2). The recognized problem that "typical conventional immunoassays" could not reliably measure the extremely low concentrations of tau in blood (Prior Art 3) would directly motivate the POSA to pursue or adapt more sensitive assay technologies. The patent itself notes that such "recent advancements in technology" made the determination of low concentrations possible with "sufficient accuracy and precision." Therefore, applying or developing a highly sensitive immunoassay to measure tau in a blood-derived sample for brain injury assessment would be an obvious endeavor to overcome a known technical limitation and achieve a desired clinical benefit. This combination would directly render Claim 1 obvious.

• Motivation to Combine 4 and 5 (Correlation for Hypoxic Events):
  Given the knowledge that tau protein concentrations change in response to hypoxic events (Prior Art 4), and the explicit acknowledgment that these changes "has not been correlated with specific diagnostic indications and/or methods of treatment" (Prior Art 5), a POSA would be strongly motivated to establish such correlations. Once the technical hurdle of sensitive tau measurement in blood (as discussed above) was overcome through available or developing technology, the next logical step would be to perform standard biomarker research: collect serial samples, measure biomarker concentrations, and statistically correlate these measurements (e.g., using parameters like AUC, as described in dependent claims) with patient prognoses and treatment responses. The patent's statement that these correlations were "now discoverable" due to technological advancements further underscores this as a logical and obvious research direction once sensitive measurement became feasible. This addresses the obviousness of claims pertaining to hypoxic events (e.g., Claim 2) and the establishment of correlations for prognosis and treatment (e.g., Claim 7-9, 17-20).

• Motivation for Specific Assay Sensitivity (e.g., Claims 3-6):
  The need for extremely low limits of detection and quantification is explicitly articulated as a requirement to overcome the problem of low tau concentrations in blood (Prior Art 3). The patent states that "assay methods which have very low limits of quantification (LOQ) and/or limits of detection (LOD) are generally necessary" for statistically significant results. The continuous drive in diagnostic assay development is to improve sensitivity for low-abundance analytes. Therefore, striving to achieve specific, improved LODs (e.g., < 0.2 pg/mL, < 0.05 pg/mL, < 0.02 pg/mL) and LOQs (e.g., < 0.04 pg/mL) for tau in blood would be an obvious developmental goal for a POSA, leveraging the "recent advancements in technology" mentioned in the patent.

In conclusion, the combination of the known utility of tau as a brain injury biomarker, the recognized advantages of blood sampling, the acknowledged problem of low tau concentrations in blood with conventional assays, and the contemporaneous availability of (or motivation to develop) ultra-sensitive assay technologies, along with the recognized need to correlate biomarker changes with clinical outcomes for hypoxic events, would render the claims of US11275092 obvious to a person having ordinary skill in the art at the time of the invention. The specific numerical values for sensitivity, time points for sampling, and AUC thresholds would represent routine optimization and validation studies once the core method was established.

To provide a comprehensive overview of US Patent 11275092, I will use the USPTO resources to gather detailed information on its prosecution history and projected expiration.

Patent Term Adjustments (PTA) and Extensions (PTE):

• Patent Term Adjustment (PTA): PTA is designed to compensate patent owners for delays caused by the USPTO during the prosecution of a utility or plant patent application. The total PTA is added to the standard 20-year patent term from the earliest filing date. Delays that can trigger PTA include failure by the USPTO to: issue a first Office Action or Notice of Allowance within 14 months of filing; respond to an applicant's reply within four months; or issue the patent within four months of payment of the issue fee. The patent term will also be extended if the USPTO fails to issue a patent within three years of the actual filing date. However, applicant delays can reduce any accrued PTA.
  • To determine the specific PTA for US11275092, a direct calculation using the USPTO's official records (Patent Center or a specific PTA determination notice for this patent) would be necessary. Such a calculation would involve analyzing the prosecution history against the statutory timeframes.
• Patent Term Extension (PTE): PTE, established under the Hatch-Waxman Act, is available for patents claiming certain human drug products, medical devices, animal drugs, and food or color additives. It aims to restore some of the patent term lost due to pre-market government regulatory review by agencies like the FDA. PTE is limited to a maximum of five years, and the total patent life with a PTE cannot exceed 14 years from the date of FDA approval. Only one patent can be extended per regulatory review period.
  • Given that US11275092 relates to methods for determining a treatment protocol and prognosis for brain injury using tau protein biomarkers, it could potentially be eligible for PTE if the tau protein measurement or a related therapeutic product claimed by the patent requires FDA approval. However, the available information does not specify if a PTE has been applied for or granted for this patent.

Continuation and Divisional Applications:

• US Patent 11275092 is explicitly identified as a continuation of U.S. patent application Ser. No. 15/269,142, filed Sep. 19, 2016. This, in turn, is a continuation of U.S. patent application Ser. No. 14/111,326, filed Jun. 24, 2014, which itself is a national stage of International Patent Application Ser. No. PCT/US2012/033343, filed Apr. 12, 2012. The international application claims priority to U.S. Provisional Patent Application Ser. No. 61/474,315, filed Apr. 12, 2011, and U.S. Provisional Patent Application Ser. No. 61/524,693, filed Aug. 17, 2011.
• No specific divisional applications are mentioned in the provided text for US11275092.

Related Family Members:

• Priority Applications:
  • US Provisional Patent Application Ser. No. 61/474,315, filed Apr. 12, 2011.
  • US Provisional Patent Application Ser. No. 61/524,693, filed Aug. 17, 2011.
• International Application: PCT/US2012/033343, filed Apr. 12, 2012, and published as WO 2012/142460 A1.
• National Stage Applications:
  • U.S. patent application Ser. No. 14/111,326, filed Jun. 24, 2014.
  • U.S. patent application Ser. No. 15/269,142, filed Sep. 19, 2016.
• Published Applications:
  • US20200124620A1.
  • US20220229074A1.
  • US12571803B2.
  • US12540950B2.

Projected Expiration Date:

• The Google Patents entry for US11275092B2 states its "Adjusted expiration" date is June 17, 2032.
• The standard patent term for utility patents filed on or after June 8, 1995, is 20 years from the earliest filing date (or priority date in the case of continuations/divisionals). Since the earliest priority date for US11275092 is April 12, 2011 (U.S. Provisional Patent Application Ser. No. 61/474,315), a 20-year term from this date would suggest an expiration around April 12, 2031. The stated "Adjusted expiration" of June 17, 2032 implies that a Patent Term Adjustment (PTA) has been granted, adding approximately 1 year and 2 months to the patent term.

Defensive Disclosure: Derivatives of US Patent 11275092

Current Date: 2026-05-15

This document outlines derivative variations of US Patent 11275092, titled "Methods of determining a treatment protocol for and/or a prognosis of a patient's recovery from a brain injury." These disclosures are intended to serve as prior art, rendering future incremental improvements by competitors obvious or non-novel, thereby strengthening our defensive publishing strategy.

Derivations based on Independent Claim 1:

A method of determining a treatment protocol for and/or a prognosis of a patient's recovery from a brain injury, comprising performing an assay on a blood sample from the patient and/or plasma and/or serum derived from the blood sample to determine a measure of the concentration of tau protein in the sample, wherein the assay has a limit of detection of tau protein of less than about 0.2 pg/mL, and the measured concentration of tau protein is less than about 5 pg/mL; and determining a prognosis of the patient's recovery from the brain injury and/or a method of treatment based at least in part on the measured concentration of tau protein present in the sample.

1.1. Material & Component Substitution: Plasmon-Enhanced Nanoparticle Immunoassay

Enabling Description: A method wherein the tau protein assay utilizes surface plasmon resonance (SPR) enhanced gold nanoparticles as the detection label, replacing enzyme conjugates. Monoclonal anti-tau antibodies are conjugated to 50 nm gold nanoparticles. Capture antibodies are immobilized on a functionalized SPR sensor surface. Upon binding of tau protein from a patient's serum sample and subsequent binding of the gold nanoparticle-conjugated detection antibodies, the localized surface plasmon resonance (LSPR) shift or intensity change is measured directly by a spectrograph. This optical signal provides a highly sensitive, label-free (after initial conjugation) or plasmon-enhanced detection, achieving a limit of detection below 0.1 pg/mL for tau protein, enabling detection of concentrations less than 5 pg/mL in plasma. The sensor surface is regenerated after each measurement.

graph TD
    A[Patient Blood Sample] --> B{Plasma/Serum Separation};
    B --> C[SPR Sensor Surface with Capture Ab];
    C --> D{Tau Protein Binding};
    D --> E[Gold Nanoparticle-conjugated Detection Ab Binding];
    E --> F[LSPR Signal Measurement via Spectrograph];
    F --> G[Data Analysis for Tau Concentration];
    G --> H{Prognosis / Treatment Determination};

1.2. Operational Parameter Expansion: Ultra-High Throughput Microfluidic Analysis at Elevated Temperatures

Enabling Description: A method employing a microfluidic chip array designed for ultra-high-throughput processing of hundreds of patient samples simultaneously. Each microfluidic channel integrates bead-based capture and fluorescence detection. The assay is performed at an elevated temperature, specifically 37°C ± 0.5°C, maintained by integrated resistive heaters and temperature sensors within the microfluidic chip. This elevated temperature accelerates the kinetics of antibody-antigen binding and enzyme-substrate reactions, reducing incubation times by 50% compared to room temperature assays, thus increasing throughput. Sample volumes are reduced to 5 µL per assay, and automated robotic handling ensures sample loading and reagent addition. Detection occurs within 10 minutes per sample.

graph TD
    A[Patient Blood Samples (Batch)] --> B{Automated Sample Preparation};
    B --> C[Microfluidic Chip Loading (5 µL/sample)];
    C --> D{Incubation at 37°C};
    D --> E[Accelerated Tau-Antibody Binding];
    E --> F[Fluorescence Detection Array];
    F --> G[High-Throughput Data Acquisition];
    G --> H{Prognosis / Treatment Determination};

1.3. Cross-Domain Application: Industrial Robotics Predictive Maintenance

Enabling Description: A method applied to industrial robotic systems to predict structural integrity compromise. Instead of tau protein, the biomarker is a specific wear particulate or micro-fracture byproduct protein (e.g., a specific alloy degradation protein, ADP-1) released into the robot's hydraulic fluid or lubricant. Samples of the hydraulic fluid are periodically drawn and assayed using a single-molecule digital immunoassay adapted for ADP-1, with a limit of detection less than 0.2 ng/mL. A measured ADP-1 concentration above 5 ng/mL indicates a high likelihood of impending structural failure (analogous to poor prognosis for brain injury), triggering predictive maintenance protocols or shutdown. The system provides data to inform a maintenance schedule for robotic components.

graph TD
    A[Industrial Robot] --> B{Hydraulic Fluid Sample Collection};
    B --> C[Ultra-Sensitive ADP-1 Immunoassay];
    C --> D{ADP-1 Concentration Data (ng/mL)};
    D --> E{Predictive Maintenance Protocol Trigger};
    E --> F{Robot Shutdown / Component Replacement};

1.4. Integration with Emerging Tech: AI-Driven Personalized Treatment Recommendation

Enabling Description: A method where the ultra-sensitive tau protein concentration data (LOD < 0.2 pg/mL, measured conc < 5 pg/mL) from a patient's blood sample is fed into an AI-driven clinical decision support system. This system, trained on vast datasets of patient outcomes, treatment efficacies, genetic profiles, and concurrent biomarker levels, employs a deep neural network to generate a personalized treatment protocol. The AI considers the specific tau concentration, patient demographics, co-morbidities, and previous treatment responses, providing a probabilistically weighted recommendation for therapeutic agent dosage or intervention strategy, rather than a fixed prognosis. IoT sensors embedded in the assay instrument transmit real-time performance metrics to the AI for continuous calibration and drift correction.

graph TD
    A[Patient Blood Sample] --> B[Ultra-Sensitive Tau Assay (LOD < 0.2 pg/mL)];
    B --> C[IoT Sensor Data (Assay Performance)];
    C --> D[Secure Data Gateway];
    D --> E{AI Clinical Decision Support System};
    E --> F[Deep Neural Network Analysis];
    F --> G{Personalized Treatment Recommendation};
    G --> H[Healthcare Provider];

1.5. The "Inverse" or Failure Mode: Low-Power, Qualitative Triage Assay

Enabling Description: A method for rapid, qualitative triage of brain injury in remote or resource-limited settings. The assay is designed to operate in a low-power, "limited-functionality" mode. Instead of precise pg/mL quantification, the system provides a binary or semi-quantitative output: "Tau Elevated" (indicating concentration > 1 pg/mL) or "Tau Not Elevated" (concentration ≤ 1 pg/mL), operating with a limit of detection of approximately 1 pg/mL. The assay utilizes a simplified lateral flow immunoassay strip with a highly sensitive luminescent reporter. Power is supplied by a compact battery pack. If the full quantitative detection module is unavailable or power is critically low, the system defaults to this rapid, less sensitive, but highly robust qualitative mode to provide immediate actionable information for emergency medical personnel. The "prognosis" is simplified to "Requires Further Assessment" or "Low Risk, Monitor."

graph TD
    A[Patient Blood Sample] --> B[Simplified Lateral Flow Immunoassay];
    B --> C{Luminescent Reporter Activation};
    C --> D{Optical Reader (Low-Power)};
    D --> E{Qualitative Output (Elevated/Not Elevated)};
    E --> F{Triage Recommendation (e.g., "Requires Further Assessment")};
    F -- Low-Power Mode --> G[Battery Status Check];

Derivations based on Independent Claim 6:

A method for performing an assay and providing data for determining a treatment protocol for and/or a prognosis of a patient's recovery from a brain injury, comprising performing an assay on a blood sample from the patient and/or plasma and/or serum derived from the blood sample to determine a measure of the concentration of tau protein in the sample, wherein the assay has a limit of detection of tau protein of less than about 0.2 pg/mL; and providing data from the assay to enable determining a prognosis of the patient's recovery from the brain injury and/or a method of treatment based at least in part on the measured concentration of tau protein present in the sample.

2.1. Material & Component Substitution: Quantum Dot-Labeled Electrochemiluminescence (ECL) Assay

Enabling Description: A method employing an electrochemiluminescence (ECL) assay format using cadmium-free quantum dots (QDs) as reporters, replacing traditional enzymatic labels. Capture antibodies are immobilized on carbon electrode arrays. After tau protein binding from the sample (plasma/serum) and subsequent binding of QD-conjugated detection antibodies, an electrical potential is applied to the electrode. This triggers a light emission from the QDs, directly proportional to the bound tau concentration. The emitted light is detected by a photomultiplier tube (PMT), and the digital signal is converted into tau concentration data. This QD-ECL system offers superior photostability and multiplexing capabilities, achieving a limit of detection below 0.1 pg/mL. The data output is streamed via a secure digital interface.

graph TD
    A[Patient Blood Sample] --> B{Plasma/Serum Separation};
    B --> C[Carbon Electrode Array with Capture Ab];
    C --> D{Tau Protein Binding};
    D --> E[QD-conjugated Detection Ab Binding];
    E --> F[Electrical Potential Application];
    F --> G[ECL Light Emission Detection (PMT)];
    G --> H[Digital Data Conversion & Transmission];
    H --> I{External Prognosis/Treatment System};

2.2. Operational Parameter Expansion: Sub-Microliter Sample Analysis with Cryogenic Storage

Enabling Description: A method specifically designed for analyzing sub-microliter patient samples (e.g., 200 nL) sourced from capillary blood draws. The assay instrument incorporates micro-pipetting robotics capable of handling these minute volumes. After sample acquisition and preparation, the samples, along with their associated metadata, are stored in a cryogenic storage unit at -80°C until batched for processing. The assay itself maintains its ultra-sensitive detection (LOD < 0.2 pg/mL) characteristics. The collected data includes not only tau concentration but also sample collection time, storage duration, and temperature history, all provided to enable precise prognosis determination, particularly for samples subject to variable pre-analytical conditions.

graph TD
    A[Capillary Blood Sample (Patient)] --> B[200 nL Sample Extraction];
    B --> C[Cryogenic Sample Storage (-80°C)];
    C --> D[Automated Thaw & Micro-Pipetting];
    D --> E[Ultra-Sensitive Tau Assay (LOD < 0.2 pg/mL)];
    E --> F[Tau Concentration Data + Metadata];
    F --> G{Data Provision for Prognosis/Treatment};

2.3. Cross-Domain Application: Environmental Toxin Monitoring in Aquatic Systems

Enabling Description: A method adapted for environmental monitoring, specifically detecting neurotoxic compounds (e.g., certain algal toxins or heavy metal complexes that induce stress responses in aquatic organisms) in water samples. The "tau protein" analog here is a specific stress-response protein released by sentinel aquatic organisms (e.g., a specific fish or invertebrate species). Water samples are processed to concentrate the protein, and an ultra-sensitive immunoassay (LOD < 0.2 ng/L) is performed. The detected concentration data for the stress protein is provided to enable determining a "prognosis" for the aquatic ecosystem's health (e.g., risk of fish kill) and/or "treatment" (e.g., initiating remediation efforts, issuing water use advisories).

graph TD
    A[Aquatic System] --> B[Water Sample Collection];
    B --> C[Concentration of Sentinel Organism Stress Protein];
    C --> D[Ultra-Sensitive Immunoassay (LOD < 0.2 ng/L)];
    D --> E[Stress Protein Concentration Data];
    E --> F{Environmental Health Prognosis / Remediation Strategy};

2.4. Integration with Emerging Tech: IoT-Enabled Real-time Data Reporting and Anonymization

Enabling Description: A method where the assay system, an IoT-enabled device, automatically performs the ultra-sensitive tau protein assay (LOD < 0.2 pg/mL) and securely transmits the raw and processed tau concentration data to a cloud-based analytics platform. Before transmission, patient-specific identifiers are anonymized using a privacy-preserving hashing algorithm. The data package includes assay run parameters, quality control metrics, and the measured tau concentration. This anonymized, real-time data is then made available to authorized clinicians or research databases for determining prognoses and treatment protocols, adhering to strict data governance policies enforced by blockchain-based access controls.

graph TD
    A[Patient Blood Sample] --> B[IoT-Enabled Assay Device];
    B --> C[Ultra-Sensitive Tau Assay (LOD < 0.2 pg/mL)];
    C --> D[Tau Concentration Data Generation];
    D --> E[Data Anonymization (Hashing)];
    E --> F[Secure IoT Transmission];
    F --> G[Cloud Analytics Platform];
    G --> H{Authorized Clinicians/Research DBs};

2.5. The "Inverse" or Failure Mode: Diagnostic Mode with Reduced Precision for Rapid Output

Enabling Description: A method where the assay system includes a "diagnostic mode" for accelerated data provision when full precision is not immediately critical, or when instrument conditions are suboptimal (e.g., partial reagent degradation). In this mode, the assay utilizes a reduced number of imaging cycles and a simplified signal processing algorithm, yielding tau concentration data with a precision of ± 20% rather than the standard ± 5%. While the limit of detection remains below 0.2 pg/mL to confirm presence, the reported concentration is an estimate, provided much faster (e.g., within 30 minutes instead of 2 hours). This allows for rapid preliminary prognoses or treatment decisions in time-sensitive situations, with a clear flag indicating "Reduced Precision Data" to the receiving system.

graph TD
    A[Patient Blood Sample] --> B[Assay System];
    B --> C{System State: Optimal?};
    C -- Yes --> D[Standard High-Precision Assay];
    C -- No / Rapid Output Needed --> E[Diagnostic Mode (Reduced Precision)];
    D --> F[High-Precision Tau Data];
    E --> G[Rapid, Reduced-Precision Tau Data];
    F --> H{Data Provision};
    G --> H{Data Provision (Flagged)};

Derivations based on Independent Claim 13:

A method of determining a treatment protocol for and/or a prognosis of a patient's recovery from a brain injury, comprising determining a measure of the concentration of tau protein in each of a plurality of samples obtained from the patient following the brain injury, wherein the measure of the concentration of tau protein is determined by performing an assay on each sample, wherein the assay has a limit of detection of tau protein of less than about 0.2 pg/mL, and the measured concentration of tau protein is less than about 5 pg/mL; and determining a prognostic of the patient's recovery from the brain injury and/or a method of treatment based at least in part on the measured concentration tau protein present in the sample.

3.1. Material & Component Substitution: Multiplexed Raman Spectroscopy with Functionalized Nanowires

Enabling Description: A method utilizing multiplexed surface-enhanced Raman spectroscopy (SERS) for simultaneous detection of tau protein and other neurological biomarkers (e.g., GFAP, NFL) in a plurality of blood samples. Gold nanowires functionalized with specific capture antibodies for each biomarker are integrated into a microfluidic array. Upon binding of biomarkers from the patient samples (LOD < 0.1 pg/mL for tau, < 0.5 pg/mL for others), a Raman-active reporter molecule is introduced, which generates a unique Raman signature for each biomarker. A tunable laser and spectrometer simultaneously acquire multiplexed Raman spectra from each nanowire array, providing kinetic profiles for multiple biomarkers. The raw spectral data is processed by chemometric algorithms to yield individual protein concentrations, forming the basis for a more comprehensive prognostic indicator and refined treatment strategy.

graph TD
    A[Patient (Serial Samples)] --> B[Blood Sample Collection (T1...Tn)];
    B --> C[Plasma/Serum Preparation];
    C --> D[Microfluidic Array with Functionalized Nanowires];
    D --> E{Multiplexed Biomarker Binding (Tau, GFAP, NFL)};
    E --> F[Raman-Active Reporter Introduction];
    F --> G[Tunable Laser & Spectrometer (SERS)];
    G --> H[Multiplexed Raman Spectra Acquisition];
    H --> I[Chemometric Data Processing];
    I --> J[Kinetic Profiles of Biomarker Concentrations];
    J --> K{Comprehensive Prognosis / Treatment};

3.2. Operational Parameter Expansion: Continuous In-Vivo Monitoring via Implantable Biosensor

Enabling Description: A method involving continuous, real-time measurement of tau protein concentration via an implantable subcutaneous biosensor. The biosensor consists of a microdialysis probe coupled to a miniature, flow-through ultra-sensitive immunoassay module (LOD < 0.1 pg/mL). The module draws interstitial fluid, performs the tau assay using localized enzymatic detection, and transmits concentration data wirelessly at 1-minute intervals. This provides a high-resolution kinetic profile of tau release and clearance. The continuous data stream, covering periods of weeks to months, allows for dynamic adjustments to treatment protocols based on immediate changes in tau levels, far exceeding the temporal resolution of discrete sampling.

graph TD
    A[Patient] --> B[Implantable Subcutaneous Biosensor];
    B --> C[Microdialysis (Interstitial Fluid)];
    C --> D[Miniature Flow-Through Immunoassay (LOD < 0.1 pg/mL)];
    D --> E[Real-time Tau Concentration Data];
    E --> F[Wireless Data Transmission (1-min intervals)];
    F --> G[Data Aggregation & Analysis Platform];
    G --> H{Dynamic Prognosis / Adaptive Treatment Protocol};

3.3. Cross-Domain Application: Structural Health Monitoring of Advanced Composite Materials

Enabling Description: A method for monitoring the structural health of advanced composite materials (e.g., in aerospace or civil engineering applications). Instead of brain injury biomarkers, the method detects specific degradation products (e.g., polymer cleavage fragments, composite delamination markers) released into a circulating tracer fluid embedded within the composite matrix. A plurality of fluid samples is collected over time from different locations within the structure. Each sample is analyzed using an ultra-sensitive immunoassay (LOD < 0.2 pg/mL) adapted to detect these degradation markers. Kinetic profiles of marker concentrations are used to determine the "prognosis" of the composite's structural integrity (e.g., risk of catastrophic failure) and inform "treatment" (e.g., repair scheduling, load reduction, or replacement).

graph TD
    A[Composite Structure] --> B[Embedded Tracer Fluid Circulation];
    B --> C[Serial Fluid Sample Collection (T1...Tn)];
    C --> D[Ultra-Sensitive Degradation Marker Assay (LOD < 0.2 pg/mL)];
    D --> E[Degradation Marker Concentration Data];
    E --> F[Kinetic Profile Analysis];
    F --> G{Structural Integrity Prognosis / Maintenance Schedule};

3.4. Integration with Emerging Tech: AI-Driven Adaptive Sampling and Prognosis Refinement

Enabling Description: A method where a machine learning algorithm dynamically optimizes the timing and frequency of sample collection for tau protein measurement. Initial tau measurements (LOD < 0.2 pg/mL, conc < 5 pg/mL) are fed into an AI model. The AI, considering the patient's initial clinical status and early tau kinetics, predicts optimal future sampling points to maximize prognostic accuracy while minimizing invasiveness. This adaptive sampling strategy (e.g., increasing frequency during expected peak times, reducing during stable phases) ensures efficient data collection. The complete time-series tau data is then processed by a recurrent neural network to continuously refine the patient's prognosis and treatment protocol as new data becomes available, with all data inputs and AI recommendations securely logged on a distributed ledger.

graph TD
    A[Patient Brain Injury] --> B[Initial Blood Sample & Tau Assay];
    B --> C[AI Adaptive Sampling Module];
    C -- Recommends --> D[Next Sample Collection (T1, T2...)];
    D --> E[Ultra-Sensitive Tau Assay];
    E --> F[Tau Concentration Data];
    F --> G[Recurrent Neural Network for Prognosis];
    G --> H[Prognosis & Treatment Refinement];
    G & F --> I[Secure Distributed Ledger (Blockchain)];

3.5. The "Inverse" or Failure Mode: Fail-Safe Trend Detection with Reduced Resolution

Enabling Description: A method where, in the event of partial sensor failure or power constraints during prolonged monitoring (plurality of samples), the system defaults to a fail-safe mode for trend detection. Instead of high-resolution quantitative data (pg/mL), it provides simplified trend indicators (e.g., "Tau Increasing," "Tau Stable," "Tau Decreasing") based on coarser concentration thresholds, or reports values as "High," "Medium," or "Low." This limited functionality ensures that even with reduced data fidelity, a critical kinetic trend (e.g., a rapid increase in tau indicating worsening injury) can still be identified and communicated for triage. The system continuously attempts to restore full functionality and logs the duration of reduced resolution operation.

graph TD
    A[Patient (Serial Samples)] --> B[Multi-Sample Tau Assay Module];
    B --> C{Sensor/Power Status Check};
    C -- Optimal --> D[High-Resolution Tau Data (pg/mL)];
    C -- Suboptimal --> E[Fail-Safe Trend Detection Mode];
    E --> F[Simplified Trend Indicators (High/Med/Low, Inc/Dec/Stable)];
    D --> G{Prognosis/Treatment Based on Full Data};
    F --> H{Triage/Emergency Action Based on Trends};

Derivations based on Independent Claim 17:

A method of determining a treatment protocol for and/or a prognosis of a patient's recovery from a brain injury, comprising (a) performing an assay on each of a plurality of samples obtained from the patient following the brain injury to determine the measured concentration of tau protein in each of the samples, wherein the plurality of samples are obtained from the patient over a period of time of at least about 48 hours, wherein the assay has a limit of detection of tau protein of less than about 0.2 pg/mL, and the measured concentration of tau protein is less than about 5 pg/mL; (b) determining the area under the curve of a graph of the tau protein concentration in the plurality of samples versus time, wherein the area is determined for the entire time period and/or for a second peak in the tau protein concentration; and (c) determining a prognosis of the patient's recovery from the brain injury and/or a method of treatment based at least in part on the area under the curve for the entire time period and/or the second peak in the tau protein concentration determined in step (b).

4.1. Material & Component Substitution: Micro-electromechanical Systems (MEMS) Based Assay with Piezoelectric Detection

Enabling Description: A method utilizing a MEMS-based microcantilever array for tau protein detection. Each cantilever is coated with capture antibodies. When tau protein from a patient sample (over 48 hours, LOD < 0.2 pg/mL, conc < 5 pg/mL) binds to the cantilever, it causes a mass-induced deflection. This deflection is precisely measured by integrated piezoelectric sensors. The array allows for parallel, label-free detection across multiple time points. The time-series deflection data is converted to mass, then to concentration, enabling calculation of the area under the curve (AUC) for both overall tau kinetics and specific peaks, particularly the "second peak," to inform prognosis and treatment. This system is highly miniaturized and robust.

graph TD
    A[Patient (Serial Samples over 48+ hrs)] --> B[MEMS Microcantilever Array];
    B --> C{Tau Protein Binding & Mass Loading};
    C --> D[Piezoelectric Deflection Measurement];
    D --> E[Time-Series Deflection Data];
    E --> F[Concentration Derivation];
    F --> G{AUC Calculation (Total and Second Peak)};
    G --> H{Prognosis / Treatment Determination};

4.2. Operational Parameter Expansion: Ultra-Dense Sampling with Fourier Transform Analysis

Enabling Description: A method involving ultra-dense sampling of tau protein concentrations (LOD < 0.2 pg/mL, conc < 5 pg/mL) obtained from a patient, with samples collected every 15 minutes over a period of at least 72 hours. This high temporal resolution generates a detailed kinetic curve. Instead of traditional AUC calculation, the data undergoes Fourier Transform analysis to decompose the complex tau protein concentration curve into its constituent frequency components. Specific frequency signatures and phase shifts, particularly those corresponding to the "second peak" observed after 24-48 hours, are correlated with prognostic outcomes. This allows for a more nuanced analysis of the kinetics, potentially identifying subtle changes indicative of recovery or deterioration, leading to highly optimized treatment protocols.

graph TD
    A[Patient (Brain Injury)] --> B[Automated Blood Sampling (15-min intervals, 72+ hrs)];
    B --> C[Ultra-Sensitive Tau Assay (LOD < 0.2 pg/mL)];
    C --> D[High-Resolution Time-Series Tau Data];
    D --> E[Fourier Transform Analysis];
    E --> F{Identification of Kinetic Signatures/Frequencies};
    F --> G{Prognosis / Treatment Optimization};

4.3. Cross-Domain Application: Precision Agriculture for Plant Stress Response

Enabling Description: A method applied in precision agriculture for determining the "prognosis" of plant health and optimizing "treatment" (e.g., nutrient delivery, pest control). The "brain injury" is analogous to environmental stress (e.g., drought, pathogen attack). The "tau protein" is a specific plant stress hormone or secondary metabolite (e.g., jasmonic acid, abscisic acid) released into the plant's sap. Sap samples are collected from a plurality of plants over a period of at least 7 days (analogous to 48+ hours). An ultra-sensitive assay (LOD < 0.2 pg/mL) determines the concentration of the stress marker. The AUC of the stress marker concentration versus time, particularly a "second peak" (e.g., indicating chronic stress response), is calculated. This AUC value determines the plant's recovery prognosis and dictates precise adjustments to environmental controls or targeted agrochemical application.

graph TD
    A[Crop Field (Stressed Plants)] --> B[Automated Sap Collection (Serial, 7+ days)];
    B --> C[Ultra-Sensitive Stress Marker Assay (LOD < 0.2 pg/mL)];
    C --> D[Time-Series Stress Marker Concentration];
    D --> E{AUC Calculation (Total and Secondary Peak)};
    E --> F{Plant Health Prognosis / Precision Ag Treatment};

4.4. Integration with Emerging Tech: Predictive AI for Multi-Factor Prognosis with Blockchain Verification

Enabling Description: A method where the calculated AUC of tau protein concentration (LOD < 0.2 pg/mL, conc < 5 pg/mL) from samples over at least 48 hours, including the "second peak" AUC, is combined with additional patient data (e.g., genomics, imaging, clinical scores, IoT vital sign data) and fed into a sophisticated predictive AI model. This AI, leveraging federated learning across multiple healthcare institutions, generates a highly accurate, multi-factor prognosis and a dynamic, adaptive treatment protocol. The entire process, from sample collection to AI output and physician override, is recorded on an immutable blockchain ledger, providing an auditable trail for regulatory compliance, insurance claims, and transparent clinical decision-making. Smart contracts on the blockchain could automate alerts for specific AUC thresholds.

graph TD
    A[Patient (Serial Samples over 48+ hrs)] --> B[Ultra-Sensitive Tau Assay];
    B --> C[Tau Concentration Time-Series];
    C --> D{AUC Calculation (Total/Second Peak)};
    D --> E[Additional Clinical Data (Genomics, Imaging, IoT Vitals)];
    E & D --> F[Predictive AI Model (Federated Learning)];
    F --> G[Multi-Factor Prognosis / Adaptive Treatment Plan];
    G --> H[Blockchain Ledger (Immutable Record)];
    H --> I{Healthcare Provider / Regulatory Body};

4.5. The "Inverse" or Failure Mode: Threshold-Based Early Warning System with AUC Estimation

Enabling Description: A method designed to prioritize early warning for potential poor outcomes, especially when full computational resources for precise AUC calculation are unavailable. For samples collected over at least 48 hours (LOD < 0.2 pg/mL), the system first establishes two simple thresholds for tau concentration: T1 (e.g., 2 pg/mL) and T2 (e.g., 4 pg/mL). If the tau concentration crosses T1 for a sustained period (e.g., >6 hours) or crosses T2 at any point, an "Early Warning" is triggered. The "second peak" is only qualitatively detected (e.g., "Secondary Elevation Present/Absent"). A simplified, computationally lightweight AUC estimation is performed using trapezoidal rule for only the first 24 hours of data, providing a rapid, albeit less precise, indicator for initial triage, deferring full AUC calculation to a high-power system when available.

graph TD
    A[Patient (Serial Samples over 48+ hrs)] --> B[Ultra-Sensitive Tau Assay];
    B --> C[Tau Concentration Time-Series];
    C --> D{Tau Threshold Check (T1, T2)};
    D -- T1 or T2 Crossed --> E[Early Warning Triggered];
    C --> F{Qualitative Secondary Peak Detection};
    C --> G[Lightweight AUC Estimation (First 24 hrs)];
    E & F & G --> H{Rapid Triage Prognosis / Initial Treatment Recommendation};

---

Combination Prior Art Scenarios

Here are at least three scenarios combining US Patent 11275092 with existing open-source standards, making further incremental improvements obvious.

1. US11275092 + Open-Source Image Processing & Data Analysis Libraries (e.g., OpenCV, SciPy, Pandas):
   The '092 patent describes performing ultra-sensitive assays, often involving imaging of microwell arrays (e.g., FIGS. 1a, 1b and Example 1). The processing of these images to detect positive wells and subsequent data analysis (e.g., AUC calculation as per Claim 17) can be directly implemented using widely available, open-source libraries. For instance, image acquisition from a CCD camera can be processed with OpenCV (Open Source Computer Vision Library) for bead detection, artifact discrimination, and signal growth analysis. The resulting digital signals and fluorescence intensities can be fed into SciPy and NumPy for numerical computations, including Poisson distribution adjustments and area under the curve calculations. Pandas can then be used for efficient management and statistical analysis of the time-series tau concentration data. The combination of these standard, open-source computational tools with the described assay methodology for tau protein analysis (LOD < 0.2 pg/mL) would be an obvious implementation for anyone skilled in the art of biomedical data processing.

2. US11275092 + Open-Source Microfluidics Design Platforms (e.g., KiCad for schematics, OpenSCAD for CAD, academic repositories):
   The '092 patent describes assay methods utilizing microfluidic structures, specifically "femtoliter-sized reaction wells etched into bundles of optical fibers" (Example 1) or "a plurality of reaction vessels in an array format" (Description). The physical design and fabrication of such microfluidic platforms are increasingly reliant on open-source hardware design principles and software tools. For example, microfluidic layouts can be designed using open-source CAD software like OpenSCAD or Blender, and electronic control systems (e.g., for heaters, fluidic pumps) can be designed using KiCad. Numerous academic research groups openly publish their microfluidic designs (e.g., on platforms like ResearchGate, university repositories, or dedicated open hardware initiatives). Combining the assay principles of US11275092 (ultra-sensitive tau detection) with existing open-source microfluidic designs for reaction vessels, fluidic routing, and bead manipulation would represent an obvious engineering integration, particularly for achieving cost-effective and reproducible assay consumables.

3. US11275092 + Health Level Seven (HL7) Fast Healthcare Interoperability Resources (FHIR) Standard for Data Exchange:
   The '092 patent's core utility lies in determining a prognosis and/or treatment protocol based on measured tau protein concentrations. For this data to be actionable within a modern healthcare system, it must be effectively communicated and integrated with electronic health records (EHRs) and other clinical decision support systems. HL7 FHIR is a widely adopted, open-source standard for exchanging healthcare information electronically. Integrating the tau protein concentration data (including time-series, AUC, and derived prognoses) generated by the methods of US11275092 into a FHIR-compliant format (e.g., as Observation or DiagnosticReport resources) would be a standard and obvious practice for any healthcare IT developer. This combination enables the seamless flow of ultra-sensitive biomarker data from the lab to the patient's digital health record, facilitating automated clinical alerts, longitudinal analysis, and population health management, thereby making the clinical application and data interoperability of the patent's output obvious.