Anti-tau antibody or antigen-binding fragment thereof.

Description

1 / 116 Anti-tau antibody or functional fragment binding to the same antigen (Divided from BR 11 2024 004559 5) CROSS-REFERENCE

[001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 242,437 filed September 9, 2021, which is incorporated by reference in its entirety. BACKGROUND

[002] The discovery of biomarkers and screening techniques for Alzheimer's disease (AD) and other tauopathies is an ongoing area of ​​development in which these tools can be applied to screening populations to determine which non-demented individuals are at higher risk of developing AD dementia, and also to assess disease progression in patients. Proteins that are reflective of AD pathology, including beta amyloid 42 (AÚ42), neurofilament light chain, and various tau isoforms, have been detected by several means. Abnormal or excessive phosphorylation of tau has been associated with the transformation of pathologically normal tau molecules into paired helical filament tau (PHF) and neurofibrillary tangles (NFTs), indicative of various tauopathy pathologies. SUMMARY

[003] Tau is an important microtubule-associated protein, abundantly expressed in neurons of the CNS, and plays critical roles in normal cellular physiology. Tau has also been found to be dysregulated in Alzheimer's disease and other tauopathies. Six isoforms of the tau protein are generated from the TAU gene by alternative splicing. The isoforms differ from each other by the presence or absence of two N-terminal insertions and a repeat called R2. All six tau protein isoforms are highly soluble under normal, healthy cellular conditions and are typically regulated by phosphorylation and Petition 870260068651, dated 10 / 07 / 2026, page 11 / 132 2 / 116 dephosphorylation. Tau has been shown to interact with microtubules and promote microtubule assembly. In neurons, tau promotes the formation of axonal microtubules and stabilizes them. Tau has additional functions in guiding neurite growth. Impaired tau interaction with microtubules may be an important component in the pathology, development, and progression of tauopathies. Tau hyperphosphorylation is a hallmark of Alzheimer's disease (AD) and other tauopathies, and the extent of hyperphosphorylation is often correlated with disease progression. Hyperphosphorylation of the tau protein can result in the self-assembly of insoluble tangles of paired helical filaments and straight tau filaments. These insoluble tangle aggregates, termed neurofibrillary tangles (NFTs), are comprised of hyperphosphorylated tau and are considered pathological markers of tauopathies.

[004] Phosphorylated tau (pTau), total tau, and A3i2, each detected in cerebrospinal fluid (CSF) and / or blood, are individual biomarkers for Alzheimer's disease and several other related tauopathies. CSF pTau is elevated in individuals subsequently confirmed to have AD, both in prodromal and dementia stages, compared to age- and sex-matched controls. CSF pTau levels exhibit a strong degree of correlation with the extent of cognitive impairment in individuals with AD. In fact, CSF pTau levels can be used with some degree of accuracy as a biomarker to predict progression from cognitively unimpaired to mild cognitive impairment (MCI) and then to AD dementia.In terms of its usefulness as a biomarker for predicting even relatively early stages of AD progression, CSF pTau has been shown to be significantly increased in samples from individuals with preclinical AD. Changes in the extent of pTau phosphorylation. Petition 870260068651, dated 10 / 07 / 2026, page 12 / 132 3 / 116 have been demonstrated in sporadic preclinical cases of AD and in early stages of autosomal dominant AD. Blood levels of pTau, total tau, and AU42 are generally lower than CSF levels when analyzed in the same individual and can be used as informative biomarkers for AD and other related tauopathies if blood levels of these biomarkers can be assayed with sufficient specificity and precision.

[005] Several phosphorylation sites have been identified that contribute to hyperphosphorylated tau aggregation in NFTs. In the longer tau isoform, 79 potential serine or threonine phosphorylation sites are present, and at least 30 of these sites have been identified as phosphorylated in NFT aggregates. A common site used to assay tau molecules for phosphorylation status is at threonine-181. CSF fluid contains an array of tau fragments in varying abundances. N-terminal and intermediate tau fragments of tau polypeptides are considerably more abundant in CSF samples than C-terminal tau fragments. Plasma samples from individuals also contain tau polypeptides and tau polypeptide fragments, however, they tend to be present at lower concentrations than in corresponding CSF samples.Being able to detect tau phosphorylation at certain amino acid residues relevant to pathology and disease progression is a critical component of diagnosis, disease staging, and as a metric for measuring treatment effectiveness for Alzheimer's disease (AD) and other tauopathies. Detecting and measuring pTau levels at specific disease-relevant residues in plasma samples would greatly aid in the development of more sensitive and accurate diagnostic, prognostic, and disease analyses for individuals who may be at risk of developing or are in the early stages of AD or other tauopathies. Tau phosphorylation at threonine 217 (pTau 217) is... Petition 870260068651, dated 10 / 07 / 2026, p. 13 / 132 4 / 116 is a residue of particular interest in the development of new biomarkers and diagnostic assays. Changes in the concentration of the pTau biomarker in CSF and plasma are believed to precede measurable behavioral or cognitive changes in AD and other tauopathies. The development of new assays to allow a continuum of specific points and extents of tau phosphorylation of certain residues would undoubtedly aid in clinically relevant medical diagnosis and treatment decisions. A comparison of the results of new assays with the results of existing assays may also yield more informative determinations from a medical standpoint.Results from plasma-based tau biomarker assays can be compared with corresponding CSF samples (detecting pTau in CSF or soluble Aβ in CSF) and also with positron emission tomography (PET) scans, detecting the extent and location of Aβ aggregates as metrics for their usefulness, especially for analysis in preclinical or early stages of the disease.

[006] Methods for detecting phosphorylated tau in a sample from an individual are provided in this document, comprising: performing an immunoassay on the sample using an antibody or antibody fragment comprising a variable domain, heavy chain region (VH) and a variable domain, light chain region (VL), wherein the VH comprises an amino acid sequence at least about 90% identical to a sequence as presented in any of the SEQ ID NOs: 30-34, and wherein the VL comprises an amino acid sequence at least about 90% identical to a sequence as presented in any of the SEQ ID NOs: 35-40. Methods for detecting phosphorylated tau in a sample from an individual are further provided in this document, wherein the phosphorylated tau is selected from the group consisting of pTau-181, pTau-212, pTau-217, pTau-231, pTau-214 and pTau-220. Petition 870260068651, dated 10 / 07 / 2026, page 14 / 132 5 / 116 methods for detecting phosphorylated tau in a sample from an individual, wherein the phosphorylated tau is pTau-217. Methods for detecting phosphorylated tau in a sample from an individual, wherein the phosphorylated tau is pTau-231, are additionally provided in this document. Methods for detecting phosphorylated tau in a sample from an individual, wherein the method detects pTau-217 and pTau-231, are additionally provided in this document. Methods for detecting phosphorylated tau in a sample from an individual, wherein the method detects pTau-212 and pTau-217, are additionally provided in this document. Methods for detecting phosphorylated tau in a sample from an individual, wherein the method detects pTau-212 and pTau-231, are additionally provided in this document. This document also provides methods for detecting phosphorylated tau in a sample from an individual, wherein the method detects pTau-181 and pTau-217.This document further provides methods for detecting phosphorylated tau in a sample from an individual, wherein the method detects pTau-181 and pTau-231. This document further provides methods for detecting phosphorylated tau in a sample from an individual, wherein the method detects pTau-181, pTau-217, and pTau-231. This document further provides methods for detecting phosphorylated tau in a sample from an individual, wherein the method detects pTau-212, pTau-217, and pTau-231. This document further provides methods for detecting phosphorylated tau in a sample from an individual, wherein the method detects pTau-217 and pTau-231 in a sample selected from the group consisting of a plasma sample and a serum sample.This document also provides methods for detecting phosphorylated tau in a sample from an individual, wherein the method detects pTau-212 and pTau-217 in a sample selected from a group consisting of a plasma sample and a serum sample. Petition 870260068651, dated 10 / 07 / 2026, page 15 / 132 Method 6 / 116 detects pTau-212 and pTau-231 in a sample selected from a group consisting of a plasma sample and a serum sample. Methods for detecting phosphorylated tau in a sample from an individual are additionally provided in this document, wherein the method detects pTau-181 and pTau-217 in a sample selected from a group consisting of a plasma sample and a serum sample. Methods for detecting phosphorylated tau in a sample from an individual are additionally provided in this document, wherein the method detects pTau-181 and pTau-231 in a sample selected from a group consisting of a plasma sample and a serum sample. Methods for detecting phosphorylated tau in a sample from an individual are additionally provided in this document, wherein the method detects pTau-181, pTau-217, and pTau-231 in a sample selected from a group consisting of a plasma sample and a serum sample.This document further provides methods for detecting phosphorylated tau in a sample from an individual, wherein the method detects pTau-212, pTau-217, and pTau-231 in a sample selected from a group consisting of a plasma sample and a serum sample. This document also provides methods for detecting phosphorylated tau in a sample from an individual, wherein the VH comprises an amino acid sequence according to any of the SEQ ID NOs: 30-34. Finally, this document provides methods for detecting phosphorylated tau in a sample from an individual, wherein the VL comprises an amino acid sequence according to any of the SEQ ID NOs: 35-40.Methods for detecting phosphorylated tau in a sample from an individual are additionally provided in this document, wherein the VH comprises an amino acid sequence according to any of the SEQ ID NOs: 30-34, and wherein the VL comprises an amino acid sequence according to any of the SEQ ID NOs: 35-40. Methods for detecting phosphorylated tau in a sample from an individual are additionally provided in this document, wherein the VH comprises a... Petition 870260068651, dated 10 / 07 / 2026, p. 16 / 132 7 / 116 amino acid sequence at least about 90% identical to SEQ ID NO: 30, and wherein the VL comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 35. Methods for detecting phosphorylated tau in a sample from an individual are additionally provided in this document, wherein the VH comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 31, and wherein the VL comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 36. Methods for detecting phosphorylated tau in a sample from an individual are additionally provided in this document, wherein the VH comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 31, and wherein the VL comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 37.This document further provides methods for detecting phosphorylated tau in a sample from an individual, wherein the VH comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 32, and wherein the VL comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 38. This document further provides methods for detecting phosphorylated tau in a sample from an individual, wherein the VH comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 33, and wherein the VL comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 39. This document further provides methods for detecting phosphorylated tau in a sample from an individual, wherein the VH comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 34, and wherein the VL comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 40.Methods for detecting phosphorylated tau in a sample from an individual are additionally provided in this document, wherein the antibody or antibody fragment comprises an amino acid sequence at least approximately 90% identical to any of the SEQ ID Nos: 41-51. These are further provided. Petition 870260068651, dated 10 / 07 / 2026, p. 17 / 132 8 / 116 in this document methods for detecting phosphorylated tau in a sample from an individual, further comprising performing an assay on the sample to determine a level of a biomarker selected from the group consisting of Aβ42, Aβ40, Aβ38, BACE1, hFABP, TREM2, YKL-40, IP-10, neurogranin, SNAP25, synaptotagmin, alpha-synuclein, TDP-43, ferritin, VILIP1, NfL, GFAP and combinations thereof. Methods for detecting phosphorylated tau in a sample from an individual are further provided in this document, wherein the sample is selected from the group consisting of a blood sample, a plasma sample, a serum sample and a cerebrospinal fluid (CSF) sample. This document also provides methods for detecting phosphorylated tau in a sample from an individual, further including establishing Alzheimer's disease in the individual based on the detection of phosphorylated tau.This document further provides methods for detecting phosphorylated tau in a sample from an individual, including establishing the individual's prognosis for the development of Alzheimer's disease based on the detection of phosphorylated tau. This document further provides methods for detecting phosphorylated tau in a sample from an individual, also determining the individual's age, genotype, or biomarker expression. This document further provides methods for detecting phosphorylated tau in a sample from an individual, wherein the biomarker is selected from the group consisting of Aβ42, Aβ40, Aβ38, BACE1, hFABP, TREM2, YKL-40, IP10, neurogranin, SNAP-25, synaptotagmin, alpha-synuclein, TDP43, ferritin, VILIP-1, NfL, GFAP, and combinations thereof.This document also provides methods for detecting phosphorylated tau in a sample from an individual, wherein the method has a specificity of at least about 80% for detecting phosphorylated tau. These methods are further provided in this document. Petition 870260068651, dated 10 / 07 / 2026, p. 18 / 132 9 / 116 methods for detecting phosphorylated tau in a sample from an individual are provided in this document, wherein the method has a specificity of at least about 85% for detecting phosphorylated tau. Methods for detecting phosphorylated tau in a sample from an individual are additionally provided in this document, wherein the method has a specificity of at least about 90% for detecting phosphorylated tau. Methods for detecting phosphorylated tau in a sample from an individual are additionally provided in this document, wherein the method has a sensitivity of at least about 80% for detecting phosphorylated tau. Methods are additionally provided in this document for detecting phosphorylated tau in a sample from an individual, wherein the method has a sensitivity of at least about 85% for detecting phosphorylated tau.Methods are further provided in this document for detecting phosphorylated tau in a sample from an individual, wherein the method has a sensitivity of at least about 90% for detecting phosphorylated tau. Methods are further provided in this document for detecting phosphorylated tau in a sample from an individual, wherein the method is capable of detecting phosphorylated tau in the sample at a detection limit of at least about 1.0 picogram per milliliter (pg / mL). Methods are further provided in this document for detecting phosphorylated tau in a sample from an individual, wherein the method is capable of detecting phosphorylated tau in the sample at a detection limit of at least about 1.5 picograms per milliliter (pg / mL). Additionally, methods are provided in this document for detecting phosphorylated tau in a sample from an individual, wherein the method is capable of detecting phosphorylated tau in the sample at a detection limit of at least about 5 picograms per milliliter (pg / mL).

[007] Also provided in this document, in certain embodiments, are anti-tau antibodies comprising i) a heavy chain comprising a variable heavy chain (VH) domain Petition 870260068651, dated 10 / 07 / 2026, page 19 / 132 10 / 116 and ii) a light chain comprising a variable light chain (VL) domain, wherein the VH domain comprises HCDR1 sequence comprising a selected sequence of SEQ ID NOs: 1-5, HCDR2 sequence comprising a selected sequence of SEQ ID NOs: 6-9, and HCDR3 sequence comprising a selected sequence of SEQ ID NOs: 10-13, and the VL domain comprises LCDR1 sequence comprising a selected sequence of SEQ ID NOs: 14-19, LCDR2 sequence comprising a selected sequence of SEQ ID NOs: 20-23, and LCDR3 sequence comprising a selected sequence of SEQ ID NOs: 24-29. In some embodiments, the HCDR1 sequence comprises SEQ ID NO: 1, the HCDR2 sequence comprises SEQ ID NO: 6, the HCDR3 sequence comprises SEQ ID NO: 10, the LCDR1 sequence comprises SEQ ID NO: 14, the LCDR2 sequence comprises SEQ ID NO: 20, and the LCDR3 sequence comprises SEQ ID NO: 24.In some embodiments, the HCDR1 sequence comprises SEQ ID NO: 2, the HCDR2 sequence comprises SEQ ID NO: 7, the HCDR3 sequence comprises SEQ ID NO: 11, the LCDR1 sequence comprises SEQ ID NO: 15, the LCDR2 sequence comprises SEQ ID NO: 21, and the LCDR3 sequence comprises SEQ ID NO: 25. In some embodiments, the HCDR1 sequence comprises SEQ ID NO: 2, the HCDR2 sequence comprises SEQ ID NO: 7, the HCDR3 sequence comprises SEQ ID NO: 11, the LCDR1 sequence comprises SEQ ID NO: 16, the LCDR2 sequence comprises SEQ ID NO: 22, and the LCDR3 sequence comprises SEQ ID NO: 26. In some embodiments, the HCDR1 sequence comprises SEQ ID NO: 3, the HCDR2 sequence comprises SEQ ID NO: 8, and The sequence for HCDR3 comprises SEQ ID NO: 10, the sequence for LCDR1 comprises SEQ ID NO: 17, the sequence for LCDR2 comprises SEQ ID NO: 20, and the sequence for LCDR3 comprises SEQ ID NO: 27.In some forms, the HCDR1 sequence comprises SEQ ID NO: 4, the HCDR2 sequence comprises SEQ ID NO: 7, the HCDR3 sequence comprises SEQ ID NO: 12, and the LCDR1 sequence comprises... Petition 870260068651, dated 10 / 07 / 2026, page 20 / 132 11 / 116 SEQ ID NO: 18, the LCDR2 sequence comprises SEQ ID NO: 23, and the LCDR3 sequence comprises SEQ ID NO: 28. In some embodiments, the HCDR1 sequence comprises SEQ ID NO: 5, the HCDR2 sequence comprises SEQ ID NO: 9, the HCDR3 sequence comprises SEQ ID NO: 13, the LCDR1 sequence comprises SEQ ID NO: 19, the LCDR2 sequence comprises SEQ ID NO: 21, and the LCDR3 sequence comprises SEQ ID NO: 29. Additionally, in some embodiments, anti-tau antibodies are provided herein comprising i) a heavy chain comprising a variable heavy chain (VH) domain and ii) a light chain comprising a variable light chain (VL) domain, wherein the VH domain comprises at least 80%, at least 85%, at least 90%, at least 95% sequence identity with a selected sequence of SEQ ID NOs: 30-34. Additionally, in some embodiments, anti-tau antibodies are provided herein comprising i) a heavy chain comprising a variable heavy chain (VH) domain and ii) a light chain comprising a variable light chain (VL) domain, wherein the VL domain comprises at least 80%, at least 85%, at least 90%, at least 95% sequence identity with a selected sequence of SEQ ID NOs: 35-40. In some embodiments, the anti-tau antibody described herein is a chimeric antibody or its antigen-binding fragment.In some embodiments, the anti-tau antibody described in this document comprises an IgG-scFv, nanobody, BiTE, diabody, DART, TandAb, scDiabody, scDiabody-CH3, triple body, miniantibody, minibody, TriBi minibody, scFv-CH3 KIH, Fab-scFv-Fc KIH, FabscFv, scFv-CH-CL-scFv, Fab', F(ab')2, F(ab')3, F(ab')2-scFv2, scFv, scFv-KIH, Fab-scFv-Fc, tetravalent HCAb, scDiabody-Fc, diabody-Fc, scFv-Fc in tandem or intrabody. In some embodiments, the anti-tau antibody described in this document is an IgG1 antibody. In some embodiments, the anti-tau antibody described in this document is an IgG2 antibody. In some... Petition 870260068651, dated 10 / 07 / 2026, p. 21 / 132 In some embodiments, the anti-tau antibody described in this document is an IgG4 antibody. Additionally, in some embodiments, anti-tau antibodies are provided in this document comprising i) a heavy chain comprising a variable heavy chain (VH) domain and ii) a light chain comprising a variable light chain (VL) domain, wherein the light chain is a kappa chain. In some embodiments, anti-tau antibodies are provided in this document comprising i) a heavy chain comprising a variable heavy chain (VH) domain and ii) a light chain comprising a variable light chain (VL) domain, wherein the anti-tau antibody has a binding affinity to human tau of about 100 pM to about 3 nM.This document provides, in some embodiments, anti-tau antibodies comprising a VH domain that is encoded by a nucleic acid comprising at least 80%, at least 85%, at least 90%, or at least 95% sequence identity with a selected sequence of SEQ IDs: 52-56. This document provides, in some embodiments, anti-tau antibodies comprising a VL domain that is encoded by a nucleic acid comprising at least 80%, at least 85%, at least 90%, or at least 95% sequence identity with a selected sequence of SEQ IDs: 57-62. This document provides, in some embodiments, anti-tau antibodies comprising a VH domain that is encoded by a nucleic acid comprising at least 80%, at least 85%, at least 90%, or at least 95% sequence identity with a selected sequence of SEQ. ID Nos: 52-56 and a VL domain that is encoded by a nucleic acid comprising at least 80%, at least 85%, at least 90%, or at least 95% sequence identity with a sequence selected from SEQ ID Nos: 57-62. In some embodiments, anti-tau antibodies comprising a VH domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID Nos: 52 are provided in this document. Petition 870260068651, dated 10 / 07 / 2026, page 22 / 132 13 / 116 56. Anti-tau antibodies comprising a VL domain encoded by a nucleic acid comprising a sequence identical to SEQ ID NOs: 57-62 are provided in some embodiments in this document. Anti-tau antibodies comprising a VH domain encoded by a nucleic acid comprising a sequence identical to SEQ ID NOs: 52-56 and a VL domain encoded by a nucleic acid comprising a sequence identical to SEQ ID NOs: 57-62 are provided in some embodiments in this document. Incorporation by Reference

[008] All publications, patents and patent applications mentioned in this descriptive report are incorporated herein by reference to the same extent as if each individual publication, patent or patent application were specifically and individually indicated for incorporation by reference. BRIEF DESCRIPTION OF THE DRAWINGS

[009] The patent file or application contains at least one drawing executed in color. Copies of this patent publication or patent application with color drawing(s) will be provided by the Institute upon request and payment of the necessary fee.

[010] FIG. 1 represents a schematic of the single-molecule array method (Simoa®) used in this document to perform tau antibody assays described herein. After the substrate is added to the sample (bead sandwich ELISA, 1.1), the sample is added to the Simoa® Disk (1.2). The beads are given time to settle into microarray wells in the disk (one bead per well) (1.3). Then, sealing oil is used to remove excess beads to allow imaging (1.4). Beads that have a sandwich complex (positive beads) will fluoresce with the substrate and appear during imaging; beads without a sandwich complex (negative) Petition 870260068651, dated 10 / 07 / 2026, page 23 / 132 14 / 116 will still appear in imaging, but will not show fluorescence (1.5). The percentage of positive beads is converted into an AEB value (average enzymes per bead).

[011] FIGS. 2A-2D represent data for Antibody 1, Antibody 2, Antibody 3, Antibody 4, Antibody 5 and Antibody 6 in the Simoa® assay.

[012] FIG. 3 represents ELISA data.

[013] FIGS. 4A-4G represent data for immunohistochemical staining of Antibody6.

[014] FIGS. 5A-5G represent data for immunohistochemical staining of Antibody5.

[015] FIGS. 6A-6G represent data for immunohistochemical staining of Antibody2.

[016] FIG. 7 represents a diagram of an indirect ELISA assay and graphs of ELISA data performing antibody binding assay to pTau-217 peptides.

[017] FIG. 8 represents a signal-to-noise (S / N) analysis graph of the ELISA assay for binding of Antibody 2 to a pTau-217 peptide for 120 plasma-derived clinical samples and a graph of a coefficient of variation (% CV) for the ELISA assay for binding of antibody 2 to a pTau-217 peptide for 120 plasma-derived clinical samples.

[018] FIG. 9 represents calibration curve graphs (Cal curves) for a Simoa®-based pTau-217 assay using Antibody 2 in QTx-designated groups (plates) of clinical samples derived from cerebrospinal fluid (68 CSF samples) and plasma (120 plasma samples) compared to the assay using DAx p204 antibody.

[019] FIG. 10 represents a graph of the results of the pTau-217 assay based on Simoa® using Antibody 2 in corresponding individual samples derived from plasma (Y-axis) or CSF (X-axis) and statistical analysis of correlated results in an individual with a diagnosis Petition 870260068651, dated 10 / 07 / 2026, page 24 / 132 15 / 116 clinical diagnosis of non-Alzheimer's disease, uncertain diagnosis, or Alzheimer's disease.

[020] FIG. 11 represents a graph of results from the Simoa®-based pTau-217 assay using Antibody 2 per sample versus results from the Simoa®-based pTau-181 assay using Antibody 2 per sample and statistical analysis of correlated results.

[021] FIG. 12 represents a graph of the results of the Simoa®-based pTau-217 assay using Antibody 2 per sample versus results of the Simoa®-based Tau assay using the Innotest pTau 181 antibody per sample and statistical analysis of correlated results.

[022] FIG. 13 represents a graph of the results of the pTau assay based on Simoa® using Antibody 2 as the capture antibody, the DAx p204 antibody as the detector antibody and a peptide as a calibrator and statistical analysis of correlated results.

[023] FIG. 14 represents a graph of the results of the pTau-217 assay based on Simoa® using Antibody 2 pooling samples from individuals with a clinical diagnosis of Alzheimer's disease and samples from control individuals derived from CSF or plasma.

[024] FIG. 15 represents a graph of the results of the Simoa®-based pTau-217 assay using Antibody 2 at various concentrations of EDTA plasma samples and a listing graph of the coefficient of variation for each sample concentration to illustrate the accuracy of the assay.

[025] FIG. 16 represents graphs of the results of the pTau-217 assay based on Simoa® using Antibody 2 represented graphically as coefficient of variation (% CV) versus measured concentration.

[026] FIG. 17 represents a graph of the results of the pTau-217 assay based on Simoa® using Antibody 2 and the Petition 870260068651, dated 10 / 07 / 2026, page 25 / 132 16 / 116 Statistical parallelism analysis that determines whether real samples containing high concentrations of endogenous analyte provide a similar degree of detection on a standard curve after dilutions.

[027] FIG. 18 represents a graph of results from the pTau-217 assay based on Simoa® using Antibody 2 and statistical linearity analysis that determines whether sample matrices enriched with analyte detection above an upper detection limit can still provide reliable quantification after dilution within standard curve ranges for four samples plus a buffer peak.

[028] FIG. 19 represents a graph of results from the pTau-217 assay based on Simoa® using Antibody 2 and statistical linearity analysis that determines whether sample matrices enriched with analyte detection above an upper detection limit can still provide reliable quantification after dilution within standard curve ranges for three samples plus one calibration sample.

[029] FIG. 20 represents a graph of the results of the Simoa®-based pTau-217 assay using Antibody 2 in a clinical validation of a clinical memory cohort and a graph of receptor operating characteristic (ROC) analysis plotted in relation to the sensitivity of the pTau-217 assay.

[030] FIG. 21 represents a graph of the results of the pTau-217 assay based on Simoa® using Antibody 2 in groups of individuals Control and with AD dementia.

[031] FIG. 22 represents a graph of results from the Simoa®-based pTau-181 assay using a Quanterix® antibody in control and AD groups of individuals with dementia and a sample stratification graph.

[032] FIG. 23 shows graphs of results from the Simoa®-based pTau-217 assay using Antibody 2, and results from the Simoa®-based pTau-181 assay using an antibody from Petition 870260068651, dated 10 / 07 / 2026, page 26 / 132 17 / 116 Quanterix® displaying precision graphs with calculated coefficient of variation.

[033] FIG. 24 represents a clinical performance graph of several pTau Simoa®-based trials comparing sensitivity and specificity and a graph with a statistical analysis of the results.

[034] FIG. 25 represents a schematic diagram of Tau indicating the relative location of various protein domains and the locations of threonine residues that can be assayed for phosphorylation state using methods disclosed in this document.

[035] FIG. 26 shows reactivity graphs to a Tau fragment with unphosphorylated T217 (Bio-pt654) and full-length Tau (Tau441) in indirect ELISA for various antibodies.

[036] FIG. 27 shows reactivity graphs to Tau fragments with phosphorylated T181 (Bio-pt126) and phosphorylated T231 (Bio-pt146) in indirect ELISA for various antibodies.

[037] FIG. 28 represents a diagram of an assay using a pTau217 monoclonal antibody as a capture tool for various synthetic peptides and a graph of results for this assay using Antibody 2 as the capture tool.

[038] FIG. 29 represents Western blot analysis using various Tau antibodies in brain lysate samples from AD patients or control subjects. DETAILED DESCRIPTION

[039] Alzheimer's disease (AD) is a complex disease and effective treatment requires accurate diagnosis. Improved compositions and methods for detecting AD comprising enhanced antibodies for use in diagnostic and / or prognostic assays are described in this document. Petition 870260068651, dated 10 / 07 / 2026, page 27 / 132 18 / 116 Certain terminologies

[040] Throughout this disclosure, various modalities are presented in an interval format. It should be understood that the interval-format description is merely for convenience and brevity and should not be interpreted as an inflexible limitation on the scope of any modalities. Therefore, the description of an interval should be considered as having specifically revealed all possible subintervals, as well as individual numerical values ​​within that interval down to the tenth of the unit of the lower limit, unless the context clearly indicates otherwise. For example, the description of an interval such as 1 to 6 should be considered as having specifically revealed subintervals, such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., as well as individual values ​​within that interval, for example, 1.1; 2; 2.3; 5 and 5.9. This applies regardless of the amplitude of the interval.The upper and lower limits of these intermediate intervals may independently be included within the smaller intervals and are also covered by the invention, subject to any limit specifically excluded in the indicated range. When the indicated range includes one or both limits, intervals that exclude one or both of the included limits are also included in the invention, unless the context clearly indicates otherwise.

[041] The terminology used in this document is intended to describe particular modalities only and is not intended to be limiting of any modality. As used in this document, the singular forms a, an, and / or are intended to include plural forms as well, unless the context clearly indicates otherwise. It will also be understood that the terms comprise and / or comprising, when used in this descriptive report, specify the presence of resources, whole numbers, steps, operations, elements, and / or components. Petition 870260068651, dated 10 / 07 / 2026, page 28 / 132 19 / 116 declared, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components and / or groups thereof. As used in this document, the term and / or includes any and all combinations of one or more of the listed associated items.

[042] Unless specifically stated or obvious from the context, as used in this document, the term about in reference to a number or range of numbers is understood to mean the stated number and the numbers + / - 10% of it, or 10% below the listed lower limit and 10% above the listed upper limit for the values ​​listed for a range.

[043] The terms being, patient or individual are used interchangeably. None of the terms requires or is limited to a situation characterized by supervision (e.g., constant or intermittent) by a health professional (e.g., a doctor, a nursing technician, a nurse, a physician assistant, a hospital assistant or a caregiver). Additionally, these terms refer to human beings or animals.

[044] The term antibody in this document is used in the broadest sense and includes monoclonal antibodies, including intact antibodies and functional antibody fragments (antigen-binding) thereof, including antigen-binding fragments (Fab), F(ab')2 fragments, Fab' fragments, Fv fragments, recombinant IgG (rIgG) fragments, single-chain antibody fragments, including variable single-chain fragments (sFv or scFv) and single-domain antibody fragments (e.g., sdAb, sdFv, nanobody). The term encompasses genetically engineered and / or otherwise modified forms of immunoglobulins, such as intracorporeal, pepticbody, chimeric antibodies and heteroconjugated antibodies, tandem di-scFv, tandem tri-scFv. Unless otherwise indicated, the term antibody should be understood as encompassing fragments Petition 870260068651, dated 10 / 07 / 2026, page 29 / 132 20 / 116 functional antibody of the same. The term also encompasses intact or complete antibodies, including antibodies of any class or subclass, including IgG and subclasses thereof, IgM, IgE, IgA, and IgD. The antibody may comprise a constant region of rabbit IgG1. The antibody may comprise a constant region of rabbit IgG4. An antibody includes, but is not limited to, native and full-length antibodies, as well as fragments and portions thereof that retain the binding specificities thereof, such as any specific binding portion thereof, including those having any number of immunoglobulin classes and / or isotypes (e.g., IgG1, IgG2, IgG3, IgG4, IgM, IgA, IgD, IgE, and IgM); and biologically relevant fragments (antigen binding) or specific binding portions thereof, including, but not limited to, Fab, F(ab')2, Fv, and scFv (single chain or related entity).A monoclonal antibody is generally one within a composition of substantially homogeneous antibodies; thus, any individual antibodies comprised in the monoclonal antibody composition are identical except for possible naturally occurring mutations that may be present in minor quantities. A monoclonal antibody may comprise a rabbit IgG1 constant region or a rabbit IgG4 constant region.

[045] The term “complementarity-determining region” or “CDR” is a segment of the variable region of an antibody that is complementary in structure to the epitope to which the antibody binds and is more variable than the rest of the variable region. Consequently, a CDR is sometimes referred to as a hypervariable region. A variable region comprises three CDRs. CDR peptides can be obtained by constructing genes that encode the CDR of an antibody of interest. Such genes are prepared, for example, using the polymerase chain reaction to synthesize the variable region from RNA cells. Petition 870260068651, dated 10 / 07 / 2026, page 30 / 132 21 / 116 produtoras de anticorpos. Ver, por exemplo, Larrick et al., Methods: A Companion to Methods in Enzymology 2: 106 (1991); Courtenay-Luck, “Genetic Manipulation of Monoclonal Antibodies,” em Monoclonal Antibodies: Production, Engineering and Clinical Application, Ritter et al. (eds.), páginas 166-179 (Cambridge University Press 1995); e Ward et al., Genetic Manipulation and Expression of Antibodies,” em Monoclonal Antibodies: Principles and Applications, Birch et al., (eds.), páginas 137-185 (WileyLiss, Inc. 1995).

[046] The term Fab” refers to a protein containing the constant domain of the light chain and the first constant domain (CH1) of the heavy chain. Fab fragments differ from Fab' fragments by the addition of some residues at the carboxy-terminal of the CH1 domain of the heavy chain, including one or more cysteine(s) from the hinge region of the antibody. Fab'-SH is the designation in this document for Fab' in which the cysteine ​​residue(s) of the constant domains carry a free thiol group. Fab' fragments are produced by reducing the disulfide bridge of the heavy chain of the F(ab')2 fragment. Other chemical couplings of antibody fragments are also known.

[047] A single-chain variable fragment (scFv) is a fusion protein of the variable regions of the heavy (VH) and light (VL) chains of an antibody, connected to a short linker peptide of ten to about 25 amino acids. The linker is usually rich in glycine for flexibility, as well as serine or threonine for solubility, and can connect the N-terminus of the VH with the C-terminus of the VL, or vice versa. This protein maintains the specificity of the original antibody despite the removal of the constant regions and the introduction of the linker. scFv antibodies are, for example, described in Houston, JS, Methods in Enzymol. 203 (1991) 46-96). Furthermore, antibody fragments comprise single-chain polypeptides having the characteristics of a VH domain, i.e., being able to be Petition 870260068651, dated 10 / 07 / 2026, page 31 / 132 22 / 116 assemble together with a VL domain, or from a VL domain, that is, being able to assemble together with a VH domain at a functional antigen-binding site and thus providing the antigen-binding property of full-length antibodies.

[048] As used in this document, the term “percentage (%) of amino acid sequence identity” with respect to a sequence is defined as the percentage of amino acid residues in a candidate sequence that are identical to the amino acid residues in the specific sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percentage of sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for the purpose of determining the percentage of amino acid sequence identity can be achieved in several ways that are within the hands of those skilled in the art, for example, using publicly available computer software such as EMBOSS MATCHER, EMBOSS WATER, EMBOSS STRETCHER, EMBOSS NEEDLE, EMBOSS LALIGN, BLAST Software, BLAST-2, ALIGN or Megalign (DNASTAR).Experts in the field can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximum alignment along the entire length of the sequences being compared.

[049] In situations where ALIGN-2 is used for amino acid sequence comparisons, the % amino acid sequence identity of a given amino acid sequence A with or against a given amino acid sequence B (which may alternatively be formulated as a given amino acid sequence A having or comprising a certain % amino acid sequence identity to, with, or against a given amino acid sequence B) is calculated as follows: 100 times the fraction X / Y, where X is the number of residues of Petition 870260068651, dated 10 / 07 / 2026, p. 32 / 132 23 / 116 amino acids marked as identical matches by the ALIGN-2 sequence alignment program in that program's alignment of A and B, where Y is the total number of amino acid residues in B. It will be appreciated that where the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % amino acid sequence identity from A to B will not be equal to the % amino acid sequence identity from B to A. Unless specifically indicated otherwise, all % amino acid sequence identity values ​​used in this document are obtained as described in the immediately preceding paragraph using the ALIGN-2 computer program.

[050] The terms “complementarity-determining region” and “CDR”, which are synonymous with “hypervariable region” or “HVR”, are known in the art as referring to non-contiguous amino acid sequences within antibody variable regions that confer antigen specificity and / or binding affinity. In general, there are three CDRs in each variable region of the heavy chain (CDR-H1, CDR-H2, CDR-H3) and three CDRs in each variable region of the light chain (CDR-L1, CDR-L2, CDR-L3). “Structural regions” and “FR” are known in the art as referring to the non-CDR portions of the variable regions of the heavy and light chains. In general, there are four FRs in each variable region of the complete heavy chain (FR-H1, FR-H2, FR-H3, and FR-H4) and four FRs in each variable region of the complete light chain (FR-L1, FR-L2, FR-L3, and FR-L4).The precise amino acid sequence boundaries of a given CDR or FR can be easily determined using any of several well-known schemes, including those described by Kabat et al. (1991), “Sequences of Proteins of Immunological Interest,” 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (Kabat numbering scheme); Al-Lazikani et al., (1997) JMB 273, 927-948 (Chothia numbering scheme); MacCallum et al.,. Petition 870260068651, dated 10 / 07 / 2026, p. 33 / 132 24 / 116 J. Mol. Biol. 262:732-745 (1996), “Antibody-antigen interactions: Contact analysis and topography of binding sites,” J. Mol. Biol. 262, 732-745.” (numbering scheme “Contact”); Lefranc MP et al., “Unique IMGT numbering scheme for immunoglobulin and T-cell receptor variable domains and V-like domains Ig superfamily,” Dev Comp Immunol, 2003 Jan;27(1):55-77 (numbering scheme “IMGT”); Honegger A and Plückthun A, “Another numbering scheme for immunoglobulin variable domains: an automated modeling and analysis tool,” J Mol Biol, 2001 June 8;309(3):657-70, (numbering scheme “Aho”); and Whitelegg NR and Rees AR, “WAM: an improved algorithm for modeling antibodies on the WEB,” Protein Eng. December 2000; 13(12):819-24 (numbering scheme “AbM”). In certain embodiments, the antibody CDRs described in this document may be defined by a method selected from Kabat, Chothia, IMGT, Aho, AbM or combinations thereof.

[051] The limits of a given CDR or FR may vary depending on the scheme used for identification. For example, the Kabat scheme is based on structural alignments, while the Chothia scheme is based on structural information. The numbering of the Kabat and Chothia schemes is based on the most common antibody region sequence lengths, with insertions accommodated by insertion letters, for example, “30a”, and exclusions appearing in some antibodies. The two schemes place certain insertions and exclusions (“indels”) in different positions, resulting in differential numbering. The contact scheme is based on the analysis of complex crystal structures and is similar in many respects to the Chothia numbering scheme.

[052] Unless defined otherwise, all technical and scientific terms used in this document have the same meaning as commonly understood by a person of ordinary skill in the art to which the methods and compositions described belong. Petition 870260068651, dated 10 / 07 / 2026, page 34 / 132 25 / 116 in this document. Although any methods and materials similar or equivalent to those described in this document may also be used in the practice or testing of the methods and compositions described in this document, representative illustrative methods and materials are now described. Tau antibodies

[053] Antibodies that bind to tau are provided in this document. In some cases, the antibodies that bind to tau are monoclonal antibodies. In certain aspects, an anti-tau antibody is disclosed in this document. In some cases, the anti-tau antibody binds specifically to mammalian tau. In some cases, the anti-tau antibody binds specifically to human tau. In some cases, the anti-tau antibody binds specifically to an N-terminal portion of tau. In some cases, the anti-tau antibody binds specifically to an N-terminal portion of human tau. In some cases, the anti-tau antibody binds specifically to a portion of tau comprising the P2 protein domain. In some cases, the anti-tau antibody binds specifically to a portion of human tau comprising the P2 protein domain. In some cases, the anti-tau antibody binds specifically to a portion of tau comprising the P1 protein domain.In some cases, the anti-tau antibody binds specifically to a portion of human tau comprising the P1 protein domain. In some cases, the anti-tau antibody binds specifically to a portion of tau comprising both the P1 and P2 protein domains. In some cases, the anti-tau antibody binds specifically to a portion of human tau comprising both the P1 and P2 protein domains.

[054] In some embodiments, the anti-tau antibody comprises i) a heavy chain comprising a variable heavy chain (VH) domain and ii) a light chain comprising a variable light chain (VL) domain. In some embodiments, the VH domain comprises a CDR1 heavy chain sequence (HCDR1) Petition 870260068651, dated 10 / 07 / 2026, page 35 / 132 26 / 116 comprising a selected sequence of SEQ ID NOs: 1-5, a heavy chain CDR2 (HCDR2) sequence comprising a selected sequence of SEQ ID NOs: 6-9, and a heavy chain CDR3 (HCDR3) sequence comprising a selected sequence of SEQ ID NOs: 10-13. In some embodiments, the VL domain comprises a light chain CDR1 (LCDR1) sequence comprising a selected sequence of SEQ ID NOs: 14-19, a light chain CDR2 (LCDR2) sequence comprising a selected sequence of SEQ ID NOs: 20-23, and a light chain CDR3 (LCDR3) sequence comprising a selected sequence of SEQ ID NOs: 24-29.

[055] In some embodiments, the VH region of the anti-tau antibody comprises HCDR1, HCDR2 and HCDR3 sequences selected from Table 1. Table 1. Amino acid sequences of HCDR SEQ ID NO: Sequence of HCDR1 1 SQKVG 2 SYAMI 3 NYKVG 4 NYAMS 5 THAMT SEQ ID NO: Sequence of HCDR2 6 IINNYGSTYYASWAKG 7 FISRSGITYYASWAKG 8 IINYYSQTYYASWAKG 9 VINPSGSAYYATWVNG SEQ ID NO: Sequence of HCDR3 10 DPDGSIVFDI 11 EFGAVGSDYYRDAFNL 12 EFGAVGSDYYRDALRL 13 DYITAGDYYMDAFDP

[056] In some embodiments, the VH region comprises the HCDR1 sequence comprising SEQ ID NO: 1; the sequence of Petition 870260068651, dated 10 / 07 / 2026, page 36 / 132 27 / 116 In some embodiments, the VH region comprises the sequence of HCDR1 comprising SEQ ID NO: 2; the sequence of HCDR2 comprising SEQ ID NO: 7; and the sequence of HCDR3 comprising SEQ ID NO: 11. In some embodiments, the VH region comprises the sequence of HCDR1 comprising SEQ ID NO: 3; the sequence of HCDR2 comprising SEQ ID NO: 8; and the sequence of HCDR3 comprising SEQ ID NO: 10. In some embodiments, the VH region comprises the sequence of HCDR1 comprising SEQ ID NO: 4; the sequence of HCDR2 comprising SEQ ID NO: 7; and the sequence of HCDR3 comprising SEQ ID NO: 12. In some embodiments, the VH region comprises the sequence of HCDR1 comprising SEQ ID NO: 5; the HCDR2 sequence comprising SEQ ID NO: 9; and the HCDR3 sequence comprising SEQ ID NO: 13.

[057] In some embodiments, the VL region of the anti-tau antibody comprises LCDR1, LCDR2 and LCDR3 sequences selected from Table 2. Table 2. Amino acid sequences of LCDR SEQ ID NO: Sequence of LCDR1 14 QSSQSVVYNNRLS 15 QASESINSWLS 16 QASQNIYSNLA 17 QSSQSVYSNKRLA 18 QASQSIGSNLA 19 QASQSISNQLS SEQ ID NO: Sequence of LCDR2 20 GASTLAS 21 RASTLAS 22 GASNLAS 23 GASTLES SEQ ID NO: LCDR3 Sequence 24 LGSYDCSSGDCHA Petition 870260068651, dated 10 / 07 / 2026, page 37 / 132 28 / 116 25 QSYYEEDGIGYA 26 QGYDYSTAGAYP 27 AGGYDCSTGDCWT 28 QSYYEGSDIGYA 29 QQGYNRDNVDNL

[058] In some embodiments, the VL region comprises the LCDR1 sequence comprising SEQ ID NO: 14; the LCDR2 sequence comprising SEQ ID NO: 20; and the LCDR3 sequence comprising SEQ ID NO: 24. In some embodiments, the VL region comprises the LCDR1 sequence comprising SEQ ID NO: 15; the LCDR2 sequence comprising SEQ ID NO: 21; and the LCDR3 sequence comprising SEQ ID NO: 25. In some embodiments, the VL region comprises the LCDR1 sequence comprising SEQ ID NO: 16; the LCDR2 sequence comprising SEQ ID NO: 22; and the LCDR3 sequence comprising SEQ ID NO: 26. In some embodiments, the VL region comprises the LCDR1 sequence comprising SEQ ID NO: 17; the LCDR2 sequence comprising SEQ ID NO: 20; and the LCDR3 sequence comprising SEQ ID NO: 27. In some embodiments, the VL region comprises the LCDR1 sequence comprising SEQ ID NO: 18; the LCDR2 sequence comprising SEQ ID NO: 23; and the LCDR3 sequence comprising SEQ ID NO: 28.In some embodiments, the VL region comprises LCDR1 sequence comprising SEQ ID NO: 19; LCDR2 sequence comprising SEQ ID NO: 21; and LCDR3 sequence comprising SEQ ID NO: 29.

[059] In some embodiments, the anti-tau antibody is a tau antigen-binding fragment. In some embodiments, the anti-tau antibody is a chimeric antibody or a tau antigen-binding fragment. In some embodiments, the anti-tau antibody comprises an IgG-scFv, nanobody, mini-antibody, minibody, scFv-CH3 KIH, Fab-scFv-Fc KIH, Fab-scFv, scFv-CH-CL-scFv, Fab', F(ab')2, F(ab')3, F(ab')2scFv2, scFv, scFv-KIH, Fab-scFv-Fc or intrabody. In some Petition 870260068651, dated 10 / 07 / 2026, page 38 / 132 In some embodiments, the anti-tau antibody comprises a bispecific antibody. In some embodiments, the anti-tau antibody comprises a multispecific antibody. In some embodiments, the anti-tau antibody is an IgG1 antibody. In some embodiments, the anti-tau antibody is an IgG2 antibody. In some embodiments, the anti-tau antibody is an IgG4 antibody. In some embodiments, the anti-tau antibody comprises a light chain in which the light chain is a cap chain.

[060] In some embodiments, the anti-tau antibody has a binding affinity to human tau of about 100 pM to about 3 nM. In some embodiments, the anti-tau antibody has a binding affinity to human tau of about 100 pM to 300 pM. In some embodiments, the anti-tau antibody has a binding affinity to human tau of about 100 pM to 500 pM. In some embodiments, the anti-tau antibody has a binding affinity to human tau of about 100 pM to 800 pM. In some embodiments, the anti-tau antibody has a binding affinity to human tau of about 300 pM to 600 pM. In some embodiments, the anti-tau antibody has a binding affinity to human tau of about 300 pM to 900 pM. In some embodiments, the anti-tau antibody has a binding affinity to human tau of approximately 400 pM to 1 nM. In some embodiments, the anti-tau antibody has a binding affinity to human tau of approximately 500 pM to 1.5 nM.In some embodiments, the anti-tau antibody has a binding affinity to human tau of approximately 500 pM to 2 nM. In some embodiments, the anti-tau antibody has a binding affinity to human tau of approximately 600 pM to 3 nM. In some embodiments, the anti-tau antibody has a binding affinity to human tau of approximately 100 pM to approximately 3 nM.

[061] In some embodiments, the anti-tau antibody has a binding affinity to phosphorylated human tau of about 100 pM to 300 pM. In some embodiments, the anti-tau antibody has a binding affinity to phosphorylated human tau of about 100 pM Petition 870260068651, dated 10 / 07 / 2026, p. 39 / 132 30 / 116 to 500 pM. In some embodiments, the anti-tau antibody has a binding affinity to phosphorylated human tau of about 100 pM to 800 pM. In some embodiments, the anti-tau antibody has a binding affinity to phosphorylated human tau of about 300 pM to 600 pM. In some embodiments, the anti-tau antibody has a binding affinity to phosphorylated human tau of about 300 pM to 900 pM. In some embodiments, the anti-tau antibody has a binding affinity to phosphorylated human tau of about 400 pM to 1 nM. In some embodiments, the anti-tau antibody has a binding affinity to phosphorylated human tau of about 500 pM to 1.5 nM. In some embodiments, the anti-tau antibody has a binding affinity to phosphorylated human tau of approximately 500 pM to 2 nM. In some embodiments, the anti-tau antibody has a binding affinity to phosphorylated human tau of approximately 600 pM to 3 nM.

[062] Antibodies comprising any sequence as presented in Table 3 or Table 4 are described in this document. Table 3. Variable Domain, Heavy Chain Name SEQ ID NO: Amino acid sequence Antibody 1 Variable domain, Heavy Chain 30 METGLRWLLLVAVLKGVQCQSLEESGGRLVTPGTPLTLT CTVSGFSLSSQKVGWVRQAPGKGLEWIGIINNYGSTYYAS WAKGRFTISKTSTTVDLRITSLTAEDTATYFCARDPDGSIV FDIWGPGTLVTVSL Antibody 2 and Antibody 3 Variable domain, Heavy Chain 31 METGLRWLLLVAVLKGVQCQSVEESGGRLVTPGTPLTLT CTVSGFSLSSYAMIWVRQAPGKGLEWIGFISRSGITYYASW AKGRFTISKTSTTVDLKMTSLTTEDTATYFCAREFGAVGS DYYRDAFNLWGPGTLVTVSS Antibody 4 Variable domain, Heavy Chain 32 METGLRWLLLVAVLKGVQCQSLEESGGRLVTPGTPLTLT CTVSGFSLNNYKVGWVRQAPGKGLEWIGIINYYSQTYYA SWAKGRFTISKTSTTVDLKLTSPTTEDTATYFCARDPDGS IVFDIWGPGTLVTVSL Petition 870260068651, dated 10 / 07 / 2026, page 40 / 132 31 / 116 Antibody 5 Variable Domain, Heavy Chain 33 METGLRWLLLVAVLKGVQCQSVEESGGGLVTPGGTLTLT CTVSGFSLSNYAMSWVRQAPGKGLEWIGFISRSGITYYAS WAKGRFTISKTSTTVDLKITSPTTEDTAAYFCAREFGAVGS DYYRDALRLWGPGTLVTVSS Antibody 6 Variable Domain, Heavy Chain 34 METGLRWLLLVAVLKGVQCQSLEESGGRLVTPGTPLTLT CTVSGIDLSTHAMTWVRQAPGKGLEWIGVINPSGSAYYA TWVNGRFTISKTSTTVDLKITSPTTGDTAKYFCARDYITA GDYYMDAFDPWGPGTLVTVSS Table 4. Variable Domain, Light Chain Name SEQ ID NO: Amino acid sequence Antibody Variable domain, Light Chain 1 35 MDTRAPTQLLGLLLLWLPGATFAQVLTQTASPVSAAVG GTVTINCQSSQSVVYNNRLSWFQQKPGQPPKLLIYGAST LASGVPSRFKGSGSGTQFTLTISDVQCDDAATYYCLGSY DCSSGDCHAFGGGTEVVVK Antibody Variable domain, Light Chain 2 36 MDMRAPTQLLGLLLLWLPGARCADIVMTQTPASVEAA VGGTVTINCQASESINSWLSWYQQKPGQPPNLLIYRAST LASGVPSRFSGGGSGTEYTLTISDLECADAVTYYCQSYY EEDGIGYAFGGGTEVVVE Antibody Variable domain, Light Chain 3 37 MDMRAPTQLLGLLLLWLPGARCADIVMTQTPSSVSAA VGGTVTINCQASQNIYSNLAWYQQKPGQRPRLLIYGAS NLASGVPSRFKGSRSGTEFTLTISDLECADAATYYCQGY DYSTAGAYPFGGGTAVVVK Variable Domain Antibody, Light Chain 4 38 MDTRAPTQLLGLLLLWLPGATFAQVLTQTASPVSAAV GSTVTINCQSSQSVYSNKRLAWFQLKPGQPPKLLIYGAS TLASGVPSRFKGSGSGTQFTLTISDVQCDDAATYYCAGG YDCSTGDCWTFGGGTEVVVT Variable Domain Antibody, Light Chain 5 39 MDMRAPTQLLGLLLLWLPGARCADIVMTQTPSSVSAA VGGTVTIKCQASQSIGSNLAWYQQKPGQPPKLLIYGAS TLESGVPSRFKGSGSGTEYTLTISDLECADAATYYCQSY YEGSDIGYAFGGGTEVVVE Antibody 6 Variable domain,40 MDTRAPTQLLGLLLLWLPGARCADIVMTQTPASVSAA VGGTVTIKCQASQSISNQLSWYQQKSGQPPKLLIYRAS TLASGVPSRFKGSGSGTEFTLTISDLECADAATYYCQQ, Petition 870260068651, dated 10 / 07 / 2026, page 41 / 132 32 / 116 Light Chain GYNRDNVDNLFGGGTEVVVK

[063] In some embodiments, the variable domain, heavy chain region (VH) comprises an amino acid sequence that has at least 70% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34. In some embodiments, the VH comprises an amino acid sequence that has at least 80% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34. In some embodiments, the VH comprises an amino acid sequence that has at least 85% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34. In some embodiments, the VH comprises an amino acid sequence that has at least 90% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34.In some embodiments, VH comprises an amino acid sequence that has at least 91% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence that has at least 92% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence that has at least 93% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence that has at least 94% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence that has at least 95% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34.In some forms, VH comprises an amino acid sequence that has at least 96% sequence identity. Petition 870260068651, dated 10 / 07 / 2026, p. 42 / 132 33 / 116 with the amino acid sequence according to any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence that has at least 97% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence that has at least 98% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence that has at least 99% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence according to any of the SEQ ID NOs: 30-34.

[064] In some embodiments, VH comprises an amino acid sequence of at least 50 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 60 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 70 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 80 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 90 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 100 consecutive amino acid residues from any of the SEQ ID NOs: 30-34.In some embodiments, the VH comprises an amino acid sequence of at least 105 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, the VH comprises an amino acid sequence of... Petition 870260068651, dated 10 / 07 / 2026, p. 43 / 132 34 / 116 at least 110 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, the VH comprises an amino acid sequence of at least 115 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, the VH comprises an amino acid sequence of at least 120 consecutive amino acid residues from any of the SEQ ID NOs: 30-34.

[065] In some embodiments, VH comprises an amino acid sequence of at least 50 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 80% sequence identity with at least 50 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 60 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 80% sequence identity with at least 60 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 70 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 80% sequence identity with at least 70 consecutive amino acid residues from any of the SEQ ID NOs: 30-34.In some embodiments, the VH comprises an amino acid sequence of at least 80 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 80% sequence identity with at least 80 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, the VH comprises an amino acid sequence of at least 90 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least less than 80% sequence identity with at least 90 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises a sequence of... Petition 870260068651, dated 10 / 07 / 2026, p. 44 / 132 35 / 116 amino acids from at least 100 consecutive amino acid residues of any of the SEQ ID NOs: 30-34 and has at least 80% sequence identity with at least 100 consecutive amino acid residues of any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 105 consecutive amino acid residues of any of the SEQ ID NOs: 30-34 and has at least 80% sequence identity with at least 105 consecutive amino acid residues of any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 110 consecutive amino acid residues of any of the SEQ ID NOs: 30-34 and has at least 80% sequence identity with at least 110 consecutive amino acid residues of any of the SEQ ID NOs: 30-34.In some embodiments, VH comprises an amino acid sequence of at least 115 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 80% sequence identity with at least 115 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 120 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 80% sequence identity with at least 120 consecutive amino acid residues from any of the SEQ ID NOs: 30-34.

[066] In some embodiments, VH comprises an amino acid sequence of at least 50 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 90% sequence identity with at least 50 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 60 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least Petition 870260068651, dated 10 / 07 / 2026, p. 45 / 132 36 / 116 less than 90% sequence identity with at least 60 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 70 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 90% sequence identity with at least 70 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 80 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 90% sequence identity with at least 80 consecutive amino acid residues from any of the SEQ ID NOs: 30-34.In some embodiments, the VH comprises an amino acid sequence of at least 90 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 90% sequence identity with at least 90 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, the VH comprises an amino acid sequence of at least 100 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 90% sequence identity with at least 100 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, the VH comprises an amino acid sequence of at least 105 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 90% sequence identity with at least 105 consecutive amino acid residues from any of the SEQ ID NOs: 30-34.In some embodiments, VH comprises an amino acid sequence of at least 110 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 90% sequence identity with at least 110 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises a sequence of... Petition 870260068651, dated 10 / 07 / 2026, p. 46 / 132 37 / 116 amino acids of at least 115 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 90% sequence identity with at least 115 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, the VH comprises an amino acid sequence of at least 120 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 90% sequence identity with at least 120 consecutive amino acid residues from any of the SEQ ID NOs: 30-34.

[067] In some embodiments, VH comprises an amino acid sequence of at least 50 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 95% sequence identity with at least 50 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 60 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 95% sequence identity with at least 60 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 70 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 95% sequence identity with at least 70 consecutive amino acid residues from any of the SEQ ID NOs: 30-34.In some embodiments, the VH comprises an amino acid sequence of at least 80 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 95% sequence identity with at least 80 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, the VH comprises an amino acid sequence of at least 90 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least... Petition 870260068651, dated 10 / 07 / 2026, p. 47 / 132 38 / 116 less than 95% sequence identity with at least 90 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 100 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 95% sequence identity with at least 100 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 105 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 95% sequence identity with at least 105 consecutive amino acid residues from any of the SEQ ID NOs: 30-34.In some embodiments, VH comprises an amino acid sequence of at least 110 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 95% sequence identity with at least 110 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 115 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 95% sequence identity with at least 115 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 120 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 95% sequence identity with at least 120 consecutive amino acid residues from any of the SEQ ID NOs: 30-34.

[068] In some embodiments, VH comprises an amino acid sequence of at least 100 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 99% sequence identity with at least 100 consecutive amino acid residues from any of the SEQ ID NOs: 30 Petition 870260068651, dated 10 / 07 / 2026, p. 48 / 132 39 / 116 34. In some embodiments, VH comprises an amino acid sequence of at least 105 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 99% sequence identity with at least 105 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 110 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 99% sequence identity with at least 110 consecutive amino acid residues from any of the SEQ ID NOs: 30-34. In some embodiments, VH comprises an amino acid sequence of at least 115 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 99% sequence identity with at least 115 consecutive amino acid residues from any of the SEQ ID NOs: 30-34.In some embodiments, VH comprises an amino acid sequence of at least 120 consecutive amino acid residues from any of the SEQ ID NOs: 30-34 and has at least 99% sequence identity with at least 120 consecutive amino acid residues from any of the SEQ ID NOs: 30-34.

[069] In some embodiments, the variable domain, light chain (VL) region comprises an amino acid sequence that has at least 70% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40. In some embodiments, the VL comprises an amino acid sequence that has at least 80% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40. In some embodiments, the VL comprises an amino acid sequence that has at least 85% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40. In some embodiments, the VL comprises an amino acid sequence that has at least 90% Petition 870260068651, dated 10 / 07 / 2026, p. 49 / 132 40 / 116 sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40. In some embodiments, the VL comprises an amino acid sequence that has at least 91% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40. In some embodiments, the VL comprises an amino acid sequence that has at least 92% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40. In some embodiments, the VL comprises an amino acid sequence that has at least 93% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40. In some embodiments, the VL comprises an amino acid sequence that has at least 94% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40.In some embodiments, VL comprises an amino acid sequence that has at least 95% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40. In some embodiments, VL comprises an amino acid sequence that has at least 96% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40. In some embodiments, VL comprises an amino acid sequence that has at least 97% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40. In some embodiments, VL comprises an amino acid sequence that has at least 98% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40. In some embodiments, VL comprises an amino acid sequence that has at least 99% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40.In some forms, the VL comprises an amino acid sequence according to any of the SEQ ID NOs: 35-40. Petition 870260068651, dated 10 / 07 / 2026, p. 50 / 132 41 / 116

[070] In some embodiments, VL comprises an amino acid sequence of at least 50 consecutive amino acid residues from any of the SEQ ID NOs: 35-40. In some embodiments, VL comprises an amino acid sequence of at least 60 consecutive amino acid residues from any of the SEQ ID NOs: 35-40. In some embodiments, VL comprises an amino acid sequence of at least 70 consecutive amino acid residues from any of the SEQ ID NOs: 35-40. In some embodiments, VL comprises an amino acid sequence of at least 80 consecutive amino acid residues from any of the SEQ ID NOs: 35-40. In some embodiments, VL comprises an amino acid sequence of at least 90 consecutive amino acid residues from any of the SEQ ID NOs: 35-40. In some embodiments, the VL comprises an amino acid sequence of at least 100 consecutive amino acid residues from any of the SEQ ID NOs: 35-40.In some embodiments, the VL comprises an amino acid sequence of at least 105 consecutive amino acid residues from any of the SEQ ID NOs: 35-40.

[071] In some embodiments, VL comprises an amino acid sequence of at least 50 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 80% sequence identity with at least 50 consecutive amino acid residues from any of the SEQ ID NOs: 35-40. In some embodiments, VL comprises an amino acid sequence of at least 60 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 80% sequence identity with at least 60 consecutive amino acid residues from any of the SEQ ID NOs: 35-40. In some embodiments, VL comprises an amino acid sequence of at least 70 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 80% sequence identity with at least 70 residues Petition 870260068651, dated 10 / 07 / 2026, p. 51 / 132 42 / 116 consecutive amino acids from any of the SEQ ID NOs: 3540. In some embodiments, VL comprises an amino acid sequence of at least 80 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 80% sequence identity with at least 80 consecutive amino acid residues from any of the SEQ ID NOs: 3540. In some embodiments, VL comprises an amino acid sequence of at least 90 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 80% sequence identity with at least 90 consecutive amino acid residues from any of the SEQ ID NOs: 3540. In some embodiments, VL comprises an amino acid sequence of at least 100 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 80% sequence identity with at least 100 consecutive amino acid residues. consecutive numbers of any of the SEQ IDs: 3540.In some embodiments, VL comprises an amino acid sequence of at least 105 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 80% sequence identity with at least 105 consecutive amino acid residues from any of the SEQ ID NOs: 35-40.

[072] In some embodiments, VL comprises an amino acid sequence of at least 50 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 90% sequence identity with at least 50 consecutive amino acid residues from any of the SEQ ID NOs: 35-40. In some embodiments, VL comprises an amino acid sequence of at least 60 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 90% sequence identity with at least 60 consecutive amino acid residues from any of the SEQ ID NOs: 35-40. In some embodiments, VL comprises a sequence of Petition 870260068651, dated 10 / 07 / 2026, p. 52 / 132 43 / 116 amino acids of at least 70 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 90% sequence identity with at least 70 consecutive amino acid residues from any of the SEQ ID NOs: 35-40. In some embodiments, the VL comprises an amino acid sequence of at least 80 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 90% sequence identity with at least 80 consecutive amino acid residues from any of the SEQ ID NOs: 35-40. In some embodiments, the VL comprises an amino acid sequence of at least 90 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 90% sequence identity with at least 90 consecutive amino acid residues from any of the SEQ ID NOs: 35-40.In some embodiments, the VL comprises an amino acid sequence of at least 100 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 90% sequence identity with at least 100 consecutive amino acid residues from any of the SEQ ID NOs: 35-40. In some embodiments, the VL comprises an amino acid sequence of at least 105 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 90% sequence identity with at least 105 consecutive amino acid residues from any of the SEQ ID NOs: 35-40.

[073] In some embodiments, VL comprises an amino acid sequence of at least 50 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 95% sequence identity with at least 50 consecutive amino acid residues from any of the SEQ ID NOs: 35-40. In some embodiments, VL comprises an amino acid sequence of at least 60 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least Petition 870260068651, dated 10 / 07 / 2026, p. 53 / 132 44 / 116 less than 95% sequence identity with at least 60 consecutive amino acid residues from any of the SEQ ID NOs: 35-40. In some embodiments, VL comprises an amino acid sequence of at least 70 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 95% sequence identity with at least 70 consecutive amino acid residues from any of the SEQ ID NOs: 35-40. In some embodiments, VL comprises an amino acid sequence of at least 80 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 95% sequence identity with at least 80 consecutive amino acid residues from any of the SEQ ID NOs: 35-40.In some embodiments, the VL comprises an amino acid sequence of at least 90 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 95% sequence identity with at least 90 consecutive amino acid residues from any of the SEQ ID NOs: 35-40. In some embodiments, the VL comprises an amino acid sequence of at least 100 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 95% sequence identity with at least 100 consecutive amino acid residues from any of the SEQ ID NOs: 35-40. In some embodiments, the VL comprises an amino acid sequence of at least 105 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 95% sequence identity with at least 105 consecutive amino acid residues from any of the SEQ ID NOs: 35-40.In some embodiments, VL comprises an amino acid sequence of at least 100 consecutive amino acid residues from any of the SEQ ID NOs: 35-40 and has at least 99% sequence identity with at least 100 consecutive amino acid residues from any of the SEQ ID NOs: 35-40. In some embodiments, VL comprises a sequence of... Petition 870260068651, dated 10 / 07 / 2026, p. 54 / 132 45 / 116 amino acids from at least 105 consecutive amino acid residues of any of the SEQ ID NOs: 35-40 and has at least 99% sequence identity with at least 105 consecutive amino acid residues of any of the SEQ ID NOs: 35-40.

[074] In some embodiments, VH comprises an amino acid sequence that has at least 70% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34; and VL comprises an amino acid sequence having at least 70% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40. In some embodiments, VH comprises an amino acid sequence having at least 80% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34; and VL comprises an amino acid sequence that has at least 80% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40.In some embodiments, VH comprises an amino acid sequence that has at least 85% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34; and VL comprises an amino acid sequence having at least 85% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40. In some embodiments, VH comprises an amino acid sequence having at least 90% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34; and VL comprises an amino acid sequence that has at least 90% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40.In some embodiments, VH comprises an amino acid sequence that has at least 91% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34; and VL comprises an amino acid sequence. Petition 870260068651, dated 10 / 07 / 2026, p. 55 / 132 46 / 116 having at least 91% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 3540. In some embodiments, VH comprises an amino acid sequence having at least 92% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34; and VL comprises an amino acid sequence having at least 92% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 3540. In some embodiments, VH comprises an amino acid sequence having at least 93% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34; and VL comprises an amino acid sequence that has at least 93% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 3540.In some embodiments, VH comprises an amino acid sequence that has at least 94% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34; and VL comprises an amino acid sequence having at least 94% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40. In some embodiments, VH comprises an amino acid sequence having at least 95% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34; and VL comprises an amino acid sequence that has at least 95% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40.In some embodiments, VH comprises an amino acid sequence that has at least 96% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34; and VL comprises an amino acid sequence that has at least 96% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40. In some embodiments, VH comprises a sequence of... Petition 870260068651, dated 10 / 07 / 2026, p. 56 / 132 47 / 116 amino acids that have at least 97% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34; and VL comprises an amino acid sequence having at least 97% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40. In some embodiments, VH comprises an amino acid sequence having at least 98% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34; and VL comprises an amino acid sequence that has at least 98% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40.In some embodiments, VH comprises an amino acid sequence that has at least 99% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 30-34; and VL comprises an amino acid sequence that has at least 99% sequence identity with the amino acid sequence according to any of the SEQ ID NOs: 35-40.

[075] In some embodiments, VH comprises an amino acid sequence that has at least 70% sequence identity with the amino acid sequence according to SEQ ID NO: 30; and VL comprises an amino acid sequence having at least 70% sequence identity with the amino acid sequence according to SEQ ID NO: 35. In some embodiments, VH comprises an amino acid sequence having at least 80% sequence identity with the amino acid sequence according to SEQ ID NO: 30; and VL comprises an amino acid sequence having at least 80% sequence identity with the amino acid sequence according to SEQ ID NO: 35. In some embodiments, VH comprises an amino acid sequence having at least 85% sequence identity with the amino acid sequence according to SEQ ID NO: 30; and VL comprises an amino acid sequence that has at least 85% sequence identity with the amino acid sequence according to SEQ ID NO: 30. Petition 870260068651, dated 10 / 07 / 2026, p. 57 / 132 48 / 116 sequence with the amino acid sequence according to SEQ ID NO: 35. In some embodiments, VH comprises an amino acid sequence having at least 90% sequence identity with the amino acid sequence according to SEQ ID NO: 30; and VL comprises an amino acid sequence having at least 90% sequence identity with the amino acid sequence according to SEQ ID NO: 35. In some embodiments, VH comprises an amino acid sequence having at least 91% sequence identity with the amino acid sequence according to SEQ ID NO: 30; and VL comprises an amino acid sequence that has at least 91% sequence identity with the amino acid sequence according to SEQ ID NO: 35.In some embodiments, VH comprises an amino acid sequence having at least 92% sequence identity with the amino acid sequence according to SEQ ID NO: 30; and VL comprises an amino acid sequence having at least 92% sequence identity with the amino acid sequence according to SEQ ID NO: 35. In some embodiments, VH comprises an amino acid sequence having at least 93% sequence identity with the amino acid sequence according to SEQ ID NO: 30; and VL comprises an amino acid sequence that has at least 93% sequence identity with the amino acid sequence according to SEQ ID NO: 35.In some embodiments, VH comprises an amino acid sequence having at least 94% sequence identity with the amino acid sequence according to SEQ ID NO: 30; and VL comprises an amino acid sequence having at least 94% sequence identity with the amino acid sequence according to SEQ ID NO: 35. In some embodiments, VH comprises an amino acid sequence having at least 95% sequence identity with the amino acid sequence according to SEQ ID NO: 30; and VL comprises an amino acid sequence that has at least 95% sequence identity with the amino acid sequence according to SEQ ID. Petition 870260068651, dated 10 / 07 / 2026, p. 58 / 132 49 / 116 NO: 35. In some embodiments, VH comprises an amino acid sequence having at least 96% sequence identity with the amino acid sequence according to SEQ ID NO: 30; and VL comprises an amino acid sequence having at least 96% sequence identity with the amino acid sequence according to SEQ ID NO: 35. In some embodiments, VH comprises an amino acid sequence having at least 97% sequence identity with the amino acid sequence according to SEQ ID NO: 30; and VL comprises an amino acid sequence that has at least 97% sequence identity with the amino acid sequence according to SEQ ID NO: 35.In some embodiments, VH comprises an amino acid sequence that has at least 98% sequence identity with the amino acid sequence according to SEQ ID NO: 30; and VL comprises an amino acid sequence having at least 98% sequence identity with the amino acid sequence according to SEQ ID NO: 35. In some embodiments, VH comprises an amino acid sequence having at least 99% sequence identity with the amino acid sequence according to SEQ ID NO: 30; and VL comprises an amino acid sequence that has at least 99% sequence identity with the amino acid sequence according to SEQ ID NO: 35.

[076] In some embodiments, VH comprises an amino acid sequence that has at least 70% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence having at least 70% sequence identity with the amino acid sequence according to SEQ ID NO: 36. In some embodiments, VH comprises an amino acid sequence having at least 80% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence that has at least 80% sequence identity with the amino acid sequence according to SEQ ID NO: 36. In some Petition 870260068651, dated 10 / 07 / 2026, p. 59 / 132 In 50 / 116 embodiments, VH comprises an amino acid sequence that has at least 85% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence having at least 85% sequence identity with the amino acid sequence according to SEQ ID NO: 36. In some embodiments, VH comprises an amino acid sequence having at least 90% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence that has at least 90% sequence identity with the amino acid sequence according to SEQ ID NO: 36.In some embodiments, VH comprises an amino acid sequence that has at least 91% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence having at least 91% sequence identity with the amino acid sequence according to SEQ ID NO: 36. In some embodiments, VH comprises an amino acid sequence having at least 92% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence that has at least 92% sequence identity with the amino acid sequence according to SEQ ID NO: 36.In some embodiments, VH comprises an amino acid sequence that has at least 93% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence having at least 93% sequence identity with the amino acid sequence according to SEQ ID NO: 36. In some embodiments, VH comprises an amino acid sequence having at least 94% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence having at least 94% sequence identity with the amino acid sequence according to SEQ ID NO: 36. In some embodiments, VH comprises an amino acid sequence having at least... Petition 870260068651, dated 10 / 07 / 2026, p. 60 / 132 51 / 116 VH comprises an amino acid sequence having at least 95% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence having at least 95% sequence identity with the amino acid sequence according to SEQ ID NO: 36. In some embodiments, VH comprises an amino acid sequence having at least 96% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence having at least 96% sequence identity with the amino acid sequence according to SEQ ID NO: 36. In some embodiments, VH comprises an amino acid sequence having at least 97% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence that has at least 97% sequence identity with the amino acid sequence according to SEQ ID NO: 36.In some embodiments, VH comprises an amino acid sequence having at least 98% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence having at least 98% sequence identity with the amino acid sequence according to SEQ ID NO: 36. In some embodiments, VH comprises an amino acid sequence having at least 99% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence that has at least 99% sequence identity with the amino acid sequence according to SEQ ID NO: 36.

[077] In some embodiments, VH comprises an amino acid sequence that has at least 70% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence having at least 70% sequence identity with the amino acid sequence according to SEQ ID NO: 37. In some embodiments, VH comprises an amino acid sequence having at least 80% identity Petition 870260068651, dated 10 / 07 / 2026, p. 61 / 132 52 / 116 of sequence with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence having at least 80% sequence identity with the amino acid sequence according to SEQ ID NO: 37. In some embodiments, VH comprises an amino acid sequence having at least 85% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence having at least 85% sequence identity with the amino acid sequence according to SEQ ID NO: 37. In some embodiments, VH comprises an amino acid sequence having at least 90% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence that has at least 90% sequence identity with the amino acid sequence according to SEQ ID NO: 37.In some embodiments, VH comprises an amino acid sequence that has at least 91% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence having at least 91% sequence identity with the amino acid sequence according to SEQ ID NO: 37. In some embodiments, VH comprises an amino acid sequence having at least 92% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence that has at least 92% sequence identity with the amino acid sequence according to SEQ ID NO: 37.In some embodiments, VH comprises an amino acid sequence that has at least 93% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence having at least 93% sequence identity with the amino acid sequence according to SEQ ID NO: 37. In some embodiments, VH comprises an amino acid sequence having at least 94% sequence identity with the amino acid sequence according to SEQ ID NO: 31. Petition 870260068651, dated 10 / 07 / 2026, p. 62 / 132 53 / 116 with SEQ ID NO: 31; and VL comprises an amino acid sequence having at least 94% sequence identity with the amino acid sequence according to SEQ ID NO: 37. In some embodiments, VH comprises an amino acid sequence having at least 95% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence having at least 95% sequence identity with the amino acid sequence according to SEQ ID NO: 37. In some embodiments, VH comprises an amino acid sequence having at least 96% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence that has at least 96% sequence identity with the amino acid sequence according to SEQ ID NO: 37.In some embodiments, VH comprises an amino acid sequence that has at least 97% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence having at least 97% sequence identity with the amino acid sequence according to SEQ ID NO: 37. In some embodiments, VH comprises an amino acid sequence having at least 98% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence that has at least 98% sequence identity with the amino acid sequence according to SEQ ID NO: 37.In some embodiments, VH comprises an amino acid sequence that has at least 99% sequence identity with the amino acid sequence according to SEQ ID NO: 31; and VL comprises an amino acid sequence that has at least 99% sequence identity with the amino acid sequence according to SEQ ID NO: 37.

[078] In some embodiments, VH comprises an amino acid sequence that has at least 70% sequence identity with the amino acid sequence according to SEQ ID NO: 32; and the Petition 870260068651, dated 10 / 07 / 2026, p. 63 / 132 54 / 116 VL comprises an amino acid sequence having at least 70% sequence identity with the amino acid sequence according to SEQ ID NO: 38. In some embodiments, VH comprises an amino acid sequence having at least 80% sequence identity with the amino acid sequence according to SEQ ID NO: 32; and VL comprises an amino acid sequence having at least 80% sequence identity with the amino acid sequence according to SEQ ID NO: 38. In some embodiments, VH comprises an amino acid sequence having at least 85% sequence identity with the amino acid sequence according to SEQ ID NO: 32; and VL comprises an amino acid sequence that has at least 85% sequence identity with the amino acid sequence according to SEQ ID NO: 38.In some embodiments, VH comprises an amino acid sequence having at least 90% sequence identity with the amino acid sequence according to SEQ ID NO: 32; and VL comprises an amino acid sequence having at least 90% sequence identity with the amino acid sequence according to SEQ ID NO: 38. In some embodiments, VH comprises an amino acid sequence having at least 91% sequence identity with the amino acid sequence according to SEQ ID NO: 32; and VL comprises an amino acid sequence that has at least 91% sequence identity with the amino acid sequence according to SEQ ID NO: 38.In some embodiments, VH comprises an amino acid sequence having at least 92% sequence identity with the amino acid sequence according to SEQ ID NO: 32; and VL comprises an amino acid sequence having at least 92% sequence identity with the amino acid sequence according to SEQ ID NO: 38. In some embodiments, VH comprises an amino acid sequence having at least 93% sequence identity with the amino acid sequence according to SEQ ID NO: 32; and VL comprises an amino acid sequence that has at least... Petition 870260068651, dated 10 / 07 / 2026, p. 64 / 132 55 / 116 93% sequence identity with the amino acid sequence according to SEQ ID NO: 38. In some embodiments, VH comprises an amino acid sequence having at least 94% sequence identity with the amino acid sequence according to SEQ ID NO: 32; and VL comprises an amino acid sequence having at least 94% sequence identity with the amino acid sequence according to SEQ ID NO: 38. In some embodiments, VH comprises an amino acid sequence having at least 95% sequence identity with the amino acid sequence according to SEQ ID NO: 32; and VL comprises an amino acid sequence that has at least 95% sequence identity with the amino acid sequence according to SEQ ID NO: 38.In some embodiments, VH comprises an amino acid sequence having at least 96% sequence identity with the amino acid sequence according to SEQ ID NO: 32; and VL comprises an amino acid sequence having at least 96% sequence identity with the amino acid sequence according to SEQ ID NO: 38. In some embodiments, VH comprises an amino acid sequence having at least 97% sequence identity with the amino acid sequence according to SEQ ID NO: 32; and VL comprises an amino acid sequence that has at least 97% sequence identity with the amino acid sequence according to SEQ ID NO: 38.In some embodiments, VH comprises an amino acid sequence that has at least 98% sequence identity with the amino acid sequence according to SEQ ID NO: 32; and VL comprises an amino acid sequence having at least 98% sequence identity with the amino acid sequence according to SEQ ID NO: 38. In some embodiments, VH comprises an amino acid sequence having at least 99% sequence identity with the amino acid sequence according to SEQ ID NO: 32; and VL comprises an amino acid sequence that has at least 99% sequence identity with the amino acid sequence of... Petition 870260068651, dated 10 / 07 / 2026, p. 65 / 132 56 / 116 in accordance with SEQ ID NO: 38.

[079] In some embodiments, VH comprises an amino acid sequence that has at least 70% sequence identity with the amino acid sequence according to SEQ ID NO: 33; and VL comprises an amino acid sequence having at least 70% sequence identity with the amino acid sequence according to SEQ ID NO: 39. In some embodiments, VH comprises an amino acid sequence having at least 80% sequence identity with the amino acid sequence according to SEQ ID NO: 33; and VL comprises an amino acid sequence that has at least 80% sequence identity with the amino acid sequence according to SEQ ID NO: 39.In some embodiments, VH comprises an amino acid sequence having at least 85% sequence identity with the amino acid sequence according to SEQ ID NO: 33; and VL comprises an amino acid sequence having at least 85% sequence identity with the amino acid sequence according to SEQ ID NO: 39. In some embodiments, VH comprises an amino acid sequence having at least 90% sequence identity with the amino acid sequence according to SEQ ID NO: 33; and VL comprises an amino acid sequence that has at least 90% sequence identity with the amino acid sequence according to SEQ ID NO: 39.In some embodiments, VH comprises an amino acid sequence having at least 91% sequence identity with the amino acid sequence according to SEQ ID NO: 33; and VL comprises an amino acid sequence having at least 91% sequence identity with the amino acid sequence according to SEQ ID NO: 39. In some embodiments, VH comprises an amino acid sequence having at least 92% sequence identity with the amino acid sequence according to SEQ ID NO: 33; and VL comprises an amino acid sequence that has at least 92% sequence identity with the amino acid sequence according to SEQ ID. Petition 870260068651, dated 10 / 07 / 2026, p. 66 / 132 57 / 116 In some embodiments, VH comprises an amino acid sequence having at least 93% sequence identity with the amino acid sequence according to SEQ ID NO: 33; and VL comprises an amino acid sequence having at least 93% sequence identity with the amino acid sequence according to SEQ ID NO: 39. In some embodiments, VH comprises an amino acid sequence having at least 94% sequence identity with the amino acid sequence according to SEQ ID NO: 33; and VL comprises an amino acid sequence that has at least 94% sequence identity with the amino acid sequence according to SEQ ID NO: 39.In some embodiments, VH comprises an amino acid sequence having at least 95% sequence identity with the amino acid sequence according to SEQ ID NO: 33; and VL comprises an amino acid sequence having at least 95% sequence identity with the amino acid sequence according to SEQ ID NO: 39. In some embodiments, VH comprises an amino acid sequence having at least 96% sequence identity with the amino acid sequence according to SEQ ID NO: 33; and VL comprises an amino acid sequence that has at least 96% sequence identity with the amino acid sequence according to SEQ ID NO: 39.In some embodiments, VH comprises an amino acid sequence having at least 97% sequence identity with the amino acid sequence according to SEQ ID NO: 33; and VL comprises an amino acid sequence having at least 97% sequence identity with the amino acid sequence according to SEQ ID NO: 39. In some embodiments, VH comprises an amino acid sequence having at least 98% sequence identity with the amino acid sequence according to SEQ ID NO: 33; and VL comprises an amino acid sequence that has at least 98% sequence identity with the amino acid sequence according to SEQ ID NO: 39. In some embodiments, VH comprises a sequence of... Petition 870260068651, dated 10 / 07 / 2026, p. 67 / 132 58 / 116 amino acids that have at least 99% sequence identity with the amino acid sequence according to SEQ ID NO: 33; and VL comprises an amino acid sequence that has at least 99% sequence identity with the amino acid sequence according to SEQ ID NO: 39.

[080] In some embodiments, VH comprises an amino acid sequence that has at least 70% sequence identity with the amino acid sequence according to SEQ ID NO: 34; and VL comprises an amino acid sequence having at least 70% sequence identity with the amino acid sequence according to SEQ ID NO: 40. In some embodiments, VH comprises an amino acid sequence having at least 80% sequence identity with the amino acid sequence according to SEQ ID NO: 34; and VL comprises an amino acid sequence that has at least 80% sequence identity with the amino acid sequence according to SEQ ID NO: 40.In some embodiments, VH comprises an amino acid sequence having at least 85% sequence identity with the amino acid sequence according to SEQ ID NO: 34; and VL comprises an amino acid sequence having at least 85% sequence identity with the amino acid sequence according to SEQ ID NO: 40. In some embodiments, VH comprises an amino acid sequence having at least 90% sequence identity with the amino acid sequence according to SEQ ID NO: 34; and VL comprises an amino acid sequence that has at least 90% sequence identity with the amino acid sequence according to SEQ ID NO: 40.In some embodiments, VH comprises an amino acid sequence that has at least 91% sequence identity with the amino acid sequence according to SEQ ID NO: 34; and VL comprises an amino acid sequence having at least 91% sequence identity with the amino acid sequence according to SEQ ID NO: 40. In some embodiments, VH comprises an amino acid sequence having at least... Petition 870260068651, dated 10 / 07 / 2026, p. 68 / 132 59 / 116 VH comprises an amino acid sequence having at least 92% sequence identity with the amino acid sequence according to SEQ ID NO: 34; and VL comprises an amino acid sequence having at least 92% sequence identity with the amino acid sequence according to SEQ ID NO: 40. In some embodiments, VH comprises an amino acid sequence having at least 93% sequence identity with the amino acid sequence according to SEQ ID NO: 34; and VL comprises an amino acid sequence having at least 93% sequence identity with the amino acid sequence according to SEQ ID NO: 40. In some embodiments, VH comprises an amino acid sequence having at least 94% sequence identity with the amino acid sequence according to SEQ ID NO: 34; and VL comprises an amino acid sequence that has at least 94% sequence identity with the amino acid sequence according to SEQ ID NO: 40.In some embodiments, VH comprises an amino acid sequence having at least 95% sequence identity with the amino acid sequence according to SEQ ID NO: 34; and VL comprises an amino acid sequence having at least 95% sequence identity with the amino acid sequence according to SEQ ID NO: 40. In some embodiments, VH comprises an amino acid sequence having at least 96% sequence identity with the amino acid sequence according to SEQ ID NO: 34; and VL comprises an amino acid sequence that has at least 96% sequence identity with the amino acid sequence according to SEQ ID NO: 40.In some embodiments, VH comprises an amino acid sequence having at least 97% sequence identity with the amino acid sequence according to SEQ ID NO: 34; and VL comprises an amino acid sequence having at least 97% sequence identity with the amino acid sequence according to SEQ ID NO: 40. In some embodiments, VH comprises an amino acid sequence having at least 98% sequence identity with the sequence of... Petition 870260068651, dated 10 / 07 / 2026, p. 69 / 132 60 / 116 amino acids according to SEQ ID NO: 34; and VL comprises an amino acid sequence having at least 98% sequence identity with the amino acid sequence according to SEQ ID NO: 40. In some embodiments, VH comprises an amino acid sequence having at least 99% sequence identity with the amino acid sequence according to SEQ ID NO: 34; and VL comprises an amino acid sequence that has at least 99% sequence identity with the amino acid sequence according to SEQ ID NO: 40.

[081] In some embodiments, antibodies or antibody fragments comprising a heavy chain sequence at least about 90% identical to a sequence as presented in any of the SEQ ID NOs: 41, 43, 46, 48 and 50 are described in this document. In some cases, the antibodies or antibody fragments comprise a heavy chain sequence of at least or about 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity with any of the SEQ ID NOs: 41, 43, 46, 48 and 50.

[082] In some embodiments, antibodies or antibody fragments comprising a light chain sequence at least about 90% identical to a sequence as presented in any of the SEQ ID NOs: 42, 44, 45, 47, 49, and 51 are described in this document. In some cases, the antibodies or antibody fragments comprise a light chain sequence of at least or about 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with any of the SEQ ID NOs: 42, 44, 45, 47, 49, and 51.

[083] In some embodiments, antibodies or antibody fragments are described in this document comprising a heavy chain sequence at least about 90% identical to a sequence as presented in any of the SEQ ID Nos: 41, 43, 46, 48 and 50 and a light chain sequence by Petition 870260068651, dated 10 / 07 / 2026, p. 70 / 132 61 / 116 less about 90% identical to a sequence as presented in any of the SEQ ID NOs: 42, 44, 45, 47, 49 and 51. In some cases, the antibodies or antibody fragments comprise a heavy chain sequence of at least or about 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to any of the SEQ ID NOs: 41, 43, 46, 48 and 50 and a light chain sequence of at least or about 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with any of the SEQ ID Nos: 42, 44, 45, 47, 49, and 51. Table 5. Heavy Chain and Light Chain Sequences Name SEQ ID NO: Amino acid sequence Antibody 1 Heavy Chain 41 METGLRWLLLVAVLKGVQCQSLEESGGRLVTPGTPLTLTCTVSG FSLSSQKVGWVRQAPGKGLEWIGIINNYGSTYYASWAKGRFTIS KTSTTVDLRITSLTAEDTATYFCARDPDGSIVFDIWGPGTLVTVSL GQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSG TLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNT KVDKTVAPSTCSKPTCPPPELLGRSSVFIFPPKPKDTLMISRTPEV TCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVV STLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKV YTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYK TTPAVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALHNH YTQKSISRSPGK Antibody 1 Light Chain 42 MDTRAPTQLLGLLLLWLPGATFAQVLTQTASPVSAAVGGTVTI NCQSSQSVVYNNRLSWFQQKPGQPPKLLIYGASTLASGVPSRF KGSGSGTQFTLTISDVQCDDAATYYCLGSYDCSSGDCHAFGGG TEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVT VTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSH KEYTCKVTQGTTSVVQSFNRGDC Petition 870260068651, dated 10 / 07 / 2026, page 71 / 132 62 / 116 Anticorpo 2 and Anticorpo 3 Cadeia Pesada 43 METGLRWLLLVAVLKGVQCQSVEESGGRLVTPGTPLTLTCTVSG FSLSSYAMIWVRQAPGKGLEWIGFISRSGITYYASWAKGRFTISK TSTTVDLKMTSLTTEDTATYFCAREFGAVGSDYYRDAFNLWGP GTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPV TVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNV AHPATNTKVDKTVAPSTCSKPTCPPPELLGRSSVFIFPPKPKDTL MISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQ FNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKAR GQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNG KAEDNYKTTPAVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVM HEALHNHYTQKSISRSPGK Anticorpo 2 Cadeia Leve 44 MDMRAPTQLLGLLLLWLPGARCADIVMTQTPASVEAAVGGTV TINCQASESINSWLSWYQQKPGQPPNLLIYRASTLASGVPSRFSG GGSGTEYTLTISDLECADAVTYYCQSYYEEDGIGYAFGGGTEVV VEGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWE VDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYT CKVTQGTTSVVQSFNRGDC Anticorpo 3 Cadeia Leve 45 MDMRAPTQLLGLLLLWLPGARCADIVMTQTPSSVSAAVGGTVT INCQASQNIYSNLAWYQQKPGQRPRLLIYGASNLASGVPSRFKG SRSGTEFTLTISDLECADAATYYCQGYDYSTAGAYPFGGGTAVV VKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCK VTQGTTSVVQSFNRGDC Antibody 4 Heavy Chain 46 METGLRWLLLVAVLKGVQCQSLEESGGRLVTPGTPLTLTCTVS GFSLNNYKVGWVRQAPGKGLEWIGIINYYSQTYYASWAKGRF TISKTSTTVDLKLTSPTTEDTATYFCARDPDGSIVFDIWGPGTLV TVSLGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVT WNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAH PATNTKVDKTVVPSTCSKPTCPPPELLGRSSVFIFPPKPKDTLMI SRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQF 47 MDTRAPTQLLGLLLLWLPGATFAQVLTQTASPVSAAVGSTVTIN CQSSQSVYSNKRLAWFQLKPGQPPKLLIYGASTLASGVPSRFKG SGSGTQFTLTISDVQCDDAATYYCAGGYDCSTGDCWTFGGGTE VVVTGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVT WEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKE YTCKVTQGTTSVVQSFNRGDC Petition 870260068651, dated 10 / 07 / 2026, page 72 / 132 63 / 116 Antibody 5 Heavy Chain 48 METGLRWLLLVAVLKGVQCQSVEESGGGLVTPGGTLTLTCTVS GFSLSNYAMSWVRQAPGKGLEWIGFISRSGITYYASWAKGRFT ISKTSTTVDLKITSPTTEDTAAYFCAREFGAVGSDYYRDALRLW GPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLP EPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPVT CNVAHPATNTKVDKTVAPSTCSKPTCPPPELLGRSSVFIFPPKPK DTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPL REQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKT ISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVE WEKNGKAEDNYKTTPAVLDSDGSYFLYSKLSVPTSEWQRGDV FTCSVMHEALHNHYTQKSISRSPGK Antibody 5 Light Chain 49 MDMRAPTQLLGLLLLWLPGARCADIVMTQTPSSVSAAVGGTVT IKCQASQSIGSNLAWYQQKPGQPPKLLIYGASTLESGVPSRFKGS GSGTEYTLTISDLECADAATYYCQSYYEGSDIGYAFGGGTEVVV EGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVD GTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSHKEYTCKV TQGTTSVVQSFNRGDC Antibody 6 Heavy Chain 50 METGLRWLLLVAVLKGVQCQSLEESGGRLVTPGTPLTLTCTVS GIDLSTHAMTWVRQAPGKGLEWIGVINPSGSAYYATWVNGRF TISKTSTTVDLKITSPTTGDTAKYFCARDYITAGDYYMDAFDPW GPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVVSVTSSSQPV TCNVAHPATNTKVDKTVAPSTCSKPTCPPPELLGRSSVFIFPPPKP KDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPP LREQQFNSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEK TISKARGQPLEPKVYTMGPPREELSRSVSLTCMINGFYPSDISV EWEKNGKAEDNYKTTPAVLDSDGSSYFLYSKLSVPTSEWQRGD VFTCSVMHEALHNHYTQKSISRSPGK Anticorpo 6 Cadeia Leve 51 MDTRAPTQLLGLLLLWLPGARCADIVMTQTPASVSAAVGGTV TIKCQASQSISNQLSWYQQKSGQPPKLLIYRASTLASGVPSRFK GSGSGTEFTLTISDLECADAATYYCQQGYNRDNVDNLFGGGT EVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTV TWEVDGTTQTTGIENSKTPQNSADCTYNLSSTLTLTSTQYNSH KEYTCKVTQGTTSVVQSFNRGDC

[084] In some embodiments, the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising at least 80%, at least 85%, at least 90%, or at least 95% sequence identity with a selected sequence of SEQ IDs 52-56. In some embodiments, the anti-tau antibody comprises a VL domain that is encoded by a nucleic acid comprising at least 80%, at least 85%, at least 90%, or at least 95% sequence identity with Petition 870260068651, dated 10 / 07 / 2026, page 73 / 132 64 / 116 a selected sequence of SEQ ID NOs: 57-62. The nucleic acid sequences for VH domains for anti-tau-tau antibodies described in this document are listed in Table 6, and the nucleic acid sequences for VL domains for anti-tau-tau antibodies described in this document are listed in Table 7. In some embodiments, the anti-tau-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 52. In some embodiments, the anti-tau-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 53. In some embodiments, the anti-tau-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 54.In some embodiments, the anti-tau-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 55. In some embodiments, the anti-tau-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 56. In some embodiments, the anti-tau-tau antibody comprises a VL domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 57. In some embodiments, the anti-tau-tau antibody comprises a VL domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 58. In some embodiments, the anti-tau-tau antibody comprises a VL domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 59.In some embodiments, the anti-tau antibody comprises a VL domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 60. In some embodiments, the anti-tau antibody... Petition 870260068651, dated 10 / 07 / 2026, p. 74 / 132 65 / 116 comprises a VL domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 61. In some embodiments, the anti-tau antibody comprises a VL domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 62. In some embodiments, the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 52 and a VL domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 57. In some embodiments, the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 53 and a VL domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 54. ID NO: 58.In some embodiments, the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 53 and a VL domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 59. In some embodiments, the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 54 and a VL domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 60. In some embodiments, the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 55 and a VL domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 61.In some embodiments, the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising at least 90% sequence identity with tau. Petition 870260068651, dated 10 / 07 / 2026, page 75 / 132 66 / 116 SEQ ID NO: 563 and a VL domain that is encoded by a nucleic acid comprising at least 90% sequence identity with SEQ ID NO: 62. In some embodiments, the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 52. In some embodiments, the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 53. In some embodiments, the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 54. In some embodiments, the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 55. In some embodiments, the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 56.In some embodiments, the anti-tau antibody comprises a VL domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 57. In some embodiments, the anti-tau antibody comprises a VL domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 58. In some embodiments, the anti-tau antibody comprises a VL domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 59. In some embodiments, the anti-tau antibody comprises a VL domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 60. In some cases, embodiments, the anti-tau antibody comprises a VL domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 61. In some embodiments, the anti-tau antibody comprises a VL domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 62.In some embodiments, the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising... Petition 870260068651, dated 10 / 07 / 2026, page 76 / 132 67 / 116 a sequence identical to SEQ ID NO: 52 and a VL domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 57. In some embodiments, the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 53 and a VL domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 58. In some embodiments, the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 53 and a VL domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 59. In some embodiments, the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 54 and a VL domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 60.In some embodiments, the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 55 and a VL domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 61. In some embodiments, the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 56 and a VL domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 62. Table 6. Nucleic acid sequences encoding VH domains SEQ ID NO: Nucleic acid sequences coding for VH domains CTGGAATGGATCGGAATCATTAATAATTATGGTAGCACATACTACGC GAGCTGGGCGAAAGGCCGATTCACCATCTCGAAAACCTCGACCACA Petition 870260068651, dated 10 / 07 / 2026, p. 77 / 132 68 / 116 GTGGATCTGAGAATCACCAGTCTGACGGCCGAGGACACGGCCACCT ATTTCTGTGCCCGTGATCCTGATGGTAGTATTGTCTTTGACATCTGGG GCCCAGGCACCCTTGTCACCGTCTCCTTG 53 ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGG TGTCCAGTGTCAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGC CTGGGACACCCCTGACACTCACCTGCACCGTCTCTGGATTCTCCCTC AGTAGCTATGCAATGATCTGGGTCCGCCAGGCTCCAGGGAAGGGGC TGGAATGGATCGGATTCATTAGTCGTAGTGGTATCACATACTACGCG AGCTGGGCAAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGG TGGATCTGAAAATGACCAGTCTGACAACCGAGGACACGGCCACCTA TTTCTGTGCCAGAGAATTCGGTGCTGTTGGTAGTGATTATTATAGGG ACGCCTTTAACTTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCA 54 ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGG TGTCCAGTGTCAGTCGCTGGAGGAGTCCGGGGGTCGCCTGGTCACG CCTGGGACACCCCTGACACTCACCTGCACAGTCTCTGGATTTTCCCT AAATAACTACAAAGTGGGCTGGGTCCGCCAGGCTCCAGGAAAGGG GCTGGAATGGATCGGAATCATTAACTATTATAGTCAGACATACTAC GCGAGCTGGGCCAAAGGCCGATTCACCATCTCGAAAACCTCGACC ACGGTG GATCTGAAGCTCACCAGTCCGACAACCGAAGACACGGCC ACCTATTTCTGTGCCCGTGATCCTGATGGTAGTATTGTCTTTGACAT CTGGGGCCCAGGCACCCTTGTCACCGTCTCCTTG 55ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGG TGTCCAGTGTCAGTCGGTGGAGGAGTCCGGAGGAGGCCTGGTAACG CCTGGAGGAACCCTGACACTCACCTGCACCGTCTCTGGATTCTCCCT CAGTAACTATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGG CTGGAATGGATCGGATTCATTAGTCGTAGTGGTATTACATACTACGC GAGCTGGGCAAAAGGCCGATTCACCATCTCCAAAACCTCGACCACG GTGGATCTGAAAATCACCAGTCCGACGACCGAGGACACGGCCGCCT ATTTCTGTGCCAGAGAATTCGGTGCTGTTGGTAGTGATTATTATAGG GACGCCTTGAGGTTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCT CA 56 ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGG TGTCCAGTGTCAGTCGCTGGAGGAGTCCGGGGGTCGCCTGGTAACG CCTGGGACACCCCTGACACTCACCTGCACAGTCTCTGGAATCGACCT CAGTACCCATGCAATGACCTGGGTCCGCCAGGCTCCAGGAAAGGGG CTGGAATGGATCGGAGTCATTAATCCTAGTGGTAGCGCATACTACG CGACCTGGGTGAATGGCCGATTCACCATCTCCAAAACCTCGACCACG GTGGATCTGAAAATCACCAGTCCGACAACCGGGGACACGGCCAAGT ATTTCTGTGCCAGAGATTATATTACTGCGGGTGATTATTATATGGAT GCTTTTGATCCCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCA Petição 870260068651, de 10 / 07 / 2026, pág. 78 / 132 69 / 116 Table 7. Nucleic acid sequences encoding domains VL SEQ ID NO: Sequências de ácidos nucleicos que codificam domínios VL 57 ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTC TGGCTCCCAGGTGCCACATTTGCCCAAGTGCTGACCCAGACTGCA TCCCCCGTGTCTGCGGCTGTTGGAGGCACAGTCACCATCAATTGC CAGTCCAGTCAGAGTGTTGTATATAACAACCGCTTATCCTGGTTT CAACAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTATGGTGCA TCCACTCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGA TCTGGGACACAGTTCACTCTCACCATCAGCGACGTGCAGTGTGAC GATGCTGCCACTTACTACTGTCTAGGCTCCTATGATTGTAGTAGT GGTGATTGCCATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAA 58 ATGGACATGAGGGCCCCCACTCAGCTGCTGGGGCTCCTACTGCTC TGGCTCCCAGGTGCCAGATGTGCTGACATTGTGATGACCCAGACT CCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAA TTGCCAAGCCAGTGAGAGCATTAATAGTTGGTTGTCCTGGTATCA GCAGAAACCAGGGCAGCCTCCCAACCTCCTGATCTACAGGGCATC CACTCTGGCATCTGGGGTCCCATCGCGGTTCAGTGGCGGTGGATC TGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGTGCCGA TGCTGTCACTTATTACTGTCAAAGCTATTATGAGGAGGATGGTAT TGGTTATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCGAA 59 ATGGACATGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTG GCTCCCAGGTGCCAGATGTGCTGACATTGTGATGACCCAGACTCCATCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAATTGCCAG GCCAGTCAGAACATTTACAGCAATTTAGCCTGGTATCAGCAGAAAC CAGGGCAGCGTCCCAGGCTCCTGATCTATGGCGCATCCAATCTGGCA TCTGGGGTCCCATCGCGGTTCAAAGGCAGTAGATCTGGGACAGAGTT CACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTACT ACTGTCAAGGCTATGATTATAGTACTGCTGGTGCCTATCCTTTCGGC GGAGGGACCGCGGTGGTGGTCAAA 60 ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTG GCTCCCAGGTGCCACATTTGCCCAAGTGCTGACCCAGACTGCATCGC CCGTGTCTGCGGCTGTGGGAAGCACAGTCACCATCAATTGCCAGTCC AGTCAGAGCGTTTATAGTAACAAGCGCTTAGCCTGGTTTCAGCTGAA ACCAGGGCAGCCTCCCAAGCTCCTGATCTATGGTGCATCCACACTGG CATCTGGGGTCCCATCGCGATTCAAGGGCAGTGGATCTGGGACACAG TTCACTCTCACCATCAGCGACGTGCAGTGTGACGATGCTGCCACTTA CTACTGTGCAGGCGGTTATGATTGTAGTACTGGTGATTGTTGGACTTT CGGCGGAGGGACCGAGGTGGTGGTCACA Petição 870260068651, de 10 / 07 / 2026, pág. 79 / 132 70 / 116 61 ATGGACATGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTC TGGCTCCCAGGTGCCAGATGTGCTGACATCGTGATGACCCAGACT CCATCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAAG TGCCAGGCCAGTCAGAGCATTGGTAGTAATTTAGCCTGGTATCAG CAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTATGGTGCATCC ACTCTGGAATCTGGGGTCCCATCGCGGTTTAAAGGCAGTGGATCT GGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGTGCCGAT GCTGCCACTTACTACTGTCAAAGCTATTATGAGGGTAGTGATATT GGTTATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCGAA 62 ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTC TGGCTCCCAGGTGCCAGATGTGCTGACATCGTGATGACCCAGACT CCAGCCTCTGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAAG TGCCAGGCCAGTCAGAGCATTAGCAACCAACTATCCTGGTATCAG CAGAAATCAGGGCAGCCTCCCAAGCTCCTGATCTACAGGGCATCT ACTCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCT GGGACAGAGTTCACTCTCACCATCAGCGACCTGGAGTGTGCCGAT GCTGCCACTTACTACTGTCAACAGGGTTATAATAGAGATAATGTT GATAATCTTTTCGGCGGAGGGACCGAGGTGGTGGTCAAA

[085] In some embodiments, the anti-tau antibody comprises a heavy chain that is encoded by a nucleic acid comprising a sequence identical to a sequence selected from SEQ ID NOs: 63-67. In some embodiments, the anti-tau antibody comprises a light chain that is encoded by a nucleic acid comprising a sequence identical to a sequence selected from SEQ ID NOs: 68-73. The nucleic acid sequences for heavy chains for anti-tau antibodies described in this document are listed in Table 8 and the nucleic acid sequences for light chains for anti-tau antibodies described in this document are listed in Table 9. The nucleic acid sequences listed in Table 8 and Table 9 can be used in the in vitro antibody production process described in this document. In some embodiments, the anti-tau antibody comprises a heavy chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 63.In some embodiments, the anti-tau antibody comprises a heavy chain that is encoded by a [Tu symbol]. Petition 870260068651, dated 10 / 07 / 2026, p. 80 / 132 71 / 116 nucleic acid antibody comprising a sequence identical to SEQ ID NO: 64. In some embodiments, the anti-tau antibody comprises a heavy chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 65. In some embodiments, the anti-tau antibody comprises a heavy chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 66. In some embodiments, the anti-tau antibody comprises a heavy chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 67. In some embodiments, the anti-tau antibody comprises a light chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 68. In some embodiments, the anti-tau antibody comprises a light chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 69.In some embodiments, the anti-tau antibody comprises a light chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 70. In some embodiments, the anti-tau antibody comprises a light chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 71. In some embodiments, the anti-tau antibody comprises a light chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 72. In some embodiments, the anti-tau antibody comprises a light chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 73. In some embodiments, the anti-tau antibody comprises a heavy chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 63 and a light chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 68.In some embodiments, the anti-tau antibody comprises a heavy chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 64 and a light chain that is... Petition 870260068651, dated 10 / 07 / 2026, p. 81 / 132 72 / 116 encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 69. In some embodiments, the anti-tau antibody comprises a heavy chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 64 and a light chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 70. In some embodiments, the anti-tau antibody comprises a heavy chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 65 and a light chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 71. In some embodiments, the anti-tau antibody comprises a heavy chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 66 and a light chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 72.In some embodiments, the anti-tau antibody comprises a heavy chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 67 and a light chain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NO: 73. Table 8. Nucleic acid sequences encoding heavy chains SEQ ID NO: Sequências de ácidos nucleicos que codificam cadeias pesadas 63 ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGGTG TCCAGTGTCAGTCGCTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGG GACACCCCTGACACTCACCTGCACAGTCTCTGGATTTTCCCTCAGTAGC CAGAAAGTGGGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAATGG ATCGGAATCATTAATAATTATGGTAGCACATACTACGCGAGCTGGGCG AAAGGCCGATTCACCATCTCGAAAACCTCGACCACAGTGGATCTGAGA ATCACCAGTCTGACGGCCGAGGACACGGCCACCTATTTCTGTGCCCGTG ATCCTGATGGTAGTATTGTCTTTGACATCTGGGGCCCAGGCACCCTTGTC ACCGTCTCCTTGGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCC CCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGT CAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCAC CCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGC CTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCC GTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAG Petição 870260068651, de 10 / 07 / 2026, pág. 82 / 132 73 / 116 ACCGTTGCGCCCTCGACATGCAGCAAGCCCACGTGCCCACCCCCTGAA CTCCTGGGGCGATCCTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACA CCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACG TGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAAC GAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAAC AGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGG CTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCC GGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGG AGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGC AGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGAC ATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAA GACCACGCCGGCCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAG CAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCAC CTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTC CATCTCCCGCTCTCCGGGTAAATGA 64 ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGG TGTCCAGTGTCAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGC CTGGGACACCCCTGACACTCACCTGCACCGTCTCTGGATTCTCCCTC AGTAGCTATGCAATGATCTGGGTCCGCCAGGCTCCAGGGAAGGGGC TGGAATGGATCGGATTCATTAGTCGTAGTGGTATCACATACTACGCG AGCTGGGCAAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTGAAAATGACCAGTCTGACAACCGAGGACAGGCCACCTA TTTCTGTGCCAGAGAATTCGGTGCTGTTGGTAGTGATTATTATAGGGA CGCCTTTAACTTGTGGGGCCAGGCACCCTGGTCACCGTCTCCTCAGG GCAACCTAAGGCTCCATCAGTCTTCCACTGGCCCCTGCTGCGGGGA CACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCT CCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACAATGG GGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTG AGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAAC GTGGCCCACCCAGCCACCAACCAAAGTGGACAAGACCGTTGCGCCC TCGACATGCAGCAAGCCCACGTGCCCACCCCTGAACTCCTGGGGCGA TCCTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCT CACGCACCCCGAGGTCACATGCGTGGTGGACGTGAGCCAGGAT GACCCCGAGGTGCAGTTCACATGGTACATAACAACGAGCAGGTGCG CACCGCCGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCC GCGTGGTCAGCACCCTCCCATCGCGCACCAGGACTGGCTGAGGGGC AAGGAGTTCAAGTCCAACAACAAGGCACTCCCGGCCCCAT CGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAG GTCTACACCATGGCCCTCCCGGGAGGAGCTGGAGCCAGGTCGGT CAGCCTGACCTGCATGATCAACGGCTTTACCCTTCCCGACATCTCGGT GGAGTGGGAGAAAGGAACGGGAGGCAGAGGCAGAGACAACTACAAGACCACGCCGGCCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTC TCATGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCC GTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTC Petition 870260068651, dated 10 / 07 / 2026, page 83 / 132 74 / 116 CCGCTCTCCGGGTAAATGA 65 ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGG TGTCCAGTGTCAGTCGCTGGAGGAGTCCGGGGGTCGCCTGGTCACG CCTGGGACACCCCTGACACTCACCTGCACAGTCTCTGGATTTTCCCT AAATAACTACAAAGTGGGCTGGGTCCGCCAGGCTCCAGGAAAGGG GCTGGAATGGATCGGAATCATTAACTATTATAGTCAGACATACTAC GCGAGCTGGGCCAAAGGCCGATTCACCATCTCGAAAACCTCGACC ACGGTG GATCTGAAGCTCACCAGTCCGACAACCGAAGACACGGCC ACCTATTTCTGTGCCCGTGATCCTGATGGTAGTATTGTCTTTGACAT CTGGGGCCCAGGCACCCTTGTCACCGTCTCCTTGGGGCAACCTAAGG CTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGC TCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCC AGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCA CCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCG TGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCC CACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGTGCCCTCGAC ATGCAGCAAGCCCACGTGCCCACCCCCTGAACTCCTGGGGCGATCCT CTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCAC GCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGAC CCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCAC CGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGGCCACCAGACTGGCTGAGGGGCAAG GAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGA GAAAACCATCTCCAAAGCCAGAGGGCAGCCCTGGAGCGAAGGTCT ACACCATGGGCCCTCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGC CTGACCTGCATGATCAACGGCTTCTACCCTTCGACATCTCGGTGGAG TGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGG CCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAG TGCCCACGAGTGAGTGGCAGCGGGCGACGTCTTCACCTGCTCCGTGA TGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCT CTCCGGGTAAATGA 66 ATGGAGACTGGGCTGCGCTGGCTTCCTGGTCGTGTGCTCAAAGG TGTCCAGTGTCAGTCGGTGGAGGAGTCCGGAGGAGGCCTGGTAACG CCTGGAGGAACCCTGACACTCACCTGCACCGTCTCTGGATTCTCCCT CAGTAACTATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGG CTGGAATGGATCGGATTCATTAGTCGTAGTGGTATTACATACTACGC GAGCTGGGCAAAAGGCCGATTCACCATCTCCAAAACCTCGACC GTGGATCTGAAAATCACCAGTCCGACGAGGACACGGCCGCCT ATTTCTGTGCCGAGAAGTCGGTGCTTTGGTAGTGATTATTATAGG GACGCCTTGAGGTTTGGGCCCAGGCACCCTGGTCACCGGTCTCCTC AGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCG GGGACACACCACGCCTCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCA CCAATGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTC Petition 870260068651, dated 10 / 07 / 2026, page 84 / 132 75 / 116 TACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGT CACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGA CCGTTGCGCCCTCGACATGCAGCAAGCCCACGTGCCCACCCCCTGAAC TCCTGGGGCGATCCTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACA CCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACG TGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAAC GAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAA CAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTG GCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCC CGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTG GAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAG CAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGA CATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTAC AAGACCACGCCGGCCGTGCTGGACAGCGACGGCTCCTACTTCCTCTA CAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTC TTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCA GAAGTCCATCTCCCGCTCTCCGGGTAAATGA 67 ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGG TGTCCAGTGTCAGTCGCTGGAGGAGTCCGGGGGTCGCCTGGTAACG CCTGGGACACCCCTGACACTCACCTGCACAGTCTCTGGAATCGACCT CAGTACCCATGCAATGACCTGGGTCCGCCAGGCTCCAGGAAAGGGGCTGGAATGGATCGGAGTCATTAATCCTAGTGGTAGCGCATACTACG CGACCTGGGTGAATGGCCGATTCACCATCTCCAAAACCTCGACCACG GTGGATCTGAAAATCACCAGTCCGACAACCGGGGACACGGCCAAGT ATTTCTGTGCCAGAGATTATATTACTGCGGGTGATTATTATATGGAT GCTTTTGATCCCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGG GCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGG ACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTAC CTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAA TGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTC GCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCT GCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTT GCGCCCTCGACATGCAGCAAGCCCACGTGCCCACCCCCTGAACTCCT GGGGCGATCCTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCC TCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTG AGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACG AGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAA CAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACT GGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACT CCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCC CTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGA GCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGA CAACTACAAGACCACGCCGGCCGTGCTGGACAGCGACGGCTCCTA Petition 870260068651, dated 10 / 07 / 2026, p. 85 / 132 76 / 116 CTTCCTCTACAGCAAGCTCTCAGTGCCCACGAAGTGAGTGGCAGCGG GGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACC ACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATGA Table 9. Nucleic acid sequences encoding light chains SEq ID Nucleic acid sequences that encode light chains NO: 68 ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTG GCTCCCAGGTGCCACATTTGCCCAAGTGCTGACCCAGACTGCATCCC CCGTGTCTGCGGCTGTTGGAGGCACAGTCACCATCAATTGCCAGTCC AGTCAGAGTGTTGTATATAACAACCGCTTATCCTGGTTTCAACAGAA ACCAGGGCAGCCTCCCAAGCTCCTGATCTATGGTGCATCCACTCTGG CATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACACA GTTCACTCTCACCATCAGCGACGTGCAGTGTGACGATGCTGCCACTT ACTACTGTCTAGGCTCCTATGATTGTAGTAGTGGTGATTGCCATGCT TTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCAC CTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGA ACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCAC CGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAG AACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCA GCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAG AGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAG CTTCAATAGGGGTGACTGTTAG 69 ATGGACATGAGGGCCCCCACTCAGCTGCTGGGGCTCCTACTGCTCTG GCTCCCAGGTGCCAGATGTGCTGACATTGTGATGACCCAGACTCCAG CCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAATTGCCAA GCCAGTGAGAGCATTAATAGTTGGTTGTCCTGGTATCAGCAGAAACC AGGGCAGCCTCCCAACCTCCTGATCTACAGGGCATCCACTCTGGCATCTGGGGTCCCATCGCGGTTCAGTGGCGGTGGATCTGGGACAGAGTAC ACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGTCACTTATTA CTGTCAAAGCTATTATGAGGAGGATGGTATTGGTTATGCTTTCGGCG GAGGGACCGAGGTGGTGGTCGAAGGTGATCCAGTTGCACCTACTGT CCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTCA CCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCACC TGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGTA AAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCACT CTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCT GCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAATAG GGGTGACTGTTAG 70 ATGGACATGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTG Petição 870260068651, de 10 / 07 / 2026, pág. 86 / 132 77 / 116 GCTCCCAGGTGCCAGATGTGCTGACATTGTGATGACCCAGACTCCAT CCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAATTGCCAG GCCAGTCAGAACATTTACAGCAATTTAGCCTGGTATCAGCAGAAACC AGGGCAGCGTCCCAGGCTCCTGATCTATGGCGCATCCAATCTGGCAT CTGGGGTCCCATCGCGGTTCAAAGGCAGTAGATCTGGGACAGAGTT CACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTACT ACTGTCAAGGCTATGATTATAGTACTGCTGGTGCCTATCCTTTCGGC GGAGGGACCGCGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTG TCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTC ACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCAC CTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAG TAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGC ACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTAC ACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCA ATAGGGGTGACTGTTAG 71 ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTG GCTCCCAGGTGCCACATTTGCCCAAGTGCTGACCCAGACTGCATCGC CCGTGTCTGCGGCTGTGGGAAGCACAGTCACCATCAATTGCCAGTCC AGTCAGAGCGTTTATAGTAACAAGCGCTTAGCCTGGTTTCAGCTGAA ACCAGGGCAGCCTCCCAAGCTCCTGATCTATGGTGCATCCACACTGG CATCTGGGGTCCCATCGCGATTCAAGGGCAGTGGATCTGGGACACAGTTCACTCTCACCATCAGCGACGTGCAGTGTGACGATGCTGCCACTTA CTACTGTGCAGGCGGTTATGATTGTAGTACTGGTGATTGTTGGACTTT CGGCGGAGGGACCGAGGTGGTGGTCACAGGTGATCCAGTTGCACCT ACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAAC AGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCG TCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAA CAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCA GCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTA CACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTC AATAGGGGTGACTGTTAG 72 ATGGACATGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTG GCTCCCAGGTGCCAGATGTGCTGACATCGTGATGACCCAGACTCCAT CCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAG GCCAGTCAGAGCATTGGTAGTAATTTAGCCTGGTATCAGCAGAAACC AGGGCAGCCTCCCAAGCTCCTGATCTATGGTGCATCCACTCTGGAAT CTGGGGTCCCATCGCGGTTTAAAGGCAGTGGATCTGGGACAGAGTA CACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTACT ACTGTCAAAGCTATTATGAGGGTAGTGATATTGGTTATGCTTTCGGC GGAGGGACCGAGGTGGTGGTCGAAGGTGATCCAGTTGCACCTACTG Petição 870260068651, de 10 / 07 / 2026, pág. 87 / 132 78 / 116 TCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTC ACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCAC CTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGT AAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCA CTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACAC CTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAAT AGGGGTGACTGTTAG 73 ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCTG GCTCCCAGGTGCCAGATGTGCTGACATCGTGATGACCCAGACTCCAG CCTCTGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAG GCCAGTCAGAGCATTAGCAACCAACTATCCTGGTATCAGCAGAAAT CAGGGCAGCCTCCCAAGCTCCTGATCTACAGGGCATCTACTCTGGCA TCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGAGTT CACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTACT ACTGTCAACAGGGTTATAATAGAGATAATGTTGATAATCTTTTCGGC GGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACTG TCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAGTC ACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGTCAC CTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAACAGT AAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCAGCA CTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTCAAT AGGGGTGACTGTTAG Methods of Revelation

[086] Methods for detecting phosphorylated tau in a sample from an individual using antibodies described in this document are disclosed in this document. In some embodiments, phosphorylated tau is selected from the group consisting of pTau-212, pTau-217, pTau-231, pTau-214, and pTau-220. In some embodiments, the methods for detecting phosphorylated tau in a sample from an individual using antibodies described in this document comprise improved specificity and sensitivity.

[087] Methods for detecting phosphorylated tau in a sample from an individual are described in this document, comprising: performing an assay on the sample using an antibody or antibody fragment that binds to phosphorylated tau. These are described in this document. Petition 870260068651, dated 10 / 07 / 2026, page 88 / 132 79 / 116 document methods for detecting phosphorylated tau in a sample from an individual comprising: performing an immunoassay on the sample using an antibody or antibody fragment that binds to phosphorylated tau. In some embodiments, the phosphorylated tau is selected from the group consisting of pTau-212, pTau-217, pTau-231, pTau-214, pTau-220 and pTau-181. In some embodiments, the phosphorylated tau is selected from the group consisting of pTau-212, pTau-217, pTau-231, pTau-214 and pTau-220. In some embodiments, the phosphorylated tau is pTau-217. In some embodiments, the tau The phosphorylated tau is pTau-231. In some embodiments, the phosphorylated tau is pTau-181. In some embodiments, the phosphorylated tau is pTau-212. In some embodiments, the phosphorylated tau is pTau-217. In some embodiments, the phosphorylated tau is pTau-214. In some embodiments, the phosphorylated tau is pTau-220. In some embodiments, the tau In some embodiments, phosphorylated tau is pTau-181 and pTau-217. In some embodiments, phosphorylated tau is pTau-181 and pTau-231. In some embodiments, phosphorylated tau is pTau-217 and pTau-231. In some embodiments, phosphorylated tau is pTau-181, pTau-217, and pTau-231.

[088] Methods for detecting phosphorylated tau in a sample from an individual are further described in this document comprising: performing an assay on the sample using an antibody or antibody fragment that binds to multiple phosphorylated tau proteins. In some embodiments, the methods detect pTau217 and pTau-231. In some embodiments, the methods detect pTau212 and pTau-217. In some embodiments, the methods detect pTau212 and pTau-231. In some embodiments, the methods detect pTau212, pTau-217 and pTau-231.

[089] Methods for detecting phosphorylated tau in a sample from an individual are described in this document, wherein the method detects pTau-217 and pTau-231 in a sample selected from the group consisting of a plasma sample and a serum sample. In some embodiments, the methods detect pTau-212 and pTau-217 in Petition 870260068651, dated 10 / 07 / 2026, page 89 / 132 80 / 116 a sample selected from the group consisting of a plasma sample and a serum sample. In some embodiments, the methods detect pTau-212 and pTau-231 in a sample selected from the group consisting of a plasma sample and a serum sample. In some embodiments, the methods detect pTau-212, pTau-217, and pTau-231 in a sample selected from the group consisting of a plasma sample and a serum sample.

[090] The methods described in this document may involve performing an assay on a sample, where the sample is selected from a group consisting of a plasma sample and a serum sample. In some cases, the sample is a blood sample. In some cases, the sample is a cerebrospinal fluid sample. The sample may be a blood sample obtained by venous blood collection. The sample may be a blood sample obtained from a finger prick blood collection. The sample may be obtained by a healthcare professional or by the individual. The method may involve obtaining a sample from an individual. In some cases, the sample is obtained from the individual during a visit to the clinic or hospital.

[091] Methods for determining the level of a biomarker selected from the group consisting of Aβ42, Aβ40, Aβ38, BACE1, hFABP, TREM2, YKL-40, IP-10, neurogranin, SNAP25, synaptotagmin, alpha-synuclein, TDP-43, ferritin, VILIP1, NfL, GFAP, and combinations thereof are further described in this document in some embodiments. In some cases, the biomarker is Aβ42. In some cases, the biomarker is Aβ40. In some cases, the biomarker is Aβ42 and Aβ40. In some cases, the biomarker is APOE. In some cases, the biomarker is selected from the group consisting of APOE2, APOE3, and APOE4. In some cases, the biomarker is APOE4.

[092] In some embodiments, the methods for detecting phosphorylated tau in a sample comprise an immunoassay or a ligand assay using antibodies or fragments of Petition 870260068651, dated 10 / 07 / 2026, pp. 90 / 132 81 / 116 antibodies described in this document. In some cases, the assay is selected from the group consisting of enzyme-linked immunosorbent assay (ELISA), a colorimetric immunoassay, a homogeneous immunoassay, a non-optical immunoassay, a fluorescence immunoassay, a chemiluminescence immunoassay, an electrochemiluminescence immunoassay, a fluorescence resonance energy transfer immunoassay (FRET), a time-resolved fluorescence immunoassay, a lateral flow immunoassay, a microspot immunoassay, a surface plasmon resonance assay, a ligand assay, a coagulation assay, a chromatography assay, and immunocapture coupled with mass spectrometry. In some cases, the assay comprises an immunoassay. In some cases, the assay is selected from the group consisting of Western blot, enzyme-linked immunosorbent assays (ELISA), and chromatography. In some cases, the immunoassays are monoplexed. In some cases, immunoassays are multiplexed.

[093] The methods as described in this document may comprise a plurality of immunoassays using the antibodies or antibody fragments described in this document. In some cases, the plurality of immunoassays is the same immunoassay (e.g., four or more ELISA assays). When the plurality of immunoassays is the same immunoassay, each of the plurality of immunoassays may detect a different phosphorylated tau. When the plurality of immunoassays is the same immunoassay, each of the plurality of immunoassays may be performed in the same reaction chamber or in a different reaction chamber. A reaction chamber may be any space suitable for performing an immunoassay. Examples of reaction chambers include, but are not limited to, a well in a microplate, an Eppendorf tube, or a microdrop.

[094] In some cases, the plurality of immunoassays are different immunoassays. When the plurality of immunoassays is Petition 870260068651, dated 10 / 07 / 2026, pp. 91 / 132 82 / 116 different immunoassays, each of the multiple immunoassays can detect a different phosphorylated tau. When the multiple immunoassays are different immunoassays, each of the multiple immunoassays can be performed in the same reaction chamber or in a different reaction chamber.

[095] In some cases, the assay comprises a non-immunoassay. In some cases, the assay is selected from the group consisting of High-Performance Liquid Chromatography (HPLC), High-Performance Liquid Chromatography Mass Spectrometry (HPLC-MS), Gas Chromatography Mass Spectrometry (GC-MS), Liquid Chromatography Mass Spectrometry (LC-MS), tandem mass spectrometry / liquid chromatography (LC-MS / MS), immunohistochemistry (IHC), polymerase chain reaction (PCR), quantitative PCR (qPCR), and combinations thereof.

[096] Methods as described in this document using the antibodies described in this document can be used to establish Alzheimer's disease in an individual based on the detection of phosphorylated tau. In some embodiments, Alzheimer's disease in the individual is presented if pTau-212, pTau-217, pTau-231, pTau-214, pTau-220 or combinations thereof are detected in the individual's sample.

[097] The methods described in this document using the antibodies described in this document can be used for the prognosis of an individual for the development of Alzheimer's disease based on the detection of phosphorylated tau. In some embodiments, the individual's prognosis for the development of Alzheimer's disease is determined if pTau-212, pTau-217, pTau231, pTau-214, pTau-220 or combinations thereof are detected in the individual's sample.

[098] Methods as described in this document using the antibodies described in this document can be used accurately and specifically establish Alzheimer's disease. Petition 870260068651, dated 10 / 07 / 2026, pp. 92 / 132 83 / 116 (AD) in an individual compared with a neurologically and cognitively intact disease, disorder, or condition, selected from a group consisting of a non-Alzheimer's disease (AD), neurodegenerative disease, a non-neurodegenerative Aβ-negative AD disease, a non-neurodegenerative Aβ-positive AD disease, behavioral variant of frontotemporal dementia (BvFTD), primary progressive aphasia (PPA), vascular dementia (VaD), Parkinson's disease (PD), PD with dementia (PDD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), Aβ-negative controls with or without cognitive impairment, and combinations thereof.In some embodiments, the methods described in this document using the antibodies described in this document comprise an improved accuracy or specificity of at least or approximately 70%, 80%, 90%, 95%, 99% or more in establishing AD compared with a neurologically and cognitively intact disease, disorder or condition.

[099] Methods as described in this document using the antibodies described in this document can be used accurately and specifically establish Alzheimer's disease (AD) in an individual compared to a neuropathological examination or clinical diagnosis. In some embodiments, the methods described in this document using the antibodies described in this document comprise an improved accuracy or specificity of at least or about 70%, 80%, 90%, 95%, 99% or more in establishing AD compared to a neuropathological examination or clinical diagnosis. In some embodiments, the neuropathological examination or clinical diagnosis comprises neurological tests, mental examinations or brain imaging (e.g., magnetic resonance imaging (MRI), computed tomography (CT) or PET scans).

[100] Methods as described in this document using the antibodies described in this document may be able to detect Petition 870260068651, dated 10 / 07 / 2026, pp. 93 / 132 84 / 116 phosphorylated tau in the sample at a low detection limit. In some embodiments, the methods described in this document using the antibodies described in this document are capable of detecting phosphorylated tau in the sample at a detection limit of at least about 1.5 picograms per milliliter (pg / mL). In some embodiments, the methods described in this document using the antibodies described in this document are capable of detecting phosphorylated tau in the sample at a detection limit of at least about 5 picograms per milliliter (pg / mL). In some embodiments, the methods described in this document using the antibodies described in this document are capable of detecting phosphorylated tau in the sample within a detection limit in a range of about 0.5 pg / mL to about 10 pg / mL, about 1 pg / mL to about 8 pg / mL, about 1.5 pg / mL to about pg / mL, about 2 pg / mL to about 6 pg / mL, or about 3 pg / mL to about 5 pg / mL. Production of Tau Antibodies

[101] In some embodiments, the antibodies or antibody fragments described in this document are produced using any method known in the art to be useful for the synthesis of antibodies or antibody fragments, in particular, by chemical synthesis or by recombinant expression, and are preferably produced by recombinant expression techniques.

[102] In some cases, an antibody or its binding fragment is recombinantly expressed, and the nucleic acid encoding the antibody or its binding fragment is assembled from chemically synthesized oligonucleotides (e.g., as described in Kutmeier et al., 1994, BioTechniques 17:242), which involves the synthesis of overlapping oligonucleotides containing portions of the antibody-encoding sequence, the annealing and ligation of these oligonucleotides, and then the amplification of the linked oligonucleotides by PCR.

[103] Alternatively, a nucleic acid molecule that Petition 870260068651, dated 10 / 07 / 2026, pp. 94 / 132 The 85 / 116 sequence encoding an antibody is optionally generated from a suitable source (e.g., an antibody cDNA library, or a cDNA library generated from any tissue or cells expressing the immunoglobulin) by PCR amplification using synthetic primers hybridizable with the 3' and 5' ends of the sequence or by cloning using an oligonucleotide probe specific for the specific gene sequence.

[104] In some cases, an antibody or its binding is optionally generated by immunizing an animal, such as a mouse, to generate polyclonal antibodies or, more preferably, by generating monoclonal antibodies, for example, as described by Kohler and Milstein (1975, Nature 256:495-497) or as described by Kozbor et al. (1983, Immunology Today 4:72) or Cole et al. (1985 in Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pages 77-96). Alternatively, a clone encoding at least the Fab portion of the antibody is optionally obtained by screening Fab expression libraries (e.g., as described in Huse et al., 1989, Science 246:1275-1281) for clones of Fab fragments that bind to the specific antigen or by screening antibody libraries (See, e.g., Clackson et al., 1991, Nature 352:624; Hane et al., 1997 Proc. Natl.

[105] In some embodiments, techniques have been developed for the production of “chimeric antibodies” (Morrison et al., 1984, Proc. Natl. Acad. Sci. 81:851-855; Neuberger et al., 1984, Nature 312:604-608; Takeda et al., 1985, Nature 314:452-454) through splicing genes from a mouse antibody molecule of appropriate antigenic specificity along with genes from a human antibody molecule of appropriate biological activity. A chimeric antibody is a molecule in which different portions are derived from different animal species, such as those Petition 870260068651, dated 10 / 07 / 2026, pp. 95 / 132 86 / 116 which have a variable region derived from a murine monoclonal antibody and a constant region of human immunoglobulin.

[106] In some embodiments, techniques described for the production of single-chain antibodies (US Patent No. 4,694,778; Bird, 1988, Science 242:423-42; Huston et al., 1988, Proc. Natl. Acad. Sci. USA 85:5879-5883; and Ward et al., 1989, Nature 334:54454) are adapted to produce single-chain antibodies. Single-chain antibodies are formed by linking heavy and light chain fragments of the Fv region through an amino acid bridge, resulting in a single-chain polypeptide. Techniques for assembling functional Fv fragments in E. coli are also optionally used (Skerra et al., 1988, Science 242:1038-1041).

[107] In some embodiments, an expression vector comprising the nucleotide sequence of an antibody or the nucleotide sequence of an antibody is transferred into a host cell by conventional techniques (e.g., electroporation, liposomal transfection, and calcium phosphate precipitation), and the transfected cells are then cultured by conventional techniques to produce the antibody. In specific embodiments, antibody expression is regulated by a constitutive, inducible, or tissue-specific promoter.

[108] In some embodiments, a variety of host expression vector systems are used to express an antibody or its binding fragment described in this document. Such host expression systems represent vehicles by which antibody coding sequences are produced and subsequently purified, but also represent cells that, when transformed or transfected with the appropriate nucleotide coding sequences, express an antibody or its binding fragment in situ. These include, but are not limited to, microorganisms such as bacteria (e.g., E. coli and B. subtilis) transformed with Petition 870260068651, dated 10 / 07 / 2026, pp. 96 / 132 87 / 116 Recombinant bacteriophage DNA, plasmid DNA, or cosmid DNA expression vectors containing an antibody or its binding fragment coding sequences; yeast (e.g., Saccharomyces Pichia) transformed with recombinant yeast expression vectors containing an antibody or its binding fragment coding sequences; insect cell systems infected with recombinant virus expression vectors (e.g., baculovirus) containing an antibody or its binding fragment coding sequences; plant cell systems infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus (CaMV) and tobacco mosaic virus (TMV)) or transformed with recombinant plasmid expression vectors (e.g., Ti plasmid) containing an antibody or its binding fragment coding sequences;or mammalian cell systems (e.g., COS, CHO, BH, 293, 293T, 3T3 cells) containing recombinant expression constructs with promoters derived from mammalian cell genomes (e.g., metallothionein promoter) or mammalian viruses (e.g., adenovirus late promoter; vaccinia virus 7.5K promoter).

[109] For long-term, high-yield production of recombinant proteins, stable expression is preferred. In some cases, cell lines that stably express an antibody are optionally genetically engineered. Instead of using expression vectors containing viral replication origins, host cells are transformed with DNA controlled by appropriate expression control elements (e.g., promoter, enhancer, sequences, transcription terminators, polyadenylation sites, etc.) and a selectable marker. After the introduction of the foreign DNA, the genetically engineered cells are then grown for 12 days in an enriched medium and then switched to a medium Petition 870260068651, dated 10 / 07 / 2026, page 97 / 132 88 / 116 selective. The selectable marker on the recombinant plasmid confers resistance to selection and allows cells to stably integrate the plasmid into their chromosomes and grow to form foci that are in turn cloned and expanded into cell lines. This method can be used advantageously to genetically manipulate cell lines that express the antibody or its binding fragments.

[110] In some cases, several selection systems are used, including, but not limited to, herpes simplex virus thymidine kinase (Wigler et al., 1977, Cell 11:223), hypoxanthine-guanine phosphoribosyltransferase (Szybalska & Szybalski, 192, Proc. Natl. Acad. Sci. USA 48:202) and adenine phosphoribosyltransferase genes (Lowy et al., 1980, Cell 22:817) are employed in tk-, hgprt- or aprt- cells, respectively. Furthermore, antimetabolite resistance is used as a basis for selection for the following genes: dhfr, which confers resistance to methotrexate (Wigler et al., 1980, Proc. Natl. Acad. Sci. USA 77:357; O'Hare et al., 1981, Proc. Natl. Acad. Sci. USA 78:1527); gpt, which confers resistance to mycophenolic acid (Mulligan & Berg, 1981, Proc. Natl. Acad. Sci. EUA 78:2072); neo, which confers resistance to the aminoglycoside G-418 (Clinical Pharmacy 12:488-505; Wu and Wu, 1991, Biotherapy 3:87-95; Tolstoshev, 1993, Ann. Rev. Pharmacol. Toxicol. 32:573-596; Mulligan, 1993, Science 260:926-932; and Morgan and Anderson, 1993, Ann. Rev. Biochem. 62:191-217; May 1993, TIB TECH 11(5):155-215) and hygro, which confers resistance to hygromycin (Santerre et al., 1984, Gene 30:147). The commonly known methods in recombinant DNA technology that can be used are described in Ausubel et al. (eds., 1993, Current Protocols in Molecular Biology, John Wiley & Sons, NY; Kriegler, 1990, Gene Transfer and Expression, A Laboratory Manual, Stockton Press, NY; and in Chapters 12 and 13, Dracopoli et al. (eds), 1994, Current Protocols in Human Genetics, John Wiley & Sons, NY.; Colberre Petition 870260068651, of 10 / 07 / 2026, p. 98 / 132) 89 / 116 Garapin et al., 1981, J. Mol. Biol. 150:1).

[111] In some cases, antibody expression levels are increased by vector amplification (for a review, see Bebbington and Hentschel, The Use of Gene Amplification-Based Vectors for the Expression of Cloned Genes in Mammalian Cells in DNA Cloning, Vol. 3 (Academic Press, New York, 1987)). When a marker in the vector system expressing an antibody is amplifiable, an increase in the level of inhibitor present in the host cell culture will increase the number of copies of the marker gene. Because the amplified region is associated with the nucleotide sequence of the antibody, antibody production will also increase (Crouse et al., 1983, Mol. Cell Biol. 3:257).

[112] In some cases, any method known in the art for the purification of an antibody is used, for example, by chromatography (e.g., ion exchange, affinity, particularly by affinity for the specific antigen after Protein A, and sizing column chromatography), centrifugation, differential solubility or by any other standard technique for protein purification. Expression vectors

[113] In some embodiments, vectors include any suitable vectors derived from eukaryotic or prokaryotic sources. In some cases, vectors are obtained from bacteria (e.g., E. coli), insects, yeasts (e.g., Pichia pastoris), algae, or mammalian sources. Examples of bacterial vectors include pACYC177, pASK75, pBAD vector series, pBADM vector series, pET vector series, pETM vector series, pGEX vector series, pHAT, pHAT2, pMalc2, pMal-p2, pQE vector series, pRSET A, pRSET B, pRSET C, pTrcHis2 series, pZA31-Luc, pZE21-MCS-1, pFLAG ATS, pFLAG CTS, pFLAG MAC, pFLAG Shift-12c, pTAC-MAT-1, pFLAG CTC, or pTAC-MAT2. Petition 870260068651, dated 10 / 07 / 2026, pp. 99 / 132 90 / 116

[114] Exemplary insect vectors include pFastBacl, pFastBac DUAL, pFastBac ET, pFastBac HTa, pFastBac HTb, pFastBac HTc, pFastBac M30a, pFastBact M30b, pFastBac, M30c, pVL1392, pVL1393, pVL1393 M10, pV.L1393 M11, pVL1393 M12, FLAG vectors such as pPolh-FLAG1 or pPolh-MAT 2, or MAT vectors such as pPolhMAT1 or pPolh-MAT2.

[115] In some cases, yeast vectors include 14Gateway® pDEST™ vector, 15Gateway® pDEST™ vector, 17Gateway® pDEST™ vector, 24Gateway® pDEST™ vector, pYES-DEST52 Gateway® vector, pBAD-DEST49 Gateway® target vector, pAO815 Pichia vector, pFLD1 Pichi pastoris vector, pGAPZA,B, & C Pichia pastoris vector, pPIC3.5K Pichia vector, pPIC6 A, B, & C Pichia vector, pPIC9K Pichia vector, pTEF1 / Zeo, pYES2 yeast vector, pYES2 / CT yeast vector, pYES2 / NT A, B and C yeast vector or pYES3 / CT yeast vector.

[116] Exemplary algal vectors include pChlamy-4 vector or MCS vector.

[117] Examples of mammalian vectors include transient expression vectors or stable expression vectors. Transient mammalian expression vectors may include pRK5, p3xFLAG-CMV 8, pFLAG-Myc-CMV 19, pFLAG-Myc-CMV 23, pFLAG-CMV 2, pFLAG-CMV 6a,b,c, pFLAG-CMV 5.1, pFLAG-CMV 5a,b,c, p3xFLAG-CMV 7.1, pFLAG-CMV 20, p3xFLAG-Myc-CMV 24, pCMV-FLAG-MAT1, pCMVFLAG-MAT2, pBICEP-CMV 3, or pBICEP-CMV 4. Stable mammalian expression vectors may include pFLAG-CMV 3, p3xFLAG-CMV 9, p3xFLAG-CMV 13, pFLAG-Myc-CMV 21, p3xFLAG-Myc-CMV 25, pFLAG-CMV 4, p3xFLAG-CMV 10, p3xFLAG-CMV 14, pFLAG-Myc-CMV 22, p3xFLAGMyc-CMV 26, pBICEP-CMV 1 or pBICEP-CMV 2.

[118] In some cases, a cell-free system is a mixture of cytoplasmic and / or nuclear components of a cell and is used for nucleic acid synthesis in vitro. In some cases, a cell-free system uses components of prokaryotic cells or components of eukaryotic cells. Petition 870260068651, dated 10 / 07 / 2026, pages 100 / 132 91 / 116 times, nucleic acid synthesis is achieved in a cell-free system based, for example, on Drosophila cells, Xenopus eggs, or HeLa cells. Examples of cell-free systems include, but are not limited to, the E. coli S30 Extract system, the E. coli T7 S30 system, or PURExpress®. Host cells

[119] In some embodiments, a host cell includes any suitable cell, such as a naturally derived cell or a genetically modified cell. In some cases, a host cell is a production host cell. In some cases, a host cell is a eukaryotic cell. In other cases, a host cell is a prokaryotic cell. In some cases, a eukaryotic cell includes fungi (e.g., yeast cells), animal cells, or plant cells. In some cases, a prokaryotic cell is a bacterial cell. Examples of bacterial cells include gram-positive bacteria or gram-negative bacteria. Sometimes, the gram-negative bacterium is anaerobic, rod-shaped, or both.

[120] In some cases, gram-positive bacteria include Actinobacteria, Firmicutes, or Tenericutes. In some cases, gram-negative bacteria include Aquificae, Deinococcus-Thermus, FibrobacteresChlorobi / Bacteroidetes (FCB group), Fusobacteria, Gemmatimonadetes, Nitrospirae, PlanctomycetesVerrucomicrobia / Chlamydiae (PVC group), Proteobacteria, Spirochaetes or Synergistetes. Other bacteria may be Acidobacteria, Chloroflexi, Chrysiogenetes, Cyanobacteria, Deferribacteres, Dictyoglomi, Thermodesulfobacteria or Thermotogae. A bacterial cell can be Escherichia coli, Clostridium botulinum or Coli bacilli.

[121] Examples of prokaryotic host cells include, but are not limited to, BL21, Mach1™, DH10B™, TOP10, DH5a, DH10Bac™, OmniMax™, MegaX™, DH12S™, INV110, TOP10F™, INVaF, Petition 870260068651, dated 10 / 07 / 2026, pages 101 / 132 92 / 116 TOP10 / P3, ccdB Survival, PIR1, PIR2, Stbl2™, Stbl3™ or Stbl4™.

[122] In some cases, animal cells include a cell from a vertebrate or an invertebrate. In some cases, an animal cell includes a cell from a marine invertebrate, fish, insect, amphibian, reptile, or mammal. In some cases, a fungal cell includes a yeast cell, such as brewer's yeast, baker's yeast, or wine yeast.

[123] Fungi include ascomycetes, such as yeasts, molds, filamentous fungi, basidiomycetes, or zygomycetes. In some cases, yeast includes Ascomycota or Basidiomycota. In some cases, Ascomycota includes Saccharomycotina (true yeasts, for example, Saccharomyces cerevisiae (baker's yeast)) or Taphrinomycotina (for example, Schizosaccharomycetes (fission yeasts)). In some cases, Basidiomycota includes Agaricomycotina (for example, Tremellomycetes) or Pucciniomycotina (for example, Microbotryomycetes).

[124] Exemplary yeasts or filamentous fungi include, for example, of the genus: Saccharomyces, Schizosaccharomyces, Candida, Pichia, Hansenula, Kluyveromyces, Zygosaccharomyces, Yarrowia, Trichosporon, Rhodosporidi, Aspergillus, Fusarium or Trichoderma. Examples of yeasts or filamentous fungi include, for example, the species: Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida utilis, Candida boidini, Candida albicans, Candida tropicalis, Candida stellatoidea, Candida glabrata, Candida krusei, Candida parapsilosis, Candida guilliermondii, Candida viswanathii, Candida lusitaniae, Rhodotorula mucilaginosa, Pichia methanolica, Pichia angusta, Pichia pastoris, Pichia anomala, Hansenula polymorpha, Kluyveromyces lactis, Zygosaccharomyces rouxii, Yarrowia lipolytica, Trichosporon pullulans, Rhodosporidium toru-Aspergillus niger, Aspergillus nidulans, Aspergillus awamori, Aspergillus oryzae, Trichoderma reesei, Yarrowia Petition 870260068651, dated 10 / 07 / 2026, pages 102 / 132 93 / 116 lipolytica, Brettanomyces bruxellensis, Candida stellata, Schizosaccharomyces pombe, Torulaspora delbrueckii, Zygosaccharomyces bailii, Cryptococcus neoformans, Cryptococcus gattii or Saccharomyces boulardii.

[125] Exemplary yeast host cells include, but are not limited to, Pichia pastoris yeast strains such as GS115, KM71H, SMD1168, SMD1168H and X-33; and Saccharomyces cerevisiae yeast strain such as INVSc1.

[126] In some cases, additional animal cells include cells obtained from a mollusk, arthropod, annelid, or sponge. In some cases, an additional animal cell is a mammalian cell, for example, from a primate, monkey, equine, bovine, swine, canine, feline, or rodent. In some cases, a rodent includes a mouse, rat, hamster, gerbil, hamster, chinchilla, house rat, or guinea pig.

[127] Examples of mammalian host cells include, but are not limited to, 293A cell line, 293FT cell line, 293F cells, 293H cells, CHO DG44 cells, CHO-S cells, CHO-K1 cells, CHOK1 KO FUT8 cells, Expi293F™ cells, T-REx™ 293Flp-In™ cell line, FlpIn™-293 cell line, Flp-In™-3T3 cell line, FlpIn™-BHK cell line, Flp-In™-CHO cell line, FlpIn™-CV-1 cell line, Flp-In™-Jurkat cell line, 293-F cells FreeStyle™, FreeStyle™ CHO-S cells, 293 MSR GripTite™ cell line, GS-CHO cell line, HepaRG™ cells, Jurkat T-REx™ cell line, Per.C6 cells, TREx™-293 cell line, T-REx™-CHO cell line, and TREx™-HeLa cell line.

[128] In some cases, a mammalian host cell is a stable cell line or a cell line that has incorporated genetic material of interest into its own genome and has the ability to express the product of the genetic material after many generations of cell division. In some cases, a cell Petition 870260068651, dated 10 / 07 / 2026, pages 103 / 132 94 / 116 A mammalian host is a transient cell line or a cell line that has not incorporated genetic material of interest into its own genome and does not have the ability to express the product of the genetic material after many generations of cell division.

[129] Exemplary insect host cells include, but are not limited to, Drosophila S2 cells, Sf9 cells, Sf21 cells, High Five™ cells and expresSF+® cells.

[130] In some cases, plant cells include an algal cell. Exemplary insect cell lines include, but are not limited to, strains of Chlamydomonas reinhardtii 137c or Synechococcus elongatus PPC 7942. NUMBERED MODALITIES

[131] Embodiment numbered 1 comprises a method for detecting phosphorylated tau in a sample from an individual comprising: performing an immunoassay on the sample using an antibody or antibody fragment comprising a variable domain, heavy chain region (VH) and a variable domain, light chain region (VL), wherein the VH comprises an amino acid sequence at least about 90% identical to a sequence as presented in any of the SEQ ID NOs: 30-34, and wherein the VL comprises an amino acid sequence at least about 90% identical to a sequence as presented in any of the SEQ ID NOs: 35-40. Embodiment numbered 2 comprises the method of embodiment numbered 1, wherein the phosphorylated tau is selected from the group consisting of pTau-181, pTau-212, pTau217, pTau-231, pTau-214 and pTau-220. Embodiment numbered 3 comprises the method of embodiments numbered 1-2, wherein the phosphorylated tau is pTau-217.Embodiment numbered 4 comprises the method of embodies numbered 1-2, wherein the phosphorylated tau is pTau-231. Embodiment numbered 5 comprises the method of embodies numbered 2, wherein the method detects pTau-217 and pTau. Petition 870260068651, dated 10 / 07 / 2026, pp. 104 / 132 95 / 116 231. Modality numbered 6 comprises the method of modality numbered 2, wherein the method detects pTau-212 and pTau-217. Modality numbered 7 comprises the method of modality numbered 2, wherein the method detects pTau-212 and pTau-231. Modality numbered 8 comprises the method of modality numbered 2, wherein the method detects pTau-181 and pTau-217. Modality numbered 9 comprises the method of modality numbered 2, wherein the method detects pTau-181 and pTau-231. Modality numbered 10 comprises the method of modality numbered 2, wherein the method detects pTau-181, pTau-217, and pTau-231. Modality numbered 11 comprises the method of modality numbered 2, wherein the method detects pTau212, pTau-217, and pTau-231. Modality numbered 12 comprises the method of modality numbered 5, wherein the method detects pTau217 and pTau-231 in a sample selected from the group consisting of a plasma sample and a serum sample.The numbered modality 13 comprises the method of the numbered modality 6, wherein the method detects pTau-212 and pTau-217 in a sample selected from the group consisting of a plasma sample and a serum sample. The numbered modality 14 comprises the method of the numbered modality 7, wherein the method detects pTau-212 and pTau-231 in a sample selected from the group consisting of a plasma sample and a serum sample. The numbered modality 15 comprises the method of the numbered modality 11, wherein the method detects pTau-181 and pTau-217 in a sample selected from the group consisting of a plasma sample and a serum sample. The numbered modality 16 comprises the method of the numbered modality 11, wherein the method detects pTau-181 and pTau-231 in a sample selected from the group consisting of a plasma sample and a serum sample.The numbered modality 17 comprises the method of the numbered modality 11, in which the method detects pTau-181, pTau-217, and pTau-231 in a sample selected from the group consisting of a plasma sample and a serum sample. The numbered modality 18 comprises the method of the numbered modality 11, in which... Petition 870260068651, dated 10 / 07 / 2026, pages 105 / 132 96 / 116 that the method detects pTau-212, pTau-217, and pTau-231 in a sample selected from the group consisting of a plasma sample and a serum sample. Embodiment numbered 19 comprises the method of embodies numbered 1 to 18, wherein VH comprises an amino acid sequence according to any of the SEQ ID NOs: 30-34. Embodiment numbered 20 comprises the method of embodies numbered 1 to 19, wherein VL comprises an amino acid sequence according to any of the SEQ ID NOs: 35-40. Embodiment numbered 21 comprises the method of embodies numbered 1 to 20, wherein VH comprises an amino acid sequence according to any of the SEQ ID NOs: 30-34, and wherein VL comprises an amino acid sequence according to any of the SEQ ID NOs: 35-40.Embodiment numbered 22 comprises the method of embodies numbered 1 to 21, wherein VH comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 30, and wherein VL comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 35. Embodiment numbered 23 comprises the method of embodies numbered 1 to 21, wherein VH comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 31, and wherein VL comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 36. Embodiment numbered 24 comprises the method of embodies numbered 1 to 21, wherein VH comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 31, and wherein VL comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 37.Embodiment numbered 25 comprises the method of embodies numbered 1-21, wherein VH comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 32, and wherein VL comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 38. Embodiment numbered 26 comprises the method of embodies numbered 1 to 21, wherein VH comprises a sequence of... Petition 870260068651, dated 10 / 07 / 2026, pp. 106 / 132 97 / 116 amino acids at least about 90% identical to SEQ ID NO: 33, and wherein VL comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 39. Embodiment numbered 27 comprises the method of embodies numbered 1 to 21, wherein VH comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 34, and wherein VL comprises an amino acid sequence at least about 90% identical to SEQ ID NO: 40. Embodiment numbered 28 comprises the method of embodies numbered 1 to 27, wherein the antibody or antibody fragment comprises an amino acid sequence at least about 90% identical to any of the SEQ ID NOs: 41-51.Modality numbered 29 comprises the method of modalities numbered 1 to 28, additionally comprising performing an assay on the sample to determine a level of a biomarker selected from the group consisting of Aβ42, Aβ40, Aβ38, BACE1, hFABP, TREM2, YKL-40, IP-10, neurogranin, SNAP-25, synaptotagmin, alpha-synuclein, TDP-43, ferritin, VILIP-1, NfL, GFAP, and combinations thereof. Modality numbered 30 comprises the method of modalities numbered 1 to 29, wherein the sample is selected from the group consisting of a blood sample, a plasma sample, a serum sample, and a cerebrospinal fluid (CSF) sample. Modality numbered 31 comprises the method of modalities numbered 1 to 30, additionally including the establishment of Alzheimer's disease in the individual based on the detection of phosphorylated tau.Modality numbered 32 comprises the method of modalities numbered 1 to 31, additionally including the establishment of the individual's prognosis for the development of Alzheimer's disease based on the detection of phosphorylated tau. Modality numbered 33 comprises the method of modality numbered 32, additionally determining the age, genotype, or expression of a biomarker of the individual. Modality numbered 34 comprises the method of modality numbered 33, where the... Petition 870260068651, dated 10 / 07 / 2026, pp. 107 / 132 The 98 / 116 biomarker is selected from the group consisting of Aβ42, Aβ40, Aβ38, BACE1, hFABP, TREM2, YKL-40, IP-10, neurogranin, SNAP25, synaptotagmin, alpha-synuclein, TDP-43, ferritin, VILIP1, NfL, GFAP, and combinations thereof. Modality numbered 35 comprises the method of modalities numbered 1 to 34, wherein the method has a specificity of at least about 80% for detecting phosphorylated tau. Modality numbered 36 comprises the method of modalities numbered 1 to 34, wherein the method has a specificity of at least about 85% for detecting phosphorylated tau. Modality numbered 37 comprises the method of modalities numbered 1 to 34, wherein the method has a specificity of at least about 90% for detecting phosphorylated tau. The numbered modality 38 comprises the method of the numbered modalities 1 to 37, wherein the method has a sensitivity of at least about 80% for detecting phosphorylated tau.Embodiment numbered 39 comprises the method of embodies numbered 1 to 37, wherein the method has a sensitivity of at least about 85% for detecting phosphorylated tau. Embodiment numbered 40 comprises the method of embodies numbered 1 to 37, wherein the method has a sensitivity of at least about 90% for detecting phosphorylated tau. Embodiment numbered 41 comprises the method of embodies numbered 1 to 40, wherein the method is capable of detecting phosphorylated tau in the sample to a detection limit of at least about 1.0 picogram per milliliter (pg / mL). Embodiment numbered 42 comprises the method of embodies numbered 1 to 40, wherein the method is capable of detecting phosphorylated tau in the sample to a detection limit of at least about 1.5 picograms per milliliter (pg / mL).The embodiment numbered 43 comprises the method of embodiments numbered 1 to 40, in which the method is capable of detecting phosphorylated tau in the sample to a detection limit of at least about 5 picograms per milliliter (pg / mL). Petition 870260068651, dated 10 / 07 / 2026, pages 108 / 132 99 / 116

[132] The embodiment numbered 44 comprises an anti-tau antibody comprising i) a heavy chain comprising a variable heavy chain (VH) domain and ii) a light chain comprising a variable light chain (VL) domain, wherein the VH domain comprises an HCDR1 sequence comprising a selected sequence of SEQ ID NOs: 1-5, an HCDR2 sequence comprising a selected sequence of SEQ ID NOs: 6-9, and an HCDR3 sequence comprising a selected sequence of SEQ ID NOs: 10-13, and the VL domain comprises an LCDR1 sequence comprising a selected sequence of SEQ ID NOs: 14-19, an LCDR2 sequence comprising a selected sequence of SEQ ID NOs: 20-23, and LCDR3 sequence comprising a selected sequence of SEQ ID NOs: 24-29. The numbered modality comprises the anti-tau antibody of numbered modality 44, wherein the HCDR1 sequence comprises SEQ ID NO: 1, the sequence of HCDR2 comprises SEQ ID NO: 6, HCDR3 sequence comprises SEQ ID NO: 10, LCDR1 sequence comprises SEQ ID NO: 14, LCDR2 sequence comprises SEQ ID NO: 20, and LCDR3 sequence comprises SEQ ID NO: 24. Embodiment numbered 46 comprises the anti-tau antibody of embodiment numbered 44, wherein HCDR1 sequence comprises SEQ ID NO: 2, HCDR2 sequence comprises SEQ ID NO: 7, HCDR3 sequence comprises SEQ ID NO: 11, LCDR1 sequence comprises SEQ ID NO: 15, LCDR2 sequence comprises SEQ ID NO: 21, and LCDR3 sequence comprises SEQ ID NO: 25. Embodiment numbered 47 comprises the anti-tau antibody of embodiment numbered 44, wherein HCDR1 sequence includes SEQ ID NO: 2, the HCDR2 sequence includes SEQ ID NO: 7, the sequence of HCDR3 comprises SEQ ID NO: 11, the sequence of LCDR1 comprises SEQ ID NO: 16, the LCDR2 sequence comprises SEQ ID NO: 22, and the LCDR3 sequence comprises SEQ ID NO: 26. The modality numbered 48 comprises the anti-tau antibody of the modality numbered 44, wherein the HCDR1 sequence comprises SEQ ID NO: Petition 870260068651, dated 10 / 07 / 2026, pp. 109 / 132 100 / 116 3, the HCDR2 sequence comprises SEQ ID NO: 8, the HCDR3 sequence comprises SEQ ID NO: 10, the LCDR1 sequence comprises SEQ ID NO: 17, the LCDR2 sequence comprises SEQ ID NO: 20, and the LCDR3 sequence comprises SEQ ID NO: 27. The embodiment numbered 49 comprises the anti-tau antibody of embodiment numbered 44, wherein the HCDR1 sequence comprises SEQ ID NO: 4, the HCDR2 sequence comprises SEQ ID NO: 7, the HCDR3 sequence comprises SEQ ID NO: 12, the LCDR1 sequence comprises SEQ ID NO: 18, the LCDR2 sequence comprises SEQ ID NO: 23, and the LCDR3 sequence comprises SEQ ID NO: 28. The embodiment numbered 50 comprises the anti-tau antibody of embodiment numbered 44, wherein the HCDR1 sequence comprises SEQ ID NO: 5, the HCDR2 sequence comprises SEQ ID NO: 9, the HCDR3 sequence comprises SEQ ID NO: 13, the LCDR1 sequence comprises SEQ ID NO: 19, the LCDR2 sequence comprises SEQ ID NO: 21, and the LCDR3 sequence comprises SEQ ID NO: 29.The numbered modality 51 comprises the anti-tau antibody of the numbered modality 44, wherein the VH domain comprises at least 80%, at least 85%, at least 90%, at least 95% sequence identity with a selected sequence of SEQ ID NOs: 3034. The numbered modality 52 comprises the anti-tau antibody of the numbered modality 44, wherein the VL domain comprises at least 80%, at least 85%, at least 90%, at least 95% sequence identity with a selected sequence of SEQ ID NOs: 3540.

[133] Embodiment numbered 53 comprises the anti-tau antibody of embodies numbered 44-52, wherein the anti-tau antibody is a chimeric antibody or its antigen-binding fragment. Embodiment numbered 54 comprises the anti-tau antibody of embodies numbered 44-53, wherein the anti-tau antibody comprises an IgG-scFv, nanobody, BiTE, diabody, DART, TandAb, scDiabody, scDiabody-CH3, triple body, miniantibody, minibody, TriBi minibody, scFv-CH3 KIH, Fab-scFv- Petition 870260068651, dated 10 / 07 / 2026, pp. 110 / 132 101 / 116 Fc KIH, Fab-scFv, scFv-CH-CL-scFv, Fab', F(ab')2, F(ab')3, F(ab')2-scFv2, scFv, scFv-KIH, Fab-scFv-Fc, tetravalent HCAb, scDiacorpo-Fc, diacorpo-Fc, scFv-Fc in tandem or intracorpo. The embodiment numbered 55 comprises the anti-tau antibody of the embodiments numbered 44-54, where the anti-tau antibody is an IgG1 antibody. The embodiment numbered 56 comprises the anti-tau antibody of the embodiments numbered 44-55, where the anti-tau antibody is an IgG2 antibody. The embodiment numbered 57 comprises the anti-tau antibody of the embodiments numbered 44-56, where the anti-tau antibody is an IgG4 antibody. The embodiment numbered 58 comprises the anti-tau antibody of the embodiments numbered 44-57, where the light chain is a cap chain. The numbered embodiment comprises the anti-tau antibody of the numbered embodiments 4458, wherein the anti-tau antibody has a binding affinity to human tau of about 100 pM to about 3 nM.Embodiment numbered 60 comprises the anti-tau antibody of embodiments numbered 44-59, wherein the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising at least 80%, at least 85%, at least 90%, or at least 95% sequence identity with a selected SEQ sequence. ID Nos: 52-56. The embodiment numbered 61 comprises the anti-tau antibody of embodiments numbered 44-60, wherein the anti-tau antibody comprises a VL domain that is encoded by a nucleic acid comprising at least 80%, at least 85%, at least 90%, at least 95% sequence identity with a selected sequence of SEQ IDs: 57-62. Embodiment numbered 62 comprises the anti-tau antibody of embodiments numbered 4461, wherein the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising at least 80%, at least 85%, at least 90%, at least 95% sequence identity with a selected sequence of SEQ IDs: 52-56 and a VL domain that is encoded by a nucleic acid comprising at least 80%, at least 85%, at least 90%, Petition 870260068651, dated 10 / 07 / 2026, pages 111 / 132 102 / 116 at least 95% sequence identity with a selected sequence of SEQ ID NOs: 57-62. Embodiment numbered 63 comprises the anti-tau antibody of embodies numbered 4462, wherein the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NOs: 52-56. Embodiment numbered 64 comprises the anti-tau antibody of embodies numbered 4463, wherein the anti-tau antibody comprises a VL domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NOs: 57-62. The embodiment numbered 65 comprises the anti-tau antibody of embodiments numbered 4464, wherein the anti-tau antibody comprises a VH domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NOs: 52-56 and a VL domain that is encoded by a nucleic acid comprising a sequence identical to SEQ ID NOs: 57-62. EXAMPLES

[134] The following examples are given for the purpose of illustrating various embodiments of the invention and are not intended to limit the present invention in any way. The present examples, together with the methods described in this document, are currently representative of preferred embodiments, are exemplary and are not intended to be limitations on the scope of the invention. Changes thereto and other uses that are encompassed by the spirit of the invention, as defined by the scope of the claims, will occur to those skilled in the art. Example 1: Tau Antibody Screening

[135] Tau antibodies that detect phosphorylated Tau were assayed in the Simoa® count assay using a 2- or 3-step protocol assay according to the manufacturer’s instructions. See Figure 1.

[136] The antibodies tested were Antibody 1, Antibody 2, Antibody 3, Antibody 4, Antibody 5 and Antibody 6. The results Petition 870260068651, dated 10 / 07 / 2026, pp. 112 / 132103 / 116 capture values ​​can be seen in Figs. 2A-2D. Fig. 2A shows data from a 2-step protocol assay in which all capture antibodies were tested against the Tau-12 detector (detects Tau in the N-terminus). The data demonstrate that all captures had similar results with improved sensitivity observed with Antibody 6. Fig. 2B shows data from a 2-step protocol assay in which all capture antibodies were tested against HT7-BT2 detectors (detects Tau in the mid-domain region). Both biotinylated antibodies were used. The data show an approximately 10-fold increase in the reference compared to the Tau-12 detector. No signal at 1000 pg / mL for any capture was detected. Fig. 2C shows data from a 3-step protocol assay in which all capture antibodies were tested against the Tau-12 detector.The data demonstrate reduced sensitivity compared to the 2-step protocol and improved sensitivity observed with Antibody 6. Fig. 2D shows data from a 3-step protocol assay in which all capture antibodies were tested against HT7-BT2 detectors. Both biotinylated antibodies were used. The data show an approximately 10-fold increase in the reference compared to the Tau-12 detector. Based on the results, the 2-step protocol was then optimized for sensitivity. Example 2. Pharmacokinetics of Tau Antibodies

[137] The antibodies were tested for their pharmacokinetic profile.

[138]

[00140] Antigen information for the antibodies is shown in Table 10. Table 10. Description Antigen Name SEQ ID NO: Sequence pT217a WZN-1A 74 RSRTPSLP(pT)PPTREPKC pT217b WZN-1B 75 TPSLP(pT)PPTREPKKVAC T217 WZN-1C 76 RSRTPSLPTPPTREPKKVAC pT212 WZN-1D 77 RSR(pT)PSLPTPPTREPKC Petition 870260068651, dated 10 / 07 / 2026, pp. 113 / 132 104 / 116 pS214 WZN-1E 78 RSRTP(pS)LPTPPTREPKC pT220 WZN-1F 79 RSRTPSLPTPP(pT)REPKKVAC pT231 WZN-1G 80 KVAVVR(pT)PPKSPSSAC T231 WZN-1H 81 KVAVVRTPPKSPSSAC

[139] Antibodies were generated and purified. Antibodies were analyzed using a standard indirect ELISA protocol. Briefly, peptide antigens corresponding to SEQ IDs NOs: 74-81 were diluted to 1 ug / ml in PBS and plated on a 96-well Greiner Bio One Microlon plate. Peptide antigens were produced by the manufacturer Abcam. WZN-1A and WZN-1B served as targets. WZN-1C, WZN-1D, WZN-1E, WZN-1F, WZN-1G, and WZN-1H served as negative controls. In peptide antigen sequences, a phosphorylated residue is indicated by (pT) for phosphorylated threonine or (pS) for phosphorylated serine. After blocking with 1% BSA in PBS pH 7.4, the antibodies were serially diluted from 1 to 4 with an initial concentration of 1 ug / ml. After incubation, unbound antibodies were washed with 1X TBST and the goat anti-rabbit secondary antibody labeled HRP was applied according to the manufacturer's instructions.Subsequently, the unbound secondary antibody was washed with 1X TBST and 3,3'5,5'-tetramethylbenzidine (TMB) was applied for 5 minutes at room temperature and the plates were read at 650 nm. The data are shown in Fig. 3. Fig. 3 shows screening data of the different monoclonal antibodies for varying peptide concentrations. Example 3. Tau Antibodies for Immunohistochemistry

[140] The Tau antibodies described in this document were tested in immunohistochemical assays.

[141] In summary, all antibodies were optimized using a concentration range (0.01 - 3.00 ug / ml) and stained using a Leica Bond RX automated IHC platform: ER1 antigen recovery (sodium citrate, pH 6) 20 minutes at 100 °C; primary antibody 15 minutes at TA; HRP detection Refine grade IVD polymer for 8 minutes at room temperature; Petition 870260068651, dated 10 / 07 / 2026, pages 114 / 132 105 / 116 Chromogen DAB was applied for 10 minutes at room temperature, followed by hematoxylin counterstaining for 5 minutes at room temperature. Antibodies that passed basic IHC staining were then subjected to IHC staining after treatment with alkaline phosphatase (AP) (200 U / ml, 37 °C for 60 minutes). A vehicle-only control (AP-free buffer) was also used. Positive antigen control tissues were normal human cerebral cortex (FFPE) and cerebral cortex from an Alzheimer's patient. Negative antigen control tissues were normal human liver (FFPE), skeletal muscle, and cardiac muscle. All tissues were grouped into a tissue microarray to simplify the IHC staining process. Negative reagent controls (detection system only) were employed and were found to be negative.The reference antibodies stained together with the test antibodies were rabbit monoclonal antibodies [EPR22524-95] for Tau (ab254256, Abcam plc) and rabbit monoclonal antibodies [EPR1884(2)] for Tau (phospho S214) (ab170892, Abcam plc).

[142] Reference antibodies demonstrated that the antibodies exhibited negative staining in negative control tissue and positive staining in positive control tissue (data not shown). Data for Tau antibodies are seen in Figs. 4A-4G (Antibody 6), Figs. 5A-5G (Antibody 5) and Figs. 6A-6G (Antibody 2). Antibody 5 and Antibody 6 demonstrated data similar to the reference antibodies, where negative staining was observed in negative control tissues that included normal heart, normal liver, and normal skeletal muscle, and normal cerebral cortex, and positive staining was observed in positive control tissues that included cerebral cortex in Alzheimer's disease. Antibodies 1-4 did not exhibit data similar to the reference antibodies. Example 4. Detection of Tau peptides using Tau antibodies.

[143] The antibodies to Tau described in this document that Petition 870260068651, dated 10 / 07 / 2026, pp. 115 / 132 106 / 116 detecting phosphorylated Tau were tested in ELISA assays. Tau antibodies were first tested for reactivity to pTau 217 by indirect ELISA. Fig. 7 shows a diagram representing the indirect ELISA assay format used. Briefly, streptavidin beads were attached to a plate and biotinylated peptide was added to the plates under conditions that allowed biotin-streptavidin binding. The biotinylated peptide was a synthetic peptide comprising a Tau moiety and possessing a phosphorylated threonine residue at position 217 (pT217). This was the target peptide. After binding of the synthetic peptide to the plate by forming the biotin-streptavidin complex, Tau antibodies were added to the plates under conditions that allow antibody-target peptide binding.After ligation, the plates were washed to remove any unbound antibody, and then a secondary antibody, or tracer antibody, was added (peroxidase-conjugated goat-mouse antibody or peroxidase-conjugated donkey-rabbit antibody) targeting the species from which the Tau antibodies were derived. After ligation, the plates were washed to remove any unbound tracer antibody, and then TMB ELISA Peroxidase (3,3',5,5'Tetramethylbenzidine) chromogenic substrate was added to visualize antibody reactivity in indirect ELISA experiments. Antibody sample binding was quantified using an ELISA microplate reader.

[144] As shown in Figure 7, five antibodies were tested for their ability to detect phosphorylated Tau using this indirect ELISA technique. mAb IBA493 corresponds to a rabbit anti-Tau antibody capable of binding to phosphorylated Tau at threonine residue 217 (pTau 217) (Eli Lilly and Company). PT3 corresponds to a selective anti-phospho(T212 / T217) mouse Tau antibody (Janssen Biotech Inc.). 30H10L2 corresponds to Petition 870260068651, dated 10 / 07 / 2026, pp. 116 / 132 107 / 116 Antibody 2 is described in this document. 71H1L2 corresponds to Antibody 6 described in this document. 62H10L7 corresponds to Antibody 5 described in this document. All five antibodies were tested for reactivity with pTau 217 in two separate ELISA instruments at the following concentrations: 10⁻², 10⁻¹, 10⁻⁰, 10¹, 10², 10³, and 10⁴ ng / mL per plate. As can be seen in the Bio-pt655 (phospho T217) and Bio-pt660 (phospho T217) graphs, both mAb IBA493 and PT3 demonstrated a robust, concentration-dependent level of reactivity to pTau 217. Antibody 2 demonstrated a more modest concentration-dependent level of reactivity to pTau 217 revealed at 10⁴ ng / mL per plate. Antibody 5 and Antibody 6 did not demonstrate reactivity to pTau 217 in these assays. A graph in Fig.Figure 7, showing the results of this ELISA assay using the five test antibodies on phosphatase-treated pTau, demonstrated the specificity of the IBA493 mAb, PT3, and Antibody 2 antibodies in detecting phosphorylated Tau.

[145] The Tau antibodies described in this document that detect phosphorylated Tau were tested in Simoa®-based assays. Figs. 8-24 show results from Simoa® assays designed for sensitive testing of Tau reactivity to antibodies described in this document. In some respects, Simoa®-based assays can have approximately 1000 times greater sensitivity in detecting a given analyte when compared to detecting the same analyte in an indirect ELISA assay. This high sensitivity of Simoa®-based assays allows the development and use of biomarkers that previously could not have generated a detectable signal using a traditional assay such as indirect ELISA. The high sensitivity of Simoa®-based assays when compared to conventional immunoassays, such as indirect ELISA, is due to the fact that the Simoa® method is capable of detecting single target molecules, while conventional immunoassays typically Petition 870260068651, dated 10 / 07 / 2026, pp. 117 / 132 108 / 116 assays require a large reaction volume and millions of fluorophores, or millions of enzymes conjugated with antibodies, reacted with a color-producing substrate before an optical signal could be detected. For assays based on Simoa®, the average enzyme per account (AEB) indicates the raw signal output.

[146] In Figure 8, Antibody 2, as described in this document and capable of detecting pTau 217, was used in a Simoa®-based assay to detect an analyte level per plasma sample derived from an individual. The signal-to-noise ratio (S / N) was determined by Simoa® for each sample and plotted on a graph. 120 plasma samples were taken from individuals and subjected to assay. The graphically represented S / N ratio indicated that all samples tested, except one, produced a signal within the expected concentration range. When the plasma samples were diluted 1:3 and then subjected to assay again, only 3 of the 120 samples produced a result below the measurement of a blank control and only 5 samples recorded an S / N measurement of 1.5, which was determined to be the limit of detection (LOD). In Fig.8. For each of the 120 plasma samples analyzed, a calculation was made to determine the coefficient of variation (% CV) for each sample, and the results were plotted graphically in relation to the measured concentration. 10 of the 120 samples produced a % CV greater than 20, and from this analysis, the estimated analytical lower limit of quantification (LLOQ) was determined to be 0.08 pg / mL. This LLOQ value represents the smallest amount of an analyte (phosphorylated Tau in T217) that can be quantitatively determined with an acceptable level of precision. These results in Figure 8 indicated the sensitivity of the Simoa® method for detecting phosphorylated Tau in T217 using Antibody 2.

[147] In Figure 9, calibration curves were generated for the pTau-217 Simoa® assay and graphically represented [AEB vs Petition 870260068651, dated 10 / 07 / 2026, pages 118 / 132 [109 / 116 log(CAL) pg / mL] using 68 CSF samples and 120 plasma samples separated into 4 plates using Antibody 2 and 4 plates using the ADx Neuroscience ADx204 antibody. In another graph of this assay performed on a separate instrument [AEB vs log(CAL) pg / mL] with AEB plotted on a logarithmic scale, it was demonstrated that fitting the data can allow for precise analyte quantification calculations when measuring samples.

[148] In Figure 10, 38 paired samples of CSF and EDTA plasma were measured with the pTau-217 Simoa® assay using the Antibody 2. This assay is also referred to as ALZpath Dx. The results were graphically represented and the samples were indicated with their clinical diagnosis (no AD, uncertain, or AD). These results, and their statistical analysis, indicated a strong correlation between pTau levels in CSF and plasma, as measured with the Simoa® pTau-217 assay using Antibody 2 (R-value ~ 0.7 and P-value for two-tailed T-test <0.0001 between non- DA and DA).

[149] In Figure 11, 42 CSF samples were measured with the Simoa® pTau-217 assay using Antibody 2 and a Simoa® pTau-181 assay using a pTau-181 antibody from Quanterix® (Quanterix® Corp., Item number 103714) and conspired against each other. This demonstrated that the Simoa® pTau-217 assay using Antibody 2 showed the expected relationship with an analyte implicated in DA detected in CSF (pTau-181). Statistical analysis indicated an R value ~ 0.8 and a P-value for a two-tailed T-test < 0.0001.

[150] In Figure 12, 42 CSF samples were measured with the Simoa® pTau-217 assay using Antibody 2 and one Simoa® pTau assay using the Innotest pTau-181 antibody and plotted against each other. This demonstrated that the Simoa® pTau-217 assay using Antibody 2 showed the expected relationship with an analyte implicated in DA detected in CSF (pTau). Statistical analysis indicated an R value ~ 0.77 and a P-value for the two-tailed T-test < 0.0001.

[151] In Figure 13, 42 CSF samples were measured with a Petition 870260068651, dated 10 / 07 / 2026, pp. 119 / 132 110 / 116 HD-X Simoa® assay using Antibody 2 as capture antibody, ADx204 antibody as detector and a peptide as calibrator. This demonstrated that Simoa® assays using known AD biomarkers showed the expected relationship. Statistical analysis indicated an R-value ~ 0.9 and a P-value for the two-tailed t-test < 0.0001.

[152] In Figure 14, CSF and plasma samples were measured with the pTau-217 Simoa® assay using Antibody 2 and represented in separate graphs. Clinical diagnosis of AD, or control without AD diagnosis, was used as a classifier for each sample. Analysis of the graph results indicated a significant difference between samples derived from individuals with a clinical diagnosis of AD versus controls for CSF and plasma samples. The calculated area under the curve (AUC) was 0.94 for CSF samples and 0.86 for plasma samples. These results indicated that the pTau-217 Simoa® assay using Antibody 2 was able to differentiate AD cases in CSF and plasma.

[153] In Figure 15, 4 EDTA plasma samples with high pTau levels served as quality controls (labeled QC_L1, QC_L2, QC_M and QC_H) were measured with the Simoa® pTau-217 assay using Antibody 2 in duplicate testing and pTau levels were calculated. Plotting the results of repeated tests demonstrated the accuracy and reproducibility of the Simoa® pTau217 assay using Antibody 2.

[154] In Figure 16, control samples from Figure 15 and additional measured samples were measured with the Simoa® pTau217 assay using Antibody 2 and plotted in two separate experiments to generate precision profiles. The precision profiles are based on the measured sample concentration and the % CV between runs of the 4 QC samples. From this experiment, a functional LLOQ of pTau-217 in this assay was determined to be 0.26 pg / mL. Petition 870260068651, dated 10 / 07 / 2026, pages 120 / 132 111 / 116

[155] In Figure 17, parallelism was evaluated in the Simoa® pTau-217 assay using Antibody 2. A determination of parallelism is also important because it shows whether a signal is specific. Parallelism determines whether real samples containing high concentrations of endogenous analyte provide the same degree of detection in the assay on a standard curve after dilutions. This may account for differences in antibody binding affinity to the endogenous analyte and to a standard or calibration analyte. This can ensure that recombinant standards are parallel to the native recognition of the endogenous analyte. In this experiment, 4 plasma samples, each from different donors, with a relatively high concentration of detected pTau-217 and an enriched dilution buffer (sample 5) were diluted by a factor of 2 in 5 steps, starting with a 3X dilution. Concentrations fell below the LLOD from the 12X dilution factor for all 4 plasma samples.In a plot of log (measured pg / mL) vs log [dilution factor (DF)], plasma measurements over peak measurements demonstrated linearity in detection across the various dilutions. It was determined that 3 of the 4 plasma samples were within the accepted range of parallelism, with Sample 4 being outside the accepted range. The accepted range of parallelism is <15%. These results demonstrated that the Simoa® pTau-217 assay using Antibody 2 in plasma samples produced consistent and accurate calculations of pTau-217 levels at various concentrations, thus demonstrating its usefulness as a biomarker assay.

[156] In Figures 18-19, dilution linearity using the pTau-217 Simoa® assay using Antibody 2 was performed to demonstrate that a sample with a peak concentration around the upper limit of quantification (ULOQ) can be diluted to a concentration within the working range while still producing a reliable assay result. In Fig. 18, three Petition 870260068651, dated 10 / 07 / 2026, pages 121 / 132 112 / 116 enriched samples (s1, s2, and s3) and the calibration sample were analyzed and plotted as log (measured pg / mL) vs log (DF) to determine the linearity of the dilution. In Fig. 19, three enriched samples (s1, s2, and s3) and the calibration sample were analyzed and plotted as log (measured pg / mL) vs log (DF) to determine the linearity of the dilution, with the highest peak point omitted from s1, s2, and s3 because it was outside the calibration range of 50 pg / mL.

[157] In Figure 20, the Simoa® pTau-217 assay using Antibody 2 was used to evaluate samples taken from a clinical memory cohort. Plasma samples were measured and plotted for calculated pTau217 concentrations. The clinical diagnosis of AD was used as the classifier. The AUC was calculated at 0.916, indicating success in distinguishing AD+ from AD- within this cohort with the Simoa® pTau-217 assay using Antibody 2. Also in Fig. 20, a receptor operating characteristic (ROC) curve was plotted to illustrate the diagnostic capability of this binary classifier system (AD+ or AD-), as it is possible that the discrimination threshold between classifiers may vary.

[158] In Figures 21-22, the clinical performance of the pTau-217 Simoa® assay using Antibody 2 was compared with a pTau-181 Simoa® assay using the P-tau181 antibody - Quanterix®. In Fig. 21, Antibody 2 was able to distinguish analyzed plasma samples from individuals with AD dementia versus Controls (P-value 1.3e-12 for Antibody 2). In Fig. 22, the commercially available Ptau181 assay - Quanterix® Simoa® (Quanterix® Corp., Item number 103714) was also able to distinguish analyzed plasma samples from individuals with AD dementia vs. Controls (P-value 9.6e-08). The data of the individuals from whom the samples were derived for the data in Figs. 21-22 are listed in Fig. 22. Petition 870260068651, dated 10 / 07 / 2026, pages 122 / 132 113 / 116

[159] In Figure 23, precision plots were generated for the Simoa® assay using P-tau217 antibody 2 and Ptau181 antibody -Quanterix® (Quanterix® Corp., Item number 103714). The calculated LLODs were 0.55 pg / mL and 0.24 pg / mL, respectively. Concentrations were not retroactively calculated and LLOD values ​​are not retroactively calculated.

[160] In Figure 24, ROC curves were plotted for the P-tau181 antibody - Quanterix® (Quanterix® Corp., Item number 103714) and P-tau217 Antibody 2. Data analysis indicated that P-tau217 Antibody 2 exhibited superior sensitivity and specificity when compared to the Simoa® assay using the P-tau181 antibody - Quanterix® in differentiating AD dementia from controls. The diagnostic accuracy of Antibody 2 for AD dementia in this Simoa® method is 92.5% when tested on plasma samples. The diagnostic specificity of Antibody 2 for AD dementia in this Simoa® method is 85% when tested on plasma samples.

[161] Fig. 25 shows a schematic diagram of the Tau polypeptide indicating the relative location of various protein domains and the locations of threonine residues that can be assayed for phosphorylation status using methods disclosed in this document. The location of pT217 within the P2 domain of Tau is indicated. pT181 resides in the P1 domain and pT231 resides near the boundary between the P2 and R1 domains.

[162] In Figure 26, several Tau antibodies were subjected to assay using indirect ELISA and the extent of reactivity to a Tau fragment with unphosphorylated T217 (Bio-pt654) and full-length Tau (Tau441) was graphically represented. mAB IBA493 and PT3 exhibited concentration-dependent reactivity to both Bio-pt654 and Tau441. Antibodies 2, 5, and 6 described in this document do not show any reactivity to Bio-pt654 or Tau441 in this assay, demonstrating precision and Petition 870260068651, dated 10 / 07 / 2026, pp. 123 / 132 114 / 116 specificity in the detection of pTau-217 for Antibodies 2, 5 and 6.

[163] In Figure 27, several Tau antibodies were subjected to assay using indirect ELISA and the extent of reactivity to a Tau fragment with phosphorylated T181 (Bio-pt126) and phosphorylated T231 (Bio-pt146) was graphically represented. The mAB IBA493 and Antibody 2 described in this document exhibited concentration-dependent reactivity to Bio-pt126. mAB IBA493 was the only antibody tested that showed concentration-dependent reactivity to Bio-pt146. This demonstrates that the mAB IBA493, PT3 and Antibody 2 described in this document were distinguishable based on the analytes with which each antibody interacted via indirect ELISA. mAB IBA493 interacts with pTau-217, non-phosphorylated T217, full-length Tau, pTau-181 and pTau-231. PT3 interacts with pTau-217, phospho-free T217, and full-length Tau. Antibody 2 interacts with pTau-217 and pTau181.The interaction of IBA493 mAB with phospho-free T217 also proved to be considerably smaller than the interaction of PT3 with phospho-free T217.

[164] Fig. 28 shows a diagram of an assay using Antibody 2 to detect the capture of specific Tau peptides. In this assay, Antibody 2 is ligated onto a plate and the sample wells of the plate are subjected to various biotinylated peptides under conditions that lead to the formation of specific antibody-ligand interactions. The samples are then washed to remove excess unbound biotinylated peptide. Streptavidin beads conjugated with peroxidase are then added to the samples to allow the formation of biotin-streptavidin complexes in peptide-bound antibodies. The TMBred substrate is then added and the samples are measured for colorimetric revelation using an ELISA plate reader. The results were plotted and of several peptides pTau-217, pTau-231 and pTau-181 tested, Adx-pt655 produced reactivity Petition 870260068651, dated 10 / 07 / 2026, pages 124 / 132 115 / 116 specific dose-dependent. These results illustrate the specificity of Antibody 2 for specific features of pTau (i.e., Tau phosphorylated at threonine 217). Antibody 5 and Antibody 6 tested by indirect ELISA under the same conditions using the same Tau peptides did not produce any specific dose-dependent reactivity towards the tested Tau peptides.

[165] Several pTau-217 antibodies corresponding to Antibody 1, Antibody 2, Antibody 3, Antibody 4, Antibody 5 and Antibody 5 described in this document were also evaluated as capture antibodies coated directly on or over streptavidin-coated plates on the Mesoscale Discovery technology platform. This system uses non-radioactive electrochemiluminescent labels, thus conferring significant advantages over traditional ELISA assays. These advantages include lower reference signal, improved sensitivity and dynamic range of detection.

[166] In Figure 29, Western blots were used to evaluate the binding of various antibodies to brain lysate samples from AD patients and control subjects. In the five Western blots shown, samples are loaded according to the same sample key shown in Fig. 29. Protein ladders were run on rows 1 and 10. Phosphatase-treated PTau loaded in an amount of 0.05 µg was run on row 2. Full-length Tau (Tau411) loaded in an amount of 0.05 µg was run on row 3. Rows 4-6 contain samples from different control subjects with a dilution factor of 5. Rows 7-9 contain samples from different AD subjects with a dilution factor of 5.The results indicated that mAb IBA394 and PT3 bound and immunoprecipitated Tau isoforms of different lengths in control samples and AD samples, and immunoprecipitated significantly more Tau in AD samples, although showing no interaction with full-length Tau. Petition 870260068651, dated 10 / 07 / 2026, pages 125 / 132 116 / 116 synthetic or pTau treated with phosphatase. Antibody 2 (30H2L10) bound to and immunoprecipitated Tau isoforms of different lengths in DA samples, but did not immunoprecipitate a significant amount of Tau in samples from control subjects. Antibody 5 and Antibody 6 did not produce detectable Western blot signals in this assay.

[167] Although preferred embodiments of the present disclosure have been shown and described in this document, it will be obvious to those skilled in the art that such embodiments are provided only as examples. Numerous variations, alterations, and substitutions will now occur to those skilled in the art without departing from the disclosure. It should be understood that various alternatives to the embodiments of the disclosure described in this document may be employed in the practice of the disclosure. The following claims are intended to define the scope of the disclosure and the methods and structures within the scope of these claims and their equivalents are covered by them. Petition 870260068651, dated 10 / 07 / 2026, pp. 126 / 132

Claims

1 / 2 CLAIMS 1. Anti-tau antibody or functional antigen-binding fragment selected from the group consisting of Fab, F(ab')2, Fab', Fv, sFv, scFv, sdAb, sdFv, or nanobody, characterized in that it comprises: a heavy chain comprising a variable heavy chain (VH) domain consisting of SEQ ID NO: 31; and a light chain comprising a variable light chain (VL) domain consisting of SEQ ID NO:

36.

2. Anti-tau antibody or functional antigen-binding fragment thereof, according to claim 1, characterized in that the heavy chain comprises SEQ ID NO: 43, and the light chain comprises SEQ ID NO:

44.

3. Anti-tau antibody or functional antigen-binding fragment thereof, according to claim 1, characterized in that the anti-tau antibody or functional antigen-binding fragment thereof binds specifically to a tau protein.

4. Anti-tau antibody or functional antigen-binding fragment thereof, according to claim 1, characterized in that the anti-tau antibody or functional antigen-binding fragment thereof binds specifically to a human tau protein.

5. Anti-tau antibody or functional antigen-binding fragment thereof, according to claim 1, characterized in that the anti-tau antibody or functional antigen-binding fragment thereof binds specifically to a phosphorylated tau protein.

6. Anti-tau antibody or functional antigen-binding fragment thereof, according to claim 5, characterized in that the phosphorylated tau protein is selected from the group consisting of pTau-181, pTau-212, pTau-217, pTau-231, pTau-214, and pTau-220. Petition 870260068651, dated 10 / 07 / 2026, pp. 127 / 132 2 / 2 7. Anti-tau antibody or functional antigen-binding fragment thereof, according to claim 6, characterized in that the phosphorylated tau protein is pTau-181, pTau217, or pTau-231.

8. Anti-tau antibody or functional antigen-binding fragment thereof, according to claim 1, characterized in that the anti-tau antibody is a monoclonal antibody.

9. Anti-tau antibody or functional antigen-binding fragment thereof, according to claim 1, characterized in that the anti-tau antibody is a rabbit monoclonal antibody.

10. Anti-tau antibody or functional antigen-binding fragment thereof, according to claim 1, characterized in that the anti-tau antibody is a chimeric antibody.

11. Anti-tau antibody or functional antigen-binding fragment thereof, according to claim 1, characterized in that the anti-tau antibody comprises a constant region of IgG1. Petition 870260068651, dated 10 / 07 / 2026, pp. 128 / 132

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