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CN-121873240-B - MTBR-tau243 specific antibody and application thereof in Alzheimer disease auxiliary diagnosis kit

CN121873240BCN 121873240 BCN121873240 BCN 121873240BCN-121873240-B

Abstract

The application discloses an MTBR-tau243 specific antibody and application thereof in an Alzheimer's disease auxiliary diagnosis kit, belongs to the technical field of immunoassay, and provides an MTBR-tau243 targeting antibody and a MTBR-tau243 detecting chemiluminescent kit. The antibody of the application has high affinity, high sensitivity and obviously shortened production period, and is more suitable for being used as a core raw material in the field of in vitro diagnostic reagents. The kit disclosed by the application can be used for auxiliary diagnosis of diseases related to MTBR-tau243, such as Alzheimer's disease.

Inventors

  • TANG BO
  • LI SHUANGFA
  • CHENG YUNLONG
  • WANG ZIMING
  • FENG SU

Assignees

  • 南京诺唯赞医疗科技有限公司
  • 湖南诺唯赞医疗科技有限公司

Dates

Publication Date
20260512
Application Date
20260323

Claims (10)

  1. 1. An antibody or antigen binding fragment thereof specifically binding MTBR-tau243 is characterized in that the amino acid sequence of heavy chain CDRH1-CDRH3 is shown as SEQ ID NO. 1-SEQ ID NO. 3, the amino acid sequence of light chain CDRL1 is shown as SEQ ID NO. 4, the amino acid sequence of light chain CDRL2 is TT, and the amino acid sequence of light chain CDRL3 is shown as SEQ ID NO. 5.
  2. 2. The antibody or antigen-binding fragment thereof according to claim 1, wherein it comprises a heavy chain variable region VH as shown in SEQ ID NO. 6 and a light chain variable region VL as shown in SEQ ID NO. 7.
  3. 3. A kit for detecting MTBR-tau243, comprising magnetic beads coated with a first antibody and a second antibody labeled with a chemiluminescent agent; Wherein the second antibody in the pair of the first antibody and the second antibody is the antibody or the antigen binding fragment thereof according to claim 1.
  4. 4. A kit according to claim 3, wherein the heavy chain CDRH1-CDRH3 amino acid sequence of the first antibody is shown in SEQ ID No. 18-SEQ ID No. 20, the light chain CDRL1 amino acid sequence is shown in SEQ ID No. 21, the light chain CDRL2 amino acid sequence is RAS, and the light chain CDRL3 amino acid sequence is shown in SEQ ID No. 22.
  5. 5. The kit according to claim 4, wherein the first antibody comprises a heavy chain variable region VH shown in SEQ ID NO. 16 and a light chain variable region VL shown in SEQ ID NO. 17.
  6. 6. The kit according to claim 3, wherein the chemiluminescent agent is at least one selected from the group consisting of acridinium esters, alkaline phosphatase, and horseradish peroxidase.
  7. 7. Use of the antibody or antigen binding fragment thereof of claim 1 in the preparation of a kit for detecting MTBR-tau243 protein.
  8. 8. Use of the antibody or antigen binding fragment thereof of claim 1 in the preparation of a kit for aiding in the diagnosis of alzheimer's disease.
  9. 9. A biomaterial, characterized by being selected from any one of the following: a. A polynucleotide encoding the antibody or antigen binding fragment thereof of claim 1; b. a vector comprising the polynucleotide of a; c. a host cell comprising b said vector or a polynucleotide of a integrated in the genome.
  10. 10. A kit for detecting MTBR-tau243 protein, comprising the antibody or antigen-binding fragment thereof of claim 1.

Description

MTBR-tau243 specific antibody and application thereof in Alzheimer disease auxiliary diagnosis kit Technical Field The application belongs to the technical field of immunoassay, and relates to an MTBR-tau243 specific antibody and application thereof in an Alzheimer disease auxiliary diagnosis kit. Background Alzheimer's Disease (AD) is an age-related, progressive and irreversible neurodegenerative Disease, frequently occurring in the elderly or in the pre-senile stages. Clinical manifestations are progressive decline of memory, thinking, analytical judgment, spatial recognition, emotion, and daily life ability without consciousness disturbance, and various neuropsychiatric symptoms and behavioral disturbance. It was found that the main pathological manifestations of AD are senile plaques formed by extracellular β -amyloid (aβ) deposition in the brain, neurofibrillary tangles consisting of hyperphosphorylated Tau protein (p-Tau) in the cell, neuronal loss and synaptic dysfunction. Among these, the aβ cascade hypothesis and the Tau protein hypothesis are two major core pathological mechanisms. Although currently commonly used cerebrospinal fluid (CSF) phosphorylates tau (e.g. p-tau181, p-tau 217) to reflect AD pathology, it is more associated with amyloid plaques (aβ), which essentially reflect downstream signals triggered by amyloid plaques, rather than specifically reflect tau entanglement pathology. In this regard, MTBR-tau243, a novel biomarker for specifically detecting AD tau protein tangle pathology, has attracted attention. MTBR-tau243 is an endogenous truncated tau protein fragment comprising residue 243 of the microtubule binding region (MTBR) and is specifically cleaved at residue 256 (valine) and deamidated at residue 255 (asparagine), this unique modification making it closely related to insoluble tau tangles formed in AD brain. Moreover, tau-Positron Emission Tomography (PET) has demonstrated that MTBR-tau243 reflects brain tau tangle pathological changes in Alzheimer's disease more than other defined markers (p-tau 181, p-tau217 and p-tau 231). This discovery provides a new potential biomarker for early diagnosis and monitoring of AD. Disclosure of Invention The present application provides specific antibodies to MTBR-tau243, i.e., provides an antibody Anti-MTBR-tau 243-rRmab-1 specific to MTBR-tau 243. The monoclonal antibody prepared by adopting the single B cell technology has higher sensitivity and obviously shortened production period, and the kit prepared by utilizing the Anti-MTBR-tau 243-rRmab-1 has high sensitivity and low detection limit, so that a tool is provided for auxiliary diagnosis of diseases related to MTBR-tau243, and the application of the antibody or the kit in auxiliary diagnosis of Alzheimer's disease is further provided. In one aspect, the application provides an antibody or antigen-binding fragment thereof that specifically binds MTBR-tau 243. In some embodiments, the antibody or antigen binding fragment comprises at least one, two, three, four, five, or six CDRs selected from (a) a CDR-H1 comprising a heavy chain variable region as having 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID No. 1; (b) a heavy chain variable region CDR-H2 comprising, for example, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO:2, (c) a heavy chain variable region CDR-H3 comprising, for example, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO:3, (d) a light chain variable region CDR-L1 comprising, for example, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO:4, (e) a light chain variable region CDR-L2 comprising, for example, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of TT, and (f) a light chain variable region CDR-L2 comprising, for example, 90%, 91%, 92%, 94%, 96%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 5. In some embodiments, the antibody or antigen binding fragment comprises at least one, at least two, or all three VH CDR sequences selected from (a) comprising a heavy chain variable region CDR-H1 as having 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO:1, (b) comprising a heavy chain variable region CDR-H2 as having 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO:2, and (c) comprising a heavy chain variable region CDR-H3 as having 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the antibody or antigen binding fragment comprises at least one, at least two, or all three VL CDR sequences selected from (a) a light