Improved methods of assessing uch-l1 status in patient samples

A UCH-L1, state-of-the-art technology, applied in chemical instruments and methods, biochemical equipment and methods, instruments, etc., can solve problems such as lack of standardization of assays, chronic neurodegenerative diseases, neuronal dysfunction, etc.

Pending Publication Date: 2019-10-25
ABBOTT LAB INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Current biomarker candidates are limited by their insufficient sensitivity in serum assays, insufficient specificity for the brain, and lack of assay standardization
Lack of acute markers available for field assays to evaluate a range of TBI injuries from hyperacute to acute
Furthermore, there is currently no way to identify mild TBI (mTBI) with persistent post-concussion brain injury that can lead to posttraumatic stress disorder (PTSD) or chronic neurodegenerative disease (chronic traumatic encephalopathy, CTE , "Boxing Drunk")
[0007] It is difficult to objectively detect mild TBI or concussion and is a daily challenge in critical care departments in military fields, emergency rooms, inpatient hospitals, outpatient clinics and sports fields around the world
Concussion usually does not cause gross pathology such as hemorrhage and is normal on routine computed tomography of the brain, but there is rapid onset neuronal dysfunction that resolves spontaneously over days to weeks

Method used

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  • Improved methods of assessing uch-l1 status in patient samples
  • Improved methods of assessing uch-l1 status in patient samples
  • Improved methods of assessing uch-l1 status in patient samples

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0389] UCH-L1 assay

[0390] Antibodies were screened using an assay format of interest (i-STAT). Pairs of antibodies that produced a signal in the assay were selected. Initial selection conditions were based on a number of factors, including detection of signal by antibody pairs when screening with low calibrator concentrations. Pairs of monoclonal antibodies were tested, eg Antibody A as capture mAb, and Antibodies B and C as detection mAbs. Antibody A is an exemplary anti-UCH-L1 antibody developed in-house at Abbott Laboratories (Abbott Park, IL). Antibody B and Antibody C are exemplary anti-UCH-L1 antibodies developed at Banyan Biomarkers, Inc. Antibodies B and C recognize different epitopes of UCH-L1 and can enhance the detection of antigens in samples. When used together, the combination of these antibodies provides a synergistic effect and may enhance signaling. Other antibodies developed in-house at Abbott Laboratories (Abbott Park, IL) have shown or are predict...

Embodiment 2

[0422] Possible Assay Interference

[0423] The UCH-L1 assay was evaluated for possible interferences and cross-reactants, as shown in Table 11. In summary, interferors were spiked into the UCH-L1 panel at target concentrations of 200-250 pg / mL. The test concentration of interfering substances is based on CLSI EP7-A2 guidance (Clinical and Laboratory Standards Institute. Interference Testing in Clinical Chemistry; Approved Guideline-Second Edition. CLSI document EP7-A2 [ISBN 1-56238-584-4]. Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2005.). Possible cross-reactants were tested at 500 ng / mL. The acceptance criterion was <10% interferents.

[0424] Specifically, the UCH-L1 assay was evaluated for possible endogenous interference. Potential interfering substances were prepared in preferred buffers / solvents and added to test samples containing the analytes of interest. Control samples were prepared where o...

Embodiment 3

[0435] TBI Population Study

[0436] The i-STAT UCH-L1 assay was used in a TBI patient population study.

[0437] Study Samples: A total of 260 subjects with moderate to severe TBI were enrolled, up to 8 time points / subject; all samples were serum. Table 12; FIG3.

[0438] Table 12

[0439]

[0440] Assignment of study samples. image 3 Median results of all UCH-L1 assay results at each time point are shown, indicating that UCH-L1 is higher on B1 samples and tends to decrease with later time points. Figure 4 Shown are boxplots (log scale) at each sample time point showing broad distribution of UCH-L1 results in the patient population. The boxes represent interquartile ranges (25th, 50th and 75th percentiles).

[0441] In all, a total of 250 subjects were available for testing. Not all time points are necessarily available from all subjects. Some samples had limited or insufficient volume. UCH-L1 results ranged from <0.05 to 12,100 pg / mL, and these results were read...

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Abstract

Disclosed herein are improved methods of assessing ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) status in a subject (such as for example, as a measure of traumatic brain injury or for other clinical reasons). Also disclosed herein are methods of assessing a subject's glial fibrillary acid protein (GFAP) and UCH-L1 status in subject (such as, for example as a measure of traumatic brain injury or for other clinical reasons).

Description

[0001] Cross References to Related Applications [0002] This application claims priority over U.S. Provisional Application No. 62 / 403,293, filed October 3, 2016, and U.S. Provisional Application No. 62 / 455,269, filed February 6, 2017, which are hereby incorporated by reference in their entirety. [0003] Inclusion of material submitted electronically by reference [0004] This Express Application contains a Sequence Listing that has been submitted in ASCII format via EFS-Web, which is incorporated by reference in its entirety. Said ASCII copy, created on October 2, 2017, has the filename 2017_10_02_12994W001-SEQ-LIST.txt and is 6,284 bytes in size. technical field [0005] The present disclosure relates to improved assessment methods of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1 ) status, eg, for use as a measure of traumatic brain injury or other clinical causes. The present disclosure relates to methods of assessing glial fibrillary acidic protein (GFAP) and UCH-L1 s...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/573
CPCG01N33/573G01N2333/916G01N2333/948G01N2333/978C12N9/16C12Y301/02015G01N33/581G01N33/566G01N33/6896G01N2800/28G01N2800/50G01N2800/52C07K2317/92C07K2317/94G01N33/535G01N2800/2871
Inventor S·德特维勒B·麦奎斯顿G·博利格尔E·布拉特J·莱普D·帕森缇
Owner ABBOTT LAB INC
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