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US 11,300,566 B2Granted
ADAM-10 as a biomarker for detecting brain injury
AssigneeUniversity of Saskatchewan
InventorsChangiz Taghibiglou, Nathan Pham, Landon Pastushok, Clarence Ronald Geyer
Life of this patent
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Abstract
The present disclosure relates to a method for detecting a brain injury in a subject by comparing the amount of ADAM10 protein in a blood sample from the subject to a reference standard or to the amount of ADAM10 in a blood sample from a control. An increase in the amount of ADAM10 in the subject blood sample relative to the reference standard or control is indicative of the subject having sustained a brain injury, in particular a traumatic brain injury (TBI). The present disclosure also provides novel antibody and antibody fragments that bind to ADAM10 at different positions.
Claims12
A method of detecting brain injury in a test subject comprising:
- (a) obtaining a blood sample from the test subject;
- (b) quantifying the amount of Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) indirectly or directly by fluorescence, radioactivity or absorbance;
- and
- (c) imaging the brain of the subject by CT scan, treating the subject by surgery, treating the subject with anti-epileptic drugs and/or treating the subject with a post-concussion protocol, wherein the subject follows the post-concussion protocol including rest, when there is an increase in the amount of ADAM10 compared to a control and wherein the control is a reference baseline level of ADAM10.
1 more element
A method of monitoring a subject with a brain injury comprising:
- (i) (a) obtaining a blood sample from the subject at a first time point;
- (b) quantifying the amount of Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) at the first time point indirectly or directly by fluorescence, radioactivity or absorbance;
- (ii) (a) obtaining a blood sample from the subject at a second time point;
- (b) quantifying the amount of ADAM10 at the second time point indirectly or directly by fluorescence, radioactivity or absorbance;
- and
- (iii) imaging the brain of the subject by CT scan, treating the subject by surgery, treating the subject with anti-epileptic drugs and/or treating the subject with a post-concussion protocol, wherein the subject follows the post-concussion protocol including rest, when the amount of ADAM10 at the first time point is lower than the amount of ADAM10 at the second time point.
3 more elements
A method of determining whether a subject has suffered a brain injury due to an injury event comprising:
- (i) (a) obtaining a blood sample from the subject at a first time point prior to the injury event;
- (b) quantifying the amount of Disintegrin and metalloproteinase domain-containing protein 10 (ADAM 10) at the first time point indirectly or directly by fluorescence, radioactivity or absorbance;
- (iii) (a) obtaining a blood sample from the subject at a second time point after the injury event;
- (b) quantifying the amount of ADAM 10 at the second time point indirectly or directly by fluorescence, radioactivity or absorbance;
- and
- (iii) imaging the brain of the subject by CT scan, treating the subject by surgery, treating the subject with anti-epileptic drugs and/or treating the subject with a post-concussion protocol, wherein the subject follows the post-concussion protocol including rest, when the amount of ADAM10 at the first time point is lower than the amount of ADAM10 at the second time point.
3 more elements
A kit for analyzing a blood sample to detect brain injury, said kit comprising:
- (a) (i) an antibody or antibody fragment that detects an amount of ADAM10 in a blood sample;
- or
- (ii) an immobilized antibody or antibody fragment that binds to ADAM10 at a first position;
- and a detectable antibody or antibody fragment that binds to ADAM10 at a second position;
- and
- (b) instructions for use in analyzing the blood sample to detect brain injury,
- wherein the antibody or antibody fragment that detects an amount of ADAM10 in a blood sample, the antibody or antibody fragment that binds to ADAM10 at a first position, or the antibody or antibody fragment that binds to ADAM10 at a second position comprises:
- the heavy chain CDR sequences of SEQ ID NOs:
- 6, 7 and 8 and the light chain CDR sequences of SEQ ID NOs:
- 1, 2 and 3 thereof;
- the heavy chain CDR sequences of SEQ ID NOs:
- 6, 7 and 9 and the light chain CDR sequences of SEQ ID NOs:
- 1, 2 and 4;
- the heavy chain CDR sequences of SEQ ID NOs:
- 6, 7 and 10 and the light chain CDR sequences of SEQ ID NOs:
- 1, 2 and 5 thereof;
- the amino acid sequence as shown in SEQ ID NO:12 or is encoded by the nucleic acid sequence as shown in SEQ ID NO:11;
- the amino acid sequence as shown in SEQ ID NO:14 or is encoded by the nucleic acid sequence as shown in SEQ ID NO:13;
- or
- the amino acid sequence as shown in SEQ ID NO:16 or is encoded by the nucleic acid sequence as shown in SEQ ID NO:15.
17 more elements
An isolated antibody or antibody fragment comprising
- a) the heavy chain CDR sequences of SEQ ID NOs:
- 6, 7 and 8 and the light chain CDR sequences of SEQ ID NOs:
- 1, 2 and 3;
- b) the heavy chain CDR sequences of SEQ ID NOs:
- 6, 7 and 9 and the light chain CDR sequences of SEQ ID NOs:
- 1, 2 and 4;
- c) the heavy chain CDR sequences of SEQ ID NOs:
- 6, 7 and 10 and the light chain CDR sequences of SEQ ID NOs:
- 1, 2 and 5;
- d) the amino acid sequence as shown in SEQ ID NO:12 or is encoded by the nucleic acid sequence as shown in SEQ ID NO:11;
- e) the amino acid sequence as shown in SEQ ID NO:14 or is encoded by the nucleic acid sequence as shown in SEQ ID NO:13;
- or
- f) the amino acid sequence as shown in SEQ ID NO:16 or is encoded by the nucleic acid sequence as shown in SEQ ID NO:15.
10 more elements
Dependencies are inferred from the claim text.