Compositions and methods for predicting therapeutic outcome
AssigneeWashington University
InventorsJieya Shao, Marc Diamond
Life of this patent
Estimating the term…
Abstract
The present disclosure provides methods to quantify VCP phosphorylation at specific amino acid residue to predict responsiveness of a subject having a cancer or tumor to a genotoxic treatment, guide treatment decisions, select subjects for clinical trials, and evaluate the clinical efficacy of certain therapeutic interventions.
Claims21
1-20. (canceled)
An isolated antibody that specifically binds to the pSer784 phosphorylation site of valosin-containing protein (pSer784-VCP) wherein the antibody comprises:
- (a) a light chain variable region comprising a complementarity determining region 1 (CDR1) comprising the amino acid sequence set forth in SEQ ID NO:13;
- a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:14, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:15;
- and (b) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
- 10, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
- 11, and a CDR3comprising the amino acid sequence set forth in SEQ ID NO:
- 12.
A method for assessing responsiveness to a genotoxic treatment in a subject having a cancer or tumor, the method comprising:
- (a) providing a biological sample obtained from the subject and measuring, in a cancer cell or tumor cell from the sample, the level of VCP phosphorylation at Ser784;
- and (b) determining the subjects responsiveness to the genotoxic therapy when the measured phosphorylation level deviates from a reference value.
A method of selecting a treatment for a subject having a cancer or tumor, the method comprising;
- (a) providing a biological sample obtained from the subject and measuring, in a cancer cell or tumor cell from the sample, the level of VCP phosphorylation at Ser784;
- (b) determining the subjects responsiveness to a genotoxic therapy when the measured phosphorylation level deviates from a reference value;
- and (c) administering a pharmaceutical composition comprising a genotoxic agent to the subject when the measured phosphorylation level is reduced relative to the reference value of a control subject or control population who are non-responsive to genotoxic therapy or administering a pharmaceutical composition comprising an inhibitor of one or more phosphatidylinositol 3-kinase-related kinases to the subject when the measured phosphorylation level is elevated relative to the reference value of a control subject or control population who are responsive to genotoxic therapy.
Dependencies are inferred from the claim text.