E3 ubiquitin ligase (ube3a) protein targets
AssigneeHoffmann-La Roche Inc.
InventorsVeronica Costa, Thomas Peter John Dunkley, Nikhil Janak Pandya, Ravi Jagasia
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Abstract
The invention relates to UBE3A protein targets and their usage as target engagement biomarkers for compounds that modulate ube3a expression.
Claims20
A method for measuring UBE3A protein expression modulation in a tissue sample comprising the steps:
- a) providing a tissue sample of an animal or cell culture which has been treated with a UBE3A modulator,
- b) measuring a protein expression level in the sample of step a) of at least one protein selected from the group consisting of:
- CCDC88A, DST, FAM127A, FAM127B, FAM127C, PEG10 and TCAF1, PPID.
- c) comparing the protein expression level of the at least one protein measured in step b) to the protein expression level of the at least one protein in a control, wherein a modulated protein expression level of the at least one protein measured in step b) compared to the protein expression level of the at least one protein in the control is indicative for UBE3A protein expression modulation.
A method for determining UBE3A target engagement of an UBE3A modulator comprising the steps:
- a) providing a tissue sample of an animal or cell culture which has been treated with a UBE3A modulator,
- b) measuring a protein expression level in the sample of step a) of at least one protein selected from the group consisting of:
- CCDC88A, DST, FAM127A, FAM127B, FAM127C, PEG10, TCAF1 and PPID.
- c) comparing the protein expression level of the at least one protein measured in step b) to the protein expression level of the at least one protein in a control, wherein a modulated protein expression level of the at least one protein measured in step b) compared to the protein expression level of the at least one protein in the control is indicative for UBE3A target engagement of the UBE3A modulator.
A screening method for the identification of UBE3A protein expression modulators comprising the steps:
- a) providing a tissue sample of an animal or cell culture which has been treated with a test compound,
- b) measuring a protein expression level in the sample of step a) of at least one protein selected from the group consisting of:
- CCDC88A, DST, FAM127A, FAM127B, FAM127C, PEG10, TCAF1 and PPID.
- c) comparing the protein expression level of the at least one protein measured in step b) to the protein expression level of the at least one protein in a control, wherein a modulated protein expression level of the at least one protein measured in step b) compared to the protein expression level of the at least one protein in the control is indicative for a UBE3A protein expression modulator.
Use of a protein selected from the group consisting of CCDC88A, DST, FAM127A, FAM127B, FAM127C, PEG10 and TCAF1 as biomarker for UBE3A protein expression level modulation.
The method of 8, wherein the UBE3A modulator is a LNA antisense oligonucleotide.
Dependencies are inferred from the claim text.