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US 10,137,205 B2Granted
Thymidylate kinase fusions and uses thereof
AssigneeUniversity Health Network
InventorsJeffrey A. Medin, Sean Devine
Life of this patent
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Abstract
The application relates to a composition comprising a stably integrating delivery vector, a modified mammalian thymidylate kinase (tmpk) that increases phosphorylation of a prodrug relative to phosphorylation of the prodrug by wild-type human tmpk, and a detection cassette fused to the tmpk. The application also relates to use of these compositions in methods of treatment of diseases, such as graft versus host disease and cancer.
Claims9
A composition comprising:
- (a) a stably integrating delivery vector;
- (b) a polynucleotide encoding a modified human thymidylate kinase (tmpk), wherein the modified human tmpk increases phosphorylation of 3′-azido-3′-deoxythymidine (AZT) relative to phosphorylation of AZT by wild-type human tmpk;
- and
- (c) a polynucleotide encoding a detection cassette polypeptide that is expressed on the surface of a cell, wherein the polynucleotide encoding the detection cassette polypeptide is fused to the polynucleotide encoding the modified human tmpk and the detection cassette polypeptide is fused to the modified human tmpk;
- wherein the modified human tmpk comprises a modification selected from the group consisting of (i) a F to Y mutation at amino acid position 105 of SEQ ID NO:
- 11;
- (ii) a R to G mutation at amino acid position 16 of SEQ ID NO:
- 12;
- and (iii) a R to A mutation at amino acid position 200 of SEQ ID NO:
- 16.
7 more elements
Dependencies are inferred from the claim text.