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US 2026/0209296 A1Published application
Compositions and methods for screening 4r tau targeting agents
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsJeffery Haines, Keith Crosby
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Abstract
Tau reporter compositions, tau reporter cells, and tau reporter animals are provided that comprise a four-repeat (4R) tau isoform linked to a first reporter protein and a three-repeat (3R) tau isoform linked to a second reporter protein that is different from the first reporter protein. Methods are provided for making such tau reporter cells and tau reporter animals and for using such tau reporter cells and tau reporter animals for assessing the activity of tau-targeting reagents.
Claims31
A method of assessing the activity of a tau-targeting reagent, comprising:
- (a) administering the tau-targeting reagent to a cell comprising a four-repeat (4R) tau isoform linked to a first reporter protein and a three-repeat (3R) tau isoform linked to a second reporter protein that is different from the first reporter protein;
- and
- (b) assessing the activity of the tau-targeting reagent in the cell, wherein:
- (I) the assessing comprises measuring 4R tau isoform messenger RNA expression and second reporter protein messenger RNA expression, wherein a larger relative decrease in 4R tau isoform messenger RNA expression compared to second reporter protein messenger RNA expression after administering the tau-targeting reagent to the cell indicates that the tau-targeting reagent is a 4R-preferential tau targeting reagent;
- (II) the assessing comprises measuring first reporter protein messenger RNA expression and second reporter protein messenger RNA expression, wherein a larger relative decrease in first reporter protein messenger RNA expression compared to second reporter protein messenger RNA expression after administering the tau-targeting reagent to the cell indicates that the tau-targeting reagent is a 4R-preferential tau targeting reagent;
- or
- (III) the assessing comprises measuring first reporter protein expression and second reporter protein expression, wherein a larger relative decrease in first reporter protein expression compared to second reporter protein expression after administering the tau-targeting reagent to the cell indicates that the tau-targeting reagent is a 4R-preferential tau targeting reagent.
4 more elements
A method of assessing the activity of a tau-targeting reagent in vivo, comprising:
- (a) administering the tau-targeting reagent to a non-human animal comprising a four-repeat (4R) tau isoform linked to a first reporter protein and a three-repeat (3R) tau isoform linked to a second reporter protein that is different from the first reporter protein;
- and
- (b) assessing the activity of the tau-targeting reagent in the non-human animal, wherein:
- (I) wherein the assessing comprises measuring 4R tau isoform messenger RNA expression and second reporter protein messenger RNA expression, wherein a larger relative decrease in 4R tau isoform messenger RNA expression compared to second reporter protein messenger RNA expression after administering the tau-targeting reagent to the non-human animal indicates that the tau-targeting reagent is a 4R-preferential tau targeting reagent;
- (II) wherein the assessing comprises measuring first reporter protein messenger RNA expression and second reporter protein messenger RNA expression, wherein a larger relative decrease in first reporter protein messenger RNA expression compared to second reporter protein messenger RNA expression after administering the tau-targeting reagent to the non-human animal indicates that the tau-targeting reagent is a 4R-preferential tau targeting reagent;
- or
- (III) wherein the assessing comprises measuring first reporter protein expression and second reporter protein expression, wherein a larger relative decrease in first reporter protein expression compared to second reporter protein expression after administering the tau-targeting reagent to the non-human animal indicates that the tau-targeting reagent is a 4R-preferential tau targeting reagent.
4 more elements
Dependencies are inferred from the claim text.