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US 2014/0179551 A1Published application
Methods for the selection of binding proteins
AssigneeBristol-Myers Squibb Company
InventorDasa Lipovsek
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Abstract
This application provides an improved screening method for the selection of target-binding proteins having desirable biophysical properties. The method combines mRNA display and yeast surface display in a way that takes advantage of the desirable attributes of both processes.
Claims26
A method for selecting at least one target-binding protein with favorable biophysical properties, comprising
- a first phase comprising selecting a first population of protein variants binding a target protein (“target-binding protein variants”) from a library comprising at least about 1012 protein variants;
- and
- a second phase comprising selecting a second population of target-binding protein variants from at least a portion of the first population of target-binding protein variants using yeast surface display, wherein the second population of target-binding protein variants comprises at least one target-binding protein with favorable biophysical properties.
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A method for selecting a target-binding protein with favorable biophysical properties comprising
- (i) selecting a first population of target-binding protein variants consisting of at most 103 target-binding protein variants from a library comprising at least about 1012 protein variants, comprising conducting a number of rounds of selection sufficient to obtain the at most 103 target-binding protein variants;
- (ii) determining whether a significant number of the at most 103 target-binding protein variants have favorable biophysical properties;
- and
- (iii) if a significant number of the at most 103 target-binding protein variants do not have favorable biophysical properties, then selecting a population of at most 103 target-binding protein variants from at least 105 target-binding protein variants obtained during the selection in step (i) using yeast surface display.
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Dependencies are inferred from the claim text.