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AssigneeThe Scripps Research Institute
InventorsHongkai Zhang, Ian A. Wilson, Richard A. Lerner
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Methods for Identifying protein modulators of eukaryotic cells by expressing a combinatorial library of potential agonists inside a eukaryotic cell and then directly selecting for an agonist of a target molecule. Some methods involve co-culturing a cell expressing a combinatorial library of potential agonists and a second cell, and then selecting agents that modulate a phenotype of or a desired cellular response in the second cell. Preferably, the agonists are antibodies introduced into and expressed in the starting cells, such as agonist anti-EpoR, anti-TpoR, or G-CSFR antibodies. Also disclosed are methods for selecting from combinatorial antibody libraries bispecific antibodies that can regulate cell phenotypes.
A method for identifying a modulator antibody of a phenotype of a eukaryotic cell type, comprising (a) expressing in a population of cells of the eukaryotic cell type a library of candidate antibodies or antigen-binding fragments thereof to produce a heterogeneous population of modified, antibody-expressing cells, and (b) selecting a specific antibody-expressing cell with an altered phenotype relative to that of an unmodified control cell of said eukaryotic cell type;
(canceled)
11-13. (canceled)
A method for identifying an antibody modulator of a eukaryotic cell type, comprising (a) expressing in a homogeneous population of cells of a second cell type a library of candidate antibodies or antigen-binding fragments thereof under conditions each cell expresses no more than 3 different antibody species to produce a heterogeneous population of antibody-expressing cells, (b) co-culturing a population of cells of said eukaryotic cell type and the population of antibody-expressing cells, and (c) selecting a specific antibody-expressing cell that alters a phenotype of said eukaryotic cell type;
26-31. (canceled)
A method for identifying a polypeptide agent capable of reprograming or trans-differentiating a target cell, comprising (1) expressing a library of candidate polypeptide agents in a reporter cell bearing a signaling receptor expressed by the target cell to produce a heterogeneous population of modified, agent-expressing reporter cells, (2) identifying a subpopulation of agent-expressing reporter cells with activated signaling of the receptor, (3) isolating a group of agonist agents from the identified subpopulation of cells, and (4) contacting the group of agonist agents with a population of the target cell and selecting a cell with a specific phenotype indicative of trans-differentiation;
38-57. (canceled)
Dependencies are inferred from the claim text.