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Abstract
The present invention is relevant to polypeptides and novel methods of polypeptide evolution. The present invention further relates to methods of identifying a cross-species mutant polypeptide from, or based upon, a template polypeptide.
Core Innovation
The invention provides a method of identifying a cross-species mutant antibody from a template antibody of a first species. The template antibody shows an activity on a target from the first species and has six complementarity determining regions comprising n amino acid residues.
The method generates a library of n separate sets of mutant antibodies, where each set contains mutant antibodies having X different predetermined amino acid residues at a single predetermined position within the six complementarity determining regions. The predetermined position of each set differs from the predetermined position of each other set, so the total number of different mutant antibodies in the library equals n×X.
The method selects mutant antibodies that show the activity on an ortholog of the target in a second, different species, and then screens the selected mutant antibodies for a cross-species mutant antibody that shows the activity on the target from the first species.
Claims Coverage
The partial content explicitly provides one independent claim. The inventive coverage centers on an end-to-end workflow that generates a position-resolved mutant antibody library from a template with six complementarity determining regions, selects mutants using ortholog activity in a second species, and screens selected mutants for activity on the original first-species target, totaling n×X mutant antibodies in the library.
Position-resolved mutant antibody library from a template with six complementarity determining regions
Generating a library of n separate sets of mutant antibodies from the template antibody, where each set comprises mutant antibodies having X different predetermined amino acid residues at a single predetermined position within the six complementarity determining regions, and where the single predetermined position of each set differs from the predetermined position of each other set, such that the total number of different mutant antibodies equals n×X.
Selection based on activity on an ortholog in a second species
Selecting mutant antibodies that show the activity on an ortholog of the target in a second, different species.
Screening selected mutants for cross-species activity on the first species target
Screening the selected mutant antibodies for a cross-species mutant antibody that shows the activity on the target from the first species.
The independent claim is centered on constructing a mutant antibody library with predetermined amino-acid substitutions at distinct positions within the six complementarity determining regions, using ortholog activity in a second species to select candidates, and then screening those candidates to obtain a mutant antibody that retains activity on the target from the first species.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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