Modified antibody variable domains
AssigneeXoma Technology Ltd.
InventorGary M. Studnicka
Life of this patent
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Abstract
Methods are described for identifying the amino acid residues of an antibody variable domain which may be modified without diminishing the native affinity of the domain for antigen while reducing its immunogenicity with respect to a heterologous species and for preparing so modified antibody variable domains which are useful for administration to heterologous species. Antibody variable regions prepared by the methods of the invention are also described.
Claims12
A protein that contains a modified variable domain, wherein the variable domain is produced by a process comprising:
- (a) identifying the low risk amino acid positions in an antibody variable domain using the paired bind and bury lines as shown in FIG. 6A or 6B;
- and
- (b) changing amino acid residues at low risk positions in the light chain variable region or the heavy chain variable region in the domain of part (a), or both, to the amino acid residue in the corresponding position in the amino acid sequence of a selected antibody light or heavy chain variable region sequence or consensus sequence.
A protein that contains a modified variable domain, the variable domain comprising an amino acid sequence modified at low risk positions such that each amino acid residue that is in a low risk position in the light chain variable region sequence of the domain is the same as the amino acid residue at the corresponding position of a selected antibody light chain variable region sequence or consensus sequence, or each amino acid residue that is in a low risk position in the heavy chain variable region sequence of the domain is the same as the amino acid residue at the corresponding position of a selected antibody heavy chain variable region sequence or consensus sequence, or each amino acid residue that is in a low risk position in both the light and heavy chain variable region sequences of the domain are the same as the amino acid residue at the corresponding position of the selected antibody light and heavy chain variable region sequence or consensus sequence, the low risk amino acid position being determined by the paired bind and bury lines of FIG. 6A or 6B.
A composition comprising the protein of claim 27 and (i) a detectable label or (ii) a pharmaceutically acceptable carrier, stabilizer, buffer or excipient.
Dependencies are inferred from the claim text.