Modified antibody variable domains
AssigneeXoma Corporation
InventorsGary M. Studnicka, Roger G. Little, II, Dianne M. Fishwild, Fred R. Kohn
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.
Claims23
A method for modifying an antibody variable domain, said method comprising:
- (a) identifying the risk assigned to amino acid positions in said 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, moderate, or low and moderate risk positions in said domain 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;
- and
- (c) obtaining a modified antibody variable domain that binds antigen.
A method for modifying the variable region sequence of an antibody light chain, said method comprising:
- (a) identifying the risk assigned to amino acid positions in said antibody light chain's variable region sequence using the paired bind and bury lines as shown in FIG. 6A;
- and
- (b) changing amino acid residues at low, moderate, or low and moderate risk positions in said variable region sequence to the amino acid residue in the corresponding position in the amino acid sequence of a selected antibody light chain variable region sequence or consensus sequence;
- and
- (c) obtaining a modified variable region sequence of an antibody light chain that, when associated with a heavy chain variable region, binds antigen.
A method for modifying the variable region sequence of an antibody heavy chain, said method comprising:
- (a) identifying the risk assigned to amino acid positions in said antibody heavy chain's variable region sequence using the paired bind and bury lines as shown in FIG. 6B;
- and
- (b) changing amino acid residues at low, moderate, or low and moderate risk positions in said variable region sequence to the amino acid residue in the corresponding position in the amino acid sequence of a selected antibody heavy chain variable region sequence or consensus sequence;
- and
- (c) obtaining a modified variable region sequence of an antibody heavy chain that, when associated with a light chain variable region, binds antigen.
Dependencies are inferred from the claim text.