Mirac proteins

A method of preparing a conditionally active antibody, the method comprising steps of:

• i. evolving a DNA which encodes a parent antibody to an antigen using one or more evolutionary techniques to create mutant DNAs;
• ii. expressing the mutant DNAs to obtain at least one mutant antibody which exhibits an increased binding activity to the antigen in an assay at an aberrant condition that deviates from a normal range of a physiological condition at a site of administration of the mutant antibody, or at a tissue or organ at a site of action of the mutant antibody, when compared to the binding activity to the antigen by the same mutant antibody in an assay at a normal physiological condition that is within the normal range of the physiological condition at the site of administration of the mutant antibody, or at the tissue or organ at the site of action of the mutant antibody;
• and
• iii. selecting the conditionally active antibody from the at least one mutant antibody which exhibits an increased binding activity to the antigen in the assay at the aberrant condition that deviates from the normal range of the physiological condition at the site of administration of the conditionally active antibody, or at the tissue or organ at the site of action of the conditionally active antibody, compared to the binding activity by the same conditionally active antibody in the assay under the normal physiological condition that is within the normal range of the physiological condition at the site of administration of the conditionally active antibody, or at the tissue or organ at the site of action of the conditionally active antibody,
• wherein the normal physiological condition and aberrant condition are a same condition selected from temperature, pH, osmotic pressure, oxidation, osmolality, and electrolyte concentration.