Mirac proteins
AssigneeBioAtla, Inc.
InventorsJay M. Short, Hwai Wen Chang, Gerhard Frey
Life of this patent
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Abstract
This disclosure relates to a method of generating conditionally active biologic proteins from wild type proteins, in particular therapeutic proteins, which are reversibly or irreversibly inactivated at the wild type normal physiological conditions. For example, evolved proteins are virtually inactive at body temperature, but are active at lower temperatures.
Claims16
An in vitro method of identifying/selecting a modified therapeutic protein that is a therapeutic anti-tumor antibody or fragment thereof for treating tumors and that has greater binding activity to a target of the therapeutic anti-tumor antibody in a tumor microenvironment in a subject compared to binding activity to the same target in a non-tumor environment in the subject, the method comprising:
- 1) testing the binding activity of a plurality of modified therapeutic proteins under a) a pH less than 7.2 and testing the binding activity of the same plurality of modified therapeutic proteins under b) a pH of 7.2-7.6, wherein:
- the binding activity of the plurality of modified therapeutic proteins in a) and b) is tested in the presence of human serum and unless specified all other testing conditions in a) and b) are the same;
- each of the plurality of modified therapeutic protein contains an amino acid replacement, insertion, and/or deletion of an amino acid residue or residues compared to an unmodified form of the therapeutic protein;
- and
- each modified protein is tested in each of a) and b);
- 2) comparing the binding activity in a) to the binding activity in b);
- and
- 3) selecting/identifying a modified therapeutic protein that has greater binding activity in a) compared to b), thereby identifying one said therapeutic anti-tumor antibody or fragment thereof that is conditionally active such that it has greater binding activity to the target in a tumor microenvironment compared to the binding activity to the same target in a non-tumor environment.
An in vitro method of identifying/selecting a modified therapeutic protein that treats tumors and that has greater activity at a) a pH less than 7.2 compared to b) a pH in a range of 7.2-7.6, the method comprising:
- 1) testing the activity of a plurality of modified therapeutic proteins at a) the pH less than 7.2 in a presence of human serum, and testing the activity of the same plurality modified therapeutic proteins at b) the pH in the range of 7.2-7.6 in a presence of human serum and unless specified all other conditions in a) and b) are the same, wherein:
- each of the plurality of modified therapeutic protein contains an amino acid replacement, insertion, and/or deletion of an amino acid residue or residues compared to an unmodified form of the therapeutic protein;
- and
- each of the plurality of modified therapeutic protein is tested in each of a) and b);
- 2) comparing the activity at a) to the activity at b);
- and
- 3) selecting/identifying a modified therapeutic protein that has greater activity at a) compared to b), thereby identifying a protein that is conditionally active such that it has greater activity at a) compared to activity at b).
Dependencies are inferred from the claim text.