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US 2023/0332135 A1Published application
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.
Claims18
A method of preparing a conditionally active biologic protein, the method comprising:
- i. selecting a wild-type biologic protein;
- ii. evolving the DNA which encodes the wild-type biologic protein using one or more evolutionary techniques to create a mutant DNA;
- iii. expressing the mutant DNA to obtain a mutant protein;
- iv. subjecting the mutant protein and the wild-type protein to an assay under a normal physiological condition and to an assay under an aberrant condition;
- and
- v. selecting the conditionally active biologic protein from those mutant proteins which exhibit both (a) a decrease in activity in the assay at the normal physiological condition compared to the wild-type protein, and (b) an increase in activity in the assay under the aberrant condition compared to the wild-type protein.
3 more elements
A method of preparing a conditionally active biological response modifier, the method comprising:
- a. selecting an inflammatory response mediator;
- b. identifying a wild-type antibody to the mediator;
- c. evolving the wild-type antibody;
- d. screening differentially for mutants that exhibit decreased binding to the mediator relative to the wild-type antibody at a first condition, and exhibit increased binding affinity to the mediator at a second condition to identify up-mutants;
- and
- e. recombining the heavy chains and the light chains of the up-mutants to create recombined up-mutants;
- and
- f. screening the recombined up-mutants for mutants that exhibit decreased binding to the mediator relative to the wild-type antibody at the first condition, and show increased binding affinity to the mediator at the second condition to identify the conditionally active biological response modifier.
5 more elements
Dependencies are inferred from the claim text.