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US 10,329,556 B2Granted
Conditionally active biological proteins
AssigneeBioAtla, Inc.
InventorsJay M. Short, Hwai Wen Chang, Gerhard Frey
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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 some physiological conditions. For example, conditionally active biologic proteins are active in tumors, but virtually inactive at other body parts, or conditionally active antibodies cap able of crossing blood-brain-barrier.
Claims13
A method of preparing a conditionally active biological protein, the method comprising steps of:
- i) evolving the DNA which encodes a parent biological protein using one or more evolutionary techniques to create mutant DNAs;
- ii) expressing the mutant DNAs to obtain mutant biological proteins;
- iii) subjecting the mutant biological proteins to an assay under a first physiological condition selected from physiological conditions of a first location selected from the group consisting of synovial fluid, a stem cell niche and cytoplasm of a diseased tissue, and to an assay under a second physiological condition selected from physiological conditions of a second location in a body that is different from the first location;
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- iv) selecting the conditionally active biologic protein from the mutant biologic proteins which exhibit an increased activity in the assay under the first physiological condition compared to the activity in the assay under the second physiological condition.
2 more elements
Dependencies are inferred from the claim text.