Polypeptides Comprising Modified IL-2 Polypeptides and Uses Thereof
AssigneeInhibrx, Inc.
InventorsJohn C. Timmer, Brendan P. Eckelman, Katelyn McKabe Willis, Florian J. Sulzmaier, Bryan R. Becklund
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Abstract
Provided herein are polypeptide comprising a modified IL-2, wherein the modified IL-2 has reduced affinity for the IL-2 receptor relative to wild type IL-2. In some embodiments, polypeptides comprising a modified IL-2 that bind and agonize activated T cells are provided. Uses of the polypeptides comprising a modified IL-2 are also provided.
Claims125
A polypeptide comprising a modified IL-2, wherein the modified IL-2 comprises at least one substitution at at least one amino acid position selected from P65, D84, E95, M23, and H16.
The polypeptide of any one of the preceding claims, wherein the modified IL-2 comprises a substitution at amino acid position P65.
The polypeptide of any one of the preceding claims, wherein the modified IL-2 comprises a substitution at amino acid position H16.
The polypeptide of any one of the preceding claims, wherein the modified IL-2 comprises a substitution at amino acid position D84.
The polypeptide of any one of the preceding claims, wherein the modified IL-2 comprises substitutions at amino acid positions P65, H16, and D84.
The polypeptide of any one of the preceding claims, wherein the modified IL-2 comprises a substitution at amino acid position M23.
The polypeptide of any one of the preceding claims, wherein the modified IL-2 comprises a substitution at amino acid position E95.
The polypeptide of any one of any one of the preceding claims, wherein the modified IL-2 comprises a substitution at amino acid position F42.
The polypeptide of any one of the preceding claims, wherein the modified IL-2 comprises at least one substitution at at least one amino acid position selected from Y45 and L72.
The polypeptide of any one of the preceding claims, wherein the modified IL-2 comprises at least one substitution at at least one amino acid position selected from T3 and C125.
The polypeptide of any one of the preceding claims, wherein the modified IL-2 comprises a set of substitutions selected from H16A-F42K;
- D84S-F42K;
- E15S-F42K;
- M23A-F42K;
- E95Q-F42K;
- P65R-H16A;
- P65R-D84S;
- P65R-E15S;
- P65R-M23A;
- P65R-E95Q;
- T3A-C125S;
- T3A-P65R-C125S;
- T3A-H16A-C125S;
- T3A-D84S-C125S;
- T3A-H16A-P65R-C125S;
- T3A-P65R-D84S-C125S;
- T3A-H16A-P65R-D84S-C125S;
- T3A-H16A-M23A-P65R-D84S-C125S;
- T3A-H16A-P65R-D84S-E95Q-C125S, and T3A-H16A-M23A-P65R-D84S-E95Q-C125 S.
The polypeptide of any one of the preceding claims, wherein the modified IL-2 comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:
- 84.
The polypeptide of any one of the preceding claims, wherein the modified IL-2 comprises an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to an amino acid sequence selected from SEQ ID NOs:
- 3-9, 11-21, and 23-31.
The polypeptide of any one of the preceding claims, wherein the modified IL-2 comprises an amino acid sequence selected from SEQ ID NOs:
- 3-9, 11-21, and 23-31.
The polypeptide of any one of the preceding claims, wherein the polypeptide comprises an Fc region.
The polypeptide of any one of the preceding claims, wherein the polypeptide comprises at least one antigen binding domain.
Dependencies are inferred from the claim text.