Engineering of dnase enzymes for manufacturing and therapy
AssigneeNeutrolis, Inc.
InventorsTobias A. FUCHS, Abdul HAKKIM R.
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Abstract
The present disclosure provides engineered human extracellular DNASE proteins (e.g., variants of DNASE1 (D1), DNASE1-LIKE 1 (D1L1), DNASE1-LIKE 2 (D1L2), DNASE1-LIKE 3 Isoform 1 (D1L3), DNASE1-LIKE 3 Isoform 2 (D1L3-2), DNASE2A (D2A), and DNASE2B (D2B)) that are useful for treating conditions characterized by neutrophil extracellular trap (NET) accumulation and/or release. In accordance with the invention, the DNase variant has advantages for therapy and/or large-scale manufacturing.
Claims21
1-101. (canceled)
A DNase1-like 3 (D1L3) variant comprising an amino acid sequence that has at least 95% sequence identity to amino acids 21 to 282 of SEQ ID NO:
- 4 or amino acids 21 to 252 of SEQ ID NO:
- 5, wherein the D1L3 enzyme comprises a substitution at the amino acid corresponding to C68 with respect to SEQ ID NO:
- 4, and wherein the D1L3 enzyme has a C-terminal deletion of at least 10 amino acids corresponding to amino acids 296-305 of the polypeptide of SEQ ID NO:
- 4.
Dependencies are inferred from the claim text.