Engineered dnase enzymes and use in therapy
AssigneeNeutrolis, Inc.
InventorsTobias A. FUCHS, Miguel JIMÉNEZ-ALCÁZAR, Josephine GÖBEL, Hanna ENGLERT
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Abstract
The present invention provides engineered DNase proteins (including DNase1-like 3 and DNase1) that are useful for treating conditions characterized by neutrophil extracellular trap (NET) accumulation and/or release. In some aspects, the invention provides compositions and methods for preventing or treating vascular occlusion involving NETs. As demonstrated herein, NETs participate in a non-canonical mechanism for vascular occlusion, which is not dependent on fibrin or platelets.
Claims26
1-157. (canceled)
A method for treating a human subject having an intravascular accumulation of neutrophil extracellular traps (NETs), the method comprising systemically administering an effective amount of a DNase1-like 3 (D1L3) enzyme comprising an amino acid sequence having at least 90% sequence identity to amino acids 21 to 305 of SEQ ID NO:
- 2 to said subject, wherein the subject has a condition selected from:
- a severe inflammatory disease selected from acute respiratory distress syndrome (ARDS), sepsis, and a viral infection;
- partially or fully occluded blood vessels;
- thrombotic microangiopathy (TMA);
- disseminated intravascular coagulation (DIC);
- venous thromboembolism;
- leukemia;
- and
- tumor metastasis.
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-175 (canceled)
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Dependencies are inferred from the claim text.