C12Y304/21076

METHODS FOR EXTRACTING NEUTROPHIL SERINE PROTEASES AND TREATING DIPEPTIDYL PEPTIDASE 1-MEDIATED CONDITIONS
20230310453 · 2023-10-05 ·

Methods are provided for extracting one or more neutrophil serine proteases (NSPs), e.g., neutrophil elastase (NE), proteinase 3 (PR3), cathepsin G (CatG), neutrophil serine protease 4 (NSP4), or a combination thereof, from a sample comprising white blood cells (WBCs) obtained from a subject. The extraction methods feature the use of nonionic surfactants and two or more cycles of repeated lysis of WBCs and their residuals. Also provided are methods for treating dipeptidyl peptidase 1 (DPP1)-mediated conditions in a patient with compositions comprising certain N-(1-cyano-2-phenylethyl)-1,4-oxazepane-2-carboxamide compounds of formula (I), including pharmaceutically acceptable salts thereof,

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that reversibly inhibit (DPP1) activity. The treatment methods provided herein use the concentration of active NSPs extracted from a patient's WBC sample as a biomarker to guide the selection of, or adjustment to, an effective dosage of the compounds of formula (I).

GLYCOENGINEERED POLYPEPTIDES TARGETING ANTI-NEUTROPHIL AUTOANTIBODIES AND USES THEREOF

Provided herein are glycoengineered polypeptides comprising a first moiety comprising one or more peptides that specifically binds to an anti-neutrophil autoantibody and a second moiety comprising one or more glycans conjugated to the first moiety at one or more glycosylation sites. Also provided herein are nucleic acid sequence encoding provided glycoengineered polypeptides. Further provided herein are compositions comprising glycoengineered polypeptides and/or nucleic acids encoding the same, as well as methods of making and using the same.