16 results about "Granulocyte Elastase" patented technology

The present invention relates to a binding agent capable of specifically binding and competitively inhibiting neutrophil elastase, the binding agent comprising an immunoglobulin single variable domain (ISVD), as well as related products, methods and uses, for example, methods and uses, particularly for the prevention, treatment or diagnosis of inflammatory diseases.

The present invention relates to an anti-neutrophil elastase (NE) antibody or antigen-binding fragment thereof that specifically binds to NE, wherein the anti-NE antibody or antigen-binding fragment thereof comprises: a heavy chain variable region (VH) including a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 1, 7, or 13, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 2, 8, or 14, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 3, 9, or 15; and a light chain variable region (VL) including a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 4, 10, or 16, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 5, 11, or 17, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 6, 12, or 18. The antibody of the present invention exhibits excellent NE neutralizing activity, and thus can be used for preventing or treating NE hyperactivation-related diseases.

The disclosed methods are directed to preparing and detecting polypeptides using neutrophil elastase, such as human neutrophil elastase. The polypeptides are optionally denatured, reduced, and / or alkylated before being subjected to a first digestion. A second digestion comprises the use of neutrophil elastase, such as human neutrophil elastase. The prepared fragments are then analyzed chromatographically, electrophoretically, or spectrometrically, or a combination of these methods. The methods are especially useful for the preparation of therapeutic polypeptides for analysis, especially those that are not easily cleaved, such as some bi-specific T-cell engager (BiTE®) molecules.

The present disclosure is directed to methods of treatment, including treatment of a myopathy by administering to a subject in need thereof an elastase inhibitor in combination with a glucocorticoid. The present disclosure is also directed to pharmaceutical compositions that include an elastase inhibitor that can be used in such treatment.

The invention discloses nucleotide of fusion protein for coding neutrophil elastase and application of the nucleotide. A nucleotide sequence for coding the fusion protein is as shown in SEQ ID NO. 8; the nucleotide sequence of mRNA (messenger ribonucleic acid) for coding the fusion protein is as shown in SEQ ID NO. 12; the fusion protein comprises an optimized human neutrophil elastase (ELANE) fragment and an optimized human alpha2-macroglobulin (A2M) fragment. The mRNA preparation which is encapsulated by the nano-lipid particles and is used for coding the wild type ELANE can achieve a tumor elimination effect only by complex intratumor injection. According to the mRNA preparation which is encapsulated by the nano-lipid particles and is used for coding the ELANE fusion protein, tumor elimination in a mouse body can be realized only through intramuscular injection administration, the operation is simpler and more convenient, and the mRNA preparation is beneficial to treatment of scattered and tiny tumor focuses in the body.

The objective was to develop a novel neutrophil elastase measurement method that can measure neutrophil elastase with high sensitivity. [Solution] A method for measuring human neutrophil elastase in a sample is provided, comprising contacting the sample with two or more antibodies or antigen-binding fragments thereof that recognize different epitopes on a complex with human neutrophil elastase. A reagent or kit for immunological measurement of human neutrophil elastase is also provided, comprising two or more antibodies or antigen-binding fragments thereof that recognize different epitopes on a complex with human neutrophil elastase and its inhibitor.

The invention discloses a fusion protein of neutrophil elastase as well as a preparation method and application of the fusion protein. The fusion protein comprises an optimized human neutrophil elastase (ELANE) fragment and an optimized human alpha2-macroglobulin (A2M) fragment; the amino acid sequence of the fusion protein is as shown in SEQ ID NO.8. The use of ELANE is limited due to intolerance to serine protease inhibitors (such as alpha-1-antitrypsin, A1AT). The optimized ELANE fragment and the optimized A2M fragment are connected to form the fusion protein, the fusion protein has high enzymatic activity, the tolerance to A1AT is greatly improved, and 83.3% of enzyme activity can still be maintained after the fusion protein acts for 2 hours through high-concentration A1AT (19200 nM). The fusion protein can efficiently eliminate mouse tumors and is safe to mice. The fusion protein is simple in preparation process and easy to industrially amplify, and a new strategy is provided for tumor treatment.

The present invention relates to a CXCR4 inhibitor compound for use in the treatment of a severe acute respiratory distress syndrome (sARDS), wherein the sARDS is characterized by a dysregulation of NETosis which may be measured by the plasmatic levels of cDNA, citrullinated histone H3, neutrophil elastase, interleukin-8, myeloperoxidase-DNA complexes and / or calprotectin. The present invention also relates to a method of prognostic of severe ARDS, a pharmaceutical composition for use in the treatment of severe acute respiratory distress syndrome (ARDS), a kit of prognostic of severe ARDS in a subject and the use of NETosis biomarkers.

To provide an improved method for treating IdiopathicPulmonaryFibrosis (IPF).SOLUTION: The invention features a polypeptide comprising a variant of plasminogen-activator inhibitor-1 (PAI-1) having a reduced capacity to bind vitronectin, a reduced capacity to interact with the PAI-1 clearance receptor LDL-receptor-related-protein 1 (LRP1), and a capacity to efficiently inhibit neutrophil elastases in presence of neutrophil extracellular traps (NETs). In some embodiments, a polypeptide of the present invention comprises a PAI-1 variant optionally fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions characterized by aberrant neutrophil elastase activity (as an example, idiopathic pulmonary fibrosis).SELECTED DRAWING: Figure 1

The invention belongs to the field of new application of medicines, and particularly relates to application of Sivelestat in preparation of cancer radiotherapy adjuvant medicines. According to the invention, Sivelestat which has been used for acute respiratory distress syndrome is creatively applied to tumor radiotherapy, and the Sivelestat inhibits the activity of neutrophil elastase and effectively blocks the formation of a neutrophil outer trapping net induced by radiotherapy, so that the invasion of tumor cells and the abnormal generation of blood vessels are inhibited, and an immunosuppression microenvironment is established. The application not only maintains the local killing effect of radiotherapy on primary tumors, but also cuts off the key path from radiotherapy to NETs to metastasis from the mechanism, and significantly reduces the risk of tumor recurrence and distant metastasis after radiotherapy. The traditional Chinese medicine composition has the transformation advantage of new use of old medicines, is clear in clinical safety, and is suitable for adjuvant therapy of various solid tumors.

The invention belongs to the technical field of medicine development, and discloses a compound with a function of degrading human neutrophil elastinase (NE) as well as a preparation method and application of the compound. Specifically, the invention discloses a compound with a general formula (I), a pharmaceutically acceptable salt, a stereoisomer and a prodrug molecule thereof, the compound has an effect of degrading target protein NE in cells, and the compound shows wide pharmacological activity related to degradation of the target protein NE. The compound can be used for preparing medicines for preventing / treating target protein NE overexpression diseases or symptoms.

The invention discloses application of ancylostoma duodenum polypeptide AdKI1 in preparation of drugs for resisting excessive inflammatory reaction, and belongs to the technical field of biological medicines. The invention discloses an application of ancylostoma duodenum polypeptide AdKI1 in preparation of a medicine for resisting excessive inflammatory reaction. The amino acid sequence of the AdKI1 is shown as SEQ ID NO.1 or SEQ ID NO.2. The invention further discloses a preparation method of the ancylostoma duodenum polypeptide AdKI1. The ancylostoma duodenum polypeptide AdKI1 can efficiently inhibit the activity of neutrophile granulocyte elastase, cathepsin G and protease 3, and can be applied to preparation of drugs for resisting excessive inflammatory reaction. AdKI1 can significantly improve lung tissue injury of LPS-induced acute lung injury mice and reduce inflammatory response; adKI1 can be used for remarkably inhibiting LPS (Lipopolysaccharide)-induced macrophages from secreting TNF (Tumor Necrosis Factor)-alpha, IL-6 and IL-1beta and promoting the secretion of IL-10.

The invention relates to application of sivelestat in preparation of a medicine for treating aortic endothelial cell injury, and belongs to the field of biological medicine. Specifically, the sivelestat reduces the formation of neutrophil extracellular traps (NETs) by inhibiting the activity of neutrophil elastase (NE), thereby reducing the aortic endothelial inflammation injury. In-vitro experiments show that sivelestat can significantly inhibit generation of NETs induced by S100A12 and expression of endothelial inflammatory factors; in-vivo experiments prove that the compound has the effects of reducing the aortic dilatation rate and rupture rate and improving the survival rate on AD model mice induced by beta-aminopropionitrile (BAPN). The invention provides a new treatment strategy for the aortic dissection.

The invention relates to the technical field of biological medicine, in particular to a biomarker combination, a kit of the biomarker combination and application of the biomarker combination in diagnosis of acute Stanford B-type aortic dissection (ATBAD). The biomarker combination comprises serum amyloid protein A1 (SAA1), serum amyloid protein A2 (SAA2), C-reactive protein (CRP), neutrophil elastinase (ELANE), matrix metalloenzyme 9 (MMP9), nest protein 1 (NID1), mannose binding lectin 2 (LMAN2) and proprotein convertase subtilisin / kexin type 9 (PCSK9), and the biomarker combination can realize high-sensitivity and high-accuracy detection of ATBAD. And the anti-interference capability is excellent.

The invention discloses a preparation method and an application of a neutrophil elastase (NE) response near-infrared two-region ratiometric fluorescent probe (DCNC). According to the DCNC, the NIR-II dual-emission fluorescence characteristic of rare earth ions is combined with a ratio-type signal response mode, the sensitivity, the signal stability and the quantitative capacity of in-vivo fluorescence imaging are greatly improved, ultralow or enhanced F1525 / EX808 fluorescence signals are shown before and after interaction with NE, the F1525 / EX980 fluorescence signals are kept unchanged, and the result shows that in-vivo fluorescence imaging can be achieved through the DCNC. Therefore, the self-calibration ratio fluorescence imaging NE activity change is realized. The activated probe shows high sensitivity, high specificity and good linear response to NE activity, can realize early stratification of immune response in a Hepa1-6 mouse tumor model by monitoring infiltration conditions of tumor-related neutrophils (TANs), and provides dynamic imaging support for optimization of individualized immunotherapy strategies.

The application discloses application of a duodenum hookworm polypeptide AdKI1 in preparation of an anti-excessive inflammation reaction medicine and belongs to the technical field of biological medicines. The application discloses the application of the duodenum hookworm polypeptide AdKI1 in preparation of the anti-excessive inflammation reaction medicine, and the amino acid sequence of AdKI1 is shown as SEQ ID NO. 1 or SEQ ID NO. 2. The duodenum hookworm polypeptide AdKI1 can efficiently inhibit activities of neutrophil elastase, cathepsin G and proteinase 3, and can be applied in preparation of the anti-excessive inflammation reaction medicine. AdKI1 can significantly improve lung tissue damage of a mouse with LPS-induced acute lung injury and reduce an inflammation reaction. AdKI1 can significantly inhibit LPS-induced secretion of TNF-alpha, IL-6 and IL-1beta by macrophages and promote secretion of IL-10.