79 results about "Neutrophil elastase" patented technology

The present provides tumor-associated HLA-restricted antigens, and in particular HLA-A2 restricted antigens, as vaccines for treating or preventing cancers in a patient. In specific aspects, neutrophil elastase peptides other than PR1, cyclin E1 peptides, cyclin D peptides, or cyclin E2 peptides are provided. Such peptides can be used to elicit specific CTLs that preferentially attack tumor cells.

The invention relates to a Kunitz domain peptide, designated DPI-14 herein, for inhibiting human neutrophil elastase. The invention also relates to a method of using a DPI-14 for treating cystic fibrosis or cystic fibrosis-related disease or disorder.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using a plurality of assays, one or more of which is configured to detect a kidney injury marker selected from the group consisting of Hyaluronic acid, Immunoglobulin A, Immunoglobulin G1, Immunoglobulin G2, Insulin-like growth factor-binding protein 7, Alpha-1 antitrypsin, Serum amyloid P component, Metalloproteinase inhibitor 2, Hepatocyte growth factor, Intercellular adhesion molecule 1, Beta-2-glycoprotein 1, Interleukin-1 beta, Neutrophil Elastase, Tumor necrosis factor receptor superfamily member 11B, Interleukin-11, Cathepsin D, C—C motif chemokine 24, C—X—C motif chemokine 6, C—C motif chemokine 13, C—X—C motif chemokines -1, -2, and -3, Matrilysin, Interleukin-2 receptor alpha chain, Insulin-like growth factor-binding protein 3, and Macrophage colony-stimulating factor 1 as diagnostic and prognostic biomarkers in renal injuries.

The invention relates to proteins comprising serine protease inhibiting peptides, such as Kunitz domain peptides (including, but not limited to, fragments and variants thereof) fused to albumin, or fragments or variants thereof. These fusion proteins are herein collectively referred to as “albumin fusion proteins of the invention.” These fusion proteins exhibit extended shelf-life and / or extended or therapeutic activity in solution. The invention encompasses, therapeutic albumin fusion proteins, compositions, pharmaceutical compositions, formulations and kits. The invention also encompasses nucleic acid molecules encoding the albumin fusion proteins of the invention, as well as vectors containing these nucleic acids, host cells transformed with these nucleic acids and vectors, and methods of making the albumin fusion proteins of the invention using these nucleic acids, vectors, and / or host cells. The invention also relates to compositions and methods for inhibiting neutrophil elastase, kallikrein, and plasmin. The invention further relates to compositions and methods for treating cystic fibrosis and cancer.

Compounds of formula (I):are useful as inhibitors of human neutrophil elastase.

Compounds of formula (I) and multimers thereof are inhibitors of human neutrophil elastase activity, and of utility in the treatment of, e.g., COPD:wherein A is aryl or heteroaryl; D is oxygen or sulphur; R1, R2 and R3 are independently each hydrogen, halogen, nitro, cyano, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, hydroxy or C1-C6-alkoxy or C2-C6-alkenyloxy, wherein C1-C6-alkyl and C1-C6-alkoxy can be further substituted with one to three identical or different radicals selected from the group consisting of halogen, hydroxy and C1-C4-alkoxy;R and R4 each independently represent a radical of formula—[X]m-[Alk1]p-[Q]n-[Alk2]q-[X1]k-Z wherein k, m, n, p and q are independently 0 or 1; Alk1 and Alk2 each independently represent an optionally substituted C1-C6 alkylene, or C2-C6 alkenylene radical which may optionally contain an ether (O—), thioether (—S—) or amino (—NRA—) link wherein RA is hydrogen or C1-C3 alkyl; Q represents (i) O—, —S—, —S(═O)—, —S(═O)2—, —S+(RA)—, —N(RA)—, —N+(RA)(RB)—, —C(═O)—, —C(═O)O—, —OC(═O)—, —C(═O)NRA—, —NRAC(═O)—, —S(O2)NRA—, —NRAS(O2)—, —NRAC(═O)NRB—, —NRAC(═NRA)NRB—, —C(═NRD)NRE, —NREC(═NRD), wherein RA, RB, RD and RE are independently hydrogen, C1-C6 alkyl, or C3-C6 cycloalkyl, or RA and RB, or RD and RE taken together with the nitrogen to which they are attached form a monocyclic heterocyclic ring of 5 to 7 ring atoms which my contain a further heteroatom selected from N, O and S, or (ii) an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 3-6 ring members; X represents —(C═O)—, —S(O2)—, —C(═O)O—, —(C═O)NRA—, or —S(O2)NRA—, wherein RA is hydrogen, C1-C6 alkyl, or C3-C6 cycloalkyl; X1 represents —O—, —S—, or —NH; and Z is hydrogen or an optionally substituted mono- or bicyclic carbocyclic or heterocyclic radical having 3-6 ring members.

The present invention relates to pharmaceutical kits and methods to treat lung inflammation and redox imbalance in human cystic fibrosis patients using pharmaceutical compositions containing N-acetylcysteine (NAC), pharmaceutically acceptable salts of N-acetylcysteine, or N-acetylcysteine derivatives. In phase I studies, treatment with oral NAC at a dose of from about 1800 mg / day to about 3000 mg / day for a period of 4 weeks produced significant positive effects, namely, it decreased absolute numbers of white blood cells and neutrophils in the sputum and produced concomitant decreases in sputum neutrophil elastase specific activity and sputum interleukin-8 levels, suggesting an amelioration of lung inflammation in the patients. These effects were associated with an increased total GSH level in whole blood as well increased staining for reduced GSH in blood neutrophils, both of which reflect an amelioration of the redox imbalance in the patients. In ongoing phase II studies, oral NAC at a dose of about 2700 mg / day administered in double-blind manner for 12 weeks showed excellent safety and significantly decreased white blood cells in sputum as compared to placebo.

The invention provides compounds of formula wherein R1, R3, R4, R5, R6, R14, X, W and Z are as defined in the specification and optical isomers, racemates and tautomers thereof, and pharmaceutically acceptable salts thereof; together with processes for their preparation, pharmaceutical compositions containing them and their use in therapy. The compounds are inhibitors of human neutrophil elastase.

Compounds of formula (I) defined herein exhibit human neutrophil elastase inhibitory properties and are useful for treating diseases and conditions in which HNE is implicated.

The invention provides compounds of formulawherein R1, R3, R4, R5, R14, X and W are as defined in the specification and optical isomers, racemates and tautomers thereof, and pharmaceutically acceptable salts thereof; together with processes for their preparation, pharmaceutical compositions containing them and their use in therapy. The compounds are inhibitors of human neutrophil elastase.

The subject invention features methods for predicting whether a subject at risk of developing Acute Respiratory Distress Syndrome (ARDS) will develop ARDS by determining the amount of elafin present in a subject sample, or by determining the ration of elafin:neutrophil elastase in a subject sample. The invention also features methods for monitoring the efficacy of a treatment regimen for ARDS as well as methods of treatment for ARDS. The invention also features methods to determine a subject's predisposition for developing ARDS by determining whether certain genomic polymorphisms are present in the subject's DNA.

Methods and compositions for identifying autoimmune diabetes are provided. One aspect provides a method for the evaluation of risk and progression of autoimmune diabetes in mammalian subjects. The method includes measuring the enzymatic activities and / or protein concentrations of neutrophil elastase and proteinase 3 in a subject and comparing the measured levels of these proteases to respective reference levels.

Provided herein are benzoxazinone compounds of formula (I) and compositions containing the compounds. The compounds and compositions are useful in the methods of inhibiting the action of serine hydrolase, including neutrophil elastase. In certain embodiments, the compounds and compositions are useful in the prevention, amelioration or treatment of serine hydrolase-mediated diseases.

Compounds of formula (I) are inhibitors of neutrophil elastase, wherein A is C—R1 or N; -X1-X2- is CR15═N— or —NR19—CO—; and R1-R6, R15 and R16 are as defined in the claims.

Acne-affected skin has been found to be accompanied by the presence of matrix-degrading enzymes such as MMPs and neutrophil elastase, induction of neutrophils, and a reduction in procollagen biosynthesis. This invention treats scarring and inflammation accompanying acne by administering, topically or systemically, at least one of (i) an inhibitor of the matrix degrading enzymes and (ii) a cytokine inhibitor that alleviates inflammation and thus also alleviate neutrophil infiltration. Alleviating the matrix degradation and renormalizing procollagen biosynthesis allows for reduced inflammation and better natural repair of acne-affected skin. Inhibiting cytokines alleviates induction of MMPs in resident skin cells, and also alleviates inflammation with its concommitant induction of neutrophils from the blood stream bringing MMPs and elastase into the acne lesion. Dimishing the presence of matrix-degrading enzymes in the acne lesion reduces imperfect repair of the skin and thus decreases scarring in acne-affected skin.

The invention relates to proteins comprising serine protease inhibiting peptides, such as Kunitz domain peptides (including, but not limited to, fragments and variants thereof) fused to albumin, or fragments or variants thereof. These fusion proteins are herein collectively referred to as “albumin fusion proteins of the invention.” These fusion proteins exhibit extended shelf-life and / or extended or therapeutic activity in solution. The invention encompasses therapeutic albumin fusion proteins, compositions, pharmaceutical compositions, formulations and kits. The invention also encompasses nucleic acid molecules and vectors encoding the albumin fusion proteins of the invention, host cells transformed with these nucleic acids and vectors, and methods of making the albumin fusion proteins of the invention using these nucleic acids, vectors, and / or host cells. The invention also relates to compositions and methods for inhibiting neutrophil elastase, kallikrein, and plasmin. The invention further relates to compositions and methods for treating cystic fibrosis and cancer.

Compounds of formula (I) are inhibitors of neutrophil elastase, wherein A is C—R1 or N; —X1-X2— is CR15═N— or —NR19—CO—; and R1-R6, R15, R15 and R19 are as defined in the claims.

The subject invention provides novel devices and methods for the detection and quantification of neutrophil elastase activity in biological samples.

Composition including a neutrophil elastase (NE)-targeting agent that counters the pathologic elements of respiratory inflammation is provided. NE-targeting agents primarily disrupt the association between NE and shed ectodomains of Syn-1, resulting in inhibition of the NE by protease inhibitors or anti-elastases. Non-anticoagulant heparin derivatives or fragments are exemplary NE-targeting agents. The composition preferably includes a carrier, such as chitosan or lactose in dry powder formulations, to facilitate delivery of the active agent. Use of the composition in manufacturing medicaments for treating respiratory diseases is also disclosed.

Embodiments are directed to: (i) neutrophil secreted factors that have the capacity to kill a broad range of cancer cells without affecting the viability of non-cancer cells. Two neutrophil killing factors have been identified by the inventors: (1) eosinophil cationic protein (ECP) and (2) neutrophil elastase (ELANE); or (ii) therapeutic compositions that include CD95 degrading polypeptide components and methods of treating cancer with the same.

Acne-affected skin has been found to be accompanied by the presence of matrix-degrading enzymes such as MMPs and neutrophil elastase, induction of neutrophils, and a reduction in procollagen biosynthesis. This invention treats scarring and inflammation accompanying acne by administering, topically or systemically, at least one of (i) an inhibitor of the matrix degrading enzymes and (ii) a cytokine inhibitor that alleviates inflammation and thus also alleviate neutrophil infiltration. Alleviating the matrix degradation and renormalizing procollagen biosynthesis allows for reduced inflammation and better natural repair of acne-affected skin. Inhibiting cytokines alleviates induction of MMPs in resident skin cells, and also alleviates inflammation with its concommitant induction of neutrophils from the blood stream bringing MMPs and elastase into the acne lesion. Dimishing the presence of matrix-degrading enzymes in the acne lesion reduces imperfect repair of the skin and thus decreases scarring in acne-affected skin.

Compounds of formula (I) described herein are imidazolone derivatives having human neutrophil elastase (HNE) inhibitory properties and are useful for the treatment of diseases and conditions in which HNE is implicated.

The invention discloses a neutral granulocyte elastase chemiluminescence detection kit and a preparation method thereof. The kit comprises a magnetic particle coupled neutral granulocyte elastase (NE)capture antibody, acridinium ester-labelled neutral granulocyte elastase (NE) detection antibody, a neutral granulocyte elastase calibration product, a chemiluminescence pre-excitation solution A, achemiluminescence pre-excitation solution B, and a cleaning solution. The kit combines a chemiluminescence technology and immunization magnetic particles, and provides a reaction system which approaches to a homogeneous phase. Compared with the prior art, the established direct chemiluminescence method has the advantages of high sensitivity, strong specificity, accuracy and rapidity, and short detection time, the detection result has higher accuracy and repetition performance, and the kit can be used for various luminescence detection apparatuses.

Antibody preparations with substantially homogeneous and unsialylated glycoforms, such as G0 and G2, are prepared by enzymatic treatment, expression under certain conditions, use of particular host cells, and contact with serum. These antibody preparations resist cleavage by proteases, such as papain, ficin, bromolein, pepsin, a matrix metalloproteinase, such as MMP-7, neutrophil elastase (HNE), stromelysin (MMP-3) and macrophage elastase (MMP-12), and glycosylation modification enzymes. The antibody preparations with substantially homogeneous and unsialylated glycoforms and methods of testing for glycosylation in an antibody are useful in connection with characterization of antibody properties and / or in diseases or conditions characterized by an increase in protease activity.

Provided are methods and compositions comprising ulinastatin polypeptides for treating diseases associated with elevated neutrophil elastase (NE), including NE-associated lung and skin diseases.

The invention provides a method for detecting human neutrophil elastase based on nucleic acid aptamer and a kit for detecting human neutrophil elastase based on nucleic acid aptamer. According to the method, the nucleic acid aptamer is modified on an ELISA Plate, used as a recognition reagent, and selectively captures neutrophil elastase molecules; the substrate is catalyzed by the neutrophil elastase to generate products; and by measuring the change of absorbance or fluorescence intensity, the high-sensitivity high-specificity detection of the human neutrophil elastase is realized. The method is easy to implement and high in specificity and sensitivity, and high throughput detection is easy to implement.

The invention belongs to the technical field of medical biology, and particularly relates to a preparation method and application of a mesenchymal stem cell preparation. According to the invention, human-derived mesenchymal stem cells (MSCs) are treated by an activating agent composed of a plurality of specific bioactive molecules and compounds to obtain activated mesenchymal stem cells (Active MSCs). The Active MSCs specifically secrete a large amount of various bioactive substances such as interleukin 6 (IL6), indoleamine 2, 3-dioxygenase (IDO), bone morphogenetic protein 6 (BMP6), neutrophil elastinase, cathepsin G, superoxide dismutase, tissue metalloproteinase inhibitory factor 3 (TIMP3), protein lysine 6 oxidase (LOX), IGFL3, TNFAIP6, CYR61, TGF beta and the like. The preparation can treat autoimmune diseases, improve the anti-tumor ability of the body, prevent aging, enhance the immunity of the body and promote the regeneration ability of the body tissue. The active MSCs obtained by inducing and activating the mesenchymal stem cells by adopting the mesenchymal stem cell activating agent have no drug residues and can highly express bioactive substances with immunoregulation and tissue regeneration capacities. Compared with chemotherapy, the active MSCs transplantation has lower toxic and side effects, has low immunogenicity, and has great significance in treatment of tumors and immune diseases and prevention of aging.

Compounds of formula (I) defined herein exhibit human neutrophil elastase inhibitory properties and are useful for the treatment of disease or conditions in which HNE is implicated.