4671 results about "Protease" patented technology

The present invention provides heterocyclic linker compounds useful for linking drug moieties to ligands. The compounds also include drug-ligand conjugates comprising a ligand capable of targeting a selected cell population, and a drug connected to the ligand by a heterocyclic linker moiety. The linker moiety comprises a peptide sequence that is a substrate for an intracellular enzyme, for example a cathepsin, that cleaves the peptide at an amide bond. The peptide further contains a self-immolating moiety which connects the drug and the protein peptide sequence. Upon cleavage of the peptide sequence by an intracellular enzyme the self-immolating moiety cleaves itself from the drug moiety such that the drug moiety is in an underivatized and active form.

The present invention provides improved compositions and methods for the collection of stem cells from an organ, e.g., placenta. The invention provides a stem cell collection composition comprising an apoptosis inhibitor and, optionally, an enzyme such as a protease or mucolytic enzyme, vasodilator, necrosis inhibitor, oxygen-carrying perfluorocarbon, or an organ preserving compound. The invention provides methods of using the stem cell collection composition to collect stem cells and to preserve populations of stem cells.

The present invention provides nucleic acid arrays and methods of using the same for expression profiling of human protease and/or osteoarthritis genes. The nucleic acid arrays of the present invention include one or more substrate supports. A substantial portion of all polynucleotide probes that are stably attached to the substrate support(s) can hybridize under stringent or nucleic acid array hybridization conditions to human protease or osteoarthritis genes. In one embodiment, the nucleic acid arrays of the present invention include a plurality of probe sets, each of which can hybridize under stringent or nucleic acid array hybridization conditions to a different respective tiling sequence selected from Attachment C, or the complement thereof.

Methods, compositions, kits, and apparatus are provided wherein the aminoacyl-tRNA synthetase system is used to analyze amino acids. The method allows very small devices for quantitative or semi-quantitative analysis of the amino acids in samples or in sequential or complete proteolytic digestions. The methods can be readily applied to the detection and/or quantitation of one or more primary amino acids by using cognate aminoacyl-tRNA synthetase and cognate tRNA. The basis of the method is that each of the 20 synthetases and/or a tRNA specific for a different amino acid is separated spatially or differentially labeled. The reactions catalyzed by all 20 synthetases may be monitored simultaneously, or nearly simultaneously, or in parallel. Each separately positioned synthetase or tRNA will signal its cognate amino acid. The synthetase reactions can be monitored using continuous spectroscopic assays. Alternatively, since elongation factor Tu:GTP (EF-Tu:GTP) specifically binds all AA-tRNAs, the aminoacylation reactions catalyzed by the synthetases can be monitored using ligand assays. Microarrays and microsensors for amino acid analysis are provided. Additionally, amino acid analysis devices are integrated with protease digestions to produce miniaturized enzymatic sequenators capable of generating either N- or C-terminal sequence and composition data for a protein or peptide. The possibility of parallel processing of many samples in an automated manner is discussed.

The present invention provides clostridial toxin substrates useful in assaying for the protease activity of any clostridial toxin, including botulinum toxins of all serotypes as well as tetanus toxins. A clostridial toxin substrate of the invention contains a donor fluorophore; an acceptor having an absorbance spectrum overlapping the emission spectrum of the donor fluorophore; and a clostridial toxin recognition sequence that includes a cleavage site, where the cleavage site intervenes between the donor fluorophore and the acceptor and where, under the appropriate conditions, resonance energy transfer is exhibited between the donor fluorophore and the acceptor.

The invention provides compositions and methods for treating pancreatic enzyme insufficiency, such as the pancreatic enzyme insufficiency associated with cystic fibrosis. The invention also provides compositions comprising lipase from Candida cylindracea, alone or in combination with amylase or amyloglucosidase, protease and/or lactase. Furthermore, the invention discloses methods for treating pancreatic enzyme insufficiency comprising administering compositions to patients in need thereof.

The present invention relates to compositions for the treatment of conditions, including pancreatic insufficiency. The compositions of the present invention comprise lipase, protease and amylase in a particular ratio that provides beneficial results in patients, such as those afflicted with pancreatic insufficiency. This invention also relates to methods using such compositions for the treatment of pancreatic insufficiency.

The present invention provides a comprehensive solution to skin problems of infants and incontinent adults related to diaper rash, also known as diaper dermatitis. This is based on certain novel divalent metal and quaternary ammonium complexes (ion-pairs) of zeolites (that are made by an in-situ process), which in synergistic combination with certain other compositions, provide a comprehensive treatment for diaper rash that encompasses the following aspects: (1) deactivation of lipase and protease enzymes on skin surface, (2) the controlled-release delivery of skin protectant compositions, such as divalent metal zinc cation, (3) trapping of acidic and alkaline chemicals deposited on skin from body exudates and enzyme activity, (4) controlled-release delivery of anti-inflammatory agents, and COX and LOX enzyme inhibitors, (5) controlled-release delivery of antibacterial and antifungal compositions, and (6) absorption of excess moisture in the diaper zone.

Disclosed are compounds of the formula I

or a stereoisomer, tautomer, or pharmaceutically acceptable salt, solvate or ester thereof, wherein U, W, X, L, Y, M, Z, c, d, e, f, g, h, s, t, R¹, R², R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷ and R¹⁸ are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I.

Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m₁ agonist or m₂ antagonist.

Disclosed are compounds of the formula I

or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W, R¹, R², R³, R⁴, R⁵, R⁶, and R⁷ are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I.

Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic antagonist.

The present invention relates to a method of removing a biofilm, which comprises at least the following steps, carried out simultaneously or consecutively: a) a solution comprising an enzyme mixture containing at least one enzyme chosen from the group of proteases, at least one enzyme chosen from the group of esterases and an amylase is prepared; b) a solution comprising a detergent with an alkaline pH is prepared; and c) said solutions are applied, by washing or by circulation, to the surface to be treated. It also relates to a kit intended for removing a biofilm, which comprises the solutions defined above and the compositions comprising the said solutions.

The present invention provides methods of improving the osteogenic and/or chondrogenic activity of a bone matrix, e.g., a dermineralized bone matrix (DBM), by exposing the bone matrix to one or more treatments or conditions. In preferred embodiments the bone matrix is derived from human bone. The treatment or condition may alter the structure of the bone matrix and/or cleave one or more specific proteins. Cleavage may generate peptides or protein fragments that have osteoinductive, osteogenic, or chondrogenic activity. Preferred treatments include collagenase and various other proteases. The invention further provides improved bone and cartilage matrix compositions that have been prepared according to the inventive methods and methods of treatment using the compositions. The invention further provides methods of preparing, testing, and using the improved bone matrix compositions. Ona assay comprises exposing relatively undifferentiated mesenchymal cells to a bone matrix composition and measuring expression of a marker characteristic of osteoblast or chondrocyte lineage(s). Increased expression of the marker relative to the level of the marker in cells that have been exposed to a control matrix (e.g., an inactivated or untreated matrix) indicates that the treatment or condition increased the osteogenic and/or chondrogenic activity of the bone matrix. Suitable cells include C2C12 cells. A suitable marker is alkaline phosphatase. The inventive methods increase the osteogenic and/or chondrogenic activity of human DBM when tested using this assay system.

Compounds of formula (I):

wherein R¹, R², X, R³, D, and the dotted line b are as defined herein; or a pharmaceutically acceptable salt or ester thereof, are useful as inhibitors of the HCV NS3 protease.

This invention provides a fibrin sealant dressing, wherein said fibrin sealant may be supplemented with at least one composition selected from, for example, one or more regulatory compounds, antibody, antimicrobial compositions, analgesics, anticoagulants, antiproliferatives, antiinflammatory compounds, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like. Also disclosed are methods of preparing and/or using the unsupplemented or supplemented fibrin sealant dressing.

The present invention provides an array for rapidly identifying a host cell population capable of producing heterologous protein with improved yield and/or quality. The array comprises one or more host cell populations that have been genetically modified to increase the expression of one or more target genes involved in protein production, decrease the expression of one or more target genes involved in protein degradation, or both. One or more of the strains in the array may express the heterologous protein of interest in a periplasm compartment, or may secrete the heterologous protein extracellularly through an outer cell wall. The strain arrays are useful for screening for improved expression of any protein of interest, including therapeutic proteins, hormones, a growth factors, extracellular receptors or ligands, proteases, kinases, blood proteins, chemokines, cytokines, antibodies and the like.

A collection container and a method for collecting a biological sample, particularly whole blood, that includes at least one stabilizing agent in an amount effective to stabilize and inhibit protein degradation and/or fragmentation. The stabilizing agent is able to stabilize proteases in the biological sample, particularly at the point of collection, by inhibiting protein degradation and/or fragmentation in the sample when the sample is stored. The stabilizing agent includes one or more protease inhibitors.

An orally administered composition for improving food absorption and digestion contains therapeutically effective dosages of digestive enzymes and L-glutamine as active ingredients. The digestive enzymes include at least one each of a lipase, a protease, and an amylase, and at least a portion of each of these enzymes is enteric coated.

The present invention provides a manufacturing method for polypeptides that are produced in insect cells using a baculoviral expression system. In one example, the insect cell culture is supplemented with a lipid mixture immediately prior to infection (e.g., one hour prior to infection). The polypeptides are isolated from the insect cell culture using a method that employs anion exchange or mixed-mode chromatography early in the purification process. This process step is useful to remove insect-cell derived endoglycanases and proteases and thus reduces the loss of desired polypeptide due to enzymatic degradation. In another example, mixed-mode chromatography is combined with dye-ligand affinity chromatography in a continuous-flow manner to allow for rapid processing of the insect-cell culture liquid and capture of the polypeptide. In yet another example, a polypeptide is isolated from an insect cell culture liquid using a process that combines hollow fiber filtration, mixed-mode chromatography and dye-ligand affinity in a single unit operation producing a polypeptide solution that is essentially free of endoglycanase and proteolytic activities. In a further example, the isolated polypeptides are glycopeptides having an insect specific glycosylation pattern, which are optionally conjugated to a modifying group, such as a polymer (e.g., PEG) using a glycosyltransferase and a modified nucleotide sugar.

The present invention in one aspect relates to a coating composition comprising at least one enzyme capable of acting on a compound, wherein said action results in the formation of an antifouling species comprising an antifouling activity, and wherein said compound does not form part of said coating composition. The coating composition preferably comprises at least one oxidase capable of acting on a compound, such as a substrate for said oxidase, wherein said action results in the formation of an antifouling species including an antimicrobial species comprising an antimicrobial activity. More preferred, the oxidase comprises an activity which results in the formation of a peroxide. The oxidase can be present in said coating composition in combination with one or more additional enzymes including, but not limited to, an esterase, including a lipase, an amidase, including a protease, and a polysaccharide degrading enzyme, wherein said one or more additional enzyme(s), alone or in any combination, can be included in the presence or absence of one or more substrates for one or more of said enzymes.

Compositions and methods of modulating cellular function and treatment of disease in mammals comprising locally administering a regulated SNARE inhibitor and a translocating agent to the mammal. Regulated SNARE inhibitors include clostridial neurotoxins, tetanus neurotoxin and their free light chain portions and IgA protease. Translocating agents include acids, encapsulating vectors, and transduction domains.

The invention relates to an antimicrobial skin treatment composition and methods for producing and using an antimicrobial skin treatment composition. The antimicrobial skin treatment composition includes an antimicrobial package that can provide extended protection against germs and bacteria. The antimicrobial package can include any of the following: a quaternium ammonium antimicrobial agent, a protease enzyme, a preservative, a natural antimicrobial agent, or a lower alcohol. The composition can also include, among other ingredients, a thickening agent, a skin healing ingredient, a humectant, an emollient, a skin moisturizer, or water.

A method for reducing leaching of protein A during protein A affinity chromatography is described which involves reducing temperature or pH of, or by adding one or more protease inhibitors to, a composition that is subjected to protein A affinity chromatography.

Compounds of formula (I):

wherein R¹ is (C_1-8)alkyl, (C_3-7)cycloalkyl, {(C_1-6)alkyl-(C_3-7)cycloalkyl} or Het, which are all optionally substituted from 1 to 3 times with halo, cyano, nitro, O—(C_1-6)alkyl, amido, amino or phenyl, or R¹ is C₆ or C₁₀ aryl which is optionally substituted from 1 to 3 times with halo, cyano, nitro, (C_1-6)alkyl, O—(C_1-6)alkyl, amido, amino or phenyl; or a pharmaceutically acceptable salt thereof, useful as an inhibitor of the HCV NS3 protease.

An assay method is disclosed which isolates and detects the presence of a disease related conformation of a protein (e.g., PrPSc) present in a sample also containing the non-disease related conformation of the protein (e.g., PrPC). The sample is treated (e.g., contacted with protease) in a manner which hydrolyzes the disease related conformation and not the non-disease related conformation. The treated sample is contacted with a binding partner (e.g., a labeled antibody which binds PrPSc) and the occurrence of binding provides and indication that PrPSc is present. Alternatively the PrPSc of the treated sample is denatured (e.g., contacted with guanadine) or unfolded. The unfolded PrPSc is contacted with a binding partner and the occurrence of binding indicates the presence of PrPSc in the sample. In another embodiment, PrPSc and PrPC are reacted with a labeled antibody that binds both conformations and a conformation that binds only the disease related conformation, and the presence of the disease related conformation is determined by comparing the two.

The present invention provides biologically active peptidomimetic macrocycles with improved properties, such as protease resistance, relative to their corresponding polypeptides. The invention additionally provides methods of preparing and using such macrocycles, for example in therapeutic applications.

An improved infant formula resulting in reduced constipation, abdominal discomfort and gastrointestinal problems, comprises at least one protein component having a phosphorus content of less than 0.75 g P/100 g protein, and at least one lipid component that can be easily digested by an infant. Preferably, it further comprises at least one prebiotic component, and at least one viscosity-improving component. The protein fraction of the formula is preferably a hydrolysate prepared by hydrolysing a protein starting material, especially a whey protein with a combination of at least one endo- and at least one exoproteinase.

Disclosed are compounds of the formula I

or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein U, W, R, R¹, R^{2, R3} and R⁴ are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I.

Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m₁ agonist or m₂ antagonist.

A method of preparing a library of tagged nucleic acid fragments including contacting a population of cells directly with a lysis reagent having one or more protease to generate a cell lysate; inactivating the protease to generate an inactivated cell lysate, and applying a transposase and a transposon end composition containing a transferred strand to the inactivated cell lysate under conditions wherein the target nucleic acid and the transposon end composition undergo a transposition reaction.

The present invention relates to a pasteurized food product having a water activity of at least 0.80, preferably at least 0.85 and containing a proline specific protease.

The present invention discloses a method of cross-linking amnion to be an improved biomedical material. The present invention adopts the amnion cross-linked by EDC (N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimide HCI) or NHS (N-hydroxysuccinimide), and the cross-linked amnion not only has more resistance to protease, but also binds specific extracellular matrix (ECM) such as heparin by using cross-linked functional group. Further, by using the affinity of the ECM with specific growth factors, the amnion can be an efficient carrier for specific growth factor. Hence, some specific diseases may be treated.