1784results about "Peptidases" patented technology

This invention provides a tetrahedral antibody comprising a first, second, third, and fourth domain, wherein the first and second domains are Fab or Fc domains; wherein each of the first and second domains comprise a first polypeptide chain comprising a first N-terminus of the domain, and a second polypeptide chain comprising a second N-terminus of the domain; wherein the first N-terminus of the first domain and the first N-terminus of the second domain are joined to each other by a non-peptidyl linkage, which can be a covalent linkage or a non-covalent linkage between first and second dimerizing polypeptides attached to the first N-termini of the first and second domains, respectively; and wherein the third and fourth domains are attached at their respective C-termini to the second N-termini of the first and second domains, respectively, or the N-termini of the first and second dimerizing polypeptides.

Disclosed are, inter alia, double stranded RNAi (dsRNAi) agents inhibiting expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), for example, human HMGCR, compositions including the same, and methods of treatment using the same.

The present invention discloses an interfering RNA for inhibiting PCSK9 gene and use thereof. The interfering RNA comprises a nucleotide sequence set forth in any one or two or more of SEQ ID NOs: 1-40, 73-96. The interfering RNA of the present invention can better target and silence hepatic PCSK9 mRNA, reduce the protein level of PCSK9, enhance LDL-C metabolism, and reduce serum cholesterol, providing a solid technical foundation for the development of siRNA medicaments for the prevention, treatment, and symptom alleviation of PCSK9 gene-mediated diseases.

The invention discloses an interfering RNA (Ribonucleic Acid) for inhibiting a PCSK9 gene and application of the interfering RNA. The interfering RNA comprises any one or more than two nucleotide sequences as shown in SEQ ID NO: 1-40 and SEQ ID NO: 73-96. The interfering RNA can better target and silence mRNA of the liver PCSK9, reduce the protein level of the PCSK9, enhance LDL-C metabolism and reduce serum cholesterol, and a solid technical basis is provided for research and development of siRNA drugs for prevention and treatment of PCSK9 gene mediated diseases and symptom relief.

The present disclosure provides proteins useful for preventing, treating, suppressing and / or eliminating infestations and infections of plants by various phytopathogenic pests, as well as formulations comprising such proteins, polynucleotides encoding such proteins, organisms expressing such proteins, and methods of using such proteins, formulations, polynucleotides and organisms in agriculture and other fields of endeavor.

In accordance with the purpose(s) of the present disclosure, as embodied and broadly described herein, the disclosure, in one aspect, relates to lipid nanoparticles for use as drug delivery agents. The lipid nanoparticles are composed of lipopeptide conjugates, where a peptide is bonded to a lipid. The lipid nanoparticles described herein represent a new approach in drug delivery, addressing critical challenges in balancing biodegradability, biocompatibility, and organspecific targeting. The lipid nanoparticles can selectively target and deliver bioactive agents to specific tissues in a subject by modifying specific amino acids and ratios thereof in the peptide of the lipopeptide conjugate.

The present disclosure relates to isolated nucleic acid molecules comprising at least two double-stranded inhibitory ribonucleic acid (RNA) molecules adapted to silence the same or different genes by RNA interference to enhance silence, thereby modulating gene expression.

The invention provides a separation and purification method of urokinase, and relates to the technical field of separation and extraction. The separation and purification method comprises the following steps: S1, regulating the pH value of male urine to 8.5, standing, and taking supernate; s2, mixing the supernate with an adsorption material, and eluting with an eluent to obtain a urokinase crude product solution; the adsorption material is a core-shell silica gel polymer, Fe3O4atSiO2-NH2 is taken as a core, and polystyrene is taken as a shell; the eluent is a sodium citrate buffer solution with the concentration of 0.5 to 0.15 M, acetonitrile with the concentration of 1 to 5 weight percent and EDTA (Ethylene Diamine Tetraacetic Acid) with the concentration of 0.5 to 1.5 mM; and S3, carrying out anion exchange column chromatography on the urokinase crude product solution, eluting with an eluent, and precipitating to obtain the urokinase. The urokinase prepared by the method has the advantages of high polymer urokinase content, high recovery rate and high activity yield.

The invention belongs to the technical field of gene engineering, and particularly relates to an acid protease mutant as well as a coding gene, a preparation method and application thereof. The amino acid sequence of the acid protease mutant is as shown in SEQ ID NO. 2. The acid protease mutant provided by the invention has the advantages of high enzyme activity, strong pH and temperature adaptability, good high temperature resistance and the like, can react in a wide pH value (pH 2.0-6.0) and temperature range (30-70 DEG C), is beneficial for improving the flexibility of a production process, particularly can adapt to industrial production at a relatively high temperature and can meet a relatively long-time high-temperature catalytic environment, and the acid protease mutant has a wide application prospect. The enzyme prepared by the method is high in enzyme activity, not easy to inactivate in a high-temperature environment, can maintain 70% or more of enzyme activity for 1 h at 50 DEG C, can maintain 55% or more of enzyme activity for 1 h at 55 DEG C, and shows good market prospects and industrial application values in the fields of wine brewing, feed processing, leather softening and the like.

The invention belongs to the technical field of walnut protein preparation, and particularly relates to walnut protein powder with high digestibility, low sensitization and low bitterness as well as a preparation method and application of the walnut protein powder. According to the preparation method of the walnut protein powder with high digestibility, low sensitization and low bitterness provided by the invention, proline specific endo protease, recombinant trypsin and carboxypeptidase B are cooperatively used, so that accurate damage to an anti-digestion structure and a sensitization epitope of walnut protein can be realized; according to the method, ultrahigh digestibility (greater than or equal to 92%), thorough desensitization (greater than 99.8%), bitterness inhibition and functional peptide enrichment are synchronously realized, so that the defects of low digestibility, sensitization residue, obvious bitterness, low yield of functional peptide, complex process and the like caused by uncontrollable cutting in the existing random enzymolysis technology are overcome, and meanwhile, the core technical bottleneck of high-value utilization of walnut protein is overcome.

An implantable device for delivery of a macromolecular drug compound is provided. The device comprises a core having an outer surface and a membrane layer positioned adjacent to the outer surface of the core. The core comprises a core polymer matrix within which is dispersed a drug compound having a molecular weight of about 5 kDa or more, the polymer matrix containing a hydrophobic polymer. The membrane polymer matrix includes from about 70 wt. % to about 99 wt. % of an ethylene vinyl acetate copolymer.

Antigen-binding molecules (ABMs) that bind to Porphyromonas gingivalis are described. The ABMs may be human or humanized ABMs. The ABMs find use in treating infections involving P. gingivalis, such as periodontal disease. Also provided are methods of treating or preventing a disorder or disease by administering the ABM.

In the present invention new protease enzymes are provided. More specifically, genetically engineered protease enzymes, compositions comprising the enzymes, and methods of making and using the enzymes or compositions comprising the enzymes are provided.

Provided are an siRNA which inhibits plasma coagulation factor XI gene expression, a pharmaceutical composition containing the siRNA, a conjugate, a reagent kit, and a use of the siRNA, the pharmaceutical composition thereof and the conjugate in preparing a drug used for treating and / or preventing thrombotic diseases and ischemic strokes.

A method for preparing nondenatured collagen type II for alleviating joint pain includes pulverizing a cartilage raw material and defatting to obtain a total protein crude extract; adding anhydrous ethanol to the total protein crude extract, soaking, stirring, and centrifuging to obtain an anhydrous ethanol insoluble material; dissolving the anhydrous ethanol insoluble material in water, adjusting pH to acidic, stirring and centrifuging to obtain an acid-insoluble material; dissolving the acid-insoluble material in water, performing enzymatic hydrolysis and centrifuging to obtain an enzymatic hydrolysis precipitate; dissolving the enzymatic hydrolysis precipitate in water, followed by performing co-fermentation, and centrifuging to obtain a fermentation precipitate; and adding a water activity regulator to the fermentation precipitate, and then drying to obtain the nondenatured collagen type II. The content of protein, hydroxyproline and nondenatured collagen type II in the prepared nondenatured collagen type II is high, and the shelf life is prolonged.

The invention belongs to the technical field of bioengineering and food safety, and particularly relates to a fusion enzyme for degrading aflatoxin B1 (AFB1) and / or zearalenone (ZEN) and application of the fusion enzyme. The fusion enzyme S1-AsDPP III disclosed by the invention can effectively degrade AFB1 and ZEN, the fusion enzyme is obtained by fusing a section of self-assembled amphiphilic oligopeptide S1 sequence at the N end of wild type AsDPP III, and the thermal stability of the fusion enzyme and the amphipathy of the fusion enzyme in an oil-water coexistence system can be remarkably improved. Under mild reaction conditions, the fusion enzyme can efficiently degrade AFB1 and ZEN in vegetable oil, and is especially suitable for detoxification treatment of common edible oil such as peanut oil and corn oil. The invention provides a green, safe and efficient scheme for removing fungaltoxin from grease food, and the method has a good industrial application prospect.

The invention relates to the technical field of red algae polysaccharide extraction, and provides a preparation technology for preparing instant red algae polysaccharide through a compound enzyme method, and the preparation technology comprises the following steps: S100, washing a red algae raw material, and sequentially carrying out mechanical crushing treatment and freeze drying treatment to obtain red algae powder; s200, sequentially performing enzymolysis treatment, centrifugal treatment and filtration treatment on the red algae powder to obtain supernatant liquid; and S300, sequentially carrying out concentration treatment, purification treatment, spray drying treatment and fluidization granulation treatment on the supernatant to obtain the red algae polysaccharide. The red algae raw material is efficiently separated and purified by adopting the compound enzyme, so that the efficient degradation of the red algae cell wall and the efficient extraction and preparation of the red algae polysaccharide are realized, a new technical way is provided for the efficient preparation and wide application of the red algae polysaccharide, and the method has important industrial application value and market prospect.

The invention belongs to the technical field of food or medicine, and particularly relates to a preparation method of nattokinase sustained-release microspheres, which comprises the following steps: mixing an emulsifier span-80 with liquid paraffin to obtain an oil phase; adding chitosan into an acetic acid solution to prepare a chitosan water solution as a water phase; dropwise adding the water phase into the oil phase to prepare W / O type emulsion, dropwise adding a cross-linking agent A into the emulsion to obtain chitosan microspheres, and taking a chitosan microsphere nattokinase solution and a cross-linking agent B to obtain nattokinase-chitosan core microspheres; mixing the nattokinase-chitosan core microsphere with a cortisol aptamer solution, and incubating to enable the aptamer to be combined on the surface of the nattokinase-chitosan core microsphere; and adding a casein-PEG copolymer solution and a cross-linking agent C into the microspheres to obtain the cortisol response type intelligent switch microspheres. The nattokinase release amount can be dynamically adjusted day and night, the circadian thrombus risk rhythm is matched, the anti-thrombus effect is remarkably improved, side effects are reduced, and the nattokinase can be widely applied to the fields of functional food and drugs.

Among other things, the present disclosure provides designed oligonucleotides and compositions thereof. In some embodiments, oligonucleotides and compositions of the present disclosure can provide high levels of adenosine editing. In some embodiments, oligonucleotides and compositions of the present disclosure are useful for treating various conditions, disorders or diseases, e.g., alpha-1 antitrypsin deficiency. In some embodiments, the present disclosure provides methods for treating various conditions, disorders or diseases that can benefit from adenosine editing.

The present application relates to a novel Bacillus promoter variant and a protein production method using same. When the novel Bacillus promoter variant of the present application is used, the expression of a target protein can be significantly increased in a host cell, and thus the novel Bacillus promoter variant can be effectively used in the production of biotechnologically, medically, and industrially useful proteins through the mass production of proteins and target proteins such as polypeptide drugs.

Provided are polypeptides that include, from N-terminus to C-terminus, a chimeric antigen receptor (CAR), a protease, and a degron, where the polypeptide further includes a cleavage site for the protease disposed between the CAR and the degron. Also provided are cells that include such polypeptides (e.g., where the cells express the CAR on their surface) and pharmaceutical compositions including such cells. Nucleic acids that encode the polypeptides, cells including such nucleic acids, and pharmaceutical compositions including such cells, are also provided. Also provided are methods for controlling the expression of a CAR on the surface of a cell, and methods of using the cells of the present disclosure, including methods of using such cells to administer a regulatable CAR cell-based therapy (e.g., a regulatable CAR T cell therapy) to an individual.

The present invention relates to clinical diagnostics including diagnosis, prognosis, prediction, risk assessment and / or risk stratification of preterm birth (PTB) and subsequent treatment in a pregnant subject, and corresponding methods and products. The invention provides decision tools to help clinicians choosing the most appropriate management for the pregnant women. In particular, the present invention relates to a method for the diagnosis, prognosis, prediction, risk assessment and / or risk stratification of preterm birth (PTB) in a pregnant subject, the method comprising determining a level of one or more biomarkers in a sample that has been isolated from said pregnant subject, wherein the one or more biomarkers comprise at least one of matrix metallopeptidase 9 (MMP9) or fragment(s) thereof and Pappalysin-2 (PAPP-A2) or fragment(s) thereof, wherein the level of the one or more biomarkers in the sample is indicative of the presence or absence of a subsequent PTB.

The invention relates to an isolated polypeptide comprising an ACE2 moiety and a stability-increasing polypeptide moiety, wherein the ACE2 moiety consists of amino acid residues 18 to 728 of the ACE2 protein ( SEQ ID NO : 1; UniProt Q9BYF1, ACE2_HUMAN) or a biologically active ACE2 mutant or ACE2 variant polypeptide thereof; and wherein the stability-increasing polypeptide moiety increases the stability of the ACE2 moiety in the course of administration to a patient. The polypeptide according to the present invention shows an increased biological activity and stability compared to the ACE2 polypeptides available in the prior art.

The present invention provides antagonizing antibodies that bind to complement factor D (CFD), conjugates thereof, and methods of using same. The anti-CFD antibodies can be used therapeutically alone or in combination with other therapeutics to treat age related macular degeneration and other diseases.

The present invention relates to enzyme compositions with improved cleaning and / or anti-redeposition effect.

The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents such as small interfering RNA (siRNA) molecules, able to inhibit proprotein convertase subtilisin kexin 9 (PCSK9) gene expression. Also disclosed are pharmaceutical compositions that include PCSK9 RNAi agents and methods of use thereof. The PCSK9 RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that comprise N-acetyl-galactosamine, to facilitate the delivery to hepatocyte cells. Delivery of the PCSK9 RNAi agents in vivo provides for in vivo provides for inhibition of PCSK9 gene expression and thereby reduction of PCSK9 protein. The RNAi agents can be used in methods of treatment of diseases or disorders mediated at least in part by PCSK9 gene expression, including among others hypercholesterolemia, familial hypercholesterolemia including heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH), familial hypobetalipoproteinemia, hyperlipidemia, coronary artery disease, polygenic dyslipidemia, heart disease, cardiovascular disease (CVD) including clinical atherosclerotic cardiovascular disease (ASCVD).

The invention belongs to the technical field of bioengineering, and particularly relates to collagen tripeptide as well as a preparation method and application thereof. The method comprises the following steps: carrying out depolymerization treatment on a raw material containing collagen to construct a magnetic immobilized enzyme; by utilizing the magnetic immobilized enzyme, raw materials subjected to depolymerization treatment are subjected to enzymolysis at a certain temperature, pH and reaction time, and with the assistance of a magnetic field, rapid separation and cyclic utilization of the immobilized enzyme can be realized. And finally, carrying out enzyme deactivation, solid-liquid separation and ultrafiltration to obtain the collagen tripeptide with GPH content of more than or equal to 59wt.%, and compared with the existing collagen tripeptide, the collagen tripeptide has higher GPH content. The preparation method is simple in process, easy and convenient to operate, low in cost, capable of achieving mass production and suitable for industrialization, and has remarkable practicability and economic benefits.

Provided is an RNA inhibitor inhibiting PCSK9 gene expression, comprising an antisense strand, the antisense strand comprising a complementary region complementary to at least a portion of mRNA encoding PCSK9, and the length of the complementary region being 17-23 nucleotides; the antisense strand comprises any one of the following nucleotide sequences: SEQ ID NO.: 328-654, 1045-1107, 1125-1146 or 1149-1170, or a sequence differing therefrom by no more than 3 nucleotides. Also provided is a pharmaceutical composition, comprising the described RNA inhibitor inhibiting PCSK9 gene expression, and further comprising a delivery medium, and / or a pharmaceutically acceptable excipient and / or carrier and / or diluent.

Provided herein are methods for coating a microparticle, cell, or therapeutic agent with a biomimetic zona pellucida (BZP). Also provided herein are BZP-coated cells prepared using the enclosed methods. The methods for using the BZP-coated microparticle to treat diabetes are also provided.

The invention discloses an acid protease mutant PepA4 with improved heat resistance and application thereof, and relates to the technical field of gene engineering and enzyme engineering. The amino acid sequence of the acid protease mutant PepA4 is obtained by carrying out D67A, E103D, E304K and S368L point mutation on an amino acid sequence as shown in SEQ ID NO: 1, and the amino acid sequence of the acid protease mutant PepA4 is as shown in SEQ ID NO: 2. The high-temperature-resistant acid protease disclosed by the invention can still maintain the enzyme activity of 80% or above at 75 DEG C for 5 minutes. The acid protease provided by the invention has better acid resistance, and can be widely applied to food processing, leather processing and feed processing industries.