43 results about "Kexin" patented technology

An human antibody or antigen-binding fragment of a human antibody that specifically binds and inhibits human proprotein convertase subtilisin / kexin type 9 (hPCSK9) characterized by the ability to reduce serum LDL cholesterol by 40-80% over a 24, 60 or 90 day period relative to predose levels, with little or no reduction in serum HDL cholesterol and / or with little or no measurable effect on liver function, as determined by ALT and AST measurements.

The invention relates to an shRNA (short hairpin Ribonucleic Acid) interference sequence of a targeted silence PCSK9 gene and a construction method and lipid-lowering application of a recombinant adeno-associated virus vector of the shRNA interference sequence. Hyperlipidaemia is a metabolic disease characterized by abnormal rising of cholesterol and triglyceride levels in blood, and the design of lipid-lowering drugs is the focus of attention to improvement of hyperlipidaemia. Proprotein convertase subtilisin / kexin type 9 (PCSK9) can be combined with a low-density lipoprotein receptor (LDL-R) and degrade the LDL-R, so that accumulation of LDL-C in blood is further promoted, and hyperlipidemia is caused. Aiming at the key target PCSK9, a specific shRNA interference sequence is designed, and a recombinant adeno-associated virus vector (rAAV) carrying the sequence is constructed by an enzyme digestion-connection method. In-vitro experiments prove that the vector can remarkably reduce the expression level of PCSK9 protein, so that the cyclic utilization of a low-density lipoprotein receptor (LDL-R) is promoted, and the concentration of low-density lipoprotein cholesterol (LDL-C) in plasma is reduced. The rAAV vector provided by the invention has the characteristics of low production cost, high transfection efficiency, lasting action time and the like, and provides a new thought for gene therapy of hyperlipidemia.

Provided are a small interfering RNA (siRNA) used to inhibit the expression of proprote in convertase subtilisin / kexin type 9 (PCSK9) in a cell, a vector comprising nucleotides encoding same, and a cell, as well as a method using the siRNA, the vector or the cell for the treatment of diseases or symptoms associated with the expression of PCSK9 in a subject.

The present disclosure relates to small molecule inhibitors of proprotein convertase subtilisin-like / kexin type 9 (PCSK9), pharmaceutical compositions comprising said compounds, and their use in the prevention and treatment of diseases and disorders associated with PCSK9.

This invention provides an antigen-binding protein that binds to proprotein converterase subtilisin kexin type 9 (PCSK9), as well as a method for using and producing the antigen-binding protein. [Solution] The present invention provides an isolated neutralizing antigen-binding protein that interacts with proprotein converterase subtilisin kexin type 9 (PCSK9), and which contains a specific amino acid sequence that binds to the PCSK9 protein and reduces the LDLR-reducing effect of PCSK9 on LDLR.

The present invention belongs to the field of biomedical technologies, and specifically relates to the use of a biomarker in the preparation of a product for diagnosing sepsis. The biomarker is proprotein convertase subtilisin / kexin type 6 (PCSK6), which has significantly high sensitivity and specificity in diagnosing sepsis.

The present disclosure provides pharmaceutical compositions comprising fibronectin based scaffold domain proteins that bind, for example, proprotein convertase subtilisin kexin-9 (PCSK9).

Provided herein are gene repressor systems comprising fusion proteins, such as fusion proteins comprising a DNA binding domain such as a TALE, zinc finger or catalytically-dead CRISPR protein and guid

The invention relates to Proprotein Convertase Subtilisin Kexin type 9 (PCSK9) antagonists, such as antibodies and fragments, as well as methods, uses and combinations.

The present invention relates to a dual-targeting siRNA agent, which comprises two different siRNAs targeting two different genes or pharmaceutically acceptable salts thereof, and the two different siRNAs or salts thereof are linked by a pharmaceutically acceptable ligand. The siRNA is a dsRNA composed of a sense strand and an antisense strand. The two different genes are selected from two of angiotensinogen (AGT), proprotein convertase subtilisin / kexin type 9 (PCSK9), and angiopoietin-like protein 3 (ANGPTL3). The present invention provides the application of the dual-targeting siRNA agent in the preparation of a drug for preventing or treating diseases related to hypertension or / and lipid disorders. The dual-targeting siRNA agent of the present invention can effectively inhibit the expression of two target genes in vivo simultaneously, and has the advantages of strong non-antagonistic activity and high safety. The present invention also provides siRNAs corresponding to the genes of the above dual-targeting siRNA agent and their use for preventing or treating diseases related to hypertension or / and lipid disorders.

The present invention relates to methods of treating or preventing cholesterol related disorders, such as hypercholesterolemia, hyperlipidemia or dyslipidemia, using antibodies against proprotein convertase subtilisin / kexin type 9 (PCSK9). Formulations and methods of producing said formulations are also described.

The present invention relates to a dual-targeting siRNA agent comprising two distinct siRNAs targeting two different genes or their pharmaceutically acceptable salts, wherein the two distinct siRNAs or their salts are linked by a pharmaceutically acceptable ligand. The siRNA is a dsRNA composed of a sense strand and an antisense strand, and the two different genes are selected from a group consisting of angiotensinogen (AGT), proprotein convertase subtilisin / kexin type 9 (PCSK9), and human angiopoietin-like protein 3 (ANGPTL3). The present invention provides the application of the dual-targeting siRNA agent in the preparation of drugs for preventing or treating diseases associated with hypertension and / or dyslipidemia. The dual-targeting siRNA agent described in the present invention can effectively inhibit the expression of two target genes simultaneously in vivo, offering the advantages of strong non-antagonistic activity and high safety. The present invention also provides the siRNAs targeting corresponding genes for the aforementioned dual-targeting siRNA agent and their use for preventing or treating diseases associated with hypertension and / or dyslipidemia.

This provides a method to reduce cardiovascular risk in patients with a genetic profile associated with a response to proprotein converter subtilisin / kexin type 9 (PCSK9) inhibitor therapy. [Solution] A method for treating a patient at risk of major cardiovascular adverse events (MACE) includes: determining the patient's polygenetic risk score (CAD-PRS), which includes a weighted sum of multiple gene variants associated with coronary artery disease; identifying the patient as being at high risk of MACE if the patient has a CAD-PRS greater than a threshold CAD-PRS determined from a reference population; and administering a PCSK9 inhibitor to the patient if the patient has been identified as being at high risk of MACE.

Compositions and methods relating to ApoA-1 fusion polypeptides are disclosed. The fusion polypeptides include a first polypeptide segment corresponding to an ApoA-1 polypeptide or ApoA-1 mimetic, and may also include a dimerizing domain such as, e.g., an Fc region, which is typically linked carboxyl-terminal to the first polypeptide segment via a flexible linker. In some embodiments, the fusion polypeptide further includes a second polypeptide segment located carboxyl-terminal to the first polypeptide segment and which confers a second biological activity (e.g., an RNase, paraoxonase, platelet-activating factor acetylhydrolase, cholesterol ester transfer protein, lecithin-cholesterol acyltransferase, polypeptide that specifically binds to proprotein convertase subtilisin / kexin type 9, or polypeptide that specifically binds to amyloid beta). Also disclosed are dimeric proteins comprising first and second ApoA-1 fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

Disclosed herein is a wearable drug delivery device including a container filled at least partially with a drug including at least one of a PCSK9 (Proprotein Convertase Subtilisin / Kexin Type 9) specific antibody, a granulocyte colony-stimulating factor (G-CSF), a sclerostin antibody, or a calcitonin gene-related peptide (CGRP) antibody. The wearable drug delivery device may include a needle and an insertion mechanism configured to insert the needle into a patient. A fluid pathway connector may define a sterile fluid flowpath between the container and the insertion mechanism. Optionally, a cannula initially disposed about the needle may be included. The cannula may be retained in the patient at an injection site created by the needle after the needle is withdrawn from the patient. Methods of assembly and operation are also provided.

The present disclosure provides compositions and methods for modifying the PCSK9 gene. In some aspects, the disclosure provides a guide RNA, compositions thereof, and pharmaceutical compositions comprising guide RNAs or compositions as described herein. In some aspects, the disclosure also provides uses and methods of use of guide RNAs, compositions or pharmaceutical compositions thereof, as described herein, the present invention relates to a PCSK9 inhibitor for inducing a double-strand break or a single-strand break in the PCSK9 gene, for reducing expression of the PCSK9 gene in a cell or subject, and for treating a patient suffering from or at risk of suffering from a PCSK9-related disease or condition.

Provided herein are gene repressor systems comprising a fusion protein, such as a fusion protein comprising a DNA binding domain, such as TALE, a zinc finger, or a CRISPR protein of catalyzed death, and a guide nucleic acid (gRNA) useful for repressing a proprotein convertase subtilisin / kexin type 9 (PCSK9) gene. Also provided are methods of using such systems to repress PCSK9 transcription.

Immunogenic compositions comprising non-naturally occurring generic fungal kexin peptides are described and characterized and the use of such compositions in the treatment or prevention of various diseases or severe diseases and / or symptoms thereof in a subject, in particular in the treatment or prevention of various diseases or severe diseases and / or symptoms thereof, in particular in the treatment or prevention of diseases associated with fungal pathogens (e.g., fungal pathogens). The present invention relates to a method for treating diseases or severe diseases and / or symptoms thereof associated with infection by genus Pneumocystis, Aspergillus, Candida, or Cryptococcus, e.g., Aspergillus, Candida, or Cryptococcus. The immunogenic peptides or immunogenic fragments thereof may be recombinantly produced, recombined, and / or isolated.

This specification provides a gene repressor system comprising a fusion protein, such as a fusion protein containing a non-catalyzed class 2, type V CRISPR protein useful for repressing the precursor protein-converting enzyme subtilisin / kexin type 9 (PCSK9) gene, and a guide nucleic acid (gRNA). Methods for constructing and using such a system for repressing PCSK9 transcription are also provided.

A low-molecular weight compound having an activity of inhibiting the functions of proprotein convertase subtilisin / kexin type 9 (PCSK9), a PCSK9 inhibitor containing a compound represented by formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, as an active component, and a medicament containing the PCSK9 inhibitor as an active component for use in prevention or treatment of one or more symptoms, diseases, or disorders, related to the functions of PCSK9.

The present invention relates to methods of treating or preventing cholesterol related disorders, such as hypercholesterolemia, hyperlipidemia or dyslipidemia, using antibodies against proprotein convertase subtilisin / kexin type 9 (PCSK9). Formulations and methods of producing said formulations are also described.

The present disclosure provides methods of treating subjects having sepsis, SIRS, septic shock, and / or MODS, methods of identifying subjects having an increased risk of developing sepsis, SIRS, septic shock, and / or MODS, and methods of detecting Proprotein Convertase Subtilisin / Kexin Type 9 (PCSK9) and / or Low Density Lipoprotein Receptor (LDLR) variant nucleic acid molecules and variant polypeptides.

An siRNA which inhibits proprotein convertase subtilisin / kexin type 9 (PCSK9) gene expression, a pharmaceutical composition containing the siRNA, and a conjugate. Each nucleotide in the siRNA is independently a modified or unmodified nucleotide. The siRNA contains a sense strand and an antisense strand. The sense strand contains nucleotide sequence I; nucleotide sequence I having the same length as the nucleotide sequence shown in SEQ ID NO: 1, with no more than three nucleotides differences. The antisense strand contains nucleotide sequence II, nucleotide sequence II having the same length as the nucleotide sequence shown in SEQ ID NO: 2, with no more than three nucleotides differences. The siRNA, pharmaceutical composition thereof and the conjugate can effectively treat and / or prevent hypercholesterolemia.

An siRNA which inhibits proprotein convertase subtilisin / kexin type 9 (PCSK9) gene expression, a pharmaceutical composition containing the siRNA, and a conjugate. Each nucleotide in the siRNA is independently a modified or unmodified nucleotide. The siRNA contains a sense strand and an antisense strand. The sense strand contains nucleotide sequence I; nucleotide sequence I having the same length as the nucleotide sequence shown in SEQ ID NO: 1, with no more than three nucleotides differences. The antisense strand contains nucleotide sequence II, nucleotide sequence II having the same length as the nucleotide sequence shown in SEQ ID NO: 2, with no more than three nucleotides differences. The siRNA, pharmaceutical composition thereof and the conjugate can effectively treat and / or prevent hypercholesterolemia.

Provided herein are gene repressor systems comprising fusion proteins, such as fusion proteins comprising a DNA binding domain such as a TALE, zinc finger or catalytically-dead CRISPR protein and guide nucleic acid (gRNA), which are useful in the repression of a proprotein convertase subtilisin / kexin Type 9 (PCSK9) gene. Also provided are methods of using such systems to repress transcription of PCSK9.

The application discloses a polynucleotide sequence for simultaneously reducing blood fat and blood pressure and application thereof. Cell and mouse experiments show that the application can significantly inhibit the expression levels of multiple blood fat and blood pressure molecular targets such as proprotein convertase subtilisin / kexin type 9 (PCSK9), angiotensinogen (AGT) and beta-hydroxy-beta-methylglutaryl-coenzyme a reductase (HMGCR), thereby reducing the blood fat and blood pressure levels of a related disease model mouse. The application is expected to be applied to treating related cardiovascular and cerebrovascular diseases complicated with high blood fat and high blood pressure symptoms.

Aspects of the technology relate to a composition comprising: (i) a first RNAi agent that targets Proprotein convertase subtilisin / kexin type 9 (PCSK9) and a second RNAi agent that targets angiotensinogen (AGT); (ii) a first RNAi agent that targets PCSK9 and a third RNAi agent that targets Apolipoprotein A (LPA); (iii) a second RNAi agent that targets AGT and a third RNAI agent that targets LPA, or (iv) a first RNAi agent that targets PCSK9, a second RNAi agent that targets AGT, and the third RNAi agent that targets LPA.

Described and featured are immunogenic compositions comprising non-naturally occurring pan-fungal kexin peptides and methods of using such compositions for the treatment or prevention of various diseases or severe diseases, and / or the symptoms thereof, particularly those associated with infection by fungal pathogens (e.g., Pneumocystis, Aspergillus, Candida, or Cryptococcus) in the subject. The immunogenic peptides or immunogenic fragments thereof may be recombinantly produced, recombinant, and / or isolated.