60 results about "Kexin" patented technology

The present invention relates to methods for treating diseases or conditions in which proprotein convertase subtilisin / kexin type 9 (PCSK9) expression or activity causes an impact by administration of PCSK9-specific antibodies or antigen-binding fragments thereof and preferably by additional administration of an inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-COA reductase). The present invention further relates to PCSK9-specific antibodies or antigen-binding fragments thereof for use in the treatment of diseases or conditions in which PCSK9 expression or activity causes an impact.The present invention also relates to articles of manufacture comprising packaging material, PCSK9-specific antibodies or antigen-binding fragments thereof, and a label or packaging insert indicating which groups of patients can be treated with said antibodies or fragments, which groups of patients must not be treated with said antibodies or fragments, and which dosage regimen should be used.The present invention further relates to methods of testing the efficacy of PCSK9-specific antibodies or antigen-binding fragments thereof for the treatment of certain diseases or conditions and for the treatment of specific sub-groups of patients.

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.

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.

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 prevention and treatment of diseases and conditions associated with PCSK9.

The disclosure relates to inhibitors of PCSK9 useful in the treatment of lipid metabolism, and other diseases in which PCSK9 plays a role, having the Formula (I):or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein R1, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, and X13 are described herein.

Provided are a small interfering RNA (siRNA) for inhibiting expression of proprotein convertase subtilisin / kexin type 9 (PCSK9) in a cell, a vector and a cell comprising a nucleotide encoding the same, and a method for treating a disease or symptom associated with PCSK9 expression in a subject using the siRNA, the vector or the cell.

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

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.

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 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).

To provide a dsRNA composition targeting PCSK9, a method for inhibiting PCSK9 gene expression, and a method for treating one or more diseases associated with PCSK9 gene expression.SOLUTION: Provided herein is a double stranded ribonucleic acid (dsRNA) comprising a sense strand comprising a first sequence and an antisense strand comprising a second sequence, where the first and second sequences are complementary, and the first sequence comprises a specific sequence. The dsRNA is optionally a small interfering RNA (siRNA) or a short hairpin RNA (shRNA), and optionally inhibits the expression of proprotein converting enzyme subtilisin-kexin 9 (PCSK9) gene.SELECTED DRAWING: None

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 provides methods for reducing lipoprotein(a) (Lp(a)) in patients. The methods of the present invention comprise selecting a patient who exhibits elevated serum Lp(a), and administering to the patient a pharmaceutical composition comprising a PCSK9 inhibitor. In certain embodiments, the PCSK9 inhibitor is an anti-PCSK9 antibody such as the exemplary antibody referred to herein as mAb316P.

To provide: an siRNA which inhibits proprotein convertase subtilisin / kexin type 9 (PCSK9) gene expression; a pharmaceutical composition containing the siRNA; and a conjugate.SOLUTION: 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 a nucleotide sequence I, the nucleotide sequence I having the same length as a specific nucleotide sequence 1, with three or less nucleotide differences. The antisense strand contains a nucleotide sequence II, the nucleotide sequence II having the same length as another specific nucleotide sequence 2, with three or less nucleotide differences. The siRNA, pharmaceutical composition thereof and the conjugate can effectively treat and / or prevent hypercholesterolemia.SELECTED DRAWING: Figure 3

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.

The present disclosure relates to PCSK9 inhibitors useful for treating cholesterol lipid metabolism and other diseases in which PCSK9 plays a role, wherein the PCSK9 inhibitor has formula (I): #imgabs0# or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, N-oxide or tautomer thereof, wherein R1, R1, R1, R1, R1, R1, R1, R1, R1, X1, X2, and X3 are described herein.

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.

Disclosed are Nanoformulated compounds that modulate the physiological action of the proprotein convertase subtilisin kexin type 9 (PCSK9), as well as therapeutic methods for use of such compounds to reduce LDL- and related cholesterol levels and / or for the treatment and / or prevention of cardiovascular disease (CVD), including treatment of hypercholesterolemia.

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.

Compositions and methods are disclosed which comprise a guide polynucleotide corresponding to a protospacer sequence on the Angiopoietin-like protein 3 gene with a view to base editing the proprotein

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.