79 results about "Proprotein convertase" patented technology

Described are RNAi agents, compositions that include RNAi agents, and methods for dual inhibition of an Apolipoprotein C-III (APOC3) and Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene. The APOC3-PCSK9 RNAi agents disclosed herein inhibit the expression of an APOC3 and a PCSK9 gene. Pharmaceutical compositions that include one or more APOC3-PCSK9 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described TSLP RNAi agents to hepatic cells, in vivo, provides for inhibition of APOC3 and / or PCSK9 gene expression, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including hypertriglyceridemia and hypercholesterolemia.

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.

Provided is a nucleic acid structure which enhances an antigen-specific immune response. The nucleic acid structure comprises a polynucleotide encoding a SNARE protein, a polynucleotide encoding a proprotein convertase recognition sequence, and a polynucleotide encoding an antigen, wherein the polynucleotide encoding a SNARE protein and the polynucleotide encoding an antigen are linked via the polynucleotide encoding a proprotein convertase recognition sequence.

The invention belongs to the technical field of biological medicine, and particularly relates to application of a biomarker in preparation of a product for diagnosing sepsis, the biomarker is proprotein convertase subtilisin 6 (PCSK6), and the biomarker has remarkably high sensitivity and specificity in the aspect of sepsis diagnosis.

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.

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.

To provide an injection device for subcutaneous administration, for preventing cardiovascular events in a human subject.SOLUTION: The present invention provides an injection device for subcutaneous administration, comprising a fixed dose of 275 mg to 325 mg of an interfering ribonucleic acid (RNAi) agent. The device comprises a double-stranded ribonucleic acid comprising a sense strand and an antisense strand forming a double-stranded region, where the antisense strand comprises the nucleotide sequence of 5'-asCfsaAfAfAfgCfaAfaAfcAfgGfuCfuagsasa-3' (SEQ ID NO: 3), and the sense strand comprises the nucleotide sequence of 5'-csusagacCfuGfudTuugcuuuugu-3' (SEQ ID NO: 4), where a, g, c and u are 2'-O-methyl (2'-OMe) A, G, C, or U; Af, Gf, Cf or Uf are 2'-fluoro A, G, C or U; dT is 2'-deoxythymidine; and s is a phosphorothioate linkage.SELECTED DRAWING: None

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 disclosure relates to isolated oligonucleotides comprising duplex regions targeting Proprotein convertase subtilisin kexin 9 (PCSK9), and delivery systems, kits and compositions comprising same, and methods of using same for inhibiting or downregulating PCSK9.

This invention discloses the application of a polypeptide in inhibiting inflammatory pain, belonging to the field of biomedicine. The polypeptide is Mexneurin-3 (Mx-3), one of three Mexneurin polypeptides formed by the cleavage of ProMexneurin, a protein precursor found in the mammalian central nervous system, by proprotein convertase. This invention reveals that Mx-3, as an endogenous polypeptide, has significant analgesic effects, inhibiting both acute and chronic inflammatory pain with fewer side effects and greater safety. This invention also elucidates the analgesic mechanism of Mx-3, finding that it upregulates diacylglycerol (DAG) levels in the spinal cord and activates protein kinase C (PKC). The application of Mx-3 in inhibiting inflammatory pain provided by this invention can be used to develop safer and more effective novel analgesics, providing new ideas and references for the treatment of inflammatory pain.

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

The present invention relates to a method of reducing low density lipoprotein cholesterol or preventing a cardiac event in a subject at risk of having an atherosclerotic cardiovascular disease or an atherosclerotic cardiovascular disease, comprising administering to the subject a prophylactically effective amount of an RNAi agent. In addition, the present invention relates to a method of preventing the development of an atherosclerotic cardiovascular disease in a subject, comprising administering to the subject a prophylactically effective amount of an RNAi agent. Furthermore, the present invention relates to a method of treating a subject at risk of having an atherosclerotic cardiovascular disease or equal to an atherosclerotic cardiovascular disease, comprising administering to the subject a therapeutically effective amount of an RNAi agent.

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.

Method of lowering low-density lipoprotein cholesterol or preventing a cardiac event in a subject who has atherosclerotic cardiovascular disease or who is atherosclerotic cardiovascular disease risk equivalent, involving administering to the subject a prophylactically effective amount of an RNAi agent. Also, a method of preventing development of atherosclerotic cardiovascular disease in a subject involving administering to the subject a prophylactically effective amount of an RNAi agent. Further, a method of treating a subject who has atherosclerotic cardiovascular disease or who is atherosclerotic cardiovascular disease risk equivalent involving administering to the subject a therapeutically effective amount of an RNAi agent.

This invention provides the use of RNA interferants that inhibit PCSK9 synthesis in prophylactic or therapeutic methods. [Solution] A method for reducing low-density lipoprotein cholesterol or preventing cardiac events in a subject having atherosclerotic cardiovascular disease or being at equivalent risk to atherosclerotic cardiovascular disease, comprising the step of administering a prophylactic effective amount of RNAi to the subject. Also, a method for preventing the onset of atherosclerotic cardiovascular disease in a subject, comprising the step of administering a prophylactic effective amount of RNAi to the subject. Furthermore, a method for treating a subject having atherosclerotic cardiovascular disease or being at equivalent risk to atherosclerotic cardiovascular disease, comprising the step of administering a therapeutic effective amount of RNAi to the subject.

To provide an injection device for subcutaneous administration, for preventing cardiovascular events in a human subject.SOLUTION: The present invention provides an injection device for subcutaneous administration, comprising a fixed dose of 275 mg to 325 mg of an interfering ribonucleic acid (RNAi) agent. The device comprises a double-stranded ribonucleic acid comprising a sense strand and an antisense strand forming a double-stranded region, where the antisense strand comprises the nucleotide sequence of 5'-asCfsaAfAfAfgCfaAfaAfcAfgGfuCfuagsasa-3' (SEQ ID NO: 3), and the sense strand comprises the nucleotide sequence of 5'-csusagacCfuGfudTuugcuuuugu-3' (SEQ ID NO: 4), where a, g, c and u are 2'-O-methyl (2'-OMe) A, G, C, or U; Af, Gf, Cf or Uf are 2'-fluoro A, G, C or U; dT is 2'-deoxythymidine; and s is a phosphorothioate linkage.SELECTED DRAWING: None