222 results about "PCSK9" patented technology

Antagonists of human proprotein convertase subtilisin-kexin type 9 (“PCSK9”) are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

Antagonists of human proprotein convertase subtilisin-kexin type 9 (“PCSK9”) are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression and / or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and / or activity of genes involved in Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions. Specifically, the invention relates to double stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. The present invention also relates to small nucleic acid molecules, such as siNA, siRNA, and others that can inhibit the function of endogenous RNA molecules, such as endogenous micro-RNA (miRNA) (e.g, miRNA inhibitors) or endogenous short interfering RNA (siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of RISC (e.g., RISC inhibitors), to modulate PCSK9 gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs (e.g., RISC), including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules and are useful, for example, in providing compositions to prevent, inhibit, or reduce metabolic diseases traits and conditions, including but not limited to hyperlipidemia, hypercholesterolemia, cardiovascular disease, atherosclerosis, hypertension, diabetis (e.g., type I and / or type II diabetis), insulin resistance, obesity and / or other disease states, conditions, or traits associated with PCSK9 gene expression or activity in a subject or organism.

Antagonists of human proprotein convertase subtilisin-kexin type 9 (“PCSK9”) are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

The present invention provides compositions and methods for treating disorders of cholesterol and lipid metabolism by administration of an anti-PCSK9 antibody or a peptide inhibitor of PCSK9.

The present invention provides antibody antagonists against proprotein convertase subtilisin / kexin type 9a (“PCSK9”) and methods of using such antibodies.

Antagonists of human proprotein convertase subtilisin-kexin type 9 (“PCSK9”) are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

The present invention provides antibodies and antigen-binding fragments thereof that specifically bind proprotein convertase subtilisin / kexin-9 (PCSK9) with greater affinity at neutral pH than at acidic pH. The antibodies of the invention may possess one or more amino acid changes as compared to antibodies that do not exhibit pH-dependent binding properties. For example, the present invention includes anti-PCSK9 antibodies which possess one or more histidine substitutions in one or more complementarity determining regions. The antibodies of the invention, with pH-dependent binding properties, remain in circulation and exhibit cholesterol lowering activity for prolonged periods of time in animal subjects as compared to anti-PCSK9 antibodies that do not exhibit pH-dependent binding properties. The antibodies of the invention are therefore useful for treating diseases and disorders related to elevated HDL cholesterol, wherein the antibodies of the invention can be administered to a patient at a lower dose and / or with less frequent dosing as compared to antibodies that do not exhibit pH-dependent binding properties.

Disclosed herein are antisense compounds and methods for decreasing LDL-C in an individual having elevated LDL-C. Additionally disclosed are antisense compounds and methods for treating, preventing, or ameliorating hypercholesterolemia and / or atherosclerosis. Further disclosed are antisense compounds and methods for decreasing coronary heart disease risk. Such methods include administering to an individual in need of treatment an antisense compound targeted to a PCSK9 nucleic acid. The antisense compounds administered include gapmer antisense oligonucleotides.

The invention discloses a novel anti-human PCSK9 monoclonal antibody or its fragment prepared by using a bacteriophage antibody library technology for screening and using a gene engineering method. The novel anti-human PCSK9 monoclonal antibody has high affinity to human PCSK9. The antibody can be a full-length antibody, a basically complete antibody, a Fab fragment, a F(ab')2 fragment or a single-chain Fv fragment. The monoclonal antibody or its fragment is used for treating disease mediated by human PCSK9, and the disease comprises, but not limited to, primary hypercholesterolemia, combined hyperlipidemia and familial hypercholesterolemia.

The invention relates to the technical field of genetically engineered antibodies, in particular to a full human monoclonal antibody specific to pro-protein convertase subtilisin / kexin 9 (PCSK9) and a preparation method and an application of a full length antibody. According to a variable region gene, at least 80% identity between variable region code polypeptide of a heavy chain of the gene and a sequence that is shown in SEQ ID NO.1 can be achieved, and at least 80% identity between variable region code polypeptide of a light chain of the gene and a sequence that is shown in SEQ ID NO.2 can be achieved. Specifically, a human monoclonal antibody phage display library is used for screening Fab antibody specific to human PCSK9, and a complete full length antibody is obtained by a genetic engineering method. The antibody can be specifically combined with PCSK9, interaction of PCSK9 and low density lipoprotein receptor (LDLR) is effectively affected, LDLR degradation is inhibited, and the antibody can be applied to curing cholesterol and lipid metabolism diseases.

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression and / or activity. Specifically, the invention relates to double stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules.

The invention relates to a preparation method and application of an electrochemical immunosensor for a biomarker, namely a recombinant proprotein convertase subtilisin kexin type 9 (pcsk9) protein for predicting and diagnosing cardiovascular diseases, and belongs to the technical field of electrochemical detection. The preparation method is characterized by comprising the following steps: firstly, performing nitrogen doping on a graphene nanobelt (n-gnrs), performing amination on a fullerene-palladium-platinum nanoparticle (n-C60 / pdpt) composite material and a staphylococcus aureus a protein (spa), and performing layer-by-layer self-assembling so as to immobilize a pcsk9 antibody (ab1); mixing the synthesized nanoparticle-poly-methylene blue (pt-pmb) with the pcsk9 antibody (ab2), and preparing a nano beacon, thereby obtaining the electrochemical immunosensor for pcsk9 protein detection. The electrochemical immunosensor has the advantages of being high in sensitivity, good in specificity and rapid and convenient in detection. A novel method for pcsk9 protein detection is provided, and useful information is provided for clinical prediction and diagnosis on cardiovascular diseases.

The present invention relates to oligomer compounds (oligomers), which target PCSK9 mRNA in a cell, leading to reduced expression of PCSK9. Reduction of PCSK9 expression is beneficial for the treatment of certain medical disorders, such as hypercholesterolemia and related disorders.

Aromatic-ring azacyclo derivatives and an application thereof are provided. The invention relates to compounds represented by the formula (V), and a preparation method and an application thereof in medicines. In particular, the invention relates to derivatives of the compounds represented by the general formula (V), and a preparation method and the application thereof as therapeutic agents in prevention and treatment of hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hepatic steatosis, type-II diabetes, hyperglycemia, obesity or insulin resistance syndromes and metabolic syndromes. The compounds disclosed by the invention also can reduce total cholesterol, LDL-cholesterol and triglycerides, increase the expression of hepatic LDL receptors and inhibit the expression of PCSK9.

The invention relates to new methods of modulating cholesterol by inhibiting proprotein convertase subtilisin / kexin type 9 (PCSK9) with fatty acid derivatives; and new methods for treating or preventing a metabolic disease comprising the administration of an effective amount of a fatty acid derivative. The present invention is also directed to fatty acid bioative derivatives and their use in the treatment of metabolic diseases.

The present invention provides a method for detecting autoprocessed, secreted PCSK9, a protein involved in cholesterol homeostasis, and for effectively identifying compounds that inhibit autocleavage and secretion from cells. The disclosed method involves the insertion of an epitope tag into a PCSK9 expression construct immediately C-terminal to the pro domain ending at an amino acid residue corresponding to Q152 of human PCSK9. Upon autoprocessing, the epitope tag is exposed and capable of recognition by anti-epitope antibodies or other suitable identification system, allowing for the selective and exclusive identification and / or quantification of processed PCSK9. The present disclosure thus advances the goal of providing enabling technology to the art for the effective identification of therapeutics effective in combating coronary heart disease.

Antagonists of human proprotein convertase subtilisin-kexin type 9 ('PCSK9') are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for the use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

The invention provides a nano antibody. The nano antibody comprises the characteristics that (1) an amino acid sequence shown in SEQ ID NO:1 is achieved; or (2) compared with the (1), the at least 70%identity, the at least 75% identity, the at least 80% identity, the at least 85% identity, the at least 90% identity, the at least 95% identity, and the at least 99% identity are achieved. The nano antibody is an antibody specifically targeting PCSK9, the native conformation PCSK9 can be combined, and the nano antibody has the high water solubility, high tolerance, high stability, high antigen bondability, low immunogenicity, high tissue penetrating power, and high expressivity.

The invention discloses an anti-human PCSK9 (pro-protein convertase subtilisin / kexin 9) chimeric antibody, and preparation and application thereof. The preparation method comprises the following steps: respectively amplifying mouse light chain and heavy chain variable region genes from mouse hybridoma cells, respectively carrying out chimerism with light chain and heavy chain constant region genes of human IgG, and carrying out recombination expression to obtain the human-mouse chimeric antibody. The human-mouse chimeric antibody has favorable affinity with human PCSK9, obviously inhibits the degradation activity of the PCSK9 for liver cell low-density lipoprotein receptors (LDLR), enhances the ingestion of liver cells for LDL-cholesterol (LDL-C), and lowers the cholesterol level in blood.

The invention belongs to the field of antibodies and particularly relates to an anti-human PCSK9 monoclonal antibody and application of the antibody in preparation of drugs for reducing lipoprotein level in blood and preventing or treating cardiovascular diseases or disorders and thrombosis-obstructive diseases or disorders. The anti-human PCSK9 monoclonal antibody has higher affinity and a good application prospect.

The present invention relates to the technical field of monoclonal antibodies, particularly to a PCSK9 antagonist. The present invention further provides a method for obtaining the antibodies, uses of the antibodies to reduce the low density lipoprotein (LDL)-cholesterol level, and / or a treatment method for treatment and / or prevention of cardiovascular diseases (including hypercholesterolemia).

The present invention discloses design and application of a PCSK9 targeting recombinant vaccine, and specifically discloses a PCSK9 targeting recombinant vaccine. Experimental results show that the recombinant vaccine can effectively induce animal body to produce immunoreaction aiming at PCSK9, and effectively reduce cholesterol level. The invention also provides an antigen epitope peptide and fusion protein based on the PCSK9.

The present invention relates to a compound as shown in a formula (VII), a preparation method and applications thereof in medicines. In particular, the present invention relates to a derivative of the compound as shown in the formula (VII), a preparation method, and the applications of the derivative used as a therapeutic agent in prevention and treatment of hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hepatic steatosis, II-type diabetes, hyperglycemia, obesity or insulin resistance syndrome and metabolic syndrome. The compound disclosed by the present invention can also reduce total cholesterol, LDL-cholesterol and triglyceride, and increases expression of a liver LDL receptor and decreases expression of PCSK9.

A method for treating and / or preventing a proprotein convertase subtilisin / kexin type 9 preproprotein (PCSK9)-susceptible viral infection comprising increasing a PCSK9 activity and / or expression in a biological system infected by the virus, whereby the increased PCSK9 activity and / or expression treats and / or prevents the viral infection in the biological system. Methods of classifying subjects, methods of screening and kits therefore.

The invention provides application of PCSK9-targeted microRNA or a drug composition containing the same in preparing drug for inhibiting PCSK9 protein level. In addition, the invention further relatesto a drug composition for treating low-density lipoprotein cholesterol related metabolic disease. The drug composition comprises (a) drug in effective treatment amount and clinically for treating thelow-density lipoprotein cholesterol related metabolic disease and (b) PCSK9-targeted microRNA or the drug composition containing the same in effective treatment amount. Experiments verify that 31 types of microRNA can inhibit PCSK9 protein level in liver cells or liver cell culture liquid, thereby being capable of lowering level of LDLC so as to treat the LDLC related metabolic disease.