97 results about "Proprotein Convertase Inhibitors" 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.

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.

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 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.

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 present invention provides methods and compositions for inhibiting atherosclerotic plaque formation in a subject. In certain embodiments, the methods of the present invention comprise selecting a subject who has, or is at risk of developing, atherosclerosis, and administering to the subject a pharmaceutical composition comprising a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. In certain embodiments, the PCSK9 inhibitor is an anti-PCSK9 antibody, or antigen binding protein.

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 discloses a construction method of a gene detection library of familial hypercholesterolemia and a gene detection kit and relates to gene mutation of LDLR (Low-Density Lipoprotein Receptor), APOB (Apolipoprotein B) and PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9). In order to ensure that all target regions (including an entire coding region and an alternative splicing regionof a gene to be detected) are covered and prevent a primer dimer or a short segment from being formed between primers of adjacent amplicons, a PCR (Polymerase Chain Reaction) amplification primer isdivided into two independent primer pools; then primer sequence digestion, sequencing connector connection, library purification and quality detection are carried out; finally, the detection library is constructed. The method has the advantages that library establishment steps are simple and rapid, the cost is effectively reduced, the working amount is reduced, variation types are comprehensive, the detection accuracy reaches 100 percent and the flux is high.

The invention belongs to the technical field of medicine biologics, relates to functions and mechanisms of PCSK9 (Proprotein Convertase Subtilisin/Kexin 9) in treating T-cell medicated inflammatory-immune diseases, application of a PCSK9 inhibitor in preparing a medicine for treating T-cell medicated inflammatory-immune diseases, and in particular relates to application of a PCSK9 small-molecule interference RNA or PCSK9 small-molecule inhibitor in preparing medicines for preparation systems or external skin application in treating psoriasis, atopic dermatitis or urticaria. Psoriasis is adopted as a testing bed for inflammatory-immune disease research, results show that the PCSK9 small-molecule inhibitor or small-molecule interference RNA has treatment effects which are remarkably prior tothose of PCSK9 monoclonal antibodies in treating inflammation such as psoriasis. The PCSK9 small-molecule interference RNA or PCSK9 small-molecule inhibitor can be further developed into novel medicines for treating inflammatory-immune diseases such as psoriasis, and is small in side effect, low in cost and remarkable in treatment effect.

A chimera protein comprising in the following order: a signal peptide, a proprotein convertase subtilisin/kexin type 9 preproprotein (PCSK9) sequence consisting of amino acid residues at positions 35 to 696 of SEQ ID NO: 38, a transmembrane domain and a cytosolic domain, wherein said cytosolic (CT) domain comprises a sequence able to recycle the protein from the cellular membrane to endosomes.

A chimeric protein comprising in sequence a signal peptide, a first amino acid tag, a proteinase bait, a second amino acid tag, a transmembrane domain and a cytosolic domain, wherein the cytosolic (CT) domain comprises a sequence able to recycle the protein from the cellular membrane to endosomes. A cell line expressing the chimeric protein and an assay using the cell line.

The present invention relates to a method for diagnosis and/or prognosis of cancer and for monitoring the progression of cancer and/or the therapeutic efficacy of an anti-cancer treatment in a subject by determining the molecular form of cadherin at the cell surface of cancer cells in the subject. The invention also relates to a method for preventing, inhibiting or treating cancer or its metastasis in a subject by increasing the adhesive forms of cadherin and/or decreasing the non-adhesive forms of cadherin at the cell surface. The invention also relates to a method step of determining the expression level of furin and proprotein convertase 5A (PC5A).

The present invention discloses a lipid nanoparticle comprising a lipopeptide molecule, dioleoyl phosphoethanolamine, cholesterol, and polyethylene glycol, and the lipid nanoparticle encapsulates Cas9mRNA and a sgRNA molecule in a gene conserved region of target mouse and human Proprotein Convertase subtilisin/kexin type 9 ( PCSK9). The present invention also discloses a preparation method and use of the lipid nanoparticle, and a pharmaceutical composition and formulation comprising the lipid nanoparticle. The lipid nanoparticle and the biological preparation can be used as a novel delivery system for a PCSK9 inhibitor hypolipidemic drug.

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.