127 results about "Apolipoproteins E" patented technology

Oligonucleotide compounds modulate expression and / or function of an apolipoprotein (ApoA1) polynucleotides and encoded products thereof. Methods for treating diseases associated with apolipoprotein-A1 (ApoA1) comprise administering one or more Oligonucleotide compounds designed to inhibit the Apo-A1 natural antisense transcript to patients.

Methods of utilizing a combined administration or a unit dosage of a combination of an HMG-CoA inhibitor and omega-3 fatty acids for the reduction of apolipoprotein-B levels. The methods are especially useful in the treatment of patients with hypertriglyceridemia or hypercholesterolemia or mixed dyslipidemia, coronary heart disease (CHD), vascular disease, atherosclerotic disease and related conditions, and for the prevention or reduction of cardiovascular, cardiac, and vascular events.

Disclosed are high density lipoprotein-nucleic acid particles, wherein the particles include (a) an apolipoprotein; (b) a nucleic acid component comprising a therapeutic nucleic acid segment; and (c) a polypeptide comprising a positively charged region, wherein the positively-charged region of the polypeptide associates with the nucleic acid component. Also disclosed are pharmaceutical compositions that include a) an apolipoprotein; (b) a nucleic acid component comprising a therapeutic nucleic acid segment; and (c) a polypeptide comprising a positively charged region. Methods that concern the particles and pharmaceutical compositions of the present invention are also set forth, as well as kits.

The present invention relates to materials and methods for the in vivo transport and deliver of nucleic acids. More particularly, it concerns the use of lipoproteins, including but not limited to, low density lipoproteins ("LDL"), and / or apolipoproteins for the binding and in vivo transport of nucleic acids. In addition, the present invention relates to the use of lipoproteins in the early detection of cancer and / or metastatic cancer and / or arteriosclerosis.

The invention relates to a pharmaceutical composition comprising an apolipoprotein construct, to an apolipoprotein construct, a nucleic acid sequence encoding the apolipoprotein construct, a vector comprising the nucleic acid sequence, a method for producing the apolipoprotein construct, and a method of treatment comprising administering the apolipoprotein construct. The presented data document that the constructs according to the invention are capable of binding lipids, are capable of binding cubilin, which is a strong Apo Al receptor, stronger than native Apo A-I and that the plasma half life of the constructs is at least tripled compared to native Apo A-I. Together these data document that the constructs according to the invention are strong candidates for treatment of cardiovascular diseases.

Compounds, compositions and methods are provided for modulating the expression of apolipoprotein(a). The compositions comprise oligonucleotides, targeted to nucleic acid encoding apolipoprotein(a). Methods of using these compounds for modulation of apolipoprotein(a) expression and for diagnosis and treatment of disease associated with expression of apolipoprotein(a) are provided.

Antisense compounds, compositions and methods are provided for modulating the expression of apolipoprotein B. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding apolipoprotein B. Methods of using these compounds for modulation of apolipoprotein B expression and for treatment of diseases associated with expression of apolipoprotein B are provided.

The invention provides methods of treating or preventing a condition or disorder associated with dyslipidemia with compositions comprising apolipoprotein-sphingomyelin complexes. The methods of the invention permit reduction, by 4- to 20-fold, of the amount of apolipoprotein required for therapeutic administration to bring about an ameliorative effect.

The present disclosure provides therapeutic agents for the treatment of age-related macular degeneration (AMD) and other eye disorders. One or more therapeutic agents can be used to treat any stages (including the early, intermediate and advance stages) of AMD, and any phenotypes of AMD, including geographic atrophy (including non-central GA and central GA) and neovascularization (including types 1, 2 and 3 NV). In some embodiments, the one or more therapeutic agents are or include an anti-dyslipidemic agent, an antioxidant, an anti-inflammatory agent, a complement inhibitor, a neuroprotector or an anti-angiogenic agent, or any combination thereof. In certain embodiments, the one or more therapeutic agents are or include an anti-dyslipidemic agent (e.g., an apolipoprotein mimetic or / and a statin). In some embodiments, the one or more therapeutic agents are mixed with, non-covalently associated with or covalently bonded to a cell-penetrating peptide (CPP), encapsulated in CPP-conjugated nanoparticles, micelles or liposomes, or modified (e.g., stapled, prenylated, lipidated or coupled to a small-molecule α-helix mimic) to acquire membrane-translocating ability. In certain embodiments, the one or more therapeutic agents are administered by eye drop.

Methods for the rapid and long-term lowering of lipid levels in human subjects and for the treatment of conditions associated with elevated LDL-cholesterol and elevated apolipoprotein B are provided.

A pharmaceutical composition has an adequate pharmaceutical carrier or diluent and an element selected from a pharmaceutical composition having an adequate pharmaceutical carrier or diluent and an element selected from: —apolipoprotein apoL-III; —a pharmaceutically active fragment of this apolipoprotein apoL-III; —a nucleotide sequence encoding this apolipoprotein apoL-III or the fragment; —a vector having the nucleotide sequence; —a cell transformed by the nucleotide sequence or the vector; —an inhibitor or activator directed against the apolipoprotein apoL-III, its fragment or its nucleotide sequence, —an anti-inhibitor or anti-activator directed against the inhibitor or activator or its encoding nucleotide sequence.

This invention relates to protein separation and purification methods for both alpha-1-antitrypsin (AAT, also known as alpha-1 proteinase inhibitor, API, and A1-PI) and Apolipoprotein A-I (ApoA-1) from, for example, a fraction of human blood plasma. In certain embodiments, the invention provides methods for separating AAT from ApoA-1 at the initial stage of purification, so that the same starting material can be used as a source for both proteins. The methods further pertain to providing compositions of AAT and of ApoA-1 suitable for pharmaceutical use and are suitable for large-scale purification.

The present invention provides a nanodisc without a membrane scaffold protein. The nanodisc includes a telodendrimer and a lipid; the nanodisc does not include a membrane scaffold protein. The telodendrimer has the general formula PEG-L-D-(R)n, wherein D is a dendritic polymer; L is a bond or a linker linked to the focal point group of the dendritic polymer; each PEG is a poly(ethylene glycol) polymer; each R is and end group of the dendritic polymer, or and end group with a covalently bound hydrophobic group, hydrophilic group, amphiphilic compound, or drug; and subscript n is an integer from 2 to 20. Methods of making the nanodiscs are also provided.

In vitro protein synthesis systems and methods are provided that produce membrane proteins in soluble form. In some aspects, the invention provides methods of synthesizing proteins using in vitro protein synthesis systems that include an apolipoprotein, in which higher yields of soluble protein are produced than in the absence of the apolipoprotein. Apolipoproteins useful in the present invention include naturally occurring apolipoproteins, as well as sequence variants of wild-type apolipoproteins, and engineered apolipoproteins. The apolipoproteins can be provided in an in vitro protein synthesis system associated with lipid or not associated with lipid. The invention also provides compositions and kits for synthesis of proteins in soluble form, in which the compositions and kits include cell extracts for protein translation and at least one apolipoprotein biomolecule.

Oligonucleotide compounds modulate expression and / or function of an apolipoprotein (ApoA1) polynucleotides and encoded products thereof. Methods for treating diseases associated with apolipoprotein-A1 (ApoA1) comprise administering one or more Oligonucleotide compounds designed to inhibit the Apo-A1 natural antisense transcript to patients.

In vitro protein synthesis systems and methods are provided that produce membrane proteins in soluble form. In some aspects, the invention provides methods of synthesizing proteins using in vitro protein synthesis systems that include an apolipoprotein, in which higher yields of soluble protein are produced than in the absence of the apolipoprotein. Apolipoproteins useful in the present invention include naturally occurring apolipoproteins, as well as sequence variants of wild-type apolipoproteins, and engineered apolipoproteins. The apolipoproteins can be provided in an in vitro protein synthesis system associated with lipid or not associated with lipid. The invention also provides compositions and kits for synthesis of proteins in soluble form, in which the compositions and kits include cell extracts for protein translation and at least one apolipoprotein biomolecule.

The present invention relates to reconstituted high density lipoprotein (rHDL) formulations comprising an apolipoprotein, a lipid and a lyophilization stabilizer. Said formulations have reduced renal toxicity and good long-term stability, especially in lyophilized form.

The invention relates to a lipoprotein (a) detection kit which comprises a reagent R1, a reagent R2 and a reference substance, wherein the reagent R1 is an HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) buffer system which comprises 0.5-10 g / L HEPES, 2-20 g / L sodium chloride, 0.05-1.0 ml / L Tween-20, 0.1-2 g / L bovine serum albumin, 5-25 g / L polyethyleneglycol-6000, 1-5 g / L EDTA (ethylene diamine tetraacetic acid) and 0.1-2 g / L Proclin 300; the reagent R2 comprises a polystyrene latex particle mixture which is prepared by a chemical crosslinking method, coated with an anti-human-apolipoprotein (a) polyclonal antibody and provided with carboxylic groups on the surface, a 0.5-10 g / L HEPES buffer solution and aspartame, wherein the weight-to-volume ratio of the aspartame to the reagent R2 is (0.01-0.5):100 (g / L); and the reference substance is a human serum or serum-matrix-like liquid with human recombinant apolipoprotein (a). The kit provided by the invention has the advantages of high detection sensitivity, high accuracy, favorable precision, favorable linearity within detection range, high stability, low production cost and low blank absorbance, and has anti-interference performance.

The invention discloses an A beta targeted recombinant lipoprotein nano drug carrier and a preparation method and application thereof. The A beta targeted recombinant lipoprotein nano drug carrier comprises lipid, apolipoprotein and a drug, the drug is an alzheimer disease targeting therapeutic or diagnostic drug, and comprises one or a plurality of small molecule chemical therapeutic drugs and large molecule polypeptide, protein, gene therapeutic and diagnostic drugs. By construction of the drug carrier, the defects of scarce sources, cumbersome preparation, low quality controllability and the like of natural lipoprotein can be solved, and the drug carrier provides a new and more effective and safe solution for delivery of the alzheimer disease targeting therapeutic or diagnostic drug, and has the important research value and clinical application prospects.

This invention relates to a highly efficient artificial low-density lipoprotein (LDL) carrier system for the targeted delivery therapeutic agents across the blood-brain barrier (BBB). In particular, this invention relates to artificial LDL particles comprised of three lipid elements: phosphatidyl choline, fatty-acyl-cholesterol esters, and at least one apolipoprotein. The present invention further relates to compositions, methods and kits comprising artificial LDL particles for targeting drugs to and across the BBB for the prevention and treatment of brain diseases.

Anti-hedgehog antibodies directed at blocking the binding of hedgehog to its receptor patched-1, will impair lipid metabolism and storage. This invention presents methods for the treatment of a variety of lipid metabolism and lipid storage disorders, aberrant apolipoprotein expression, atherosclerosis and other lipid associated disorders using lipid modulators such as hedgehog antagonists or hedgehog agonists.

Systems and methods are provided for producing a protein of interest that is typically not amenable to expression in soluble form in in vitro expression systems. In some aspects, the invention provides methods of synthesizing proteins using in vitro protein synthesis systems that include a scaffold protein such as apolipoprotein or an amphipathic alpha helix containing (“AAHC”) protein, in which higher yields of soluble protein are produced than in the absence of the scaffold protein. The scaffold proteins may be provided in an in vitro protein synthesis system associated with lipid or not associated with lipid. The scaffold protein may be provided as a protein per se or may be encoded by a nucleic acid template and co-expressed with the protein of interest. The invention also provides compositions and kits for synthesis of proteins in soluble form, in which the compositions and kits include cell extracts for protein expression and isolation.

The present invention is directed to methods of measuring the concentration of lipoprotein particles and / or lipoprotein-specific apolipoproteins in a biological fluid using an immunoassay, without the need of preliminary physical separation of the various types of lipoprotein particles present in the biological fluid.

A new approach to targeting imaging agents to macrophage-rich sites of interest is disclosed. Compositions of the invention are rHDL and HDL-like liposomal compositions, protein constituents of which, apolipoproteins A-I and / or A-II or fragments thereof are used not only as structural but also as targeting agents. This is achieved by certain controlled chemical or enzymatic modification of apolipoproteins A-I or A-II or fragments thereof. Such modification converts these apolipoproteins to substrates for macrophage scavenger receptors and results in the improvement of contrast agent-(HDL / modified apolipoprotein)-particle association with macrophages and / or absorption (uptake) by macrophages when compared to that of the contrast agent-(HDL / apolipoprotein)-particle constructed with non-modified naturally occurring apo A-I. The compositions can be used for noninvasive specific in vivo molecular detection and localization of macrophage-rich sites of interest using imaging techniques such as computed tomography (CT), gamma-scintigraphy, positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI).

The invention provides methods of treating or preventing a condition or disorder associated with dyslipidemia with compositions comprising apolipoprotein-sphingomyelin complexes. The methods of the invention permit reduction, by 4- to 20-fold, of the amount of apolipoprotein required for therapeutic administration to bring about an ameliorative effect.

Provided are peptides, compositions thereof, and methods for treating or preventing dyslipidemia, a cardiovascular disease, endothelial dysfunction, a macrovascular disorder, or a microvascular disorder.

Methods of utilizing a combined administration or a unit dosage of a combination of an HMG-CoA inhibitor and omega-3 fatty acids for the reduction of apolipoprotein-B levels. The methods are especially useful in the treatment of patients with hypertriglyceridemia or hypercholesterolemia or mixed dyslipidemia, coronary heart disease (CHD), vascular disease, atherosclerotic disease and related conditions, and for the prevention or reduction of cardiovascular, cardiac, and vascular events.

The invention provides a method of diagnosing tuberculosis (TB) in a test subject, said method comprising: (i) providing expression data of two or more markers in a subject, wherein at least two of said markers are selected from transthyretin, neopterin, C-reactive protein (CRP), serum amyloid A (SAA), serum albumin, apoliopoprotein-A1 (Apo-A1), apolipoprotein-A2 (Apo-A2), hemoglobin beta, haptoglobin protein, DEP domain protein, leucine-rich alpha-2-glycoprotein (A2GL) and hypothetical protein DFKZp667I032; and (ii) comparing said expression data to expression data of said marker from a group of control subjects, wherein said control subjects comprise patients suffering from inflammatory conditions other than TB, thereby determining whether or not said test subject has TB.