38 results about "Asialoglycoprotein receptor" patented technology

The present disclosure is directed to bifunctional small molecules which contain a circulating protein binding moiety (CPBM) linked through a linker group to a cellular receptor binding moiety (CRBM) which is a membrane receptor of degrading cell such as a hepatocyte or other degrading cell. In certain embodiments, the (CRBM) is a moiety which binds to asialoglycoprotein receptor (an asialoglycoprotein receptor binding moiety, or ASGPRBM) of a hepatocyte. In additional embodiments, the (CRBM) is a moiety which binds to a receptor of other cells which can degrade proteins, such as a LRP1, LDLR, FcγRI, FcRN, Transferrin or Macrophage Scavenger receptor.

Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

The invention discloses a substance composition. The present invention relates to a conjugate comprising a deglycosylated IgA-binding moiety, a cell receptor-binding moiety that binds to a hepatocyte or other degraded cell of a patient or subject through an asialoglycoprotein receptor (ASGPR) on the surface of the hepatocyte or other degraded cell, and optionally a linker moiety that links the deglycosylated IgA-binding moiety and the cell receptor-binding moiety, wherein the composition of matter can be used to remove galactose deficient IgA1 in a patient or subject.

Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

Provided is an accurate guide RNA (gRNA) screening method for base editing of an asialoglycoprotein receptor 1 (ASGR1) gene, including the following steps: (1) gRNA design; (2) primer design; (3) in vitro transcription of gRNA; (4) cell transfection; (5) collection of cells, and extraction and polymerase chain reaction (PCR) of a genome; and (6) Sanger sequencing.

Extracellular protein degraders and compositions with improved pharmacokinetic properties are provided that have a potent asialoglycoprotein receptor (ASGPR) Binding Ligand bound to an Extracellular Protein Targeting Ligand for the selective degradation of the Target Extracellular Protein, for example immunoglobulin in vivo to treat disorders mediated by the extracellular protein.

Provided is a modified regulatory T cell capable of recognizing cells of the liver, capable of treating and / or preventing transplant rejection or immune-mediated damage, and capable of promoting regeneration of cells of the liver.SOLUTION: The present invention provides engineered regulatory T cells (Tregs) comprising a chimeric antigen receptor (CAR), wherein said CAR comprises an antigen recognition domain that specifically binds to the asialoglycoprotein receptor (ASGR). The invention also provides a method of promoting liver tissue repair and / or regeneration in a subject, said method comprising administering to said subject a modified Treg comprising a CAR, or a pharmaceutical composition comprising said modified Treg, wherein said CAR comprises a liver-specific antigen recognition domain.SELECTED DRAWING: None

This invention provides extracellular protein degraders and compositions that have an asialoglycoprotein receptor (ASGPR) Binding Ligand bound to an Extracellular Protein Targeting Ligand for the selective degradation of the Target Extracellular Protein for example an immunoglobulin or other extracellular protein in vivo to treat disorders mediated by that protein.

The application belongs to the technical field of biological medicine, and particularly relates to a galactosamine-doxetaxel conjugate as well as a preparation method and application thereof. First, doxetaxel and 3,3'-diseleno-dipropionic acid are used as raw materials, and after heating reaction, 3,3'-diseleno-dipropionic acid doxetaxel is obtained. Then, the obtained 3,3'-diseleno-dipropionic acid doxetaxel and galactosamine are used as raw materials, and after heating reaction, galactosamine-3,3'-diseleno-dipropionic acid doxetaxel conjugate is obtained through column chromatography separation and purification. The obtained conjugate can be specifically recognized by endogenous lectin receptors (such as asialoglycoprotein receptor ASGPR) which are highly expressed on the surface of hepatoma cells, so as to be taken up by hepatoma cells through a receptor-mediated pathway, and has application prospect in the direction of hepatoma targeted treatment.

The invention relates to an anti-inflammatory and lipid-lowering-based nano preparation for treating fatty liver and a preparation method of the nano preparation. Galactose modified polyethylene glycol-polylactic acid-glycolic acid copolymer (PEG-PLGA) is used as a targeting carrier, and a lipid-lowering drug fenofibrate and an anti-inflammatory drug curcumin are co-loaded; the particle size of the nano preparation is 150-200nm, and the drug encapsulation efficiency is greater than or equal to 85%. Galactose modified PEG-PLGA is adopted as a carrier, galactose can be specifically combined with an asialoglycoprotein receptor (ASGPR) specifically expressed on the surface of liver cells, active targeting of the liver is achieved, the drug enrichment amount of the liver lesion position is remarkably increased, meanwhile, accumulation of drugs in extrahepatic tissue is reduced, extrahepatic toxicity is effectively reduced, and the drug delivery effect is improved. According to the present invention, the anti-inflammatory drug curcumin and the fenofibrate are combined, such that the biological safety of the preparation is improved, the lipid lowering drug fenofibrate and the anti-inflammatory drug curcumin are innovatively co-loaded, and the fenofibrate and the anti-inflammatory drug curcumin form the synergistic effect system: fenofibrate can activate peroxisome proliferator-activated receptor alpha (PPAR alpha), promote liver lipid catabolism, and reduce lipid deposition;

The invention relates to the technical field of liver targeting compounds, in particular to a cyclic peptide ligand of a targeting asialoglycoprotein receptor, pharmaceutically acceptable salt of the cyclic peptide ligand, application of the pharmaceutically acceptable salt and a pharmaceutical composition. The invention provides a cyclic peptide ligand of a targeted asialoglycoprotein receptor, a pharmaceutically acceptable salt of the cyclic peptide ligand, an application of the pharmaceutically acceptable salt and a pharmaceutical composition. The cyclic peptide ligand has better endocytosis activity.

The invention relates to an application of a multifunctional supramolecular nano-platform drug, in particular to an application of a multifunctional supramolecular nano-platform in preparation of a drug for treating liver ischemia reperfusion injury. The multifunctional supramolecular nano platform is a GalAC4A supramolecular carrier loaded with naringenin NAR. The multifunctional supramolecular nano platform is prepared from naringenin NAR, galactose Gal and CAC4A in azo calixarene. The multifunctional supramolecular nano platform is a nano compound of NAR (at) GalAC4A. The multifunctional supramolecular nano platform realizes specific targeting of hepatocytes through endocytosis mediated by an asialoglycoprotein receptor. The invention provides a novel'receptor recognition-hypoxia response-collaborative treatment ', a three-party design strategy is provided, a GalAC4A supermolecular carrier loaded with naringenin (NAR) is successfully constructed, and the NAR-coated GalAC4A nano-composite is formed.

Conjugates that target an asialoglycoprotein receptor, such as in the liver, and comprise an active agent (e.g., a therapeutic or an imaging agent) and rigid linker components; pharmaceutical compositions; and methods of use in the delivery of conjugates, and the imaging and treating of the liver (e.g., in a subject with NASH) with conjugates.

Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

The present invention is based on the discovery of a proteolysis targeting compound having tissue targeting capability and use thereof, relating to medicinal products, and to such a compound or a pharmaceutically acceptable salt thereof, a stereoisomer, a solvate, or a polymorph. The compound is a proteolysis targeting chimera (PROTAC) with specific tissue targeting ability. The compound structure comprises three parts, i.e., A-BD-CON, wherein the part A is a PROTAC, one end of the structure thereof is a target protein ‘binding ligand, and the other end is a ubiquitin ligase ligand; and the part CON is a ligand of an asialoglycoprotein receptor (ASGPR), enabling the specific tissue targeting function. The compound enriches in liver tissue and is able to target cells in the tissue. The invention achieves improved druggability of the PROTAC with higher solubility and cellular membrane permeability, therefore produces enhanced pharmaceutical effect on the specific target tissue.

The disclosure describes compounds of Formula Ia, which in non-limiting aspects contain an asialoglycoprotein receptor (ASGPR) binding moiety and an anti-β1AR binding moiety. Compounds of Formula Ia are useful in preventing, treating, and / or ameliorating heart failure in a subject when administered in therapeutically effective amounts.

The present invention relates to an RNAi construct for inhibiting the expression of an asialoglycoprotein receptor 1 (ASGR1) gene, a pharmaceutical composition comprising the same, and uses thereof. The RNAi construct achieves the purpose of disease prevention and / or treatment by inhibiting expression of the ASGR1 gene in the liver.

Provided herein are a complex for diagnosing non-alcoholic steatohepatitis, use of the complex, and a contrast agent comprising the complex. The complex for diagnosing non-alcoholic steatohepatitis comprises hexa-lactoside, a metal chelator coupled to the hexa-lactoside, and a radionuclide labeling the metal chelator. The complex is capable of binding to an asialoglycoprotein receptor, so that the complex has potential for use as a radiological diagnostic agent.

The present invention provides an antisense oligomer having the base sequence depicted in SEQ ID NO: 26, an antisense oligomer having a base sequence resulting from substitution, deletion, insertion, or addition of 1 to 6 bases in the base sequence depicted in SEQ ID NO: 26, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable hydrate thereof, an oligonucleotide conjugate in which the antisense oligomer is bound with a molecule capable of binding to an asialoglycoprotein receptor, and a pharmaceutical composition containing the same.

Disclosed herein are polynucleic acid conjugate compositions comprising a polynucleic acid molecule and one or more targeting moiety such as an asialoglycoprotein receptor targeting moiety and a lipophilic moiety, for targeted delivery of the polynucleic acid molecule to a target cell. Disclosed herein are also pharmaceutical compositions comprising polynucleic acid conjugate composition. Further, provided herein are methods and / or uses of polynucleic acid conjugate composition and pharmaceutical composition comprising polynucleic acid conjugate composition described herein.

Disclosed herein are binding polypeptides that bind to asialoglycoprotein receptor 1 (ASGR1), and methods of use thereof for inducing immune tolerance against antigens of interest, for example, for treating, ameliorating, inhibiting, or preventing disease or disorders associated with unwanted immune response against the antigens of interest, such as autoimmune diseases.

The present disclosure describes compounds that contain, in a non-limiting aspect, an asialoglycoprotein receptor (ASGPR) binding moiety and an anti-CCP (anti-cyclic citrullinated peptide binding moiety). These compounds are useful for preventing, treating and / or ameliorating various types of arthritis, including rheumatoid arthritis (RA), in a subject when administered in therapeutically effective amounts.

The disclosure describes compounds of Formula Ia, which in non-limiting aspects contain an asialoglycoprotein receptor (ASGPR) binding moiety and an anti-β1AR binding moiety. Compounds of Formula Ia are useful in preventing, treating, and / or ameliorating heart failure in a subject when administered in therapeutically effective amounts.

The present invention is directed to bifunctional small molecules which contain a circulating protein binding moiety (CPBM) linked through a linker group to a cellular receptor binding moiety (CRBM) which is a membrane receptor of degrading cell such as a hepatocyte or other degrading cell. In embodiments, the (CRBM) is a moiety which binds to asialoglycoprotein receptor (an asialoglycoprotein receptor binding moiety, or ASGPRBM) of a hepatocyte. In additional embodiments, the (CRBM) is a moiety which binds to a receptor of other cells which can degrade proteins, such as a LRP1, LDLR, FcγRI, FcRN, Transferrin or Macrophage Scavenger receptor. Pharmaceutical compositions based upon these bifunctional small molecules represent an additional aspect of the present invention. These compounds and / or compositions may be used to treat disease states and conditions by removing circulating proteins through degradation in the hepatocytes or macrophages of a patient or subject in need of therapy. Methods of treating disease states and / or conditions in which circulating proteins are associated with the disease state and / or condition are also described herein.

The present invention is directed to the bifunctional compounds and the use of such bifunctional compounds to lower plasma levels of extracellular target molecules by lysosomal degradation. Such bifunctional compounds have a cell surface receptor ligand covalently linked to a ligand that is capable of binding to an extracellular target molecule (such as a ligand for a growth factor, a cytokine, a chemokine, a hormone, a neurotransmitter, a capsid, a soluble receptor, an extracellular secreted protein, an antibody, a lipoprotein, an exosome, a virus, a cell, or a plasma membrane protein), where the cell surface receptor is associated with receptor mediated endocytosis, including asialoglycoprotein receptor (ASGPR) mediated lysosomal degradation and mannose-6-phosphate (M6PR) mediated lysosomal degradation. Pharmaceutical compositions comprising such bifunctional compounds and methods of treating a disease or disorder mediated by an extracellular molecule using such bifunctional compounds are also provided herein.

This invention provides extracellular protein degraders and compositions that have an asialoglycoprotein receptor (ASGPR) Binding Ligand bound to a specific Extracellular Protein Targeting Ligands for the selective degradation of the Target Extracellular Protein for example an immunoglobulin or other extracellular protein in vivo to treat disorders mediated by that protein.

The present invention relates to an RNAi construct for inhibiting asialoglycoprotein receptor 1 (ASGR1) gene expression, a pharmaceutical composition comprising the same, and use thereof. The RNAi construct achieves the purpose of disease prevention and / or treatment by inhibiting the expression of the ASGR1 gene in the liver.

The present invention relates to bifunctional small molecules containing a circulating protein binding moiety (CPBM) linked to a cell receptor binding moiety (CRBM) by a linking group, the CRBM being a membrane receptor of a degrading cell such as a hepatocyte or other degrading cell. In certain embodiments, the (CPBM) is a moiety that binds to immunoglobulin G. In certain embodiments, the (CRBM) is a moiety that binds to an asialoglycoprotein receptor of a hepatocyte (an asialoglycoprotein receptor binding moiety, or an ASGPRBM).

The present disclosure provides lysosomal targeting bifunctional molecules that target anti-MuSK autoantibodies that cause disease for degradation. The lysosomal targeting bifunctional molecule comprises a ligand moiety that specifically binds to an asialoglycoprotein receptor (ASGPR), and the ligand moiety is linked via a carrier protein to a muscle-specific kinase (MuSK) polypeptide that specifically binds to a target anti-MuSK autoantibody.