49 results about "Sialoglycoprotein" 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.

The present disclosure provides lysosomal targeting bifunctional molecules that target disease causing anti-TSHR autoantibodies for degradation. The lysosomal targeting bifunctional molecules include a ligand moiety that specifically binds to an asialoglycoprotein receptor (ASGPR), and which is linked via a carrier protein to a thyroid stimulating hormone receptor (TSHR) polypeptide that specifically binds target anti-TSHR autoantibodies.

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.

A composition of matter including an anti-PLA2R antibody-binding moiety, a cellular receptor-binding moiety which binds to hepatocytes or other degrading cells through asialoglycoprotein receptors (ASGPR) on the surface of hepatocytes or other degrading cells in a patient or subject, and optionally, a linker moiety connecting the anti-PLA2R antibody-binding moiety and the cellular receptor-binding moiety, wherein the composition of matter is useful for removing anti-PLA2R antibody in a patient or subject.

An agent including a glycan-specific IgG antibody moiety, a cellular receptor binding moiety which binds to hepatocytes or other degrading cells through asialoglycoprotein (ASGPR) receptors of hepatocytes or other cell receptors which are on the surface degrading cells in a patient or subject, and optionally, a linker moiety connecting the glycan-specific IgG antibody moiety and the cellular receptor binding moiety.

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.

The present invention belongs to the field of biomedicine technology and specifically relates to a small molecule ligand-rucaparib conjugate and a preparation method thereof. The small molecule ligand-rucaparib conjugate is a combination of one or both of a biotin-rucaparib conjugate and a lactobionic acid-rucaparib conjugate. Rucaparib is coupled to the small molecule ligand through an amidation reaction, thereby improving rucaparib's tumor targeting ability and thereby enhancing its inhibitory effect on tumor cells. In particular, the dual-targeting effect of biotin / lactobionic acid-rucaparib composite nanoparticles, which are self-assembled from the small molecule ligand complex, is more significantly inhibited against double-positive tumor cells such as biotin receptors and asialoglycoprotein receptors. Furthermore, the biotin / lactobionic acid-rucaparib composite nanoparticles have a significant application prospect due to their safety advantage over normal cells.

The invention discloses an oligonucleotide pharmacobiological analysis system based on a GalNAc technology, and relates to the technical field of drug analysis, and the oligonucleotide pharmacobiological analysis system is technically characterized in that in a GalNAc conjugate coupling delivery module, a coupling unit covalently couples an oligonucleotide drug and a GalNAc-trimer through a click chemical reaction to form a liver-targeted delivery carrier; the targeting unit is specifically combined with an asialoglycoprotein receptor on the surface of a hepatocyte by utilizing the vector to realize endocytosis; in the RT-qPCR quantitative analysis module, a magnetic separation purification unit adsorbs oligonucleotides by using carboxylated magnetic beads; the reverse transcription unit uses a stem-loop primer to convert oligonucleotide into cDNA (complementary deoxyribonucleic acid) under the action of heat-resistant reverse transcriptase; the fluorescence quantification unit adopts an FAM-labeled TaqMan probe to monitor amplification, and the absolute concentration of the medicine is calculated in combination with a standard curve; according to the invention, the technical problems of poor targeting, serious off-target effect and poor stability are solved, and high-quality drug effect evaluation can be carried out.

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 present application relates to the technical field of food processing, in particular to a solid beverage based on edible bird's nest sialic acid derivative and a preparation method thereof, which solves the problems of single functional factor, poor stability and poor brewing property in existing intelligence drinks; by using edible bird's nest stewing material as a natural nutritional wall material, the sialic acid-glycoprotein therein and algal oil form an intelligence "synergistic functional matrix", produce an enhancing effect, and combined with freeze-drying and low-temperature fluidized bed granulation technology, the low-temperature stable embedding of active components is realized, the intelligence activity of nutritional factors of the product, the storage stability and the use convenience are improved, and the product is suitable for brain health conditioning and daily supplement of different people.

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.

The invention provides an antibody for resisting an asialoglycoprotein receptor as well as a preparation method and application of the antibody. The antibody for resisting the asialoglycoprotein receptor comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises a heavy chain variable region HCDR1-HCDR3; and the light chain variable region comprises a light chain variable region LCDR1-LCDR3. According to the present invention, the affinity of the anti-asialoglycoprotein receptor antibody to the human asialoglycoprotein receptor is 0.425 nM, and the antigen recognition ability is strong; the compound disclosed by the invention can be used for remarkably inhibiting the DNA expression of HBsAg, HBeAg and HBV of HepG2.2. 15 cells and HepAD38 cells, has a function of inhibiting the replication of the hepatitis B virus, and has a great application prospect in medicines for preventing and / or treating hepatitis B virus infection and / or preventing and / or treating related diseases caused by the hepatitis B virus infection.

Disclosed herein are extracellular vesicle (EV) composites and their uses in the treatment of liver injury, particularly, acute liver failure (ALF). The EV composite includes an EV derived from a mesenchymal stem cell (MSC), and a recombinant polypeptide conjugated to the EV via a click chemistry reaction. Preferably, the recombinant polypeptide is a single-chain variable fragment (scFv) that recognizes and binds to asialoglycoprotein receptor 1 (ASGR1) or ASGR2. The present disclosure thus also encompasses a method of treating ALF in a subject. The method includes the step of administering an effective amount of the EV composite to the subject to alleviate symptoms associated with the ALF.

A composition of matter including a deglycosylated IgA-binding moiety, a cellular receptor-binding moiety that binds to hepatocytes or other degrading cells through asialoglycoprotein receptors (ASGPR) on the surface of hepatocytes or other degrading cells in a patient or subject, and optionally, a linker moiety connecting deglycosylated IgA-binding moiety and the cellular receptor-binding moiety, wherein the composition of matter is useful for removing galactose-deficient IgA1 in a patient or subject.

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.

The invention discloses preparation of a liver-targeted fucoxanthin nano delivery system based on probiotic vesicles and application of the liver-targeted fucoxanthin nano delivery system in improvement of bioavailability, and belongs to the field of biological medicine. Pure mycoderm fragments are obtained by combining a differential centrifugation-tangential flow filtration system, the pure mycoderm fragments are treated by an ultrasonic-assisted technology to form complete membrane nano-vesicles, galactosamine with sialic acid glycoprotein receptor targeting ability is modified to distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000-carboxyl through an amide reaction, and the sialic acid glycoprotein receptor targeting galactosamine nano-vesicles are prepared. The hepatic parenchymal cell sialoglycoprotein receptor targeting ligand is obtained. And co-incubating the hepatocyte sialoglycoprotein receptor targeted nano-vesicle with the nano-vesicle to obtain the hepatocyte sialoglycoprotein receptor targeted nano-vesicle. The hydrophobic food functional factors or drugs are encapsulated in the nano-vesicles, so that the water solubility, oxidation resistance, environmental stability and gastrointestinal digestive system stability of the hydrophobic food functional factors or drugs can be improved, and the bioavailability of blood and liver of oral administration of the hydrophobic food functional factors or drugs can be improved.

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 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.

Application of a multifunctional supramolecular nanoplatform drug: The application of a multifunctional supramolecular nanoplatform in the preparation of drugs for liver ischemia-reperfusion injury. The multifunctional supramolecular nanoplatform is a GalAC4A supramolecular carrier loaded with naringenin (NAR). The multifunctional supramolecular nanoplatform is prepared from naringenin (NAR), galactose (Gal), and CAC4A from azocalixarene. The multifunctional supramolecular nanoplatform is a NAR@GalAC4A nanocomposite. The multifunctional supramolecular nanoplatform achieves hepatocyte-specific targeting through desialyl glycoprotein receptor-mediated endocytosis. This invention proposes a novel "receptor recognition-hypoxia response-synergistic therapy" three-pronged design strategy, successfully constructing a GalAC4A supramolecular carrier loaded with naringenin (NAR) to form a NAR@GalAC4A nanocomposite.