62 results about "ANGPTL3" patented technology

A method for simultaneously regulating the expression and / or activity of a dual-target gene. The method comprises: providing a complex or a nucleic acid encoding the complex, wherein the complex comprises a DNA binding domain and a gene expression modulator. For example, the method simultaneously regulates the expression and / or activity of PCSK9 gene and ANGPTL3 gene. For example, the method simultaneously regulates the expression and / or activity of APOC3 gene and the ANGPTL3 gene. For example, the method simultaneously regulates the expression and / or activity of the PCSK9 gene and the APOC3 gene.

The present invention provides methods for treating patients suffering from familial hypercholesterolemia, including both HeFH and HoFH. The methods of the invention provide for lowering at least one lipid parameter in the patient by administering a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds to ANGPTL3 in combination with a therapeutically effective amount of a statin, a first lipid lowering agent other than a statin, and a second lipid lowering agent other than a statin. The first non-statin lipid lowering agent is an agent that inhibits cholesterol uptake (e.g. ezetimibe) and the second non-statin lipid-lowering agent is an inhibitor of microsomal triglyceride transfer protein (e.g. lomitapide). The combination therapy is useful in treating hypercholesterolemia, as well as hyperlipidemia, hyperlipoproteinemia and dyslipidemia, including hypertriglyceridemia, chylomicronemia, and to prevent or treat diseases or disorders, for which abnormal lipid metabolism is a risk factor, such as cardiovascular diseases.

The present invention relates to use of an anti-ANGPTL3 antibody in treating hyperlipidemia and a method. Specifically, the present invention relates to use of an anti-ANGPTL3 antibody or an antigen-binding fragment thereof in preparing a drug for treating hyperlipemia patients, wherein the hyperlipemia patients are subject to the risk of atherosclerosis cardiovascular disease.

The present disclosure relates to the field of genetic engineering technology, and more specifically, to a targeting ligand. The targeting ligand provided herein forms a siRNA conjugate with a specific small interfering RNA sequence, which targets ANGPTL3 and degrades ANGPTL3 gene transcripts in cells, thereby reducing ANGPTL3 protein expression. Therefore, the siRNA conjugate formed with the targeting ligand provided herein can be used to prevent and / or treat dyslipidemia.

The present application relates to a nucleic acid molecule inhibiting ANGPTL3 gene expression. The nucleic acid molecule contains or consists of substantially complementary sense and antisense sequences, wherein the sense sequence and / or antisense sequence has a nucleotide length of 14-30 nt. The nucleic acid molecule can better specifically silence an ANGPTL3 gene.

Provided are a siRNA for inhibiting the expression of an angiopoietin-like protein 3 (ANGPTL3) gene, and a pharmaceutical composition and a conjugate comprising the siRNA; wherein each nucleotide in the siRNA is independently a modified or unmodified nucleotide, and the siRNA comprises a sense strand and an antisense strand; the sense strand comprises a nucleotide sequence A, the nucleotide sequence A having the same length as the nucleotide sequence as represented by SEQ ID NO:1 with no more than 3 nucleotide differences; the antisense strand comprises a nucleotide sequence B, the nucleotide sequence B having the same length as the nucleotide sequence as represented by SEQ ID NO:2 with no more than 3 nucleotide differences.

The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ANGPTL3 gene, as well as methods of inhibiting expression of ANGPTL3 and methods of treating subjects having a disorder of lipid metabolism, such as hyperlipidemia or hypertriglyceridemia, using such dsRNA compositions.

Provided herein are compositions related to Cas12b guide RNAs. Also provided herein are methods for modifying target polynucleotide sequences and methods of treating or preventing a condition in a subject in need thereof, such as conditions resultant from the expression of ANGPTL3 or mutations thereto.

There are disclosed certain double-stranded RNA (dsRNA) or siRNA agents for inhibition of angiopoietin-like 3 gene expression, compositions that include angiopoietin-like 3 agents and methods of use thereof. The double-stranded RNA (dsRNA) or siRNA agents are particularly useful in the treatment or prophylaxis of cardiovascular disease and metabolic conditions as well as in the treatment of heart failure and chronic kidney disease.

The present disclosure provides compositions and methods for modifying an ANGPTL3 gene. In some aspects, the present disclosure provides a guide RNA, compositions thereof, and pharmaceutical compositions comprising a guide RNA or a composition as described herein. In some aspects, the present disclosure also provides uses and methods of using a guide RNA, a composition thereof, or a pharmaceutical composition as described herein, for inducing a double-stranded break in an ANGPTL3 gene, for reducing expression of an ANGPTL3 gene in a cell or subject, and for treating a patient having or at risk of having an ANGPTL3 -related disease or condition.

The invention relates to an RNAi agent of angiogenin-like 3 and a preparation method and application of the RNAi agent, and the RNAi agent can inhibit expression of ANGPTL3 and is used for treating ANGPTL3 related diseases and symptoms.

A chemically modified polynucleotide encoding a fusion protein, wherein the chemically modified polynucleotide comprises a sequence of SEQ ID NO: 701 is claimed wherein the fusion comprises a Cas9 nickase and and deaminase, such as an adenosine deamnase TadA. and which further comprises a protospacer found on a gene encoding Angiopoietin-like 3 protein (ANGPTL3). The chemical modifications may include phosphorothioate linkages and 2'-O-methyl modfied nucleosides. Use of such fusions in treating cardiovascular conditions is further claimed. [Figure 3]

The present disclosure provides methods for treating a subject with renal disease or preventing a subject from developing renal disease, as well as methods for identifying a subject at increased risk for developing renal disease, by administering an angiopoietin-like 3 (ANGPTL3) inhibitor and a solute carrier family 5 member 2 (SLC5A2) inhibitor.

The present invention provides an iRNA composition that affects the cleavage of the RNA transcript of the ANGPTL3 gene, which is mediated by the RNA-induced silence complex (RISC). The ANGPTL3 may be in a cell, e.g., in a subject, e.g., in a cell in the body of a person. The invention also provides methods of using the iRNA compositions of the invention for inhibiting the expression of the ANGPTL3 gene and / or for treating a subject that would benefit from inhibition or reduction of the expression of the ANGPTL3 gene, such as a subject experiencing or susceptible to dysregulation of lipid metabolism, such as a subject who would benefit from inhibition or reduction of the expression of the ANGPTL3 gene. Such as a subject suffering from or susceptible to hyperlipidemia or hypertriglyceridemia.

Provided are anti-ANGPTL3-FLD nanobodies and the use thereof. The three prepared anti-ANGPTL3-FLD nanobodies are VHH128, VHH252 and VHH376 respectively; fusion proteins are 128-Fc, 252-Fc and 376-Fc, and the three nanobody fusion proteins VHH-Fc all have good thermal stability and colloidal stability, and have similar particle sizes. The three nano-fusion proteins have good affinity with the antigen hANGPTL3-His, the KD value of 128-Fc being 1.59E-10M, the KD value of 252-Fc being 3.82E-10M, and the KD value of 376-Fc being 1.65E-10M. The purities of the prepared nanobody fusion proteins are up to 100%.

According to the anti-ANGPTL3 antibody and the application thereof, the antibody can be specifically combined with ANGPTL3, inhibition of the ANGPTL3 on lipoprotein lipase activity is effectively relieved, and lipid metabolism is promoted.

The present disclosure relates to an siRNA for inhibiting the expression of an angiopoietin-like protein 3 (ANGPTL3) gene, an siRNA conjugate, and a pharmaceutical composition thereof, and a method for reducing the expression of the ANGPTL3 gene by using the siRNA, the siRNA conjugate, and the pharmaceutical composition thereof. The siRNA, the siRNA conjugate, and the pharmaceutical composition thereof of the present disclosure can be used for treating and / or preventing an ANGPTL3 gene-mediated disease or disorder.

The present invention relates to a dual-targeting siRNA agent comprising two distinct siRNAs targeting two different genes or their pharmaceutically acceptable salts, wherein the two distinct siRNAs or their salts are linked by a pharmaceutically acceptable ligand. The siRNA is a dsRNA composed of a sense strand and an antisense strand, and the two different genes are selected from a group consisting of angiotensinogen (AGT), proprotein convertase subtilisin / kexin type 9 (PCSK9), and human angiopoietin-like protein 3 (ANGPTL3). The present invention provides the application of the dual-targeting siRNA agent in the preparation of drugs for preventing or treating diseases associated with hypertension and / or dyslipidemia. The dual-targeting siRNA agent described in the present invention can effectively inhibit the expression of two target genes simultaneously in vivo, offering the advantages of strong non-antagonistic activity and high safety. The present invention also provides the siRNAs targeting corresponding genes for the aforementioned dual-targeting siRNA agent and their use for preventing or treating diseases associated with hypertension and / or dyslipidemia.

The present disclosure relates to CRISPR-related genome editing systems and components for targeting, editing and / or modulating the expression of a target nucleic acid sequence of interest, for example, an ANGPTL3 target nucleic acid sequence encoding the ANGPTL3 protein. The present disclosure is also directed to methods and applications thereof in connection with the treatment and / or management of metabolic disease.

The invention relates to a dual-targeting siRNA agent, which comprises two different siRNAs targeting two different genes or pharmaceutically acceptable salts thereof, the two different siRNAs or salts thereof are connected through pharmaceutically acceptable ligands, the s-RNA is dsRNA composed of a sense strand and an antisense strand, and the s-RNA is dsRNA composed of a positive-sense strand and a negative-sense strand. The two different genes are selected from two of angiotensinogen (AGT), proprotein convertase subtilisin 9 (PCSK9) and human angiopoietin-like protein 3 (ANGPTL3). The invention provides application of the dual-targeting s iRNA agent in preparation of drugs for preventing or treating diseases related to hypertension or / and lipid disorder. The dual-targeting siRNA agent can effectively inhibit expression of two target genes in vivo at the same time, and has the advantages of being high in mutual non-antagonistic activity and high in safety. The invention also provides the s iRNA of the corresponding gene of the dual-targeting s iRNA agent and application of the s iRNA to prevention or treatment of diseases related to hypertension or / and lipid disorder.

Disclosed herein are polynucleic acid molecules that can be utilized for suppressing the expression of Angiopoietin-like protein 3 (ANGPTL3) gene. Also, described herein are pharmaceutical compositions comprising polynucleic acid molecules targeting Angiopoietin-like protein 3 (ANGPTL3) mRNA. Further, provided herein are methods for suppressing the expression of ANGPTL3 by utilizing the polynucleic acid molecules described herein.

The present invention relates to use of an anti-ANGPTL3 antibody in treating hyperlipidemia and a method. Specifically, the present invention relates to use of an anti-ANGPTL3 antibody or an antigen-binding fragment thereof in preparing a drug for treating hyperlipemia patients, wherein the hyperlipemia patients are subject to the risk of atherosclerosis cardiovascular disease.

The present invention discloses the use of ANGPTL3 in the prognosis of hepatitis B-related acute-on-chronic liver failure, relating to the fields of disease prognosis and biomedicine technology. The present invention discloses the use of ANGPTL3 as a biomarker in the preparation of products for the diagnosis and / or course diagnosis and / or prognosis assessment of hepatitis B-related acute-on-chronic liver failure. The beneficial effect of the present invention is that ANGPTL3 can be used as a biomarker for the prognosis of hepatitis B-related acute-on-chronic liver failure. By using ELISA technology to absolutely quantify the level of ANGPTL3 in blood samples of patients in different groups of HBV-ACLF patients and to absolutely quantify the dynamic level of ANGPTL3, the phenomenon and course of hepatitis B-related acute-on-chronic liver failure can be timely discovered, and other related indicators can be detected, thereby using ANGPTL3 to provide scientific guidance for the management and decision-making of hepatitis B-related acute-on-chronic liver failure.

The present invention pertains to the use of gene editing and miRNA technologies for improving recombinant production of ANGPTL3 mimetics in CHO cells. The gene expression modifications are used for knock-out / knock-down of the endogenous protein CCL2 of the CHO cells which is difficult to separate from ANGPTL3 mimetics during purification.

To provide iRNA compositions which effect RNA-induced silencing complex (RISC)-mediated cleavage of RNA transcripts of an ANGPL3 gene.SOLUTION: A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of ANGPTL3 comprises a sense strand and an antisense strand. The sense strand comprises at least 15 contiguous nucleotides differing by 3 or less nucleotides from the nucleotide sequence of SEQ ID NO:1. The antisense strand comprises at least 15 contiguous nucleotides differing by 3 or less nucleotides from the nucleotide sequence of SEQ ID NO:5.SELECTED DRAWING: None

The invention belongs to the field of biological medicine, and particularly relates to an ANGPTL3 (anti-ANGPTL3) humanized monoclonal antibody stably transformed strain and application thereof. According to the application, an anti-ANGPTL3 humanized monoclonal antibody expression vector containing different nucleotide sequences is introduced into a host cell through electrotransfection, and a recombinant cell line with the highest yield is preliminarily screened out. The recombinant cell line is further screened for multiple times through main cloning and subcloning, and finally an ANGPTL3-resistant humanized monoclonal antibody cell strain with the advantages of high expression quantity, stability and controllability is screened out. The invention further discloses an ANGPTL3 humanized monoclonal antibody based on the cell, and the monoclonal antibody can be used for preparing a reagent for detecting ANGPTL3 and can also be used for preparing a medicine for preventing and / or treating kidney diseases or metabolism-related diseases.

The present invention pertains to the use of gene editing and miRNA technologies for improving recombinant production of ANGPTL3 mimetics in CHO cells. The gene expression modifications are used for knock-out / knock-down of the endogenous protein CCL2 of the CHO cells which is difficult to separate from ANGPTL3 mimetics during purification.

Provided are an anti-ANGPTL3 humanized monoclonal antibody and a use thereof. An original antibody is used to perform humanized transformation, and the prepared anti-ANGPTL3 humanized monoclonal antibody has higher affinity than the original antibody, indicating that the humanized antibody has high affinity with an antigen and exhibits good human-mouse cross-species reactivity, showing a good treatment effect on a mouse model of kidney disease; and the humanized monoclonal antibody has the characteristic of long half-life period, can be stably present in a mouse body for a long time, and has high safety.

The present invention relates to novel monovalent anti-ANGPTL3 antibodies for use in medicine and in particular for lowering of plasma triglycerides levels in patients in need thereof, such as patients suffering from or at risk of hypertriglyceridemia and / or cardiovascular disease, such as atherosclerotic cardiovascular disease (ASCVD) as well as pharmaceutical compositions suitable for subcutaneous administration and kits comprising such compounds and compositions.

A gene editing system comprising: (a) a gene editor fusion protein comprising a Cas protein and a deaminase, or a nucleic acid encoding the gene editor fusion protein, and (b) a hybrid guide nucleic acid comprising a spacer sequence, wherein the spacer sequence comprises at least one deoxyribonucleotide and a plurality of ribonucleotide is claimed. A 2’ hydroxyl group of a ribose on at least one ribonucleotide may be covalently linked to a methyl group (2’-OMe). The gene editing system for use in treating or preventing an atherosclerotic cardiovascular disease, or lowering blood low-density lipoprotein cholesterol (LDL-C) levels or lowering blood triglyceride levels is further claimed. [None]