81 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 disclosure provides methods of treating a subject having a kidney disease or preventing a subject from developing into a kidney disease by administering an angiopoietin-like 3 (ANGPTL3) inhibitor and a solute carrier family 5 member 2 (SLC5A2) inhibitor, and methods of identifying a subject having an increased risk of developing into a kidney disease.

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 invention relates to a molecular target capable of specifically reducing cholesterol level without interfering triglyceride metabolism and application of the molecular target. The molecular target is the C terminal of ANGPTL3 protein. The invention also relates to an application of the inhibitor of the C terminal of the targeted ANGPLT3 protein (Angiopoietin-like3, angiopoietin-like protein 3) in preparation of a medicine, and the medicine is used for treating hypercholesteremia, atherosclerosis and coronary heart disease, and also relates to an application of the inhibitor of the C terminal of the targeted ANGPLT3 protein (Angiopoietin-like protein 3) in preparation of the medicine.

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.

The invention discloses application of ANGPTL3 in prognosis of hepatitis B related chronic-acute liver failure, and relates to the technical field of disease prognosis and biological medicine. The invention discloses application of ANGPTL3 as a biomarker in preparation of a product for diagnosis and / or disease course diagnosis and / or prognosis evaluation of hepatitis B related chronic plus acute liver failure. The invention has the following beneficial effects: ANGPTL3 can be used as a biomarker for prognosis of hepatitis B-related chronic-acute liver failure, blood sample levels of patients in different groups of HBV-ACLF and dynamic ANGPTL3 levels are absolutely quantified by ELISA technology, and hepatitis B-related chronic-acute liver failure phenomena and disease courses can be timely found and detected with other related indexes; therefore, the ANGPTL3 is utilized to provide scientific guidance for management and decision-making of hepatitis B related chronic plus acute liver failure.

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%.

The present invention relates to a dual-targeting siRNA agent, which comprises two different siRNAs targeting two different genes or pharmaceutically acceptable salts thereof, and the two different siRNAs or salts thereof are linked by a pharmaceutically acceptable ligand. The siRNA is a dsRNA composed of a sense strand and an antisense strand. The two different genes are selected from two of angiotensinogen (AGT), proprotein convertase subtilisin / kexin type 9 (PCSK9), and angiopoietin-like protein 3 (ANGPTL3). The present invention provides the application of the dual-targeting siRNA agent in the preparation of a drug for preventing or treating diseases related to hypertension or / and lipid disorders. The dual-targeting siRNA agent of the present invention can effectively inhibit the expression of two target genes in vivo simultaneously, and has the advantages of strong non-antagonistic activity and high safety. The present invention also provides siRNAs corresponding to the genes of the above dual-targeting siRNA agent and their use for preventing or treating diseases related to hypertension or / and lipid disorders.

To provide RNAi agents and compositions for inhibiting expression of angiopoietin-like 3 (ANGPTL3), and to provide methods of use thereof.SOLUTION: The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit Angiopoietin-like 3 (also called ANGPTL3, ANGPL3, angiopoietin-like protein 3) gene expression, and compositions that include ANGPTL3 RNAi agents. Also disclosed are methods of use of ANGPTL3 RNAi agents and compositions. The ANGPTL3 RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Pharmaceutical compositions that include one or more ANGPTL3 RNAi agents, optionally with one or more additional therapeutics, are described.SELECTED DRAWING: None

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.

Methods of treating diseases and conditions in human subjects in need thereof using pharmaceutical compositions comprising an ANGPTL3 RNAi agent are described, the treatment being partially mediated by reducing expression of the ANGPTL3 gene. When administered to a human subject in need thereof according to the methods disclosed herein, the disclosed pharmaceutical compositions comprising an ANGPTL3RNAi agent treat diseases and conditions associated with elevated triglyceride (TG) levels and / or elevated low density lipoprotein cholesterol (LDL-C), such as hypertriglyceridemia (including severe hypertriglyceridemia (SHTG)), homozygous familial hypercholesterolemia (HoFH), hypertriglyceridemia-induced pancreatitis, metabolic syndrome, obesity, hyperlipidemia, mixed dyslipidemia, abnormal lipid and / or cholesterol metabolism, atherosclerosis, cardiovascular disease, type II diabetes, coronary artery disease, and the like. The present invention relates to compounds of formula (I), in particular to compounds of formula (I), such as non-alcoholic steatohepatitis, non-alcoholic fatty liver disease, heterozygous familial hypercholesterolemia (HeFH), statin-resistant hypercholesterolemia, other dyslipidemia, and other metabolism-related conditions and diseases.

Compositions and methods are disclosed which comprise a guide polynucleotide corresponding to a protospacer sequence on the Angiopoietin-like protein 3 gene with a view to base editing the Angiopoieti

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 present invention belongs to the fields of biotechnology and antibody engineering pharmaceuticals, and specifically relates to an anti-ANGPTL3-FLD nanobody and its application. The three prepared anti-ANGPTL3-FLD nanobodies are VHH128, VHH252, and VHH376, and the fusion proteins are 128-Fc, 252-Fc, and 376-Fc. The three nanobody fusion proteins VHH-Fc all have good thermal stability and colloidal stability, and similar particle sizes; the three nanobody fusion proteins have good affinity with the antigen hANGPTL3-His. The KD value of 128-Fc is 1.59E-10 M, the KD value of 252-Fc is 3.82E-10 M, and the KD value of 376-Fc is 1.65E-10 M3; the purity of the prepared nanobody fusion protein is as high as 100%.

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.