56 results about "Transthyretin" patented technology

Based on co-drugs representing two different chemical entities and the co- and sequential administration of the two chemical entities, novel therapies for macular degeneration and TTR amyloidosis are provided. The first component (“selective TTR ligand”) is a chemical entity that binds to TTR in the RBP4 (retinol-binding protein 4)-TTR (transthyretin) complex, which participates in the delivery of retinol to the retina. This component reduces retinol transport from circulation to the retina and provides stabilization of the TTR tetramer. The second component (“C20-D3-visual chromophore-generating compound”) is a C20-D3 modified retinoid or carotenoid that, when metabolized in mammals, ultimately produces a C20-D3 visual chromophore, which is presented in the retina as C20-D3-9-cis-retinal or C20-D3-11-cis-retinal. Deuteration at C20 reduces the formation of lipofuscin biretinol, but other functions (such as providing a precursor for the synthesis of the visual chromophore 11-cis-retinaldehyde in vivo) are not reduced.

The invention relates to a method of treating ocular amyloidosis by reducing TTR expression in a subject by administering a double-stranded ribonucleic acid (dsRNA) that targets a TTR gene to the retinal pigment epithelium of the subject.

A modified-release tablet dosage form containing tolcapone is disclosed. The tablet dosage form provides a pulsatile, pH-dependent release profile of tolcapone to both the gastric cavity and the small intestine. Methods for treating or preventing a disease selected from transthyretin amyloidosis (ATTR), Parkinson's disease, and obsessive-compulsive disorder using the dosage form are provided.

Disclosed is a method for diagnosing a cancer health state, or a change in cancer health state in a patient, or for diagnosing a risk of the change or presence of a cancer in a patient, comprising determining, in a plasma sample from said patient, one or more biomarker values that correspond to transthyretin-containing complex structures, and assigning the patient as having or not having cancer, or having or not having a change in cancer health state, or having or not having a risk of cancer based on said biomarker values, wherein said cancer is preferably lung cancer (LC).

The disclosure relates to RNAi constructs, such as siRNA, for reducing expression of the TTR gene. Methods of using such RNAi constructs to treat or prevent cardiac disease, such as transthyretin-associated cardiomyopathy (ATTR-CM), are also described.

Compositions and regimens useful in treating type I citrullenemia are provided. The compositions include recombinant adeno-associated virus (rAAV) with a transthyretin enhancer and promoter driving expression of a human Argininosuccinate Synthase 1 (ASS1).

To provide an effective therapeutic method for TTR-associated diseases.SOLUTION: The present invention provides iRNA agents, for example, double-stranded iRNA agents, that target the transthyretin (TTR) gene, and methods of using such iRNA agents for treating or preventing TTR-associated diseases.SELECTED DRAWING: None

Immunotherapy for musculoskeletal disorders and conditions associated with transthyretin amyloidosis is provided.

Transthyretin (TTR) is a soluble protein involved in thyroxine and retinol transport in the body. Under certain conditions, the TTR protein adopts a misfolded, misassembled, and / or aggregated TTR conformation, which can be toxic and lead to transthyretin-mediated amyloidosis (ATTR). Provided herein, inter alia, are compositions (e.g., pharmaceutical compositions) containing anti-TTR antibodies or antigenic fragments thereof, and related articles of manufacture. Further provided herein, inter alia, are methods for treating or preventing ATTR using the pharmaceutical compositions described herein.

To provide compositions and methods for treating pathological conditions and diseases, such as a TTR amyloidosis, in a mammal caused by expression of a transthyretin (TTR) gene.SOLUTION: There is provided a double-stranded ribonucleic acid (dsRNA) for inhibiting transthyretin (TTR) expression, where the dsRNA comprises a sense strand and an antisense strand, the antisense strand comprising a region complementary to a portion of an mRNA encoding transthyretin (TTR), where the region of complementarity is less than 30 nucleotides in length, and where the antisense strand comprises 15 or more contiguous nucleotides of a specific sequence.SELECTED DRAWING: None

Described herein are methods for treating transthyretin (TTR) amyloidosis with Compound 1 in a subject comprising certain mutations in the TTR protein (Compound 1). The methods include specific dosing regimens that have great efficacy in treating the subjects and that are well tolerated in subjects.

The present invention provides novel non-invasive methods for detecting misfolded transthyretin (TTR) proteins, and for diagnosing and monitoring amyloidosis and related disorders.

Pharmaceutical compositions for treating human subjects suffering from or at risk of developing a TTR-related disorder are provided. [Solution] A pharmaceutical composition comprising a double-stranded RNAi agent administered at a fixed dose of approximately 50 mg, the double-stranded RNAi agent comprising a sense strand complementary to an antisense strand, wherein the sense strand comprises the nucleotide sequence 5'-usgsggauUfuCfAfUfguaaccaaga-3' (SEQ ID NO: 10), and the antisense strand comprises the nucleotide sequence 5'-usCfsuugGfuuAfcaugAfaAfucccasusc-3' (SEQ ID NO: 7), wherein a, c, g, and u are 2'-O-methyl (2'-OMe) A, C, G, or U; Af, Cf, Gf, and Uf are 2'-fluoro A, C, G, or U; and s is a phosphorothioate linkage.

Provided are: a transthyretin tetramer stabilizing agent; and a transthyretin amyloidosis preventing agent or progression suppressing agent.　The present invention relates to a transthyretin tetramer stabilizing agent containing a Glycyrrhiza glabra hydrophobic extract that includes Glycyrrhiza-glabra glabra polyphenol, and also to a transthyretin amyloidosis preventing agent or progression suppressing agent containing a Glycyrrhiza glabra hydrophobic extract that includes Glycyrrhiza-glabra glabra polyphenol.

Compositions and regimens useful in treating phenylketonuria are provided. The compositions include recombinant adeno-associated virus (rAAV) with a transthyretin enhancer and promoter driving expression of a human phenylalanine hydroxylase.

Based on co-drugs representing two different chemical entities and the co- and sequential administration of the two chemical entities, novel therapies for macular degeneration and TTR amyloidosis are provided. The first component (“Bispecific RBP4 / TTR ligand”) is a chemical entity that binds to both TTR and RBP4 in the RBP4 (retinol-binding protein 4)-TTR (transthyretin) complex, which participates in the delivery of retinol to the retina. This component reduces retinol transport from circulation to the retina and provides stabilization of the TTR tetramer. The second component (“C20-D3-visual chromophore-generating compound”) is a C20-D3 modified retinoid or carotenoid that, when metabolized in mammals, ultimately produces a C20-D3 visual chromophore, which is presented in the retina as C20-D3-9-cis-retinal or C20-D3-11-cis-retinal. Deuteration at C20 reduces the formation of lipofuscin biretinol, but other functions (such as providing a precursor for the synthesis of the visual chromophore 11-cis-retinaldehyde in vivo) are not reduced.

According to the oligonucleotide of the targeted transthyretin and the application of the oligonucleotide, the targeted oligonucleotide can remarkably inhibit the gene expression level of the transthyretin, and the drug effect is lasting.

Disclosures herein are directed to polypeptide probes that may be used to detect transthyretin (TTR) oligomers or fibrils in patient samples obtained from subjects with wildtype and mutant TTR alleles. Also provided are methods of using the provided probes to diagnose subjects with a TTR-associated disease or condition or for monitoring the efficacy of a therapeutic administered to treat a TTR-associated disease or condition.

The invention belongs to the technical field of protein detection, and provides an amyloid transthyretin detection kit and application thereof, the kit comprises the following reagents: normal recombinant TTR protein, a TTR-PFF standard substance, a fluorescent tracer and a buffer solution system; the TTR-PFF standard substance comprises a TTR substrate and an RT-QuIC reaction mixed solution, and the pH value of the RT-QuIC reaction mixed solution is 4.0 to 4.5; the buffer solution system comprises a PBS / N2 sample dilution buffer solution and a phosphate buffer solution. According to the detection kit, TTR-PFF is adopted as a reference, a subject sample is combined with normal recombinant human transthyretin, a fluorescent tracer is added, ATTR in a body can convert normal recombinant monomer TTR protein into amyloid fiber, and existence and activity of the ATTR are detected by detecting a fluorescence value of the ATTR. The detection has ultrahigh sensitivity and specificity, minimally invasive or non-invasive sampling is operated, the operation is simple and convenient, a key technical foundation is laid for developing a simple, convenient, efficient and clinical ATTR amyloidosis detection platform, especially an early detection platform, and the kit has a wide market application prospect.

The present disclosure provides a solid pharmaceutical composition comprising of tafamidis, a solubilizer, and one or more pharmaceutically acceptable excipients; and process of making such compositions. The present disclosure also provides a solid pharmaceutical composition comprising of tafamidis indicated for the treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization.

To provide treatment methods useful for transthyretin associated diseases.SOLUTION: Disclosed herein are RNAi agents including a certain pattern of chemical modifications (e.g., an alternating pattern) and a ligand, targeting a Transthyretin (TTR) gene. Further disclosed are agents including one or more motifs of three identical modifications on three consecutive nucleotides, where one such motif is at or near a cleavage site of the agents. Also disclosed are, e.g., double stranded RNAi agents, and methods of using such RNAi agents for treating or preventing TTR-associated diseases.SELECTED DRAWING: None

Provided are a transthyretin tetramer stabilizer and an agent for preventing or suppressing the progress of transthyretin amyloidosis.　The present invention relates to a transthyretin tetramer stabilizer containing glabridin, glabrene, and glabrol and an agent for preventing or suppressing the progress of transthyretin amyloidosis, the agent containing glabridin, glabrene, and glabrol.

Provided herein are anti-TTR antibody dosing regimens useful for treating transthyretin amyloid cardiomyopathy (ATTR-CM) in adult human patients. In embodiments, patients are treated with anti-TTR antibodies, including NI006 / ALXN2220.

The present application relates to a kind of photocontrol activation covalent probe for transthyretin and its synthesis method.The probe has the structure shown in formula I, raw material is low in price, method is simple and easy to operate, and easy to purify;This kind of probe can target transthyretin, and under the irradiation of ultraviolet light or white light, it is activated to produce carbene, and then covalently labeled protein;It can be applied to the field such as quantitative analysis of transthyretin.

This invention provides saponin derivatives with improved therapeutic concentration ranges. [Solution] The present invention relates to a saponin-based saponin derivative comprising a triterpene aglycone and a first glycan and / or a second glycan, wherein the saponin derivative comprises: an aglycone core structure containing a derivatized aldehyde group; and / or the first glycan, wherein the first glycan contains a derivatized carboxyl group; and / or the second glycan, wherein the second glycan contains at least one derivatized acetoxy group. The present invention also provides use in the treatment or prevention of cancer, infectious diseases, viral infections, hypercholesterolemia, primary hyperoxaluria, hemophilia A, hemophilia B, alpha-1 antitrypsin-related liver disease, acute hepatic porphyria, transthyretin-mediated amyloidosis, or autoimmune diseases.

The invention relates to methods of treating, preventing, or ameliorating symptoms associated with one or more conditions associated with metabolic syndrome in a subject having transthyretin (TTR) dysfunction by administration of a TTR stabilizer. Particularly, the methods described herein may be used to treat or prevent in a subject having TTR dysfunction diabetes, insulin resistance, dyslipidemia, or obesity.

Disclosures herein are directed to polypeptide probes that may be used to detect transthyretin (TTR) oligomers or fibrils in patient samples obtained from subjects with wildtype and mutant TTR alleles. Also provided are methods of using the provided probes to diagnose subjects with a TTR-associated disease or condition or for monitoring the efficacy of a therapeutic administered to treat a TTR-associated disease or condition.

The invention provides antibodies that specifically bind transthyretin (TTR). The antibodies can be used to treat or prevent diseases or disorders associated with TTR accumulation or accumulation of TTR deposits (e.g., TTR amyloidosis). The antibodies can also be used to diagnose TTR amyloidosis and inhibit or reduce TTR accumulation, among other applications.

Based on co-drugs representing two different chemical entities, and the co-administration and sequential administration of said two chemical entities, novel therapies are provided for macular degeneration, non-alcoholic fatty liver disease (NAFLD), and gouty arthritis (gout). The first component (“Selective RBP4 Antagonist”) is a chemical entity that interacts with RBP4 (retinol-binding protein 4), part of the RBP4-TTR (transthyretin) complex that delivers retinol to the retina. This component reduces the transport of retinol from circulation to the retina. The second component (“C20-D3-Visual Chromosome-Generating Compound”) is a C20-D3-modified retinoid or carotenoid that, when metabolized in mammals, ultimately produces a C20-D3 visual chromophore in the retina representing either C20-D3-9-cis-retinal or C20-D3-11-cis-retinal. Deuteration at the C20 position reduces the formation of lipofuscin biretinol, while other functions (such as providing a precursor for the in vivo synthesis of visual chromophore 11-cis-retinaldehyde) are not reduced.

Compositions for modifying or editing a polynucleotide (e.g., a gene) and methods of using the same to treat or prevent conditions associated with the extracellular deposition in various tissues of amyloid fibrils formed by the aggregation of misfolded transthyretin (TTR) proteins. Such conditions include, but are not limited to, polyneuropathy due to hereditary transthyretin amyloidosis (hATTR-PN) and hereditary cardiomyopathy due to transthyretin amyloidosis (hATTR-CM), both associated with autosomal dominant mutations of the TTR gene, and an age-related cardiomyopathy associated with wild-type TTR proteins (ATTRwt), also known as senile cardiac amyloidosis are disclosed. Compositions and methods for editing TTR polynucleotides using base editor systems are disclosed.