77 results about "Transthyretin" patented technology

Provided herein are anti-TTR antibody dosing regimens useful for the treatment of thyroxine transporter amyloid cardiomyopathy (ATTR-CM) in adult patients. In an embodiment, the patient is treated with an anti-TTR antibody comprising NI006 / ALXN2220.

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 treated human umbilical cord composition for use in the treatment of Perony's disease by in vivo injection in a subject in need thereof using an effective amount of the composition. The composition comprises a water-based human umbilical cord filtrate, wherein endogenous hyaluronic acid (HA) and / or hyaluronic acid, fibronectin, insulin growth factor binding protein-1 (IGFBP-1), sulfated glycosaminoglycan (sGAG), exosomes, interleukin-1 receptor antagonist (IL-1ra), hepatocyte growth factor (HGF), transthyretin, metalloproteinase tissue inhibitor 1 (TIMP-1), and / or a pharmaceutically acceptable salt thereof in an amount effective to reduce the size of Pteroid disease plaques. The present invention relates to an aggregation glycan, or a combination thereof.

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.

The invention relates to a conjugate for transferring an effector molecule from outside a cell into said cell, the conjugate comprising at least one effector molecule to be transferred into the cell, at least one saponin of the mono-desmosidic triterpene glycoside type or the bi-desmosidic triterpene glycoside type, and at least one single-domain antibody (sdAb), covalently bound to each other, wherein the sdAb is capable of binding to a cell-surface molecule of said cell. The invention also relates to a pharmaceutical composition comprising the conjugate of the invention. Furthermore, the invention relates to a pharmaceutical composition of the invention, for use as a medicament. In addition, the invention relates to a pharmaceutical composition of the invention, for use in the treatment or the prophylaxis of any one or more of: a cancer, an auto-immune disease such as rheumatoid arthritis, an enzyme deficiency, a disease related to an enzyme deficiency, a gene defect, a disease relating to a gene defect, an infection such as a viral infection, hypercholesterolemia, primary hyperoxaluria, haemophilia A, haemophilia B, alpha-1 antitrypsin related liver disease, acute hepatic porphyria, an amyloidosis and transthyretin-mediated amyloidosis. The invention also relates to an in vitro or ex vivo method for transferring the conjugate from outside a cell to inside said cell or for transferring the effector molecule comprised by the conjugate of the invention from outside a cell to inside said cell, preferably to the cytosol of said cell.

Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized TRKB locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized TRKB locus express a human TRKB protein or a chimeric transthyretin protein, fragments of which are from human TRKB. Methods are provided for using such non-human animals comprising a humanized TRKB locus to assess in vivo efficacy of human-TRKB-targeting reagents such as nuclease agents designed to target human TRKB.

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.

Provided herein are compounds of formula (I): or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein T, L, LB, E, and D1 are as defined elsewhere herein. Also provided are methods of preparing compound of formula (I).

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.

Biomarkers for detecting cognitive dysfunction diseases and methods for detecting cognitive dysfunction diseases using the biomarkers are provided. A method for detecting cognitive dysfunction diseases comprising measuring one or more biomarkers for detecting cognitive dysfunction diseases selected from the following (a), (b), and (c) in a biological sample simultaneously or separately: (a) a biomarker for detecting cognitive dysfunction diseases consisting of an intact protein of apolipoprotein A1 comprising the amino acid sequence represented by SEQ ID NO:1 or a partial peptide thereof; (b) a biomarker for detecting cognitive dysfunction diseases consisting of an intact protein of transthyretin comprising the amino acid sequence represented by SEQ ID NO:2 or a partial peptide thereof; and (c) a biomarker for detecting cognitive dysfunction diseases consisting of an intact protein of complement C3 comprising the amino acid sequence represented by SEQ ID NO:3 or a partial peptide thereof.

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.

The invention relates to a pharmaceutical combination comprising: a first conjugate comprising at least one effector molecule and a single-domain antibody (sdAb) for binding to a first cell-surface molecule; and comprising a saponin, a derivative thereof, or a second conjugate comprising a binding molecule for binding to a second cell-surface molecule and the saponin and / or the derivative thereof, wherein the saponin or the derivative thereof is a monodesmosidic or bidesmosidic triterpene glycoside. The invention also relates to a composition comprising the first conjugate and the saponin (derivative) or the second conjugate comprising the saponin (derivative). In addition, the invention relates to a pharmaceutical combination or composition of the invention, for use as a medicament, and for use in the treatment or the prophylaxis of a cancer, an auto-immune disease such as rheumatoid arthritis, an enzyme deficiency, a gene defect, a disease relating to a gene defect, an amyloidosis, a disease related to an enzyme deficiency, an infection such as a viral infection, hypercholesterolemia, primary hyperoxaluria, haemophilia A, haemophilia B, alpha-1 antitrypsin related liver disease, acute hepatic porphyria, transthyretin-mediated amyloidosis. Furthermore, the invention relates to an in vitro or ex vivo method for transferring the first conjugate of the invention from outside a cell to inside said cell, preferably to the cytosol of said cell.

To provide a method for treating hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) in a human patient.SOLUTION: The method according to the invention comprises administering to a patient a patisiran medicinal formulation at a dose of 0.3 mg siRNA per kg of body weight, wherein the patisiran medicinal formulation is administered intravenously once every 3 weeks, and the method results in stabilization or improvement of a FAP stage, a PND score, a modified Neuropathy Impairment Score (mNIS+7) or other neuropathy-related clinical endpoints, a serum percent TTR concentration, a cardiac marker and / or an echocardiographic parameter.SELECTED DRAWING: Figure 3

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.

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).

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.