99 results about "Transthyretin" patented technology

An RNAi agent and composition for inhibiting the expression of transthyretin (TTR), which can be used for treating and / or preventing ATTR-related diseases comprising ATTR-PN (transthyretin amyloidosis polyneuropathy), ATTR-CM (transthyretin amyloidosis cardiomyopathy), senile systemic amyloidosis diseases, and leptomeningeal / central nervous system amyloidosis diseases.

[Problems] The purpose of the present technology is to accurately detect cognitive impairment or risk thereof.[Solution] The present technology provides a cognitive impairment determination system comprising an information processing device that executes a determination step of determining presence or absence cognitive impairment or risk of cognitive impairment, based on amounts of the following biomarkers (a), (b), (c), (d), and (e) contained in a biological sample: (a) a biomarker consisting of an intact protein of Apolipoprotein A1 comprising an amino acid sequence represented by SEQ ID NO: 1, or a partial peptide thereof, (b) a biomarker consisting of an intact protein of Transthyretin comprising an amino acid sequence represented by SEQ ID NO: 2, or a partial peptide thereof, (c) a biomarker consisting of an intact protein of Complement C3 having an amino acid sequence represented by SEQ ID NO: 3, or a partial peptide thereof, (d) a biomarker Aβ1-40 consisting of a peptide having an amino acid sequence represented by SEQ ID NO: 4, and (e) a biomarker Aβ1-42 consisting of a peptide having an amino acid sequence represented by SEQ ID NO: 5.

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.

The present invention relates to transthyretin (TTR) fusions useful in the dimerization and tetramerization of antibodies and antibody fragments, such as Fabs. The TTR fusions proteins described herein are particularly useful in increasing antibody avidity and in enhancing antigen clustering. Methods for treating diseases using the fusion proteins of the present invention are described herein.

The invention relates to methods of treating subjects that would benefit from reduction in expression of transthyretin (TTR), such as subjects having a TTR-associated disease, disorder, or condition, e.g., transthyretin-mediated amyloidosis, or Stargardt disease, using double-stranded ribonucleic acid (dsRNA) compositions targeting the TTR gene. The invention also provides methods for preventing at least one symptom in a subject having a TTR-associated disease, disorder, or condition, e.g., transthyretin-mediated amyloidosis, or Stargardt disease.

The invention provides methods of detecting transthyretin (TTR) using a capture antibody and a reporter antibody. The capture antibody binds preferentially to misfolded TTR over native tetrameric form of TTR. The capture antibody binds to an epitope within amino acid residues 89-97 or TTR or to an epitope within amino acid residues 101-109 of TTR. 9D5 and 18C5 are examples of suitable capture antibodies. The methods can be used for diagnosing diseases or disorders associated with TTR accumulation or accumulation of TTR deposits (e.g., TTR amyloidosis) and for monitoring the efficacy of TTR therapies, among other applications.

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.

Compositions and methods useful to reduce expression of TTR gene and for treatment of TTR-associated diseases and conditions are provided. Provided are TTR dsRNA agents, TTR antisense polynucleotide agents, compositions comprising TTR dsRNA agents, and compositions comprising TTR antisense polynucleotide agents that can be used to reduce TTR expression in cells and subjects.

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.

Peptide identified as SEQ ID NO: 1, for use in the manufacture of a medicine for treatment of a disease involving an affection of apolipoprotein A-I (Apo-AI) or transthyretin (TTR). In particular, the peptide may be useful for treatment of a disease characterized by an impairment in lipid homeostasis or in the stability of TTR. Method of treatment of a disease involving an affection in Apo-AI or TTR, which is characterized by administration of a therapeutically effective amount of a pharmaceutical composition comprising the peptide identified as SEQ ID NO: 1.

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.

Provided are novel human-derived antibodies specific for transthyrelin (TTR), preferably capable of binding misfolded, misassembled, and / or aggregated TTR species, as well as methods related thereto. In addition, methods of diagnosing and / or monitoring diseases and treatments thereof which are associated with TTR amyloidosis are provided. Assays and kits related to anti-bodies specific for TTR or TTR deposits and aggregates are also disclosed. The novel anti-TTR antibodies can be used in pharmaceutical and diagnostic compositions for TTR targeted immunotherapy and diagnostics.

Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine.

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.