The present invention provides methods to determine whether a patient with a lysosomal storage disorder will benefit from treatment with a specific pharmacological chaperone. The present invention exemplifies an in vitro method for determining α-galactosidase A responsiveness to a pharmacological chaperone such as 1-deoxygalactonojirimycin in a cell line expressing a mutant from of α-galactosidase A. The invention also provides a method for diagnosing Fabry disease in patients suspected of having Fabry disease.
A61K 31/445 - Pipéridines non condensées, p. ex. pipérocaïne
C07K 14/00 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés
C12Q 1/34 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir une hydrolase
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
Provided are a recombinant acid α-glucosidase and pharmaceutical composition comprising a recombinant acid α-glucosidase, wherein the recombinant acid α-glucosidase is expressed in Chinese hamster ovary (CHO) cells and comprises an increased content of N-glycan units bearing one or two mannose-6-phosphate residues when compared to a content of N-glycan units bearing one or two mannose-6-phosphate residues of alglucosidase alfa. Also provided herein are methods of producing, purifying, and formulating the recombinant acid α-glucosidase or pharmaceutical composition for administration to a subject and methods of treating a disease or disorder such as Pompe disease using the recombinant acid α-glucosidase or pharmaceutical composition.
Provided herein are compositions and methods for treating Mucopolysaccharidosis IIIA (MPS IIIA) comprising enzyme replacement therapy and gene therapy constructs described herein.
Methods of determining a disease score of a patient diagnosed with lysosomal storage disease (LSD) are described. The disease score includes one or more of the following: (i) one or more biofluid biomarkers; (ii) one or more neurophysiological measurements; and (iii) one or more neurobehavior measurement. Also described method of treating LSD including determining the disease score and administering to the patient a therapy. The therapy includes one or more of the following: (i) enzyme replacement therapy, (ii) gene therapy; and (iii) a small molecule.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
A61B 5/00 - Mesure servant à établir un diagnostic Identification des individus
A61B 5/398 - Électrooculographie [EOG], p. ex. pour la détection du nystagmusÉlectrorétinographie [ERG]
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
G01N 33/92 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des lipides, p. ex. le cholestérol
7.
Neurotensin Variants And Tagged Proteins Comprising Neurotensin Or Sortilin Propeptide
The disclosure provides amino acid sequences for neurotensin variants as well as recombinant proteins that contain neurotensin, sortilin propeptide, or variants thereof. The disclosure also provides method of production and method for determining cellular uptake for the recombinant proteins. Gene therapy compositions, pharmaceutical compositions, methods of treatment, and uses of the gene therapy compositions and the recombinant proteins are also disclosed.
Provided are methods of treating a patient diagnosed with Fabry disease and methods of enhancing α-galactosidase A in a patient diagnosed with or suspected of having Fabry disease. Certain methods comprise administering to a patient a therapeutically effective dose of a pharmacological chaperone for α-galactosidase A, wherein the patient has a mutation in the nucleic acid sequence encoding α-galactosidase A. Also described are uses of pharmacological chaperones for the treatment of Fabry disease and compositions for use in the treatment of Fabry disease.
A61K 31/7008 - Composés ayant un groupe amino lié directement à un atome de carbone du radical saccharide, p. ex. D-galactosamine, ranimustine
C12Q 1/6883 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique
G16B 20/20 - Détection d’allèles ou de variantes, p. ex. détection de polymorphisme d’un seul nucléotide
G16H 50/20 - TIC spécialement adaptées au diagnostic médical, à la simulation médicale ou à l’extraction de données médicalesTIC spécialement adaptées à la détection, au suivi ou à la modélisation d’épidémies ou de pandémies pour le diagnostic assisté par ordinateur, p. ex. basé sur des systèmes experts médicaux
9.
Methods of Treating Fabry Disease in Pediatric Patients
Provided are methods of treating a patient diagnosed with Fabry disease and methods of enhancing α-galactosidase A in a patient diagnosed with or suspected of having Fabry disease. Certain methods comprise administering to a patient a therapeutically effective dose of a pharmacological chaperone for α-galactosidase A, wherein the patient has a mutation in the nucleic acid sequence encoding α-galactosidase A. Also described are uses of pharmacological chaperones for the treatment of Fabry disease and compositions for use in the treatment of Fabry disease.
The present disclosure relates to recombinant adeno-associated virus (rAAV) delivery of an acid alpha-glucosidase (GAA) polynucleotide. The disclosure provides rAAV vectors and methods of using the rAAV vectors for GAA gene therapy for Pompe disease.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
C07K 14/65 - Facteurs de croissance analogues à l'insuline, c.-à-d. somatomédines, p. ex. IGF-1, IGF-2
C12N 9/24 - Hydrolases (3.) agissant sur les composés glycosyliques (3.2)
12.
Methods Of Treating Fabry Disease In Patients Having A Mutation In The GLA Gene
Provided are methods of treating a patient diagnosed with Fabry disease and methods of enhancing α-galactosidase A in a patient diagnosed with or suspected of having Fabry disease. Certain methods comprise administering to a patient a therapeutically effective dose of a pharmacological chaperone for α-galactosidase A, wherein the patient has a mutation in the nucleic acid sequence encoding α-galactosidase A. Also described are uses of pharmacological chaperones for the treatment of Fabry disease and compositions for use in the treatment of Fabry disease.
A61K 31/7008 - Composés ayant un groupe amino lié directement à un atome de carbone du radical saccharide, p. ex. D-galactosamine, ranimustine
C12Q 1/6883 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique
G16B 20/20 - Détection d’allèles ou de variantes, p. ex. détection de polymorphisme d’un seul nucléotide
G16H 50/20 - TIC spécialement adaptées au diagnostic médical, à la simulation médicale ou à l’extraction de données médicalesTIC spécialement adaptées à la détection, au suivi ou à la modélisation d’épidémies ou de pandémies pour le diagnostic assisté par ordinateur, p. ex. basé sur des systèmes experts médicaux
13.
METHODS OF IMPROVING THE PHARMACOKINETICS OF MIGALASTAT
A61K 31/435 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines ayant des cycles à six chaînons avec un azote comme seul hétéro-atome d'un cycle
A61K 31/395 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines
Provided herein are methods of treating Pompe disease comprising administering a population of recombinant human acid a-glucosidase molecules or a pharmaceutical composition or formulation thereof, and a pharmacological chaperone.
Provided herein are methods for treating Pompe disease in pediatric patients by administering to a subject a population of recombinant human acid α-glucosidase molecules or a pharmaceutical composition or formulation thereof, and a pharmacological chaperone.
Provided herein are methods for treating Pompe disease in pediatric patients by administering to a subject a population of recombinant human acid α-glucosidase molecules or a pharmaceutical composition or formulation thereof, and an enzyme stabilizer.
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
The presently disclosed subject matter provides a formulation for the use of 1-deoxygalactonojirimycin and/or enzyme replacement therapy for the treatment of Fabry disease.
Provided herein are novel IGF2 peptides, fusion proteins, and nucleic acid sequences encoding novel IGF2 peptides and fusion proteins for the treatment of lysorsomal storage disorders, wherein the IGF2 peptides confer enhanced properties, such as enhanced expression, secretion and cellular uptake. The constructs provided herein are useful in treating lysosomal storage disorders by both enzyme replacement therapy and gene therapy.
A61K 38/48 - Hydrolases (3) agissant sur des liaisons peptidiques (3.4)
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
Provided are pharmaceutical formulations comprising a recombinant acid α-glucosidase, wherein the recombinant acid α-glucosidase is expressed in Chinese hamster ovary (CHO) cells and comprises an increased content of N-glycan units bearing one or two mannose-6-phosphate residues when compared to a content of N-glycan units bearing one or two mannose-6-phosphate residues of alglucosidase alfa; at least one buffer selected from the group consisting of a citrate, a phosphate and combinations thereof; and at least one excipient selected from the group consisting of mannitol, polysorbate 80, and combinations thereof, wherein the formulation has a pH of from about 5.0 to about 7.0. Also provided are methods of treating Pompe disease using these pharmaceutical formulations.
A61K 47/12 - Acides carboxyliquesLeurs sels ou anhydrides
A61K 47/26 - Hydrates de carbone, p. ex. polyols ou sucres alcoolisés, sucres aminés, acides nucléiques, mono-, di- ou oligosaccharidesLeurs dérivés, p. ex. polysorbates, esters d’acide gras de sorbitan ou glycyrrhizine
C12N 9/26 - Hydrolases (3.) agissant sur les composés glycosyliques (3.2) agissant sur les liaisons alpha-glucosidiques-1, 4, p. ex. hyaluronidase, invertase, amylase
The disclosure provides a novel method for treating genetic disorders where a peptide sequence targets proteins produced via gene therapy into exosomes. These protein-loaded exosomes can enter into non-transduced cells and correct pathology. Also, gene therapy compositions, protein replacement therapy composition, pharmaceutical compositions, methods of treatment, and uses of the gene therapy compositions and the recombinant proteins are also disclosed. The method can also be used to improve in vitro recombinant protein yield.
C07K 14/705 - RécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire
C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
09 - Appareils et instruments scientifiques et électriques
Produits et services
Downloadable computer application software for mobile devices, namely, software for Pompe disease patients to administer and comply with their dosing regimen.
25.
Methods of treating Fabry patients having renal impairment
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
The present invention provides dosing regimens for administering pharmacological chaperones to a subject in need thereof. The dosing regimens can be used to treat disorders caused by improper protein misfolding, such as lysosomal storage disorders.
Provided herein are methods for treating Pompe disease by administering to a subject a population of recombinant human acid α-glucosidase molecules or a pharmaceutical composition or formulation thereof, and an enzyme stabilizer.
Provided are methods of producing Active Pharmaceutical Ingredient (API) grade migalastat hydrochloride, and for purifying intermediate grade migalastat hydrochloride. Further provided are methods of producing [(2R,3S,4R,5S)-1-butyl-2-(hydroxymethyl)piperidine-3,4,5-triol hydrochloride (lucerastat hydrochloride) and other 1-deoxygalactonojirimycin compounds, as well as methods of purifying intermediate grade lucerastat hydrochloride and other 1-deoxygalactonojirimycin compounds.
Provided are dosing regimens for the treatment of Fabry disease in a patient. Certain methods relate to the treatment of ERT-experienced or ERT-naïve Fabry patients. Certain methods comprise administering to the patient about 123 mg free base equivalent of migalastat for improving left ventricular mass and/or improving podocyte globotriaosylceramide.
09 - Appareils et instruments scientifiques et électriques
Produits et services
Downloadable computer application software for mobile
devices, namely, software for pompe disease patients to
administer and comply with their dosing regimen.
09 - Appareils et instruments scientifiques et électriques
Produits et services
(1) Downloadable computer application software for mobile devices, namely, software for pompe disease patients to administer and comply with their dosing regimen.
05 - Produits pharmaceutiques, vétérinaires et hygièniques
Produits et services
Pharmaceutical preparations for the treatment of Pompe disease; Pharmaceutical preparations for the treatment of genetic diseases; Enzyme replacement therapy preparations for medical purposes
05 - Produits pharmaceutiques, vétérinaires et hygièniques
Produits et services
Pharmaceutical preparations for the treatment of Pompe disease; Pharmaceutical preparations for the treatment of genetic diseases; Enzyme replacement therapy preparations for medical purposes
Provided herein are improved gene therapy vectors and methods of use, in some embodiments, comprising sequences for improved expression and cellular targeting of a therapeutic protein.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
C07K 16/38 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre des inhibiteurs de protéase de structure peptidique
C07K 16/40 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre des enzymes
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
Methods for the continuous production, capturing and purification of biologics such as recombinant proteins are described. Also described are pharmaceutical compositions comprising such biologics, as well as methods of treatment and uses of such biologics.
Recombinant human alpha glucosidase (rhGAA) composition derived from CHO cells that contains a more optimized glycan composition consisting of a higher amount of rhGAA containing N-glycans carrying mannose-6-phosphate (M6P) or bis-M6P than conventional rhGAAs, along with low amount of non-phosphorylated high mannose glycans, and low amount of terminal galactose on complex oligosaccharides. Compositions containing the rhGAA, and methods of use are described.
C12N 9/40 - Hydrolases (3.) agissant sur les composés glycosyliques (3.2) agissant sur les liaisons alpha-galactose-glycoside, p. ex. alpha-galactosidase
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
The Trustees of the University of Pennsylvania (USA)
Amicus Therapeutics, Inc. (USA)
Inventeur(s)
Wilson, James M.
Hordeaux, Juliette
Do, Hung V.
Gotschall, Russell
Tuske, Steven
Abrégé
Provided herein is a method for reducing the progression of abnormal muscle pathology and/or reversing abnormal muscle pathology in a patient, wherein the patient has been diagnosed with Pompe disease or is suspected of having Pompe disease. The method comprising administering to the patient a recombinant AAV (rAAV) having an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises: (a) a 5′ inverted terminal repeat (ITR); (b) a promoter; (c) a nucleotide sequence encoding a chimeric fusion protein comprising a signal peptide and a vIGF2 peptide fused to a human acid-a-glucosidase (hGAA), (d) a poly A; and (e) a 3′ ITR. Also provided are pharmaceutical composition comprising an rAAV described herein for use in treating a patient having or suspected of having Pompe disease.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
A61K 38/18 - Facteurs de croissanceRégulateurs de croissance
A61K 38/47 - Hydrolases (3) agissant sur des composés glycosyliques (3.2), p. ex. cellulases, lactases
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
A61P 3/00 - Médicaments pour le traitement des troubles du métabolisme
Described are compositions comprising α-galactosidase A enzymes with unique carbohydrate profiles, as well as methods for manufacturing and purifying such enzymes. Also described methods of treating, preventing, and/or ameliorating Fabry Disease by administering such enzymes to a subject in need thereof. Also described are compositions comprising migalastat in combination with such α-galactosidase A enzymes.
A61K 38/47 - Hydrolases (3) agissant sur des composés glycosyliques (3.2), p. ex. cellulases, lactases
A61K 31/445 - Pipéridines non condensées, p. ex. pipérocaïne
C12N 9/40 - Hydrolases (3.) agissant sur les composés glycosyliques (3.2) agissant sur les liaisons alpha-galactose-glycoside, p. ex. alpha-galactosidase
C12P 21/00 - Préparation de peptides ou de protéines
44.
GENE THERAPY FOR TREATMENT OF MUCOPOLYSACCHARIDOSIS IIIA
THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA (USA)
AMICUS THERAPEUTICS, INC. (USA)
Inventeur(s)
Hordeaux, Juliette
Wilson, James, M.
Rassouli-Taylor, Leida
Do, Hung
Tuske, Steven
Abrégé
Provided herein is a recombinant AAV (rAAV) comprising an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises an AAV 5' inverted terminal repeat (ITR), an engineered nucleic acid sequence encoding a functional hSGSH, optionally comprising stabilizing amino acid changes, a regulatory sequence which direct expression of hSGSH in a target cell, and an AAV 3' ITR. Also provided is a pharmaceutical composition comprising a rAAV as described herein in a formulation buffer, and a method of treating a human subject diagnosed with MPS IIIA.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
Provided herein are compositions and methods for treating Mucopolysaccharidosis IIIA (MPS IIIA) comprising enzyme replacement therapy and gene therapy constructs described herein.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
Provided are methods of treating a patient diagnosed with Fabry disease and methods of enhancing α-galactosidase A in a patient diagnosed with or suspected of having Fabry disease. Certain methods comprise administering to a patient a therapeutically effective dose of a pharmacological chaperone for α-galactosidase A, wherein the patient has a mutation in the nucleic acid sequence encoding α-galactosidase A. Also described are uses of pharmacological chaperones for the treatment of Fabry disease and compositions for use in the treatment of Fabry disease.
THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA (USA)
AMICUS THERAPEUTICS, INC. (USA)
Inventeur(s)
Schmid, Ralf
Percival, Justin
Katz, Evan
Clark, Sean
Abrégé
Provided is a recombinant adeno-associated virus (rAAV) having an AAV capsid and a vector genome which comprises a human CDKL5 (hCDKLK5) expression cassette. Also provided are a production system useful for producing the rAAV, a pharmaceutical composition comprising the rAAV, and a method of treating a subject having CDD, or ameliorating symptoms of CDD, or delaying progression of CDD via administrating an effective amount of the rAAV to a subject in need thereof.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
C12N 15/52 - Gènes codant pour des enzymes ou des proenzymes
Methods of determining a disease score of a patient diagnosed with lysosomal storage disease (LSD) are described. The disease score includes one or more of the following: (i) one or more biofluid biomarkers; (ii) one or more neurophysiological measurements; and (iii) one or more neurobehavior measurement. Also described method of treating LSD including determining the disease score and administering to the patient a therapy. The therapy includes one or more of the following: (i) enzyme replacement therapy, (ii) gene therapy; and (iii) a small molecule.
G01N 33/68 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des protéines, peptides ou amino-acides
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
G01N 33/92 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique faisant intervenir des lipides, p. ex. le cholestérol
49.
IN THE FIGHT TO REMAIN AT THE FOREFRONT OF THERAPIES FOR RARE AND ORPHAN DISEASES
44 - Services médicaux, services vétérinaires, soins d'hygiène et de beauté; services d'agriculture, d'horticulture et de sylviculture.
Produits et services
Providing medical services for the treatment of rare genetic diseases; Providing health information in the field of rare genetic diseases; Providing medical information in the field of rare genetic diseases
50.
Method For Selection Of High M6P Recombinant Proteins
Methods for the production, capturing and purification of recombinant human lysosomal proteins are described. Such recombinant human lysosomal proteins can have high content of mannose-6-phosphate residues. Also described are pharmaceutical compositions comprising such recombinant human lysosomal proteins, as well as methods of treatment and uses of such recombinant human lysosomal proteins.
C12N 9/26 - Hydrolases (3.) agissant sur les composés glycosyliques (3.2) agissant sur les liaisons alpha-glucosidiques-1, 4, p. ex. hyaluronidase, invertase, amylase
51.
DETERMINATION OF GENE TRANSDUCTION POTENCY IN NEURON-LIKE CELLS
Compositions for CDKL5 gene therapy are provided, as well as recombinant CDKL5 proteins. Such CDKL5 gene therapy compositions and/or recombinant CDKL5 proteins may incorporate cell-penetrating polypeptides and/or leader signal polypeptides. Also provided are methods of producing such gene therapy compositions and recombinant CDKL5 proteins, as well as pharmaceutical compositions, methods of treatment, and uses of the gene therapy compositions and recombinant CDKL5 proteins.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
A61P 25/28 - Médicaments pour le traitement des troubles du système nerveux des troubles dégénératifs du système nerveux central, p. ex. agents nootropes, activateurs de la cognition, médicaments pour traiter la maladie d'Alzheimer ou d'autres formes de démence
C12N 9/12 - Transférases (2.) transférant des groupes contenant du phosphore, p. ex. kinases (2.7)
The disclosure provides amino acid sequences for neurotensin variants as well as recombinant proteins that contain neurotensin, sortilin propeptide, or variants thereof. The disclosure also provides method of production and method for determining cellular uptake for the recombinant proteins. Gene therapy compositions, pharmaceutical compositions, methods of treatment, and uses of the gene therapy compositions and the recombinant proteins are also disclosed.
Provided are methods of treating a patient diagnosed with Fabry disease. Certain methods treat a pregnant patient with a therapeutically effective dose of migalastat or a salt thereof. Other methods treat a patient of childbearing potential with a therapeutically effective dose of migalastat or a salt thereof. Also described are the successful outcomes of pregnancies during which the pregnant patient is treated with migalastat.
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
A method for treating Pompe disease including administration of recombinant human acid α-glucosidase having optimal glycosylation with mannose-6-phosphate residues in combination with an amount of miglustat effective to maximize tissue uptake of recombinant human acid α-glucosidase while minimizing inhibition of the enzymatic activity of the recombinant human acid α-glucosidase is provided.
The present application provides for compositions comprising high concentrations of acid α-glucosidase in combination with an active site-specific chaperone for the acid α-glucosidase, and methods for treating Pompe disease in a subject in need thereof, that includes a method of administering to the subject such compositions. The present application also provides methods for increasing the in vitro and in vivo stability of an acid α-glucosidase enzyme formulation.
A61K 38/47 - Hydrolases (3) agissant sur des composés glycosyliques (3.2), p. ex. cellulases, lactases
C12N 9/96 - Stabilisation d'une enzyme par formation d'un adduct ou d'une compositionFormation de conjugaisons d'enzymes
A61K 31/445 - Pipéridines non condensées, p. ex. pipérocaïne
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 31/7008 - Composés ayant un groupe amino lié directement à un atome de carbone du radical saccharide, p. ex. D-galactosamine, ranimustine
C12N 9/26 - Hydrolases (3.) agissant sur les composés glycosyliques (3.2) agissant sur les liaisons alpha-glucosidiques-1, 4, p. ex. hyaluronidase, invertase, amylase
A61K 47/22 - Composés hétérocycliques, p. ex. acide ascorbique, tocophérol ou pyrrolidones
60.
Methods Of Treating Fabry Disease In Patients Having Renal Impairment
Provided are methods for treatment of Fabry disease in a patient having renal impairment. Certain methods comprise administering to the patient about 100 mg to about 300 mg free base equivalent of migalastat or salt thereof at a frequency of greater than once every other day, such as once every four or seven days. Certain methods comprise measuring lyso-Gb3 and/or migalastat in one or more plasma samples from the patient.
The present invention provides novel compounds as well as compositions and methods using the same for preventing and/or treating degenerative disorders of the central nervous system and/or lysosomal storage disorders. In particular, the present invention provides methods for preventing and/or treating Parkinson's disease, Alzheimer's disease and/or Gaucher's disease.
C07C 215/44 - Composés contenant des groupes amino et hydroxy liés au même squelette carboné ayant des groupes amino ou des groupes hydroxy liés à des atomes de carbone de cycles autres que des cycles aromatiques à six chaînons du même squelette carboné liés à des atomes de carbone du même cycle ou du même système cyclique condensé
A61P 25/28 - Médicaments pour le traitement des troubles du système nerveux des troubles dégénératifs du système nerveux central, p. ex. agents nootropes, activateurs de la cognition, médicaments pour traiter la maladie d'Alzheimer ou d'autres formes de démence
C07C 233/06 - Amides d'acides carboxyliques ayant des atomes de carbone de groupes carboxamide liés à des atomes d'hydrogène ou à des atomes de carbone acycliques ayant les atomes d'azote des groupes carboxamide liés à des atomes d'hydrogène ou à des atomes de carbone de radicaux hydrocarbonés non substitués avec des atomes de carbone de groupes carboxamide liés à des atomes de carbone d'un squelette carboné saturé acyclique ayant l'atome d'azote d'au moins un des groupes carboxamide lié à un atome de carbone d'un cycle autre qu'un cycle aromatique à six chaînons
62.
RECOMBINANT HUMAN ACID ALPHA-GLUCOSIDASE AND USES THEREOF
Provided herein are methods of treating Pompe disease comprising administering a population of recombinant human acid a-glucosidase molecules or a pharmaceutical composition or formulation thereof, and a pharmacological chaperone.
Provided herein are methods of treating Pompe disease comprising administering a population of recombinant human acid a-glucosidase molecules or a pharmaceutical composition or formulation thereof, and a pharmacological chaperone.
The present disclosure relates to recombinant adeno-associated virus (rAAV) delivery of a ceroid lipofuscinosis neuronal 3 (CLN3) polynucleotide. The disclosure provides rAAV and methods of using the rAAV for CLN3 gene therapy of the neuronal ceroid lipofuscinosis or CLN3-Batten Disease.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
Provided are methods of producing Active Pharmaceutical Ingredient (API) grade migalastat hydrochloride, and for purifying intermediate grade migalastat hydrochloride. Further provided are methods of producing [(2R,3S,4R,5S)-1-butyl-2-(hydroxymethyl)piperidine-3,4,5-triol hydrochloride (lucerastat hydrochloride) and other 1-deoxygalactonojirimycin compounds, as well as methods of purifying intermediate grade lucerastat hydrochloride and other 1-deoxygalactonojirimycin compounds.
Provided are methods of producing Active Pharmaceutical Ingredient (API) grade migalastat hydrochloride, and for purifying intermediate grade migalastat hydrochloride. Further provided are methods of producing [(2R,3S,4R,5S)-1-butyl-2-(hydroxymethyl)piperidine-3,4,5-triol hydrochloride (lucerastat hydrochloride) and other 1-deoxygalactonojirimycin compounds, as well as methods of purifying intermediate grade lucerastat hydrochloride and other 1-deoxygalactonojirimycin compounds.
Provided are methods of producing Active Pharmaceutical Ingredient (API) grade migalastat hydrochloride, and for purifying intermediate grade migalastat hydrochloride. Further provided are methods of producing [(2R,3S,4R,5S)-1-butyl-2-(hydroxymethyl)piperidine-3,4,5-triol hydrochloride (lucerastat hydrochloride) and other 1-deoxygalactonojirimycin compounds, as well as methods of purifying intermediate grade lucerastat hydrochloride and other 1-deoxygalactonojirimycin compounds.
The Trustees of the University of Pennsylvania (USA)
Amicus Therapeutics, Inc. (USA)
Inventeur(s)
Wilson, James M.
Hordeaux, Juliette
Do, Hung V.
Gotschall, Russell
Tuske, Steven
Abrégé
A recombinant adeno-associated virus (rAAV) useful for treating type II glycogen storage disease (Pompe) disease is provided. The rAAV comprises an AAV capsid which targets cells of at least one of muscle, heart, kidney, and the central nervous system and which has packaged therein a vector genome comprising a nucleic acid sequence encoding a a chimeric fusion protein comprising a signal peptide and a vIGF2 peptide fused to a human acid-α-glucosidase hGAA780I protein under the control of regulatory sequences which direct its expression. Also provided are methods of making and using this rAAV.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
C07K 14/65 - Facteurs de croissance analogues à l'insuline, c.-à-d. somatomédines, p. ex. IGF-1, IGF-2
C12N 9/26 - Hydrolases (3.) agissant sur les composés glycosyliques (3.2) agissant sur les liaisons alpha-glucosidiques-1, 4, p. ex. hyaluronidase, invertase, amylase
A61P 3/00 - Médicaments pour le traitement des troubles du métabolisme
69.
Highly purified batches of pharmaceutical grade migalastat and methods of producing the same
Provided are methods of producing a batch of 1,2,3,6-tetrapivaloyl-D-galactofuranoside; 5-azido-5-deoxy-1,2,3,6-tetrapivaloyl-D-galactofuranoside; intermediate grade migalastat hydrochloride; and/or migalastat hydrochloride. Also provided are methods of determining the purity of a batch of 1,2,3,6-tetrapivaloyl-D-galactofuranoside; 5-azido-5-deoxy-1,2,3,6-tetrapivaloyl-D-galactofuranoside; intermediate grade migalastat hydrochloride; and/or migalastat hydrochloride. Also provided are methods of distributing a batch of 1,2,3,6-tetrapivaloyl-D-galactofuranoside; 5-azido-5-deoxy-1,2,3,6-tetrapivaloyl-D-galactofuranoside; intermediate grade migalastat hydrochloride; and/or migalastat hydrochloride. Also provided are methods of assessing suitability of migalastat hydrochloride for medical use.
G16H 20/10 - TIC spécialement adaptées aux thérapies ou aux plans d’amélioration de la santé, p. ex. pour manier les prescriptions, orienter la thérapie ou surveiller l’observance par les patients concernant des médicaments ou des médications, p. ex. pour s’assurer de l’administration correcte aux patients
70.
Methods of treating Fabry patients having renal impairment
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
Recombinant human alpha glucosidase (rhGAA) composition derived from CHO cells that contains a more optimized glycan composition consisting of a higher amount of rhGAA containing N-glycans carrying mannose-6-phosphate (M6P) or bis-M6P than conventional rhGAAs, along with low amount of non-phosphorylated high mannose glycans, and low amount of terminal galactose on complex oligosaccharides. Compositions containing the rhGAA, and methods of use are described.
C12N 9/40 - Hydrolases (3.) agissant sur les composés glycosyliques (3.2) agissant sur les liaisons alpha-galactose-glycoside, p. ex. alpha-galactosidase
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
Provided are in vitro and in vivo methods for determining whether a patient with Fabry disease will respond to treatment with a specific pharmacological chaperone.
A61K 31/445 - Pipéridines non condensées, p. ex. pipérocaïne
A61K 31/45 - Pipéridines non condensées, p. ex. pipérocaïne ayant des groupes oxo liés directement à l'hétérocycle, p. ex. cycloheximide
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
C07D 211/46 - Atomes d'oxygène liés en position 4 comportant un atome d'hydrogène comme second substituant en position 4
G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 9/48 - Préparations en capsules, p. ex. de gélatine, de chocolat
78.
Methods of treating Fabry patients having renal impairment
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
Provided are methods of treating a patient diagnosed with Fabry disease and methods of enhancing α-galactosidase A in a patient diagnosed with or suspected of having Fabry disease. Certain methods comprise administering to a patient a therapeutically effective dose of a pharmacological chaperone for α-galactosidase A, wherein the patient has a splice site mutation in intron 4 of the nucleic acid sequence encoding α-galactosidase A. Also described are uses of pharmacological chaperones for the treatment of Fabry disease and compositions for use in the treatment of Fabry disease.
09 - Appareils et instruments scientifiques et électriques
Produits et services
Downloadable computer application software for mobile devices, namely, software for Pompe disease patients to administer and comply with their dosing regimen
81.
Methods of treating fabry patients having renal impairment
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
Provided are methods for the treatment of Fabry disease in a patient and/or reducing the risk of reducing the risk of a cerebrovascular (CBV) event in a patient having Fabry disease. Certain methods relate to the treatment of ERT-experienced or ERT-nave Fabry patients. Certain methods comprise administering to the patient about 100 mg to about 150 mg free base equivalent of migalastat for reducing the risk of a CBV event.
A61K 31/445 - Pipéridines non condensées, p. ex. pipérocaïne
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
The disclosure provides a novel method for treating genetic disorders where a peptide sequence targets proteins produced via gene therapy into exosomes. These protein-loaded exosomes can enter into non-transduced cells and correct pathology. Also, gene therapy compositions, protein replacement therapy composition, pharmaceutical compositions, methods of treatment, and uses of the gene therapy compositions and the recombinant proteins are also disclosed. The method can also be used to improve in vitro recombinant protein yield.
A61K 47/42 - ProtéinesPolypeptidesLeurs produits de dégradationLeurs dérivés p. ex. albumine, gélatine ou zéine
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
The disclosure provides a novel method for treating genetic disorders where a peptide sequence targets proteins produced via gene therapy into exosomes. These protein-loaded exosomes can enter into non-transduced cells and correct pathology. Also, gene therapy compositions, protein replacement therapy composition, pharmaceutical compositions, methods of treatment, and uses of the gene therapy compositions and the recombinant proteins are also disclosed. The method can also be used to improve in vitro recombinant protein yield.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
Provided herein are polypeptides comprising one or more non-native cysteine residues that form a disulfide bridge between non-native cysteines within the protein or between non-native cysteines of two monomers of the protein. Such modified human polypeptides are useful in treatment of genetic diseases via enzyme replacement therapy and/or gene therapy.
A61K 38/47 - Hydrolases (3) agissant sur des composés glycosyliques (3.2), p. ex. cellulases, lactases
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
A61P 43/00 - Médicaments pour des utilisations spécifiques, non prévus dans les groupes
C07H 21/04 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p. ex. acides nucléiques avec le désoxyribosyle comme radical saccharide
Provided are a recombinant acid α-glucosidase and pharmaceutical composition comprising a recombinant acid α-glucosidase, wherein the recombinant acid α-glucosidase is expressed in Chinese hamster ovary (CHO) cells and comprises an increased content of N-glycan units bearing one or two mannose-6-phosphate residues when compared to a content of N-glycan units bearing one or two mannose-6-phosphate residues of alglucosidase alfa. Also provided herein are methods of producing, purifying, and formulating the recombinant acid α-glucosidase or pharmaceutical composition for administration to a subject and methods of treating a disease or disorder such as Pompe disease using the recombinant acid α-glucosidase or pharmaceutical composition.
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA (USA)
Inventeur(s)
Wilson, James M.
Hordeaux, Juliette
Do, Hung V.
Gotschall, Russell
Tuske, Steven
Abrégé
Provided herein is a method for reducing the progression of abnormal muscle pathology and/or reversing abnormal muscle pathology in a patient, wherein the patient has been diagnosed with Pompe disease or is suspected of having Pompe disease. The method comprising administering to the patient a recombinant AAV (rAAV) having an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises: (a) a 5' inverted terminal repeat (ITR); (b) a promoter; (c) a nucleotide sequence encoding a chimeric fusion protein comprising a signal peptide and a vIGF2 peptide fused to a human acid-a-glucosidase (hGAA), (d) a poly A; and (e) a 3' ITR. Also provided are pharmaceutical composition comprising an rAAV described herein for use in treating a patient having or suspected of having Pompe disease.
THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA (USA)
AMICUS THERAPEUTICS, INC. (USA)
Inventeur(s)
Wilson, James, M.
Hordeaux, Juliette
Do, Hung, V.
Gotschall, Russell
Tuske, Steven
Abrégé
Provided herein is a method for reducing the progression of abnormal muscle pathology and/or reversing abnormal muscle pathology in a patient, wherein the patient has been diagnosed with Pompe disease or is suspected of having Pompe disease. The method comprising administering to the patient a recombinant AAV (rAAV) having an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises: (a) a 5' inverted terminal repeat (ITR); (b) a promoter; (c) a nucleotide sequence encoding a chimeric fusion protein comprising a signal peptide and a vIGF2 peptide fused to a human acid-a-glucosidase (hGAA), (d) a poly A; and (e) a 3' ITR. Also provided are pharmaceutical composition comprising an rAAV described herein for use in treating a patient having or suspected of having Pompe disease.
Provided are methods of treating a patient diagnosed with Fabry disease and methods of enhancing α-galactosidase A in a patient diagnosed with or suspected of having Fabry disease. Certain methods comprise administering to a patient a therapeutically effective dose of a pharmacological chaperone for α-galactosidase A, wherein the patient has a mutation in the nucleic acid sequence encoding α-galactosidase A. Also described are uses of pharmacological chaperones for the treatment of Fabry disease and compositions for use in the treatment of Fabry disease.
Provided are methods of treating a patient diagnosed with Fabry disease and methods of enhancing ?-galactosidase A in a patient diagnosed with or suspected of having Fabry disease. Certain methods comprise administering to a patient a therapeutically effective dose of a pharmacological chaperone for ?-galactosidase A, wherein the patient has a mutation in the nucleic acid sequence encoding ?-galactosidase A. Also described are uses of pharmacological chaperones for the treatment of Fabry disease and compositions for use in the treatment of Fabry disease.
