Abstract

The invention relates to a nucleic acid construct for gene therapy of FGF-23 related hypophosphatemic diseases, in particular gene therapy directed to muscle, liver or hematopoietic tissue, more particularly liver tissue. The invention relates also to a vector comprising the nucleic acid construct, and their use for the treatment of FGF-23 related hypophosphatemic diseases, in particular XLH, by gene therapy.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61K 38/18 - Growth factorsGrowth regulators
• A61P 7/00 - Drugs for disorders of the blood or the extracellular fluid
• C12N 15/86 - Viral vectors

Abstract

The present invention concerns a micro-utrophin comprising the structure NTDH1R1R2R3H2R22H4CRD and two further rod domains selected from the group consisting of: - the R4 to R10 rod domains of utrophin; - the R16 and R17 rod domains of dystrophin; a nucleic acid sequence encoding such a micro-utrophin, a recombinant adeno-associated virus (rAAV) vector comprising such a sequence, and their use for treating a muscular dystrophy such as Duchenne Muscular Dystrophy (DMD) or Becker Muscular Dystrophy (BMD).

IPC Classes  ?

• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals

Abstract

The present invention concerns mididystrophins comprising at least the rod domains R1, R8, R9, R10, R11, R12, R16, R17 and R24 of the dystrophin and their use for treating a muscular dystrophy, in particular a Duchenne muscular dystrophy (DMD).

IPC Classes  ?

• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C12N 15/864 - Parvoviral vectors
• C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 15/62 - DNA sequences coding for fusion proteins
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system

Abstract

The present invention relates to functional N-terminal truncated GDE polypeptides for the treatment of glycogen storage disease III.

IPC Classes  ?

• C12N 9/10 - Transferases (2.)
• A61K 38/00 - Medicinal preparations containing peptides
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 9/44 - Hydrolases (3.) acting on glycosyl compounds (3.2) acting on alpha-1, 6-glucosidic bonds, e.g. isoamylase, pullulanase
• C12N 15/52 - Genes encoding for enzymes or proenzymes
• C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression
• C12N 15/86 - Viral vectors

Abstract

A fluidic system for producing extracellular vesicles from producer cells, including at least one container, a liquid medium contained by the container and producer cells, characterised in that it also includes microcarriers suspended in the liquid medium, the majority of producer cells being adherent to the surface of the microcarriers, and a liquid medium agitator, the agitator and the dimensions of the container being adapted to control a turbulent flow of the liquid medium in the container.

IPC Classes  ?

• C12M 3/06 - Tissue, human, animal or plant cell, or virus culture apparatus with filtration, ultrafiltration, inverse osmosis or dialysis means
• C12M 1/00 - Apparatus for enzymology or microbiology
• C12M 1/12 - Apparatus for enzymology or microbiology with sterilisation, filtration, or dialysis means

Abstract

The invention relates to a lentiviral vector comprising a tricistronic expression cassette encoding: - tyrosine hydroxylase of SEQ ID NO 1; - GTP cyclohydrolase I of SEQ ID NO 2; and - aromatic L-amino acid decarboxylase of SEQ ID NO 3, or a functional variant of said enzymes having a nucleic sequence that is at least 80% identical to SEQ ID NOs 1, 2 and 3. The vector is characterised in that the three enzymes are expressed under the control of the same human PGK-1 promoter, or a functional variant of said human PGK-1 promoter having a nucleic sequence that is at least 80% identical to SEQ ID NO 4.

IPC Classes  ?

• C12N 15/86 - Viral vectors
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy

Abstract

The present invention relates to the generation and use of machine learning models in order to predict some characteristics of a phenotype of a biological object such as an adeno-associated virus. It also relates to the preparation of a reduced training dataset for improving the efficiency and the explicability of the machine learning models generated.

IPC Classes  ?

• G16B 15/10 - Nucleic acid folding
• G16B 15/30 - Drug targeting using structural dataDocking or binding prediction
• G16B 20/30 - Detection of binding sites or motifs
• G16B 35/20 - Screening of libraries
• G16B 40/30 - Unsupervised data analysis
• G16B 40/20 - Supervised data analysis

Abstract

The present invention relates to novel hybrid promoters. The invention further relates to expression cassettes and vectors containing said hybrid promoters. Also disclosed herein are methods implementing these hybrid promoters, in particular methods of gene therapy.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 15/86 - Viral vectors

Abstract

The invention relates to a recombinant adeno-associated virus (AAV) capsid protein, which is a hybrid between AAV serotype 9 (AAV9) and AAV serotype 74 (AAVrh74) capsid proteins, wherein said recombinant hybrid AAV capsid protein has a reduced liver tropism compared to the parent AAV9 and AAVrh74 capsid proteins. The invention relates also to the derived hybrid AAV serotype vector particles packaging a gene of interest and their use in gene therapy, in particular for treating neuromuscular genetic diseases.

IPC Classes  ?

• C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• C07K 14/075 - Adenoviridae
• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
• C12N 9/22 - Ribonucleases
• C12N 15/11 - DNA or RNA fragmentsModified forms thereof
• C12N 15/86 - Viral vectors

Abstract

The invention relates to an AAV vector comprising the combination of a tandem liver-muscle selective promoter and a liver detargeted AAV capsid protein modified with a muscle-targeting peptide and its use in gene therapy of muscle diseases, in particular genetic neuromuscular diseases.

IPC Classes  ?

• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
• C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression
• C12N 15/79 - Vectors or expression systems specially adapted for eukaryotic hosts
• C12N 15/86 - Viral vectors
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy

Goods & Services

Diagnostic biomarkers for neuromuscular clinical research. Pharmaceutical, veterinary and hygienic products; chemical preparations for medical and pharmaceutical use or for veterinary use; biological preparations for medical and pharmaceutical use or for veterinary use; enzyme preparations for medical and pharmaceutical use or for veterinary use; microorganism cultures for medical and pharmaceutical use or for veterinary use; culture media for bacteriology; nutritional substances for microorganisms; preparations of micro-organisms, of genetically modified organisms and of cells for medical and pharmaceutical use or for veterinary use, particularly for gene therapy and cell therapy; compounds acting on genetic or other pathologies, in human beings and animals, particularly on muscle and neuromuscular diseases, diseases of the immune system, cardiovascular diseases, dermatological diseases, diseases of the central and peripheral nervous system, cancers, asthma, allergies, lipid disorders, obesity and diabetes and infectious diseases; kits for preparing cells or for selecting biologically active compounds; diagnostic products for medical or veterinary use; diagnostic reagents for medical or veterinary use; diagnostic reagents for in-vitro use in biochemistry, clinical chemistry and microbiology; hygienic products for medical use. Scientific and research apparatus and instruments; apparatus and instruments for recording, transmitting, reproducing or processing sound, images or data; patient databases (electronic); software; mobile applications; downloadable Software as a Medical Device [SaMD]; downloadable computer programs; computer platforms in the form of recorded or downloadable software. Surgical, medical apparatus and instruments; testing apparatus for medical use; diagnostic apparatus for medical use; cell culture instruments for medical use; surgical, medical apparatus and instruments intended for use in gene therapy and cell therapy; medical devices for neuromuscular clinical research. Business management assistance; commercial business appraisals; business management and organization consultancy; business management consultancy; business expertise; business information; business inquiries; commercial administration of the licensing of third-party goods and services; commercial or industrial company management assistance; advice on development strategy for scientific and technological projects (business management assistance); administrative management of contracts relating to research; price comparison services; compilation of statistics; collection of data in a central file; systematization of data in a central file; computer file management; market research and studies; organization of fairs, exhibitions, trade fairs and job fairs for commercial or advertising purposes; searching for industrial or commercial partners; economic forecasting; sales promotion for third parties; advertising; commercial administration, commercial management advisory services, marketing advisory services, commercial strategy advisory services, business management advisory services, as well as office functions for the development and innovation of businesses in the health sector; commercial feasibility studies, business appraisals, marketing studies, accounting, economic forecasting, and searching for sponsors to implement development plans for companies in the health sector; computerized file management for streamlining the business branches of companies in the health sector; administrative and commercial management and creation of services enabling the organization of networks and matching partners and/or service providers in areas of technological, innovation expertise, financing various projects; database management; compilation of information in computer databases; advisory and consultancy services relating to company development; advice and assistance to companies, particularly in the context of a program for the selection, coaching and acceleration of projects; sponsorship search; company audits (commercial analyses). Providing financing for inventions; financing services in the field of health; financial analysis; financial appraisal; providing financial information; administration and management of grants for medical research; providing financial subsidies; providing project grants for health awareness projects; financial investments; investment research; advice with respect to financing and investment; fundraising services; raising or investing capital; fund investment; searching for financial partners. Education; training; entertainment; sporting and cultural activities; information relating to entertainment or education; publication of books; organization of competitions (education or entertainment); organization of exhibitions for cultural or educational purposes; electronic publication of books and journals online; electronic desktop publishing; organizing and conducting training workshops, colloquiums, conferences, congresses, seminars, symposiums for cultural or educational purposes; planning of receptions (entertainment); drafting and publication of texts other than advertising texts; publishing the results of clinical trials conducted on patients and scientific articles in relation to clinical and genetic diseases; providing non-downloadable electronic publications from a global computer network or the Internet; publishing services for magazines in paper and in electronic form. Evaluations, assessments and research in the fields of science and technology provided by engineers; appraisals and assessments in the field of medical research; research in the medical field; industrial analysis and research services in the health sector; research and development of new products (for others); technical project studies; scientific research for medical purposes; clinical trials; medical research laboratory services; biological, bacteriological, gene and cell therapy, chemical and genetic research; programming of software for Internet platforms; hosting of platforms on the Internet; development of databases; providing imaging and physiology platforms; research and development of pharmaceutical, veterinary and sanitary products for third parties; sorting and selection of molecules; developing and validating biological tests, cell tests, genetic tests and immunological tests; fundamental and applied research in the scientific, technological or industrial field; technical research; activities in functional genomics for identifying, characterizing, validating or developing biologically active molecules; technical project study; professional consultancy unrelated to business operations in the field of scientific research and therapies. Medical and surgical services; medical and surgical diagnosis; medical testing; hygienic and beauty care for human beings; health services; advice with respect to health; medical assistance; hospital services; nursing homes; convalescence or rest homes; consultation with respect to pharmacy; provision of information in the pharmaceutical field; medical imaging services; human tissue bank services; behavioral analysis for medical purposes; providing medical information; conducting medical examinations; medical consultation services; medical testing for the diagnosis and treatment of persons; genetic testing services for medical purposes; telemedicine services; therapeutic services.

Abstract

The invention relates to a peptide-modified AAV capsid with improved tropism, in particular increased muscle tropism and/or reduced liver tropism. The invention relates also to the derived recombinant AAV vector particle packaging a gene of interest, and its use in gene therapy, in particular for treating muscle diseases.

IPC Classes  ?

• C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
• C12N 15/86 - Viral vectors

Abstract

The present invention is directed to a therapeutic agent for use in the treatment of a disease associated with gain-of-function of androgen receptor (AR) and/or with overexpression of an AR coactivator, such as Kennedy disease or cancer. The therapeutic agent of the invention comprises at least one inhibitor of an androgen receptor (AR) coactivator, selected from protein arginine methyltransferase 6 (PRMT6) inhibitor, lysine specific demethylase 1 (LSD1) inhibitor, or combinations thereof.

IPC Classes  ?

• A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
• A61P 35/00 - Antineoplastic agents
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

Abstract

The invention relates to a method for predicting treatment efficiency in the research phase. The steps of the method comprise detecting at least one biological parameter in a histological section image; determining a mosaic of the image (squares or rectangles, also referred to as tiles); defining an image with smaller dimensions (also referred to as a density map) by integrating marked biological parameters in each fraction of the mosaic; applying deep learning algorithms, which are implemented, for example, by a convolutional neural network on the images generated in step c. in order to determine a proximity score for the images of treated tissues with respect to images of healthy tissues or untreated diseased tissues.

IPC Classes  ?

• G06V 10/82 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using neural networks

Abstract

The invention relates to a hybrid AAV vector comprising a transgene of interest operably linked to an hepatocyte-specific promoter, which enhances transgene expression in the liver and its use for liver-directed gene therapy.

IPC Classes  ?

• C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
• C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
• C12N 15/09 - Recombinant DNA-technology
• C12N 15/86 - Viral vectors
• C12N 15/864 - Parvoviral vectors
• A61K 35/76 - VirusesSubviral particlesBacteriophages

Abstract

The invention relates to an immune cell engineered to express a chimeric antigen receptor (CAR) which specifically binds Fibroblast Activation Protein (FAP) for use in the treatment of skeletal muscle fibrosis in muscular dystrophies.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
• C07K 14/725 - T-cell receptors
• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants
• C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 15/861 - Adenoviral vectors

Goods & Services

Pharmaceutical, veterinary and hygienic products; chemical preparations for medical and pharmaceutical use or for veterinary use; biological preparations for medical and pharmaceutical use or for veterinary use; enzyme preparations for medical and pharmaceutical use or for veterinary use; microorganism cultures for medical and pharmaceutical use or for veterinary use; culture media for bacteriology; nutritional substances for microorganisms; preparations of micro-organisms, of genetically modified organisms and of cells for medical and pharmaceutical use or for veterinary use, particularly for gene therapy and cell therapy; compounds acting on genetic or other pathologies, in human beings and animals, particularly on muscle and neuromuscular diseases, diseases of the immune system, cardiovascular diseases, dermatological diseases, diseases of the central and peripheral nervous system, cancers, asthma, allergies, lipid disorders, obesity and diabetes and infectious diseases; kits for preparing cells or for selecting biologically active compounds; diagnostic products for medical or veterinary use; diagnostic reagents for medical or veterinary use; diagnostic reagents for in-vitro use in biochemistry, clinical chemistry and microbiology; hygienic products for medical use; diagnostic biomarkers for use in neuromuscular clinical research for medical use. Scientific and research apparatus and instruments; apparatus and instruments for recording, transmitting, reproducing or processing sound, images or data; patient (electronic) database; software; mobile applications; downloadable Software as a Medical Device [SaMD]; downloadable computer programs; computer platforms in the form of recorded or downloadable software. Surgical, medical apparatus and instruments; testing apparatus for medical use; diagnostic apparatus for medical use; cell culture instruments for medical use; surgical, medical apparatus and instruments intended for use in gene therapy and cell therapy; medical devices. Business management assistance; commercial business appraisals; business management and organization consultancy; business management consultancy; business expertise; business information; business inquiries; commercial administration of the licensing of third-party goods and services; commercial or industrial company management assistance; advice on development strategy for scientific and technology projects (business management assistance); administrative management of contracts relating to research; price comparison services; establishing statistics; compilation of information into computer databases; systematization of data in a central file; computer file management; market research and studies; organization of fairs, exhibitions, trade fairs and job fairs for commercial or advertising purposes; searching for industrial or commercial partners; searching for financial partners; economic forecasting; sales promotion for others; advertising; commercial administration, commercial management advice, marketing advice, commercial strategy advice, business management advice, as well as office functions for the development and innovation of companies in the health sector; commercial feasibility studies, business appraisals, marketing studies, accounting, economic forecasting, and searching for sponsors to implement development plans for companies in the health sector; computerized file management for streamlining the business branches of companies in the health sector; administrative and commercial management and creation of services enabling the organization of networks and matching partners and/or service providers in areas of technological, innovation expertise, financing various projects; database management; compilation of information in computer databases; consultancy and advisory services with respect to company creation; advice and assistance to companies, particularly in the context of a program for the selection, coaching and acceleration of projects; sponsorship search; company audits (commercial analyses). Providing financing for inventions; financing services in the field of health; financial analysis; financial appraisal; providing financial information; administration and management of grants for medical research; providing financial subsidies; providing project grants for health awareness projects; financial investments; investment research; advice with respect to financing and investment; fundraising services; raising or investing capital; fund investment. Education; training; entertainment; sporting and cultural activities; information relating to entertainment or education; publication of books; organization of competitions (education or entertainment); organization of exhibitions for cultural or educational purposes; electronic publication of books and journals online; electronic desktop publishing; organizing and conducting training workshops, colloquiums, conferences, congresses, seminars, symposiums for cultural or educational purposes; planning of receptions (entertainment); drafting and publication of texts other than advertising texts; publishing the results of clinical trials conducted on patients and scientific articles in relation to clinical and genetic diseases; providing non-downloadable electronic publications from a global computer network or the Internet; publishing services for magazines in paper and in electronic form. Evaluations, assessments and research in the fields of science and technology provided by engineers; appraisals and assessments in the field of medical research; research in the medical field; industrial analysis and research services in the health sector; research and development of new products (for others); technical project studies; scientific research for medical purposes; clinical trials; medical research laboratory services; biological, bacteriological, gene and cell therapy, chemical and genetic research; programming of software for Internet platforms; hosting of platforms on the Internet; development of databases; providing imaging and physiology platforms; research and development of pharmaceutical, veterinary and sanitary products for third parties; sorting and selection of molecules; developing and validating biological tests, cell tests, genetic tests and immunological tests; fundamental and applied research in the scientific, technological or industrial field; technical research; activities in functional genomics for identifying, characterizing, validating or developing biologically active molecules; technical project study; professional consultancy unrelated to business operations in the field of scientific research and therapies. Medical and surgical services; medical and surgical diagnosis; medical testing; hygienic and beauty care for human beings; health service; advice with respect to health; medical assistance; hospital services; nursing homes; convalescence or rest homes; consultation with respect to pharmacy; provision of information in the pharmaceutical field; medical imaging services; human tissue bank services; behavioral analysis for medical purposes; providing medical information; conducting medical examinations; medical consultation services; medical testing for the diagnosis and treatment of persons; genetic testing services for medical purposes; telemedicine services; therapeutic services.

Abstract

The present invention relates to variants of lysosomal acid lipase (LAL) and uses thereof.

IPC Classes  ?

• C12N 9/20 - Triglyceride splitting, e.g. by means of lipase
• A61P 3/00 - Drugs for disorders of the metabolism
• C12N 5/0789 - Stem cellsMultipotent progenitor cells
• C12N 15/86 - Viral vectors

Abstract

The invention relates to a nucleic acid sequence useful in the treatment of hyperbilirubinemia, in particular in the treatment of Crigler-Najjar syndrome. More particularly, the nucleic acid sequence of the present invention is a codon-optimized UGT1A1 coding sequence.

IPC Classes  ?

• A61K 38/45 - Transferases (2)
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 9/10 - Transferases (2.)
• C12N 15/86 - Viral vectors
• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof

IPC Classes  ?

• C12N 9/10 - Transferases (2.)
• C12N 9/44 - Hydrolases (3.) acting on glycosyl compounds (3.2) acting on alpha-1, 6-glucosidic bonds, e.g. isoamylase, pullulanase

IPC Classes  ?

• C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
• C12N 15/86 - Viral vectors

Abstract

The present invention relates to a functional N-terminal truncated GDE polypeptide for the treatment of glycogen storage disease III.

IPC Classes  ?

• C12N 9/10 - Transferases (2.)
• C12N 9/44 - Hydrolases (3.) acting on glycosyl compounds (3.2) acting on alpha-1, 6-glucosidic bonds, e.g. isoamylase, pullulanase
• A61K 38/00 - Medicinal preparations containing peptides

Abstract

The invention relates to a peptide-modified AAV capsid having an increased muscle transduction efficiency. The invention relates also to the derived recombinant AAV vector particle packaging a gene of interest, and its use in gene therapy, in particular for treating muscle diseases.

IPC Classes  ?

• C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
• C12N 15/86 - Viral vectors

Goods & Services

(1) Produits pharmaceutiques, vétérinaires et hygiéniques; préparations chimiques à usage médical, pharmaceutique ou à usage vétérinaire; préparations biologiques à usage médical, pharmaceutique ou à usage vétérinaire; préparations enzymatiques à usage médical, pharmaceutique ou à usage vétérinaire; cultures de micro-organismes à usage médical, pharmaceutique ou vétérinaire; bouillons de culture pour la bactériologie; substances nutritives pour micro-organismes; préparations de micro-organismes, d'organismes génétiquement modifiées et de cellules à usage médical, pharmaceutique ou à usage vétérinaire, en particulier pour la thérapie génique et la thérapie cellulaire; composés actifs sur les pathologies génétiques ou non, des êtres humains et des animaux, notamment sur les maladies musculaires, neuromusculaires, du système immunitaire, cardio-vasculaires, les maladies dermatologiques, les maladies du système nerveux central et périphérique, les cancers, l'asthme, les allergies, les désordres lipidiques, l'obésité et le diabète, les maladies infectieuses; kits pour la préparation de cellules ou pour la sélection de composés biologiquement actifs; produits pour le diagnostic à usage médical ou vétérinaire; réactifs pour le diagnostic à usage médical ou vétérinaire; réactifs pour le diagnostic pour un usage in vitro en biochimie, chimie clinique et en microbiologie; produits hygiéniques à usage médical; biomarqueurs de diagnostic pour la recherche clinique neuromusculaire à usage médical. (2) Appareils et instruments scientifiques, de recherche; appareils et instruments pour l'enregistrement, la transmission, la reproduction ou le traitement de sons, d'images ou de données; base de données (électronique) de patients; logiciels; applications mobiles; logiciels en tant que dispositifs médicaux [SaMD] téléchargeables; programmes informatiques téléchargeables; plateformes informatiques sous forme de logiciels enregistrés ou téléchargeables. (3) Appareils et instruments chirurgicaux, médicaux; appareils pour l'analyse à usage médical; appareils pour le diagnostic à usage médical; instruments de culture cellulaire à usage médical; appareils et instruments chirurgicaux, médicaux destinés à la thérapie génique et la thérapie cellulaire; dispositifs médicaux. (1) Aide à la direction des affaires; estimations en affaires commerciales; conseils en organisation et direction des affaires; consultations pour la direction des affaires; expertises en affaires; informations d'affaires; renseignements d'affaires; administration commerciale de licences de produits et de services de tiers; aide à la direction d'entreprises industrielles ou commerciales; conseil en stratégie de développement de projets scientifiques et technologie (aide à la direction des affaires); gestion administrative de contrats en lien avec la recherche; services de comparaison de prix; établissement de statistiques; recueils de données dans un fichier central; systématisation de données dans un fichier central; gestion de fichiers informatiques; études et recherches de marchés; organisation de salons, d'expositions, de foires à buts commerciaux ou de publicité; recherche de partenaires industriels ou commerciaux; recherche de partenaires financiers; prévisions économiques; promotions des ventes pour des tiers; publicité; administration commerciale, prestations de conseils en gestion commerciale, prestations de conseils en marketing, prestations de conseil en stratégie commerciale, prestations de conseils en direction des affaires, ainsi que travaux de bureau pour le développement et l'innovation des entreprises dans le secteur de la santé; étude de faisabilité commerciale, estimation d'affaire, étude de marché, comptabilité, prévisions économiques, et recherche de parraineurs pour la réalisation de plans de développement à destination des entreprises du secteur de la santé; gestion de fichiers informatiques pour la rationalisation des branches d'activité des entreprises du secteur de la santé; services de gestion et de création administrative et commerciale de prestations permettant l'organisation de réseaux et de mise en contact de partenaires et/ou prestataires sur des pôles de compétences technologiques, d'innovation, de financement de projets divers; gestion de bases de données; services de compilation de données dans des bases de données informatiques; services de consultations et de conseils en matière de création d'entreprise; services de conseils et d'aide aux entreprises, notamment dans le cadre d'un programme de sélection, d'accompagnement et d'accélération de projets; recherche de parraineurs; audits d'entreprises (analyses commerciales). (2) Mise à disposition de financement pour des inventions; services de financement dans le domaine de la santé; analyse financière; estimation financière; mise à disposition d'informations financières; administration et gestion de subventions pour la recherche médicale; mise à disposition de subventions financières; mise à disposition de subventions de projets dans le cadre de projets de sensibilisation aux questions de santé; investissements financiers; recherche en investissement; conseils en matière de financement et d'investissement; collectes de fonds; constitution ou investissement de capitaux; placement de fonds. (3) Éducation; formation; divertissement; activités sportives et culturelles; informations en matière de divertissement ou d'éducation; publication de livres; organisation de concours (éducation ou divertissement); organisation d'expositions à buts culturels ou éducatifs; publication électronique de livres et de périodiques en ligne; micro-édition; organisation et conduite d'ateliers de formation, de colloques, de conférences, de congrès, de séminaires, de symposiums à des fins culturelles ou éducatives; planification de réceptions (divertissement); rédaction et publication de textes autres que textes publicitaires; publication de résultats d'essais cliniques réalisés sur des malades et d'articles scientifiques en rapport avec les maladies cliniques et génétiques; mise à disposition de publications électroniques, non téléchargeables, à partir d'un réseau informatique mondial ou d'Internet; services de publication de magazines papiers et sous forme électronique. (4) Evaluations, estimations et recherches dans les domaines scientifique et technologique rendues par des ingénieurs; évaluations et estimations dans le domaine de la recherche médicale; recherches dans le domaine médical; services d'analyse et de recherches industrielles dans le secteur de la santé; recherche et développement de nouveaux produits (pour des tiers); études de projets techniques; recherches scientifiques à but médical; essais cliniques; services de laboratoire de recherche médicale; recherches biologiques, en bactériologie, en thérapie génique et cellulaire, en chimie et en génétique; programmation de logiciels pour des plateformes Internet; hébergement de plateformes sur Internet; développement de bases de données; mise à disposition de plateformes d'imagerie et de physiologie; services de recherche et développement de produits pharmaceutiques, vétérinaires et hygiéniques pour des tiers; triage et sélection de molécules; développement et validation de tests biologiques, de tests cellulaires, de tests génétiques et de tests immunologiques; recherche fondamentale et appliquée dans le domaine scientifique, technologique ou industrielle; recherches techniques; activités de génomique fonctionnelle, pour identifier, caractériser, valider ou développer des molécules biologiquement actives; étude de projets techniques; consultations professionnelles sans rapport avec la conduite des affaires dans le domaine de la recherche scientifique et des thérapies. (5) Services médicaux et chirurgicaux; diagnostic médical et chirurgical; tests médicaux; soins d'hygiène et de beauté pour êtres humains; service de santé; conseils en matière de santé; assistance médicale; services hospitaliers; maisons médicalisées; maisons de convalescence ou de repos; consultation en matière de pharmacie; mise à disposition d'informations dans le domaine pharmaceutique; services d'imagerie médicale; services de banques de tissus humains; analyses comportementales à des fins médicales; mise à disposition d'informations médicales; réalisation d'examens médicaux; services de consultations médicales; analyses médicales pour le diagnostic et le traitement de personnes; services de dépistage génétique à des fins médicales; services de télémédecine; services thérapeutiques.

Goods & Services

Pharmaceutical, veterinary products, namely gene and cell therapy products for the treatment of diseases; chemical preparations for medical and pharmaceutical use or for veterinary use, namely gene and cell therapy products for the treatment of diseases; biological preparations for medical and pharmaceutical use or for veterinary use, namely gene and cell therapy products for the treatment of diseases; enzyme preparations for medical and pharmaceutical use or for veterinary use, namely gene and cell therapy products for the treatment of diseases; microorganism cultures for medical and pharmaceutical use or for veterinary use; culture media for bacteriology; nutritional substances for microorganisms; preparations of micro-organisms, of genetically modified organisms and of cells for medical and pharmaceutical use or for veterinary use, particularly for gene therapy and cell therapy; compounds acting on genetic or other pathologies, in human beings and animals, particularly on muscle and neuromuscular diseases, diseases of the immune system, cardiovascular diseases, dermatological diseases, diseases of the central and peripheral nervous system, cancers, asthma, allergies, lipid disorders, obesity and diabetes and infectious diseases; kits for preparing cells or for selecting biologically active compounds; diagnostic products for medical or veterinary use; diagnostic reagents for medical or veterinary use; diagnostic reagents for in-vitro use in biochemistry, clinical chemistry and microbiology; diagnostic biomarkers for use in neuromuscular clinical research for medical use Patient (electronic) database; downloadable Software for artificial intelligence and machine learning software; downloadable mobile applications for artificial intelligence and machine learning software; downloadable Software as a Medical Device [SaMD]; downloadable computer programs for artificial intelligence and machine learning software; Computer platforms in the form of recorded or downloadable software for artificial intelligence and machine learning software Surgical, medical apparatus and instruments for medical use; testing apparatus for medical use for the diagnosis and/or follow-up the evolution of diseases namely genetic diseases; Diagnostic apparatus for medical use for the diagnosis and/or follow-up the evolution of diseases namely genetic diseases; cell culture instruments for medical use; surgical, medical apparatus and instruments intended for use in gene therapy and cell therapy; medical devices Business management assistance; commercial business appraisals; business management and organization consultancy; business management consultancy; Business expertise, in particular for start-up creation, mentoring programs; business information; business inquiries; commercial administration of the licensing of third-party goods and services; commercial or industrial company management assistance; advice on development strategy for scientific and technology projects (business management assistance); administrative management of contracts relating to research; price comparison services; establishing statistics; compilation of information into computer databases; systematization of data in a central file; computer file management; market research and studies; organization of fairs, exhibitions, trade fairs and job fairs for commercial or advertising purposes; searching for industrial or commercial partners; searching for financial partners; economic forecasting; sales promotion for others; advertising; commercial administration, commercial management advice, marketing advice, commercial strategy advice, business management advice, as well as office functions for the development and innovation of companies in the health sector; commercial feasibility studies, business appraisals, marketing studies, accounting, economic forecasting, and searching for sponsors to implement development plans for companies in the health sector; computerized file management for streamlining the business branches of companies in the health sector; administrative and commercial management and creation of services enabling the organization of networks and matching partners and/or service providers in areas of technological, innovation expertise, financing various projects; database management; compilation of information in computer databases; consultancy and advisory services with respect to company creation; advice and assistance to companies, particularly in the context of a program for the selection, coaching and acceleration of projects; sponsorship search; company audits (commercial analyses) Providing financing for inventions through, in particular, public financing ; financing services in the field of health; financial analysis; Financing appraisal through monitoring of use of public financing; providing financial information; administration and management of grants for medical research; providing financial subsidies; providing project grants for health awareness projects; financial investments; Investment research through, in particular, public financing; advice with respect to financing and investment; fundraising services; raising or investing capital; fund investment Education in the nature of digital training platforms, development of training digital content, photography and video for education purposes; training in the nature of organization of exhibitions for educational purposes, arranging and conducting of conferences, congresses and symposiums, publication of content; information relating to entertainment or education; publication of books; organization of competitions (education or entertainment); organization of exhibitions for cultural or educational purposes; electronic publication of books and journals online; electronic desktop publishing; organizing and conducting training workshops, colloquiums, conferences, congresses, seminars, symposiums for cultural or educational purposes; planning of receptions (entertainment); drafting and publication of texts other than advertising texts; publishing the results of clinical trials conducted on patients and scientific articles in relation to clinical and genetic diseases; providing non-downloadable electronic publications from a global computer network or the Internet; publishing services for magazines in paper and in electronic form Evaluations, assessments and research in the fields of science and technology provided by engineers; appraisals and assessments in the field of medical research; research in the medical field; industrial analysis and research services in the health sector; research and development of new products (for others); technical project studies; scientific research for medical purposes; clinical trials; medical research laboratory services; biological, bacteriological, gene and cell therapy, chemical and genetic research; programming of software for Internet platforms; hosting of platforms on the Internet; development of databases; providing imaging and physiology platforms; research and development of pharmaceutical, veterinary and sanitary products for third parties; sorting and selection of molecules; developing and validating biological tests, cell tests, genetic tests and immunological tests; fundamental and applied research in the scientific, technological or industrial field; technical research; activities in functional genomics for identifying, characterizing, validating or developing biologically active molecules; technical project study; professional consultancy unrelated to business operations in the field of scientific research and therapies Medical and surgical services; medical and surgical diagnosis; medical testing; hygienic and beauty care for human beings; health service; advice with respect to health; medical assistance; hospital services; nursing homes; convalescence or rest homes; consultation with respect to pharmacy; provision of information in the pharmaceutical field; medical imaging services; human tissue bank services; behavioral analysis for medical purposes; providing medical information; conducting medical examinations; medical consultation services; medical testing for the diagnosis and treatment of persons; genetic testing services for medical purposes; telemedicine services

Abstract

The present invention relates to compositions and methods for the delivery of therapeutic proteins to the CNS using recombinant AAV vectors. More specifically, the invention relates to compositions and methods for delivering proteins into the cerebrospinal fluid of mammalian subjects through peripheral administration of AAV vectors. The invention may be used to treat various disorders of the central nervous system, including degenerative diseases and motor neuron diseases.

IPC Classes  ?

• C12N 15/86 - Viral vectors
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

The present invention relates to the combination of a proteasome inhibitor and a histone deacetylase (HDAC) inhibitor and its use for the treatment of a genetic disease linked to a conformational disorder of at least one protein, said disorder causing the proteasome degradation of the protein.

IPC Classes  ?

• A61K 31/4965 - Non-condensed pyrazines
• A61K 38/06 - Tripeptides
• A61K 31/5355 - Non-condensed oxazines containing further heterocyclic rings
• A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• A61K 31/18 - Sulfonamides
• A61K 31/422 - Oxazoles not condensed and containing further heterocyclic rings
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

The present invention concerns synthetic polynucleotides encoding a human fukutin-related protein (FKRP) wherein the synthetic polynucleotides contain at least a mutation avoiding supplementary transcript(s) generated from frameshift start codon(s). The synthetic polynucleotides are useful, especially for treating a pathology linked to a FKRP deficiency or induced by a defect in α-dystroglycan (α-DG) glycosylation, such as LGMD2I.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C12N 15/86 - Viral vectors

Abstract

The present invention relates to a functional C-terminal truncated GDE polypeptide for the treatment of glycogen storage disease III.

IPC Classes  ?

• C12N 9/10 - Transferases (2.)
• C12N 15/86 - Viral vectors
• A61P 3/00 - Drugs for disorders of the metabolism

Abstract

The invention relates to the use of bazedoxifene as representing third-generation SERM, namely compounds comprising a 2-phenylindole group, for increasing muscle survival, in particular in the treatment of dysferlinopathies.

IPC Classes  ?

• A61K 31/404 - Indoles, e.g. pindolol
• A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
• A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system

Abstract

The present invention concerns a novel short promoter characterized by a high activity in the skeletal muscles and a low activity in the heart. It then constitutes a valuable candidate especially for driving the expression of transgenes encoding proteins useful for the treatment of muscular dystrophies.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 15/86 - Viral vectors
• C12N 9/64 - Proteinases derived from animal tissue, e.g. rennin
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system

Abstract

The invention relates to the treatment of dilated cardiomyopathies, in particular genetic dilated cardiomyopathies, using non-expressible inhibitors of the WNT pathway or TGF-β pathway, alone or in combination.

IPC Classes  ?

• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
• A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
• A61P 9/00 - Drugs for disorders of the cardiovascular system

Abstract

The invention relates to a composition for enhancing utrophin expression in cell by inducing mutations within a target sequence comprising a utrophin repressor binding site using a gene editing enzyme and the use thereof for the treatment of a dy-strophinopathy.

IPC Classes  ?

• C12N 15/90 - Stable introduction of foreign DNA into chromosome
• C12N 15/11 - DNA or RNA fragmentsModified forms thereof
• C12N 9/22 - Ribonucleases
• C12N 5/077 - Mesenchymal cells, e.g. bone cells, cartilage cells, marrow stromal cells, fat cells or muscle cells

Abstract

The present invention concerns an expression system for systemic administration comprising a sequence encoding a FKRP protein, and: a promoter sequence allowing the expression at a therapeutically acceptable level of FKRP in the skeletal muscles and a target sequence of an miRNA expressed in the heart; or a promoter sequence allowing the expression at a therapeutically acceptable level of FKRP in the skeletal muscles and presenting a promoter activity at a toxically acceptable level in the heart; and its use for the treatment of various diseases linked to FKRP deficiencies.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system

Abstract

The invention relates to the treatment of genetic dilated cardiomyopathies using expressible modulators of the Wnt pathway or TGF-β pathway, preferably using gene transfer.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• C12N 15/86 - Viral vectors

Abstract

The present invention concerns an expression system for systemic administration comprising a sequence encoding gamma-sarcoglycan (SGCG) placed under the control of a promoter allowing an adequate expression of SGCG in the skeletal muscles and in the heart, and its use for the treatment of Limb-Girdle Muscular Dystrophy type C.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy

Abstract

The present invention relates to the treatment of dilated cardiomyopathies, in particular to the use of an activator of NRF2.

IPC Classes  ?

• C12N 15/86 - Viral vectors
• A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans

Abstract

The invention relates to a method of preparation of a recombinant hybrid adeno-associated virus (AAV) capsid protein with improved tropism and to the recombinant hybrid AAV capsid protein obtainable by the method. The invention relates also to the derived expression vector, modified cell, and hybrid capsid AAV vector particle packaging a gene of interest, and its use in tissue-targeted gene therapy for treating various diseases.

IPC Classes  ?

• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12N 15/86 - Viral vectors

Abstract

The present disclosure relates to the treatment of dilated cardiomyopathies, in particular to 5 the use of an inhibitor of CILP-1.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contractionDrugs for heart failure
• C12N 15/86 - Viral vectors

Abstract

The invention relates to an adeno-associated virus (AAV) vector comprising a nucleic acid construct for the expression of a glucose-6-phosphatase-a (G6Pase-a) in a cell, the construct comprising a nucleic acid sequence encoding the G6Pase-a, wherein the nucleic acid sequence encoding the G6Pase-a is operably linked to a human alpha-1 antitrypsin (hAAT) promoter, a cell transformed with the vector of the invention, a composition comprising the vector or the cell of the invention, and the use thereof.

IPC Classes  ?

• C12N 15/86 - Viral vectors
• C07K 14/81 - Protease inhibitors
• C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)

Abstract

The present invention relates to a method for obtaining stable pseudotyped lentiviral particles including a heterologous gene of interest, comprising the following steps: a) transfecting at least one plasmid in appropriate cell lines, wherein said at least one plasmid comprises the gene of interest, the rev, gag and pol genes, and a sequence coding for an ERV syncytin, wherein the rev, gag and pol genes are retroviral genes; b) incubating the transfected cells obtained in a), so that they produce the stable pseudotyped lentiviral particles in the supernatant; and c) harvesting and concentrating the stable lentiviral particles obtained in b). The present invention relates to a method for obtaining stable pseudotyped lentiviral particles including a heterologous gene of interest, comprising the following steps: a) transfecting at least one plasmid in appropriate cell lines, wherein said at least one plasmid comprises the gene of interest, the rev, gag and pol genes, and a sequence coding for an ERV syncytin, wherein the rev, gag and pol genes are retroviral genes; b) incubating the transfected cells obtained in a), so that they produce the stable pseudotyped lentiviral particles in the supernatant; and c) harvesting and concentrating the stable lentiviral particles obtained in b). The present invention also relates to a method to transduce immune cells using lentiviral vectors pseudotyped with an ERV syncytin glycoprotein. The method can be performed on non-stimulated blood cells or on cells stimulated briefly with IL7, and the cells can be expanded. The present invention relates to a method for obtaining stable pseudotyped lentiviral particles including a heterologous gene of interest, comprising the following steps: a) transfecting at least one plasmid in appropriate cell lines, wherein said at least one plasmid comprises the gene of interest, the rev, gag and pol genes, and a sequence coding for an ERV syncytin, wherein the rev, gag and pol genes are retroviral genes; b) incubating the transfected cells obtained in a), so that they produce the stable pseudotyped lentiviral particles in the supernatant; and c) harvesting and concentrating the stable lentiviral particles obtained in b). The present invention also relates to a method to transduce immune cells using lentiviral vectors pseudotyped with an ERV syncytin glycoprotein. The method can be performed on non-stimulated blood cells or on cells stimulated briefly with IL7, and the cells can be expanded. The stable pseudotyped lentiviral particles obtained are particularly useful in gene therapy.

IPC Classes  ?

• C12N 15/86 - Viral vectors
• A61K 35/76 - VirusesSubviral particlesBacteriophages
• C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
• C12N 5/0781 - B cellsProgenitors thereof
• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes

Abstract

Despite the eye's immune-privileged status, a secondary loss of vision in some patients treated with AAV led the inventors to question the immunogenicity of AAV vectors after a subretinal injection. The inventors thus characterized anti-transgene and anti-capsid immune responses induced in the periphery after the subretinal AAV injection. Different doses of AAV8 encoding reporter proteins fused with the HY male antigen were injected at day 0 into the subretinal space of adult immunocompetent C57BL/6 female mice. Subretinal AAV injection induced a dose-dependent proinflammatory immune response to the transgene product, correlated with local transgene expression. In order to trigger a subretinal-associated immune inhibition (SRAII) mechanism, some mice were co-injected subretinally at day 0 with AAV and HY peptides. Interestingly, this subretinal co-injection of AAV8 with peptides of the transgene product modulated the anti-transgene T-cell immune response, even at high dose of vector (5.1010 vg). This immunodulation was also confirmed in a pathophysiological murine model of retinal degeneration. The inventors also demonstrated that injection of AAV8 in the subretinal space induces proinflammatory peripheral immune responses to the transgene and the capsid that could be counteracted y co-injection with transgene peptides. Accordingly, the object of the present invention is to provide methods for preventing induction of immune responses to the transgene product and the AAV capsid after ocular gene therapy.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61K 38/16 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
• A61P 27/02 - Ophthalmic agents

Abstract

The present invention relates to a gene expression construct comprising an expression cassette containing a transgene encoding a gamma-sarcoglycan protein and modified ITR sequences, said transgene encoding the gamma-sarcoglycan protein consisting of the sequence of SEQ ID NO: 3 or a functional variant thereof having a polynucleotide sequence that is at least 80% identical to SEQ ID NO: 3; said modified ITR sequences consisting of - a modified 5'-ITR sequence of SEQ ID NO: 1; and - a modified 3'-ITR sequence of SEQ ID NO: 2. The invention also relates to a recombinant vector comprising the gene expression construct of the invention, said gene expression construct or recombinant vector can be included in a gene therapy and used as a medicament, in particular for the treatment of limb girdle muscular dystrophy by sarcoglycanopathy.

IPC Classes  ?

• C12N 15/86 - Viral vectors
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals

Abstract

The present invention relates to a gene expression construct comprising an expression cassette containing a transgene encoding a calpain-3 protein and modified ITR sequences, said transgene encoding the calpain-3 protein consisting of the sequence of SEQ ID NO: 4 or a functional variant thereof having a polynucleotide sequence that is at least 80% identical to SEQ ID NO: 4; said modified ITR sequences consisting of - a modified 5'-ITR sequence of SEQ ID NO: 1; and - a modified 3'-ITR sequence of SEQ ID NO: 2 or SEQ ID NO: 3. The invention also relates to a recombinant vector comprising the gene expression construct of the invention, said gene expression construct or recombinant vector can be included in a gene therapy and used as a medicament, in particular for the treatment of limb girdle muscular dystrophy by calpainopathy.

IPC Classes  ?

• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals

Abstract

The present invention relates to vectors and compositions for the treatment of glycogen storage disease III.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 3/08 - Drugs for disorders of the metabolism for glucose homeostasis
• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
• C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)

Abstract

The present invention relates to a gene expression construct comprising an expression cassette containing a transgene encoding an alpha-sarcoglycan protein and modified ITR sequences, said transgene encoding the alpha-sarcoglycan protein consisting of the sequence of SEQ ID NO: 3 or a functional variant thereof having a polynucleotide sequence that is at least 80% identical to SEQ ID NO: 3; said modified ITR sequences consisting of - a modified 5'-ITR sequence of SEQ ID NO: 1; and - a modified 3'-ITR sequence of SEQ ID NO: 2. The invention also relates to a recombinant vector comprising the gene expression construct of the invention, said gene expression construct or recombinant vector can be included in a gene therapy and used as a medicament, in particular for the treatment of limb girdle muscular dystrophy by sarcoglycanopathy.

IPC Classes  ?

• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals

Abstract

The present invention relates to a gene expression construct comprising an expression cassette containing a transgene encoding a fukutin related protein and modified ITR sequences, said transgene encoding the fukutin related protein consisting of the sequence of SEQ ID NO: 3 or a functional variant thereof having a polynucleotide sequence that is at least 80% identical to SEQ ID NO: 3; said modified ITR sequences consisting of - a modified 5'-ITR sequence of SEQ ID NO: 1; and - a modified 3'-ITR sequence of SEQ ID NO: 2. The invention also relates to a recombinant vector comprising the gene expression construct of the invention, said gene expression construct or recombinant vector can be included in a gene therapy and used as a medicament, in particular for the treatment of limb girdle muscular dystrophy with FKRP deficiency.

IPC Classes  ?

• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals

Abstract

The invention relates to the use of a recombinant porcine adeno-associated virus (AAV) vector comprising a peptide-modified porcine AAV serotype 1 (AAVpol) capsid in gene therapy of muscle and/or central nervous system (CNS) disorders, in particular neuromuscular diseases such as genetic neuromuscular diseases.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system

Abstract

The present invention relates to a vector comprising an ASAH1 open reading frame, for use in the treatment of acid ceramidase deficiency.

IPC Classes  ?

• C12N 15/86 - Viral vectors
• A61P 3/00 - Drugs for disorders of the metabolism
• A61K 38/50 - Hydrolases (3) acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase

Abstract

Disclosed herein are methods for treating patients that may develop or already have pre-existing gene therapy neutralizing antibodies by administering a protease that cleaves peptide bonds present in immunoglobulins or by administering a glycosidase that cleaves carbohydrate residues present on immunoglobulins, or other similar enzymatic cleavage of immunoglobulins in vivo. Also disclosed are methods for utilizing IdeS and other immunoglobulin G-degrading enzyme polypeptides for gene therapy treatment of a disease in a patient in need thereof.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 9/24 - Hydrolases (3.) acting on glycosyl compounds (3.2)
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12N 15/86 - Viral vectors
• A61K 38/48 - Hydrolases (3) acting on peptide bonds (3.4)
• C12N 9/64 - Proteinases derived from animal tissue, e.g. rennin
• C12N 15/861 - Adenoviral vectors

Abstract

The present invention relates to peptides and compositions for use in improving transduction efficiency of viruses into target cells.

IPC Classes  ?

• C12N 15/87 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
• C12N 15/86 - Viral vectors
• C07K 14/82 - Translation products from oncogenes
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals

Abstract

The present invention relates to novel hybrid promoters. The invention further relates to expression cassettes and vectors containing said hybrid promoters. Also disclosed herein are methods implementing these hybrid promoters, in particular methods of gene therapy.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
• C12N 15/86 - Viral vectors
• C12N 15/864 - Parvoviral vectors

Abstract

The present invention relates to novel hybrid promoters. The invention further relates to expression cassettes and vectors containing said hybrid promoters. Also disclosed herein are methods implementing these hybrid promoters, in particular methods of gene therapy.

IPC Classes  ?

• C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 15/86 - Viral vectors

Abstract

The present invention relates to a method for producing a recombinant viral vector from hairy roots of a plant, in particular from hairy roots of a plant belonging to the Brassicaceae family. The invention also relates to a transgenic plant, a hairy root culture and a recombinant viral vector obtainable by the method of the invention.

IPC Classes  ?

• C12N 15/82 - Vectors or expression systems specially adapted for eukaryotic hosts for plant cells
• C12N 15/86 - Viral vectors

Abstract

The present invention relates to a nucleic acid molecule encoding a chimeric polypeptide comprising a peptide of interest fused to one or more heterologous moieties, wherein at least one of the heterologous moieties is a ligand of the Sortilin receptor. The invention also relates to a chimeric polypeptide encoded by said nucleic acid molecule and uses thereof.

IPC Classes  ?

• C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
• C12N 15/86 - Viral vectors
• A61P 3/00 - Drugs for disorders of the metabolism

Abstract

The invention relates to a kit of parts comprising (i) pharmacological chaperones or a pharmaceutically acceptable salt thereof and (ii) a therapeutic acid-alpha glucosidase (GAA) polypeptide or a nucleic acid molecule encoding a therapeutic GAA polypeptide, wherein said pharmacological chaperones are 1-deoxynojirimycin (DNJ) or a derivative thereof and ambroxol (ABX) or a derivative thereof.

IPC Classes  ?

• A61K 38/47 - Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• A61K 31/44 - Non-condensed pyridinesHydrogenated derivatives thereof
• A61K 31/137 - Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine
• A61P 3/00 - Drugs for disorders of the metabolism

Abstract

Adeno-associated virus (AAV) is a defective mono-stranded DNA virus, endemic in human population (35-80%). Recurrent clonal AAV2 insertions are associated with the pathogenesis of rare human hepatocellular carcinoma (HCC) developed on normal liver. The aimed of the inventors was to characterize the natural history of AAV infection in the liver. Viral DNA was thus quantified in tumor and non-tumor liver tissues of 1461 patients. Presence of episomal form and viral mRNA expression were analyzed using a DNAse/TaqMan based assay and quantitative RT-PCR. In silico analyses using viral capture data explored viral variants and new clonal insertions. AAV DNA was detected in 21% of the patients equally distributed in 2 major viral subtypes: one similar to AAV2, the other hybrid between AAV2 and AAV13 sequences. Thus the inventors provided an integrated analysis of the wild type AAV infection in the liver with the identification of viral genotypes, molecular forms, helper virus relationship and viral integrations. These findings are important to understand wild type AAV biology and particularly relevant considering the large usage of AAV vector in liver-targeted gene therapy. Thus, the present invention relates to new adeno-associated virus (AAV) variants and uses thereof for gene therapy.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
• C12N 15/86 - Viral vectors

Abstract

The present invention relates to variants of acid-alpha glucosidase and uses thereof.

IPC Classes  ?

• C12N 15/86 - Viral vectors
• A61K 35/34 - MusclesSmooth muscle cellsHeartCardiac stem cellsMyoblastsMyocytesCardiomyocytes
• A61K 35/407 - LiverHepatocytes

Abstract

The present invention relates to the industrialization of the production of recombinant lentiviral vectors in order to manufacture sufficient materials for therapeutic applications such as gene therapy and/or DNA vaccination, for use in clinical trials and/or commercial use.

IPC Classes  ?

• C12N 15/86 - Viral vectors
• C12N 7/02 - Recovery or purification
• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof

Abstract

A combination of two recombinant adeno-associated viral (rAAV) vectors comprising in the first a capsid and a cassette comprising a 5′ ITR sequence, a liver-specific promotor, a nucleic acid sequence coding for a transgene of interest useful to be tolerated by the immune system and a poly A chain and in the second a capsid and a cassette comprising a 5′ ITR sequence, a promotor specific for a tissue of interest, a nucleic acid sequence corresponding to the nucleic acid sequence inserted into the cassette of the first rAAV vector, a transmembrane sequence, a poly A chain, wherein the nucleic acid sequences is administered towards to the tissue of interest, is disclosed. Said combination can be used in inducing an immune tolerance to a protein product encoded, and so be used as a drug in a subject, particularly for treating muscular dystrophies. Pharmaceutical compositions, kits and methods are also disclosed.

IPC Classes  ?

• C12N 15/86 - Viral vectors
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
• A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy

Abstract

The present invention concerns a quasidystrophin (QD) having the structure CH1CH2H1R1R2R3H2R8R9 in its N-terminal part and advantageously further comprising the R16 and R17 rod domains, as well as the dual AAV vector system which allows producing it.

IPC Classes  ?

• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C12N 5/077 - Mesenchymal cells, e.g. bone cells, cartilage cells, marrow stromal cells, fat cells or muscle cells
• C12N 15/86 - Viral vectors
• A61K 35/76 - VirusesSubviral particlesBacteriophages
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system

Abstract

The present invention relates to a genetically modified hematopoietic stem cell (HSC) comprising, in at least one α-globin gene comprised in the genome thereof, at least one transgene encoding a functional β-like globin protein, the said transgene being placed under the control of the endogenous promoter of the said at least one α-globin gene.

IPC Classes  ?

• A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• C12N 5/0789 - Stem cellsMultipotent progenitor cells
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C07K 14/805 - HaemoglobinsMyoglobins

Abstract

The present invention relates to variants of lysosomal acid lipase (LAL) and uses thereof.

IPC Classes  ?

• C12N 9/20 - Triglyceride splitting, e.g. by means of lipase

Abstract

The present invention concerns a method of treating Duchenne muscular dystrophy (DMD) in a human, comprising systemically administering by intravascular injection a gene therapy product that comprises an adeno-associated viral (AAV) vector of serotype 8, which harbors a nucleic acid sequence encoding a human ΔR4-R23/ΔCT microdystrophin. Advantageously, the gene therapy product is injected up to 1E14 vg/kg.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
• C12N 15/86 - Viral vectors
• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans

Abstract

The present invention relates to variants of lysosomal acid lipase (LAL) and uses thereof.

IPC Classes  ?

• C12N 9/20 - Triglyceride splitting, e.g. by means of lipase

Abstract

The present invention relates to hybrid promoters to drive gene expression in muscles.

IPC Classes  ?

• C12N 15/86 - Viral vectors
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy

Abstract

The #β-hemoglobinopathies #β-thalassemia (BT) and sickle cell disease (SCD) are the most frequent genetic disorders worldwide. These diseases are caused by mutations causing reduced or abnormal synthesis of the β-globin chain of the adult hemoglobin (Hb) tetramer. Here, the inventors intend to improve HSC-based gene therapy for β-thalassemia and SCD by developing an innovative, highly infectious LV vector expressing a potent anti-sickling β-globin transgene and a second biological function either increasing fetal γ-globin expression (for β-thalassemia and SCD). More particularly, the inventors have designed a novel lentivirus (LV), which carry two different functions: βAS3 gene addition and gene silencing. This last strategy allows the re-expression of the fetal γ-globin genes (HBG1 and HBG2) and production of the endogenous fetal hemoglobin (HbF). Elevated levels of HbF and HbAS3 (Hb tetramer containing βAS3-globin) will benefit the β-hemoglobinopathy phenotype by increasing the total amount of β-like globin that will: (i) reduce the alpha precipitates and improve the alpha/non alpha ratio in β-thalassemia, and (ii) reduce the sickling in SCD. This combined strategy will improve the β-hemoglobinopathy phenotype at a lower vector copy number (VCN) per cell compared to a LV expressing the βAS3 alone.

IPC Classes  ?

• A61K 35/545 - Embryonic stem cellsPluripotent stem cellsInduced pluripotent stem cellsUncharacterised stem cells
• C12N 15/86 - Viral vectors
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12N 5/0735 - Embryonic stem cellsEmbryonic germ cells
• A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• A61P 7/06 - Antianaemics

Abstract

The invention relates to a composition for enhancing utrophin expression in cell by inducing mutations within a target sequence comprising a utrophin repressor binding site using a gene editing enzyme and the use thereof for the treatment of a dystrophinopathy.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12N 15/11 - DNA or RNA fragmentsModified forms thereof
• A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links

Abstract

The invention relates to a composition for enhancing utrophin expression in cell by inducing mutations within a target sequence comprising a utrophin repressor binding site using a gene editing enzyme and the use thereof for the treatment of a dystrophinopathy.

IPC Classes  ?

• A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• C12N 15/11 - DNA or RNA fragmentsModified forms thereof
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

Abstract

The invention relates to a peptide-modified AAV capsid with improved tropism, in particular increased muscle tropism and/or reduced liver tropism. The invention relates also to the derived recombinant AAV vector particle packaging a gene of interest, and its use in gene therapy, in particular for treating muscle diseases.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
• C07K 14/015 - Parvoviridae, e.g. feline panleukopenia virus, human parvovirus
• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
• C12N 15/86 - Viral vectors
• C12N 15/864 - Parvoviral vectors

Abstract

The invention relates to a peptide-modified AAV capsid with improved tropism, in particular increased muscle tropism and/or reduced liver tropism. The invention relates also to the derived recombinant AAV vector particle packaging a gene of interest, and its use in gene therapy, in particular for treating muscle diseases.

IPC Classes  ?

• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 15/864 - Parvoviral vectors
• C07K 14/015 - Parvoviridae, e.g. feline panleukopenia virus, human parvovirus
• C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
• C12N 15/86 - Viral vectors

Abstract

The present invention relates to a functional C-terminal truncated GDE polypeptide for the treatment of glycogen storage disease III.

IPC Classes  ?

• C12N 9/10 - Transferases (2.)
• C12N 9/44 - Hydrolases (3.) acting on glycosyl compounds (3.2) acting on alpha-1, 6-glucosidic bonds, e.g. isoamylase, pullulanase
• A61K 38/00 - Medicinal preparations containing peptides

Abstract

The present invention relates to a recombinant expression cassette comprising a polynucleotide encoding a SMN protein. This cassette can be included in a gene therapy vector and used in a method for the treatment of spinal muscular atrophy (SMA).

IPC Classes  ?

• C12N 15/861 - Adenoviral vectors
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy

Abstract

IPEX (Immune dysregulation Polyendocrinopathy X linked) syndrome is a primary immunodeficiency caused by mutations in the gene encoding the transcription factor forkhead box P3 (FOXP3), which leads to the loss of function of thymus-derived CD4+CD25+ regulatory T (tTreg) cells. Preclinical and clinical studies suggest that T cell gene therapy approaches designed to selectively restore the repertoire of Treg cells by transfer of wild type FOXP3 gene is a promising potential cure for IPEX. However, there is still a need for a vector that can be used efficiently for the preparation of said Treg cells. The inventors thus compared 6 different lentiviral constructs according to 4 criteria (vector titers, level of transduction of human CD4+ T cells, level of expression of FOXP3 and ΔLNGFR genes, degree of correlation between both expression) and selected one construct comprising a bidirectional PGK-EF1a promoter that showed remarkable efficiency.

IPC Classes  ?

• C12N 15/86 - Viral vectors
• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
• A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes

Abstract

The present invention concerns a novel short promoter characterized by a high activity in the skeletal muscles and a low activity in the heart. It then constitutes a valuable candidate especially for driving the expression of transgenes encoding proteins useful for the treatment of muscular dystrophies.

IPC Classes  ?

• C12N 15/86 - Viral vectors

Abstract

The present invention concerns a novel short promoter characterized by a high activity in the skeletal muscles and a low activity in the heart. It then constitutes a valuable candidate especially for driving the expression of transgenes encoding proteins useful for the treatment of muscular dystrophies.

IPC Classes  ?

• C12N 15/86 - Viral vectors

Abstract

The invention relates to a method of preparation of a recombinant hybrid adeno-associated virus (AAV) capsid protein with improved tropism and to the recombinant hybrid AAV capsid protein obtainable by the method. The invention relates also to the derived expression vector, modified cell, and hybrid capsid AAV vector particle packaging a gene of interest, and its use in tissue-targeted gene therapy for treating various diseases.

IPC Classes  ?

• C12N 15/86 - Viral vectors
• C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses

Abstract

The invention relates to a method of preparation of a recombinant hybrid adeno-associated virus (AAV) capsid protein with improved tropism and to the recombinant hybrid AAV capsid protein obtainable by the method. The invention relates also to the derived expression vector, modified cell, and hybrid capsid AAV vector particle packaging a gene of interest, and its use in tissue-targeted gene therapy for treating various diseases.

IPC Classes  ?

• C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
• C12N 15/86 - Viral vectors

Abstract

The present invention concerns an expression system for systemic administration comprising a sequence encoding gamma-sarcoglycan (SGCG) placed under the control of a promoter allowing an adequate expression of SGCG in the skeletal muscles and in the heart, and its use for the treatment of Limb-Girdle Muscular Dystrophy type C.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 15/86 - Viral vectors
• C12N 15/87 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation

Abstract

The present invention concerns an expression system for systemic administration comprising a sequence encoding gamma-sarcoglycan (SGCG) placed under the control of a promoter allowing an adequate expression of SGCG in the skeletal muscles and in the heart, and its use for the treatment of Limb-Girdle Muscular Dystrophy type C.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 15/86 - Viral vectors
• C12N 15/87 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation

Abstract

The present disclosure relates to the treatment of dilated cardiomyopathies, in particular to 5 the use of an inhibitor of CILP-1.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
• A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The invention relates to the treatment of dilated cardiomyopathies, in particular genetic dilated cardiomyopathies, using non-expressible inhibitors of the WNT pathway or TGF-β pathway, alone or in combination.

IPC Classes  ?

• A61K 31/18 - Sulfonamides
• A61K 31/351 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
• A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
• A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
• A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
• A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
• A61P 9/00 - Drugs for disorders of the cardiovascular system

Abstract

The present invention relates to the treatment of dilated cardiomyopathies, in particular to the use of an activator of NRF2.

IPC Classes  ?

• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The invention relates to the treatment of dilated cardiomyopathies, in particular genetic dilated cardiomyopathies, using non-expressible inhibitors of the WNT pathway or TGF-ß pathway, alone or in combination.

IPC Classes  ?

• A61K 31/18 - Sulfonamides
• A61K 31/351 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
• A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
• A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
• A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
• A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
• A61P 9/00 - Drugs for disorders of the cardiovascular system

Abstract

The present disclosure relates to the treatment of dilated cardiomyopathies, in particular to 5 the use of an inhibitor of CILP-1.

IPC Classes  ?

• A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
• A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

Abstract

The invention relates to the treatment of genetic dilated cardiomyopathies using expressible modulators of the Wnt pathway or TGF-ß pathway, preferably using gene transfer.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C12N 15/115 - Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith
• C12N 15/12 - Genes encoding animal proteins
• C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
• C12N 15/864 - Parvoviral vectors

Abstract

The invention relates to the treatment of genetic dilated cardiomyopathies using expressible modulators of the Wnt pathway or TGF-β pathway, preferably using gene transfer.

IPC Classes  ?

• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
• C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies

Abstract

The present invention relates to the treatment of dilated cardiomyopathies, in particular to the use of an activator of NRF2.

IPC Classes  ?

• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy

Abstract

The invention relates to an adeno-associated virus (AAV) vector comprising a nucleic acid construct for the expression of a glucose-6-phosphatase-a (G6Pase-a) in a cell, the construct comprising a nucleic acid sequence encoding the G6Pase-a, wherein the nucleic acid sequence encoding the G6Pase-a is operably linked to a human alpha-1 antitrypsin (hAAT) promoter, a cell transformed with the vector of the invention, a composition comprising the vector or the cell of the invention, and the use thereof.

IPC Classes  ?

• C12N 15/86 - Viral vectors

Abstract

The invention relates to an adeno-associated virus (AAV) vector comprising a nucleic acid construct for the expression of a glucose-6-phosphatase-a (G6Pase-a) in a cell, the construct comprising a nucleic acid sequence encoding the G6Pase-a, wherein the nucleic acid sequence encoding the G6Pase-a is operably linked to a human alpha-1 antitrypsin (hAAT) promoter, a cell transformed with the vector of the invention, a composition comprising the vector or the cell of the invention, and the use thereof.

IPC Classes  ?

• C12N 15/86 - Viral vectors

Abstract

The invention relates to a peptide that specifically binds to an AAV capsid, said peptide comprising an amino acid sequence having at least 80% identity with an amino acid sequence selected from SEQ ID NO : 1, SEQ ID NO : 2, SEQ ID NO : 3, SEQ ID NO : 4, SEQ ID NO : 5 or SEQ ID NO : 6, The invention further relates to a composition comprising one or more peptides of the invention, a kit-of-parts comprising (i) a peptide of the invention or a composition of the invention and (ii) an AAV vector. The invention also relates to Molecularly imprinted polymer (MIP) particle that specifically binds to a peptide of the invention.

IPC Classes  ?

• A61K 38/10 - Peptides having 12 to 20 amino acids
• A61K 39/12 - Viral antigens
• A61K 39/42 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum viral
• C07K 16/08 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses
• A61K 31/74 - Synthetic polymeric materials
• A61M 1/34 - Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration, diafiltration

Abstract

The invention relates to a peptide that specifically binds to an AAV capsid, said peptide comprising an amino acid sequence having at least 80% identity with an amino acid sequence selected from SEQ ID NO : 1, SEQ ID NO : 2, SEQ ID NO : 3, SEQ ID NO : 4, SEQ ID NO : 5 or SEQ ID NO : 6. The invention further relates to a composition comprising one or more peptides of the invention, a kit-of-parts comprising (i) a peptide of the invention or a composition of the invention and (ii) an AAV vector. The invention also relates to Molecularly imprinted polymer (MIP) particle that specifically binds to a peptide of the invention.

IPC Classes  ?

• A61K 38/10 - Peptides having 12 to 20 amino acids
• A61K 39/12 - Viral antigens
• A61K 39/42 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum viral
• C07K 16/08 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses
• A61K 31/74 - Synthetic polymeric materials
• A61M 1/34 - Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration, diafiltration

Abstract

The present invention relates to hybrid transcription regulatory elements to drive gene expression, in particular hybrid promoters, designed by the fusion of at least two transcription regulatory elements with different tissue selectivity, such as two promoters driving expression in different tissues in a tissue-selective manner.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 15/86 - Viral vectors
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids

Abstract

The invention relates to the use of a recombinant porcine adeno-associated virus (AAV) vector comprising a peptide-modified porcine AAV serotype 1 (AAVpo1) capsid in gene therapy of muscle and/or central nervous system (CNS) disorders, in particular neuromuscular diseases such as genetic neuromuscular diseases.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
• C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
• C12N 15/86 - Viral vectors

Abstract

The present invention concerns synthetic polynucleotides encoding a human fukutin-related protein (FKRP) wherein the synthetic polynucleotides contain at least a mutation avoiding supplementary transcript(s) generated from frameshift start codon(s). The synthetic polynucleotides are useful, especially for treating a pathology linked to a FKRP deficiency or induced by a defect in α-dystroglycan (α-DG) glycosylation, such as LGMD2I.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
• C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
• C12N 15/86 - Viral vectors
• A61K 38/00 - Medicinal preparations containing peptides

Abstract

The invention relates to the use of a recombinant porcine adeno-associated virus (AAV) vector comprising a peptide-modified porcine AAV serotype 1 (AAVpo1) capsid in gene therapy of muscle and/or central nervous system (CNS) disorders, in particular neuromuscular diseases such as genetic neuromuscular diseases.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
• C12N 15/86 - Viral vectors
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system

Abstract

Despite the eye's immune-privileged status, a secondary loss of vision in some patients treated with AAV led the inventors to question the immunogenicity of AAV vectors after a subretinal injection. The inventors thus characterized anti-transgene and anti-capsid immune responses induced in the periphery after the subretinal AAV injection. Different doses of AAV8 encoding reporter proteins fused with the HY male antigen were injected at day 0 into the subretinal space of adult immunocompetent C57BL/6 female mice. Subretinal AAV injection induced a dose-dependent proinflammatory immune response to the transgene product, correlated with local transgene expression. In order to trigger a subretinal-associated immune inhibition (SRAII) mechanism, some mice were co-injected subretinally at day 0 with AAV and HY peptides. Interestingly, this subretinal co-injection of AAV8 with peptides of the transgene product modulated the anti-transgene T-cell immune response, even at high dose of vector (5.1010 vg). This immunodulation was also confirmed in a pathophysiological murine model of retinal degeneration. The inventors also demonstrated that injection of AAV8 in the subretinal space induces proinflammatory peripheral immune responses to the transgene and the capsid that could be counteracted by co-injection with transgene peptides. Accordingly, the object of the present invention is to provide methods for preventing induction of immune responses to the transgene product and the AAV capsid after ocular gene therapy.

IPC Classes  ?

• A61K 38/00 - Medicinal preparations containing peptides
• A61K 39/12 - Viral antigens
• A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 27/02 - Ophthalmic agents
• C12N 15/86 - Viral vectors

Abstract

Despite the eye's immune-privileged status, a secondary loss of vision in some patients treated with AAV led the inventors to question the immunogenicity of AAV vectors after a subretinal injection. The inventors thus characterized anti-transgene and anti-capsid immune responses induced in the periphery after the subretinal AAV injection. Different doses of AAV8 encoding reporter proteins fused with the HY male antigen were injected at day 0 into the subretinal space of adult immunocompetent C57BL/6 female mice. Subretinal AAV injection induced a dose-dependent proinflammatory immune response to the transgene product, correlated with local transgene expression. In order to trigger a subretinal-associated immune inhibition (SRAII) mechanism, some mice were co-injected subretinally at day 0 with AAV and HY peptides. Interestingly, this subretinal co-injection of AAV8 with peptides of the transgene product modulated the anti-transgene T-cell immune response, even at high dose of vector (5.1010 vg). This immunodulation was also confirmed in a pathophysiological murine model of retinal degeneration. The inventors also demonstrated that injection of AAV8 in the subretinal space induces proinflammatory peripheral immune responses to the transgene and the capsid that could be counteracted by co-injection with transgene peptides. Accordingly, the object of the present invention is to provide methods for preventing induction of immune responses to the transgene product and the AAV capsid after ocular gene therapy.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 27/02 - Ophthalmic agents
• A61K 39/12 - Viral antigens
• A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
• C12N 15/86 - Viral vectors
• A61K 38/00 - Medicinal preparations containing peptides

Abstract

The present invention relates to a vector comprising an ASAH1 open reading frame, for use in the treatment of acid ceramidase deficiency.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 15/86 - Viral vectors
• A61P 3/00 - Drugs for disorders of the metabolism
• A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system

Abstract

The present invention relates to a vector comprising an ASAH1 open reading frame, for use in the treatment of acid ceramidase deficiency.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
• A61P 3/00 - Drugs for disorders of the metabolism
• C12N 15/86 - Viral vectors