Disclosed is a method of making and using a therapeutically potent cell for treating degenerative muscle disease. More specifically, disclosed is a method of making and using therapeutic cells, the method including identity and potency release assays for selecting an confirming therapeutic cells useful in ameliorating cardiac muscle and/or skeletal muscle degeneration associated with muscular dystrophy.
C12N 5/00 - Cellules non différenciées humaines, animales ou végétales, p. ex. lignées cellulairesTissusLeur culture ou conservationMilieux de culture à cet effet
C12Q 1/6881 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour le typage de tissu ou de cellule, p. ex. sondes d’antigène leucocytaire humain [HLA]
G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique
2.
CELL THERAPY COMPOSITIONS AND METHODS OF MANUFACTURE
Disclosed is a method of making and using a therapeutically potent cell for treating degenerative muscle disease. More specifically, disclosed is a method of making and using therapeutic cells, the method including identity and potency release assays for selecting an confirming therapeutic cells useful in ameliorating cardiac muscle and/or skeletal muscle degeneration associated with muscular dystrophy.
A61P 9/00 - Médicaments pour le traitement des troubles du système cardiovasculaire
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
3.
ACTIVATION-INDUCED TISSUE-EFFECTOR CELLS SUITABLE FOR CELL THERAPY AND EXTRACELLUAR VESICLES DERIVED THEREFROM
The present invention provides a method of inducing activation of a non-potent or insufficiently potent cell to convert the cell into a tissue-effector cell, thereby producing an activation-induced tissue-effector cell suitable for use in cell therapy—e.g., an activated specialized tissue-effector cell (ASTEC) suitable for cell therapy for a particular tissue type. The present invention further provides activation-induced tissue-effector cells produced thereby, as well as extracellular vesicles, e.g. exosomes, derived therefrom (e.g., ASTEX). The present invention further provides a method of improving the efficacy of a cell therapy by converting non-potent or insufficiently potent cells into activation-induced tissue-effector cells having increased potency suitable for cell therapy. The present invention further provides a method for treating a disease or condition amenable to cell therapy in a subject in need thereof, the method comprising administering a therapeutically effective amount of activation-induced tissue-effector cells or extracellular vesicles derived therefrom.
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
A61P 29/00 - Agents analgésiques, antipyrétiques ou anti-inflammatoires non centraux, p. ex. agents antirhumatismauxMédicaments anti-inflammatoires non stéroïdiens [AINS]
4.
ARGINASE BEARING VESICLE COMPOSITION AND METHOD OF USE
Disclosed are compositions containing exosomes loaded with arginase or arginase chimeras for treating hyperammonemia due to arginase deficiency, and methods for treating hyperammonemia by administering compositions containing exosomes loaded with arginase or arginase chimeras.
Disclosed are compositions containing exosomes loaded with arginase or arginase chimeras for treating hyperammonemia due to arginase deficiency, and methods for treating hyperammonemia by administering compositions containing exosomes loaded with arginase or arginase chimeras.
C12N 9/78 - Hydrolases (3.) agissant sur les liaisons carbone-azote autres que les liaisons peptidiques (3.5)
A61K 38/00 - Préparations médicinales contenant des peptides
A61K 47/69 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament le conjugué étant caractérisé par sa forme physique ou sa forme galénique, p. ex. émulsion, particule, complexe d’inclusion, stent ou kit
C07K 14/705 - RécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire
The present disclosure relates to compositions and methods for targeting vesicles to specific tissue and cell types. Also disclosed are compositions and methods for delivering therapeutic molecules, including nucleic acids and nucleic acid derivatives, to specific cells or tissues using vesicles with cell and tissue-specific targeting moieties expressed on their surfaces.
A61K 9/127 - Vecteurs à bicouches synthétiques, p. ex. liposomes ou liposomes comportant du cholestérol en tant qu’unique agent tensioactif non phosphatidylique
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
C07K 17/00 - Peptides fixés sur un support ou immobilisésLeur préparation
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
C07H 21/04 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p. ex. acides nucléiques avec le désoxyribosyle comme radical saccharide
A61K 35/12 - Substances provenant de mammifèresCompositions comprenant des tissus ou des cellules non spécifiésCompositions comprenant des cellules souches non embryonnairesCellules génétiquement modifiées
C12N 15/00 - Techniques de mutation ou génie génétiqueADN ou ARN concernant le génie génétique, vecteurs, p. ex. plasmides, ou leur isolement, leur préparation ou leur purificationUtilisation d'hôtes pour ceux-ci
The present disclosure relates to compositions and methods for targeting vesicles to specific tissue and cell types. Also disclosed are compositions and methods for delivering therapeutic molecules, including nucleic acids and nucleic acid derivatives, to specific cells or tissues using vesicles with cell and tissue-specific targeting moieties expressed on their surfaces.
A61K 47/64 - Conjugués médicament-peptide, médicament-protéine ou médicament-acide polyaminé, c.-à-d. l’agent de modification étant un peptide, une protéine ou un acide polyaminé lié par covalence ou complexé à un agent thérapeutiquement actif
A61K 47/68 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un anticorps, une immunoglobuline ou son fragment, p. ex. un fragment Fc
C07K 14/705 - RécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
8.
METHOD FOR SURFACE EXPRESSION OF MEMBRANE PROTEINS THAT HAVE A CYTOPLASMIC C-TERMINAL TAIL
Coronavirus egress is mediated by lysosomal exocytosis. It is demonstrated herein that the D614G mutation enhances Spike trafficking to lysosomes and the lysosomal accumulation of newly synthesized virus particles, augments Spike-mediated disruption of endomembrane homeostasis, and causes a 3-fold reduction in cell surface Spike expression. Moreover, it is shown that the D614G mutation is an intragenic suppressor of the 12 nucleotide-long furin cleavage site (FCS) insertion, restoring Spike trafficking to lysosomes and TMPRSS2-independent infectivity, both of which had been impaired by the prior FCS insertion mutation. This data identifies enhanced lysosomal sorting as the earliest known manifestation of the D614G mutation, have implications for virus evolution, immunity, and vaccine design, and support a lysosomal model of coronavirus biogenesis and entry.
Disclosed generally are methods of purifying and concentrating exosomes produced in cell culture. Disclosed specifically are methods of purifying and concentrating native or engineered exosomes produced in cell culture by cell culture clarification, filtration, concentration by filtration, removal from contaminants by molecular sieve, and additional concentration by filtration to a concentration on the order of trillions (E12) of exosomes per milliliter.
A61K 9/127 - Vecteurs à bicouches synthétiques, p. ex. liposomes ou liposomes comportant du cholestérol en tant qu’unique agent tensioactif non phosphatidylique
C12N 15/88 - Introduction de matériel génétique étranger utilisant des procédés non prévus ailleurs, p. ex. co-transformation utilisant la micro-encapsulation, p. ex. utilisant des vésicules liposomiques
12.
COMBINATION EXOSOMAL IMMUNOGENIC COMPOSITIONS AND METHODS
The present disclosure relates to compositions and methods for vaccinating a subject against multiple SARS-CoV-2 variants and other respiratory viruses that involves the making and delivery of extracellular vesicles expressing on their surface engineered spike protein, engineered nucleocapsid protein, engineered hemagglutinin protein, and/or engineered respiratory syncytial virus prefusion or fusion (RSV F) protein to the subject. The present invention also relates to compositions and methods for the design, preparation, manufacture, formulation, and/or use of spike-display, nucleocapsid-display, hemagglutinin-display, and/or RSV F-display vesicular vaccines designed to elicit strong humoral and cellular immune responses against multiple respiratory viruses and variants.
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
C12N 15/88 - Introduction de matériel génétique étranger utilisant des procédés non prévus ailleurs, p. ex. co-transformation utilisant la micro-encapsulation, p. ex. utilisant des vésicules liposomiques
A61K 39/215 - Coronaviridae, p. ex. virus de la bronchite infectieuse aviaire
A61K 38/16 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés
A61K 39/145 - Orthomyxoviridae, p. ex. virus de l'influenza
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
The present disclosure relates to compositions and methods for vaccinating a subject against multiple SARS-CoV-2 variants that involves the making and delivery of extracellular vesicles expressing on their surface engineered spike protein and/or engineered nucleocapsid protein to the subject. The present invention also relates to compositions and methods for the design, preparation, manufacture, formulation, and/or use of spike-display and nucleocapsid-display vesicular vaccines designed to elicit strong humoral and cellular immune responses against multiple SARS-CoV-2 variants.
A61K 39/215 - Coronaviridae, p. ex. virus de la bronchite infectieuse aviaire
A61K 47/62 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant une protéine, un peptide ou un acide polyaminé
A61K 47/69 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament le conjugué étant caractérisé par sa forme physique ou sa forme galénique, p. ex. émulsion, particule, complexe d’inclusion, stent ou kit
A61P 31/14 - Antiviraux pour le traitement des virus ARN
The present invention generally relates to the use of extracellular vesicles derived from cardiosphere-derived cells (CDC-EVs) as an anti-shock therapeutic. For instance, the present invention relates to a method of using CDC-EVs to treat polytrauma associated with coagulopathy and hemorrhagic shock in a subject in need thereof, wherein the lactate, glucose and/or creatinine levels in the subject are decreased upon being treated with a therapeutically effective amount of CDC-EVs. The results presented herein are of great relevance to the development of EV products for use in combat casualty care, as the studies presented herein show that CDC-EVs have the potential to be an anti-shock therapeutic if administered immediately after injury involving trauma associated with hemorrhagic shock and/or coagulopathy.
A61K 9/127 - Vecteurs à bicouches synthétiques, p. ex. liposomes ou liposomes comportant du cholestérol en tant qu’unique agent tensioactif non phosphatidylique
A61P 7/04 - AntihémorragiquesProfacteurs de coagulationAgents hémostatiquesAgents antifibrinolytiques
16.
METHODS AND COMPOSITIONS FOR TREATING SKELETAL MUSCULAR DYSTROPHY
Some embodiments provide a method of treating skeletal muscular myopathy, e.g., Duchenne muscular dystrophy (DMD), with cardiosphere-derived cells (CDCs), wherein a therapeutically effective amount of CDCs is delivered to a targeted dystrophic skeletal muscle. Some embodiment enable delivery of a therapeutically effective amount of CDCs via intramuscular injection directly at a skeletal muscle or systemic administration, e.g., intravenous injection, in a single dose or multiple doses, to treat a targeted dystrophic skeletal muscle. Some embodiments provide a method for improving exercise capabilities in DMD patients. Additional embodiments relate to exosome mediated transfer of noncoding RNAs ameliorates Duchenne muscular dystrophy by restoring dystrophin in heart and skeletal muscle. Delivery of noncoding RNA species found in CDC-derived exosomes mimics the ability of CDCs and CDC-derived exosomes to increase dystrophin protein levels.
A61P 25/14 - Médicaments pour le traitement des troubles du système nerveux pour traiter les mouvements anormaux, p. ex. chorée, dyskinésie
A61P 21/00 - Médicaments pour le traitement des troubles du système musculaire ou neuromusculaire
A61K 31/7105 - Acides ribonucléiques naturels, c.-à-d. contenant uniquement des riboses liés à l'adénine, la guanine, la cytosine ou l'uracile et ayant des liaisons 3'-5' phosphodiester
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
17.
METHODS OF TREATING SYSTEMIC GRAFT- VERSUS-HOST DISEASE WITH EXTRACELLULAR VESICLES
The present invention relates to a method of treating acute or chronic systemic graft-versus-host disease (GVHD) with extracellular vesicles, e.g., exosomes obtained from human cardiospheres or cardiosphere-derived cells (CDCs), wherein systemic GVHD involves, e.g., at least two organs selected from the group consisting of the skin, mucosa, gastrointestinal tract, liver, lungs, joints and fascia, genitalia, and eyes. The present invention also provides a pharmaceutical formulation comprising extracellular vesicles, e.g., exosomes obtained from human cardiospheres or CDCs, for systemic administration, e.g., intravenous infusion, to a human subject in need of treatment of systemic GVHD.
A61P 37/06 - Immunosuppresseurs, p. ex. médicaments pour le traitement du rejet de greffe
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 35/28 - Moelle osseuseCellules souches hématopoïétiquesCellules souches mésenchymateuses de toutes origines, p. ex. cellules souches dérivées de tissu adipeux
The present invention provides extrcellular vesicles, such as exosomes, engineered to be loaded with miR-345, which may be further loaded with, e.g., miR-146a and let-7b, and/or further be depleted of miR-10a and/or miR-10b. The present invention also provides an assay method, wherein the amounts of miR-345, miR146a, and let-7b in a sample of extracellular vesicles are positively associated with potency, and wherein the amount of miR-10b in a sample of extracellular vesicles is negatively associated with potency.
C12N 15/88 - Introduction de matériel génétique étranger utilisant des procédés non prévus ailleurs, p. ex. co-transformation utilisant la micro-encapsulation, p. ex. utilisant des vésicules liposomiques
A61K 35/28 - Moelle osseuseCellules souches hématopoïétiquesCellules souches mésenchymateuses de toutes origines, p. ex. cellules souches dérivées de tissu adipeux
C12N 15/11 - Fragments d'ADN ou d'ARNLeurs formes modifiées
19.
SELECTABLE MARKER PROTEINS, EXPRESSION VECTORS, ENGINEERED CELLS AND EXTRACELLULAR VESICLES FOR THE PRODUCTION OF VIRUS-LIKE PARTICLES FOR THERAPEUTIC AND PROPHYLACTIC APPLICATIONS
The present invention relates to engineered selectable marker proteins for recombinant protein expression, as well as novel expression vector designs for achieving high-level recombinant protein expression, and cells transfected therewith as a platform technology for producing extracellular vesicle-based therapeutic or prophylactic compositions, wherein one or more recombinant proteins of interest are displayed on the surface of the extracellular vesicles. As an example, the present invention relates to a virus-like article composition comprising such extracellular vesicles displaying one or more antigens configured to induce immune responses against SARS-CoV-2.
C12N 15/85 - Vecteurs ou systèmes d'expression spécialement adaptés aux hôtes eucaryotes pour cellules animales
A61K 9/127 - Vecteurs à bicouches synthétiques, p. ex. liposomes ou liposomes comportant du cholestérol en tant qu’unique agent tensioactif non phosphatidylique
Several embodiments of the methods and compositions disclosed herein relate to methods of treating viral infections, such as those caused by coronaviruses. In some embodiments, CDCs are administered to a patient, to treat the viral infection. In some embodiments, CDC-derived exosomes are administered to a patient. In some embodiments combinations of CDCs and CDC-derived exosomes are used. In still additional embodiments, combination therapies, such as CDCs or CDC-derived exosomes in combination with another therapeutic, such as an anti-inflammotry or other immune modulator are used to treat viral infections. In some embodiments, the viral infection is COVID-19, which is caused by SARS-CoV-2.
The present invention relates to modular systems for vaccination against infectious agents that involves the delivery of, e.g., exosome-loaded, antigen-encoding mRNAs to and into cells and tissues of the immunized subject. The present invention also relates to compositions and methods for the design, preparation, manufacture, formulation, and/or use of vaccines, e.g., nucleic acid vaccines, loaded into extracellular vesicles, e.g., exosomes loaded with synthetic mRNAs encoding multiple surface and cytoplasmic antigens of interest, e.g., antigenic polypeptides derived from an infectious virus, e.g., SARS-CoV-2, designed to elicit strong humoral and cellular immune responses due to the simultaneous expression of antigens in their native state and as exosome-associated antigens.
A61K 9/127 - Vecteurs à bicouches synthétiques, p. ex. liposomes ou liposomes comportant du cholestérol en tant qu’unique agent tensioactif non phosphatidylique
A61K 31/7105 - Acides ribonucléiques naturels, c.-à-d. contenant uniquement des riboses liés à l'adénine, la guanine, la cytosine ou l'uracile et ayant des liaisons 3'-5' phosphodiester
A61K 35/28 - Moelle osseuseCellules souches hématopoïétiquesCellules souches mésenchymateuses de toutes origines, p. ex. cellules souches dérivées de tissu adipeux
A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
A61P 31/14 - Antiviraux pour le traitement des virus ARN
C12N 9/06 - Oxydoréductases (1.), p. ex. luciférase agissant sur des composés contenant de l'azote comme donneurs (1.4, 1.5, 1.7)
C12N 15/85 - Vecteurs ou systèmes d'expression spécialement adaptés aux hôtes eucaryotes pour cellules animales
C12N 15/88 - Introduction de matériel génétique étranger utilisant des procédés non prévus ailleurs, p. ex. co-transformation utilisant la micro-encapsulation, p. ex. utilisant des vésicules liposomiques
22.
EXOSOMAL NUCLEIC ACID VACCINE COMPOSITION FOR PROTECTION AGAINST SARS-COV-2 INFECTION AND DISEASE
The present invention relates to an extracellular vesicle (EV)-based nucleic acid composition or vaccine (EV-NAV), comprising EVs loaded with polynucleotides each encoding, e.g., the SARS-CoV-2 spike protein, and polynucleotides each encoding, e.g., SARS-CoV-2 nucleocapsid protein, wherein said polynucleotides are designed to be simultaneously expressed, and to induce a humoral immune response and/or a cellular immune response, in a subject. The present invention also relates to compositions and methods for the design, preparation, manufacture, formulation, and therapeutic or prophylactic use of said EV-NAVs, e.g., exosomes loaded with mRNAs encoding multiple surface and cytoplasmic antigens derived from, e.g., SARS-CoV-2, to elicit strong humoral and cellular immune responses.
A61K 39/215 - Coronaviridae, p. ex. virus de la bronchite infectieuse aviaire
A61K 9/127 - Vecteurs à bicouches synthétiques, p. ex. liposomes ou liposomes comportant du cholestérol en tant qu’unique agent tensioactif non phosphatidylique
C07K 14/165 - Coronaviridae, p. ex. virus de la bronchite infectieuse aviaire
23.
METHOD FOR SURFACE EXPRESSION OF MEMBRANE PROTEINS THAT HAVE A CYTOPLASMIC C-TERMINAL TAIL
Coronavirus egress is mediated by lysosomal exocytosis. It is demonstrated herein that the D614G mutation enhances Spike trafficking to lysosomes and the lysosomal accumulation of newly synthesized virus particles, augments Spike-mediated disruption of endomembrane homeostasis, and causes a 3-fold reduction in cell surface Spike expression. Moreover, it is shown that the D614G mutation is an intragenic suppressor of the 12 nucleotide-long furin cleavage site (FCS) insertion, restoring Spike trafficking to lysosomes and TMPRSS2-independent infectivity, both of which had been impaired by the prior FCS insertion mutation. This data identifies enhanced lysosomal sorting as the earliest known manifestation of the D614G mutation, have implications for virus evolution, immunity, and vaccine design, and support a lysosomal model of coronavirus biogenesis and entry.
Several embodiments relate to methods of generating cells with therapeutic potency. Several embodiments relate to generating cells as a source of exosomes with therapeutic potency. The cells and exosomes with therapeutic potency are useful for repairing and/or regenerating damaged or diseased tissue, for example.
A61P 9/00 - Médicaments pour le traitement des troubles du système cardiovasculaire
G01N 33/50 - Analyse chimique de matériau biologique, p. ex. de sang ou d'urineTest par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligandsTest immunologique
25.
EXTRACELLULAR VESICLES DERIVED FROM CARDIOSPHERE-DERIVED CELLS AS ANTI-SHOCK THERAPEUTICS
THE GOVERNMENT OF THE UNITED STATES AS REPRESENTED BY THE SECRETARY OF THE ARMY (USA)
CAPRICOR, INC. (USA)
Inventeur(s)
Bynum, James A.
Marban, Linda
Abrégé
The present invention generally relates to the use of extracellular vesicles derived from cardiosphere-derived cells (CDC-EVs) as an anti-shock therapeutic. For instance, the present invention relates to a method of using CDC-EVs to treat polytrauma associated with coagulopathy and hemorrhagic shock in a subject in need thereof, wherein the lactate, glucose and/or creatinine levels in the subject are decreased upon being treated with a therapeutically effective amount of CDC-EVs. The results presented herein are of great relevance to the development of EV products for use in combat casualty care, as the studies presented herein show that CDC-EVs have the potential to be an anti-shock therapeutic if administered immediately after injury involving trauma associated with hemorrhagic shock and/or coagulopathy.
The present invention provides extracellular vesicles, such as exosomes, engineered to be loaded with miR-345, which may be further loaded with, e.g., miR-146a and let-7b, and/or further be depleted of miR-10a and/or miR-10b. The present invention also provides an assay method, wherein the amounts of miR-345, miR146a, and let-7b in a sample of extracellular vesicles are positively associated with potency, and wherein the amount of miR-10b in a sample of extracellular vesicles is negatively associated with potency.
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61P 9/00 - Médicaments pour le traitement des troubles du système cardiovasculaire
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
A61K 35/12 - Substances provenant de mammifèresCompositions comprenant des tissus ou des cellules non spécifiésCompositions comprenant des cellules souches non embryonnairesCellules génétiquement modifiées
A61K 35/28 - Moelle osseuseCellules souches hématopoïétiquesCellules souches mésenchymateuses de toutes origines, p. ex. cellules souches dérivées de tissu adipeux
27.
CARDIOSPHERE-DERIVED CELL (CDC) THERAPY FOR THE TREATMENT OF VIRAL INFECTIONS
Several embodiments of the methods and compositions disclosed herein relate to methods of treating viral infections, such as those caused by coronaviruses. In some embodiments, CDCs are administered to a patient, to treat the viral infection. In some embodiments, CDC-derived exosomes are administered to a patient. In some embodiments combinations of CDCs and CDC-derived exosomes are used. In still additional embodiments, combination therapies, such as CDCs or CDC-derived exosomes in combination with another therapeutic, such as an anti-inflammotry or other immune modulator are used to treat viral infections. In some embodiments, the viral infection is COVID-19, which is caused by SARS-CoV-2.
The present invention relates to engineered selectable marker proteins for recombinant protein expression, as well as novel expression vector designs for achieving high-level recombinant protein expression, and cells transfected therewith as a platform technology for producing extracellular vesicle-based therapeutic or prophylactic compositions, wherein one or more recombinant proteins of interest are displayed on the surface of the extracellular vesicles. As an example, the present invention relates to a virus-like particle composition comprising such extracellular vesicles displaying one or more antigens configured to induce immune responses against SARS-CoV-2.
C12N 15/65 - Introduction de matériel génétique étranger utilisant des vecteursVecteurs Utilisation d'hôtes pour ceux-ciRégulation de l'expression utilisant des marqueurs
C12N 15/11 - Fragments d'ADN ou d'ARNLeurs formes modifiées
The present invention relates to modular systems for vaccination against infectious agents that involves the delivery of, e.g., exosome-loaded, antigen-encoding mRNAs to and into cells and tissues of the immunized subject. The present invention also relates to compositions and methods for the design, preparation, manufacture, formulation, and/or use of vaccines, e.g., nucleic acid vaccines, loaded into extracellular vesicles, e.g., exosomes loaded with synthetic mRNAs encoding multiple surface and cytoplasmic antigens of interest, e.g., antigenic polypeptides derived from an infectious virus, e.g., SARS-CoV-2, designed to elicit strong humoral and cellular immune responses due to the simultaneous expression of antigens in their native state and as exosome-associated antigens.
C12P 19/34 - Polynucléotides, p. ex. acides nucléiques, oligoribonucléotides
A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
C12N 15/88 - Introduction de matériel génétique étranger utilisant des procédés non prévus ailleurs, p. ex. co-transformation utilisant la micro-encapsulation, p. ex. utilisant des vésicules liposomiques
30.
ACTIVATION-INDUCED TISSUE-EFFECTOR CELLS SUITABLE FOR CELL THERAPY AND EXTRACELLUAR VESICLES DERIVED THEREFROM
The present invention provides a method of inducing activation of a non-potent or insufficiently potent cell to convert the cell into a tissue-effector cell, thereby producing an activation-induced tissue-effector cell suitable for use in cell therapy—e.g., an activated specialized tissue-effector cell (ASTEC) suitable for cell therapy for a particular tissue type. The present invention further provides activation-induced tissue-effector cells produced thereby, as well as extracellular vesicles, e.g., exosomes, derived therefrom (e.g., ASTEX). The present invention further provides a method of improving the efficacy of a cell therapy by converting non-potent or insufficiently potent cells into activation-induced tissue-effector cells having increased potency suitable for cell therapy. The present invention further provides a method for treating a disease or condition amenable to cell therapy in a subject in need thereof, the method comprising administering a therapeutically effective amount of activation-induced tissue-effector cells or extracellular vesicles derived therefrom.
A61P 9/10 - Médicaments pour le traitement des troubles du système cardiovasculaire des maladies ischémiques ou athéroscléreuses, p. ex. médicaments antiangineux, vasodilatateurs coronariens, médicaments pour le traitement de l'infarctus du myocarde, de la rétinopathie, de l'insuffisance cérébro-vasculaire, de l'artériosclérose rénale
A61P 29/00 - Agents analgésiques, antipyrétiques ou anti-inflammatoires non centraux, p. ex. agents antirhumatismauxMédicaments anti-inflammatoires non stéroïdiens [AINS]
31.
Methods of treating ocular inflammation and chemical injuries of the eye with extracellular vesicles
The present invention relates to a method of treating a chemical injury of the eye, in particular alkali burn of the cornea, as well as ocular GVHD and similar inflammatory ocular conditions, with extracellular vesicles, in particular exosomes obtained from human cardiospheres or cardiosphere-derived cells. The present invention also provides a formulation comprising extracellular vesicles, in particular exosomes obtained from human cardiospheres or cardiosphere-derived cells, for subconjunctival or topical administration to the eye in the treatment of a chemical injury of the eye, in particular alkali burn of the cornea, as well as ocular GVHD and similar inflammatory ocular conditions.
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 35/65 - Amphibiens, p. ex. crapauds, grenouilles, salamandres ou tritons
A61K 35/12 - Substances provenant de mammifèresCompositions comprenant des tissus ou des cellules non spécifiésCompositions comprenant des cellules souches non embryonnairesCellules génétiquement modifiées
32.
Methods and compositions for treating skeletal muscular dystrophy
Some embodiments provide a method of treating skeletal muscular myopathy, e.g., Duchenne muscular dystrophy (DMD), with cardiosphere-derived cells (CDCs), wherein a therapeutically effective amount of CDCs is delivered to a targeted dystrophic skeletal muscle. Some embodiment enable delivery of a therapeutically effective amount of CDCs via intramuscular injection directly at a skeletal muscle or systemic administration, intravenous injection, in a single dose or multiple doses, to treat a targeted dystrophic skeletal muscle. Some embodiments provide a method for improving exercise capabilities in DMD patients. Additional embodiments relate to exosome, mediated transfer of noncoding RNAs ameliorates Duchenne muscular dystrophy by restoring dystrophin in heart and skeletal muscle. Delivery of noncoding RNA species found in CDC-derived exosomes mimics the ability of CDCs and CDC-derived exosomes to increase dystrophin protein levels.
A61P 25/14 - Médicaments pour le traitement des troubles du système nerveux pour traiter les mouvements anormaux, p. ex. chorée, dyskinésie
A61P 21/00 - Médicaments pour le traitement des troubles du système musculaire ou neuromusculaire
A61K 31/7105 - Acides ribonucléiques naturels, c.-à-d. contenant uniquement des riboses liés à l'adénine, la guanine, la cytosine ou l'uracile et ayant des liaisons 3'-5' phosphodiester
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
33.
Methods of treating systemic graft-versus-host disease with extracellular vesicles
The present invention relates to a method of treating acute or chronic systemic graft-versus-host disease (GVHD) with extracellular vesicles, e.g., exosomes obtained from human cardiospheres or cardiosphere-derived cells (CDCs), wherein systemic GVHD involves, e.g., at least two organs selected from the group consisting of the skin, mucosa, gastrointestinal tract, liver, lungs, joints and fascia, genitalia, and eyes. The present invention also provides a pharmaceutical formulation comprising extracellular vesicles, e.g., exosomes obtained from human cardiospheres or CDCs, for systemic administration, e.g., intravenous infusion, to a human subject in need of treatment of systemic GVHD.
A61P 37/06 - Immunosuppresseurs, p. ex. médicaments pour le traitement du rejet de greffe
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 35/28 - Moelle osseuseCellules souches hématopoïétiquesCellules souches mésenchymateuses de toutes origines, p. ex. cellules souches dérivées de tissu adipeux
The present invention relates to a method of treating dermatitis, in particular radiation-induced dermatitis, with extracellular vesicles, in particular exosomes obtained from human cardiospheres or cardiosphere-derived cells. The present invention also provides a formulation comprising extracellular vesicles, in particular exosomes obtained from human cardiospheres or cardiosphere-derived cells, for use in the treatment of dermatitis, in particular radiation-induced dermatitis.
A61K 9/127 - Vecteurs à bicouches synthétiques, p. ex. liposomes ou liposomes comportant du cholestérol en tant qu’unique agent tensioactif non phosphatidylique
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 35/28 - Moelle osseuseCellules souches hématopoïétiquesCellules souches mésenchymateuses de toutes origines, p. ex. cellules souches dérivées de tissu adipeux
A61K 47/10 - AlcoolsPhénolsLeurs sels, p. ex. glycérolPolyéthylène glycols [PEG]PoloxamèresAlkyléthers de PEG/POE
A61P 17/02 - Médicaments pour le traitement des troubles dermatologiques pour traiter les blessures, les ulcères, les brûlures, les cicatrices, les cheloïdes, ou similaires
35.
METHODS OF TREATING SYSTEMIC GRAFT-VERSUS-HOST DISEASE WITH EXTRACELLULAR VESICLES
The present invention relates to a method of treating acute or chronic systemic graft-versus-host disease (GVHD) with extracellular vesicles, e.g., exosomes obtained from human cardiospheres or cardiosphere-derived cells (CDCs), wherein systemic GVHD involves, e.g., at least two organs selected from the group consisting of the skin, mucosa, gastrointestinal tract, liver, lungs, joints and fascia, genitalia, and eyes. The present invention also provides a pharmaceutical formulation comprising extracellular vesicles, e.g., exosomes obtained from human cardiospheres or CDCs, for systemic administration, e.g., intravenous infusion, to a human subject in need of treatment of systemic GVHD.
Some embodiments provide a method of treating skeletal muscular myopathy, e.g., Duchenne muscular dystrophy (DMD), with cardiosphere-derived cells (CDCs), wherein a therapeutically effective amount of CDCs is delivered to a targeted dystrophic skeletal muscle. Some embodiment enable delivery of a therapeutically effective amount of CDCs via intramuscular injection directly at a skeletal muscle or systemic administration, e.g., intravenous injection, in a single dose or multiple doses, to treat a targeted dystrophic skeletal muscle. Some embodiments provide a method for improving exercise capabilities in DMD patients. Additional embodiments relate to exosome mediated transfer of noncoding RNAs ameliorates Duchenne muscular dystrophy by restoring dystrophin in heart and skeletal muscle. Delivery of noncoding RNA species found in CDC-derived exosomes mimics the ability of CDCs and CDC-derived exosomes to increase dystrophin protein levels.
The present disclosure relates generally to methods for the increased processing of tissue for the generation of cardiac stem cells, wherein the stem cells are suitable for use in cardiac stem cell therapy. In particular, several embodiments relate to the processing of allogeneic donor cardiac tissue for the generation of multiple patient doses of cardiac stem cells.
C12N 5/00 - Cellules non différenciées humaines, animales ou végétales, p. ex. lignées cellulairesTissusLeur culture ou conservationMilieux de culture à cet effet
C12N 5/077 - Cellules mésenchymateuses, p. ex. cellules osseuses, cellules de cartilage, cellules stromales médulaires, cellules adipeuses ou cellules musculaires
A61K 35/00 - Préparations médicinales contenant des substances ou leurs produits de réaction de constitution non déterminée
38.
METHOD OF PREVENTING OR TREATING RADIATION-INDUCED DERMATITIS WITH EXTRACELLULAR VESICLES
The present invention relates to a method of treating dermatitis, in particular radiation-induced dermatitis, with extracellular vesicles, in particular exosomes obtained from human cardiospheres or cardiosphere-derived cells. The present invention also provides a formulation comprising extracellular vesicles, in particular exosomes obtained from human cardiospheres or cardiosphere-derived cells, for use in the treatment of dermatitis, in particular radiation-induced dermatitis.
A61P 17/02 - Médicaments pour le traitement des troubles dermatologiques pour traiter les blessures, les ulcères, les brûlures, les cicatrices, les cheloïdes, ou similaires
A61K 8/00 - Cosmétiques ou préparations similaires pour la toilette
A61K 8/30 - Cosmétiques ou préparations similaires pour la toilette caractérisés par la composition contenant des composés organiques
A61K 8/64 - ProtéinesPeptidesLeurs dérivés ou produits de dégradation
A61P 17/00 - Médicaments pour le traitement des troubles dermatologiques
39.
METHODS OF TREATING OCULAR INFLAMMATION AND CHEMICAL INJURIES OF THE EYE WITH EXTRACELLULAR VESICLES
The present invention relates to a method of treating a chemical injury of the eye, in particular alkali bum of the cornea, as well as ocular GVHD and similar inflammatory ocular conditions, with extracellular vesicles, in particular exosomes obtained from human cardiospheres or cardiosphere-derived cells. The present invention also provides a formulation comprising extracellular vesicles, in particular exosomes obtained from human cardiospheres or cardiosphere-derived cells, for subconjunctival or topical administration to the eye in the treatment of a chemical injury of the eye, in particular alkali bum of the cornea, as well as ocular GVHD and similar inflammatory ocular conditions.
The invention encompasses methods for generating exosomes comprising culturing cells in less than 20% oxygen for at least 2 days and harvesting exosomes from the cells. The invention further encompasses exosome preparations generated from cells cultured in less than 20% oxygen for at least 2 days.
The invention encompasses methods for generating stable exosome formulations and encompasses stable exosome formulations. The exosome formulations encompass stable liquid exosome formulations and stable lyophilized exosome formulations. In some embodiments, the exosome formulations can be generated by ultrafiltration and diafiltration. The exosome formulations can be suitable for administration to a human.
A61K 31/7105 - Acides ribonucléiques naturels, c.-à-d. contenant uniquement des riboses liés à l'adénine, la guanine, la cytosine ou l'uracile et ayant des liaisons 3'-5' phosphodiester
A61K 31/7068 - Composés ayant des radicaux saccharide et des hétérocycles ayant l'azote comme hétéro-atome d'un cycle, p. ex. nucléosides, nucléotides contenant des cycles à six chaînons avec l'azote comme hétéro-atome d'un cycle contenant des pyrimidines condensées ou non-condensées ayant des groupes oxo liés directement au cycle pyrimidine, p. ex. cytidine, acide cytidylique
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
42.
Optimized methods for generation of cardiac stem cells from cardiac tissue and their use in cardiac therapy
The present disclosure relates generally to methods for the increased processing of tissue for the generation of cardiac stem cells, wherein the stem cells are suitable for use in cardiac stem cell therapy. In particular, several embodiments relate to the processing of allogeneic donor cardiac tissue for the generation of multiple patient doses of cardiac stem cells.
The present disclosure relates generally to methods for the increased processing of tissue for the generation of cardiac stem cells, wherein the stem cells are suitable for use in cardiac stem cell therapy. In particular, several embodiments relate to the processing of allogeneic donor cardiac tissue for the generation of multiple patient doses of cardiac stem cells.
A61K 35/12 - Substances provenant de mammifèresCompositions comprenant des tissus ou des cellules non spécifiésCompositions comprenant des cellules souches non embryonnairesCellules génétiquement modifiées
A61K 45/00 - Préparations médicinales contenant des ingrédients actifs non prévus dans les groupes
A61P 9/00 - Médicaments pour le traitement des troubles du système cardiovasculaire
C12N 5/02 - Propagation de cellules individuelles ou de cellules en suspensionLeur conservationMilieux de culture à cet effet
The present application relates to cardiac stem cells and a method of using cardiac stem cells to repair damaged heart tissue. In one embodiment, cardiac stem cells, such as cardiosphere-derived cells and/or cardiospheres, can be seeded, embedded and/or cultured in a biomaterial or matrix made from, for example, a hydrogel, that is subsequently administered to a subject to repair damaged heart tissue.
