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 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
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 - Drugs for disorders of the cardiovascular system
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
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 - 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
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
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.
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
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 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 17/00 - Carrier-bound or immobilised peptidesPreparation thereof
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
A61K 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified cells
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
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 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
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.
C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
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 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
A61K 39/215 - Coronaviridae, e.g. avian infectious bronchitis virus
A61K 38/16 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
A61K 39/145 - Orthomyxoviridae, e.g. influenza virus
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
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, e.g. avian infectious bronchitis virus
A61K 47/62 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
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.
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 - Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
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 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
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.
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 of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
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.
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 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C12N 9/06 - Oxidoreductases (1.), e.g. luciferase acting on nitrogen containing compounds as donors (1.4, 1.5, 1.7)
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
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.
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.
THE GOVERNMENT OF THE UNITED STATES AS REPRESENTED BY THE SECRETARY OF THE ARMY (USA)
CAPRICOR, INC. (USA)
Inventor
Bynum, James A.
Marban, Linda
Abstract
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 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61P 9/00 - Drugs for disorders of the cardiovascular system
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 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified cells
A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
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.
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 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
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 - 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
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
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.
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 - Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
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 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 9/00 - Medicinal preparations characterised by special physical form
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.
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.
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.
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.
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 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
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.
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.
