The present invention relates generally to isolated mitochondria derived from mtDNA-depleted cells (RhoO-mito) that are advantageously used as delivery vehicles for heterogenous proteins or nucleic acids or chemical agents. In some embodiments, proteins or nucleic acids or chemical agents are introduced into a cell, transported into, transferred or expressed in the mitochondria, thereafter or before mtDNA is removed and mtDNA-free mitochondria are extracted from the cell. These mitochondria are used for therapeutic treatment of mitochondria-related diseases such as maple syrup syndrome, citrin deficiency, Nieman-Pick disease, X-linked adrenoleukodystrophy (X-ALD), Pyruvate Dehydrogenase Deficiency, respiratory chain diseases, mutations in mitochondrial respiratory chain proteins, fatty acid metabolism disorders, or cancer with reduced likelihood of causing an immunogenic response. Additionally, in some embodiments the present invention relates to isolated mitochondria, including but not necessarily isolated mitochondria derived from mtDNA-depleted cells (RhoO-mito), that are exogenously introduced into cells to enhance production of endogenous or heterogenous proteins.
The present invention provides stem cells enriched with healthy functional mitochondria, and therapeutic methods utilizing such cells for the alleviation of debilitating conditions, including aging, and age-related diseases as well as the debilitating effects of anti-cancer therapies in subjects in need thereof.
A61K 35/15 - Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cellsMyeloid precursor cellsAntigen-presenting cells, e.g. dendritic cells
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
The present disclosure provides cells enriched with mitochondria to treat myelodysplastic syndrome (MDS). diseases and disorders. The disclosure provides pharmaceutical compositions of mitochondrially-enriched stem cells and/or progenitor cells. methods of treatment of myelodysplastic syndrome. and methods to alleviate symptoms of MDS and/or prevent the progression of MDS using mitochondrially-enriched stem cells and/or progenitor cells.
The present invention relates to mitochondrial compositions and therapeutic methods of using same. The invention discloses compositions of partially purified functional mitochondria and methods of using the compositions to treat conditions which benefit from increased mitochondrial function by administering the compositions to a subject in need thereof.
The present disclosure is based on the discovery that cells enriched with mitochondria are useful for treating diseases and disorders. The present invention provides methods of identifying or detecting such cells enriched with exogenous mitochondria. Specifically, the identification or detection of mitochondria-enriched cells is determined by utilization of a substrate such as tryptamine. This includes determining levels of MonoAmine oxidase A (MAO-A), Mono Amine oxidase-B (MAO-B), glycerol-3-phosphate dehydrogenase or a combination thereof. The present invention also provides kits for the identification or detection of mitochondria-enriched cells.
The present invention relates to products and methods for treatment of hair loss. Specifically, the present application relates to compositions and methods for prevention and treatment of hair loss, comprising administration of a composition comprising intact mitochondria, ruptured mitochondria and/or mitochondrial constituents.
A61K 8/98 - Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof, of undetermined constitution of animal origin
A61K 9/00 - Medicinal preparations characterised by special physical form
The present invention provides methods and compositions which cause the bone marrow to increase production of leukocyte cells. Specifically, the invention provides methods and compositions for increasing levels of CD45+ cells in a subject by providing mitochondrially-enriched cells. Further the present application provides methods for increasing bone marrow cellularity, engraftment of CD34+ cells and differentiation.
The present disclosure provides cells enriched with mitochondria to treat myelodysplastic syndrome (MDS), diseases and disorders. The disclosure provides pharmaceutical compositions of mitochondrially-enriched stem cells and/or progenitor cells, methods of treatment of myelodysplastic syndrome, and methods to alleviate symptoms of MDS and/or prevent the progression of MDS using mitochondrially-enriched stem cells and/or progenitor cells.
Tel Hashomer Medical Research Infrastructure and Services Ltd. (Israel)
Inventor
Yivgi-Ohana, Natalie
Sher, Noa
Blumkin, Moriya
Jacoby, Elad
Abstract
The present invention is based on the discovery that cells enriched with mitochondria are useful for treating diseases and disorders. Disclosed are pharmaceutical compositions of mitochondrially-enriched genetically engineered T cells and methods of treatment using mitochondrially-enriched genetically engineered T cells.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
The present disclosure is based on the discovery that cells enriched with mitochondria are useful for treating diseases and disorders. The present invention provides methods of identifying or detecting such cells enriched with exogenous mitochondria. Specifically, the identification or detection of mitochondria-enriched cells is determined by utilization of a substrate such as tryptamine. This includes determining levels of MonoAmine oxidase A (MAO- A), Mono Amine oxidase-B (MAO-B), glycerol-3 -phosphate dehydrogenase or a combination thereof. The present invention also provides kits for the identification or detection of mitochondria-enriched cells.
C12Q 1/26 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving oxidoreductase
C12Q 1/32 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving oxidoreductase involving dehydrogenase
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
11.
MITOCHONDRIAL AUGMENTATION THERAPY WITH STEM CELLS ENRICHED WITH FUNCTIONAL MITOCHONDRIA
The present invention provides stem cells enriched with healthy functional mitochondria, and therapeutic methods utilizing such cells for the alleviation of debilitating conditions, including aging, and age-related diseases as well as the debilitating effects of anti-cancer therapies in subjects in need thereof.
A61K 35/15 - Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cellsMyeloid precursor cellsAntigen-presenting cells, e.g. dendritic cells
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
TEL HASHOMER MEDICAL RESEARCH INFRASTRUCTURE AND SERVICES LTD. (Israel)
Inventor
Yivgi-Ohana, Natalie
Sher, Noa
Blumkin, Moriya
Jacoby, Elad
Abstract
The present invention is based on the discovery that cells enriched with mitochondria are useful for treating diseases and disorders. Disclosed are pharmaceutical compositions of mitochondrially-enriched genetically engineered T cells and methods of treatment using mitochondrially-enriched genetically engineered T cells.
The present invention provides methods and compositions which cause the bone marrow to increase production of leukocyte cells. Specifically, the invention provides methods and compositions for increasing levels of CD45+ cells in a subject by providing mitochondrially- enriched cells. Further the present application provides methods for increasing bone marrow cellularity, engraftment of CD34+ cells and differentiation.
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
14.
Mitochondrial augmentation therapy of muscle diseases
The present invention provides stem cells enriched with healthy functional mitochondria, pharmaceutical compositions comprising these cells and methods of use thereof for treating muscle diseases, disorders and symptoms thereof where the disease may or may not be associated with acquired mitochondrial dysfunction.
A61K 35/15 - Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cellsMyeloid precursor cellsAntigen-presenting cells, e.g. dendritic cells
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
The present invention provides stem cells enriched with healthy functional mitochondria, pharmaceutical compositions comprising these cells and methods of use thereof for treating renal diseases, disorders and symptoms thereof where the disease may or may not be associated with acquired mitochondrial dysfunction.
A61K 35/15 - Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cellsMyeloid precursor cellsAntigen-presenting cells, e.g. dendritic cells
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
The present invention provides stem cells enriched with healthy functional mitochondria, pharmaceutical compositions comprising these cells and methods of use thereof for treating brain diseases, disorders and symptoms thereof where the disease may or may not be associated with acquired mitochondrial dysfunction.
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 35/15 - Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cellsMyeloid precursor cellsAntigen-presenting cells, e.g. dendritic cells
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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
17.
Mitochondrial augmentation therapy of ocular diseases
The present invention provides stem cells enriched with healthy functional mitochondria, pharmaceutical compositions comprising these cells and methods of use thereof for treating ocular diseases, disorders and symptoms thereof where the disease may or may not be associated with acquired mitochondrial dysfunction.
A61K 35/15 - Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cellsMyeloid precursor cellsAntigen-presenting cells, e.g. dendritic cells
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
The present invention provides human stem cells enriched with functional mitochondria, wherein the healthy functional exogenous mitochondria constitute at least 3% and less than 33% of the total mitochondria in the mitochondrially-enriched human stem cells. Further disclosed are methods for the production of such cells, and uses thereof for the treatment of primary mitochondrial diseases.
The present invention provides stem cells enriched with healthy functional mitochondria, pharmaceutical compositions comprising these cells and methods of use thereof for treating liver diseases, disorders and symptoms thereof where the disease may or may not be associated with acquired mitochondrial dysfunction.
A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
20.
MITOCHONDRIAL AUGMENTATION THERAPY OF PANCREATIC DISEASES
The present invention provides stem cells enriched with healthy functional mitochondria, pharmaceutical compositions comprising these cells and methods of use thereof for treating pancreatic diseases, disorders and symptoms thereof where the disease may or may not be associated with acquired mitochondrial dysfunction.
A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 35/15 - Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cellsMyeloid precursor cellsAntigen-presenting cells, e.g. dendritic cells
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
The present invention provides stem cells enriched with healthy functional mitochondria, pharmaceutical compositions comprising these cells and methods of use thereof for treating renal diseases, disorders and symptoms thereof where the disease may or may not be associated with acquired mitochondrial dysfunction.
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 35/15 - Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cellsMyeloid precursor cellsAntigen-presenting cells, e.g. dendritic cells
A61K 9/00 - Medicinal preparations characterised by special physical form
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
22.
METHODS FOR ELEVATION OF LIPID AND CHOLESTEROL METABOLISM
The present invention relates to methods of using compositions comprising intact mitochondria and/or ruptured mitochondria for elevating lipid metabolism in cells. The present invention further provides methods for treating diseases which benefit from elevation of lipid and cholesterol metabolism and methods for inducing weight loss or reducing weight gain comprising administering compositions comprising intact mitochondria and/or ruptured mitochondria to a subject in need thereof.
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Scientific research in the field of assessing the level of
healthy mitochondria or mutated mitochondria, mitochondrial
activity, mitochondrial related diseases; medical research
relating to assessing the level of healthy mitochondria or
mutated mitochondria, mitochondrial activity, mitochondrial
related diseases; scientific advisory services relating to
technical diagnostic products, chemistry, biotechnology,
biochemistry; biotechnology and biological research and
testing; scientific research services, namely, gene analysis
and sequencing, DNA analysis and sequencing, and nucleic
acid analysis; scientific research services, namely, protein
analysis and protein sequencing services; software as a
service (saas) in relation to diagnostic and assay products;
software as a service (saas) in relation to assessing the
level of healthy mitochondria or mutated mitochondria,
mitochondrial activity, mitochondrial related diseases;
diagnostic and assay products consulting services in the
fields of laboratory testing and diagnostics. Medical diagnostic testing, monitoring and reporting
services; medical diagnostic services, namely, assessing the
level of healthy mitochondria or mutated mitochondria,
mitochondrial activity, mitochondrial related diseases;
medical diagnostic testing and reporting services in the
fields of DNA sequencing, DNA and RNA analysis, and genetic
analysis; medical diagnostic testing and reporting services,
namely, protein sequencing services and protein analysis;
medical consultancy services in relation to diagnostic and
assay products; consulting services in the field of
diagnostic medical testing.
24.
Compositions of functional mitochondria and uses thereof
The present invention relates to mitochondrial compositions and therapeutic methods of using same. The invention discloses compositions of partially purified functional mitochondria and methods of using the compositions to treat conditions which benefit from increased mitochondrial function by administering the compositions to a subject in need thereof.
The present invention provides human bone-marrow cells enriched with functional mitochondria, methods for their production, and therapeutic methods utilizing such cells.
The present invention provides human stem cells enriched with functional mitochondria, wherein the healthy functional exogenous mitochondria constitute at least 3% and less than 33% of the total mitochondria in the mitochondrially-enriched human stem cells. Further disclosed are methods for the production of such cells, and uses thereof for the treatment of primary mitochondrial diseases.
The present invention provides stem cells enriched with healthy functional mitochondria, pharmaceutical compositions comprising these cells and methods of use thereof for treating brain diseases, disorders and symptoms thereof where the disease may or may not be associated with acquired mitochondrial dysfunction.
A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
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
The present invention provides stem cells enriched with healthy functional mitochondria, pharmaceutical compositions comprising these cells and methods of use thereof for treating pancreatic diseases, disorders and symptoms thereof where the disease may or may not be associated with acquired mitochondrial dysfunction.
The present invention provides stem cells enriched with healthy functional mitochondria, and therapeutic methods utilizing such cells for the alleviation of debilitating conditions, including aging, and age-related diseases as well as the debilitating effects of anti-cancer therapies in subjects in need thereof.
The present invention provides stem cells enriched with healthy functional mitochondria, pharmaceutical compositions comprising these cells and methods of use thereof for treating renal diseases, disorders and symptoms thereof where the disease may or may not be associated with acquired mitochondrial dysfunction.
The present invention provides stem cells enriched with healthy functional mitochondria, pharmaceutical compositions comprising these cells and methods of use thereof for treating ocular diseases, disorders and symptoms thereof where the disease may or may not be associated with acquired mitochondrial dysfunction.
The present invention provides stem cells enriched with healthy functional mitochondria, pharmaceutical compositions comprising these cells and methods of use thereof for treating liver diseases, disorders and symptoms thereof where the disease may or may not be associated with acquired mitochondrial dysfunction.
The present invention provides stem cells enriched with healthy functional mitochondria, pharmaceutical compositions comprising these cells and methods of use thereof for treating muscle diseases, disorders and symptoms thereof where the disease may or may not be associated with acquired mitochondrial dysfunction.
The present invention provides human bone-marrow cells enriched with functional mitochondria, methods for their production, and therapeutic methods utilizing such cells.
The present invention relates to methods of using compositions comprising intact mitochondria and/or ruptured mitochondria for elevating lipid metabolism in cells. The present invention further provides methods for treating diseases which benefit from elevation of lipid and cholesterol metabolism and methods for inducing weight loss or reducing weight gain comprising administering compositions comprising intact mitochondria and/or ruptured mitochondria to a subject in need thereof.
Mitochondrial compositions and therapeutic methods of using same. Compositions of partially purified functional mitochondria and methods of using the compositions to treat conditions which benefit from increased mitochondrial function by administering the compositions to a subject in need thereof.
The present invention relates to products and methods for treatment of hair loss. Specifically, the present application relates to compositions and methods for prevention and treatment of hair loss, comprising administration of a composition comprising intact mitochondria, ruptured mitochondria and/or mitochondrial constituents.
The present invention provides human bone-marrow cells enriched with functional mitochondria, methods for their production, and therapeutic methods utilizing such cells.
Mitochondrial compositions and therapeutic methods of using same. Compositions of partially purified functional mitochondria and methods of using the compositions to treat conditions which benefit from increased mitochondrial function by administering the compositions to a subject in need thereof.
The present invention relates to compositions and methods of inducing angiogenesis and methods of treating a pathology that would benefit from angiogenesis by use of a composition comprising partially purified intact mitochondria and/or ruptured mitochondria 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
A61K 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified cells
45.
COMPOSITIONS OF FUNCTIONAL MITOCHONDRIA AND USES THEREOF
The present invention relates to mitochondrial compositions and therapeutic methods of using same. The invention discloses compositions of partially purified functional mitochondria and methods of using the compositions to treat conditions which benefit from increased mitochondrial function by administering the compositions to a subject in need thereof.
