Claims for Patent: 9,804,151

Summary for Patent: 9,804,151

Title:	Compositions comprising human embryonic stem cells and their derivatives, methods of use, and methods of preparation
Abstract:	The present invention relates to a pharmaceutical composition comprising of preparations of human embryonic stem (hES) cells and their derivatives and methods for their transplantation into the human body, wherein transplantation results in the clinical reversal of symptoms, cure, stabilization or arrest of degeneration of a wide variety of presently incurable and terminal medical conditions, diseases and disorders. The invention further relates to novel processes of preparing novel stem cell lines which are free of animal products, feeder cells, growth factors, leukaemia inhibitory factor, supplementary mineral combinations, amino acid supplements, vitamin supplements, fibroblast growth factor, membrane associated steel factor, soluble steel factor and conditioned media. This invention further relates to the isolation, culture, maintenance, expansion, differentiation, storage, and preservation of such stem cells.
Inventor(s):	Shroff; Geeta (New Delhi, IN)
Assignee:
Application Number:	14/063,573
Patent Claims:	1. A method of treating a disease, disorder, or condition comprising: (1) introducing hES cells, derivatives of hES cells, or combinations thereof in a cell culture medium consisting of minimal essential medium, a progestin, and a .beta.-human chorionic gonadotrophin (.beta.hCG) agonist, wherein the derivatives of hES cells are selected from the group consisting of hematopoietic stem cell progenitors, neuronal stem cell progenitors, mesenchymal stem cell progenitors, insulin producing stem cell progenitors, bilirubin producing stem cell progenitors, albumin producing stem cell progenitors, hepatocytic stem cell progenitors, cardiac stem cell progenitors, epithelial stem cell progenitors, and combinations thereof; (2) expanding the cells obtained in (1) at a temperature of about 34.degree. C. to about 38.degree. C. in an environment of about 3.5% to about 6% carbon dioxide for about 12 hours to about 48 hours; and (3) administering to a subject a therapeutically effective amount of the cells obtained in (2). 2. A method of treating a disease, disorder, or condition comprising: (1) introducing hES cells, derivatives of hES cells, or combinations thereof in a cell culture medium consisting of minimal essential medium, a progestin, and a .beta.human chorionic gonadotrophin (.beta.hCG) agonist. wherein the derivatives of hES cells are selected from the group consisting of hematopoietic stem cell progenitors, neuronal stem cell progenitors, mesenchymal stem cell progenitors, insulin producing stem cell progenitors, bilirubin producing stem cell progenitors, albumin producing stem cell progenitors, hepatocytic stem cell progenitors, cardiac stem cell progenitors, epithelial stem cell progenitors, and combinations thereof; (2) expanding the cells obtained in (1) at a temperature of about 34.degree. C. to about 38.degree. C. in an environment of about 3.5% to about 6% carbon dioxide for about 12 hours to about 48 hours; (3) introducing the expanded cells obtained in (2) in a cell culture medium consisting of minimal essential medium; (4) incubating the cells at a temperature of about 34.degree. C. to about 38.degree. C. in an environment of about 3.5% to about 6% carbon dioxide for about 12 hours to about 48 hours, wherein the cells are incubated in a biocompatible container under substantially aerobic conditions, and wherein the cells differentiate on proliferation; and (5) administering to a subject a therapeutically effective amount of the cells obtained in (4). 3. The method of claim 2 wherein the disease, disorder, or condition is selected from the group consisting of cancer, stroke, genetic disorders, liver disorders, developmental disorders, degenerative disorders, familial disorders, traumatic disorders of the nervous system, vascular disorders, skin diseases and disorders, auto immune disorders, eye disorders, kidney disorders, cardiac disorders, musculoskeletal disorders, reproductive and fertility disorders, arthritis, and blood disorders. 4. The method of claim 3 wherein the disease, disorder, or condition is a developmental disorder selected from the group consisting of Autism, Cerebral Palsy, Erb's Palsy, Mental Retardation, and Progressive Supranuclear Palsy. 5. The method of claim 3 wherein the disease, disorder, or condition is a degenerative disorder selected from the group consisting of Alzheimer's Disease, Corticobasal Degeneration, Deafness (Auditory Nerve Atrophy), Dementia, Friedereich's Ataxia, Motor Neuron Disease, Multiple Sclerosis, Olivo Ponto Cerebellar Atrophy, Parkinson's Disease, and Spino Cerebellar Ataxia. 6. The method of claim 3 wherein the disease, disorder, or condition is a traumatic disorder of the nervous system selected from the group consisting of Brain Damage, Coma, Post Electric Shock Encephalopathy, Post Rabies Vaccine Encephalopathy, Spinal Cord Damage or Injury, and Vegetative State. 7. The method of claim 3 wherein the disease, disorder, or condition is a vascular disorder and is Cerebro Vascular Accident or Stroke. 8. The method of claim 3 wherein the disease, disorder, or condition is a familial disorder selected from the group consisting of Hereditary Spino Motor Neuron Disease and Huntington's Chorea. 9. The method of claim 3 wherein the disease, disorder, or condition is a liver and kidney disorder selected from the group consisting of Cirrhosis of the Liver, End Stage Renal Disease, Nephrotic Syndrome, and Niemann Pick disease. 10. The method of claim 3 wherein the disease, disorder, or condition is a skin disorder selected from the group consisting of Arthritis, Artherosclerosis, Burns, Non-Healing Ulcers, Pressure Sores, Psoriasis, Systemic Lupus Erythematosus, and Sarcoidosis. 11. The method of claim 3 wherein the disease, disorder, or condition is an auto immune disorder selected from the group consisting of Thrombocytopenia, Systemic Lupus Erythematosus, Sarcoidosis, and Ulcerative Colitis. 12. The method of claim 3 wherein the disease, disorder, or condition is a genetic disorder selected from the group consisting of Down's syndrome, Ankylosing Spondylitis, Thalassemia, and Huntington's Chorea. 13. The method of claim 3 wherein the disease, disorder, or condition is an eye disorder selected from the group consisting of Optic Nerve Atrophy, Pthysis Bulbi, Macular Degeneration, Retinitis Pigmentosa, Corneal Abrasion, Corneal Graft Rejection, and Corneal Ulcers. 14. The method of claim 3 wherein the disease, disorder, or condition is a musculoskeletal disorder selected from the group consisting of Duchenne's Muscular Dystrophy, Fascio Scapular Muscular Dystrophy, Limb Girdle Dystrophy, Spinal Muscular Atrophy, and Becker's Muscular Dystrophy. 15. The method of claim 3 wherein the disease, disorder, or condition is a cardiac disorder selected from the group consisting of Myocardial Infarction, Right Bundle Branch Block, Restrictive Cardiomyopathy, Heart failure, Sinus Bradycardia, and Coronary Artery disease. 16. The method of claim 3 wherein the disease, disorder, or condition is selected from the group consisting of Acute Myeloid Leukaemia, Adenocarcinoma of the Adrenal Gland, Astrocytoma, Hepatocellular Carcinoma, and Spinal Cord Tumour. 17. The method of claim 3, wherein the disease is Diabetes Mellitus. 18. A method for treating a subject with a disease, disorder, or condition comprising: (1) introducing hES cells, derivatives of hES cells, or combinations thereof in a cell culture medium consisting of minimal essential medium, a progestin, and a .beta.-human chorionic gonadotrophin (.beta.hCG) agonist, wherein the derivatives of hES cells are selected from the group consisting of hematopoietic stem cell progenitors, neuronal stem cell progenitors, mesenchymal stem cell progenitors, insulin producing stem cell progenitors, bilirubin producing stem cell progenitors, albumin producing stem cell progenitors, hepatocytic stem cell progenitors, cardiac stem cell progenitors, epithelial stem cell progenitors, and combinations thereof; (2) expanding the cells obtained in (1) at a temperature of about 34.degree. C. to about 38.degree. C. in an environment of about 3.5% to about 6% carbon dioxide for about 12 hours to about 48 hours; and (3) administering to a subject a therapeutically effective amount of the cells obtained in (2) via intramuscular injection, intravenous injection, caudal injection, intravitreous injection, intrastriatal injection, intraparenchymal injection, epidural injection, epidural catheter infusion, retrobulbar injection, subcutaneous injection, intracardiac injection, intracystic injection, intrathecal injection, intra-articular injection, sub arachnoid block catheter infusion, topical application, local application, intralesional application, intravenous infusion, nebulizer, spray, intravaginal routes, local eye drops, or ear drops. 19. A method for treating a subject with a disease, disorder, or condition comprising: (1) introducing hES cells, derivatives of hES cells, or combinations thereof in a cell culture medium consisting of minimal essential medium, a progestin, and a .beta.-human chorionic gonadotrophin (.beta.hCG) agonist. wherein the derivatives of hES cells are selected from the group consisting of hematopoietic stem cell progenitors, neuronal stem cell progenitors, mesenchymal stem cell progenitors, insulin producing stem cell progenitors, bilirubin producing stem cell progenitors, albumin producing stem cell progenitors, hepatocytic stem cell progenitors, cardiac stem cell progenitors, epithelial stem cell progenitors, and combinations thereof; (2) expanding the cells obtained in (1) at a temperature of about 34.degree. C. to about 38.degree. C. in an environment of about 3.5% to about 6% carbon dioxide for about 12 hours to about 48 hours; (3) introducing the cells obtained in (2) in a cell culture medium consisting of minimal essential medium; (4) incubating the cells at a temperature of about 34.degree. C. to about 38.degree. C. in an environment of about 3.5% to about 6% carbon dioxide for about 12 hours to about 48 hours, wherein the cells are incubated in a biocompatible container under substantially aerobic conditions, and wherein the cells differentiate on proliferation; and (5) administering to a subject a therapeutically effective amount of the cells obtained in (4) via intramuscular injection, intravenous injection, caudal injection, intravitreous injection, intrastriatal injection, intraparenchymal injection, epidural injection, epidural catheter infusion, retrobulbar injection, subcutaneous injection, intracardiac injection, intracystic injection, intrathecal injection, intra-articular injection, sub arachnoid block catheter infusion, topical application, local application, intralesional application, intravenous infusion, nebulizer, spray, intravaginal routes, local eye drops, or ear drops. 20. The method of claim 19 wherein the therapeutically effective amount of hES cells, derivatives of hES cells, or combinations thereof is about 750,000 to about 160 million cells. 21. The method of claim 19 wherein the disease is selected from the group consisting of cancer, stroke, genetic disorders, liver disorders, developmental disorders, degenerative disorders, familial disorders, traumatic disorders of the nervous system, vascular disorders, skin diseases and disorders, auto immune disorders, eye disorders, kidney disorders, cardiac disorders, musculoskeletal disorders, reproductive and fertility disorders, arthritis, and blood disorders. 22. The method of claim 19 wherein the disease, disorder, or condition is selected from the group consisting of Acute Myeloid Leukaemia, Adenocarcinoma, Arthritis, Astrocytoma, Auditory Nerve Atrophy, Autism, Auto Immune Disorders, Alzheimer's disease, Ankylosing Spondylitis, Becker's Muscular Dystrophy, Brain Damage, Burns, Cerebro Vascular Accident, Cerebral Palsy, Coma, Corneal Ulcers, Corneal Graft Rejection, Cortico-Basal Degeneration of the Nervous System, Coronary Artery Disease, Diabetes, Dementia, Downs Syndrome, Duchenne's Muscular Dystrophy, End-Stage Renal Disease, Erb's Palsy, Fascio Scapular Muscular Dystrophy, Fertility Disorders, Friedereich's Ataxia, Heart Failure, Hepato Cellular Carcinoma, Hereditary Spino Motor Neuron Disease, Huntington's Chorea, Krabbe's Disease, Limb Girdle Dystrophy, Liver Cirrhosis, Macular Degeneration, Mental Retardation, Multiple Sclerosis, Motor Neuron Disease, Myocardial Infarction, Nephrotic Syndrome, Niemann Pick Disease, Non-Healing Ulceration of the Skin, Olivo-Ponto Cerebellar Atrophy, Optic Nerve Atrophy, Parkinson's Disease, Post Electric Shock Encephalopathy, Post-Rabies Vaccine Encephalopathy, Pressure Sores, Progressive Supranuclear Palsy, Psoriasis, Pthysis Bulbi, Restrictive Cardiomyopathy, Retinitis Pigmentosa, Right Bundle Branch Block, Sarcoidosis, Sinus Bradycardia, Spinal Cord Tumour, Spinal Muscular Dystrophy, Spino Cerebellar Ataxia, Steven Johnson's Syndrome, Systemic Lupus Erythematosus, Thrombocytopenia, Thalassemia, Ulcerative Colitis, Vegetative State, Cystic Fibrosis, Interstitial Lung Disease, Azoospermia, Primary Ovarian Failure, Aphthous Ulcers, Hormone Imbalance, Osteo-Arthritis, Homer's Syndrome, Osteogenic Imperfecta, Channelopathy, and Hypogammaglobulinemia. 23. The method of claim 19 wherein the administration of hES cells, derivatives of hES cells, or combinations thereof does not cause tumours, teratomas, or chromosomal changes. 24. The method of claim 19, wherein the disorder is Spinal Cord Injury (SCI) and the administration comprising: (a) administering about 750,000 to about 80 million hES cells, derivatives of hES cells, or combinations thereof via subcutaneous injection; (b) repeating step (a) after a pre-determined period and thereafter administering a therapeutically effective amount of hES cells, derivatives of hES cells, or combinations thereof via intramuscular injection; (c) administering a therapeutically effective amount of hES cells, derivatives of hES cells, or combinations thereof, wherein said cells comprise neuronal stem cell progenitors and hematopoietic stem cell progenitors, via intravenous injection or infusion; (d) administering a therapeutically effective amount of hES cells, derivatives of hES cells, or combinations thereof, wherein said cells comprise neuronal stem cell progenitors, via epidural injection and repeating said dose after a pre-determined period depending upon the condition of the subject as assessed by clinical examination, neurological examination, or combinations thereof; (e) administering a therapeutically effective amount of hES cells, derivatives of hES cells, or combinations thereof, wherein said cells comprise neuronal stem cell progenitors, via caudal injection; (f) administering a therapeutically effective amount of hES cells, derivatives of hES cells, or combinations thereof, wherein said cells comprise neuronal stem cell progenitors via intrathecal injection or sub arachnoid block catheter infusion; (g) administering a therapeutically effective amount of hES cells, derivatives of hES cells, or combinations thereof, wherein said cells comprise neuronal stem cell progenitors via epidural injection or epidural catheter infusion; (h) administering a therapeutically effective amount of hES cells, derivatives of hES cells, or combinations thereof via deep spinal injection on either side of the spine; and (i) administering a therapeutically effective amount of hES cells, derivatives of hES cells, or combinations thereof via intravenous infusion; wherein steps (a) and (b) are carried out first and the remaining steps may be carried out in any order. 25. The method of claim 24 further comprising repeating step (f) followed by step (g), until the subject exhibits clinical signs of recovery from said SCI. 26. The method of claim 24 wherein said cells in step (a) and step (b) comprise hematopoietic stem cell progenitors and neuronal stem cell progenitors, and are suspended in 0.25 to 1.0 ml of a biocompatible solution. 27. The method of claim 24 wherein said cells in step (f) comprise hematopoietic stem cell progenitors and neuronal stem cell progenitors, and are suspended in 2.0 to 4.0 ml of a biocompatible solution. 28. The method of claim 24 wherein said cells in step (g) comprise hematopoietic stem cell progenitors and neuronal stem cell progenitors, and are suspended in 15 to 40 ml of a biocompatible solution. 29. The method of claim 24 wherein said treatment of subjects with SCI results in the amelioration of bed sores. 30. The method of claim 20 wherein the disease, disorder, or condition is developmental disorders, degenerative disorders, familial disorders, or traumatic disorders of the nervous system, wherein said cells comprise neuronal stem cell progenitors, hematopoietic stem cell progenitors, or combinations thereof, and wherein the cells are administered via intravenous injection, subcutaneous injection, intramuscular injection, intrathecal injection, epidural catheter infusion, or sub arachnoid block catheter infusion. 31. The method of claim 20 wherein said cells comprise hematopoietic stem cell progenitors, wherein the disease, disorder, or condition is skin disorders, and wherein the cells are administered via local application or topical application. 32. The method of claim 31 wherein said hES cells, hematopoietic stem cell progenitors, or combinations thereof are mixed in a biocompatible carrier to be applied to the damaged skin. 33. The method of claim 32 wherein said biocompatible carrier is a gel, ointment, paste, or aerosol spray. 34. The method of claim 20, wherein the disease, disorder, or condition is bed sores, and wherein the cells are administered via local application, topical application, or intramuscular injection. 35. The method of claim 20, wherein the disease, disorder, or condition is auto immune disorders, and wherein the cells are administered via intramuscular injection, intravenous injection, subcutaneous injection, intra-articular injection, intravenous infusion, or combinations thereof. 36. The method of claim 20 wherein said cells comprise neuronal stem cell progenitors, hematopoietic stem cell progenitors, or combinations thereof, wherein the disease, disorder, or condition is genetic disorders, and wherein the cells are administered via intravenous injection, subcutaneous injection, intramuscular injection, intrathecal injection, epidural catheter infusion, sub arachnoid block catheter infusion, or combinations thereof. 37. The method of claim 20, wherein the disease, disorder, or condition is gangrene, and wherein the cells are administered via intravenous injection, intramuscular injection, local application at the junction of viable and dead tissue, or combinations thereof. 38. The method of claim 20, wherein the disease, disorder, or condition is ageing, and wherein the cells are administered via intravenous injection, subcutaneous injection, intramuscular injection, local application in suspension, or mixed in a biocompatible carrier. 39. The method of claim 38 wherein said biocompatible carrier is a gel, ointment, paste, or aerosol spray. 40. The method of claim 20, wherein the cells are human embryonic insulin producing progenitor cells, wherein the disease, disorder, or condition is Diabetes Mellitus, wherein the cells are administered via intravenous injection, intramuscular injection, or both. 41. The method of claim 20, wherein said cells comprise hematopoietic stem cell progenitors, wherein the disease, disorder, or condition is Cardiovascular Disorders, and wherein the cells are administered via intravenous injection, subcutaneous injection, intramuscular injection, intracardiac injection, or combinations thereof. 42. The method of claim 40 wherein said administration is during angiography. 43. The method of claim 20, wherein said cells comprise hematopoietic stem cell progenitors, albumin producing stem cell progenitors, and bilirubin producing stem cell progenitors, wherein the disease, disorder, or condition is Liver and Kidney Disorders, and wherein the cells are administered via intravenous injection, subcutaneous injection, intramuscular injection, intravenous infusion, local injection, or combinations thereof. 44. The method of claim 20, wherein said cells comprise hematopoietic stem cell progenitors, wherein the disease, disorder, or condition is Fertility and Reproductive Disorders, and wherein the cells are administered via local intramuscular injection, intratesticular injection, through subcutaneous skin injection near the epididymis, or combinations thereof. 45. The method of claim 20, wherein the disease, disorder, or condition is Musculoskeletal disorders, wherein said cells comprise neuronal stem cell progenitors, hematopoietic stem cell progenitors, or combinations thereof, and wherein the cells are administered via intravenous injection, subcutaneous injection, intramuscular injection, intravenous catheter infusion, or combinations thereof. 46. The method of claim 20, wherein said cells comprise neuronal stem cell progenitors, hematopoietic stem cell progenitors, mesenchymal stem cell progenitors, or combinations thereof, wherein the disease, disorder, or condition is Eye Disorders, and wherein the cells are administered via local intravenous injection, subcutaneous injection, intramuscular injection, retrobulbar injection, intravitreous injection, topical application, or combinations thereof. 47. The method of claim 46 wherein said cells comprise neuronal stem cell progenitors, and wherein the cells are administered via retrobulbar injection. 48. The method of claim 46 wherein said cells comprise neuronal stem cell progenitors, and wherein the cells are administered via intravitreous injection. 49. The method of claim 46 wherein said cells comprise mesenchymal stem cell progenitors, and wherein the cells are applied to contact lenses for the treatment of corneal abrasion. 50. The method of claim 20, wherein said cells comprise neuronal stem cell progenitors, hematopoietic stem cell progenitors, or combinations thereof, wherein the disease, disorder, or condition is Lung Disorders, and wherein the cells are administered via intramuscular injection, intravenous injection, spray, nebulizer, or combinations thereof. 51. The method of claim 20, wherein said cells comprise neuronal stem cell progenitors, hematopoietic stem cell progenitors, or combinations thereof, wherein the disease, disorder, or condition is Hormone Disorders, and wherein the cells are administered via intramuscular injection, intravenous injection, or combinations thereof. 52. The method of claim 20, wherein said cells comprise neuronal stem cell progenitors, hematopoietic stem cell progenitors, or combinations thereof, wherein the disease, disorder, or condition is Aphthous Ulcers, and wherein the cells are administered via intramuscular injection, intravenous injection, or combinations thereof. 53. The method of claim 20, wherein said cells comprise neuronal stem cell progenitors, hematopoietic stem cell progenitors, or combinations thereof, wherein the disease, disorder, or condition is Osteo-arthritis of the knee and hip joint, and wherein the cells are administered via intramuscular injection, intravenous injection, intra-articular injection, or combinations thereof.

Details for Patent 9,804,151

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bavarian Nordic A/s	RABAVERT	rabies vaccine	For Injection	103334	10/20/1997		2026-03-07
Sanofi Pasteur Sa	IMOVAX RABIES	rabies vaccine	For Injection	103931	02/04/2000		2026-03-07