Compositions comprising human embryonic stem cells and their derivatives, methods of use, and methods of preparation

• US 10,545,135 B2
• Filed: 03/06/2007
• Issued: 01/28/2020
• Est. Priority Date: 03/07/2006
• Status: Active Grant

• Current Assignee: Geeta Shroff
• Original Assignee: Geeta Shroff
• Inventors: Shroff, Geeta
• Primary Examiner(s): Lankford, Blaine
• Application Number:
  US12/224,839
• Publication Number:
  US 20090123433A1
• Time in Patent Office: 4,711 Days
• Field of Search: None
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/48 Reproductive organs
• CPC Class Codes: A61K 35/545 Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 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
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 39/00 : General protective or antinoxious agents
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12N 2501/31 : Pituitary sex hormones, e.g. follicle-stimulating hormone [FSH], luteinising hormone [LH]; Chorionic gonadotropins
• CPC Class Codes: C12N 2501/392 : Sexual steroids
• CPC Class Codes: C12N 5/0603 : Embryonic cells production of embryos, nuclear transfer A01K67/027; Embryoid bodies
• CPC Class Codes: C12N 5/0606 : Pluripotent embryonic cells, e.g. embryonic stem cells [ES] embryonic germ cells C12N5/0611, induced pluripotent stem cells C12N5/0696
• CPC Class Codes: G01N 33/5044 : involving specific cell types

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.

Claims

1. A pharmaceutical composition for the treatment of diseases, disorders, or conditions comprising a therapeutic effective amount of human embryonic stem (hES) cells, derivatives of hES cells, or combinations thereof, wherein said hES cells, derivatives of hES cells, or combinations thereof are free from feeder cells, animal products, growth factors, leukemia inhibiting factor, fibroblast growth factor, vitamin supplements, membrane associated steel factor, soluble steel factor, and conditioned media, wherein the hES cells, derivatives of hES cells, or combinations thereof do not give rise to teratomas upon administration, wherein said hES cells, derivatives of hES cells, or combinations thereof are suspended in a pharmaceutically acceptable biocompatible solution, wherein said derivatives of hES cells are selected from the group consisting of hematopoietic stem cell progenitors, neuronal stem cell progenitors, a combination of hematopoietic stem cell progenitors and neuronal stem cell progenitors, mesenchymal stem cell progenitors, insulin producing stem cell progenitors, hepatocytic stem cell progenitors, cardiac stem cell progenitors, and epithelial stem cell progenitors, and wherein the composition contains trace amounts of a progestin and a β

-human chorionic gonadotrophin (β

hCG) agonist.

2. The pharmaceutical composition of claim 1 wherein said composition is in a ready-to-use form.

3. The pharmaceutical composition of claim 2, wherein said ready-to-use form is a prefilled syringe.

4. The pharmaceutical composition of claim 2 wherein the stem cells have sufficient viability to be therapeutically effective.

5. The pharmaceutical composition of claim 4 wherein the viability of the stem cells is greater than 40%.

6. The pharmaceutical composition of claim 1 wherein said biocompatible solution is saline.

7. The pharmaceutical composition of claim 1 wherein said biocompatible solution further comprises an antimicrobial agent, antibacterial agent or other pharmaceutical agent.

8. The pharmaceutical composition of claim 1 wherein the composition comprises a therapeutically effective amount of hematopoietic stem cell progenitors and neuronal stem cell progenitors.

9. The pharmaceutical composition of claim 1 wherein the composition comprises a therapeutically effective amount of mesenchymal stem cell progenitors.

10. The pharmaceutical composition of claim 1 wherein the composition comprises a therapeutically effective amount of insulin producing stem cell progenitors.

11. The pharmaceutical composition of claim 1 wherein the composition comprises a therapeutically effective amount of hepatocytic stem cell progenitors.

12. The pharmaceutical composition of claim 1 wherein the composition comprises a therapeutically effective amount of cardiac stem cell progenitors.

13. The pharmaceutical composition of claim 1 wherein the composition comprises a therapeutically effective amount of epithelial stem cell progenitors.

14. The pharmaceutical composition of claim 1 wherein the therapeutically effective amount of hES cells, derivatives or hES cells, or combinations thereof is about 750,000 to about 160 million cells in about 0.25 ml to about 100 ml of the biocompatible solution.

15. The pharmaceutical composition of claim 1 wherein the therapeutically effective amount of hES cells, derivatives or hES cells, or combinations thereof is 750,000 to about 80 million cells in about 0.25 ml to about 10 ml of the biocompatible solution.

16. The pharmaceutical composition of claim 1 wherein the diseases, disorders or conditions are selected from the group consisting of cancer, stroke, genetic disorders, liver disorders, developmental disorders, degenerative disorders, familial disorders or 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.

17. The pharmaceutical composition of claim 1 wherein the diseases, disorders, or conditions are 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.

18. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises combinations of hES cells and derivatives of hES cells.

19. The pharmaceutical composition of claim 1, wherein the total population of (hES) cells, derivatives of hES cells, or combinations thereof contains no more than 40% undifferentiated stem cells.

20. The composition of claim 19, wherein the hES cells and derivatives of hES cells were obtained by expanding in a cell culture medium consisting of minimal essential medium, a progestin, and a β

hCG agonist.

21. The pharmaceutical composition of claim 1 wherein the composition comprises a therapeutically effective amount of hematopoietic stem cell progenitors.

22. The pharmaceutical composition of claim 21 wherein the therapeutically effective amount of hematopoietic stem cell progenitors in the composition is about 750,000 to about 160 million cells.

23. The pharmaceutical composition of claim 1 wherein the composition comprises a therapeutically effective amount of neuronal stem cell progenitors.

24. The pharmaceutical composition of claim 23 wherein the therapeutically effective amount of neuronal stem cells in the composition is about 750,000 to about 160 million cells.

25. A composition of matter comprising hES cells, derivatives of hES cells, or combinations thereof, wherein said hES cells, derivatives of hES cells, or combinations thereof are free from feeder cells, animal products, growth factors, leukemia inhibiting factor, fibroblast growth factor, vitamin supplements, membrane associated steel factor, soluble steel factor, and conditioned media, wherein the hES cells, derivatives of hES cells, or combinations thereof do not give rise to teratomas upon administration, wherein said hES cells, derivatives of hES cells, or combinations thereof are entrapped in a biocompatible structure or matrix, wherein the biocompatible structure or matrix is selectively permeable, wherein said hES cell derivatives are selected from the group consisting of hematopoietic stem cell progenitors, neuronal stem cell progenitors, a combination of hematopoietic stem cell progenitors and neuronal stem cell progenitors, mesenchymal stem cell progenitors, insulin producing stem cell progenitors, hepatocytic stem cell progenitors, cardiac stem cell progenitors, and epithelial stem cell progenitors, and wherein the composition contains trace amounts of a progestin and a β

-human chorionic gonadotrophin (β

hCG) agonist.

26. The composition of matter of claim 25 wherein the hES cells, derivatives of hES cells, or combinations thereof comprise hematopoietic stem cell progenitors.

27. The composition of matter of claim 25, wherein the hES cells, derivatives of hES cells, or combinations thereof comprise neuronal stem cell progenitors.

28. The composition of matter of claim 25, wherein the hES cells, derivatives of hES cells, or combinations thereof comprise a combination of hematopoietic stem cells and neuronal stem cell progenitors.

29. The composition of matter of claim 25, wherein the biocompatible, selectively permeable structure or matrix is selected from the group consisting of biopolymers, polypeptides, proteins, polysaccharides, fibronectin, collagen, laminin, keratin, fibrin, fibrinogen, hyaluronic acid, heparin sulfate, chondroitin sulfate, agarose, and gelatin.

30. The composition of matter of claim 25, wherein the hES cells, derivatives of hES cells, or combinations thereof are entrapped in a mixture of agarose and collagen or a mixture of agarose and gelatin.

31. The composition of claim 25, wherein the composition comprises combinations of hES cells and derivatives of hES cells.

32. The composition of claim 25, wherein the total population of (hES) cells, derivatives of hES cells, or combinations thereof contains no more than 40% undifferentiated stem cells.

33. The composition of claim 32, wherein the hES cells and derivatives of hES cells were obtained by expanding in a cell culture medium consisting of minimal essential medium, a progestin, and a β

hCG agonist.