CELLULAR COMPOSITIONS FOR USE IN THERAPY

• US 20120076854A1
• Filed: 12/07/2009
• Published: 03/29/2012
• Est. Priority Date: 12/05/2008
• Status: Active Grant

• Current Assignee: ReNeuron Limited (ReNeuron Group Plc)
• Original Assignee: ReNeuron Limited (ReNeuron Group Plc)
• Inventors: Miljan, Erik, Sinden, John, Hope, Andrew
• Granted Patent: US 9,265,795 B2
• Time in Patent Office: Days
• US Class Current: 424/451
• CPC Class Codes: A61K 2035/128 capsules, e.g. microcapsules
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• 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 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 38/063 Glutathione
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• 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 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 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/10 for petit-mal
• 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• 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 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• 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

Abstract

The present invention provides a therapeutic composition comprising:

• • (i) Trolox, Na⁺, K⁺, Ca²⁺, Mg²⁺, Cl⁻, H₂PO₄⁻, HEPES, lactobionate, sucrose, mannitol, glucose, dextran-40, adenosine, glutathione; and
  • (ii) stem cells or progenitor cells,
    wherein the composition does not comprise a dipolar aprotic solvent, in particular DMSO.

The present invention also relates to methods of formulating said composition for cryopreservation and subsequent direct administration to a patient, and medicaments comprising said composition.

Claims

1. A composition comprising:

i) Trolox, Na⁺, K⁺, Ca²⁺, Mg²⁺, Cl⁻

, H₂PO₄⁻

, HEPES, lactobionate, sucrose, mannitol, glucose, dextran-40, adenosine and glutathione; and

ii) stem cells or progenitor cells,

wherein the composition does not include a dipolar aprotic solvent, in particular DMSO.

2. The composition according to claim 1, wherein the cells are human stem cells or human progenitor cells.

3. The composition according to claim 2, wherein the cells are hematopoietic stem cells.

4. The composition according to claim 2, wherein the cells are mesenchymal stem cells.

5. The composition according to claim 2, wherein the cells are neural stem cells.

6. The composition according to claim 2, wherein the cells are retinal progenitor cells.

7. The composition according to claim 1, wherein the cells are comprised in a polymeric scaffold or micro-carrier.

8. The composition according to claim 7, wherein the polymeric scaffold or microcarrier is PLGA.

9. A method of formulating stem cells or progenitor cells for administration to a patient, comprising suspending the cells in a composition comprising:

Trolox, Na⁺, K⁺, Ca²⁺, Mg²⁺, Cl⁻

, H₂PO₄⁻

, HEPES, lactobionate, sucrose, mannitol, glucose, dextran-40, adenosine and glutathione.

10. The method according to claim 9, wherein the cells are recovered from a cell-culture system.

11. The method according to claim 9, wherein the method comprises the following initial steps:

(a) suspending the cells in a composition comprising;

Trolox, Na⁺, K⁺, Ca²⁺, Mg²⁺, Cl⁻

, H₂PO₄⁻

, HEPES, lactobionate, sucrose, mannitol, glucose, dextran-40, adenosine and glutathione;

(b) storing the cell suspension of step (a) at a cryothermic temperature; and

(c) thawing the suspension of step (b).

12. The method according to claim 11, wherein step (b) is carried out at a temperature of −

70°

C. to −

200°

C.

13. The method according to claim 11, wherein the cell suspension is stored at a hypothermic temperature after step (b) or step (c).

14. The method according to claim 13, wherein the hypothermic storage is carried out at a temperature of 2°

C. to 8°

C.

15. The method according to claim 9, wherein the cells are human stem cells or human progenitor cells.

16. The method according to claim 15, wherein the cells are hematopoietic stem cells.

17. The method according to claim 15, wherein the cells are mesenchymal stem cells.

18. The method according to claim 15, wherein the cells are neural stem cells.

19. The method according to claim 15, wherein the cells are retinal progenitor cells.

20. The method according to claim 9, wherein the cells are comprised in a polymeric scaffold or micro-carrier.

21. The method according to claim 20, wherein the polymeric scaffold or a microcarrier is PLGA.

22. The method according to claim 9, wherein the cells are encapsulated.

23. The method according to claim 22, wherein the cells are encapsulated in a substance selected from alginate, chitosan, PEG, PLL, poly-L-ornithine14, poly(methylene-co-guanidine) hydrochloride, pluronics, glycerol phosphate, hyaluronic acid, cellulose phosphate, starch, agarose, carrageenan, silk fibroin, gelatine and gellan gum.

24. The method according to claim 9, wherein the formulation is administered via a cell delivery cannula.

25. A medicament in a unit dose form, comprising a composition comprising:

i) Trolox, Na⁺, K⁺, Ca²⁺, Mg²⁺, Cl⁻

, H₂PO₄⁻

, HEPES, lactobionate, sucrose, mannitol, glucose, dextran-40, adenosine and glutathione; and

ii) stem cells or progenitor cells,

wherein the composition does not include a dipolar aprotic solvent.

26. The medicament according to claim 25, wherein the medicament is administered directly to a patient in need thereof via implantation into tissue or systemic delivery.