Cellular compositions for use in therapy

• US 9,265,795 B2
• Filed: 12/07/2009
• Issued: 02/23/2016
• 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
• Primary Examiner(s): Ton, Thaian N
• Application Number:
  US13/132,475
• Publication Number:
  US 20120076854A1
• Time in Patent Office: 2,269 Days
• US Class Current: 1/1
• 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 method of formulating human neural stem cells, mesenchymal stem cells, or retinal progenitor cells for direct administration to a patient, comprising:

(i) suspending the cells in a composition comprising;

Trolox, Na⁺, K⁺, Ca²⁺, Mg²⁺, Cl⁻

, H₂PO₄⁻

, HEPES, lactobionate, sucrose, mannitol, glucose, dextran-40, adenosine and glutathione, wherein the composition does not include a dipolar aprotic solvent,

(ii) storing the cell suspension at a cryothermic temperature; and

(iii) thawing the stored suspension,

wherein at least 70% of the cells are viable after thawing.

2. The method according to claim 1, wherein the cells are recovered from a cell-culture system.

3. The method according to claim 1, wherein said storing is carried out at a temperature of −

70°

C. to −

200°

C.

4. The method according to claim 1, wherein the cell suspension is stored at a hypothermic temperature after said storing or said thawing.

5. The method according to claim 4, wherein the hypothermic storage is carried out at a temperature of 2°

C. to 8°

C.

6. The method according to claim 1, wherein the cells are mesenchymal stem cells.

7. The method according to claim 1, wherein the cells are neural stem cells.

8. The method according to claim 1, wherein the cells are retinal progenitor cells.

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

10. The method according to claim 9, wherein the polymeric scaffold or microcarrier is PLGA.

11. The method according to claim 1, wherein the cells are encapsulated.

12. The method according to claim 11, 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.

13. The method according to claim 1, further comprising loading the suspended cells into a cell delivery cannula.

14. A method for delivery of human neural stem cells, mesenchymal stem cells, or retinal progenitor cells, comprising:

thawing a composition stored at a cryothermic or hypothermic temperature, wherein the composition comprises the neural stem cells, mesenchymal stem cells, or retinal progenitor cells, Trolox, Na⁺, K⁺, Ca²⁺, Mg²⁺, Cl⁻

, H₂PO₄⁻

, HEPES, lactobionate, sucrose, mannitol, glucose, dextran-40, adenosine and glutathione, wherein the composition does not include a dipolar aprotic solvent; and

directly administering the composition to a patient in need thereof, wherein the method includes no rinsing of the composition after said thawing and before said administering, wherein the cells of the administered composition are viable and differentiate in vivo, and wherein at least 70% of the cells are viable after thawing.

15. The method according to claim 14, wherein the composition is administered via implantation into tissue or systemic delivery.

16. The method according to claim 14, wherein the composition is administered to the patient via a cell delivery cannula.