Enhanced MSC preparations

Patent metadata

Field	Value
Publication number	US-12410405-B2
Application number	US-202318331353-A
Country	US
Kind code	B2
Filing date	Jun 8, 2023
Priority date	Oct 8, 2010
Publication date	Sep 9, 2025
Grant date	Sep 9, 2025

Abstract

The present invention provides preparations of MSCs with important therapeutic potential. The MSC cells are non-primary cells with an antigen profile comprising less than about 1.25% CD45+ cells (or less than about 0.75% CD45+), at least about 95% CD105+ cells, and at least about 95% CD166+ cells. Optionally, MSCs of the present preparations are isogenic and can be expanded ex vivo and cryopreserved and thawed, yet maintain a stable and uniform phenotype. Methods are taught here of expanding these MSCs to produce a clinical scale therapeutic preparations and medical uses thereof.

First claim

What is claimed is:

1. A mesenchymal stem cell (MSC) preparation comprising:
cultured human bone-marrow-derived MSCs expanded from a cryopreserved in-process intermediate MSC preparation; wherein the cultured human bone-marrow-derived MSCs
(a) have an antigen profile comprising:
i. less than 0.75% CD45+ cells;
ii. at least 95% CD105+ cells; and
iii. at least 95% CD166+ cells; and

(b) are capable of inhibiting IL2Rα expression by CD3/CD28-activated PBMCs by at least 30% relative to a control.

2. The MSC preparation of claim 1 , wherein the MSCs express at least 13 pg TNFR1 per million MSCs.

3. The MSC preparation of claim 1 , wherein the MSCs express at least 108 pg TNFR1 per million MSCs.

4. The MSC preparation of claim 1 , wherein the MSCs express about 13 pg to about 179 pg TNFR1 per million MSCs.

5. The MSC preparation of claim 1 , wherein the MSCs express 108 pg to 368 pg TNFR1 per million MSCs.

6. The MSC preparation of claim 1 , wherein the MSCs express TNFR1 at a minimum of 272 pg/mL and a maximum of 1471 pg/mL.

7. A frozen cell suspension composition comprising:
(a) cultured human bone-marrow-derived MSCs expanded from a cryopreserved in-process intermediate MSC preparation with an antigen profile comprising: i. less than 0.75% CD45+ cells; ii. at least 95% CD105+ cells; and iii. at least 95% CD166+ cells; wherein the cultured human bone-marrow-derived MSCs are capable of inhibiting IL2Ra expression by CD3/CD28-activated PBMCs by at least 30% relative to a control;
(b) an electrolyte solution,
(c) 5% human serum albumin, and
(d) 10% DMSO.

8. A method of treating steroid refractory acute Graft versus Host Disease (aGvHD) in a pediatric patient comprising intravenously administering eight biweekly therapeutic doses of 2×10 6 mesenchymal stem cells/kg.

9. The method of claim 8 , wherein the MSCs express at least 13 pg TNFR1 per million MSCs.

10. The method of claim 8 , wherein the MSCs express at least 108 pg TNFR1 per million MSCs.

11. The method of claim 8 , wherein the MSCs express about 13 pg to about 179 pg TNFR1 per million MSCs.

12. The method of claim 8 , wherein the MSCs express about 13 pg to about 44 pg TNFR1 per million MSCs.

13. The method of claim 8 , wherein the MSCs express 108 pg to 368 pg TNFR1 per million MSCs.

14. The method of claim 8 , wherein the MSCs express TNFR1 at a minimum of 272 pg/mL and a maximum of 1471 pg/mL.

15. The method of claim 8 , wherein the MSC are autologous.

16. The method of claim 8 , wherein the MSC are allogeneic.

Assignees

• Mesoblast Int Sarl

Inventors

• Tom Samson
• Ton Christopher
• Danilkovitch Alla

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61K2035/122

  for inducing tolerance or supression of immune responses · CPC title

• A61K47/6901

  Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title

• A61M37/00

  Other apparatus for introducing media into the body (for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30); Percutany, i.e. introducing medicines into the body by diffusion through the skin (salt baths A61H33/04) · CPC title