	US 12,233,092 B2
	MSC-NTF specific exosomes and use thereof
Revital Aricha, Giv'at Shmuel (IL); Haggai Kaspi, Ganei Tikva (IL); Jonathan Semo, Giv'atayim (IL); and Yael Gothelf, Kiryat Ono (IL)
Assigned to BRAINSTORM CELL THERAPEUTICS LTD., Petach Tikva (IL)
Appl. No. 16/981,757
Filed by BRAINSTORM CELL THERAPEUTICS LTD., Petach Tikva (IL)
PCT Filed Apr. 10, 2019, PCT No. PCT/IL2019/050401 § 371(c)(1), (2) Date Sep. 17, 2020, PCT Pub. No. WO2019/198077, PCT Pub. Date Oct. 17, 2019.
Claims priority of provisional application 62/665,558, filed on May 2, 2018.
Claims priority of provisional application 62/655,249, filed on Apr. 10, 2018.
Prior Publication US 2021/0030807 A1, Feb. 4, 2021
Int. Cl. A61K 35/28 (2015.01); C07K 14/475 (2006.01); C07K 14/49 (2006.01); C07K 14/52 (2006.01); C07K 14/54 (2006.01); A61K 38/00 (2006.01); A61P 25/16 (2006.01)

CPC A61K 35/28 (2013.01) [C07K 14/475 (2013.01); C07K 14/49 (2013.01); C07K 14/521 (2013.01); C07K 14/5415 (2013.01); C07K 14/5437 (2013.01); A61K 38/00 (2013.01); A61P 25/16 (2018.01)]

9 Claims

1. A pharmaceutical composition comprising an isolated exosome population derived from mesenchymal stem cells secreting-neurotrophic factors (MSC-NTF cells), said isolated exosomes comprising an increased quantity of at least one cargo protein, wherein said at least one cargo protein comprises a neurotrophic factor (NTF), compared with the quantity of said at least one cargo protein in an isolated exosome population derived from control non-differentiated MSCs, wherein said NTF comprises a leukemia inhibitory factor (LIF) protein, a vascular endothelial growth factor A (VEGFA) protein, or a growth differentiation factor 15 (GDF15) protein, or any combination thereof,

wherein said MSC-NTF cells are cultured in a three-dimensional (3D) bioreactor in no shear stress, and propagated in Dulbecco's Modified Eagle's Medium (DMEM) comprising platelet lysate,

wherein said exosomes are purified by removing the culture media from the three-dimensional (3D) bioreactor, filtered using a 1.2 μM filter and Tangential Flow Filtration (TFF), and further filtered through a 0.22 μM filter.