Granted Patent B2

US 12,680,082 · App. 18/151,625 · Granted Jul 14, 2026

Inventors: Dhruv Sareen (Porter Ranch, CA); Loren A. Ornelas (Los Angeles, CA); Clive Svendsen (Pacific Palisades, CA)

Assignee: Cedars-Sinai Medical Center

C12N5/0696C12N5/0018C12N2500/12C12N2500/38C12N2501/115C12N2501/2302C12N2501/2303C12N2501/2306C12N2501/33C12N2501/60C12N2501/602C12N2501/603C12N2501/604C12N2501/606C12N2501/998C12N2506/11C12N2506/115C12N2510/00C12N2533/52

Abstract

Claims (22)

1 . A blood cell derived induced pluripotent stem cell (BC-iPSC) line,

wherein the BC-iPSC line is derived from non-expanded peripheral blood mononuclear cells (PBMCs) that are T-cells and comprises T-cell receptor gene rearrangement, and

wherein the BC-iPSC line does not show statistically significant differences between a first and a repeat G-band karyotype analysis, wherein the first or the repeat G-band karyotype analysis occurs during passages 10-23.

2 . The BC-iPSC line of claim 1 , wherein:

the BC-iPSC line has lower incidences of genomic aberrations compared to iPSC lines generated from fibroblast-derived iPSCs (Fib-iPSCs);

the BC-iPSC line exhibits less than 5% abnormal karyotype after 4-8 passages; and/or

the BC-iPSC line exhibits less than 2.8% abnormal karyotype after 4 passages.

3 . The BC-iPSC line of claim 1 , wherein the BC-iPSC line is produced by a reprogramming process comprising:

delivering a quantity of EBNA1 and reprogramming factors comprising Oct-4, Sox-2, Klf-4, l-Myc, Lin-28, SV40 Large T Antigen (“SV40LT”), and short hairpin RNAs targeting p53 (“shRNA-p53”) into isolated non-expanded PBMCs, wherein the reprogramming factors are encoded in one or more oriP/EBNA1 derived vectors; and

culturing the isolated non-expanded PBMCs in a reprogramming media for at least 4 days.

4 . The BC-iPSC line of claim 3 , wherein the one or more oriP/EBNA1 derived vectors comprise pEP4 E02S ET2K, pCXLE-hOCT3/4-shp53-F, pCXLE-hSK, pCXLE-hUL, and pCXWB-EBNA1.

5 . The BC-iPSC line of claim 3 , wherein the one or more oriP/EBNA1 derived vectors comprise:

a first vector encoding Oct4, Sox2, SV40LT and Klf4;

a second vector encoding Oct4 and shRNA-p53;

a third vector encoding Sox2 and Klf4; and

a fourth vector encoding l-Myc and Lin-28.

6 . The BC-iPSC line of claim 5 , wherein the quantity of EBNA1 is encoded by a fifth vector encoding EBNA1.

7 . A blood cell derived induced pluripotent stem cell (BC-iPSC) line,

wherein the BC-iPSC line is derived from non-expanded peripheral blood mononuclear cells (PBMCs) that are T-cells and comprises T-cell receptor gene rearrangement, and

wherein the BC-iPSC line exhibits less than 2.8% abnormal karyotype after 4 passages.

8 . The BC-iPSC line of claim 7 , wherein the BC-iPSC line exhibits less than 5% abnormal karyotype after 4-8 passages.

9 . The BC-iPSC line of claim 8 , wherein the BC-iPSC line does not show statistically significant differences between a first and a repeat G-band karyotype analysis, wherein the first or the repeat G-band karyotype analysis occurs during passages 10-23.

Assignments (1)

Continuity (3)

References Cited (116)