	US 11,987,628 B2
	Methods and compositions for modulating CAR-T activity
Sonja Schrepfer, San Mateo, CA (US); Lindong Weng, Seattle, WA (US); and Terry J. Fry, Denver, CO (US)
Assigned to Sana Biotechnology, Inc., Seattle, WA (US)
Filed by Sana Biotechnology, Inc., Seattle, WA (US)
Filed on Jun. 21, 2023, as Appl. No. 18/339,157.
Application 18/339,157 is a continuation of application No. 17/666,523, filed on Feb. 7, 2022, granted, now 11,802,157.
Application 17/666,523 is a continuation of application No. 17/561,659, filed on Dec. 23, 2021.
Claims priority of provisional application 63/288,477, filed on Dec. 10, 2021.
Claims priority of provisional application 63/255,795, filed on Oct. 14, 2021.
Claims priority of provisional application 63/175,003, filed on Apr. 14, 2021.
Claims priority of provisional application 63/136,172, filed on Jan. 11, 2021.
Claims priority of provisional application 63/133,171, filed on Dec. 31, 2020.
Prior Publication US 2024/0002507 A1, Jan. 4, 2024
Int. Cl. A61K 35/17 (2015.01); A61P 35/00 (2006.01); C07K 14/705 (2006.01); C07K 14/725 (2006.01); C07K 14/74 (2006.01); C07K 16/28 (2006.01); C12N 5/0783 (2010.01); C12N 15/86 (2006.01); A61K 39/00 (2006.01)

CPC C07K 16/2803 (2013.01) [A61K 35/17 (2013.01); A61P 35/00 (2018.01); C07K 14/70503 (2013.01); C07K 14/7051 (2013.01); C07K 14/70539 (2013.01); C12N 5/0636 (2013.01); C12N 15/86 (2013.01); A61K 2039/505 (2013.01); A61K 2039/5156 (2013.01); A61K 2039/5158 (2013.01); C07K 2317/76 (2013.01); C07K 2319/02 (2013.01); C07K 2319/03 (2013.01); C07K 2319/30 (2013.01); C07K 2319/33 (2013.01); C12N 2510/00 (2013.01); C12N 2740/15043 (2013.01)]

30 Claims

1. An engineered T cell comprising (a) reduced expression of B2M, CIITA, and/or T cell receptor (TCR)-alpha relative to a control T cell, (b) expression of CD47 encoded by a first exogenous polynucleotide so that the engineered T cells comprise increased CD47 expression relative to the control T cell, and (c) expression of a CD22-specific chimeric antigen receptor (CAR) encoded by a second exogenous polynucleotide,

wherein the engineered T cell is derived from a primary T cell,

wherein the CAR comprises an antigen binding domain comprising:

(i) a light chain variable region comprising a light chain CDR1, a light chain CDR2, and a light chain CDR3, wherein the light chain CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 51, the light chain CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 52, and the light chain CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 53, and

(ii) a heavy chain variable region comprising a heavy chain CDR1, a heavy chain CDR2, and a heavy chain CDR3 amino acid, wherein the heavy chain CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 47, the heavy chain CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 48, and the heavy chain CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 49,

wherein the first exogenous polynucleotide is inserted into a locus of at least one allele of the engineered T cell, and

wherein the second exogenous polynucleotide is inserted into a locus of at least one allele of the engineered T cell.