US 12,016,908 B2
Compositions and methods for treating hemoglobinopathies
Ian Slaymaker, Cambridge, MA (US); Nicole Gaudelli, Cambridge, MA (US); Yi Yu, Cambridge, MA (US); Bernd Zetsche, Cambridge, MA (US); David A. Born, Cambridge, MA (US); Seung-Joo Lee, Cambridge, MA (US); and Michael Packer, Cambridge, MA (US)
Assigned to Beam Therapeutics Inc., Cambridge, MA (US)
Filed by Beam Therapeutics Inc., Cambridge, MA (US)
Filed on Jul. 26, 2022, as Appl. No. 17/815,128.
Application 17/815,128 is a division of application No. 17/720,186, filed on Apr. 13, 2022, granted, now 11,752,202.
Application 17/720,186 is a division of application No. 17/214,643, filed on Mar. 26, 2021, granted, now 11,344,609, issued on Mar. 31, 2022.
Application 17/214,643 is a continuation of application No. PCT/US2020/018193, filed on Feb. 13, 2020.
Claims priority of provisional application 62/966,526, filed on Jan. 27, 2020.
Claims priority of provisional application 62/941,569, filed on Nov. 27, 2019.
Claims priority of provisional application 62/931,747, filed on Nov. 6, 2019.
Claims priority of provisional application 62/931,722, filed on Nov. 6, 2019.
Claims priority of provisional application 62/852,228, filed on May 23, 2019.
Claims priority of provisional application 62/852,224, filed on May 23, 2019.
Claims priority of provisional application 62/805,277, filed on Feb. 13, 2019.
Claims priority of provisional application 62/805,271, filed on Feb. 13, 2019.
Prior Publication US 2023/0128472 A1, Apr. 27, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 38/50 (2006.01); A61K 31/7088 (2006.01); A61K 35/15 (2015.01); A61K 35/18 (2015.01); A61K 35/28 (2015.01); A61K 38/46 (2006.01); A61P 7/00 (2006.01); A61P 7/06 (2006.01); C07K 14/47 (2006.01); C12N 5/078 (2010.01); C12N 9/22 (2006.01); C12N 9/78 (2006.01); C12N 15/11 (2006.01); C12N 15/90 (2006.01)
CPC A61K 38/50 (2013.01) [A61K 31/7088 (2013.01); A61K 35/15 (2013.01); A61K 35/18 (2013.01); A61K 35/28 (2013.01); A61K 38/465 (2013.01); A61P 7/00 (2018.01); A61P 7/06 (2018.01); C07K 14/4717 (2013.01); C12N 5/0641 (2013.01); C12N 9/22 (2013.01); C12N 9/78 (2013.01); C12N 15/11 (2013.01); C12N 15/907 (2013.01); C12Y 305/04004 (2013.01); C07K 2319/09 (2013.01); C12N 2310/20 (2017.05); C12N 2506/11 (2013.01); C12N 2510/00 (2013.01); C12N 2800/80 (2013.01)] 14 Claims
 
1. A method of treating sickle cell disease or beta-thalassemia in a subject comprising administering to said subject a cell comprising an edited hemoglobin subunit gamma 1 and/or 2 (HBG1/2) promoter, wherein said edited HBG 1/2 promoter comprises an A to G alteration at position 5 and/or position 8 of the nucleotide sequence of SEQ ID NO: 177, wherein the cell is prepared by contacting the cell with a guide RNA and a base editor comprising a polynucleotide programmable DNA binding domain and an adenosine deaminase domain, wherein the adenosine deaminase domain comprises an arginine (R) or a threonine (T) at amino acid position 147 of the following amino acid sequence, wherein the adenosine deaminase has at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 2, wherein said guide RNA targets said base editor to effect a deamination of a nucleobase of the HBG1/2 promoter in the cell, thereby effecting said A to G alteration at position 5 and/or position 8 of the nucleotide sequence of SEQ ID NO: 177, wherein deamination of the nucleobase of the HBG1/2 promoter in the cell effects an increase in gamma globin (HbF) expression in the subject when administered to said subject as compared to a subject without said cell administered.