US 11,965,165 B2
Compositions and methods for TTR gene editing and treating ATTR amyloidosis
Arti Mahendra Prakash Kanjolia, Malden, MA (US); Shobu Odate, Arlington, MA (US); Jessica Lynn Seitzer, Windham, NH (US); Reynald Michael Lescarbeau, Medford, MA (US); and Walter Strapps, Dedham, MA (US)
Assigned to Intellia Therapeutics, Inc., Cambridge, MA (US)
Filed by Intellia Therapeutics, Inc., Cambridge, MA (US)
Filed on Dec. 9, 2022, as Appl. No. 18/063,972.
Application 18/063,972 is a division of application No. 16/828,573, filed on Mar. 24, 2020.
Application 16/828,573 is a continuation of application No. PCT/US2018/053382, filed on Sep. 28, 2018.
Claims priority of provisional application 62/671,902, filed on May 15, 2018.
Claims priority of provisional application 62/566,236, filed on Sep. 29, 2017.
Prior Publication US 2023/0257747 A1, Aug. 17, 2023
Int. Cl. A61P 25/28 (2006.01); C12N 9/22 (2006.01); C12N 15/10 (2006.01); C12N 15/113 (2010.01); A61K 48/00 (2006.01); C12N 15/11 (2006.01)
CPC C12N 15/113 (2013.01) [A61P 25/28 (2018.01); C12N 9/22 (2013.01); C12N 15/102 (2013.01); A61K 48/00 (2013.01); A61K 48/0091 (2013.01); C12N 15/111 (2013.01); C12N 2310/20 (2017.05); C12N 2310/321 (2013.01); C12N 2800/80 (2013.01)] 21 Claims
OG exemplary drawing
 
1. A method of treating amyloidosis associated with TTR (ATTR), comprising administering a composition to a subject in need thereof, wherein the composition comprises (i) an RNA-guided DNA binding agent or a nucleic acid encoding an RNA-guided DNA binding agent and (ii) a single guide RNA comprising in 5′ to 3′ order, 1) one of the following (a)-(c): a. a guide sequence comprising the sequence of SEQ ID NO: 23; b. a guide sequence that is at least 17, 18, or 19 contiguous nucleotides of the sequence of SEQ ID NO: 23; or c. a guide sequence that is at least 90% identical to the sequence of SEQ ID NO: 23, and (2) the sequence of SEQ ID NO: 125, wherein the sequence of SEQ ID NO: 125 comprises a modification pattern of nucleotides 21-100 of SEQ ID NO: 3 (GUUUUAGAmGmCmUmAmGmAmAmAmUmAmGmCAAGUUAAAAUAAGGCU AGUCCGUUAUCAmAmCmUmUmGmAmAmAmAmAmGmUmGmGmCmAmCmC mGmAmGmUmCmGmGmUmGmCmU*mU*mU*mU), thereby treating ATTR, wherein a * indicates a phosphorothioate (PS) linkage and a lower case “m” indicates that the nucleotide is 2′-O-Me modified.