	US 11,987,821 B2
	Compositions and methods for treating mitochondrial neurogastrointestinal encephalopathy
Natarajan Sethuraman, Boston, MA (US); Jason Ruth, Boston, MA (US); Louis A. Tartaglia, Boston, MA (US); Dehua Pei, Columbus, OH (US); and Ziqing Qian, Boston, MA (US)
Assigned to Entrada Therapeutics, Inc., Boston, MA (US)
Filed by Entrada Therapeutics, Inc., Boston, MA (US)
Filed on Oct. 6, 2021, as Appl. No. 17/495,238.
Application 17/495,238 is a division of application No. 16/821,018, filed on Mar. 17, 2020, granted, now 11,168,310.
Application 16/821,018 is a continuation of application No. PCT/US2019/019117, filed on Feb. 22, 2019.
Claims priority of provisional application 62/796,823, filed on Jan. 25, 2019.
Claims priority of provisional application 62/633,933, filed on Feb. 22, 2018.
Prior Publication US 2022/0033787 A1, Feb. 3, 2022
Int. Cl. C12N 9/00 (2006.01); A61K 38/45 (2006.01); A61K 47/60 (2017.01); C07K 7/64 (2006.01); C12N 9/10 (2006.01)

CPC C12N 9/1077 (2013.01) [A61K 38/45 (2013.01); A61K 47/60 (2017.08); C07K 7/64 (2013.01); C12Y 204/02004 (2013.01); C07K 2319/00 (2013.01)]

18 Claims

1. A compound having a stricture according to Formula I-A:

CPP-L-TP (I-A),

wherein:

CPP is a cyclic cell-penetrating peptide (cCPP);

TP is thymidine phosphorylase, or an active fragment or analog thereof; and has an amino acid sequence that is at least 95% identical to SEQ ID NO. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13;

L is a linker; and

wherein L is a covalently bound to the side chain of an amino acid on the CPP and to the N-terminus of the TP;

the cCPP has a sequence comprising any of Formula IV-A-D:

wherein:

each of AA_H1and AA_H2are independently a D or L hydrophobic aromatic amino acid;

at each instance and when present, each of AA_Uand AA_Zare independently a D or L amino acid;

m and n are independently selected from a number from 0 to 6; and

wherein Formula IV-A-D comprise at least three consecutive arginine, and at least three-consecutive hydrophobic aromatic amino acids.