US 12,239,715 B2
Peptide oligonucleotide conjugates
Gunnar J. Hanson, Cambridge, MA (US); and Ming Zhou, Cambridge, MA (US)
Assigned to Sarepta Therapeutics, Inc., Cambridge, MA (US)
Filed by Sarepta Therapeutics, Inc., Cambridge, MA (US)
Filed on Apr. 6, 2023, as Appl. No. 18/296,697.
Application 18/296,697 is a continuation of application No. 17/403,403, filed on Aug. 16, 2021, granted, now 11,672,871.
Application 17/403,403 is a continuation of application No. 16/860,292, filed on Apr. 28, 2020, granted, now 11,097,011, issued on Aug. 24, 2021.
Application 16/860,292 is a continuation of application No. 15/574,734, granted, now 10,675,356, issued on Jun. 9, 2020, previously published as PCT/US2016/033276, filed on May 19, 2016.
Claims priority of provisional application 62/337,536, filed on May 17, 2016.
Claims priority of provisional application 62/163,960, filed on May 19, 2015.
Prior Publication US 2023/0310625 A1, Oct. 5, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/64 (2017.01); A61K 47/18 (2017.01); C07K 7/06 (2006.01); C07K 7/08 (2006.01); A61K 38/00 (2006.01)
CPC A61K 47/645 (2017.08) [A61K 47/18 (2013.01); C07K 7/06 (2013.01); C07K 7/08 (2013.01); A61K 38/00 (2013.01); Y02A 50/30 (2018.01)] 27 Claims
 
1. A peptide-oligonucleotide-conjugate, or a pharmaceutically acceptable salt thereof, of Formula (I):

OG Complex Work Unit Chemistry
wherein:
z is 8-40;
each R1 is independently selected from OH and —NR3R4, wherein each R3 and R4 are independently at each occurrence —C1-6 alkyl;
each R2 is independently selected from H, a nucleobase, and a nucleobase functionalized with a chemical protecting-group, wherein the nucleobase independently at each occurrence comprises pyridine, pyrimidine, triazinane, purine, or deaza-purine;
A′ is selected from —NHCH2C(O)NH2, —N(C1-6-alkyl)CH2C(O) NH2,

OG Complex Work Unit Chemistry
R5 is —C(O)(O-alkyl)x-OH, wherein x is 3-10 and each alkyl group is independently at each occurrence C2-6-alkyl, or R5 is selected from —C(O)C1-6 alkyl, trityl, monomethoxytrityl, —(C1-6-alkyl)R6, —(C1-6 heteroalkyl)-R6, aryl-R6, heteroaryl-R6, —C(O)O—(C1-6 alkyl)-R6, —C(O)O-aryl-R6, —C(O)O-heteroaryl-R6, and -L-(J)t—G;
R6 is selected from OH, SH, and NH2, or R6 is O, S, or NH, covalently linked to a solid support;
E′ is selected from H, —C1-6 alkyl, —C(O)C1-6 alkyl, benzoyl, stearoyl, trityl, monomethoxytrityl, dimethoxytrityl, trimethoxytrityl,

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Q is —C(O)(CH2)6C(O)— or —C(O)(CH2)2S2(CH2)2C(O)—,
R7 is —(CH2)2OC(O)N(R8)2;
R8 is —(CH2)6NHC(═NH)NH2;
R11 is selected from —OH and —NR3R4;
-L-(J)t—G is selected from:

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R is arginine;
d is 0 or 1; and
M is:

OG Complex Work Unit Chemistry

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each R10 is independently at each occurrence H or a halogen,
wherein at least one of the following conditions is true:
1) A′ is

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2) E′ is -L-(J)t-G; or 3) E′ is

OG Complex Work Unit Chemistry