US 12,383,624 B2
Cargo delivery system and composition comprising the same
Yong Tae Kwon, Seoul (KR); Chang Hoon Ji, Seoul (KR); Srinivasrao Ganipisetti, Seoul (KR); Hee Yeon Kim, Seoul (KR); Su Ran Mun, Seoul (KR); Chan Hoon Jung, Seoul (KR); Eui Jung Jung, Seoul (KR); Ki Woon Sung, Seoul (KR); Hyun Tae Kim, Seoul (KR); Jeong Eun Na, Seoul (KR); Eun Hye Jeong, Seoul (KR); Ji Eun Lee, Seoul (KR); Min Ju Lee, Seoul (KR); Chang Min Park, Seoul (KR); and Su Jin Kim, Seoul (KR)
Assigned to SEOUL NATIONAL UNIVERSITY R&DB FOUNDATION, Seoul (KR); and AUTOTAC INC., Seoul (KR)
Filed by SEOUL NATIONAL UNIVERSITY R&DB FOUNDATION, Seoul (KR); and AUTOTAC INC., Seoul (KR)
Filed on Feb. 15, 2023, as Appl. No. 18/169,734.
Application 18/169,734 is a continuation in part of application No. 17/262,157, granted, now 12,129,218, previously published as PCT/KR2019/009205, filed on Jul. 24, 2019.
Claims priority of provisional application 62/702,473, filed on Jul. 24, 2018.
Prior Publication US 2023/0190938 A1, Jun. 22, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/55 (2017.01); A61K 47/54 (2017.01)
CPC A61K 47/545 (2017.08) [A61K 47/55 (2017.08)] 8 Claims
OG exemplary drawing
 
1. A cargo delivery system, comprising
an autophagy targeting ligand; and
a target-binding ligand, which is cargo, carried by the autophagy targeting ligand,
wherein the autophagy targeting ligand is connected to the target-binding ligand by a linker,
wherein the autophagy targeting ligand connected to the target-binding ligand by a linker is selected from the group consisting of compounds shown in the following table:
 
No. Name of Compound
 
 1 (2E,4E,6E,8E)-N-(2-(2-(2-(((R)-3-(3,4-bis
 
 (benzyloxy)phenoxy)-2-hydroxypropyl)amino)
 
 ethoxy)ethoxy)ethyl)-3,7-dimethyl-9-(2,6,6-
 
 trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-
 
 tetraenamide
 2 (2E,4E,6E,8E)-N-(2-(2-(2-((3,4-bis(benzyloxy)
 
 benzyl)amino)ethoxy)ethoxy)ethyl)-3,7-
 
 dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)
 
 nona-2,4,6,8-tetraenamide
 3 (R)-N-(15-(3,4-bis(benzyloxy)phenoxy)-14-
 
 hydroxy-3,6,9-trioxa-12-azapentadecyl)-4-
 
 phenylbutaneamide
 4 N-(1-(3,4-bis(benzyloxy)phenyl)-5,8,11-trioxa-
 
 2-azatridecan-13-yl)-4-phenylbutanamide
 5 3-(3-(benzo[d][1,3]dioxol-5-yl)-1H-pyrazol-
 
 5-yl)-N-(2-(2-(2-((3-((4-fluorobenzyl)oxy))
 
 benzyl)amino)ethoxy)ethoxy)ethyl)aniline
 6 (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-
 
 methyl-3-(3-methylbut-2-en-1-yl)oxirane-2-yl)-
 
 1-oxaspiro[2.5]octan-6-yl(13E,15E,17E,19E)-1-
 
 (3-(benzyloxy)phenyl)-12-oxo-5,8-dioxa-2,11-
 
 diazahenicosa-13,15,17,19-tetraene-21-oate
 7 3-(3,5-dichlorophenyl)-5-((R)-15-(3,4-
 
 diphenethoxyphenoxy)-14-hydroxy-6,9-dioxa-
 
 3,12-diazapentadecyl)-5-methyloxazolidine-
 
 2,4-dione
 8 (R)-1-(4-(benzyloxy)-3-(3-phenylpropoxy)
 
 phenoxy)-3-((2-(2-(2-(4-(2-phenyl-5,7-bis
 
 (trifluoromethyl)pyrazolo[1,5-a]pyrimidin-
 
 3-yl)phenoxy)ethoxy)ethoxy)ethyl)amino)
 
 propan-2-ol
 9 (R,Z)-4-((2-(2-(2-((3-(3,4-diphenethoxyphenoxy)-
 
 2-hydroxypropyl)amino)ethoxy)ethoxy)ethyl)
 
 imino)-2-phenyl-4H-chromene-5,6,7-triol
10 (E)-5-(4-(2-(2-(2-((3,4-bis(benzyloxy)benzyl)
 
 amino)ethoxy)ethoxy)ethoxy)styryl)benzene-
 
 1,3-diol
11 (R)-2-(4-(benzo[d]thiazol-2-yl)phenyl)-14-(3,4-
 
 bis(benzyloxy)phenoxy)-5,8-dioxa-2,11-
 
 diazatetradecane-13-ol
12 (1E,6E)-1-(4-(2-(2-(2-(((R)-3-(3-(benzyloxy)-
 
 4-phenethoxyphenoxy)-2-hydroxypropyl)
 
 amino)ethoxy)ethoxy)ethoxy)-3-methoxyphenyl)-
 
 7-(4-hydroxy-3-methoxyphenyl)hepta-
 
 1,6-diene-3,5-dione
13 (R)-1-(3-phenethoxyphenoxy)-3-((2-(2-(2-((6-
 
 (trifluoromethoxy))benzo[d]thiazol-2-yl)amino)
 
 ethoxy)ethoxy)ethyl)amino)propan-2-ol
14 N-(2-(2-(2-(((R)-3-(3,4-bis(benzyloxy)phenoxy)-
 
 2-hydroxypropyl)amino)ethoxy)ethoxy)
 
 ethyl)-2-((S)-4-(4-chlorophenyl)-2,3,9-trimethyl-
 
 6H-thieno[3,2-f][1,2,4]triazolo[4,3-a]
 
 [1,4]diazepin-6-yl)acetamide
15 (1s, 4s)-N-(2-(2-(2-((3,4-bis(benzyloxy)benzyl)
 
 amino)ethoxy)ethoxy)ethyl)-4-cyano-4-(3-
 
 (cyclopentyloxy)-4-methoxyphenyl)cyclohexane-
 
 1-carboxamide
16 (R)-1-(3-phenethoxyphenoxy)-3-((2-(2-(2-(4-(4-
 
 (3-(quinolin-5-yl)pyrazolo[1,5-a]pyrimidin-6-
 
 yl)phenyl)piperazin-1-yl)ethoxy)ethoxy)ethyl)
 
 amino)propan-2-ol
17 5-(3-fluorophenyl)-N-((S)-1-(2-(2-(2-(((R)-2-
 
 hydroxy-3-(3-phenethoxyphenoxy)propyl)
 
 amino)ethoxy)ethoxy)ethyl)piperidin-3-yl)-
 
 3-ureidothiophene-2-carboxamide
18 (R)-2-((6-(4-(15-(4-(benzyloxy)-3-(3-
 
 phenylpropoxy)phenoxy)-14-hydroxy-6,9-dioxa-
 
 3,12-diazapentadecyl)piperazin-1-yl)-2-
 
 methylpyrimidin-4-yl)amino)-N-(2-chloro-6-
 
 methylphenyl)thiazole-5-carboxamide
19 (R)-5-((3-((2-(2-(2-((3-(4-(benzyloxy)-3-
 
 phenethoxyphenoxy)-2-hydroxypropyl)amino)
 
 ethoxy)ethoxy)ethyl)amino)phenyl)amino)
 
 benzo[c][2,6]naphthyridine-8-carboxylic acid
20 N-(7-((1-(3-(benzyloxy)phenyl)-5,8-dioxa-
 
 2,11-diazatridecan-13-yl)oxy)-6-(tert-butylsulfonyl)
 
 quinazolin-4-yl)benzo[d]thiazol-5-amine
21 ((2-(((5S,8S,10aR)-8-(((S)-5-amino-1-
 
 (benzhydrylamino)-1,5-dioxopentan-2-
 
 yl)carbamoyl)-3-((R)-1-(3,4-bis((4-fluorobenzyl)
 
 oxy)phenoxy)-2-hydroxy-7,10,13,16-tetraoxa-
 
 4-azaicosan-20-oyl)-6-oxodecahydropyrrolo
 
 [1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indol-5-
 
 yl)difluoromethyl)phosphonic acid
22 ((2-(((5S,8S,10aR)-8-(((S)-5-amino-1-
 
 (benzhydrylamino)-1,5-dioxopentan-2-yl)
 
 carbamoyl)-3-(1-(3,4-bis(benzyloxy)phenyl)-
 
 5,8,11,14-tetraoxa-2-azaoctadecan-18-oyl)-6-
 
 oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-
 
 yl)carbamoyl)-1H-indol-5-yl)difluoromethyl)
 
 phosphonic acid
23 (4-((1-(3,4-bis(benzyloxy)phenyl)-16-ethyl-
 
 5,8-dioxa-2,11,16-triazaoctadecan-18-yl)oxy)
 
 phenyl)(6-hydroxy-2-(4-hydroxyphenyl)
 
 benzo[b]thiophen-3-yl)methanone
24 (R)-5-((3-((21-(3,4-bis((4-fluorobenzyl)oxy)
 
 phenoxy)-20-hydroxy-3,6,9,12,15-pentaoxa-
 
 18-azahenicosyl)amino)-5-chlorophenyl)amino)
 
 benzo[c][2,6]naphthyridine-8-carboxylic acid
25 (S)-3-(6-(3-((4-(1-(4-(benzyloxy)-3-
 
 phenethoxyphenyl)-5,8,11,14-tetraoxa-2-
 
 azahexadecan-16-yl)piperazin-1-yl)methyl)-
 
 1,2,3,4-tetrahydroisoquinoline-2-carbonyl)
 
 benzo[d][1,3]dioxol-5-yl)-N-(4-hydroxyphenyl)-N-
 
 phenyl-5,6,7,8-tetrahydroindolizine-1-carboxamide
26 (R)-1-((4-(benzo[d]thiazol-5-ylamino)-6-(tert-
 
 butylsulfonyl)quinazolin-7-yl)oxy)-24-
 
 (3,4-bis((4-fluorobenzyl)oxy)phenoxy)-
 
 6,9,12,15,18-pentaoxa-3,21-diazatetracosan-23-ol
27 N-(1-(3,4-bis(benzyloxy)phenyl)-5,8,11,14,17-
 
 pentaoxa-2-azanonadecan-19-yl)-4-
 
 phenylbutanamide
28 N-(1-(3,4-bis(benzyloxy)phenyl)-5,8,11,14,17,20,23-
 
 heptaoxa-2-azapentacosan-25-yl)-4-
 
 phenylbutanamide
29 (R)-N-(15-(3,4-bis((4-fluorobenzyl)oxy)phenoxy)-
 
 14-hydroxy-3,6,9-trioxa-12-azapentadecyl)-
 
 4-phenylbutanamide
30 (R)-N-(15-(3-((4-fluorobenzyl)oxy)phenoxy)-
 
 14-hydroxy-3,6,9-trioxa-12-azapentadecyl)-4-
 
 phenylbutanamide
31 N-(7-((1-(3,4-bis(benzyloxy)phenyl)-5,8,11-
 
 trioxa-2-azatridecan-13-yl)(methyl)amino)-3H-
 
 phenothiazin-3-ylidene)-N-methylmethanaminium
 
 2,2,2-trifluoroacetate
32 (R)-N-(7-((15-(3,4-bis((4-fluorobenzyl)oxy)
 
 phenoxy)-14-hydroxy-3,6,9-trioxa-12-
 
 azapentadecyl)(methyl)amino)-3H-phenothiazin-
 
 3-ylidene)-N-methylmethanaminium
 
 2,2,2-trifluoroacetate
33 (R)-N-(7-((15-(3-((4-fluorobenzyl)oxy)phenoxy)-
 
 14-hydroxy-3,6,9-trioxa-12-azapentadecyl)
 
 (methyl)amino)-3H-phenothiazin-3-ylidene)-
 
 N-methylmethanaminium 2,2,2-trifluoroacetate.