US 2026/0191973 A1Published application

Stimuli-responsive engineering platform for intracellular payload delivery

OwnerJiangbing Zhou, Zefeng Wang +9inventors

InventorsJiangbing Zhou, Zefeng Wang, Jiang Yu, Jiali Fan, Zewei Tu, Conrad Leung, Amy Liao, Min-Han Lin, Ying Xiao, Ying Xie, Huacan Lin

Life of this patent

Estimating the term…

patentgrep

Loading patent…

Abstract

Compounds having the following structure: wherein Y= wherein: [R2bR2a] represents a reaction product between R2b and R2a of Formulas (2) and (1), respectively, R3 functions as a cell penetration moiety, and R1 functions as a binding moiety to bind to the payload (P) to form a conjugate with P, wherein R1, R3, A, D, L1, L2, L3, L4, L5, L6, L7, r, m, s, n, p, and q are as defined in further detail elsewhere in this disclosure. Also described herein are methods of producing compounds of Formulas (1), (2), and (3), conjugates thereof with a payload (P), pharmaceutical compositions thereof, methods of delivering the conjugates to subjects or cells, and methods of treating a disease or condition by administering such conjugates.

Claims128

Dependent claims

A compound having the following structure:

wherein:
R2a is a first reactive group that forms a linkage with a second reactive group;
L1 is a linker selected from a bond, C(O), CH2, C(O)NH, and C(O)O;
L2, L4, and L5 are linkers independently selected from a bond, CH2, C(O), NH, O, S, C(O)NH, C(O)O, OC(O)NH, OC(O)O, NHC(O)NH, and —OC(O)O—Ar—, or a CH2 bound to any of the foregoing linkers, wherein Ar is an aromatic ring, and wherein an O atom can optionally be replaced with an S atom in any of the foregoing linkers;
L3 is a linker selected from the group consisting of a bond, CH2, CH2CH2, S—S, C(O)O, OC(O)O, C(O)NH, OC(O)O—Ar, wherein Ar is an aromatic ring, and linked combinations of any two or more of the foregoing linkers;
R1 is an aromatic or aliphatic ring or polycyclic ring system, wherein the aromatic or aliphatic ring or polycyclic ring system optionally contains one or more ring heteroatoms selected from N, O, and S, and the aromatic or aliphatic ring or polycyclic ring system optionally contains one or more non-H substituents selected from halogen atoms;
oxo;
linear or branched, cyclic or acyclic, saturated or unsaturated, halogenated or non-halogenated hydrocarbon groups containing 1-30 carbon atoms;
NO2;
NR3R4;
CN;
C(O)R5;
C(O)OR6;
OC(O)R6;
OR7;
C(O)NR3R4;
and NHC(O)R8;
wherein R3, R4, R5, R6, R7, and R8 are independently selected from H and linear or branched alkyl groups containing 1-3 carbon atoms;
and R1 is optionally connected to L5 by a CRaRb linker, wherein Ra and Rb are independently selected from H;
R9;
OR9;
NR10R11;
CN;
C(O)R12;
C(O)OR13;
OC(O)R14;
C(O)NR10R11;
and NHC(O)R15;
wherein R9, R10, R11, R12, R13, R14, and R15 are independently selected from H and alkyl, alkenyl, and cycloalkyl groups containing 1-6 carbon atoms and optionally containing one or halogen atoms;
n is selected from an integer in the range of 0-100;
p is an integer of 0-10;
and
q is an integer of 0-50.

30 more elements

A compound having the following structure:

wherein:
R2b is a second reactive group that forms a linkage with a first reactive group;
r and s are independently selected from an integer in the range of 1-6;
L6 is either:
(i) a non-branching linker selected from CH2, C(O), NH, O, S, C(O)NH, C(O)O, OC(O)NH, OC(O)O, and NHC(O)NH, or one or more of these attached together, wherein r is 1;
or (ii) a branching linker selected from C, CH, N, B, or a linear or branched, cyclic or acyclic hydrocarbon linker group Ro containing 2-50 carbon atoms on which an r number of R3-A arms are attached, wherein Re optionally contains one or more heteroatoms selected from N, O, and S;
or (iii) one or more non-branching linkers in (i) attached to a branching linker (ii);
L7 is either:
(i) a non-branching linker selected from CH2, C(O), NH, O, S, C(O)NH, C(O)O, OC(O)NH, OC(O)O, and NHC(O)NH, in which case s is 1;
or (ii) a branching linker selected from C, CH, N, B, or a linear or branched, cyclic or acyclic hydrocarbon linker group Re containing 2-50 carbon atoms on which an s number of R2b-D arms are attached, wherein Re optionally contains one or more heteroatoms selected from N, O, and S, or (iii) one or more non-branching linkers in (i) attached to a branching linker (ii);
A is a bond or a linker containing 1-50 carbon atoms and optionally containing one or more heteroatoms selected from N, O, and S;
D is a bond or a linker containing 1-50 carbon atoms and optionally containing one or more heteroatoms selected from N, O, and S;
R3 is independently a linear or branched, cyclic or acyclic, saturated or unsaturated hydrocarbon group containing 4-30 carbon atoms optionally containing one or more heteroatoms selected from N, O, S, and B and which functions as a cell penetration moiety;
and
m is selected from an integer in the range of 0-100.

12 more elements

Dependencies are inferred from the claim text.

Facts

Application: 19/443,130Filed 8 Jan 2026
Priority: 9 Jan 2025
Published: 9 Jul 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

A61K 47/60
Obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes: the organic…
A61K 47/543
The modifying agent being an organic compound: lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
A61K 47/554
The modifying agent being an organic compound: the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid
A61K 48/0008
Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy:…