Granted Patent B2

US 12,629,425 · App. 18/590,455 · Granted May 19, 2026

Inventor: Tracy Matray (Snohomish, WA)

Assignee: SONY GROUP CORPORATION

A61K47/6455A61K47/60A61K47/605A61K47/64A61K47/6851

Abstract

Claims (63)

1 . A compound having the following structure (II):

or a stereoisomer, pharmaceutically acceptable salt or tautomer thereof, wherein:

G is, at each occurrence, independently a moiety comprising a reactive group capable of forming a covalent bond with a complementary reactive group, the reactive group is selected from the group consisting of: an aldehyde, oxime, hydrazone, alkyne, amine, azide, acylazide, nitrile, nitrone, sulfhydryl, disulfide, sulfonyl halide, isothiocyanate, imidoester, activated ester, ketone, α,β-unsaturated carbonyl, alkene, maleimide, α-haloimide, epoxide, aziridine, tetrazine, tetrazole, phosphine, biotin and thiirane;

L 1a is, at each occurrence, independently an optional alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, heteroalkynylene or heteroatomic linker;

L 1 , L 2 , L 3 and L 4 are, at each occurrence, independently an optional heteroalkylene linker, wherein at least one of L 1 and L 4 is present;

R 1 is, at each occurrence, independently a side chain of a natural or unnatural amino acid;

R 2 is —NH 2 ;

R 3 is —H, —OH, —SH, alkyl, alkoxy, alkylether, heteroalkyl, alkylaminyl, alkylcarbonyl, alkoxycarbonyl, Q or a protected form thereof, or L′, wherein the alkyl, alkoxy, alkylether, heteroalkyl, alkylaminyl, alkylcarbonyl and alkyloxycarbonyl are optionally substituted with hydroxyl, amino, sulfhydryl, phosphate, thiophosphate, phosphoalkyl, thiophosphoalkyl, phosphoalkylether or thiophosphoalkylether, or combinations thereof;

Q is, at each occurrence, independently a moiety comprising a sulfhydryl, disulfide, activated ester, isothiocyanate, azide, alkyne, alkene, diene, dienophile, acid halide, sulfonyl halide, phosphine, α-haloimide, biotin, amino or maleimide functional group, wherein the activated ester is an N-succinimide ester, imidoester or polyflourophenyl ester, and wherein the azide is an alkyl azide or acyl azide;

L′ is, at each occurrence, independently a linker comprising a covalent bond to Q, a targeting moiety, a linker comprising a covalent bond to a targeting moiety, a linker comprising a covalent bond to a solid support or solid support residue, a linker comprising a covalent bond to a solid support or solid support residue or a linker comprising a covalent bond to a further compound of structure (II);

m is, at each occurrence, independently an integer of zero or greater; and

n is an integer of one or greater.

2 . The compound of claim 1 , wherein R 1 is, at each occurrence, independently H, alkyl, —CH 2 CO 2 , —CH 2 CH 2 CO 2 ,

—

⁢

CH

2

⁢

CH

2

⁢

CH

2

⁢

CH

2

⁢

NH

3

+

,

—CH 2 CH 2 CH 2 NHC(=NH 2 +) NH 2 or imidazolyl.

3 . The compound of claim 1 , wherein R 1 , L 1 and m are selected such that

has an amino acid sequence of (G) 10 , (GDGDGDGDGD) or (GKGKGKGKGK).

4 . The compound of claim 1 , wherein R 1 , L 1 and m are selected such that

has an amino acid sequence capable of forming an α-helix or β-sheet secondary structure.

5 . The compound of claim 4 , wherein the amino acid sequence is (GGEEFMLVYKFARKHGG) or (GGMSMVVSGG).

6 . The compound of claim 1 , wherein at least one occurrence of L 1 or L 4 , or both, has the following structure:

7 . The compound of claim 1 , wherein at least one occurrence of L 1 or L 4 , or both, has the following structure:

8 . The compound of claim 1 , wherein R 3 is L′ and L′ is a linker comprising a covalent bond to a polymeric bead or non-polymeric bead.

9 . The compound of claim 1 , wherein R 3 is L′ and L′ is a targeting moiety or a heteroalkylene linker to a targeting moiety.

10 . The compound of claim 1 , wherein the targeting moiety is an antibody or cell surface receptor antagonist.

11 . The compound of claim 10 , wherein the antibody or cell surface receptor antagonist is an epidermal growth factor receptor (EGFR) inhibitor, a hepatocyte growth factor receptor (HGFR) inhibitor, an insulin-like growth factor receptor (IGFR) inhibitor, a folate, or a MET inhibitor.

12 . The compound of claim 1 , wherein R 3 is —OP(═R a )(R b ) OL′ or L′, and L′ is the antibody or a linker comprising a covalent bond to the antibody.

13 . The compound of claim 1 , wherein:

L 2 and L 4 are, at each occurrence, absent;

L 3 is, at each occurrence, independently a heteroalkylene linker; and

R 1 , L 1 and m are selected such that

has an amino acid sequence of (G) 10 , (GDGDGDGDGD) or (GKGKGKGKGK).

14 . The compound of claim 13 , having one of the following structures:

15 . The compound of claim 1 , wherein G is alkynyl, azide, amino (NH 2 ), isothiocyanate, or an activated ester.

16 . The compound of claim 15 , wherein G is alkynyl, wherein the alkynyl is ethynyl.

17 . The compound of claim 15 , wherein G is the activated ester, wherein the activated ester is as an ester of N-hydroxysuccinimide.

18 . A method, comprising:

preparing a first compound by reacting the compound having structure (II) of claim 1 with a second compound comprising an M moiety covalently bonded to a reactive group complementary to the G moiety of the compound having structure (II),

wherein the M moiety is a biologically active moiety selected from an NSAID, a kinase inhibitor, an anthracycline, an EGFR inhibitor, an alkylating agent and an anti-cancer drug, and

wherein preparing includes forming a covalent bond between the M moiety and the G moiety by reaction of the G moiety and the reactive group complementary to the G moiety.

19 . A method, comprising:

reacting a reactive polymer compound having structure (II) of claim 1 with a plurality of compounds comprising an M moiety covalently bonded to a reactive group complementary to the G moiety of the reactive polymer compound,

wherein the M moiety is a fluorescent dye or a biologically active moiety selected from an NSAID, a kinase inhibitor, an anthracycline, an EGFR inhibitor, an alkylating agent and an anti-cancer drug,

wherein a first compound of the plurality of compounds comprises the M moiety being the fluorescent dye,

wherein a second compound of the plurality of compounds comprises the M moiety being the biologically active moiety, and

wherein reacting includes forming a covalent bond between the M moiety and the G moiety by reaction of the G moiety and the reactive group complementary to the G moiety.

Continuity (4)

References Cited (400)