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US 9,980,926 B1Granted
Affinity medicant conjugate
AssigneeAF Chemicals, LLC
InventorMichael Kelner
Life of this patent
Estimating the term…
Abstract
In an embodiment of the invention, a composition for treating a cell population comprises an Affinity Medicant Conjugate (AMC). The medicant moiety can be a toxin including an acylfulvene or a drug moiety. The affinity moiety can be an antibody, a binding protein, a steroid, a lipid, a growth factor, a protein, a peptide or non peptidic. The affinity moiety can be covalently bound to the medicant via a linker. Novel linkers that can be directed to cysteine, arginine or lysine residues based on solution pH allow greater flexibility in preserving and/or generating specific epitopes in the AMC.
Claims15
A compound of the formula:
- or a pharmaceutically acceptable salt thereof, where X is selected from the group consisting of —NH—, —NR8—, —S—, —O—, —CH2—, —CHR8—, —CHR8R9—, —HC═CH—, —R8C—CR9—, —NR3—, —CHR3—, —CR3R4—, —OC(═O)O—, —OC(═O)—, —C(═O)O—, —CR3(═N)—, —CR3(═N)NR3—, —CR3(═N)NR3S(═O)2—, —CR3(═N)O—, —N(OH)—, —N(OR3)—, —C(C═O)NR3—, —N(OR3)C(═O)—, —N(OR3)C(═O)NR3—, —N(R3)S—, —N(R3)S(═O)—, —N(R3)S(═O)2—, —OC(═O)NR3—, —N(OR3)C(═O)O—, —N(R3)C(═S)—, —O(S(═O)2—, —O(S(═O)2NR3—, —S(═O)—, —S(═O)2—, —N(R3)S(═O)2NR3—, —NR3(C═O)—, —NR3(C═O)O—, —NR3(C═O)N—, —N(═N)—, and —CR3(═N—N═)CR3—;
- R1 represents a bi-functional linker with a first terminus including a first functional group, and a second terminus including a second functional group, where X is covalently bonded to the first functional group, where the bifunctional linker is selected from the group consisting of a fluorosulfonyl benzoyl (FSB) linker, a maleimide or maleic (Mal1) derivative linker, a bridging amino acid linker and an azlactone linker;
- R2 represents a peptide affinity moiety, where R2 is covalently bonded to the second functional group;
- and R3, R4, R5, R6, R7 each independently represent H, —OH, —OCH3, —OC(═O)CH3—, —CH3, —CH2—CH3, —CH—(CH3)2, —C(CH3)3, —CH2—CH2—CH3, —CH2—CH—(CH3)2, —CH—C—(CH3)3, C(═O)CH3, CH2OH, and (C1-C4)alkyl;
- and R8, R9 each independently represent —CH2—, -, —CH2—CH2—, —CH(CH3)—CH2—, —C(CH3)2—CH2—, —CH2—CH2—CH2—, —CH2—CH(CH3)—CH2—, —CH—C(CH3)2—CH2—, —C(═O)CH2—, —CH2O—, or racemic mixtures of any enantiomers thereof.
2 more elements
A compound of the formula:
- or a pharmaceutically acceptable salt thereof, where X is selected from the group consisting of —NH—, —NR8—, —S—, —O—, —CH2—, —CHR8—, —CHR8R9—, —HC═CH—, —R8C—CR9—, —NR3—, —CHR3—, —CR3R4—, —OC(═O)O—, —OC(═O)—, —C(═O)O—, —CR3(═N)—, —CR3(═N)NR3—, —CR3(═N)NR3S(═O)2—, —CR3(═N)O—, —N(OH)—, —N(OR3)—, —C(C═O)NR3—, —N(OR3)C(═O)—, —N(OR3)C(═O)NR3—, —N(R3)S—, —N(R3)S(═O)—, —N(R3)S(═O)2—, —OC(═O)NR3—, —N(OR3)C(═O)O—, —N(R3)C(═S)—, —O(S(═O)2—, —O(S(═O)2NR3—, —S(═O)—, —S(═O)2—, —N(R3)S(═O)2NR3—, —NR3(C═O)—, —NR3(C═O)O—, —NR3(C═O)N—, —N(═N)—, and —CR3(═N—N═)CR3—;
- R1 represents a bi-functional linker with a first terminus including a first functional group, and a second terminus including a second functional group, where X is covalently bonded to the first functional group, where the bifunctional linker is selected from the group consisting of a fluorosulfonyl benzoyl (FSB) linker, a maleimide or maleic (Mal1) linker, a bridging amino acid linker, and an azlactone linker;
- R2 represents a protein affinity moiety, where R2 is covalently bonded to the second functional A group;
- and R3, R4, R5, R6, R7 each independently represent H, —OH, —OCH3, —OC(═O)CH3—, —CH3, —CH2—CH3, —CH—(CH3)2, —C(CH3)3, —CH2—CH2—CH3, —CH2—CH—(CH3)2, —CH—C—(CH3)3, C(═O)CH3, CH2OH, and (C1-C4)alkyl;
- and R8, R9 each independently represent —CH2—, -, —CH2—CH2—, —CH(CH3)—CH2—, —C(CH3)2—CH2—, —CH2—CH2—CH2—, —CH2—CH(CH3)—CH2—, —CH—C(CH3)2—CH2—, —C(═O)CH2—, —CH2O—, or racemic mixtures of any enantiomers thereof.
2 more elements
Dependencies are inferred from the claim text.