Patent ID: 11857565
Assignee: SEAGEN INC.
Field: Pharmaceuticals (Chemistry)
Classification: CPC C  A | IPC A

Claim 5:
6. The Ligand Drug Conjugate compound of claim 1, wherein
(a) W is an amino acid sequence comprising a dipeptide, wherein the dipeptide has the structure of:, wherein
the wavy line at the dipeptide N-terminus indicates the site of covalent attachment via an amide bond to an auristatin F compound through its C-terminal component's carboxylic acid residue;
the wavy line at the dipeptide C-terminus indicates the site of covalent attachment to the remainder W or to A, or a subunit thereof, as when AO is present as A2;
R34 is hydrogen, or the side chain of a naturally occurring α-amino acid except proline, in particular —CH3, —C(CH3)2, —CH2COOH, —CH2CH2COOH, or —CH2CH2CH2CH2NH2; and
R35 is hydrogen, methyl, isopropyl, sec-butyl, benzyl, p-hydroxy-benzyl, —CH2OH, —CH(OH)CH3, —CH2CH2SCH3, —CH2C(═O)NH2, —CH2COOH, —CH2CH2C(═O)NH2, —CH2CH2COOH, —CH2CH2CH2NHC(═NH)NH2, —CH2CH2CH2NH2, —CH2CH2CH2NH—C(═O)CH3, —CH2CH2CH2NH—C(═O)H, —CH2CH2CH2CH2NHC(═NH)NH2, —CH2CH2CH2CH2NH2—, —CH2CH2CH2CH2NH—C(═O)CH3, —CH2CH2CH2CH2NH—C(═O)H, —CH2CH2CH2NHC(═O)NH2, —CH2CH2CH2CH2NHC(═O)NH2, —CH2CH2CH(OH)CH2NH2, 2-pyridylmethyl, 4-pyridylmethyl, phenyl, or cyclohexyl, or
R35 has the structure of one of:, wherein the wavy line indicates the site of covalent attachment to the dipeptide backbone; or
(b) W is a glutamic acid residue, an aspartic acid residue, or a peptide sequence comprising an N-terminal glutamic acid residue or N-terminal aspartic acid residue, wherein W is covalently attached through its α-amino nitrogen atom to the hydrophobic auristatin F compound C-terminal component's carboxylic acid residue, and wherein W is covalently attached through its a-carboxyl carbon atom to A′, wherein both attachments are through amide bonds,
wherein A′ is a C2-C12 alkylene diamine, in particular a C2-C6 or a C2-C4 alkylene diamine having a carboxylic acid substituent, wherein the nitrogen atom of one of the amines of A′ is covalently attached via an amide bond to W, and the nitrogen atom of the other amine of A′ is covalently attached to A, or a subunit thereof, as when AO is present as A2; or
(c) -A′-W— has the structure of:, wherein
the wavy line adjacent to the glutamic acid alpha-amino nitrogen atom indicates the site of covalent attachment via an amide bond to the hydrophobic auristatin F compound through its C-terminal component's carboxylic acid residue,
and the wavy line adjacent to the lysine epsilon amine nitrogen atom indicates the site of covalent attachment to A or subunit thereof as when AO is present as A2.