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US 2020/0347149 A1Published application
Monomethylvaline compounds capable of conjugation to ligands
AssigneeSeattle Genetics, Inc.
InventorsSvetlana O. DORONINA, Peter D. SENTER, Brian E. Toki, Toni Beth KLINE
Life of this patent
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Abstract
Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo.
Claims21
(canceled)
An antibody-drug conjugate having the formula:
- or a pharmaceutically acceptable salt thereof, wherein:
- Ab is an antibody,
- A is a Stretcher unit, having the structure of
- a is 1,
- —Ww— unit is a tetrapeptide;
- wherein each —W— unit is independently an Amino Acid unit having the formula denoted below in the square bracket:
- wherein R19 is hydrogen, methyl, isopropyl, isobutyl, sec-butyl, benzyl, p-hydroxybenzyl, —CH2OH, —CH(OH)CH3, —CH2CH2SCH3, —CH2CONH2, —CH2COOH, —CH2CH2CONH2, —CH2CH2COOH, —(CH2)3NHC(═NH)NH2, —(CH2)3NH2, —(CH2)3NHCOCH3, —(CH2)3NHCHO, —(CH2)4NHC(═NH)NH2, —(CH2)4NH2, —(CH2)4NHCOCH3, —(CH2)4NHCHO, —(CH2)3NHCONH2, —(CH2)4NHCONH2, —CH2CH2CH(OH)CH2NH2, 2-pyridylmethyl-, 3-pyridylmethyl-, 4-pyridylmethyl-, phenyl, cyclohexyl,
- Y is a Spacer unit,
- y is 0, 1, or 2,
- D is a drug moiety, and
- p ranges from 1 to about 20, and
- wherein the Stretcher unit A is linked to the antibody via a sulfur atom on a cysteine residue of the antibody.
9 more elements
A method of preparing an antibody-drug conjugate having the formula:
- or a pharmaceutically acceptable salt thereof, wherein:
- Ab is an antibody,
- A is a Stretcher unit, having the structure of
- a is 1,
- —Ww— unit is a tetrapeptide;
- wherein each —W— unit is independently an Amino Acid unit having the formula denoted below in the square bracket:
- wherein R19 is hydrogen, methyl, isopropyl, isobutyl, sec-butyl, benzyl, p-hydroxybenzyl, —CH2OH, —CH(OH)CH3, —CH2CH2SCH3, —CH2CONH2, —CH2COOH, —CH2CH2CONH2, —CH2CH2COOH, —(CH2)3NHC(═NH)NH2, —(CH2)3NH2, —(CH2)3NHCOCH3, —(CH2)3NHCHO, —(CH2)4NHC(═NH)NH2, —(CH2)4NH2, —(CH2)4NHCOCH3, —(CH2)4NHCHO, —(CH2)3NHCONH2, —(CH2)4NHCONH2, —CH2CH2CH(OH)CH2NH2, 2-pyridylmethyl-, 3-pyridylmethyl-, 4-pyridylmethyl-, phenyl, cyclohexyl,
- Y is a Spacer unit,
- y is 0, 1 or 2,
- D is a drug moiety, and
- p ranges from 1 to about 20, and
- wherein the Stretcher unit A is covalently attached to the antibody via a sulfur atom on acystene residue of the antibody,
- comprising conjugating a drug linker having the formula:
- to the antibody Ab.
11 more elements
Dependencies are inferred from the claim text.