Antibody comprising a glutamine-containing light chain c-terminal extension, conjugates thereof, and methods and uses
AssigneeBristol-Myers Squibb Company
InventorsPavel STROP, Chetana RAO-NAIK, Xiaodi DENG, Paul O. SHEPPARD, Patrick G. HOLDER, Sayumi YAMAZOE
Life of this patent
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Abstract
An antibody has a glutamine-containing extension at the C-terminus of a light chain thereof, making it suitable for conjugation via transglutaminase-mediated transamidation.
Claims23
A full length antibody having on the C-terminus of a light chain thereof a glutamine-containing extension comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, NO:2, NO:3, NO:4, NO:5, NO:6, NO:7, NO:8, NO:9, NO:10, NO:11, NO:12, NO:13, NO:14, NO:15, NO:16, NO:17, NO:18, NO:19, NO:20, NO:21, NO:22, NO:23, NO:24, NO:25, NO:26, NO:29, NO:30, NO:31, NO:32, NO:33, NO:34, NO:35, NO:36, NO:37, NO:38, NO:39, and NO:40.
A conjugate of the formula (IV)
- wherein
- Ab is a full length antibody having on the C-terminus (carboxy terminus) of a light chain thereof a glutamine-containing extension comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, NO:2, NO:3, NO:4, NO:5, NO:6, NO:7, NO:8, NO:9, NO:10, NO:11, NO:12, NO:13, NO:14, NO:15, NO:16, NO:17, NO:18, NO:19, NO:20, NO:21, NO:22, NO:23, NO:24, NO:25, NO:26, NO:29, NO:30, NO:31, NO:32, NO:33, NO:34, NO:35, NO:36, NO:37, NO:38, NO:39, and NO:40;
- L is a linker moiety bonded to Ab via the amide bond
- to a glutamine in a glutamine containing extension;
- and
- D is selected from the group consisting of a protein, a radioisotope, an assay agent, and a therapeutic agent.
A method of making an antibody conjugate, comprising the steps of
- (a) mixing a full length antibody having on the C-terminus (carboxy terminus) of a light chain thereof a glutamine-containing extension comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, NO:2, NO:3, NO:4, NO:5, NO:6, NO:7, NO:8, NO:9, NO:10, NO:11, NO:12, NO:13, NO:14, NO:15, NO:16, NO:17, NO:18, NO:19, NO:20, NO:21, NO:22, NO:23, NO:24, NO:25, NO:26, NO:29, NO:30, NO:31, NO:32, NO:33, NO:34, NO:35, NO:36, NO:37, NO:38, NO:39, and NO:40 with an amine donor compound comprising a primary amine and a moiety selected from the group consisting of a protein, a radioisotope, an assay agent, and a therapeutic agent, in the presence of a transglutaminase;
- and
- (b) allowing the transglutaminase to catalyze the formation of an amide bond between the side chain carboxamide of a glutamine of the glutamine-containing extension and the primary amine of the amine donor compound, thereby making the antibody conjugate.
A method of making an antibody conjugate, comprising the steps of
- (a) mixing a full length antibody having on the C-terminus (carboxy terminus) of a light chain thereof a glutamine-containing extension comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, NO:2, NO:3, to NO:4, NO:5, NO:6, NO:7, NO:8, NO:9, NO:10, NO:11, NO:12, NO:13, NO:14, NO:15, NO:16, NO:17, NO:18, NO:19, NO:20, NO:21, NO:22, NO:23, NO:24, NO:25, NO:26, NO:29, NO:30, NO:31, NO:32, NO:33, NO:34, NO:35, NO:36, NO:37, NO:38, NO:39, and NO:40 with a first compound, which first compound is an amine donor compound having a primary amine and a first reactive functional group, in the presence of a transglutaminase;
- (b) allowing the transglutaminase to catalyze the formation of an amide bond between the side chain carboxamide of a glutamine of the glutamine-containing extension and the primary amine of the first compound, to make an adduct of the antibody and the first compound;
- (c) contacting the adduct with a second compound having a second reactive functional group and a moiety selected from the group consisting of a protein, a radioisotope, an assay agent, and a therapeutic agent;
- the second reactive functional group being capable of reacting with the first reactive functional group to form a covalent bond therebetween;
- and
- (d) allowing the first and second reactive functional groups to react and form a covalent bond therebetween, thereby making the antibody conjugate.
Dependencies are inferred from the claim text.