Combination of antibody-pyrrolobenzodiazepine derivative conjugate and PARP inhibitor
AssigneeDaiichi Sankyo Company, Limited
InventorsNaoya Harada, Michiko Kitamura
Life of this patent
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Abstract
A pharmaceutical composition for treatment of cancer or a method for treating cancer, wherein an antibody-pyrrolobenzodiazepine derivative conjugate and a PARP inhibitor are administered in combination.
Claims58
A pharmaceutical composition for treatment of cancer, the pharmaceutical composition comprising an antibody-pyrrolobenzodiazepine derivative conjugate and a PARP inhibitor, wherein the antibody-pyrrolobenzodiazepine derivative conjugate and the PARP inhibitor are administered in combination, and the conjugate has the following formula:
- wherein, in each structural formula shown above,
- m1 is an integer of 1 or 2;
- Ab is an antibody or a functional fragment of the antibody;
- the N297 glycan is any one of N297-(Fuc)MSG1, N297-(Fuc)MSG2, and a mixture thereof, and N297-(Fuc)SG, with N297-(Fuc)MSG1, N297-(Fuc)MSG2, and N297-(Fuc)SG having structures represented by the following formulas:
- wherein
- each wavy line represents bonding to Asn297 of the antibody,
- L(PEG) in the N297 glycan represents *—(CH2CH2—O)3—CH2CH2—NH—, wherein the amino group at the right end is bound via an amide bond to carboxylic acid at the 2-position of a sialic acid at the non-reducing terminal in each or either one of the 1-3 and 1-6 branched chains of β-Man in the N297 glycan, and the asterisk * at the left end represents bonding to a nitrogen atom at the 1- or 3-position of the triazole ring in the corresponding structural formula.
A method for treating a cancer that expresses CLDN6 and/or CLDN9, wherein an antibody-pyrrolobenzodiazepine derivative conjugate and a PARP inhibitor are administered in combination, and the conjugate has the following formula:
- wherein, in each structural formula shown above,
- m1 is an integer of 1 or 2;
- Ab is an antibody or a functional fragment of the antibody;
- the N297 glycan is N297-(Fuc)MSG1, N297-(Fuc)MSG2, or a mixture thereof, or N297-(Fuc)SG, with N297-(Fuc)MSG1, N297-(Fuc)MSG2, and N297-(Fuc)SG having structures represented by the following formulas:
- wherein
- each wavy line represents bonding to Asn297 of the antibody,
- L(PEG) in the N297 glycan represents *—(CH2CH2—O)3—CH2CH2—NH—, wherein the amino group at the right end is bound via an amide bond to carboxylic acid at the 2-position of a sialic acid at the non-reducing terminal in each or either one of the 1-3 and 1-6 branched chains of β-Man in the N297 glycan, and the asterisk * at the left end represents bonding to a nitrogen atom at the 1- or 3-position of the triazole ring in the corresponding structural formula.
Dependencies are inferred from the claim text.