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US 2022/0177601 A1Published application
Anti-her2 antibody-pyrrolobenzodiazepine derivative conjugate
AssigneeDaiichi Sankyo Company, Limited
InventorsNaoya HARADA, Kozo YONEDA, Ichiro HAYAKAWA
Life of this patent
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Abstract
A novel anti-HER2 antibody-pyrrolobenzodiazepine (PBD) derivative conjugate, a medicine having therapeutic effect against tumor with the antibody-drug conjugate, and a method for treating a tumor by using the antibody-drug conjugate or medicine.
Claims73
An antibody-drug conjugate represented by the following formula:
- wherein
- m1 represents an integer of 1 or 2;
- D is any one selected from the following group:
- wherein
- each asterisk * represents bonding to L;
- L is a linker linking the glycan bonding to Asn297 of Ab (N297 glycan) and D;
- the N297 glycan is optionally remodeled;
- and
- Ab represents an antibody or a functional fragment of the antibody, wherein the antibody specifically binds to HER2 and comprises a heavy chain comprising CDRH1 consisting of an amino acid sequence represented by SEQ ID NO:
- 1, CDRH2 consisting of an amino acid sequence represented by SEQ ID NO:
- 2, and CDRH3 consisting of an amino acid sequence represented by SEQ ID NO:
- 3 or an amino acid sequence having one to several amino acid substitutions in the amino acid sequence represented by SEQ ID NO:
- 3, and a light chain comprising CDRL1 consisting of an amino acid sequence represented by SEQ ID NO:
- 5, CDRL2 consisting of an amino acid sequence consisting of amino acid residues 1 to 3 of SEQ ID NO:
- 6, and CDRL3 consisting of an amino acid sequence represented by SEQ ID NO:
- 7 or an amino acid sequence having one to several amino acid substitutions in the amino acid sequence represented by SEQ ID NO:
- 7.
14 more elements
An antibody-drug conjugate represented by the following formula:
- wherein, in each structural formula shown above,
- m1 represents an integer of 1 or 2;
- Ab represents an antibody or a functional fragment of the antibody, wherein the antibody specifically binds to HER2 and comprises a heavy chain comprising CDRH1 consisting of an amino acid sequence represented by SEQ ID NO:
- 1, CDRH2 consisting of an amino acid sequence represented by SEQ ID NO:
- 2, and CDRH3 consisting of an amino acid sequence represented by SEQ ID NO:
- 3 or an amino acid sequence having one to several amino acid substitutions in the amino acid sequence represented by SEQ ID NO:
- 3, and a light chain comprising CDRL1 consisting of an amino acid sequence represented by SEQ ID NO:
- 5, CDRL2 consisting of an amino acid sequence consisting of amino acid residues 1 to 3 of SEQ ID NO:
- 6, and CDRL3 consisting of an amino acid sequence represented by SEQ ID NO:
- 7 or an amino acid sequence having one to several amino acid substitutions in the amino acid sequence represented by SEQ ID NO:
- 7,
- 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 —NH—CH2CH2—(O—CH2CH2)3—*,
- wherein the amino group at the left end is bound via an amide bond to carboxylic acid at the 2-position of a sialic acid at the non-reducing terminal of 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 right end represents bonding to a nitrogen atom at the 1- or 3-position of the triazole ring in the corresponding structural formula.
13 more elements
An antibody-drug conjugate represented by the following formula:
- wherein, in each structural formula shown above,
- m1 represents an integer of 1 or 2;
- Ab represents an antibody or a functional fragment of the antibody, wherein the antibody specifically binds to HER2 and comprises a heavy chain comprising CDRH1 consisting of an amino acid sequence represented by SEQ ID NO:
- 1, CDRH2 consisting of an amino acid sequence represented by SEQ ID NO:
- 2, and CDRH3 consisting of an amino acid sequence represented by SEQ ID NO:
- 3 or an amino acid sequence having one to several amino acid substitutions in the amino acid sequence represented by SEQ ID NO:
- 3, and a light chain comprising CDRL1 consisting of an amino acid sequence represented by SEQ ID NO:
- 5, CDRL2 consisting of an amino acid sequence consisting of amino acid residues 1 to 3 of SEQ ID NO:
- 6, and CDRL3 consisting of an amino acid sequence represented by SEQ ID NO:
- 7 or an amino acid sequence having one to several amino acid substitutions in the amino acid sequence represented by SEQ ID NO:
- 7,
- 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 —NH—CH2CH2—(O—CH2CH2)3—*,
- wherein the amino group at the left end is bound via an amide bond to carboxylic acid at the 2-position of a sialic acid at the non-reducing terminal of 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 right end represents bonding to a nitrogen atom at the 1- or 3-position of the triazole ring in the corresponding structural formula.
13 more elements
An antibody-drug conjugate represented by the following formula:
- wherein, in each structural formula shown above,
- m1 represents an integer of 1 or 2;
- Ab represents an antibody or a functional fragment of the antibody, wherein the antibody specifically binds to HER2 and comprises a heavy chain comprising CDRH1 consisting of an amino acid sequence represented by SEQ ID NO:
- 1, CDRH2 consisting of an amino acid sequence represented by SEQ ID NO:
- 2, and CDRH3 consisting of an amino acid sequence represented by SEQ ID NO:
- 3 or an amino acid sequence having one to several amino acid substitutions in the amino acid sequence represented by SEQ ID NO:
- 3, and a light chain comprising CDRL1 consisting of an amino acid sequence represented by SEQ ID NO:
- 5, CDRL2 consisting of an amino acid sequence consisting of amino acid residues 1 to 3 of SEQ ID NO:
- 6, and CDRL3 consisting of an amino acid sequence represented by SEQ ID NO:
- 7 or an amino acid sequence having one to several amino acid substitutions in the amino acid sequence represented by SEQ ID NO:
- 7,
- 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 —NH—CH2CH2—(O—CH2CH2)3—*,
- wherein the amino group at the left end is bound via an amide bond to carboxylic acid at the 2-position of a sialic acid at the non-reducing terminal of 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 right end represents bonding to a nitrogen atom at the 1- or 3-position of the triazole ring in the corresponding structural formula.
13 more elements
An antibody-drug conjugate represented by the following formula:
- wherein, in each structural formula shown above,
- m1 represents an integer of 1 or 2;
- Ab represents an antibody or a functional fragment of the antibody, wherein the antibody specifically binds to HER2 and comprises a heavy chain comprising CDRH1 consisting of an amino acid sequence represented by SEQ ID NO:
- 1, CDRH2 consisting of an amino acid sequence represented by SEQ ID NO:
- 2, and CDRH3 consisting of an amino acid sequence represented by SEQ ID NO:
- 3 or an amino acid sequence having one to several amino acid substitutions in the amino acid sequence represented by SEQ ID NO:
- 3, and a light chain comprising CDRL1 consisting of an amino acid sequence represented by SEQ ID NO:
- 5, CDRL2 consisting of an amino acid sequence consisting of amino acid residues 1 to 3 of SEQ ID NO:
- 6, and CDRL3 consisting of an amino acid sequence represented by SEQ ID NO:
- 7 or an amino acid sequence having one to several amino acid substitutions in the amino acid sequence represented by SEQ ID NO:
- 7,
- 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 —NH—CH2CH2—(O—CH2CH2)3—*,
- wherein the amino group at the left end is bound via an amide bond to carboxylic acid at the 2-position of a sialic acid at the non-reducing terminal of 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 right end represents bonding to a nitrogen atom at the 1- or 3-position of the triazole ring in the corresponding structural formula.
13 more elements
An antibody or a functional fragment of the antibody, wherein the antibody specifically binds to HER2 and comprises a heavy chain comprising CDRH1 consisting of an amino acid sequence represented by SEQ ID NO:
- 1, CDRH2 consisting of an amino acid sequence represented by SEQ ID NO:
- 2, and CDRH3 consisting of an amino acid sequence represented by SEQ ID NO:
- 3 or an amino acid sequence having one to several amino acid substitutions in the amino acid sequence represented by SEQ ID NO:
- 3, and a light chain comprising CDRL1 consisting of an amino acid sequence represented by SEQ ID NO:
- 5, CDRL2 consisting of an amino acid sequence consisting of amino acid residues 1 to 3 of SEQ ID NO:
- 6, and CDRL3 consisting of an amino acid sequence represented by SEQ ID NO:
- 7 or an amino acid sequence having one to several amino acid substitutions in the amino acid sequence represented by SEQ ID NO:
- 7.
5 more elements
Dependencies are inferred from the claim text.