Bispecific antibody-camptothecin drug conjugate and pharmaceutical use thereof

An antibody-drug conjugate, which is:

• or a pharmaceutically acceptable salt thereof, wherein each instance of
• is independently and optionally replaced
• wherein SI-1×6.4 is a bispecific antibody comprising two IgG1 heavy chains, two κ light chains, and two scFvs, wherein the first IgG1 heavy chain and the first scFv form a construct comprising the amino acid sequence of SEQ ID NO:
• 4;
• the second IgG1 heavy chain and the second scFv form a construct comprising the amino acid sequence of SEQ ID NO:
• 4;
• the first κ light chain comprises the amino acid sequence of SEQ ID NO:
• 2;
• and the second κ light chain comprises the amino acid sequence of SEQ ID NO:
• 2, and
• wherein n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

An antibody-drug conjugate, which is:

• wherein each instance of
• is independently and optionally replaced by
• wherein SI-1×6.4 is a bispecific antibody comprising two IgG1 heavy chains, two κ light chains, and two scFvs, wherein the first IgG1 heavy chain and the first scFv form a construct comprising the amino acid sequence of SEQ ID NO:
• 4;
• the second IgG1 heavy chain and the second scFv form a construct comprising the amino acid sequence of SEQ ID NO:
• 4;
• the first κ light chain comprises the amino acid sequence of SEQ ID NO:
• 2;
• and the second κ light chain comprises the amino acid sequence of SEQ ID NO:
• 2, and wherein n is 5, 6, 7, or 8.

An antibody-drug conjugate, which is a pharmaceutically acceptable salt of:

• wherein each instance of
• is independently and optionally replaced by
• wherein SI-1×6.4 is a bispecific antibody comprising two IgG1 heavy chains, two κ light chains, and two scFvs, wherein the first IgG1 heavy chain and the first scFv form a construct comprising the amino acid sequence of SEQ ID NO:
• 4;
• the second IgG1 heavy chain and the second scFv form a construct comprising the amino acid sequence of SEQ ID NO:
• 4;
• the first κ light chain comprises the amino acid sequence of SEQ ID NO:
• 2;
• and the second κ light chain comprises the amino acid sequence of SEQ ID NO:
• 2, and wherein n is 5, 6, 7, or 8.

An antibody-drug conjugate, which is:

• wherein each instance of
• is independently and optionally replaced by
• wherein Ab is a bispecific antibody or antigen-binding fragment thereof, wherein the Ab comprises an IgG having binding specificity for EGFR and a single-chain Fv (scFv) having binding specificity for HER3, wherein the IgG comprises a heavy chain and a κ light chain, wherein the heavy chain of the IgG comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO:29, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO:30, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO:31, and wherein the κ light chain of the IgG comprises a light chain CDR1 comprising the amino acid sequence of SEQ ID NO:25, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO:26, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO:27;
• and
• wherein the scFv comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO:32, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO:33, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO:34, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO:35, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO:36, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO:37, and
• wherein n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

An antibody-drug conjugate, which is:

• wherein SI-1×6.4 is a bispecific antibody comprising two IgG1 heavy chains, two κ light chains, and two scFvs, wherein the first IgG1 heavy chain and the first scFv form a construct comprising the amino acid sequence of SEQ ID NO:
• 4;
• the second IgG1 heavy chain and the second scFv form a construct comprising the amino acid sequence of SEQ ID NO:
• 4;
• the first κ light chain comprises the amino acid sequence of SEQ ID NO:
• 2;
• and the second κ light chain comprises the amino acid sequence of SEQ ID NO:
• 2, and
• wherein n is 8.

An antibody-drug conjugate, which is:

• wherein SI-1×6.4 is a bispecific antibody comprising two IgG1 heavy chains, two κ light chains, and two scFvs, wherein the first IgG1 heavy chain and the first scFv form a construct comprising the amino acid sequence of SEQ ID NO:
• 4;
• the second IgG1 heavy chain and the second scFv form a construct comprising the amino acid sequence of SEQ ID NO:
• 4;
• the first κ light chain comprises the amino acid sequence of SEQ ID NO:
• 2;
• and the second κ light chain comprises the amino acid sequence of SEQ ID NO:
• 2, and
• wherein n is 8.

An antibody-drug conjugate, which is:

• wherein SI-1×6.4 is a bispecific antibody comprising two IgG1 heavy chains, two κ light chains, and two scFvs, wherein the first IgG1 heavy chain and the first scFv form a construct comprising the amino acid sequence of SEQ ID NO:
• 4;
• the second IgG1 heavy chain and the second scFv form a construct comprising the amino acid sequence of SEQ ID NO:
• 4;
• the first κ light chain comprises the amino acid sequence of SEQ ID NO:
• 2;
• and the second κ light chain comprises the amino acid sequence of SEQ ID NO:
• 2, and
• wherein n is 8.