Biparatopic fr-alpha antibodies and immunoconjugates

An immunoconjugate represented by the following formula:

• or a pharmaceutically acceptable salt thereof, wherein:
• CBA is a biparatopic antibody or an antigen-binding fragment comprising the amino acid sequences of SEQ ID NOs:
• 41-43;
• and wherein D1 is a maytansinoid.

An immunoconjugate represented by the following formula:

• or a pharmaceutically acceptable salt thereof, wherein:
• CBA is a bivalent biparatopic antibody or antigen-binding fragment thereof that specifically binds human folate receptor 1 (FRα), wherein the antibody or antigen-binding fragment comprises:
• (i) a first FRα-binding domain comprising a first variable heavy chain (VH) and a first variable light chain (VL), wherein (a) the first VH comprises VH CDR1-3 comprising the amino acid sequences of SEQ ID NOs:
• 10-12, respectively, or SEQ ID NOs:
• 15, 16, and 12, respectively;
• and (b) the first VL comprises VL CDR1-3 comprising the amino acid sequences of SEQ ID NOs:
• 4-6, respectively;
• and
• (ii) a second FRα-binding domain comprising a second VH and a second VL, wherein the second VH comprises VH CDR1-3 comprising the amino acid sequences of (a) SEQ ID NOs:
• 7-9, respectively, or (b) SEQ ID NOs:
• 13, 14, and 9, respectively;
• and the second VL comprises VL CDR1-3 comprising the amino acid sequences of SEQ ID NOs:
• 1-3, respectively;
• wherein the first FRα-binding domain comprises an single-chain variable fragment (scFv) and the second FRα-binding domain comprises a VH and a VL on separate polypeptides or wherein the second FRα-binding domain comprises an single-chain variable fragment (scFv) and the first FRα-binding domain comprises a VH and a VL on separate polypeptides;
• wherein the bivalent biparatopic antibody or antigen-binding fragment thereof comprises an IgG heavy chain constant region and a light chain constant region;
• and
• wherein D1 is a maytansinoid.