Anti-steap1 antigen-binding protein

A nucleic acid composition comprising:

• a) a first nucleic acid encoding a first monomer comprising a first heavy chain comprising:
• 1) a first variable heavy domain;
• 2) a first constant heavy chain comprising a first CH1 domain and a first Fc domain;
• and 3) a scFv that binds human CD3 and comprises a scFv variable light domain comprising light chain CDRs comprising amino acid sequences vlCDR1 SEQ ID NO:
• 174, vlCDR2 SEQ ID NO:175, and vlCDR3 SEQ ID NO:
• 176, an scFv linker, and a scFv variable heavy domain comprising heavy chain CDRs comprising amino acid sequences vhCDR1 SEQ ID NO:
• 170, vhCDR2 SEQ ID NO:
• 171, and vhCDR3 SEQ ID NO:
• 172;
• wherein said scFv is covalently attached between the C-terminus of said CH1 domain and the N-terminus of said first Fc domain using domain linker(s);
• b) a second nucleic acid encoding a second monomer comprising a second heavy chain comprising a second variable heavy domain and a second constant heavy chain comprising a second Fc domain;
• and
• c) a third nucleic acid encoding a common light chain comprising a variable light domain and a constant light domain;
• wherein said first variable heavy domain and said variable light domain bind human STEAP1, said second variable heavy domain and said variable light domain bind human STEAP1, and wherein
• (i) the first variable heavy domain and the second variable heavy domain comprise heavy chain CDRs comprising amino acid sequences vhCDR1 SEQ ID NO:
• 14, vhCDR2 SEQ ID NO:
• 15 or SEQ ID NO:
• 21, and vhCDR3 SEQ ID NO:
• 16, and the variable light domain comprises light chain CDRs comprising amino acid sequences vlCDR1 SEQ ID NO:
• 11, vlCDR2 SEQ ID NO:
• 12, and vlCDR3 SEQ ID NO:
• 13;
• or
• (ii) the first variable heavy domain and the second variable heavy domain comprise heavy chain CDRs comprising amino acid sequences vhCDR1 SEQ ID NO:
• 33, vhCDR2 SEQ ID NO:
• 34, and vhCDR3 SEQ ID NO:
• 35, and the variable light domain comprises light chain CDRs comprising amino acid sequences vlCDR1 SEQ ID NO:
• 30, vlCDR2 SEQ ID NO:
• 31, and vlCDR3 SEQ ID NO:
• 32.

A nucleic acid composition comprising:

• a) a first expression vector comprising a first nucleic acid encoding a first monomer comprising a first heavy chain comprising:
• 1) a first variable heavy domain;
• 2) a first constant heavy chain comprising a first CH1 domain and a first Fc domain;
• and 3) a scFv that binds human CD3 and comprises a scFv variable light domain comprising light chain CDRs comprising amino acid sequences vlCDR1 SEQ ID NO:
• 174, vlCDR2 SEQ ID NO:175, and vlCDR3 SEQ ID NO:
• 176, an scFv linker, and a scFv variable heavy domain comprising heavy chain CDRs comprising amino acid sequences vhCDR1 SEQ ID NO:
• 170, vhCDR2 SEQ ID NO:
• 171, and vhCDR3 SEQ ID NO:
• 172;
• wherein said scFv is covalently attached between the C-terminus of said CH1 domain and the N-terminus of said first Fc domain using domain linker(s) of any one of claims 43-58;
• b) a second expression vector comprising a second nucleic acid encoding the second monomer comprising a second heavy chain comprising a second variable heavy domain and a second constant heavy chain comprising a second Fc domain;
• and
• c) a third expression vector comprising a third nucleic acid encoding a common light chain comprising a variable light domain and a constant light domain;
• wherein said first variable heavy domain and said variable light domain bind human STEAP1, said second variable heavy domain and said variable light domain bind human STEAP1, and wherein
• (i) the first variable heavy domain and the second variable heavy domain comprise heavy chain CDRs comprising amino acid sequences vhCDR1 SEQ ID NO:
• 14, vhCDR2 SEQ ID NO:
• 15 or SEQ ID NO:
• 21, and vhCDR3 SEQ ID NO:
• 16, and the variable light domain comprises light chain CDRs comprising amino acid sequences vlCDR1 SEQ ID NO:
• 11, vlCDR2 SEQ ID NO:
• 12, and vlCDR3 SEQ ID NO:
• 13;
• or
• (ii) the first variable heavy domain and the second variable heavy domain comprise heavy chain CDRs comprising amino acid sequences vhCDR1 SEQ ID NO:
• 33, vhCDR2 SEQ ID NO:
• 34, and vhCDR3 SEQ ID NO:
• 35, and the variable light domain comprises light chain CDRs comprising amino acid sequences vlCDR1 SEQ ID NO:
• 30, vlCDR2 SEQ ID NO:
• 31, and vlCDR3 SEQ ID NO:
• 32.