Anti-CD123 antibodies and conjugates and derivatives thereof

An immunoconjugate having the following formula:

• CBACyL1)wL,
• wherein:
• WL is an integer from 1 to 20;
• and
• CyL1 is represented by the following formula:
• or a pharmaceutically acceptable salt thereof, wherein:
• the double line between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is —H or a (C1-C4)alkyl;
• and when it is a single bond, X is —H or an amine protecting moiety, and Y is —OH or —SO3M;
• wherein M is H+ or a cation;
• L′ is represented by the following formula:
• —NR5—P—C(═O)—(CRaRb)m—C(═O)— (B1′);
• R5 is —H or a (C1-C3)alkyl;
• P is an amino acid residue or a peptide containing between 2 to 20 amino acid residues;
• Ra and Rb, for each occurrence, are each independently —H, (C1-C3)alkyl, or a charged substituent or an ionizable group Q, wherein Q is —SO3M;
• and
• m is an integer from 1 to 6;
• and
• CBA is an anti-CD123 antibody or antigen-binding fragment thereof that is covalently linked through a lysine residue to CyL1, wherein the antibody or antigen-binding fragment thereof comprises:
• a) a heavy chain variable region CDR1 having the amino acid sequence selected from the group consisting of SEQ ID NOs:
• 1, 5, and 12;
• a heavy chain variable region CDR2 having the amino acid sequence selected from the group consisting of SEQ ID NOs:
• 2, 3, 6-10, 13, and 14;
• and a heavy chain variable region CDR3 having the amino acid sequence selected from the group consisting of:
• SEQ ID NOs:
• 4, 11, 15, and 70;
• and
• b) a light chain variable region CDR1 having the amino acid sequence selected from the group consisting of:
• SEQ ID NOs:
• 16, 19, 20, 23 and 72;
• a light chain variable region CDR2 having the amino acid sequence selected from the group consisting of:
• SEQ ID NOs:
• 17, 21, 24 and 71;
• and a light chain variable region CDR3 having the amino acid sequence selected from the group consisting of:
• SEQ ID NOs:
• 18, 22, and 25;
• wherein the antibody or antigen-binding fragment thereof binds an epitope within amino acids 101 to 346 of human CD123 or IL3-Rα antigen and inhibits IL3-dependent proliferation in antigen-positive TF-1 cells.