CPC A61K 47/6803 (2017.08) [A61K 31/4745 (2013.01); A61K 47/55 (2017.08); A61K 47/6851 (2017.08); C07K 16/18 (2013.01); A61K 2039/505 (2013.01)] | 42 Claims |
1. An immunoconjugate having Formula (I),
Ab-[S-L1-L2-L3-L4-L5-L6-L7-D]n (I)
wherein:
Ab is an antibody or an antigen-binding fragment thereof;
L1 is
L2 is absent,
Z1 and Z2 are each individually hydrogen, halogen, NO2, —O—(C1-C6 alkyl), or C1-C6 alkyl;
L3 is —(CH2)n1-C(═O)— or —(CH2CH2O)n1-(CH2)n1C(═O)—;
each n1 is independently an integer of 0 to 12;
L4 is a tetrapeptide residue;
L5 is absent or —[NH(CH2)n2]n3-;
n2 is an integer of 0 to 6;
n3 is an integer of 0 to 2;
L6 is absent or
L7 is absent,
D is a drug moiety; and
n is an integer from 1 to 10, wherein said antibody or binding fragment thereof is selected from:
an antibody or binding fragment thereof comprising:
a heavy chain comprising:
VHCDR 1 comprising an amino acid sequence of SEQ ID NO:29;
VHCDR 2 comprising an amino acid sequence of SEQ ID NO:30; and
VHCDR 3 comprising an amino acid sequence of SEQ ID NO:31; and
a light chain comprising:
VLCDR 1 comprising an amino acid sequence of SEQ ID NO:36;
VLCDR 2 comprising an amino acid sequence of DAS; and
VLCDR 3 comprising an amino acid sequence of SEQ ID NO:38;
wherein the antibody or antigen-binding fragment specifically binds to the extracellular domain of human receptor tyrosine kinase like orphan receptor 1 (ROR1).
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