Antibodies with low immunogenicity and uses thereof

An antibody or an antigen-binding fragment thereof, comprising a heavy chain variable region (VH) that comprises four VH framework regions (VH FR1-4) and three VH complementarity determining regions (VH CDR1-3) in the following N-terminal to C-terminal order:

• VH FR1-VH CDR1-VH FR2-VH CDR2-VH FR3-VH CDR3-VH FR4, wherein VH FR1, VH FR2, VH FR3 and VH FR4 comprise the amino acid sequence of
• XH1XH2XH3QLVQSGXH4EVKKXH5GXH6XH7VKXH8SCKXH9S (SEQ ID NO:
• 1);
• WVXH10QAXH11GXH12XH13LEWXH14G (SEQ ID NO:
• 2);
• YAXH15KXH16QXH17RVTXHl8TXH19XH20XH21 SXH22XH23TXH24YMELXH25XH26LRAXH27DTA XH28YYC (SEQ ID NO:
• 3);
• and
• WGXH29GTXH30VTVSS (SEQ ID NO:
• 4), respectively,
• wherein XH1 is M or no amino acid, XH2 is Q or E, XH3 is V or M, XH4 is A or P, XH5 is P or T, XH6 is A, S, or T, XH7 is S or T, XH8 is V or I, XH9 is A or V, XH10 is R or Q, XH11 is P, R, or T, XH12 is Q or K, XH13 is G, R, or A, XH14 is M or I, XH15 is Q or E, XH16 is F or L, XH17 is G, D, or E, XH18 is M or I, XH19 is R, T, E or A, XH20 is D or N, XH21 is T, R, M, E, or K, XH22 is I, A T, or M, XH23 is S or D, XH24 is A or V, XH25 is S or R, XH26 is S or R, XH27 is D or E, XH28 is V or M, XH29 is Q or R, and XH30 is L, M or T.

An antibody or an antigen-binding fragment thereof, comprising a VL that comprises four VL framework regions (VL FR1-4) and three VL complementarity determining regions (VL CDR1-3) in the following N-terminal to C-terminal order:

• VL FR1-VL CDR1-VL FR2-VL CDR2-VL FR3-VL CDR3-VL FR4, wherein VL FR1, VL FR2, VL FR3 and VL FR4 comprise the amino acid sequence of
• NIQMTQSPSXL1XL2SASVGDRVTITC (SEQ ID NO:
• 8);
• WXL3QQKPGKXL4PKHLIY (SEQ ID NO:
• 9);
• GVPSRF SGSGSGTEFTLTIS SLQPEDFATYYC(SEQ ID NO:
• 10);
• and
• FGGGTKVEIK (SEQ ID NO:
• 11), respectively,
• wherein XL1 is A or S, XL2 is M or L, XL3 is F or Y, and XL4 is V or A, and at least one of the following is satisfied:
• XL1 is S, XL2 is L, XL3 is Y, and XL4 is A.