Amino acid sequences of the IGK V-J-REGION and IGH V-D-J-REGION are displayed, according to the IMGT unique numbering for V-DOMAIN.
A.4.6.1 (or muMAb-VEGF) is a murine anti-VEGF-A antibody. The Fab was humanized and designated as F(ab)-12 [1], and later as Fab-12 in the literature. By fusion of the Fab-12 to a human Fc, the humanized 12-IgG1 (or rhuMAb-VEGF) antibody was obtained [2], which corresponds to bevacizumab (INN name) or AVASTIN®.
IMGT/3Dstructure-DB 1bj1 [2].
The Fab-12 variant Y0317 was obtained by four amino acid changes: in the VH (CDR1-IMGT: T29>D, N36>H, CDR3-IMGT: H109>Y, S112.2>T) and one amino acid change in V-KAPPA (M4>L). Note that there is also an additional change in the hinge (T10>L) for construct [3]. This Fab-12 variant Y0317 corresponds to ranibizumab (INN name) or LUCENTIS®.
IMGT/3Dstructure-DB 1cz8.
Humanized monoclonal antibodies
________________________________________________________________________________________________________________________________________________________________ IGK V-REGION FR1-IMGT CDR1-IMGT FR2-IMGT CDR2-IMGT FR3-IMGT CDR3-IMGT FR4-IMGT (1-26) (27-38) (39-55) (56-65) (66-104) (105-117) (118-128) ______________________ __________________________ ____________ _________________ __________ _______________________________________ _____________ ______________ 1 10 20 30 40 50 60 70 80 90 100 110 120 .........|.........|...... ...|........ .|.........|..... ....|..... ....|.........|.........|.........|.... .....|....... ..|........ Murine A.4.6.1 DIQMTQTTSSLSASLGDRVIISCSAS QDI......SNY LNWYQQKPDGTVKVLIY FT.......S SLHSGVP.SRFSGSG..SGTDYSLTISNLEPEDIATYYC QQYST....VPWT FGGGTKLEIKR Human humκI DIQMTQSPSSLSASVGDRVTITCRAS QSI......SNY LAWYQQKPGKAPKLLIY AA.......S SLESGVP.SRFSGSG..SGTDFTLTISSLQPEDFATYYC QQYNS....LPWT FGQGTKVEIKR Humanized F(ab)-12 DIQMTQSPSSLSASVGDRVTITCSAS QDI......SNY LNWYQQKPGKAPKVLIY FT.......S SLHSGVP.SRFSGSG..SGTDFTLTISSLQPEDFATYYC QQYST....VPWT FGQGTKVEIKR Fab-12 variant Y0317 DIQLTQSPSSLSASVGDRVTITCSAS QDI......SNY LNWYQQKPGKAPKVLIY FT.......S SLHSGVP.SRFSGSG..SGTDFTLTISSLQPEDFATYYC QQYST....VPWT FGQGTKVEIKR
________________________________________________________________________________________________________________________________________________________________ IGH V-REGION FR1-IMGT CDR1-IMGT FR2-IMGT CDR2-IMGT FR3-IMGT CDR3-IMGT FR4-IMGT (1-26) (27-38) (39-55) (56-65) (66-104) (105-117) (118-128) ______________________ __________________________ ____________ _________________ __________ _______________________________________ ________________ ___________ 1 10 20 30 40 50 60 70 80 90 100 110 120 .........|.........|...... ...|........ .|.........|..... ....|..... ....|.........|.........|.........|.... .....|.121...... ..|........ Murine A.4.6.1 EIQLVQSGP.ELKQPGETVRISCKAS GYTF....TNYG MNWVKQAPGKGLKWMGW INTY..TGEP TYAADFK.RRFTFSLETSASTAYLQISNLKNDDTATYFC AKYPHYYGSSHWYFDV WGAGTTVTVSS Human humIII EVQLVESGG.GLVQPGGSLRLSCAAS GFTF....SSYA MSWVRQAPGKGLEWVSV ISGD..GGST YYADSVK.GRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARG..........FDY WGQGTLVTVSS Humanized F(ab)-12 EVQLVESGG.GLVQPGGSLRLSCAAS GYTF....TNYG MNWVRQAPGKGLEWVGW INTY..TGEP TYAADFK.RRFTFSLDTSKSTAYLQMNSLRAEDTAVYYC AKYPHYYGSSHWYFDV WGQGTLVTVSS Fab-12 variant Y0317 EVQLVESGG.GLVQPGGSLRLSCAAS GYDF....THYG MNWVRQAPGKGLEWVGW INTY..TGEP TYAADFK.RRFTFSLDTSKSTAYLQMNSLRAEDTAVYYC AKYPYYYGTSHWYFDV WGQGTLVTVSS
(1) | In green, murine "grafted" region on the human sequence or individual amino acid changes [1]. |
(2) | In blue, amino acid changes of Fab-12 variant Y0317 (ranibizumab) compared to Fab-12 (bevacizumab). |
[1] | Presta L.G. et al., Cancer Res., 57, 4593-4599 (1997). PMID: 9377574 |
[2] | Muller Y.A. et al., Structure 6, 1153-1167 (1998). PMID: 9753694 |
[3] | Chen Y. et al., J. Mol. Biol., 293, 865-881 (1999). PMID: 10543973 |