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

Humanization of the IGK V-J-REGION

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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

Humanization of the IGH V-D-J-REGION

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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
IMGT notes:
(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).
IMGT references:
[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