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Human Antibody Production from Transgenic Mice

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Creative Biolabs has developed the Fully Human Antibody Technology™ (FHAT) to produce fully human monoclonal antibodies in mice. As a leading custom service provider in human antibody production field, Creative Biolabs has in-licensed two strains of "humanized" transgenic mice (FHAT mice) and successfully demonstrated their applications in discovery and production of unique fully human antibodies against various targets.


By introducing human immunoglobulin loci into the germ line of mice with inactivated mouse antibody machinery, the in-licensed mouse strains can directly generate high affinity, fully human antibodies, which avoid the subsequent costly and tedious in vitro affinity maturation and antibody humanization process. Upon immunization, the immunoglobulin transgenes undergo V(D)J joining, random nucleotide (N region) addition, class switching, and somatic mutation to generate high affinity monoclonal antibodies.

Human Antibody Production from Transgenic Mice 

Since the first EGFR targeting antibody panitumumab (Vectibix) from humanized mice has obtained regulatory approval in 2005, dozens of additional transgenic mouse-derived mAbs have entered human clinical testing, i.e., CD20 (Ofatumumab), CD4 (Zanolimumab), CD70 (MDX-1411), etc. These genetically "humanized" mouse strains have become an extremely powerful toolbox for antibody drug discovery.

The FHAT transgenic mice genetically engineered with a "humanized humoral immune" system can be of better valuable in therapeutic antibody development, since the derivative antibodies are preselected in vivo. In contrast, antibodies derived from non-animal sources have very artificial antibody sequences that do not exist in nature. These non-nature-selected antibody sequences may perform well in vitro but will behave completely different in vivo. One of the common problems is that the artificial antibodies will disappear in vivo without disclosing their whereabouts. This could due to the fact that the antibodies bind to unknown epitopes. Alternatively, the antibodies are captured by cells or simply degraded or sliced in vivo. Antibodies derived from live animals have passed nature-selection and usually do not have such issues.




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