VelocImmune™ is our technology for producing fully human monoclonal antibodies. The embodiment of the technology is the VelocImmune mouse, the largest mammalian genetic engineering project ever accomplished — a mouse capable of producing fully human antibodies.
The VelocImmune mouse uniquely expresses human antibody genes in the same robust fashion that the mouse genes are typically expressed. Using VelociGene® technology, we replaced 6 megabases (6 million units) of mouse DNA that code for the production of immune system proteins (immunoglobulin) with the corresponding human DNA. Antibodies are composed of unique variable regions that are specific for the target, and common constant regions that interact with mouse signaling machinery to produce a large variety and number of antibodies. The VelociGene technology allows for such precision that we were able to create a mouse that expresses human variable regions but preserves the mouse constant regions, which are critical for the mouse to mount a robust immune response. This mouse becomes a living factory that greatly increases the speed and efficiency for the generation of fully-human therapeutic antibodies. The productivity of VelocImmune can be seen in the pipeline of fully-human antibodies we have in clinical development, and the many other antibodies we have in preclinical development.
Fully-human monoclonal antibodies are highly desirable as therapeutics, for in addition to the advantages of being very specific for and tightly binding to their therapeutic targets, fully-human antibodies avoid potential immune responses that may occur in patients receiving antibodies that contain nonhuman (typically mouse) components.
Previously engineered human monoclonal antibody-producing mice were generated with old technologies that resulted in removal of the mouse constant regions that, as just described, are critical for the mouse to make a strong immune response. In contrast, VelocImmune mice preserve the mouse constant regions and, therefore, have immune systems that mount a robust, humoral-immune response that is indistinguishable from that of a normal, wild-type mouse.
In other words, we rely on our genetically-engineered VelocImmune mice to make antibodies that have fully human variable regions and mouse constant regions. After we select and isolate the antibodies with the required immune properties from the VelocImmune mouse, in a standard technical step, we combine the human variable sequences from the VelocImmune antibodies with the desired human constant region to generate fully human antibody that is ready for testing as a potential drug candidate.