Therapeutic Antibodies

Fully-human monoclonal antibodies are highly desirable as therapeutics. In addition to the advantages of having high specificity and affinity for the therapeutic target, fully-human antibodies avoid potential immune responses in patients receiving antibodies containing nonhuman components.

Creating Fully-human, Therapeutic, Monoclonal Antibodies

The VelocImmune mouse is a genetic engineering tour de force, creating a humanized, therapeutic, monoclonal antibody. VelocImmune increases the speed and efficiency of fully-human therapeutic antibody development. Regeneron is using this technology to produce its next generation of drug candidates.

Previously engineered human monoclonal antibody-producing mice make antibodies with human constant regions, potentially resulting in inefficient protein-protein interactions that are critical for the generation of high affinity antibodies. In contrast, VelocImmune mice have immune systems that mount a robust, humoral-immune response that is indistinguishable from that of a normal, wild-type mouse including:

• Normal B cell development in bone marrow
• Normal numbers of mature B cells in the blood, spleen, and lymph nodes
• Normal allelic exclusion
• Normal serum levels for all immunoglobulin isotypes
• Normal ratios of kappa:lambda light chain
• Normal somatic hypermutation rates and class switching
• Normal responses to antigens
• Normal rates of hybridoma production

Once antibodies are isolated from the VelocImmune mouse, human variable sequences from VelocImmune antibodies are easily subcloned and joined to the desired human constant region.

The versatility of VelocImmune can be further enhanced by combining it with VelociGene. This allows the rapid knockout of mouse genes in the VelocImmune mouse that encode proteins that are homologous to target antigens and potentially recognized as "self" proteins by the mouse. This approach allows the production of antibodies against antigens that are highly conserved between mice and humans.