Big Pharma vies for mice
Tarrytown, New York–based Regeneron has inked two lucrative, nonexclusive licensing deals recently for its VelocImmune humanized mouse antibody system designed to accelerate the discovery and development of fully human antibodies. In March, Astellas Pharma of Tokyo agreed to pay $20 million upfront with additional annual payments to total up to $120 million depending on milestones, as well as mid-single-digit royalties to Regeneron on any resulting products. In February, London-based AstraZeneca signed an identical deal. Existing humanized mice suffer from depressed immune systems, requiring more work to produce an effective antibody. Part of the problem is the fully humanized nature of the antibodies. Genes controlling the antibody variable regions must be human because that is the critical variable that leads to evolution of high affinity. But existing systems incorporate human constant regions as well, and those human regions don't interact well with the rest of the mouse immune system because they didn't evolve there, according to George Yancopoulos, CSO at Regeneron. Random insertions of human genes might also be causing disruptions. VelocImmune mice, however, have mouse constant regions that can be easily swapped out for human regions when antibodies go to large-scale production. Regeneron had previously developed technologies to create gene mutations in mouse stem cells as well as exchange very large (up to six megabases) sets of mouse sequences with human sequences. The mice can then be grown directly from the stem cell, bypassing breeding, which is a big time-saver, Yancopoulos says. “Existing [humanized] mice are a breeding nightmare. These can be bred like normal mice, and you don't have to do such large samplings to get good antibodies.” The mice are the most valuable ever created, Yancopoulos claims. “Efficiency and speed are the name of the game,” he says. “These mice afford that.” JK
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