Replies to post #35564 on Biotech Values

[Biowatch]

Re: mAbs

Wikipedia has a decent section on it, but doesn't add much to the Nature Medicine article.

http://en.wikipedia.org/wiki/Humanized_antibody

Basically, the murine antibodies get cleared from circulation too quickly, can cause inflammatory and immune responses. Plus, since the human patient develops antibodies against the mouse antibody, so subsequent doses become even less effective with time.

I don't think anyone is pursuing murine antibodies as drugs any more, but they are quite useful for all kinds of preclinical research and for assays.

Chimeric antibodies retain more of the murine antibody than humanized antibodies. Consequently, chimeric antibodies are more likely than humanized antibodies to trigger an immune response and get cleared more quickly. They pick the best murine antibody they can find initially, then tinker with it to chimerize or humanize it. This tinkering can reduce the binding affinity relative to the original murine antibody, so there are trade offs.

Both MEDX and ABGX (which was bought by AMGN) developed mice that contain the genes to make fully human antibodies, saving a lot of work in the R&D process.

I'd meant to ask earlier if phage display and affinity maturation tends to produce products with higher binding affinities than antibodies, or if this is the luck of the draw.