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Biotech / Medical : IDPH--Positive preliminary results for pivotal trial of ID
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To: Richard Belanger who wrote (316)1/27/1997 3:02:00 PM
From: Pseudo Biologist   of 1762
 
Hi, regarding your comment " Apparently, the mouse-based products would have much
greater appeal in terms of large-scale production." Well, no. Both primatized and "humanized antibodies" are actually genetically engineered constructs expressed in particular cell lines. In primatized Abs you get the variable domains from an ape or monkey, then you make a construct in which you combine those with human constant domains. For humanized Abs you have to do a little more work after you get the mouse variable domains. Essentially you have to engineer those mouse domains as to make them "look" as human as possible while still preserving binding affinity and specificity. Then, you combine those "designed" domains with human constant domains exactly as with primatized Abs. Thus, there is no intrinsic productivity advantage in one technology or the other.

As far as immunogenicity is concerned, there are a number of trials with humanized Abs (not necessarily using IMGN's approach) and for the most part they seem to be non immunogenic. The most advanced drug of this type appears to be Zenapax whose active component is a humanized Ab against the interleukin-2 receptor. This molecule was originally produced by PDL Inc and licensed to Roche; it recently completed a successful phase III clinical trial for prevention of rejection of kidney transplants. I believe IPEC has at least one drug in development that also has "humanized" variable domains. See the prospectus for their most recent secondary.

Finally, in the past when I've looked at IMGN's use of the term "small molecule" they have meant "small molecule conjugated to an antibody," so the actual drug is not a small molecule. Their lead drug uses a macromolecule (toxin) conjugated to a an antibody (I believe still a mouse Ab).

Hope this helps,

Max
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