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Biotech / Medical : Cambridge Antibody Technology Group -- Ignore unavailable to you. Want to Upgrade?

To: paradigm7241 who wrote (41)	1/31/2000 11:26:00 AM
From: Jongmans	Respond to of 625

Cambridge Antibody Technology up 255pence(+22,6%) at Pst 13,82 now martin

To: paradigm7241 who wrote (41)	1/31/2000 2:06:00 PM
From: Pseudo Biologist	Read Replies (1) \| Respond to of 625

Paradigm, thanks for clarifying CAT's use of large libraries of fragments followed by engineering as full MAbs of a few clones. The reference you mentioned re. TGF-beta is linked here (medline abstract) to make it easier for others to see. Nice choice on your part to illustrate the process compactly: ncbi.nlm.nih.gov One, perhaps minor, point is that Remicade is a chimeric antibody, where the entire V domains are derived from mouse, while the Celltech molecule is humanized where only the CDRs, give or take a few amino acids, are derived from mouse. This makes the first molecule "theoretically" 66% human, and the second one 90% human. I am not sure if there will be any clinical significance to this difference. CAT's molecule is "theoretically" 100% human, with the caveat that, at least, the CDR3 of the heavy chain is in all likelihood product of the equivalent of unique recombination and/or somatic mutation events as to make it hard to say if it is "human" or something else. Same may apply to other CDRs, IF there has been sufficient mutation from the germline sequences. The possibility of an anti-idiotypic response cannot be ruled out, although, in theory, one would expect this to arise sooner in chimeric than humanized than human (phage- or transgenic-derived). Clinical evidence of this to date, and to my knowledge, is still inconclusive. There is much more to try to digest from your fine post, but, alas, there is that day job. PB