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Biotech / Medical : Biogen
BIIB 229.50-2.6%Dec 1 4:00 PM EST

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To: scaram(o)uche who wrote (1661)3/11/2010 1:48:28 PM
From: Pseudo Biologist  Read Replies (1) of 1682
 
We can start with the what

As you may recall Rituxan is chimeric 2B8

Ocrelizumab is humanized 2H7

So, the CDRs are not 100% identical, though they are very close:

In the LC each of the 3 CDRs differs from 2H7 vs 2B8 by 1-2 amino acids. In the HC 2 of the 3 CDRs are identical and the third differs by a few amino acids.

For reasons that are not altogether clear, ocrelizumab has better ADCC and slightly worse CDC than Rituxan. (see for example ncbi.nlm.nih.gov where the ADCC item is stated; I have seen the actual data presented in conferences, but I am not sure this second if published more formally).

No need to tell you this, but I think without more detail on dosing and the like it is hard to say for sure that ocrelizumab is indeed worse (more toxic). Even assuming one could an apples to apples comparison of trials, it is hard to see why the ADCC/CDC observations alone would account for such a difference. Data on how patients with different Fc receptor polymorphisms do may shed some light on this.

Very tricky business this one of making so-called "bio betters."

PB
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