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DewDiligence

07/23/07 2:47 PM

#4250 RE: Pre_Clinical #4249

Re: Two isoforms of antithrombin

>…so let me guess this straight, there are two glycoforms of AT produced in transgenic goats, one form that is essentially bio-equivalent to pAT, and another form that is more rapidly cleared.<

This is inaccurate on two counts:

1. Both ATryn and endogenous AT have two isoforms: AT-alpha and AT-beta. The beta isoform has a shorter half-life. In endogenous AT (and plasma-derived AT), the alpha isoform comprises 90-95% of total AT and the beta isoform comprises 5-10%:

http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=12372930&dopt=...

In ATryn, the beta isoform comprises considerably more than 10% of total AT (but GTC has not publicly disclosed the actual number). This is what gives ATryn a shorter half-life than plasma-derived AT.

2. To my knowledge, the two isoforms of AT are not variant glycoforms, as you assumed. Thus, the PK difference between ATryn and plasma-derived AT is not a glycosylation issue.

Regards, Dew