Replies to post #4252 on GTC Biotherapeutics (fka GTCB)

[DewDiligence]

>In plasma, the alpha glycoform, the fully glycosylated form, comprises about 90-95% of the total protein. So the real question is, what % of the material produced in goats is the beta glycoform, the under-glycosylated form (ie lacking glycosylation at Asn135)?<

This is proprietary (although the EMEA clearly knows the answer). If I recall correctly, Dr. Meade said at the 2005 annual meeting that the beta isoform makes up more than half of ATryn.

However, I don’t understand why you call this “the real question.” Dr. Meade acknowledged that the way the ATryn isoforms came out beneficially (for acute indications warranting a short half-life) was just the luck of the draw. Had the ATryn isoforms turned out disadvantageously, GTC would presumably have engineered a post-translational modification into the Atryn production process.

The key point, IMO, is that each drug candidate produced by GTC has to be evaluated on its own merits. The proportions of the AT isoforms in ATryn do not provide much useful information on how other transgenically-produced proteins will compare to variants of the same proteins derived from plasma or manufactured using CHO cells.

>“The total molecular weight for ATalpha, which is glycosylated at four amino acid residue positions (asparagines 96, 135, 155, and 172), is approximately 58 kDa, while ATbeta, which does not have the Asn135 glycosylation, has a molecular weight of about 56 kDa.”<

Thanks for that citation. I retract point #2 in my previous message (that the two AT isoforms are not variant glycoforms). Regards, Dew