indicates that mammalian cells, such as CHO cells, would be expected to express antibodies in
glycosylated form, barring any intervention to inhibit glycosylation.
On the other hand, Dr. Youle testified that in mammalian cells, “the addition of a special
‘leader sequence’ would be required to steer the protein to the secretory pathway” that would be
necessary “for any hope of proper glycosylation of the antibodies.” According to Dr. Youle, the
Cabilly application does not teach the addition of such a leader sequence (FF 51). Thus, a
portion of Dr. Youle’s testimony indicates that, absent an appropriate leader sequence, CHO
cells would not be expected to express antibodies having “proper glycosylation.”
Glaxo does not argue in its preliminary motions 3 and 5 that the Cabilly applications do
not teach a leader sequence required for “proper glycosylation”. In its preliminary motions 3 and
5, Glaxo offers no sufficient explanation of the significance of Dr. Youle’s testimony regarding
the need for a leader sequence. Without further explanation of what Dr. Youle means by “proper
glycosylation” and “special leader sequence”, we are left to speculate as to the significance of
this portion of Dr. Youle’s testimony. We will not speculate on the testimony’s significance for
at least the reason that it would be unfair to Cabilly for us to do so.
We note that regarding “proper glycosylation”, Glaxo states that (Paper 51 at 11):
Thus, to achieve proper glycosylation and produce antibodies that are therapeutically
effective in humans and have proper effector functions, the recombinant antibodies should be
produced in a cell system which glycosylates the antibodies with a glycosylation pattern that is
very similar to the glycosylation pattern in a human B-cell (the cell type which produces
antibodies in vivo).
Glaxo does not explain why the CHO cells system described by Cabilly would not allow
for “proper glycosylation”. We further note that Cabilly teaches expression vectors for use in
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