Appeal No. 1997-3511
Application No. 08/233,663
instability during processes such as filtration. (Id.). The examiner further urges that Wang
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teaches the use of polysorbate surfactants, such as Tween , to inhibit denaturation.
(Answer, page 5). The examiner acknowledges that Wang does not teach the use of
histidine as the buffering agent. (Id.). However, Wang talks only in terms of proteins, in
general, and does not explicitly describe any formulations of coagulation factor proteins
which could reasonable be said to relate to factor IX of the present claims.
Further, it does not appear that the examiner fully appreciates the complete
disclosure of this reference. At page S12, column 1, 4th full paragraph, in discussing the
use of cryoprotectant with proteins the reference states "[w]ithout elaborative research, it is
difficult to delineate the true mechanism of stabilization in any particular circumstance."
Further, at pages S20-21, the reference discusses the "Special Considerations" relating
to stability of proteins under freezing conditions and lyophilization and in column 1 of page
S21 states that "proper selection of a buffer system is extremely important." At column 2,
of page S21, last full paragraph, the reference states that:
Knowledge of the mechanisms for aggregation makes it easier to
understand the stabilization observed. Molecules of surfactants composed
of a hydrophilic end group and long hydrocarbon moieties, form a
hydrophobic core of micelles in which the protein molecule can be sheltered
from interaction with another protein molecule. The presence of surfactant
also reduces the concentration of protein at the interface.
In addition, at column 1 of page S22, Wang provides a discussion of the important role that
pH plays in the stabilization of a protein or peptide. These portions of Wang would appear
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