Appeal No. 1999-1181
Application 08/480,332
2. Woodle and Klibanov
Woodle is discussed above. Klibanov teaches that long-circulating liposomes can
be prepared by coating the surface of the liposomes with a polymer such as polyethylene
glycol (PEG). On pages 329-331 of Klibanov, the attachment of ligands such as
antibodies to PEG-liposomes is discussed as a means of targeting the liposomes to a
specific cell or tissue. In figure 3A, antibodies are depicted as being attached directly to
the outer surface of a liposome, which is similar to what is taught by Woodle. Klibanov
discloses that an arrangement such as depicted in Fig. 3A provides a steric barrier on the
surface of the liposome and interferes with the interaction of the liposome-attached
ligands. In order to avoid this steric hindrance and produce long-circulating
immunoliposomes with a high affinity to a target, Klibanov teaches that a ligand can be
attached directly to the far ends of the PEG chains which are already bound to the
liposome membrane, as depicted in Fig. 3B. However, Klibanov indicates that it is
uncertain whether the presence of the ligand on the distal ends of the PEG chains will
influence and interfere with the circulation parameters of the modified liposomes.
From a review of Woodle and Klibanov, it appears that the examiner has provided
some of the pieces required by the claims on appeal, but has provided no plausible
reasons why one of ordinary skill in the art would have found it obvious to combine the two
references. The primary reference to Woodle discloses the active
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