Appeal No. 1996-1273
Application 07/956,003
to intrinsic factor, the VB12.IF complex interacts with a membrane bound receptor for
IF located on the terminal ileum of the small intestine. The receptor-IF-VB12 complex is
then internalized by a process of receptor mediated endocytosis . . . Allen and Majerus . .
. demonstrated that it is possible to chemically modify VB12, couple it to a resin and use the
VB12-resin to affinity purify IF. This finding suggested to us that it may be possible to
couple large macromolecules (such as the resin used by Allen and Majerus) to VB12 and
to still preserve it’s ability to interact specifically with intrinsic factor. By coupling
molecules to VB12 in such a way as to preserve the ability of VB12 to interact with intrinsic
factor it was hoped that we could use the natural uptake mechanism for VB12 [to] deliver
VB12 and various molecules coupled to it, to deliver various proteins, drugs or other
pharmaceutically active molecules to the circulation. [Pages 1-2; emphasis supplied.]
Based on this disclosure of Russell-Jones, the principal issue raised on the record before us is similar
to the question initially posed by Russell-Jones (page 2): would one of ordinary skill in this art have
found in the combined teachings of the applied prior art the suggestion to couple a microsphere to
Vitamin B with the reasonable expectation of preserving the ability of Vitamin B to interact12 12
specifically with intrinsic factor to form a complex capable of further interacting with a membrane bound
receptor for intrinsic factor located on the terminal ileum of the small intestine and thus effective to
transport the complex into the circulation or lymphatic drainage system of a host via the intestinal
mucosal epithelium wherein the substance contained in the microsphere is released, as required by the
appealed claims? We find that the examiner has not supplied the evidence and/or scientific explanation
which answers this question in the affirmative.
We find that Russell-Jones discloses that the uptake mechanism for Vitamin B is an exception to the
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uptake mechanisms for dietary molecules and receptor mediated endocytosis for intestinal mucosa
binding proteins and antigens or haptens coupled thereto. Indeed, Vitamin B , that is, cobalamin, a
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complex compound containing cobalt, must bind to intrinsic factor released into the intestine in such
manner as to form a complex capable of further interacting with a membrane bound receptor for
intrinsic factor located on the terminal ileum of the small intestine. We further find that based on the
discussion in Russell-Jones, one of ordinary skill in this art would have reasonably expected that the
epithelial uptake across bowel mucosa of the heparin microspheres of Ranney Examples 1 and 2, the
heparin surface coated dextran microsphere of Ranney Example 3 and heparin nanosphere of Ranney
Example 14 as disclosed in Ranney Example 15, would be obtained via a different uptake mechanism
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