Appeal No. 2004-0250 Page 4
Application No. 09/226,412
desirable to increase patient compliance and to avoid the discomfort associated with
subcutaneous injections. Id., pages 1 and 3. Appellants report that insulin
administration by way of an inhalation aerosol has been known since 1925. Id., page 3.
As observed, the claimed invention is not directed to the administration of human
insulin, but monomeric insulin analogs. As explained:
Insulin is a peptide hormone with a molecular weight of approximately
5,800 Daltons. In the presence of zinc, human insulin self-associates into
a stable hexamer form. The dissociation of the stable hexamer is
believed to be the rate limiting step in the absorption of insulin from the
subcutaneous injection site to the blood stream. Rapid-acting insulin
analogs, however, do not readily form stable hexamers. These analogs
are known as monomeric insulin analogs because they are less prone to
self-associated to stable higher-ordered complexes. This lack of self-
association is due to modifications in the amino acid sequence of human
insulin that decrease association by disrupting the formation of dimers.
Unfortunately, the modifications to insulin which cause these analogs to
be monomeric, also result in non-specific aggregation of monomers. This
non-specific aggregation can render the analogs insoluble and unstable.
Specification, paragraph bridging pages 5 and 6. A preferred monomeric insulin analog
used in the present invention is AspB28 and an “even more preferred” monomeric insulin
analog used in the present invention is LysB28ProB29 (Lyspro). Id., page 8.
The working examples of the present specification report the results of
experiments involving pulmonary administration of Lyspro to beagle dogs. Dogs were
chosen since “they are large animals with respiratory tract deposition of particles similar
to man.” Id., page 23.
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