Ex parte Wolozin et al.

Board of Patent Appeals and Interferences

Mar 27, 1998

07605788 (B.P.A.I. Mar. 27, 1998)

Application for patent filed October 30, 1990. According1
to appellants, this application is a continuation-in-part of
Application 07/487,894, now abandoned.
THIS OPINION WAS NOT WRITTEN FOR PUBLICATION
The opinion in support of the decision being entered today (1)
was not written for publication in a law journal and (2) is not
binding precedent of the Board.
Paper No. 41
UNITED STATES PATENT AND TRADEMARK OFFICE
_____________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
_____________
Ex parte BENJAMIN L. WOLOZIN
and HAYDEN G. COON
_____________
Appeal No. 95-4464
Application 07/605,7881
______________
ON BRIEF
_______________
Before RONALD H. SMITH, WILLIAM F. SMITH and ELLIS,
Administrative Patent Judges.
ELLIS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal from the final rejection of claims 20, 21
and 23, all the claims pending in the application.
Claim 20, which is illustrative of the subject matter on
appeal, reads as follows:
Appeal No. 95-4464
Application 07/605,788
2
20. A method of diagnosing Alzheimer’s disease comprising
the steps of:
i) isolating human tissue containing olfactory neurons;
ii) growing said tissue in a suitable medium under a first
membrane comprising collagen and laminin, establishig a human
olfactory neuron culture;
iii) separating said first membrane from neurons;
iv) replating said neurons on a surface coated with a second
membrane comprising collagen and laminin;
v) culturing said neurons of step (iv) under conditions
allowing replication;
vi) contacting said cultured neurons with a calcium salt;
vii) contacting said neurons of step (vi) with an ionophore;
viii) detecting AD-specific changes in amyloid precursor
protein or A68 as compared to normal; and
ix) diagnosing tissue as AD afflicted, if any AD-specific
changes of said proteins of step (viii) are detected.
The references relied on by the examiner are:
Talamo, et al., (Talamo) “Pathological Changes in Olfactory
Neurons in Patients with Alzheimer’s Disease”, Nature, Vol. 337,
pp. 736-739 (1989).
Coon, et al., (Coon) “Cell Cultures of Neuroblasts from Rat
Olfactory Epithelium that Show Odorant Responses”,Proc. Natl.
Acad. Sci. USA, Vol. 86, pp. 1703-1707 (1989).
Wolozin, et al., (Wolozin) “A Neuronal Antigen in the Brains of
Alzheimer Patients”, Science, Vol. 232, pp. 648-650 (1986).
Appeal No. 95-4464
Application 07/605,788
3
Cole, et al., (Cole) “Stimulated Platelets Release Amyloid $-
Protein Precursor”, Biochem. Biophys. Res. Commun., Vol. 170, No.
1, pp. 288-295 (1990).
A reference relied on by the appellants and this merits
panel is:
Microbiology, Second Edition, “Characterization of Cultures of
Animal Cells”, (Harper & Row, N.Y. 1973), pp. 1122.
Claims 20, 21 and 23 stand rejected under 35 U.S.C. § 103 as
being unpatentable over Talamo in view of Coon, Wolozin and Cole.
We reverse.
The claimed invention is directed to a method of diagnosing
Alzheimer’s disease (AD) which involves isolating and growing
human olfactory neurons in vitro, contacting said neurons first
with a calcium salt and then an ionophore, and detecting AD-
specific changes in amyloid precursor protein (APP) or A68.
Talamo discloses that “nasal epithelium tissue taken at
autopsy shows unique pathological changes in morphology,
distribution, and immunoreactivity of neuronal structures in
patients with Alzheimer’s disease.” Talamo, p. 736, para. 1.
Talamo reports that “[n]euritic masses in AD olfactory epithelium
were also stained in some cases with antibody ALZ50, which was
reported to be completely specific to Alzheimer’s tissue.”
Talamo, p. 738, para. 2. Talamo suggests neurons in the
Appeal No. 95-4464
Application 07/605,788
4
olfactory epithelium could be used as source of living nerve
cells for the study of Alzheimer’s disease provided “they can be
shown to have the characteristics of this disease.” Talamo,
p. 736, para. 1. Specifically, Talamo states that because
olfactory neurons “have the unusual property of arising from stem
cells throughout the life of the organism, they are good
candidates for the development of cell cultures or cell lines
which may express the disorder from living patients.” Id.
Coon discloses a method of isolating and culturing
neuroblasts derived from rat olfactory epithelium. Coon,
p. 1703, the abstract.
Wolozin discloses the preparation of a monoclonal antibody
(Alz-50) which recognizes a single antigen (with a molecular
weight of 68,000) which is said to be present in much higher
concentrations in certain regions of the brain of Alzheimer’s
patients than in normal brain. Wolozin, p. 232, the abstract.
Cole discloses that the platelets of Alzheimer’s patients
can be stimulated with thrombin or ionomycin to secrete soluble
truncated amyloid $-protein precursor (APP) and particulate
membrane fragments which contain C-terminal and N-terminal
immunoreactive amyloid $-protein precursor. Cole, p. 288,
Appeal No. 95-4464
Application 07/605,788
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para. 1.
The examiner argues that
[i]t would have been prima facie obvious to one of ordinary
skill in the art at the time of the invention to culture
human olfactory epithelial neurons using Coon’s method of
culturing olfactory epithelial neurons obtained from rats
because Talamo suggests that neurons in the olfactory
epithelium are good candidates for development of cell
culture of cell lines for studying Alzheimer’s disease and
Coon teaches a method of establishing continuous cultures of
the neuronal stem cells using olfactory epithelial tissue.
Thus one would have reasonably expected to successfully
culture neuron-containing olfactory epithelium from humans
using Coon’s method which has been show [sic, shown] to
allow for continuously [sic, continuous] culture [of] the
same cells isolated from another vertebrate species. It
would have been obvious to detect AD-specific changes as
taught by Talamo et al in the cultured cells because Talamo
teaches that olfactory epithelium from patients with
Alzheimer’s disease exhibits differential binding as
compared to normal olfactory tissue using antibody ALZ50
which Wolozin teaches is specific for AD. One would have
been motivated to add an ionophore as taught by Cole et al
to cultured cells as a means of increasing calcium-mediated
expression of APP as an AD marker because Cole teaches that
ionomycin causes release of C-terminal APP in membrane
fragments [Answer, p. 6].
In response, the appellants focus their arguments primarily
on whether the combined teachings of Talamo and Coon would have
suggested to one of ordinary skill in the art, the culturing of
human AD olfactory neurons and whether said person would have had
a reasonable expectation of success of culturing human olfactory
neurons using the disclosed rat medium. In re O’Farrell, 853
Appeal No. 95-4464
Application 07/605,788
The appellants refer to the declaration of Dr. Kohn,2
executed March 23, 1993, Paper No. 23.
6
F.2d 894, 904-905, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988).
Specifically, the appellants argue that (1) “Dr. Kohn’s expert
opinion that a medium specifically designed to maintain the
growth of a cell type of one species, would not be expected to be
useful in the maintenance and growth of a cell type of a
different species,” (Brief, p. 8) and (2) it is unpredictable as2
to whether the response of cells to stimuli in culture will mimic
their response to the same stimuli in situ (Brief, p. 10).
Although argued extensively by the appellants in the Brief
(Paper No. 32), Reply Brief (Paper No. 35) and supplemental Reply
Brief (Paper No. 37), and by the examiner in the Answer (Paper
No. 33), supplemental Answer (Paper No. 36), and second
supplemental Answer (Paper No. 38) we find it unnecessary to pass
on the merits of the relative positions with respect to issue
(1). Rather, we find conspicuous in its absence, any rebuttal by
the examiner to the appellants’ second argument. That is, the
examiner fails to contest the appellants’ position that due to
the potential differences between the neurons disclosed by Talamo
which are derived from autopsies (and, therefore, comprise fully
differentiated neurons), those skilled in the art would not have
Appeal No. 95-4464
Application 07/605,788
The appellants have submitted an excerpt from the textbook3
Microbiology, Second Edition, Davis, et al., Harper & Row,
publishers, NY, p. 1122 (1973).
7
expected that neuroblasts derived from AD patients and cultured
in vitro to express AD-specific markers.
Thus, even if we assume, arguendo, that the culturing of
human olfactory neurons would have been obvious to one of
ordinary skill in the art in view of the teachings of Talamo and
Coon, the question remains as to whether the neuroblasts derived
from AD patients would, after their adaptation to tissue culture
conditions and/or differentiation in vitro, express AD-specific
markers. Here, the appellants have presented evidence that the
phenotype and genotype of animal cells may be altered when they
are placed in culture. Thus, on this record, it appears that3
the mere fact that Talamo reports that the neurotic masses in
olfactory epithelium comprising differentiated cells derived from
AD patients and taken at autopsy, could be stained with the AD-
specific monoclonal antibody, ALZ-50, would not necessarily have
suggested that neuroblasts derived from AD patients, or neuro-
blasts from AD patients and placed in culture, would express the
antigen recognized by ALZ-50.
Similarly, even if we assume, arguendo, that the culturing
Appeal No. 95-4464
Application 07/605,788
8
of human olfactory neurons would have been obvious to one of
ordinary skill in the art in view of the teachings of Talamo and
Coon, it would appear, on this record, that the mere fact that
Talamo observed morphological differences and staining with the
monoclonal antibody ALZ-50 in olfactory neurons taken from AD
patients at autopsy, would not necessarily have suggested to
those of ordinary skill in the art the release of APP from
neuroblasts derived from AD patients, or neuroblasts from AD
patients and placed in culture, in response to an ionophore as
described by Cole.
Accordingly, on this record, we reverse the examiner’s
rejection.
The decision of the examiner is reversed.
REVERSED
RONALD H. SMITH )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
WILLIAM F. SMITH ) APPEALS AND
Administrative Patent Judge ) INTERFERENCES
)
)
)
JOAN ELLIS )
Administrative Patent Judge )
Appeal No. 95-4464
Application 07/605,788
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OFFICE OF TECHNOLOGY TRANSFER
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