Ex Parte Zanin-Zhorov et al

Patent Trial and Appeal Board

Sep 29, 2016

12968690 (P.T.A.B. Sep. 29, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/968,690 12/15/2010 Alexandra Zanin-Zhorov
26259 7590 10/03/2016
LICATA & TYRRELL P,C
66 E. MAIN STREET
MARLTON, NJ 08053
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www .uspto.gov
ATTORNEY DOCKET NO. CONFIRMATION NO.
NYU0006US 2837
EXAMINER
VISONE, THOMAS J
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
10/03/2016 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address( es):
PTOactions@licataandtyrrell.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ALEXANDRA ZANIN-ZHOROV
and MICHAEL L. DUSTIN1
Appeal2015-002262
Application 12/968,690
Technology Center 1600
Before DONALD E. ADAMS, ERIC B. GRIMES, and JOHN G. NEW,
Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
1 Appellants state "[t]he real party in interest is New York University." App.
Br. 1.
Appeal2015-002262
Application 12/968,690
SUMMARY
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner's Final Rejection of claims 1--4, 8, and 12.2 Specifically, claims
1--4 stand rejected as unpatentable under 35 U.S.C. § 103(a) as being
obvious over the combination of Fleming et al. (WO 2005/066139 A2, July
12, 2005) ("Fleming") and Rao et al. (US 2004/0166099 Al, August 26,
2004) ("Rao").
Claims 8 and 12 stand rejected as unpatentable under 35 U.S.C.
§ 103(a) as being obvious over the combination of Fleming, Rao, and L.
Steidler et al., Treatment of Murine Colitis by Lactococcus lactis Secreting
Interleukin-I 0, 289 SCIENCE 1352-55 (2000) ("Steidler"). 3
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
NATURE OF THE CLAIMED INVENTION
Appellants' invention is directed to methods for reducing tumor
necrosis factor inactivation of regulatory T cells, restoring the activity of
defective regulatory T cells, and enhancing the function of regulatory T cells
using Protein Kinase C theta (PKC-8) inhibitors. The enhancement in
2 Claims 5-7, and 9-11 are canceled. App. Br. 14-15.
3 Claims 1--4, 8, and 12 were also rejected by the Examiner under the
nonstatutory doctrine of obviousness-type double patenting over Appellants'
co-pending Application No. 13/266,757. Final Act. 7. Appellants "will
address filing a Terminal Disclaimer in the present case upon allowance of
claims in the above-referenced application, or in the prosecution of US
13/266,757 should claims be allowed first in the present application." App.
Br. 12. Stated differently, Appellants waived the Appeal as to the
obviousness-type double patenting rejection.
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regulatory T cell function is of use in facilitating adoptive immunotherapy in
the treatment of immunological disorders. Abstract.
REPRESENTATIVE CLAIM
Claim 1 is representative of the claims on appeal and recites:
1. A method for reducing tumor necrosis factor
inactivation of regulatory T cells comprising isolating regulatory
T cells and then contacting the isolated regulatory T cells with a
Protein Kinase C theta (PKC-8) inhibitor at an amount that
reduces inactivation of the isolated regulatory T cells and reduces
tumor necrosis factor-induced down-regulation of FoxP3.
App. Br. 9.
ISSUES AND ANALYSES
We agree with, and adopt, the Examiner's findings and conclusion
that the appealed claims are prima facie obvious over the cited prior art
references. We address the arguments raised by Appellants on appeal
below.
A. Claims 1--4
Issue
Did the Examiner err in finding the combination of Fleming and Rao
teaches or suggests the limitations of claim 1? App. Br. 8.
Analysis
Appellants first point out that the Examiner admits that neither Rao
nor Fleming teaches a reduction of FoxP3 down-regulation. App. Br. 8
(citing Final Act. 4). However, Appellants dispute the Examiner's finding
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that reduction of FoxP3 down-regulation must be an inherent result of
practicing the method taught by Fleming and Rao, arguing that a finding of
inherency is improper in the context of an obviousness analysis. Id. (citing
In re Rijckaert, 9 F.3d 1531 (Fed. Cir. 1983). According to Appellants,
because the use of a protein kinase C-theta ("PKC-8") inhibitor was not
known to reduce tumor necrosis factor-induced down-regulation of FoxP3 in
isolated regulatory T cells, the claimed method cannot be considered
inherent and therefore obvious. Id.
Appellants next point to the limitations of claims 1 and 3, which
require that the "isolated regulatory T cells are contacted with a PKC-8
inhibitor at an amount that reduces inactivation of the isolated regulatory T
cells and reduces tumor necrosis factor-induced down regulation of FoxP3"
or "restores activity of the isolated regulatory T cells." App. Br. 8.
Appellants assert that Fleming teaches a class of PKC-8 inhibitors, useful in
the treatment of autoimmune diseases, but is silent with respect to reducing
tumor necrosis factor-induced down regulation ofFoxP3. Id. at 9 (citing
Fleming ii 7).
Appellants argue that Rao, which the Examiner relies upon as
teaching isolation of immune cells, contacting them with a PKC-8 inhibitor
and then administering the treated cells to a subject, also teaches data that,
Appellants contend, demonstrates that PKC-8 inhibitors have no
physiological effect upon regulatory T cells. Id. at 9. Appellants point to
Example 1 of Rao, which Appellants assert, teaches that, amongst the genes
preferentially used by activated effector T cells compared to regulatory T
cells, were genes encoding proteins known to be required for signal
transduction in activated T cells through PKC-8. Id. (citing Rao ii 212).
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Furthermore, argue Appellants, Examples 2 and 3 of Rao demonstrate
that whereas PKC-8 is preferentially used by effector T cells, PKC-8 is not
required to activate regulatory T cells and that, although PKC-8 inhibitors
inhibit the proliferation of Thl and Th2 cells, PKC-8 inhibitors had little
stimulatory or inhibitory effect on regulatory T cells. Id. (citing Rao
iii! 213-220). Consequently, Appellants contend, a person of ordinary skill
in the art would reasonably expect, from the teachings of Rao, that a PKC-8
inhibitor would have little effect on the activation or proliferation of
regulatory T cells. Id. at 9-10.
Consequently, Appellants argue the combined teachings of Fleming
and Rao do not teach that application of a PKC-8 inhibitor "reduces tumor
necrosis factor-induced down-regulation of FoxP3" nor would they have
provided a person of ordinary skill in the art with a reasonable expectation of
success in doing so. App. Br. 10.
The Examiner responds that, although the references do not explicitly
teach a reduction of FoxP3 down-regulation, such a result would be an
inherent property of practicing the method taught by the prior art. Ans. 4.
The Examiner observes that it is well settled that "the discovery of a
previously unappreciated property of a prior art composition, or of a
scientific explanation for the prior art's functioning, does not render the old
composition patentably new to the discoverer." Id. (quoting Atlas Powder
Co. v. Ireco Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999)). Therefore, the
Examiner finds, the claiming of a new use, new function or unknown
property which is inherently present in the prior art does not necessarily
make the claim patentable. Id. (citing In re Best, 562 F.2d 1252, 1254
(CCPA 1977)).
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Moreover, the Examiner finds, there is no requirement that a person of
ordinary skill in the art would have recognized the inherent disclosure at the
time of invention, but only that the subject matter is in fact inherent in the
prior art reference. Ans. 4 (citing Schering Corp. v. Geneva Pharm. Inc.,
339 F.3d 1373, 1377 (Fed. Cir. 2003)).
The Examiner finds that Fleming and Rao, both individually and
together, teach administration or application of a PKC-8 inhibitor, which
would result in the inhibitor contacting regulatory T cells. Ans. 8. The
Examiner therefore finds the teachings inherently, and necessarily, teach
reduction in tumor necrosis factor-induced down-regulation of FoxP3 in
regulatory T cells. Id. at 8-9.
With respect to Appellants' argument concerning Example 1 of Rao,
the Examiner finds Rao teaches PKC-8 exerts an inhibitory effect on
regulatory T cells. Ans. 10. Therefore, the Examiner finds, one of ordinary
skill in the art would not expect active regulatory T cells to be transcribing
messages for molecules utilized in a PKC-8 inhibitory pathway; indeed, the
Examiner finds, Appellants' invention is directed to reducing the
inactivation of regulatory T cells. Id. Moreover, the Examiner finds
Example 1 of Rao is directed to normal, activated, regulatory T cells, rather
than Appellants' defective, inactivated regulatory T cells, which would have
a different profile with respect to PKC-8 expression. Id.
With respect to Examples 2 and 3 of Rao, the Examiner finds that they
do not show what would be the result of inducing PKC-8 activity in normal,
active regulatory T cells. Ans. 11. The Examiner finds that Rao, therefore,
does not teach that PKC-8 exerts no effect in the context of defective,
inactivated regulatory T cells. Id.
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Finally, the Examiner finds that independent claim 3 and claim 4,
which depends from claim 3, do not require reducing tumor necrosis factor-
induced down-regulation of FoxP3 and that Appellants' arguments are not
applicable to all the claims on appeal. Ans. 9.
We are not persuaded by Appellants' arguments. As an initial matter,
Appellants' contention that a finding of inherency is inappropriate in the
context of an obviousness rejection under 35 U.S.C. § 103 is incorrect.
Inherency is a question of fact that arises both in the context of anticipation
and obviousness rejections. In re Napier, 55 F.3d 610, 613 (Fed. Cir. 1995).
"In relying upon the theory of inherency, the examiner must provide a basis
in fact and/or technical reasoning to reasonably support the determination
that the allegedly inherent characteristic necessarily flows from the
teachings of the applied prior art." Ex parte Levy, 17 USPQ2d 1461, 1464
(BP AI 1990) (emphasis in original).
Both the teachings of the prior art and the disclosures of Appellants'
Specification reveal that it was well known in the art at the time Appellants'
application was filed that PKC-8 was known to inhibit the activities of T
cells, including regulatory T cells and that inhibition of PKC-8 could prevent
regulatory T-cell inactivation. See, e.g., Spec. ,-i 7 ("Inflammatory signals
delivered by cytokines like tumor necrosis factor (TNF)-a decrease Treg
(regulatory T-cell) activity (Flores-Borja, et al. (2008) Eur. J. Immunol.
38:934; Valencia, et al. (2006) Blood 108:253)").
The sole remaining portion of the limitations of claim 1 that were not
already known in the prior art, is the mechanism of action by which the
inhibition of PKC-8 reduces inactivation of regulatory T cells, viz., that
PKC-8 reduces tumor necrosis factor-induced down-regulation of FoxP3.
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The Examiner finds, and we agree, that application of a PKC-8 inhibitor
would necessarily have this effect, that is, although tumor necrosis factor-
induced down-regulation of FoxP3 was not appreciated in the prior art as a
cause of regulatory T-cell reduced activity, or that inhibition of PKC-8 could
reduce that inactivity by reducing the down-regulation of FoxP3 induced by
tumor necrosis factor, these phenomena were naturally and necessarily
occurring as the underlying cause of the phenomena already known in the
prior art. "[T]he discovery of ... a scientific explanation for the prior art's
functioning, does not render the old composition patentably new to the
discoverer." Atlas Powder, 190 F.3d at 1347 (Fed. Cir. 1999).
Nor are we persuaded by Appellants' arguments with respect to
Examples 1-3 of Rao. We agree with the Examiner's findings that the
regulatory T cells that were the subject of these examples were not
regulatory T cells inactivated by tumor necrosis factor. We consequently
agree with the Examiner that one of ordinary skill in the art would not
expect active regulatory T cells to be transcribing messages for molecules
utilized in a PKC-8 inhibitory pathway. Indeed, the purpose of Example 2
of Rao is to show that PKC-8 is not required to activate regulatory T cells.
See Rao ,-i,-i 213-215. But, as we have explained, it was already known in
the prior art that inhibition of PKC-8 protects regulatory T cells from
inactivation by TNF.
Appellants reply that the examples of Rao do not support of the use of
a PKC-8 inhibitor to reduce tumor necrosis factor inactivation of regulatory
T cells, or restore the activity of a defective regulatory T cell or facilitate
adoptive immunotherapy in the prevention of autoimmune colitis by
contacting isolated regulatory T cells with a PKC-8 inhibitor as presently
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claimed. Reply Br. 5. Nevertheless, the disclosures of Appellants'
Specification concerning what was known in the art at the time of filing
reveal that it was known that TNF decreases the activity of regulatory T cells
and that inhibition of PKC-8 enhances the function of regulatory T cells.
Spec. ii 8.
In summary, we agree with the Examiner that discovering the
mechanism by which inhibition of PKC-8 can protect regulatory T cells
from inactivation by tumor necrosis factor, i.e., by reducing the down-
regulation of FoxP3, is inherent to the application of PKC-8 inhibitors to
inactivated regulatory T cells is inherent because it necessarily occurs when
inactivated regulatory T cells are exposed to a PKC-8 inhibitor. That is,
reduction of FoxP3 down regulation naturally and necessarily follows from
inhibition of a PKC-8 inhibitor. We consequently affirm the Examiner's
rejection of claims 1--4.
B. Claims 8 and 12
Appellants rely upon their arguments presented above that the
combined teachings of Fleming and Rao would not have suggested to one of
ordinary skill in the art that a PKC-8 inhibitor would have any physiological
effect on regulatory T cells. App. Br. 11. Appellants assert Fleming
suggests the treatment of disease without providing any demonstration that
the compounds therein exhibit activity in even a cell-based assay and Rao
provides data indicating that PKC-8 inhibition has little or no effect on the
activation or proliferation of regulatory T cells. Id. Consequently,
Appellants argue, a person of ordinary skill in the art would not have had a
reasonable expectation of success in combining the teachings of Fleming
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and Rao to arrive at the claimed methods of facilitating adoptive
immunotherapy in the prevention of autoimmune colitis by contacting
isolated regulatory T cells with a PKC-8 inhibitor.
The Examiner responds that the practice of the claimed method is
indistinguishable from the practice of the prior art methods; that is, all the
methods contemplate the administration of a PKC-8 inhibitor to treat
autoimmune disorders. Ans. 11. The Examiner finds that a person of
ordinary skill in the art does not practice the underlying molecular
mechanism of a method; rather, one of ordinary skill in the art practices the
method, which results in the molecular mechanism. Id. at 12. With regard
to the claims on appeal, the Examiner finds the prior art teaches the
administration of PKC-8 inhibitors in a manner that is essentially identical to
the instant method and that, therefore, the inherent result of practicing the
prior art methods would be the underlying molecular mechanisms recited by
the instant claims; i.e., reducing inactivation of isolated regulatory T cells;
reducing tumor necrosis factor-induced down-regulation of FoxP3; restoring
the activity of a defective regulatory T cell; and facilitating adoptive
immunotherapy.
We agree with the Examiner's reasoning for the reasons we have set
forth supra, and we therefore affirm the Examiner's rejection of claims 8
and 12.
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DECISION
The Examiner's rejection of claims 1--4, 8, and 12 as unpatentable
under 35 U.S.C. § 103(a) is affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § l.136(a)(l). See 37 C.F.R.
§ l.136(a)(l )(iv).
AFFIRMED
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