Ex Parte Hodge et al

Patent Trial and Appeal Board

Aug 21, 2018

13264846 (P.T.A.B. Aug. 21, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/264,846 01/12/2012
120207 7590 09/07/2018
Sheridan Ross P.C.
1560 Broadway, Suite 1200
Denver, CO 80202
FIRST NAMED INVENTOR
James Hodge
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.
3923-24-PUS 9907
EXAMINER
CHESTNUT, BARRY A
ART UNIT PAPER NUMBER
1648
NOTIFICATION DATE DELIVERY MODE
09/07/2018 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):
e-docket@sheridanross.com
ADomitrovich@sheridanross.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JAMES HODGE, JEFFREY SCHLOM,
and ALEX FRANZUSOFF 1
Appeal2017-008687
Application 13/264,846
Technology Center 1600
Before RICHARD M. LEBOVITZ, JEFFREY B. ROBERTSON,
and RY ANH. FLAX Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to first and second
immunotherapy compositions and methods of using the immunotherapy
compositions to reduce tumor burden or inhibit tumor growth and/or to
induce a therapeutic immune response against one or more cancer antigens
in an individual. The Examiner rejected the claims as obvious under 35
1 The Appeal Brief ("Appeal Br.") 3 lists GLOBEIMMUNE, INC., an
assignee of record and THE UNITED STATES OF AMERICA, AS
REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH
AND HUMAN SERVICES, as the real parties in interest.
Appeal2017-008687
Application 13/264,846
U.S.C. § 103. Appellants appeal the rejection pursuant to 35 U.S.C. § 134.
We have jurisdiction under 35 U.S.C. § 6(b ). The rejections are affirmed.
STATEMENT OF THE CASE
Claims 1, 26, 29, 32, 34, 41, 73, and 79--95 stand finally rejected by
the Examiner as follows:
Claims 1, 29, 32, 34, 41, 73, 79--89 and 91-95 under pre-AIA 35
U.S.C. §103(a) in view of Michael B. Bernstein et al., Recombinant
Saccharomyces cerevisiae (yeast-CEA) as a potent activator of murine
dendritic cells, VACCINE (2008) 26:509--521) (herein referred to as
"Bernstein") and Duke et al. (WO 2007 /092792 A2, published Aug. 16,
2007) (herein referred to as "Duke"). Examiner's Answer ("Ans.") 2.
Claims 26 and 90 under pre-AIA 35 U.S.C. § 103(a) in view of
Bernstein, Duke, and Wansley et al., Vaccination with a Recombinant
Saccharomyces cerevisiae Expressing a Tumor Antigen Breaks Immune
Tolerance and Elicits Therapeutic Antitumor Responses, CLIN CANCER RES
2008, 14(13):4316-4325 (July 1, 2008)) (herein referred to as "Wansley").
Ans. 10.
Appellants did not provide separate arguments for the claims.
Consequently, the claims stand or fall together. 37 C.F.R. § 4I.37(c)(l)(iv).
Claim 1 is selected as representative of the rejected claims to decide all
issues in this appeal. Claim 1 is reproduced below:
1. A method to reduce tumor burden or inhibit tumor
growth and/ or to induce a therapeutic immune response against
one or more cancer antigens in an individual, comprising
administering two immunotherapy compositions within one
dosing of the individual in order to prime the immune system
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with each of the compositions, the two immunotherapy
compositions comprising:
a) a first immunotherapy composition comprising a
recombinant vaccinia virus comprising nucleic acid sequences
encoding costimulatory molecules B7-l, ICAM-1 and LFA-3,
and nucleic acid sequences encoding at least one cancer antigen
or immunogenic domain thereof; and
b) a second immunotherapy composition comprising
a whole inactivated yeast that has recombinantly expressed,
prior to administration, at least one cancer antigen or
immunogenic domain thereof;
wherein the administration of the first and second
immunotherapy compositions reduces tumor burden or inhibits
tumor growth in the individual and/or induces a therapeutic
immune response against one or more cancer antigens in the
individual.
REJECTION BASED ON BERNSTEIN AND DUKE
Claim 1 is directed to a method "to reduce tumor burden or inhibit
tumor growth and/or to induce a therapeutic immune response against one or
more cancer antigens in an individual, comprising administering" first and
second immunotherapy compositions "within one dosing of the individual."
The Examiner cited Bernstein for its description of the claimed first and
second immunotherapy compositions, i.e., a vaccinia virus and a whole
inactivated yeast, each expressing a cancer antigen ("CEA"). Final Act. 3.
The Examiner acknowledged that Bernstein does not describe
administering the immunotherapy compositions ("vaccine compositions")
"within one dosing" as required by claim 1. Id. We interpret "within one
dosing" to mean that the first and second compositions are administered
concurrently at one time, although not necessarily at the same precise
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moment. Specification ("Spec.") ,r 134. To meet the "within one dosing"
requirement of the claims, the Examiner cited Duke as teaching concurrent
administration of combinations of vaccine compositions. Final Act. 3. The
Examiner determined it would have been obvious to one of ordinary skill in
the art to administer both vaccine compositions of Bernstein "within one
dosing" in view of Duke's teaching of concurrent vaccine administration to
provide enhanced protection against infection and disease. Id. at 4.
Appellants challenge the Examiner's finding that Duke describes
"administering two different immunotherapy compositions (specifically, a
yeast-based immunotherapeutic and a viral vector-based
immunotherapeutic) within one dosing of the individual in order to prime
the immune system with each of the compositions" as required by claim 1.
Appeal Br. 1 7. Appellants contend that "Duke refers to combinations of
vaccines, but the only detailed description is a 'prime-boost' protocol, where
the yeast vaccine is used to prime an immune response and immunization
boosts are provided by delivery of a conventional vaccine ... once the initial
immune response has waned." Id. at 19.
This argument does not persuade us that the Examiner erred.
We agree with Appellants that Duke describes a prime and boost
protocol in which one vaccine composition is delivered first and then
sequentially followed by delivery of a second vaccine composition at a later
time. Duke 19:27-20: 14. However, the Examiner cited a different
embodiment in Duke describing the concurrent administration of two
different vaccines:
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Application 13/264,846
In addition, yeast vehicles described herein can be combined
with other types of vaccines, either concurrently or sequentially
( e.g., in a priming and boosting protocol) to further direct the
immune response and to provide enhanced protection against
infection and disease.
Duke 19:31-20: 1 (emphasis added).
This disclosure describes two embodiments: a first embodiment in
which a yeast-based vaccine and other type of vaccine is administered
concurrently and a second embodiment in which the two different vaccines
are administered sequentially in a prime and boost protocol. The Examiner
relied on the first embodiment in finding that Duke suggests "administering
two immunotherapy compositions within one dosing of the individual,"
where the vaccine compositions are those described in Bernstein. Final Act
4.
Appellants acknowledge this teaching, but argue:
[T]he section of Duke cited by the rejection pertains to the
administration of a yeast-based vaccine and another
conventional vaccine in a "diversified prime-boost" protocol.
More specifically, Duke refers to combinations of vaccines, but
the only detailed description is a "prime-boost" protocol, where
the yeast vaccine is used to prime an immune response and
immunization boosts are provided by delivery of a conventional
vaccine. As known in the art, the first exposure of the immune
system to a vaccine is the "priming dose."
Reply Br. 6.
Appellants not did identify where the term "diversified prime-boost"
protocol appears in Duke. However, we found the term in the Specification
where the inventors distinguished the concurrent use of vaccines to target the
same cancer antigen from a diversified prime-boost vaccination strategy
using different recombinant vectors, each comprising the same cancer
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antigen. Spec. ,r 9. Although it is not explained, we understand - based on
Appellants' arguments -that the diversified prime-boost protocol involves
priming with one vector, and then subsequently, and not concurrently as
claimed, boosting the immune response with a second vector containing the
same antigen.
Appellants' arguments ignore the express disclosure of the first
embodiment described in Duke of the use of "yeast vehicles" that are
"combined with other types of vaccines ... concurrently." Duke 19:31-
20: 1. Concurrent administration is thus expressly described in Duke and the
Specification characterizes its invention as "the concurrent use of two
different immunotherapeutic compositions" (Spec. ,r 4 ), and distinguishes
the concurrent use of immunotherapy compositions from the prime and
boost protocol (id. at ,r 9). Thus, Duke teaches the same "concurrent"
administration strategy which is claimed and asserted in the Specification to
be the invention.
Appellants' arguments focus on the prime and boost teachings in
Duke, and other ways in which yeast vectors are taught to be used by Duke
to modify the immune response. Appeal Br. 20. However, while these
approaches may be preferred by Duke, the teachings of a prior art
publication are not limited to its preferred embodiments. In re Pfizer, Inc. v.
Apotex, Inc., 480 F.3d 1348, 1370 (Fed. Cir. 2007). "[T]he fact that a
specific [embodiment] is taught to be preferred is not controlling, since all
disclosures of the prior art, including unpreferred embodiments, must be
considered." In re Merck & Co., Inc. v. Biocraft Laboratories, Inc., 874
F.2d 804, 807 (Fed. Cir. 1989).
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Unexpected results
Appellants contend that the "method of the present invention ...
yields unexpected results that were not predicted at the time of the invention,
and that represent in an improvement over use of the claimed
immunotherapy compositions individually." Appeal Br. 21. Appellants
state that the Specification "demonstrates that the two distinct
immunotherapy platforms (viral vector-based and yeast-based, as claimed),
when administered within one dosing of the individual to prime the immune
system, do not inhibit each other, and in fact, surprisingly synergize to
improve anti-tumor efficacy." Id. at 21-22. Appellants state that Example 6
and Figure 6 of the Specification provide a working example of this
unexpected result. Id. at 22.
The Examiner did not find the results persuasive for two reasons.
First, the Examiner found that Duke suggests that yeast-based and non-
yeast-based vectors may work "in a synergy manner" in a combinatorial
approach and thus "a synergistic effect at the time of the claimed invention"
would have been expected. Final Act. 13. Second, the Examiner found that
the results are not commensurate with the scope of the claims. Id.
With regard to the Examiner's first reason, we agree with Appellants
that Duke does not teach that two different vaccines compositions, when
administered concurrently in a single dosing, work in a synergistic manner.
Appeal Br. 18-19. Duke teaches:
In such "prime-boost" strategies, a strong cell-mediated
response elicited as a result of the first immunization (priming)
improves the efficacy of subsequent boosts and in some
embodiments, can actually provide synergistic effects,
particularly when the boosting vaccine is a different type of
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vaccine than the priming vaccine and/ or contains different
antigens as compared to the priming vaccine.
Duke 20: 10-14. The reference further states,
By priming the immune response using the yeast-based
vaccines and methods of the invention, both cell-mediated and
humoral immunological memory is generated (i.e., memory B
cells and T cells that selectively recognize the antigens of
interest are generated). As a result, upon subsequent exposure
to the antigen, e.g .. through vaccination boosts, disease, or
infection, the immune system will respond more quickly and
more efficaciously, and importantly with respect to vaccination
boosts, lower antigen doses can be used in boosters of non-
yeast-based vaccines (see, for example, Example 2 and Figs. 14
and -16). In addition, the yeast vehicles may work in synergy
with non-yeast-based vaccines, such that immune responses are
optimized by the combinatorial approach, such as by combining
DNA vaccines with yeast-based vaccines. As such, the
vaccines may need to be administered only once and/or in a
lower amount for efficacy.
Id. at 20: 15-25 ( emphasis added).
As indicated in the above-reproduced passages from Duke, Duke
describes synergy in the prime-boost strategy where the immune system is
first primed with a yeast-based vector and then subsequently boosted with a
non-yeast based vaccine of a different type. Id. at 20: 10-14. The
"combinatorial approach" of two different types of vaccines which "may
work in synergy" is with respect to "priming" and subsequent "vaccination
boosts." With respect to the prime and boost strategy, Duke teaches that
"the immune system will respond more quickly and more efficaciously, and
importantly with respect to vaccination boosts, lower antigen doses can be
used in boosters of non-yeast-based vaccines." Id. at 20:15-25.
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Thus, the Examiner's determination that synergy would have been
expected when two vectors are administered concurrently in a single dosing
as claimed is not supported by a preponderance of the evidence.
However, the Examiner provided adequate reasoning that the results
provided by Appellants are not commensurate with the full scope of the
claim.
Appellants provided evidence of unexpected results. Appellants state:
Example 6 and Fig. 6 of the specification provide a working
example in which administration of a viral vector-based
immunotherapy (known as rV/F-CEA/TRICOM) and yeast-
based immunotherapy (known as "yeast-CEA") within one
dosing of the individual in order to prime the immune system
with each of the compositions resulted in a significantly lower
number of tumors as compared to untreated controls, and as
compared to the administration of either immunotherapy alone
to prime the immune system.
Appeal Br. 22.
The rV/F-CEA/TRICOM is a recombinant vaccinia (rV) and
recombinant fowlpox (rF) viruses containing the murine B7-1, ICAM-1, and
LFA-3 genes, and the human carcinoembryonic antigen (CEA) gene. Spec.
,r,r 8, 171. The claimed first immunotherapy vector requires vaccinia virus
and the B7-1, ICAM-1, and LFA-3 genes, but is not limited to a murine
origin. Further, the claims are not limited to a specific cancer antigen.
According to the Specification, the "yeast-CEA" expresses full-length
CEA protein and is the same vector described in Bernstein. Spec. ,r 1 71.
Example 6 of the Specification describes administering rV /F-
CEA/TRICOM alone, yeast-CEA alone, and rV/F-CEA/TRICOM and yeast-
CEA combined to mice expressing human CEA ("CEA-Tg"). Spec. ,r,r 170,
201. CEA-Tg mice were injected i.v. with LL2-CEA tumor cells. Id. at
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,r 201. Mice were primed rV/F-CEA/TRICOM alone, yeast-CEA alone, and
rV/F-CEA/TRICOM and yeast-CEA, and then boosted every 7 days for the
duration of the treatment with the corresponding vector alone or
combination of vectors. Id. On day 45, mice were sacrificed and lungs were
harvested, stained, and fixed. Id. The data shown in Fig. 6 represent the
number of lung metastases per mouse from two separate experiments. Id.
The Specification reported:
Untreated mice had an average of 10.84 tumors per mouse
(+2.41). Mice vaccinated with rV/FCEA/TRICOM had an
average of7.50 metastases per mouse (+2.02), and mice
vaccinated with yeast-CEA had an average of 9.71 metastases
per mouse ( + 1.22). However, mice vaccinated with the
combination ofrV/F-CEA/ TRICOM and yeast-CEA had 2.80
metastases per mouse ( +O. 77); this combination group was the
only group with a significantly lower number of metastases
compared to the untreated control (p=0.015). Also, the
maximum number of metastases per mouse for the untreated,
rV/F-CEA/TRICOM, and yeast-CEA groups was 36, 24, and
18, respectively, while the maximum number of metastases in
the combination group was 7.
Id. at i1202.
The Specification discloses statistical significance between the group
administered rV/F-CEA/ TRICOM and yeast-CEA concurrently and the
rV/F-CEA/TRICOM and yeast groups, alone. Id.
It is stated in the Specification that "[ s ]urprisingly, the inventors
discovered that administering two vaccines targeting the same antigen
induces distinct T-cell populations and results in significantly higher
antitumor immunity in a murine orthotopic pulmonary metastasis model
(Fig. 6)." Spec. ,r 49. The Examiner did not provide arguments or evidence
that the data in Figure 6 would not have been surprising to one of ordinary
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skill in the art, but rather found the results are not commensurate in scope
with the claims because "the claim is broad and does not support the result
for reducing tumor burden or inhibit tumor growth and/ or induce a
therapeutic immune response against one or more cancer antigens in any
tumor." Final Act. 13. We agree with the Examiner's analysis.
When unexpected results are proffered by an appellant to rebut a
prima facie case of obviousness, the appellant must "provide[] an adequate
basis to support the conclusion that other embodiments falling within the
claim will behave in the same manner" in order to "establish that the
evidence is commensurate with [the] scope of the claims." In re Kao, 639
F.3d 1057, 1068 (Fed. Cir. 2011). One data point is insufficient "to
ascertain a trend in the exemplified data which would allow [ one having
ordinary skill in the art] to reasonably extend the probative value thereof."
In re Kollman, 595 F.2d 48, 56 (CCPA 1979).
As indicated by the Examiner, claim 1 is not restricted to a specific
cancer antigen, and does not even require the two compositions to express
the same antigen. In contrast, in Example 6, both immunotherapy
compositions comprise the same cancer antigen, CEA, and were used in a
mouse model in which tumor cells were introduced into the mouse.
Appellants did not address the Examiner's finding about the lack of data for
the full breadth of the claim nor explain why the result of the single cancer
antigen under one set of conditions (priming and boost every seven days, in
a mouse model hosting one specific tumor cell line) would establish the
asserted unexpected result for the full scope of claim 1, e.g., different cancer
antigens in any cancer.
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Smnmary
For the foregoing reasons, the rejection of claim 1 as obvious based
on Bernstein and Duke. Claims 29, 32, 34, 41, 73, 79--89 and 91-95 fall
with claim 1.
REJECTION BASED ON BERNSTEIN, DUKE, AND WANSLEY
The Examiner further cited Wansley to address the limitations in
dependent claims 26 and 90. Appellants contend that Wansley in
combination with Bernstein and Duke does not remedy the deficiencies of
Bernstein and Duke. Appeal Br. 25. We thus affirm the rejection of claims
26 and 90 for the same reason as for claim 1.
TIME PERIOD
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l )(iv).
AFFIRMED
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