Trizell Ltd.

Patent Trials and Appeals Board

Jan 26, 2021

2020000133 (P.T.A.B. Jan. 26, 2021)

UNITED STATES PATENT AND TRADEMARK OFFICE
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
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
15/287,909 10/07/2016 Timothy FARRIES Gliotherapy - GB09/16997 1058
22925 7590 01/26/2021
Pharmaceutical Patent Attorneys, LLC
801 Brickell Avenue
Suite 800
Miami, FL 33131-4924
EXAMINER
HAMMELL, NEIL P
ART UNIT PAPER NUMBER
1636
NOTIFICATION DATE DELIVERY MODE
01/26/2021 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):
administration@LicensingLaw.net
docket@LicensingLaw.net
mark.pohl@licensinglaw.net
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte TIMOTHY FARRIES and DAVID ECKLAND

Appeal 2020-000133
Application 15/287,909
Technology Center 1600
Before JEFFREY N. FREDMAN, RYAN H. FLAX, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.

NEWMAN, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 1–22. We have jurisdiction under
35 U.S.C. § 6(b).
We AFFIRM.

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42. Appellant identifies the real party in interest as Trizell
Limited, a U.S. limited liability company. Appeal Br. v.
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STATEMENT OF THE CASE
The Specification states:
Cancers are a major cause of mortality. High grade
gliomas are particularly devastating malignant tumours, for
which there is currently no effective cure and for which the
outcome is normally fatal. Certain treatments can prolong
survival, but they do not cure the cancer.
. . . current standard therapy [for tumours] involves
surgically removing the solid tumour mass and initiating
radiotherapy and/or chemotherapy. Even when the solid
tumour mass is being removed, precancerous or isolated
cancerous cells can exist in the brain. In the majority of these
patients, a new tumour grows and a repeat operation is
frequently required. Currently most available cancer medicines
are generally very toxic and many do not readily reach the brain
tumour. They often cause severe side effects that can reduce
the patient’s quality of life significantly.
Spec. 1:6–18.
The present invention is based on a study showing that locally
administered antigens in combination with a pre-existing
immunoresponsiveness to those antigens enhances the efficacy of an
adenoviral-based gene therapy treatment for glioma. Id. at 2:28–31.

CLAIMED SUBJECT MATTER
The claims are directed to a method of treating cancer using a virus.
Claims 1 and 22 are illustrative:
1. A method of treating cancer in a human, comprising:
a. Diagnosing cancer in a human, and then
b. Determining the level of immunity in the human against a
viral vector, and then
c. Confirming said human has a measurable level of
immunity against said vector, and then
d. Administering to said human said viral vector, in an
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amount effective to treat said cancer.

22. A method for the treatment of cancer in a human, said method
comprising diagnosing cancer in a human and then administering to
said human an agent which can stimulate an anti-viral immune
response, said agent administered in an amount sufficient to stimulate
an anti-viral immune response in said human strong enough to
improve the survival of said human.
Appeal Br. 28 (Claims App.).
REJECTIONS
A. Claims 16–20 and 22 are rejected under 35 U.S.C. § 112, second
paragraph, as being indefinite. Ans. 3.
B. Claims 16–20 and 22 are rejected under 35 U.S.C. § 112, first
paragraph, as failing to comply with the written description
requirement. Ans. 4.
C. Claims 1–7, 9–20, and 22 are rejected under pre-AIA 35 U.S.C.
§ 103(a) as being unpatentable as obvious over Sandmair2 and
Bramson.3 Ans. 5.
D. Claims 8 and 21 are rejected under pre-AIA 35 U.S.C. § 103(a) as
being unpatentable as obvious over Sandmair, Bramson, and Ulasov.4

2 Anu-Maaria Sandmair et al., Thymidine Kinase Gene Therapy for Human
Malignant Glioma, Using Replication-Deficient Retroviruses or
Adenoviruses, 11 HUMAN GENE THERAPY 2197–2205 (2000).
3 J. L. Bramson et al., Pre-existing immunity to adenovirus does not prevent
tumor regression following intratumoral administration of a vector
expressing IL-12 but inhibits virus dissemination, 4 GENE THERAPY 1069–
1076 (1997).
4 I. V. Ulasov et al. Combination of adenoviral virotherapy and
temozolomide chemotherapy eradicates malignant glioma through
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Ans. 9–10.
OPINION
A. Indefiniteness5
The Examiner rejects claims 16–20 and 22 as indefinite because
independent claim 22, upon which all other rejected claims depend, recites
“‘an anti-viral immune response’ in the third line and again in the fourth line
[of the claim.]” Ans. 3. The Examiner finds “[i]t is not clear how these two
anti-viral responses relate to each other. It is not clear if they are referring to
the same thing or different things.” Id. The Examiner additionally finds
dependent claims 18–20 further recite “anti-viral immune response” and that
it is unclear “which ‘anti-viral immune response’ is being referred to by
claims 18-20.” Id.
Appellant argues that because claim 22 “requires an agent which can
stimulate an immune response, and requires ‘said agent’ in an amount which
in fact does stimulate an immune response,” that use of “said” indicates
“we’re here talking about the same agent twice, not two different agents.”
Appeal Br. 6. Appellant further argues the Examiner fails to make a prima
facie case of indefiniteness because “the Examiner fails to cite any evidence
showing that the artisan could not understand what is claimed.” Appeal Br.
6–7; see also Reply Br. 2. With respect to claims 18–20, Appellant argues
that the claims are not indefinite because they recite “the” anti-viral response
rather than “an” anti-viral response. Appeal Br. 7.

autophagic and apoptotic cell death in vivo, 100 BRITISH JOURNAL OF
CANCER 1154–1164 (2009).
5 The Examiner withdrew the remaining additional bases for rejection under
35 U.S.C. § 112, second paragraph. Answer 1–11.
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The Examiner responds that Appellant’s argument fails to address the
merits because it focuses on the word “agent” rather than both recitations of
“an anti-viral immune response.” Ans. 12. The Examiner finds that
Appellant’s argument “do[es] not establish whether or not the anti-viral
immune response that the agent ‘can stimulate’ is the same anti-viral
immune response that is actually stimulated in the human.” Id. Regarding
claims 18–20, the Examiner finds Appellant’s argument regarding use of
“the” to refer to the stimulating agent is not persuasive because these claims
depend on independent claim 22, which recites “the” anti-viral response
twice, without clarification. Ans. 12.
In reply, Appellant argues that the Examiner’s response is
unreasonable because it does not apply an interpretation “consistent with the
evidence.” Reply Br. 2. Appellant argues “[i]n the instant case, the immune
response to viruses is quite well-characterized. For example, exposure to
enough adenovirus will trigger a specific, well-characterized response.” Id.
Appellant argues the Examiner implies, unreasonably and without evidence,
that a patient could have a “completely different antiviral response.” Id. at
3.
“Applying the broadest reasonable interpretation of a claim . . . the
Office establishes a prima facie case of indefiniteness with a rejection
explaining how the metes and bounds of a pending claim are not clear
because the claim contains words or phrases whose meaning is unclear. See
In re Packard, 751 F.3d 1307, 1310 (Fed. Cir. 2014).” Ex parte McAward,
Appeal 2015-006416, 2017 WL 3947829, at *5 (PTAB Aug. 25, 2017)
(Section I.B. designated as precedential). However, “the definiteness of the
language employed must be analyzed—not in a vacuum, but always in light
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of the teachings of the prior art and of the particular application disclosure as
it would be interpreted by one possessing the ordinary level of skill in the
pertinent art.” In re Moore, 439 F.2d 1232, 1235 (CCPA 1971).
We agree with Appellant that the meaning of “an anti-viral immune
response” as used in claim 22 and its dependent claims is reasonably clear
when the phrase is read in light of the Specification; the phrase refers to the
immune response generated in response to an immunostimulant that is
administered with the specific goal of generating that anti-viral immune
response. See, e.g., claim 22, Spec. 4:3–15. The Specification describes
administration of Herpes Simplex virus-thymidine kinase gene therapy with
subsequent GCV for the treatment of patients with operable primary
glioblastoma, and assessment of the immune response generated by the virus
using the method described in claim 22. Spec. 7:29–10:16. We agree with
Appellant that a skilled artisan having read the disclosure would reasonably
understand that the anti-viral immune response being referred to in both
instances of claim 22 is a response to the supplied immunostimulant, and not
a different response. We, therefore, reverse the rejection of claims 16–20
and 22 under 35 U.S.C. § 112, second paragraph.

B. Written description
The Examiner rejects claims 16–20 and 22, finding that “the new
limitation of ‘strong enough to improve survival of said human’ in claim 22
appears to represent new matter.” Ans. 4. The Examiner finds that no basis
for the limitation was found in the Specification or was identified by
Appellant. Id.
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Appellant argues that the Specification describes “treatment of
cancer,” “sufficiency for the treatment of cancer, “[e]nhanced efficacy . . .
when administered to patients with higher immunoresponsiveness,” and “the
value of ‘imnmunoresponsiveness of a patient to . . . predict the efficacy’ of
therapy.” Appeal Br. 9, citing Spec. 3:26–27; 10:9–16. Appellant argues
that the Specification “teaches to measure and compare survival to
determine whether survival has been improved.” Id. Appellant cites to
Tables 1 and 2 of the Specification, reproduced below, for support for the
contention that the Specification discloses improved immune responsiveness
as measured by antibody titre was consistent with longer survival. Table 1 is
shown below:

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Table 1 above shows the time to reintervention (additional treatment for
cancer) or death for 904 treated versus untreated patients, where treatment
involved administration of Cerepro following surgical resection of the tumor
and 14-day treatment with GCV. Spec. 9–10, Table 1.
Table 2 is shown below:

which compares the time

Table 2 shows “[h]azard ratios and p values for Cerepro compared with
Standard Care in patients with different titres of anti-adenoviral antibodies at
baseline. The p-values are calculated from a Cox model including terms for
treatment, temozolomide use, age and Karnofsky Performance [Score at]
Day 19 (D19KPS) in the various subgroups. Temozolomide and D19 KPS
are fitted as time dependent covariates.” Spec. 10:1–7.
Appellant further notes that the preamble of Claim 22, “[a] method of
treating cancer in a human, comprising:” supports that the inventors’
disclosure describes cancer treatment. Appeal Br. 9–10. Appellant argues
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that treating cancer “inherently and unavoidably entails improving survival”
and could not be intervention without such improvement. Id. at 10.
The Examiner responds that Appellant fails to address the limitation,
“strong enough to improve the survival of said human,” as a whole, focusing
instead on the recitation “improve the survival of said human.” Ans. 12–13.
The Examiner finds that because the entire claim term is used to “refer to the
strength of the ‘anti-viral immune response,’” Appellant has not identified
support in the Specification for the term. Id. at 13.
The Examiner notes that Table 1, relied upon by Appellant to
demonstrate improved survival, reflects “a substantial overlap in the
survivals of the patients, with many patients having pre-existing antibodies
or pre-existing antibodies >100 with shorter survivals than patients having
no-preexisting antibodies.” Id. The Examiner concludes that support for the
claim limitation “strong enough to improve the survival of said human”
cannot be inherent to the disclosure where the Specification does not show
“support for strengths of immune response that inherently improve[s]
survival.” Id.
In reply, Appellant argues that the legal standard “requires that the
disclosure correspond to the claims ‘substantially,’ not exactly,” and that the
Specification’s description of enhanced efficacy as cited above, provides
such support. Reply Br. 3–5.
We agree with Appellant (see Appeal Br. 9–10) that the Specification
discloses an induced immune response that results in some lengthened
survival. We also agree that the Specification must disclose the elements
required by the claim, but this is not an ipsis verbis test, i.e., identity of
terminology is not required. Quake v. Lo, 928 F.3d 1365, 1374 (Fed. Cir.
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2019). The inventors describe an agent administered in the disclosed
amount and a resulting anti-viral immune response that is strong enough to
improve the survival of humans, as described.6 Id. “It is not necessary that
every permutation within a generally operable invention be effective in order
for an inventor to obtain a generic claim, provided that the effect is
sufficiently demonstrated to characterize a generic invention.” Capon v.
Eshhar, 418 F.3d 1349, 1359, (Fed. Cir. 2005).
In view of the foregoing, we reverse the rejection of claims 16–20,
and 22 under 35 U.S.C. § 112, first paragraph.

C. Obviousness7
The Examiner finds that the claims are “directed to administering an
adenoviral gene therapy in a subject having a preexisting immune response
to the viral vector.” Ans. 15.
The Examiner finds that Sandmair teaches the claimed subject matter
of treating cancer in a human by diagnosing the cancer and administering an
adenoviral vector. Ans. 5. The Examiner notes that “Sandmair specifically
teaches treating human malignant glioma by delivery of adenovirus for gene
therapy to the resected glioma tumor cavity” and discloses that Herpes
Simplex virus thymidine kinase gene therapy is “one of the most promising
novel treatment modalities among attempts to change the survival of

6 With this statement, we do not make findings regarding the sufficiency of
the Specification’s disclosure to enable the skilled artisan to practice the
invention commensurate with the scope of any rejected claim.
7 The Examiner withdrew the nonstatutory double patenting rejection of
claims over claims 1–28 of US 9,603,912. Ans. 8.
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malignant glioma patients and further that adenoviral gene therapy can be
successfully used for the treatment of malignant glioma.” Id. The Examiner
finds Sandmair teaches that treatment with adenovirus-mediated gene
therapy showed “MRI stable disease” and statistically significant “longer
mean survival time.” Id. The Examiner therefore concludes that Sandmair
“teaches administering to the human an amount effective to treat the
cancer.” Id.
The Examiner finds “Sandmair does not explicitly teach determining
the level of immunity against a viral vector and then confirming that the
human has a measurable level of immunity against the vector, wherein the
determining and confirming occur after diagnosing cancer in the human but
before administering to the human the viral vector.” Id.
The Examiner finds Bramson “similarly teaches methods for treating
cancer by administering an adenoviral vector to a tumor” and also
“determining the level of immunity against a viral vector . . . and then
determining the effect that a pre-existing immunity to an adenovirus had on
the effectiveness and dissemination of an adenovirus.” Id. The Examiner
notes that Bramson “teaches that virus dissemination can result in organ
destruction or can cause profound systemic toxicities if expression is not
localized to the tumor.” Id. at 5–6. The Examiner finds that the
experimental results “strongly support the clinical utility of Ad-based cancer
gene therapy and suggest that Ad immunity may be advantageous in that it is
not a complete block to gene transfer in the tumor and it greatly reduces
virus dissemination.” Id. at 6.
The Examiner concludes the skilled artisan would have found it
obvious to determine and confirm that
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the human has a measurable level of immunity against a viral
vector in the method of Sandmair for the advantage of greatly
reducing the virus dissemination as discussed by Bramson.
One would have been motivated to have reduced the virus
dissemination because Bramson teaches that virus
dissemination can result in organ destruction or can cause
profound systemic toxicities if expression is not localized to the
tumor. One would have had a reasonable expectation of
success in achieving reduced virus dissemination in the subjects
of Sandmair because each of Sandmair and Bramson teach
similar methods of delivering adenovirus to a tumor for gene
therapy.
Id.
The Examiner makes additional findings regarding specific teachings
of Sandmair and Bramson that teach specific limitations recited in
independent claims 9 and 22 and dependent claims 2–7, 10–15, and 16–20
relating to, e.g., the timing of steps of the method, the viral vector used, the
cancer targeted, the amount of viral vector used, and the drugs co-
administered with viral vector treatment. Ans. 6–9.
In a second rejection, the Examiner additionally cites Ulasov as
rendering obvious modifying the “method of Sandmair by further
administering a therapeutic dose of temozolomide.” Ans. 10.
Appellant contends that the Examiner fails to establish a prima face
case that the cited references teach each claimed limitation and fails to show
that a skilled artisan would have had reason to combine the cited references
to arrive at the claimed invention, with a reasonable expectation of success.
Appeal Br. 10–26. Finally, with respect to claims 8, 9, and 18–22, Appellant
contends that the cited references do not disclose the additional specific
limitations recited by those claims. Appeal Br. 21–26.
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The issues with respect to these rejections are (1) whether a
preponderance of evidence supports the Examiner’s conclusion that a skilled
artisan would have had a reason to combine the cited references to arrive at
the claimed invention, with a reasonable expectation of success; and (2)
whether a preponderance of evidence supports the Examiner’s conclusion
that the cited prior art combination teaches or suggests the additional
limitations recited in dependent claims 8, 9, and 18–22.8
Claims 1–7 and 10–17
With the exception of claims 8, 9, and 18–22, Appellant does not
separately argue the claims. We, therefore, focus our analysis on claim 1 as
representative of the remaining claims. Unless otherwise noted, we adopt
the Examiner’s findings of fact and reasoning on scope and content of the
prior art with respect to claim 1 (Final Act. 5–14; Ans. 5–10) and agree that
claim 1 is obvious over Sandmair and Bramson. We respond to Appellant’s
arguments below. Only those arguments timely made by Appellant in the
briefs have been considered; arguments not so presented are waived. See
37 C.F.R. § 41.37(c)(1)(iv) (2015); see also Ex parte Borden, 93 USPQ2d
1473, 1474 (BPAI 2010) (informative) (“Any bases for asserting error,
whether factual or legal, that are not raised in the principal brief are
waived.”).
Appellant contends that Sandmair teaches an expectation of failure,
not success, because it “shows that anti-virus antibody makes survival
worse, not better.” Appeal Br. 10; Reply Br. 6–8. According to Appellant,

8 Appellant does not present evidence of secondary considerations that,
when considered together with evidence of obviousness, shows the claims to
be nonobvious.
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the data in Table 1 of Sandmair “teaches that immune competence worsens
survival” because patients having detectable Adenovirus antibodies two
weeks after vaccination survived fewer months than those not having such
antibodies. Id. at 11–12. Appellant further argues that, because the antibody
titre was not detected in patients 17, 20, 21, and 22, these patients “could not
have been vaccinated with an amount enough to stimulate an antiviral
response.” Id. at 12. Therefore, Appellant argues, the teachings of
Sandmair do not support a reasonable expectation of success in using the
claimed method.
We are not persuaded, as Appellant’s assessment of these results of
Table l is without sufficient evidence. Table 1, reflecting the results of
patients treated with brain tumor gene therapy, is reproduced below.

Sandmair and Bramson
Claim 1 – Appellant says doesn’t teach

Some evidence both ways, not absolute expectation, just a reasonable one
Table 1 shows the results of fifteen tumors in fourteen patients treated with
HSV tk gene therapy. Sandmair at 2198–2199. Appellant cites to column
10 of Table 1, “Virus antibodies,” as evidence that patients 16, 18, and 19,
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each of whom was vaccinated with Adv/tk adenovirus (see Table 1, column
9, “Gene therapy”), “showed antiviral antibodies two weeks after
vaccination.” Appeal Br. 11; Reply Br. 7–8. Appellant acknowledges that
“[w]e cannot say whether Sandmair’s Ad/tk induced the antiviral antibodies
because Sandmair does not provide baseline antibody data.” Id. We agree
that Sandmair did not provide baseline antibody data, and therefore also
agree with the Examiner that the data in Sandmair cannot be used to draw
the conclusion that pre-existing adenovirus infection causes a negative
survival effect (Ans. 16). Appellant agrees that “Sandmair Table 1 does not
teach pre-existing adenoviral immunity.” Reply Br. 8.
What remains of Appellant’s argument is mere speculation. Appellant
claims “Sandmair Table 1 teaches immune competence . . . [and] suggests
that immune competence worsens survival.” Reply Br. 8. Appellant argues
that the amount of adenovirus in Sandmair was insufficient to generate an
antiviral response in some patients, and that those patients lived longer as a
result. Appeal Br. 12.
We are unpersuaded that the skilled artisan reading Sandmair would
have reached that same conclusion, and we disagree that the Examiner
“disavows Sandmair” in the Examiner’s examination of this case (Reply Br.
10–11). Sandmair’s focus was the use of adenovirus to deliver thymidine
kinase gene therapy. Sandmair at 2198. Appellant fails to account for the
effect of this therapy in the survival of these patients. Sandmair
demonstrates statistically significant success in improving survival in this
regard, and notes that “significant increases in anti-adenovirus antibodies
were related to gene therapy with high-titer adenoviruses.” Id. at 2200–
2204. Sandmair thus considers its adenovirus titer “high” and does not
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disclose that any patients were given different doses of vaccination with
Adv/tk; therefore, we find no basis to conclude that the lower survival of
patients having detectable antibodies two weeks after treatment was because
of higher levels of adenovirus stimulation. Sandmair supports equally
reasonable speculations that the adenovirus response in patients 16, 18, and
19 was generated too late to permit the thymidine kinase treatment to have
had an effect, or that these patients experienced a higher level of
disseminated virus based on differences in their tumor resection procedures,
which led to antibody detectability. See also Sandmair at 2204 (“The
difference in survival may also be related to other factors, such as age,
functional status, duration of symptoms, histological differences in
malignancy, and subtotal versus partial surgical resection.”). Appellant
provides no evidence otherwise or to support its claim that a skilled artisan
would have believed its theory regarding antibody immunity levels being
responsible for the decrease in survival. Attorney arguments and conclusory
statements that are unsupported by factual evidence are entitled to little
probative value. See In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997).
For these reasons, we agree with the Examiner that Appellant’s
argument regarding the post-treatment antibody detectability aspect of
certain patients Sandmair is unpersuasive as to the teachings that a skilled
artisan would have taken from the reference. Rather, we agree with the
Examiner that Sandmair teaches an improved survival of Adv/tk-treated
patients, with a recommendation to pursue further studies (Sandmair at
2197) and that the skilled artisan would have had reason to pursue such
studies.
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Appellant next argues that Sandmair and Bramson teach away from
each other’s approaches and cannot be combined. Appeal Br. 15; Reply Br.
12–14. Appellant argues that Sandmair teaches surgical removal of tumors
prior to vaccination with viral vector, while Bramson “teaches that retaining
the tumor is critical because tumors provide a beneficial function.” Id. at
15–16. Appellant further argues that Sandmair’s teachings that anti-viral
immunity worsens survival would have discouraged the skilled artisan from
making the combination. Id. at 17. Appellant also argues that the
combination is impossible because the approaches cannot be combined
physically and would have been thought to fail based on predicted worsened
survival. Id. Appellant states “[m]odifying Sandmair by eliminating viral
‘dissemination’ outside the protected tumor environment would eliminate
the virus entirely . . . [and does not] provide a motive to combine Bramson
with Sandmair.” Appeal Br. 19; Reply Br. 15–16.
We are not persuaded. “Under the proper legal standard, a reference will
teach away when it suggests that the developments flowing from its
disclosures are unlikely to produce the objective of the applicant’s
invention.” Syntex (U.S.A.) LLC v. Apotex, Inc., 407 F.3d 1371, 1380 (Fed.
Cir. 2005) (citations omitted). For the reasons discussed above, we do not
agree that the skilled artisan would have believed Sandmair taught away
from this approach because it teaches that anti-viral immunity worsens
survival. The Examiner’s rejection is based upon adding the step of
confirming that the patient has a measurable level of immunity against a
viral vector as taught by Bramson to the method of Sandmair, as well as
avoiding virus dissemination as taught by Bramson. Ans. 6. Although we
acknowledge that the Examiner’s first phrasing of the rejection states that
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the method of Sandmair would be used, which would require excision of the
tumor (Ans. 6), the Examiner also finds that the skilled artisan would “have
had a reasonable expectation of success in achieving reduced virus
dissemination in the subjects of Sandmair because each of Sandmair and
Bramson teach similar methods of delivering adenovirus to a tumor for gene
therapy.” Ans. 6. The focus of the rejection is squarely upon treatment of
cancer at a tumor site, and claim 1 does not have any limitations requiring
treatment of cancer at a particular cancerous location. Appellant’s concern
about the inability to practice the method both inside and outside the tumor
is therefore not persuasive because we find the skilled artisan would have
been able to adapt the teachings of Sandmair and Bramson as necessary.
And because Bramson teaches that restricting treatment to inside the tumor
offers the benefit of lowering dissemination of adenovirus gene transfer to
tissues outside the location targeted for treatment, with the benefit of
reduced toxicity to surrounding tissues, we agree with the Examiner that the
skilled artisan would have been motivated to adapt the teachings of both
Sandmair and Bramson, rather than to conclude that the approaches were
incapable of combination. Appellant has identified no compelling reason the
skilled artisan would have believed the disclosures of Sandmair and
Bramson could not be combined, and has provided no evidence from the
perspective of the skilled artisan to substantiate the argument.
Appellant next argues that “Bramson fails to provide a reasonable
expectation of success for her method.” Appeal Br. 18. Appellant argues
that the Examiner finds “‘Bramson explicitly teaches that virus
dissemination can result in organ destruction or can cause profound systemic
toxicities if expression is not localized to the tumor’” and warns against a
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reasonable expectation of “‘organ destruction’” and “‘profound systemic
toxicities’” Appeal Br. 20. Appellant cites Bramson’s statement that “[i]t is
‘reasonable to speculate that intratumoral gene transfer will not be as
sensitive to Ad immunity as gene transfer to other tissues’” (Bramson at
l069), but states that this does not provide a reasonable expectation of
success. Appeal Br. 18.
We are not persuaded because Appellant’s citation to Bramson’s
introduction does not account for Bramson’s ultimately successful result:
During the course of the studies, we observed that the virus
does disseminate in our model following intratumoral
administration. It was then demonstrated that Ad-immunity can
inhibit vector dissemination indicating that immunity is not a
major barrier in this model and may actually be beneficial.
Bramson 1070. It is this teaching that the Examiner cites, and that we agree
would have provided a reasonable expectation of success to the skilled
artisan. “Only a reasonable expectation of success, not absolute
predictability, is necessary for a conclusion of obviousness.” In re Longi,
759 F.2d 887, 897 (Fed. Cir. 1985).
Appellant next argues that the Examiner has not made a prima facie
case against claim 1 because “Bramson teaches mice, not humans,” and
therefore “fails to teach ‘b. Determining the level of immunity in the
human.’ [and] ‘c. Confirming said human has a measurable level.” Appeal
Br. 21; Reply Br. 17–20.
We are not persuaded. The Examiner’s rejection is for obviousness,
not anticipation. Researchers have used mice for decades to test treatments
before applying them in humans. See, e.g., In re Brana, 51 F.3d 1560,
15678 (Fed. Cir. 1995) (The National Cancer Institute has recognized
“murine tumor models as standard screening tests for determining whether
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new compounds may be useful as antitumor agents.”). We agree with the
Examiner that Bramson’s teachings in mice render use of the same method
in humans obvious. In addition, Bramson states as much: “These results
strongly support the clinical utility of Ad-based cancer gene therapy and
suggest that Ad immunity may be advantageous in that it is not a complete
block to gene transfer in the tumor and it greatly reduces virus
dissemination” (emphasis added). Bramson at 1069.
Accordingly, for the reasons above, we affirm the Examiner’s
rejection of claim 1 as obvious over Sandmair and Bramson. Claims 2–7
and 10–17, which are not separately argued, fall with claim 1.
Claims 9 and 22
Appellant argues that the combination of Sandmair and Bramson does
not teach every limitation of claims 9 and 22 because Bramson regards mice,
not humans, and because Sandmair teaches antiviral immunity worsens
survival. Appeal Br. 21–23; Reply Br. 20–21. For the same reason we
rejected those arguments with respect to claim 1 above, we do so here. We
affirm the Examiner’s rejection of claims 9 and 22 as obvious over Sandmair
and Bramson.
Claim 18
Appellant argues that the subject matter of claim 22 is not taught by
the combination of Sandmair and Bramson because “Claim 18 further
requires waiting until the patient shows that response, and then re-
administering ‘said’ agent.” Appeal Br. 23. Appellant argues:
Sandmair teaches a single administration of AdCMVTK, a
recombinant adenovirus. Bramson teaches a single (intranasal)
administration of wild-type Ad5 adenovirus, and a single
(intratumoral) injection of AdmIL-12. l, a recombinant
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adenovirus. Neither Sandmair nor Bramson teaches re-
administering the same virus twice.
Id. at 24.
The Examiner responds that the teachings of Bramson would have
rendered obvious the administration “to the human subject an adenovirus in
an amount sufficient to stimulate an anti-viral immune response in the
human prior to the viral vector treatment in the method of Sandmair for the
advantage of reducing the virus dissemination as discussed by Bramson.”
Ans. 7–8. We agree, and reiterate the logic used by Appellant (Appeal Br.
6) in its argument against the rejection of claims 18–20 for indefiniteness
that two recitations of “the anti-viral immune response” are not indefinite
because they refer to the same anti-viral immune response of claim 22,
which “requires an agent which can stimulate an immune response, and
requires that the agent be administered in an amount which in fact stimulates
a response.” The Specification states that an “agent . . . stimulates antiviral
immunity, for the treatment of cancer.” Spec. 2:32–33. Appellant’s
argument that Bramson does not administer the same virus twice ignores that
the “agent” causing the stimulus in both regards is adenovirus, and that the
focus of the claims is immunity to the same type of virus. Nor has Appellant
provided evidence to show that these different forms of the adenovirus
would not provide the same response. We affirm the Examiner’s rejection
of claims 18 as obvious over Sandmair and Bramson.
Claims 19–20
Appellant argues that claims 19 and 20 require “vaccination, and then
waiting until the patient shows an immune response, and then administering
a cytotoxic chernotherapeutic.” Appeal Br. 25. Appellant argues that
Sandmair does not teach the waiting step. Id. The Examiner responds that
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the argument is a piecemeal attack on the references and does not “address
why it would not have been obvious to have waited until the patient shows
the anti-viral immune response to the adenoviral vector and then
administering the adenoviral vector or the cytotoxic chemotherapeutic drug
as recited by claims 18–20.” Ans. 20–21.
We agree. The Examiner’s proposed combination teaches that
Bramson’s step of confirming antiviral immunity occurs first. Ans. 14–15.
Thus, we agree with the Examiner that it would have been obvious for any
treatment actions, such as adding a cytotoxic chernotherapeutic, to be made
afterward, as taught in Bramson. Ans. 20–21. Appellant does not persuade
us otherwise. We affirm the Examiner’s rejection of claims 19–20 as
obvious over Sandmair and Bramson.
Claims 8 and 21
Appellant argues that the rejection of claims 8 and 21 does not render
the claims for “an anti-cancer effective amount of temozolomide” obvious
because “Ulasov was not trying to kill cancer. Rather, he sought to observe
how cancer cells respond on a molecular level to temozolomide. To observe
this, Ulasov needed to assure that his cancer cells survived after being
exposed to temozolomide.” Appeal Br. 25–26.
The Examiner responds that Ulasov teaches
the use of adenoviral virotherapy and temozolomide to induce
cell death for the treatment of malignant glioma [and] that [] a
combination therapy comprising adenoviral-based gene therapy
with temozolomide leads to a therapeutic additive effect with an
increase in survival of mice bearing glioma xenografts (page
1159, column 1), as discussed in the rejection, thus indicating
that the amount of temozolomide administered was “an anti-
cancer effective amount of temozolomide.”
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Ans. 21–22. We agree. Ulasov states “[t]he additive cytotoxicity elicited by
[the temozolomide] treatment combination leads to a significant
prolongation of survival in mice bearing [i.e.,] human glioma xenografts.”
Ulasov at 1161 (emphasis added). It is the mice, not the cancer cells, whose
survival Ulasov sought to prolong. We affirm the Examiner’s rejection of
claims 8 and 21 as obvious over Sandmair, Bramson, and Ulasov.

CONCLUSION
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis  Affirmed Reversed
16–20, 22 112(b) Indefiniteness 16–20, 22
16–20, 22 112(a) Written Description 16–20, 22
1–7, 9–20, 22 103 Sandmair, Bramson 1–7, 9–20,
22

8, 21 103 Sandmair, Bramson,
Ulasov
8, 21
Overall
Outcome
1–22
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R.
§ 1.136(a)(1)(iv).

AFFIRMED