Etubics Corporation et al.

Patent Trials and Appeals Board

Aug 12, 2021

2020006561 (P.T.A.B. Aug. 12, 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.
15/542,005 07/06/2017 Frank R. Jones 8774ETU-13-PUS 9127
157773 7590 08/12/2021
Sheridan Ross PC
1560 Broadway
Suite 1200
Denver, CO 80202
EXAMINER
HIBBERT, CATHERINE S
ART UNIT PAPER NUMBER
1636
NOTIFICATION DATE DELIVERY MODE
08/12/2021 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):
e-docket@sheridanross.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
________________

Ex parte FRANK R. JONES, ELIZABETH GABITZSCH,
YVETTE LATCHMAN, and ADRIAN RICE
________________

Appeal 2020-006561
Application 15/542,005
Technology Center 1600
________________

Before JEFFREY N. FREDMAN, ULRIKE W. JENKS, and
TIMOTHY G. MAJORS, Administrative Patent Judges.

MAJORS, Administrative Patent Judge.

DECISION ON APPEAL
Appellant1 submits this appeal under 35 U.S.C. § 134(a) involving
claims to a composition comprising recombinant replication defective
adenovirus 5 vectors with certain gene deletions and nucleotide sequences
that encode certain antigens. The claims have been rejected for obviousness
under 35 U.S.C. § 103. We have jurisdiction under 35 U.S.C. § 6.
We AFFIRM.

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42(a). Appellant identifies Etubics Corporation as the real
party-in-interest. Appeal Br. 3.
Appeal 2020-006561
Application 15/542,005

2
STATEMENT OF THE CASE
According to the Specification, “[v]iral vaccines are currently being
developed to help fight infectious diseases and cancers.” Spec. ¶ 4. “These
viral vaccines work by inducing expression of a small fraction of genes
associated with a disease within the host’s cells, which in turn, enhance the
host’s immune system to identify and destroy diseased cells.” Id.; see also
id. ¶ 5 (discussing cancer immunotherapy by delivering tumor-associated
antigens (TAAs), and the use of adenovirus serotype-5 (Ad5) therapeutics to
induce an immune response against target TAAs)).
The Specification discloses that “[a] major problem with adenovirus
(Ad) vectors has been their inability to sustain long-term transgene
expression due largely to host immune responses that eliminates the Ad
vector and virally-transduced cells in immune competent subjects.” Spec.
¶ 6. The Specification explains that “[c]ancer targeting Ad vaccine vectors
that allow multiple vaccinations and vaccinations in individuals with
preexisting immunity to Ad are needed.” Id. ¶ 9. According to the
Specification, “the present invention provides combination multi-targeted
vaccines, immunotherapies and methods for enhanced therapeutic response
to complex diseases such as infectious diseases and cancer.” Id. ¶ 10.
Claims 159–162, 165–168, and 170 are on appeal. Claim 159 is the
only independent claim. It is illustrative and is reproduced below:
159. A composition comprising:
a recombinant replication defective adenovirus 5
vector comprising an E2b gene region deletion, an El gene
region deletion, and a nucleotide sequence encoding a
MUC1 antigen;
a recombinant replication defective adenovirus 5
vector comprising an E2b gene region deletion, an El gene
Appeal 2020-006561
Application 15/542,005

3
region deletion, and a nucleotide sequence encoding a
Brachyury antigen; and
a recombinant replication defective adenovirus 5
vector comprising an E2b gene region deletion, an El gene
region deletion, and a nucleotide sequence encoding a
CEA antigen.
Appeal Br. 10 (indentation added).
Appellant seeks review of the Examiner’s rejection of claims 159–162
under 35 U.S.C. § 103 as obvious over the combination of Hodge2 and
Colloca.3 Final Act. 3–8.4 The Examiner’s rejections of claims 165–168
over Hodge, Colloca, and Agrawal,5 and claim 170 over Hodge, Colloca,
and Berinstein6 are also on appeal. Id. at 5–8.
ANALYSIS
I. Claims 159–162: Obviousness over Hodge and Colloca
The Examiner concludes that claims 159–162 would have been
obvious over Hodge and Colloca. Final Act. 3–5, 7–8; Ans. 3–5, 10–11.
Appellant’s argument for this rejection is addressed to the claims as a group.
We focus here on claim 159, and the other claims stand or fall with claim
159. See 37 C.F.R. § 41.37(c)(iv).
The Examiner finds that Hodge teaches administration of MUC1,
Brachyury, and CEA antigens via adenoviral vectors, and that Colloca
teaches adenoviral vectors with mutations (deletions) in the E2b gene region

2 Hodge et al., US 2012/0107347 A1, published May 3, 2012.
3 Colloca et al., US 2011/0217332 A1, published Sept. 8, 2011.
4 This citation refers to the Final Rejection dated December 12, 2019 (“Final
Act.”). We also refer herein to the Examiner’s Answer on Appeal dated July
2, 2020 (“Ans.” or “Answer”).
5 Agrawal et al., US 2016/0317637 A1, published Nov. 3, 2016.
6 Berinstein et al., US 2010/0260807 A1, published Oct. 14, 2010.
Appeal 2020-006561
Application 15/542,005

4
and E1 gene region as recited in claim 159. Final Act. 3 (citing Hodge ¶¶ 34
(“In one aspect, the antigen is selected from the group of: carcinoembryonic
antigen (CEA), . . . Brachyury, MUC-1 . . . as well as combinations of such
antigens.”), 37; citing Colloca ¶ 137 (describing adenoviral vectors modified
with non-functional genes (e.g., E1A, E2B, etc.)); see also Colloca, Abstr.
(teaching “recombinant replication-defective adenoviral vectors . . . for use
for the delivery and expression of transgenes encoding immunogens against
which a boosted immune response is desired”). The Examiner finds that a
skilled artisan would have had reasons for combining the disclosures in
Hodge and Colloca to, for example: (i) obtain replication-deficient
adenoviral vectors for delivering desired genetic cargo/antigens without
causing further disease in the subject and; (ii) to provide a combination of
different and known cancer antigens for optimizing treatment in subjects
suffering from cancer with different clinical markers. Final Act. 3–4.
We agree, on this record, with the Examiner’s findings and reasoning
in support of the determination that a skilled artisan would have combined
Hodge’s and Colloca’s disclosures to arrive at claim 159’s subject matter
with a reasonable expectation of success. Final Act. 3–4; Ans. 3–5.
Appellant does not specifically challenge the Examiner’s findings or
reasoning in support of the conclusion that claim 159 would have been
prima facie obvious. See generally Appeal Br. Instead, Appellant contends
that the claimed composition produces an unexpected result that rebuts the
argument and evidence of obviousness. More specifically, Appellant argues
that its evidence shows “Tri-Ad5 vaccinated mice produced more CEA-
specific IL-2 producing cells than the Ad5 [E1-, E2b-]-CEA vaccinated
mice.” Id. at 7 (“Thus, by immunizing with MUC1/CEA/Brachyury a
Appeal 2020-006561
Application 15/542,005

5
stronger anti-CEA cell-mediate[d] immunity (CMI) response is achieved
than by immunizing with CEA alone.”). Appellant argues this result is
unexpected and, citing a declaration from Dr. Niazi,7 Appellant contends
“[t]he expected result would have been that immunizing with MUC1 or
Brach[y]ury would have been irrelevant to the output of CEA-responsive
cells.” Id. at 7–8 (citing Spec. ¶ 455, Fig. 31B, and Niazi Decl., and arguing
“the observed effect from the three-antigen combination is unexpected”).
To begin, we observe that objective indicia of nonobviousness, such
as unexpected results, are “only relevant to the obviousness inquiry ‘if there
is a nexus between the claimed invention and the [objective indicia].’” In re
Affinity Labs of Tex., LLC, 856 F.3d 883, 901 (Fed. Cir. 2017) (quoting
Ormco Corp. v. Align Tech., Inc., 463 F.3d 1299, 1312 (Fed. Cir. 2006)). In
a similar vein, “[i]t is well established that the objective evidence of
nonobviousness must be commensurate in scope with the claims.” In re
Lindner, 457 F.2d 506, 508 (CCPA 1972); In re Kao, 639 F.3d 1057, 1068
(Fed. Cir. 2011) (explaining that an applicant must provide an evidentiary
basis to support the conclusion that other embodiments within the scope of
the claims will behave the same and produce unexpected results).
The Examiner responds and urges us to sustain the rejection because
“the composition that achieved the ‘unexpected results’ argued by the
Appellant . . . is not commensurate with the scope of the claimed
composition.” Ans. 10. As noted by the Examiner, “the embodiment used
in Figure 31B and Example 8 [cited by Appellant] . . . was specifically using
Tri-Ad5 vector/vaccine” with a particular amount of viral particles for each

7 Declaration of Dr. Kayvan Niazi, dated Nov. 14, 2019 (“Niazi Decl.”).
Appeal 2020-006561
Application 15/542,005

6
antigen (1 x 1010) in a particular ratio (1x1x1 (3 x 1010 particles total)). Id. at
10–11. According to the Examiner, the “claims as written are not limited to
a ‘vaccine composition’ or even to a ‘pharmaceutical composition.’” Id. at
10. And, the Examiner explains, “the scope of the present claims do not
recite the Tri-Ad5 vaccine composition and do not mention a particular
number or ratio of virus particles required to achieve the unexpected
results.” Id. at 11 (“[N]o evidence of any embodiment other than the Tri-
Ad5 vaccine composition is presented” and Appellant has “not pointed to
any variation in the embodiment that was used for the unexpected results
other than the Tri-Ad5 vaccine composition which specifically recites virus
particles in a particular ratio.”).8
On this record, we conclude that Appellant’s alleged unexpected
results do not outweigh the evidence of obviousness. There is insufficient
evidence here to show unexpected results commensurate in scope with the
broader subject matter that is claimed. We discuss below.
Insofar as the Examiner appears to read claim 159’s composition as
not limited to virus particles as the means of nucleotide delivery, we are not
sure that interpretation is correct. Claim 159’s recitation of “adenovirus 5
vector[s]” comprising the gene mutations and the more specific nucleotide
payloads would seem to require Ad virus particles. See Spec. ¶ 117
(defining “adenovirus” and disclosing that “[t]he present invention
contemplates the use of any Ad from any of the four genera of the family
Adenoviridae . . . as the basis of an E2b deleted virus vector”). Although the
Examiner remarks that, in the relevant art, “the term vector may have the

8 Appellant did not file a Reply to the Answer.
Appeal 2020-006561
Application 15/542,005

7
meaning of a nucleic acid encoding a protein or may refer to the virus as a
vector” (Ans. 10), the Specification and claims appears to suggest the latter
meaning.9 The above being said, if prosecution continues, a clarification
may be prudent, including whether the claims are specific to a vaccine or
embrace any potential “composition” with the recited vectors.
But even if claim 159 does require viral particles, the Examiner is
correct that Appellant’s cited evidence is limited to a single embodiment that
produces the alleged unexpected results. That embodiment is much
narrower than the scope of the present claims—the embodiment using
1x1010 particles for delivery of each of the respective antigen-encoding
antigens (MUC1, Brachyury, and CEA), thus a 1:1:1 ratio. See Spec. ¶ 344.
The claims, however, read on any amount of the respective vectors in any
ratio whatsoever. There is no evidentiary showing on this record that the
result that was observed when the ratio was 1:1:1 would similarly hold true
across the breadth of compositions encompassed by claim 159. Ans. 11.
For that reason, we give Appellant’s evidence of unexpected results less
weight and it does not overcome the evidence of obviousness.10 See Pfizer,

9 The Examiner also remarks that “infection is by virus particle whereas
transfection is by nucleic acid vector.” Ans. 11. But, according to the
Specification, “transfection” includes “retroviral infection” among other
routes to transfection, such as “liposome fusion.” Spec. ¶ 122. To the extent
the Examiner was suggesting that transfection and retroviral infection are
different and mutually exclusive concepts, such suggestion is contrary to the
Specification’s use of the terms. (We need not further comment here on
whether the Specification’s use is scientifically correct and consistent with
general usage in the art).
10 The Examiner also noted that a question remained “how this [allegedly
unexpected] result is of practical or functional significance in the context of
cancer therapies,” and that the record lacked evidence of any “need for
Appeal 2020-006561
Application 15/542,005

8
Inc. v. Apotex, Inc., 480 F.3d 1348, 1372 (Fed. Cir. 2007) (“Although
secondary considerations must be taken into account, they do not necessarily
control the obviousness conclusion.”).
For the reasons above, we agree with the Examiner’s conclusion that
claim 159 would have been obvious over Hodge and Colloca. Claims 160–
162 fall with claim 159.
II. Claims 165–168: Obviousness over Hodge, Colloca, and Agrawal
The Examiner concludes that claims 165–168 would have been
obvious over Hodge, Colloca, and Agrawal. Final Act. 5–6. We agree with
and adopt the Examiner’s findings and reasoning in support of this rejection.
Appellant does not argue this rejection separately; rather, Appellant
incorporates its argument on the alleged unexpected results discussed above.
That argument is unpersuasive as already explained. Appeal Br. 8–9.
Accordingly, we determine that the preponderance of the evidence supports
the Examiner’s conclusion that claims 165–168 would have been obvious.
III. Claim 170: Obviousness over Hodge, Colloca, and Berinstein
The Examiner concludes that claim 170 would have been obvious
over Hodge, Colloca, and Berinstein. Final Act. 6. We agree with and adopt
the Examiner’s findings and reasoning in support of this rejection.

cancer vaccines that specifically stimulate IL-2 secretion in response to CEA
at the expense” of other antigen responsiveness. Final Act. 7; see MPEP
716.02(a) (“Applicants must further show that the results were greater than
those which would have been expected . . . , and that the results are of a
significant, practical advantage”). The Examiner further remarks that other
figures in the Specification (e.g., Figs. 32A and C) suggest responsiveness to
CEA is diminished, not enhanced, with the trivalent vaccine. Final Act. 7.
Appellant did not directly address these points on appeal.
Appeal 2020-006561
Application 15/542,005

9
Appellant does not argue this rejection separately; rather, Appellant
incorporates its argument on the alleged unexpected results discussed above.
Appeal Br. 9. That argument is unpersuasive as already explained.
Accordingly, we determine that the preponderance of the evidence supports
the Examiner’s conclusion that claim 170 would have been obvious.
CONCLUSION
For the reasons explained above, the preponderance of the evidence
supports the Examiner’s rejections on appeal.
In summary:
Claim(s)
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
159–162 103 Hodge, Colloca 159–162
165–168 103 Hodge, Colloca,
Agrawal
165–168
170 103 Hodge, Colloca,
Berinstein
170
Overall
Outcome
159–162,
165–168,
170

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)(1)(iv).

AFFIRMED