Martin Gilbert. Pomper et al.

Patent Trials and Appeals Board

Oct 29, 2019

14182690 - (D) (P.T.A.B. Oct. 29, 2019)

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.
14/182,690 02/18/2014 Martin Gilbert POMPER 110551-0104 6777
23524 7590 10/29/2019
FOLEY & LARDNER LLP
3000 K STREET N.W.
SUITE 600
WASHINGTON, DC 20007-5109
EXAMINER
MARVICH, MARIA
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
10/29/2019 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):
ipdocketing@foley.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte MARTIN GILBERT POMPER,
HYO-EUN BHANG, and PAUL FISHER
__________

Appeal 2018-005924
Application 14/182,690
Technology Center 1600
__________

Before ERIC B. GRIMES, JEFFREY N. FREDMAN, and
ULRIKE W. JENKS, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1,2,3 under 35 U.S.C. § 134 involving claims to a
method of imaging tumors or cancerous tissue in a subject. The Examiner
rejected the claims as non-enabled and as obvious. We have jurisdiction
under 35 U.S.C. § 6(b). We affirm but designate our affirmance as a new
ground of rejection.

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 “The Johns
Hopkins University and Virginia Commonwealth University” (see App. Br.
2).
2 We note that this case is a continuation-in-part of US 13/881,777 that was
the subject of related Appeal 2018-007074.
3 We have considered and refer to the Specification of Feb. 18, 2014
(“Spec.”); Final Action of Nov. 3, 2016 (“Final Act.”); Appeal Brief of Oct.
23, 2017 (“App. Br.”); and Examiner’s Answer of Mar. 7, 2018 (“Ans.”).
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Statement of the Case
Background
“Targeted imaging of cancer remains an important but elusive goal.
Such imaging could provide early diagnosis, detection of metastasis, aid
treatment planning and benefit therapeutic monitoring” (Spec. 1:14–16).
“Indirect methods use a reporter transgene strategy, in analogy to the use of
green fluorescent protein (GFP) in vitro, to provide a read-out on cellular
processes occurring in vivo by use of an external imaging device” (id. 1:24–
26). “Unfortunately, to date, none of these techniques has provided
sufficient specific localization of imaging agents, and unacceptably high
background noise is still prevalent” (id. 2:1–3).
The Claims
Claims 1–10 and 14 are on appeal. Claim 1 is representative and
reads as follows:
1. A method of imaging tumors or cancerous tissue in a
subject, the method comprising the steps of:
(a) administering systemically to said subject a non-
viral plasmid nucleic acid construct comprising an imaging
reporter gene operably linked to a cancer specific or a cancer
selective promoter;
(b) administering to the subject of part (a) an imaging
agent that is complementary to said imaging reporter gene
product; and
(c) screening the subject of part (b) for a signal from
the imaging agent, thereby imaging said tumors or said
cancerous tissue if present in the subject.

The Issues
A. The Examiner rejected claims 1–10 and 14 under 35 U.S.C. § 112,
first paragraph, enablement (Ans. 3–13).
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B. The Examiner rejected claims 1–10 and 14 under 35 U.S.C. § 103(a)4
as obvious over Brody5 (Ans. 14).
C. The Examiner rejected claims 1–10 and 14 on the ground of
provisional obviousness-type double patenting over claims 1, 3–6, 9–12, 16,
28, and 31–33 of US application 13/881,777 (Ans. 14–15).

A. 35 U.S.C. § 112, first paragraph, enablement
The Examiner finds “because the art of delivering DNA, molecular
imaging i.e. detection of signal and the correlation of small animal models
and humans in this art is proven and known to be unpredictable in the art,
the invention is not enabled” (Ans. 6).
Appellant contends the
Examiner’s reliance on various references in support of the
rejection is wholly misplaced. In some cases, the references
relate to methods of gene therapy, and not cancer imaging, and
are not relevant to the pending claims. In some cases, the
references are outdated and do not represent the current state of
the art. In all cases, the Examiner cites teachings of the
references out of context and exaggerates technical
considerations raised by the authors to the level of impassable
obstacle.
(App. Br. 5–6).

4 We note that in the Final Action, the ground of rejection relying on Brody
was identified as under § 102(e) while the Examiner’s Answer identified the
ground as under § 103(a). To avoid prejudice to Appellant, we will
designate our affirmance of the § 103(a) rejection as a new ground in order
to give Appellant an opportunity for further prosecution, if desired (see Final
Act. 17; cf. Ans. 14).
5 Brody et al., US 2012/0149647 A1, published June 14, 2012.
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The issue with respect to this rejection is: Does a preponderance of
the evidence of record support the Examiner’s conclusion that the
Specification does not enable the claimed invention?
Findings of Fact
Breadth of Claims
1. Claim 1, the sole independent claim, is drawn to systemic
administration of a non-viral plasmid nucleic acid construct with any
imaging reporter gene linked to any cancer specific promoter in order to
image cancers or tumors.
Presence of Working Examples
2. Example 1 of the Specification teaches systemic DNA delivery
of a plasmid with a PEG-3 promoter and HSV1tk reporter gene by injection
“into the lateral tail vein of an animal” (Spec. 33:13–34:29; esp. 34:28).
Example 1 teaches that imaging studies and immunohistochemistry was
performed on animals with induced tumors (Spec. 35:4–36:26). Example 1
teaches “[e]xpression of Luc driven by PEG-Prom was observed only in the
melanoma metastasis model (Mel) and not in control animals” (Spec. 37:17–
18).
3. Example 1 of the Specification teaches
to exclude the possibility that tumor-specific expression of Luc
. . . might have resulted from the difference in transfection
efficiency between normal and malignant mouse lung tissues,
we quantified the amount of pDNA delivered to the lung of
each animal . . . That result confirmed that the tumor-specific
expression of Luc observed in these models was due to the
tumor-selective activity of PEG-Prom rather than differential
transfection efficiency between normal and malignant lungs.
Poor vascularization and segregated large nodules most likely
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contributed to lower transfection efficiency observed in the lung
of the BCa model.
(Spec. 38:17–28).
4. Example 1 of the Specification teaches bioluminescence
imaging (BLI) “with systemically administered pPEG-Luc also enabled
imaging of small metastatic deposits, i.e., micrometastases, outside of the
lung parenchyma in both the Mel and BCa models. That was confirmed
through harvesting regions producing BLI signal above background and
performing correlative histological analysis” (Spec. 39:7–10).
5. Example 1 of the Specification teaches
we generated a more clinically relevant PEG-Prom-driven gene
expression imaging system, pPEG-HSV1 tk . . . which can be
detected using radionuclide-based techniques, namely, single
photon emission computed tomography (SPECT) or positron
emission tomography (PET), upon administration of a suitably
radiolabeled nucleoside analog. . . . We further confirmed
tumor presence in presumptive extrathoracic metastatic sites
through gross histological analysis after the 48 h imaging
session. Detected on the whole body SPECT-CT images . . .
were multiple metastatic lesions in the dorsal neck of Mel-2
that corresponded to the intact histological specimen.
(Spec. 39:23–40:9).
Amount of Direction or Guidance Presented
6. The Specification provides diagrams of specific imaging
constructs including a cancer specific promoter and one of two imaging
reporter genes, as recited in claim 1 (see Figures 1A and 1B).
7. The Specification teaches that for “systemic distribution of the
vector, the preferred routes of administration include but are not limited to:
intravenous, by injection, transdermal, via inhalation or intranasally, or via
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injection or intravenous administration of a cationic polymer-based vehicle
(e.g. vivo-jetPEI™). Liposomal delivery, which when combined with
targeting moieties will permit enhanced delivery” (Spec. 28:3–7).
8. The Specification teaches “optimal or effective tumor-inhibiting
or tumor-killing amounts are established e.g. during animal trials and during
standard clinical trials. Those of skill in the art are familiar with conversion
of doses e.g. from a mouse to a human” (Spec. 28:24–26). The Specification
provides conversion factors for relative doses (see Spec. 29:1–10).
Relative skill in the art
9. The Examiner finds the “level of skill is high for this invention.
It requires administration of DNA and agents to a subject in order to detect
cancer cells throughout the body” (Ans. 5).
State of the Prior Art and Unpredictability of the Art
10. Frangioni6 teaches the “goal of this review is to inform the
reader about why current imaging modalities are generally inadequate for
oncology and which new technologies have the potential to improve patient
care” (Frangioni 4013, col. 1).
11. Frangioni teaches imaging technologies including ultrasound,
X-Ray imaging, MRI, SPECT, PET, and optical imaging (see Frangioni
4014–5), but does not discuss the use of nucleic acid constructs with reporter
genes. Frangioni teaches:
the body has many barriers to the effective targeting of contrast
agents (and therapeutics) in vivo, including inhibitors present in
plasma, a relatively small effective endothelial pore size
(hydrodynamic diameter of approximately 5 nm) that constrains

6 Frangioni, New Technologies for Human Cancer Imaging, 26 J. CLIN.
ONCOLOGY 4012–4021 (2008).
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biodistribution, and basement membranes that act as barriers to
preinvasive cancer detection. Finally, many solid tumors have
high hydrostatic pressure, which impedes homogeneous
infiltration of diagnostic agents.
(Frangioni 4014, col. 1).
12. Frangioni teaches the “detection and imaging of small numbers
of cancer cells anywhere in the human body remains elusive. Although new
technologies, such as optical imaging, will likely play an important role in
certain clinical applications, the field of oncology needs a revolutionary
advance in the physics and chemistry of tumor detection” (Frangioni 4019,
col. 2).
13. Close7 teaches the “challenge of detecting and locating
bioluminescent light emissions from within living subjects has been met by
several commercial suppliers of in vivo imaging equipment . . . When
superimposed, regions of bioluminescence become mapped to the subject’s
anatomy for pinpoint identification of source emissions” (Close 183).
14. Min8 teaches “[n]aked therapeutic genetic molecules are
generally difficult to deliver primarily due to rapid clearance” but explains
that “specialized gene delivery vehicles (GDV) that improve delivery
efficiency and cell-specificity are preferred” (Min 15, col. 2).

7 Close et al., In Vivo Bioluminescent Imaging (BLI): Noninvasive
Visualization and Interrogation of Biological Processes in Living Animals,
11 SENSORS 180–206 (2011).
8 Min et al., Molecular Imaging of Biological Gene Delivery Vehicles for
Targeted Cancer Therapy: Beyond Viral Vectors, 44 NUCLEAR MED.
MOLECULAR IMAGING 15–24 (2010).
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15. Min teaches the “HSV1-tk gene has been utilized as an
effective reporter gene for nuclear imaging using PET or a gamma camera”
(Min 20, col. 1).
16. McCrudden9 teaches “systemic therapeutics bypass the skin,
but encounter further extracellular barriers before reaching their site of
action . . . Whilst in the circulation, however, non-viral agents can be subject
to non-specific binding by serum proteins, which can result in aggregation or
dissociation of nanoparticles” (McCrudden 216).
17. McCrudden teaches:
It is apparent that the field of non-viral gene delivery is making
significant progress in the quest for the ideal gene delivery
vehicle. What is also evident is that the most successful
systems are designed to overcome many biological barriers and
as a consequence the traditional single function systems are
now rendered obsolete. Viruses are nature’s perfect delivery
vehicle and provide the inspiration to many non-viral gene
therapy researchers in the design of state of the art multi-faceted
vehicles. Through a greater understanding and appreciation of
the biological barriers to systemic gene delivery, non- viral
gene therapy researchers are on the cusp of creating a variety of
highly efficient vehicles that will revolutionise cancer gene
therapy.
(McCrudden 234).
18. Thomas10 teaches “[v]ector TROPISM, the duration of
transgene expression and vector immunogenicity are other factors that

9 McCrudden et al., Cancer Gene Therapy – Key Biological Concepts in the
Design of Multifunctional Non-Viral Delivery Systems,
http://dx.doi.org/10.5772/54271 213–48 (2013).
10 Thomas et al., Progress And Problems With The Use Of Viral Vectors For
Gene Therapy, 4 NATURE GENETICS 346–58 (2003).
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influence the suitability of a vector for specific therapeutic applications”
(Thomas 348, col. 2).
19. Thomas teaches “[a]t the present time, viral vectors are the best
available vehicles for efficient gene transfer into most tissues. Nonviral
gene delivery is potentially safer than viral-mediated delivery, but — with
the exception of a few promising applications, such as vaccines — non-viral
systems are, at present, limited by their inefficiency” (Thomas 356, col. 2).
20. Croft11 teaches “[i]maging of animal tumors may be
accomplished by all of the ordinary techniques for imaging human tumors
. . . Optical techniques have become popular because they require less
expensive equipment and less animal preparation than do the more
instrument-intensive MRI and PET” (Croft 367, col. 2).
21. Croft teaches “HSV-thymidine kinase (TK) often is used for
such purposes, targeting TK receptors, which makes possible the use of anti-
HSV drugs as imaging and targeting agents” (Croft 373, col. 1).
22. Lee12 teaches:
Common transfection techniques were developed for in-vitro,
microscopic volume sample. It can be impractically expensive
to appl[y] to small animal work as well as inefficient, because
the small animal has relatively large body volume but very little
surface area to be exposed to agents (chemical or viral) for
transfection. A second obstacle is that the expression in this
case can often be transient, due to the inability of the living
tissue to regulate the excessive protein and to replicate the
DNA. With the reporter gene not stably incorporated into the

11 Croft, Animal models for imaging, 18 DISEASE MARKERS 365–74 (2002).
12 Lee, The Advantages of Fluorescent Proteins over Luciferase for In Vivo
Imaging, FOCAL POINTS APPLICATION NOTE FP-129 14 (2008).
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animal genome, the signal can have relatively very short (less
than 2 days) life span.
(Lee 2, col. 1).
23. Yaghoubi13 teaches a variety of PET reporter gene/probe
systems (see Yaghoubi 378, table 2).
24. Figure 5 of Yaghoubi is reproduced (in grayscale) below:

13 Yaghoubi, Positron Emission Tomography Reporter Genes and Reporter
Probes: Gene and Cell Therapy Applications, 2(4) THERANOSTICS 374–91
(2012).
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“Fig. 5. Example of direct gene therapy monitoring with PET. Direct
imaging of HSV1-sr39tk/GCV suicide gene therapy progress in C6 glioma
xenografted immunodeficient mice” (Yaghoubi 381).
Quantity of Experimentation
25. The Examiner finds that the “quantity of experimentation
needed to make or use the invention based on the content of the disclosure is
quite high as there are numerous art provided for obstacles to performing the
method but applicants have not provided adequate blaze marks on how to
overcome these obstacles” (Ans. 6).
26. The Specification teaches “[b]ased on these experiments it can
be seen that the systemic delivery of PEG-Prom-driven imaging constructs
will enable tumor-specific expression of reporter genes, not only within
primary tumor, but also in associated metastases in a manner broadly
applicable to tumors of different tissue origin or subtype” (Spec. 34:9–13).
Principles of Law
When rejecting a claim under the enablement requirement of section
112, the PTO bears an initial burden of setting forth a reasonable
explanation as to why it believes that the scope of protection provided
by that claim is not adequately enabled by the description of the
invention provided in the specification of the application.
In re Wright, 999 F.2d 1557, 1561–62 (Fed. Cir. 1993).

Factors to be considered in determining whether a disclosure would
require undue experimentation … include (1) the quantity of
experimentation necessary, (2) the amount of direction or guidance
presented, (3) the presence or absence of working examples, (4) the
nature of the invention, (5) the state of the prior art, (6) the relative
skill of those in the art, (7) the predictability or unpredictability of the
art, and (8) the breadth of the claims.
In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).
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Analysis
In addressing the Wands factors, we find that the balance of factors
does not support the Examiner’s position. There are working examples (FF
2–5) as well as detailed guidance in the Specification (FF 6–8) in a highly
skilled art (FF 9). The Examiner states that a large quantity of
experimentation would be required (FF 25) while the Specification suggests
that the experiments disclosed are sufficient (FF 26).
There is limited evidence of specific unpredictability related to
systemic imaging using the claimed nucleic acid constructs. Frangioni
teaches general imaging difficulties (FF 10–12), while Min teaches issues in
delivery of nucleic acid constructs (FF 14). McCrudden and Thomas teach
that there have been issues with administration of DNA that requires entry
into cells and expression in cells for activity including dissociation of the
particles being administered and non-specific targeting (FF 16–19).
However, Min also teaches HSV1-tk has been used as an effective
reporter gene (FF 15) as does Croft (FF 21). And while Lee teaches
administration may be transient, imaging for diagnostic purposes is desirably
transient since there is no need for long term expression of the reporter genes
in patients after the diagnosis is complete (FF 22). Moreover, Brody, cited
in the obviousness rejection, provides a detailed discussion supporting
enablement of the claims (see FF 27–34 below).
Therefore, in light of the detailed working examples and disclosure in
the Specification, the limited and predictable amount of experimentation
necessary, and despite the breadth of claim 1, we agree with the Appellant
that the evidence supports the position that the Specification enables the
scope of the claims. See In re Fisher, 427 F.2d 833, 839 (CCPA 1970)
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(“[T]he scope of the claims must bear a reasonable correlation to the scope
of enablement provided by the specification to persons of ordinary skill in
the art.”).

B. 35 U.S.C. § 103(a) over Brody
The Examiner finds Brody teaches “methods of imaging tumors in
mice wherein non-viral vectors and luciferase are administered
intravenously (which is a form of systemic administration) . . . The
luciferase was delivered with PEI . . . Delivery can be to any tumor types
such as ovarian or breast” (Ans. 14). The Examiner finds Brody teaches the
“promoter is a cancer specific promoter specific to cancer type” (Ans. 14).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that claim 1 would have been
obvious based on Brody?
Findings of Fact
27. Brody teaches a “bioluminescence imaging system (MS™
Imaging System, Xenogen Corp.) can be used to image mice and detect
nanoparticle-delivered Luc gene expression” (Brody ¶ 213).
28. Brody teaches an imaging process in which “C32-MSLN/firefly
luciferase DNA (Fluc) nanoparticles were directly injected into
subcutaneous xenografts derived from MSLN+ ovarian tumor cells, C32, to
poly(β-amino ester) polymer, or PEI was complexed to MSLN/Fluc DNA to
generate nanoparticles. Mice were optically imaged and bioluminescence
was detected in tumors 6 hrs after injection” (Brody ¶ 202).
29. Brody teaches vectors that may contain “the herpes simplex
virus thymidine kinase gene, HSV-tk, and/or a marker gene” (Brody ¶ 61).
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30. Brody teaches vectors may express genes using “a cancer
specific promoter” (Brody ¶ 51).
31. Brody teaches “constructs containing the luciferase (Luc)
sequence in place of DT-A allows the use of optical imaging to evaluate
gene expression in multiple organs easily” (Brody ¶ 219).
32. Brody teaches the “pharmaceutical composition may be
administered in a number of ways depending on whether local or systemic
treatment is desired, and on the area to be treated . . . [including]
parenterally, for example by intravenous drip” (Brody ¶ 106).
33. Brody teaches the “disclosed compositions can be used to treat
cancers including, but not limited to, pancreatic cancer, ovarian cancer,
breast cancer, non-small cell lung cancer, and liver cancer” (Brody ¶ 10).
34. Brody teaches:
There are a number of compositions and methods which can be
used to deliver nucleic acids to cells, either in vitro or in vivo.
These methods and compositions can largely be broken down
into two classes: viral based delivery systems and non-viral
based delivery systems. For example, the nucleic acids can be
delivered through a number of direct delivery systems such as,
electroporation, lipofection, calcium phosphate precipitation,
plasmids, viral vectors, viral nucleic acids, phage nucleic acids,
phages, cosmids, or via transfer of genetic material in cells or
carriers such as cationic liposomes.
(Brody ¶ 48).
Principles of Law
An anticipatory reference under 35 U.S.C. § 102 “must clearly and
unequivocally disclose the claimed compound or direct those skilled in the
art . . . without any need for picking, choosing, and combining various
disclosures . . . Such picking and choosing may be entirely proper in the
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making of a 103, obviousness rejection.” In re Arkley, 455 F.2d 586, 587–
88 (CCPA 1972).
The combination of familiar elements according to known methods is
likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability.” Id. at 417.
Analysis
As noted above, because the Examiner modified the grounds of
rejection from anticipation in the Final Action to obviousness in the
Examiner’s Answer, we designate our affirmance as a New Ground of
Rejection to provide Appellant a fair opportunity to address the new
position.
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 14; FF 27–34) and agree that the
claims are rendered obvious by Brody. We address Appellant’s arguments
(which are directed to anticipation) below.
Appellant contends “Brody does not teach all elements of the rejected
claims. In particular, the reference does not teach methods comprising
administering systemically to a subject a non-viral plasmid nucleic acid
construct comprising an imaging reporter gene operably linked to a cancer
specific or a cancer selective promoter” (App. Br. 16).
We find this argument unpersuasive because Brody teaches
“constructs containing the luciferase (Luc) sequence in place of DT-A
allows the use of optical imaging to evaluate gene expression in multiple
organs easily” (FF 31) and expressly suggests the constructs “may be
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administered in a number of ways depending on whether local or systemic
treatment is desired, and on the area to be treated . . . [including]
parenterally, for example by intravenous drip” (FF 32). Brody’s teaching to
optically image multiple organs using a luciferase construct along with the
general suggestion to administer compositions systemically reasonably
suggests systemic administration of the luciferase construct for imaging
multiple organs (FF 27, 28, 31). Brody also teaches both “viral based
delivery systems and non-viral based delivery systems” (FF 34). Lastly,
Brody expressly teaches the use of cancer selective promoters (FF 30).
While we might agree that these teachings represent too much picking
and choosing for an anticipation rejection, under the current obviousness
rejection, we agree with the Examiner’s finding that it would have been
obvious to select from the disclosed options within Brody including the
known use of systemic administration (FF 32), the known use of a non-viral
plasmid construct with an imaging reporter gene (FF 28) and a known
cancer specific promoter (FF 30) in order to achieve Brody’s goal of
imaging multiple organs at the same time (FF 31).
Appellant contends that Brody only teaches “‘nanoparticles were
directly injected into subcutaneous xenografts derived from MSLN+
ovarian tumor cells.’ Brody, paragraph [0201] (emphasis added). Hence, the
reference teaches only direct administration of compositions for imaging”
(App. Br. 17).
While Appellant is correct that Brody only exemplifies imaging using
direct injection of constructs (FF 28), Brody expressly suggests that
constructs may be administered to multiple organs (FF 31) and also suggests
systemic administration of constructs (FF 32). “A disclosure in a reference
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is not limited to its specific illustrative examples, but must be considered as
a whole to ascertain what would be realistically suggested thereby to one of
ordinary skill in the art.” In re Uhlig, 376 F.2d 320, 323 (CCPA 1967).
Indeed, “[a]ll the disclosures in a reference must be evaluated, including
nonpreferred embodiments . . . and a reference is not limited to the
disclosure of specific working examples.” In re Mills, 470 F.2d 649, 651
(CCPA 1972). Thus, the issue is not whether Brody provides an example of
systemic administration but rather whether Brody suggests systemic
administration of the nucleic acids. Brody does so (FF 32).
Appellant contends that “[p]aragraph [0010] describes the delivery of
therapeutic agents, not luciferase, to treat, not image, various cancers” (App.
Br. 18). Appellant contends “[p]aragraph [0048] describes the direct
delivery of plasmid vectors to target cells, and not systemic administration.
Paragraph [0107] describes fluid vehicles suitable for in [sic] intravenous
administration generally” (id.).
We are not persuaded by this argument as “picking and choosing may
be entirely proper in the making of a 103, obviousness rejection, where the
applicant must be afforded an opportunity to rebut with objective evidence”
Arkley, 455 F.2d at 587. That is, Brody teaches an example where nucleic
acid constructs were administered into animals in order to image tumors (FF
28), Brody suggests that nucleic acid constructs may be used to evaluate and
image multiple organs (FF 31), and Brody suggests that nucleic acid
constructs may be administered systemically (FF 32). We agree with the
Examiner that the ordinary artisan, familiar with these teachings in Brody,
would have reasonably found it obvious to administer Brody’s nucleic acids
systemically in order to image tumors in multiple organs consistent with the
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disclosures of Brody (FF 27–34). Appellant’s Appeal Brief does not
identify any objective evidence that would rebut the Examiner’s obviousness
position.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that
Brody renders the claims obvious.

C. Provisional Obviousness-Type Double Patenting
We summarily affirm the provisional obviousness-type double
patenting rejections because Appellant does not dispute the merits of this
rejection. See Manual of Patent Examining Procedure § 1205.02 (“If a
ground of rejection stated by the examiner is not addressed in the appellant’s
brief, that ground of rejection will be summarily sustained by the Board.”)

CONCLUSION
In order to provide Appellant a fair opportunity to respond to the
obviousness basis of the rejection, we designate our affirmance as a new
ground pursuant to 37 C.F.R. § 41.50(b). Section 41.50(b) provides “[a]
new ground of rejection pursuant to this paragraph shall not be considered
final for judicial review.” Section 41.50(b) also provides:
When the Board enters such a non-final decision, the
appellant, within two months from the date of the decision,
must exercise one of the following two options with respect to
the new ground of rejection to avoid termination of the appeal
as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate
amendment of the claims so rejected or new Evidence relating
to the claims so rejected, or both, and have the matter
reconsidered by the examiner, in which event the prosecution
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will be remanded to the examiner. The new ground of rejection
is binding upon the examiner unless an amendment or new
Evidence not previously of Record is made which, in the
opinion of the examiner, overcomes the new ground of rejection
designated in the decision. Should the examiner reject the
claims, appellant may again appeal to the Board pursuant to this
subpart.
(2) Request rehearing. Request that the proceeding be
reheard under § 41.52 by the Board upon the same Record. The
request for rehearing must address any new ground of rejection
and state with particularity the points believed to have been
misapprehended or overlooked in entering the new ground of
rejection and also state all other grounds upon which rehearing
is sought.

Further guidance on responding to a new ground of rejection can be
found in the Manual of Patent Examining Procedure § 1214.01.
In summary:

AFFIRMED; 37 C.F.R. § 41.50(b)

Claim(s)
Rejected
Basis Affirmed Reversed New
Ground
1–10, 14 § 112, ¶ 1,
enablement
1–10, 14
1–10, 14 § 103(a) Brody 1–10, 14
1–10, 14 Provisional
Obviousness-type
Double Patenting
1–10, 14
Overall
Outcome
1–10, 14 1–10, 14