THOMAS JEFFERSON UNIVERSITY

Patent Trials and Appeals Board

Sep 8, 2020

14767936 - (D) (P.T.A.B. Sep. 8, 2020)

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.
14/767,936 08/14/2015 Mathew L. Thakur JFU0003US.NP 3232
26259 7590 09/08/2020
LICATA & TYRRELL P.C.
66 E. MAIN STREET
MARLTON, NJ 08053
EXAMINER
ALLEN, MICHAEL D
ART UNIT PAPER NUMBER
1642
NOTIFICATION DATE DELIVERY MODE
09/08/2020 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
PTOactions@licataandtyrrell.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte MATHEW L. THAKUR and LEONARD G. GOMELLA
____________

Appeal 2019-006573
Application 14/767,936
Technology Center 1600
____________

Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
MICHAEL A. VALEK, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s
decision to reject claims 5–12, 14, and 16–18 (Appeal Br. 3). 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 “Thomas
Jefferson University” (Appellant’s April 12, 2019 Appeal Brief (Appeal Br.)
1).
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STATEMENT OF THE CASE
Appellant’s disclosure:
[P]rovides methods for detecting shed or circulating tumor cells
and diagnosing cancer by contacting a biological fluid with a
labeled pituitary adenylate cyclase activating peptide (PACAP)
or vasoactive intestinal peptide (VIP), and determining binding
of the PACAP or VIP to shed or circulating tumor cells in the
biological fluid. In one embodiment, the biological fluid is
blood, urine or cerebrospinal fluid.
(Spec. ¶ 7.) Claim 5 is reproduced below:
5. A method for detecting shed or circulating tumor cells that
overexpress a pituitary adenylate cyclase activating peptide
(PACAP) receptor comprising:
(a) contacting a biological fluid obtained from a subject
with a labeled PACAP having a label;
(b) detecting binding of the labeled PACAP to shed or
circulating tumor cells in the biological fluid; and
(c) comparing binding of the labeled PACAP to shed or
circulating tumor cells in the biological fluid to binding or lack
of binding of labeled PACAP in a control sample thereby
detecting shed or circulating tumor cells.
(Appeal Br. 21.)

Grounds of rejection before this Panel for review:2, 3
Claims 16 and 17 stand rejected under 35 U.S.C. 112(b).

2 Examiner withdrew the Final rejections under 35 U.S.C. § 101 and the
written description provision of 35 U.S.C. § 112(a) (Examiner’s July 5, 2019
Answer (Ans.) 3).
3 Office records indicate that Application 14/767,927 abandoned February
19, 2020. Therefore, the provisional nonstatutory double patenting rejection
over the claims of this Application is moot and will not be discussed further.
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Claims 5–12, 14, 16–18 stand rejected under 35 U.S.C. § 103 as
unpatentable over the combination of Thakur ’133,4 Dong,5 Russell,6 and
Fujita.7
Claims 5–12, 14, 16–18 stand rejected under the judicially created
doctrine of obviousness-type double patenting as being unpatentable over
claims 1–17 of Thakur ’308,8 in view of Thakur ’133, Dong, Russell, and
Fujita.

DEFINITENESS:
ISSUE
Does the preponderance of evidence support Examiner’s conclusion
that Appellant’s claims 16 and 17 are indefinite?
ANALYSIS
Examiner finds that Appellant’s claims 16 and 17 “depend on a
canceled claim” and “[t]herefore, their metes and bounds are indefinite”
(Ans. 9). Appellant “propose[s] to address this rejection by amending
claims 16–17 to depend from claim 5” (Appeal Br. 20). Because
Appellant’s proposed amendment was not made, the rejection is sustained
(see Ans. 23 (Examiner finds that “the proposed amendments have not yet
been made”)).

4 Thakur, US 2003/0129133 A1, published July 10, 2003.
5 Dong, WO 00/05260, published Feb. 3, 2000.
6 Russell et al., US 5,861,248, issued Jan. 19, 1999.
7 Fujita, et al., Specific detection of prostate cancer cells in urine by
multiplex immunofluorescence cytology, 40 Hum. Pathol. 924–33 (2009).
8 Thakur, US 6,855,308 B2, issued Feb. 15, 2005.
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CONCLUSION
The preponderance of evidence supports Examiner’s conclusion that
Appellant’s claims 16 and 17 are indefinite. The rejection of claims 16 and
17 under 35 U.S.C. 112(b) is affirmed.
For the purposes of this Opinion, we review the rejections of
Appellant’s claims 16 and 17 under obviousness and obviousness-type
double patenting as if both claims depended from Appellant’s claim 5.

OBVIOUSNESS:
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 1. Thakur ’133 relates “to the use of radiolabeled PACAP and
biologically active PACAP fragments and analogs for imaging or therapy of
breast and other tumors which express PACAP, VIP-R1 and VIP-R2
receptors. PACAP, VIP-R1 and VIP-R2 receptors are hereinafter
collectively referred to as ‘VPAC receptors’” (Thakur ’133 ¶ 16; see id. at
Abstract (Thakur ’133 discloses that “[t]umors expressing VPAC receptors
can be imaged or treated with compounds comprising PACAP, or a
biologically active PACAP fragment or analog”); see also Ans. 4).
FF 2. Thakur ’133 discloses that “VPAC receptors . . . are expressed in
high density on breast tumor . . . and other tumor cells,” including “ovarian,
endometrial, prostate, bladder, lung, esophageal, colonic, pancreatic,
neuroendocrine and brain tumors” (Thakur ’133 ¶ 13; see also Ans. 4).

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FF 3. Thakur ’133
provides a method of detecting tumors expressing VPAC
receptors, comprising administering an effective amount of an
imaging compound of formulae A or B to a subject who has, or
is suspected of having, such a tumor. After administration of
the imaging compound, a scintigr[a]phic image is generated of
at least part of the subject’s body.
(Thakur ’133 ¶ 17; id. ¶ 90 (Thakur ’133 discloses that in practice, “an
effective amount of an imaging compound comprising PACAP, or a
biologically active PACAP fragment or analog, is administered to a subject
by any suitable enteral or parenteral route of administration.”); id. ¶ 94
(Thakur ’133 discloses that “[a]fter the imaging compound is administered
to the subject, a scintigr[a]phic image is generated of at least part of the
subject. For example, an image is desirably obtained of that part of the
subject’s body containing, or which is suspected of containing, the tumor.”);
see also Ans. 4.)
FF 4. Thakur ’133 discloses that “[a] compound . . . comprising PACAP,
or a biologically active PACAP fragment or analog, and an imaging
radionuclide is an ‘imaging compound’” (Thakur ’133 ¶ 87; see generally
Ans. 4–5).
FF 5. Examiner relies on Dong to disclose PACAP analogues (see Ans. 5;
see also (Dong 1:5–7 (Dong “is directed to novel analogues of
PACAP . . . and the use thereof for treating . . . conditions and[/]or
diseases”); Dong 8:18–31 (Dong discloses a variety of conditions and
diseases that may be treated with its PACAP analogues)).
FF 6. Examiner finds that the combination of Thakur ’133 and Dong fail to
suggest the “detection of circulating tumor cells in [a biological fluid, such
as] urine” (Ans. 5).
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FF 7. Russell discloses “a method for identification of prostate cancer cells
in a biological sample[, such as urine,] by amplifying and detecting nucleic
acids corresponding to prostate cancer cell markers” (Russell 28:15–26; see
id. at Abstract (Russell “relates particularly to probes and methods for
evaluating the presence of RNA species that are differentially expressed in
prostate cancer compared to normal human prostate or benign prostatic
hyperplasia”); id. at 40:35–43:29 (Russell exemplifies the “Identification of
Markers of Prostate Disease by Use of RNA Fingerprinting); see also Ans.
6).
FF 8. Fujita discloses that “[i]t is known that prostate cancer cells are shed
into biological fluids, particularly when the prostate is subjected to physical
manipulation, thus creating the potential for their non-invasive detection in
wither urine or expressed prostatic fluid” (Fujita § 1; see Ans. 6–7).
FF 9. Fujita discloses the detection of prostate cancer cells in urine (Fujita,
Abstract; see id. §§ 2.2–4 (Fujita discloses an immunofluorescence assay to
detect prostate cancer cells in urine); id. § 4 (Fujita discloses that “more
prostate cancer-specific markers will [certainly] be developed over the
coming years” and that “it will be of interest to optimize and study the most
specific of these in such cohorts as well as in larger groups of men being
screened and subsequently biopsied.”); see also Ans. 6).
FF 10. Thakur declares that “[s]hed or circulating tumor cells are quite
distinct from the cells of a primary tumor” (Thakur Decl.9 ¶ 2 (citing
Pantel10 1216 and Fig. 1) (Thakur relies on Pantel to “teach that tumor cells

9 Declaration of Mathew L. Thakur, signed May 16, 2018.
10 Pantel et al., The biology of circulating tumor cells, 35 Oncogene 1216–
1224 (2016).
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undergo a number of biological processes during . . . [circulating tumor cell
(CTC)]-based metastasis) (emphasis added)).
FF 11. Thakur declares that “CTCs . . . exhibit numerous changes in gene
expression after leaving the primary tumor” (Thakur Decl. ¶ 3 (citing
LaTulippe,11 Abstract) (Thakur relies on LaTulippe to “teach that the
expression of more than 3000 tumor-intrinsic genes differ by at least 3-fold
between primary prostate cancers and metastatic prostate cancers”)
(emphasis added)).
FF 12. Thakur declares that each of Dong, Thakur ’133, Russell, and Fujita
would not have provided a person of ordinary skill in this art with the
necessary guidance to utilize a labeled PACAP to detect VPAC1 receptors
expressed on shed or circulating tumor cells in an isolated biological sample,
such as urine (Thakur Decl. ¶¶ 4–8).
FF 13. Thakur declares that “[a]s one having ordinary skill in the art,
[Thakur] find[s] that the assays of the cited prior art are so incongruent that
the ordinary artisan simply would not have sought these references out and
combined the same to arrive at the claimed method” (Thakur Decl. ¶ 9).
ANALYSIS
Thakur ’133 establishes that labeled PACAP can be used to detect and
treat cells in vivo (see FF 1–4; see generally FF 5 (Dong discloses PACAP
analogues)). Examiner appreciates that the combination of Thakur ’133 and
Dong fails to suggest the “detection of circulating tumor cells in [a
biological fluid, such as] urine” (FF 6). Examiner finds, however, that

11 LaTulippe et al., Comprehensive Gene Expression Analysis of Prostate
Cancer Reveals Distinct Transcriptional Programs Associated with
Metastatic Disease, 62 Cancer Research 4499–4506 (2002).
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Russell and Fujita disclose methods of detecting prostate cancer cells in a
biological sample, such as urine (see FF 7–9). In this regard, Fujita
discloses a binding assay, i.e. immunoassay, to detect prostate cancer cells
that are shed into urine in response to physical manipulation of the prostate
(see FF 8–9). In addition, Fujita discloses that more in vitro assays using
newly discovered prostate cancer markers will be developed, thus, providing
a reasonable expectation of success in the use of additional, i.e. newly
discovered, probes to optimize in vitro assays (see FF 9). See In re
O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988) (“Obviousness does not
require absolute predictability of success . . . all that is required is a
reasonable expectation of success.”). Thus, based on the combination of
Thakur ’133, Dong, Russell, and Fujita, we find no error in Examiner’s
conclusion that, at the time Appellant’s invention was made, it would have
been prima facie obvious to use labeled PACAP in a binding assay to detect
prostate cancer cells that are shed into urine in response to physical
manipulation of the prostate (see generally Ans. 6–7). In this regard,
Fujita’s disclosure of an interest in optimizing assays with newly developed
probes (see FF 9), such as those disclosed by Thakur ’133 (see FF 1–4),
provides the reasonable expectation of success supporting Examiner’s
conclusion on this record.
Appellant relies on the Thakur Declaration and the evidence cited
therein to support a contention that “there is no evidence of record to suggest
that shed or circulating tumor cells (CTCs) retain expression of PACAP
receptors once the cells are no longer associated with the primary tumor”
(Appeal Br. 14; see also Reply Br. 2–3; FF 10–12). We are not persuaded.
The evidence relied upon by Thakur makes clear that Thakur’s statements
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relates to cells shed as a result of CTC-based metastasis (see FF 10–11; cf.
Ans. 19 (Examiner finds that “Fujita makes clear . . . the prostate cancer
cells can be found in urine after physical manipulation of the prostate.
Therefore, no metastasis is required.”); see also FF 8–9; Appeal Br. 13–14
(Appellant appreciates that Fujita discloses, inter alia, “[i]t is known that
prostate cancer cells are shed into biological fluids, particularly when the
prostate is subjected to physical manipulation”)). Stated differently, because
Fujita’s cells are obtained from physical manipulation of the prostate and not
from metastasis, a person of ordinary skill in the art would not have
expected these cells to differ from the primary tumor. In this regard, we
note that Appellant failed to provide an evidentiary basis on this record to
support a contrary conclusion. Therefore, we are not persuaded by
Appellant’s contention that because
the cited prior art provides no evidence to demonstrate that
PACAP receptor expression on the cell surface is retained once
the shed . . . cancer cells leave the primary tumor, there can be
no reasonable expectation that these cells can be detected based
upon the combined teachings of the cited references.
(Appeal Br. 15.)
For the foregoing reasons, we are not persuaded by Appellant’s
contention that “Examiner has not provided evidence showing that a person
of ordinary skill in the art would have had a reasonable expectation of
success in replacing” the binding molecule, i.e. antibody, in Fujita’s binding
assay with the labeled binding molecule, i.e. PACAP peptide, taught by both
of Thakur ’133 and Dong (Appeal Br. 16; see also Reply Br. 3–4; FF 12).
As Examiner explains, obviousness does not require an absolute
predictatiblity of success, only a reasonable expectation of success, which,
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on this record, is provided by the combination of Thakur ’133, Dong,
Russell, and Fujita (Ans. 17–18). See O’Farrell, 853 F.2d at 903.
Two criteria have evolved for determining whether prior art is
analogous: (1) whether the art is from the same field of endeavor, regardless
of the problem addressed, and (2) if the reference is not within the field of
the inventor’s endeavor, whether the reference still is reasonably pertinent to
the particular problem with which the inventor is involved. In re Clay, 966
F.2d 656, 658–9 (Fed. Cir. 1992). On this record, Thakur ’133, Dong,
Russell, and Fujita relate to the use of binding molecules, including PACAP,
to, inter alia, detect cells, including tumor cells (see FF 1–9). Thus, we find
that Thakur ’133, Dong, Russell, and Fujita are reasonably pertinent to the
particular problem with which the inventor is involved. See Clay, 966 F.2d
at 658–9. Therefore, we are not persuaded by Appellant’s contention that
Thakur ’133, Dong, Russell, and Fujita are non-analogous art (see Appeal
Br. 15–16; see also Reply Br. 4–5; FF 13).
For the foregoing reasons, we are not persuaded by Appellant’s
contention that Examiner relied on impermissible hindsight (Appeal Br. 16).
CONCLUSION
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness. The rejection of claim 5 under 35 U.S.C.
§ 103(a) as unpatentable over the combination of Thakur ’133, Dong,
Russell, and Fujita is affirmed. Claims 6–12, 14, and 16–18 are not
separately argued and fall with claim 5.

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OBVIOUSNESS-TYPE DOUBLE PATENTING:
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness-type double patenting?
FACTUAL FINDINGS (FF)
FF 14. Thakur ’308’s claim 1 is directed to “[a] method of detecting tumors
expressing VPAC receptors in a subject who has, or is suspected of having,
such a tumor, said method comprising: (1) administering an effective
amount of an imaging compound . . . to the subject; and (2) generating a
scintigraphic image of at least part of the subject, wherein . . . [the imaging
compound comprises] . . . PACAP, or an analog or fragment thereof which
exhibits PACAP biological activity” (Thakur ’308 23:21–42; see Ans. 7–8).
FF 15. Thakur ’308’s claim 13 depends from and further limits the tumor of
Thakur ’308’s claim 1 to, inter alia, a prostate tumor (Thakur ’308 23:66–
24:24; Ans. 8).
ANALYSIS
Examiner relies on the combination of Thakur ’133, Dong, Russell,
and Fujita as discussed above (see Ans. 7–8; see also FF 1–9). Examiner
further finds that the claims of Thakur ’308 relate to in vivo “methods of
detecting VPAC receptor expressing tumors[, including prostate tumors,] in
a subject using labeled PACAP probes” (see Ans. 8; see also FF 14–15).
Thus, based on the combination of claims 1–17 of Thakur ’308, in view of
Thakur ’133, Dong, Russell, and Fujita, Examiner concludes that, at the time
Appellant’s invention was made, it would have been prima facie obvious to
use Thakur ’308’s probes to detect tumor cells in a biological sample, in
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vitro, as was made obvious by the combination of Thakur ’133, Dong,
Russell, and Fujita (see Ans. 8; see also id. at 22).
Thakur ’308 discloses PACAP probes that are useful in the detection
of tumor cells, including prostate tumors (see FF 14–15). Appellant failed to
establish an evidentiary basis on this record to support a conclusion that
Thakur ’308’s PACAP probes could not be useful in the in vitro assays
suggested by the combination of Thakur ’133, Dong, Russell, and Fujita (see
FF 1–9). Therefore, we are not persuaded by Appellant’s contention that
Thakur ’308 is distinct from the claims on this record because Thakur ’308
relates to an in vivo method as opposed to the in vitro assay claimed on this
record (Appeal Br. 15–19; Reply Br. 5–6).
For the reasons set forth above, with respect to the obviousness
rejection, we are not persuaded by Appellant’s contentions regarding the
combination of Thakur ’133, Dong, Russell, and Fujita (see Appeal Br. 18–
19; Reply Br. 5–6).
CONCLUSION
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness-type double patenting. The rejection of claim 5
under the judicially created doctrine of obviousness-type double patenting as
being unpatentable over claims 1–17 of Thakur ’308, in view of Thakur
’133, Dong, Russell, and Fujita is affirmed. Claims 6–12, 14, and 16–18 are
not separately argued and fall with claim 5.

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DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
16, 17 112(b) Indefiniteness 16, 17
5–12, 14,
16–18
103 Thakur ’133,
Dong, Russell,
Fujita
5–12, 14,
16–18

5–12, 14,
16–18
Nonstatutory
Double Patenting,
Thakur ’308,
Thakur ’133,
Dong, Russell,
Fujita
5–12, 14,
16–18

Overall
Outcome
5–12, 14,
16–18

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).

AFFIRMED