James Barbeau et al.

Patent Trials and Appeals Board

Mar 10, 2021

2020001915 (P.T.A.B. Mar. 10, 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.
14/217,822 03/18/2014 James M. Barbeau 23371-1 5392
39564 7590 03/10/2021
FisherBroyles, LLP - MAIN CN
885 Woodstock Rd, Ste. 430-383
Roswell, GA 30075
EXAMINER
WEILER, KAREN S
ART UNIT PAPER NUMBER
IPLA
NOTIFICATION DATE DELIVERY MODE
03/10/2021 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):
docketing@fisherbroyles.com
patent@fisherbroyles.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JAMES M. BARBEAU and JOHN S. DEPAOLO1
Appeal 2020-001915
Application 14/217,822
Technology Center 1600
Before DONALD E. ADAMS, ERIC B, GRIMES, and TAWEN CHANG,
Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of analyzing carcinogenesis of a tumor, which have been rejected for
reciting new matter, indefiniteness, anticipation, and obviousness. We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM IN PART.

1 Appellant identifies the real party in interest as Visible Genomics, LLC.
Appeal Br. 1. We use the word “Appellant” to refer to “applicant” as defined
in 37 C.F.R. § 1.42.
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STATEMENT OF THE CASE
Appellant’s Specification discloses “methods for revealing natural
histories of cancers. In certain embodiments, the natural histories are
revealed by systematically ‘walking through’ individual tumors, performing
extensive sampling and analysis from normal cells external to the cancers,
through the precursor lesions ‘peripheral’ to the cancers, and finally within
the cancers.” Spec. 6:21 to 7:2.
In embodiments of the present invention, upon resection,
tumor and surrounding “normal-appearing” tissue may be flash
frozen as a tissue block to preserve DNA and RNA. The tissue
block may then be sectioned into multiple vertical samples. . . .
Alternating sections may be stained with hematoxylin and eosin
(H & E) as a guide for microdissection enabling use of
observed cellular characteristics of the stained sections to guide
selection of areas for dissection. Samples may be ascertained
and collected by use of a laser capture microdissector.
Id. at 11:20 to 12:4.
Claims 1, 15–19, 21, 22, 24, and 25 are on appeal. Claims 1 and 25,
reproduced below, are illustrative:
1. A method of analyzing carcinogenesis of a single,
individual tumor by performing comparative whole genome
sequencing on cell samples derived from a tissue block of a
tissue sample, the method comprising:
selecting a selected tissue block, the selected tissue block
consisting of individual tumor tissue associated with a single,
individual tumor, precursor lesion tissue surrounding the
individual tumor tissue and associated with the single,
individual tumor, and normal tissue surrounding the portion of
precursor lesion tissue and associated with the single, individual
tumor;
removing the selected tissue block;
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flash freezing the selected tissue block;
progressively sectioning the selected tissue block into a
plurality of sections, the plurality of sections containing a series
of sections containing the normal tissue, a series of sections
containing the precursor lesion tissue, and a series of sections
containing the individual tumor tissue associated with the
single, individual tumor;
staining alternating sections of the plurality of sections,
creating alternating stained and unstained sections;
characterizing the stained sections as containing one of
normal tissue, precursor lesion tissue, and individual tumor
tissue;
collecting cell samples using laser capture
microdissection from unstained sections, using the
characterized, stained sections as a guide, wherein the collected
cell samples include normal tissue cell samples, precursor
lesion tissue cell samples, and individual tumor tissue cell
samples;
isolating DNA from the normal tissue cell samples;
performing whole genome sequencing on DNA isolated
from the normal tissue cell samples;
establishing a genetic baseline derived from the normal
tissue cell samples;
isolating DNA from the precursor lesion tissue cell
samples and the individual tumor tissue cell samples;
performing whole genome sequencing on DNA isolated
from the precursor lesion tissue cell samples and the individual
tumor tissue cell samples; and
comparing DNA sequence information of the precursor
lesion tissue cell samples and the individual tumor tissue cell
samples to the genetic baseline derived from the normal tissue
cell samples; and
identifying alterations in the DNA sequence information
associated with carcinogenesis based on the comparison of
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DNA sequence information derived from the precursor lesion
tissue cell samples and the individual tumor tissue cell samples
as compared to the genetic baseline.

25. A method for analyzing carcinogenesis in a single,
individual tumor comprising:
isolating a tissue sample, the tissue sample having a
tumor tissue, a precursor lesion tissue surrounding the tumor
tissue and associated with the individual tumor, and a normal
tissue surrounding the precursor lesion tissue and associated
with the individual tumor;
selecting and isolating a selected tissue block from the
tissue sample, the selected tissue block comprising each of the
normal tissue, the precursor lesion tissue, and the tumor tissue;
progressively sectioning the tissue block to obtain a
plurality of normal tissue sections, precursor lesion tissue
sections, and tumor tissue sections;
isolating DNA from cell samples taken from at least one
section of normal tissue;
establishing a genetic baseline derived from the isolated
DNA of cell samples taken from the section of normal tissue;
isolating DNA from cell samples taken from at least one
section of precursor lesion tissue and at least one section of
tumor tissue; and
performing comparative large scale analysis on the
isolated DNA of cell samples taken from each of the normal
tissue, the precursor lesion tissue, and the individual tumor
tissue, wherein the genetic baseline derived from the isolated
DNA of cell samples taken from the section of normal tissue is
used as a baseline in the comparative large scale analysis.

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The claims stand rejected as follows:
Claim 21 under 35 U.S.C. § 112(a) for lack of adequate written
description (Final Action2 4);
Claims 1, 15, 16, and 25 under 35 U.S.C. § 112(b) as indefinite (Final
Action 5);
Claim 25 under 35 U.S.C. §§ 102(a)(1) and 102(a)(2) as anticipated
by Czerniak3 (Final Action 7);
Claims 1, 15, and 16 under 35 U.S.C. § 103 as obvious based on
Czerniak, Gui,4 Tabor,5 Richards,6 and Doyle7 (Final Action 9);
Claims 17–19 and 21 under 35 U.S.C. § 103 as obvious based on
Czerniak, Gui, Tabor, Richards, Doyle, Guo,8 and Ukai9 (Final Action 14–
15);

2 Office Action mailed Jan. 31, 2019.
3 Czerniak et al., US 2003/0165895 A1, pub. Sept. 4, 2003.
4 Yaoting Gui et al., Frequent mutations of chromatin remodeling genes in
transitional cell carcinoma of the bladder, Nature Genetics 43: 875–78
(2011).
5 Maarten P. Tabor et al., Multiple Head and Neck Tumors Frequently
Originate from a Single Preneoplastic Lesion, Am. J. Pathology 161: 1051–
60 (2002).
6 WG Richards et al., A microaliquoting technique for precise histological
annotation and optimization of cell content in frozen tissue specimens,
Biotechnic & Histochemistry 82: 189–97 (2007).
7 Doyle et al., US 2002/0048766 A1, pub. Apr. 25, 2002.
8 Yan Guo et al., Microdissection of spatially identified single nuclei in a
solid tumor for single cell whole genome sequencing, BioTechniques 52(4):
1–3 (2012).
9 Rinzo Ukai et al., Transurethral resection in one piece (TURBO) is an
accurate tool for pathological staging of bladder tumor, Int. J. Urology 17:
708–14 (2010).
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Claim 22 under 35 U.S.C. § 103 as obvious based on Czerniak, Gui,
Doyle, Guo, and Ukai (Final Action 22); and
Claim 24 under 35 U.S.C. § 103 as obvious based on Czerniak, Gui,
and Doyle (Final Action 27).
OPINION
35 U.S.C. §§ 112(a), 112(b)
Claim 21 stands rejected under 35 U.S.C. § 112(a) on the basis that
the Specification does not support “the alternative use of hematoxylin or
eosin as a tissue stain,” and therefore the limitation of performing staining
with “either hematoxylin or eosin,” as recited in claim 21, amounts to new
matter. Final Action 4.
Claims 1, 15, 16, and 25 under 35 U.S.C. § 112(b) on the basis that
various limitations recited in these claims are indefinite. Final Action 5–6.10
Appellant acknowledges the rejections under § 112, but states that
“[t]he present appeal is directed to . . . the rejections under 35 U.S.C. §§ 102
and 103.” Appeal Br. 2.
Because Appellant has waived arguments directed to the rejections
under 35 U.S.C. §§ 112(a) and 112(b), we affirm them. See 37 C.F.R.
§ 41.37(c)(1)(iv) (The Appeal Brief must contain “[t]he arguments of
appellant with respect to each ground of rejection.”). See also Hyatt v.
Dudas, 551 F.3d 1307, 1314 (Fed. Cir. 2008) (“When the appellant fails to
contest a ground of rejection to the Board, . . . the PTO may affirm the

10 The Examiner does not point to any specific limitation of claim 15 as
being indefinite, so we assume that it is included in this rejection because it
depends from claim 1.
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rejection of the group of claims that the examiner rejected on that ground
without considering the merits of those rejections.”).
35 U.S.C. §§ 102(a)(1), 102(a)(2)
Claim 25 stands rejected as anticipated by Czerniak. The Examiner
finds that Czerniak discloses all of the limitations of claim 25, including
“isolating a tissue sample . . . (e.g. single cystectomy specimens comprising
normal urothelium, precursor intraurothelial conditions and invasive
carcinoma . . . ),” “selecting and isolating a selected tissue block from the
tissue sample . . . (e.g. an entire bladder mucosa from a bladder cancer
patient; e.g. paragraph [0344]; e.g. the bladder was opened longitudinally
along the anterior wall and pinned down to a paraffin block . . . ),” and
progressively sectioning the tissue block to obtain a plurality of
normal tissue sections, precursor lesion tissue sections, and
tumor tissue sections (e.g. separating the entire bladder mucosa
into 30–60 1x2 cm samples; e.g. paragraphs [0036], [0344]; e.g.
single histologic sections were prepared from each of the 1x2
cm tissue samples (i.e. larger sections); e.g. paragraph [0344],
wherein slicing one section from a tissue sample produces two
sections; see also Figures 27[ ]and 46AB illustrating that
sections of normal, precursor and tumor tissue were present).
Final Action 7.
Appellant argues that Czerniak does not disclose all of the limitations
of claim 25. Appeal Br. 12. Appellant argues that “Czerniak discloses
‘whole-organ histologic and genetic mapping.’ . . . The entire lining of the
bladder is stripped for analysis and mapping.” Id. at 13. Appellant argues
that
there is no disclosure of deliberately selecting a selected tissue
block that contains the normal, precursor, and tumor tissue
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associated with a single tumor. Moreover, there is no disclosure
of such a selection to allow for progressive sampling along an
uninterrupted continuum of adjacent tissue, through
individualized tumor tissue samples, precursor tissue that
surrounds this tumor tissue, and normal tissue that in turn
surrounds the precursor tissue. Czerniak, accordingly, does not
teach or suggest (a) selecting a selected tissue block consisting
of tumor, precursor, and normal tissue associated with a single
tumor, or (b) progressively sectioning such a tissue block, as
recited by the pending claims.
Id. at 14.
More specifically, Appellant argues that the Examiner cites “Figure
27 as disclosing progressive sectioning along normal, precursor, and tumor
tissue. . . . Figure 27 discloses samples derived from three cystectomies. The
histologic maps of Czerniak are not based on progressive sampling along a
continuum, nor is there any disclosure with reference with Figure 27
regarding such progressive sampling.” Appeal Br. 14. Thus, “[i]n light of the
above, Appellant respectfully submits that Czerniak fails to disclose
progressive sectioning along normal, precursor, and tumor tissue
associated with an individual tumor.” Id. at 16.
We agree with Appellant that the Examiner has not persuasively
shown that Czerniak anticipates claim 25. “Anticipation requires that all of
the claim elements and their limitations are shown in a single prior art
reference.” In re Skvorecz, 580 F.3d 1262, 1266 (Fed. Cir. 2009).
“[I]t is not enough that the prior art reference discloses part of the
claimed invention, which an ordinary artisan might supplement to make the
whole, or that it includes multiple, distinct teachings that the artisan might
somehow combine to achieve the claimed invention.” Net MoneyIN, Inc. v.
VeriSign, Inc., 545 F.3d 1359, 1371 (Fed. Cir. 2008). “[U]nless a reference
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discloses within the four corners of the document not only all of the
limitations claimed but also all of the limitations arranged or combined in the
same way as recited in the claim, it cannot be said to prove prior invention of
the thing claimed and, thus, cannot anticipate under 35 U.S.C. § 102.” Id.
Czerniak discloses “a method of detecting the genetic changes in a
subject related to the development and progression of cancers.” Czerniak
¶ 29. Czerniak states that its “methods . . . may be referred to as whole-organ
histologic and genetic mapping.” Id. ¶ 36.
Czerniak states that “[t]he simple anatomy and appropriate size of the
bladder permit histologic and genetic mapping studies of invasive cancer
and in situ preneoplastic conditions in the entire mucosa of cystectomy
specimens.” Czerniak ¶ 36.11 The Examiner interprets Czerniak’s
cystectomy specimen as the “tissue sample” that is isolated in the first step
of claim 25. Final Action 7.
Regarding the step of “selecting and isolating a selected tissue block
from the tissue sample” that is recited as the second step of claim 25, the
Examiner points to Czerniak’s disclosure that “[t]he bladder was opened
longitudinally along the anterior wall and pinned down to a paraffin block.”
Czerniak ¶ 344; see Ans. 7. The bladder that is opened and pinned down in
Czerniak’s procedure, however, is the same tissue that the Examiner points
to as the tissue sample from which a tissue block must be isolated according
to claim 25. The plain meaning of “isolating a selected tissue block from [a]

11 “A cystectomy is a surgery to remove all or part of the bladder: A radical
cystectomy removes the entire bladder. . . . A partial cystectomy removes
part of the bladder.” UVA Health, www.uvahealth.com/services/urology/
cystectomy (last accessed March 4, 2021).
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tissue sample” requires removing part (a “tissue block”) of the tissue from
the remainder of the tissue sample. Thus, manipulating the same sample
(e.g., by opening a bladder and pinning it down) is not “isolating a selected
tissue block from the tissue sample,” as required by claim 25.
In addition, claim 25 requires “progressively sectioning the tissue
block to obtain a plurality of normal tissue sections, precursor lesion tissue
sections, and tumor tissue sections.” With regard to this limitation, the
Examiner cites Czerniak’s disclosure that “the entire bladder mucosa was
separated into individual 1x2-cm samples and evaluated under a microscope
for histologic changes on frozen sections. For microscopic evaluation of
urothelium, a single histologic sections [sic] was prepared from each 1x2 cm
area.” Czerniak ¶ 344. See Final Action 7:
progressively sectioning the tissue block to obtain a plurality of
normal tissue sections, precursor lesion tissue sections, and
tumor tissue sections (e.g. separating the entire bladder mucosa
into 30–60 1x2 cm samples; e.g. paragraphs [0036], [0344]; e.g.
single histologic sections were prepared from each of the 1x2
cm tissue samples (i.e. larger sections); e.g. paragraph [0344],
wherein slicing one section from a tissue sample produces two
sections; see also Figures 27[ ]and 46AB illustrating that
sections of normal, precursor and tumor tissue were present);
In our view, the Examiner’s interpretation of the claim language—as
reading on the cited disclosure—is unreasonably broad, for two reasons.
First, as discussed above, the tissue that Czerniak describes as being
separated into 1 x 2 cm samples is the entire bladder mucosa. See Czerniak
¶ 344 (“[T]he entire bladder mucosa was separated into individual 1x2-cm
samples.”). The entire bladder mucosa is the “tissue sample” recited in claim
25. The separation of that sample into 1 x 2 cm samples therefore does not
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meet the claim limitation requiring “progressively sectioning [a] tissue
block” that was “isolat[ed] . . . from the tissue sample,” as required by claim
25.
The Examiner also appears to interpret claim 25’s “progressive
sectioning” as reading on Czerniak’s disclosure that “[f]or microscopic
evaluation of urothelium, a single histologic sections [sic] was prepared
from each 1x2 cm area.” Czerniak ¶ 344; see Final Action 7 (“slicing one
section from a tissue sample produces two sections”). This interpretation is
also unreasonably broad.
The plain meaning of “progressively sectioning” of a tissue block
requires more than cutting a single section from the tissue block;
“progressively sectioning” requires dividing the tissue block into multiple,
contiguous sections.12 Consistent with the plain meaning of the phrase,
Appellant’s Specification states that “[t]he tissue block may then be
sectioned into multiple vertical samples having approximately 5–10 μm
thickness.” Spec. 11:21–23. See also id. at 6:22 to 7:3 (“[M]ethods for
revealing natural histories of cancers . . . by systematically ‘walking
through’ individual tumors, performing extensive sampling and analysis. . . .
Embodiments of the present invention provide for progressive sampling of
tissues and analysis of data obtained from such progressive sampling.”).
In summary, the evidence does not support the Examiner’s findings
that Czerniak discloses a method that includes “selecting and isolating a
selected tissue block from the tissue sample [i.e., cystectomy specimen]” and

12 “progressively: gradually and steadily.” www.macmillandictionary.com/us/
dictionary/american/progressively (last accessed March 4, 2021).
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then “progressively sectioning the tissue block to obtain a plurality of
normal tissue sections, precursor lesion tissue sections, and tumor tissue
sections,” as required by claim 25. The Examiner therefore has not shown
that Czerniak “discloses within the four corners of the document not only all
of the limitations claimed but also all of the limitations arranged or
combined in the same way as recited in the claim.” Net MoneyIN, 545 F.3d
at 1371.
We reverse the rejection of claim 25 under 35 U.S.C. §§ 102(a)(1) and
102(a)(2) based on Czerniak.
35 U.S.C. § 103
Claims 1, 15–19, 21, 22, and 24 stand rejected under 35 U.S.C. § 103
as follows: Claims 1, 15, and 16 based on Czerniak, Gui, Tabor, Richards,
and Doyle (Final Action 9); claims 17–19 and 21 based on Czerniak, Gui,
Tabor, Richards, Doyle, Guo, and Ukai (id. at 14–15); claim 22 based on
Czerniak, Gui, Doyle, Guo, and Ukai (id. at 22); and claim 24 based on
Czerniak, Gui, and Doyle (id. at 27).
Independent claim 1, like claim 25, requires “selecting a selected
tissue block,” where the tissue block is a “tissue block of a tissue sample”
(as recited in the preamble), “removing the selected tissue block,” and
“progressively sectioning the selected tissue block into a plurality of
sections, the plurality of sections containing a series of sections.” See claim
1. Thus, claim 1 includes the same limitations that were discussed above
with regard to claim 25.
Independent claim 17 similarly recites “selecting and collecting . . .
[a] tissue block” consisting of a “portion” of a tumor and a “portion” of
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surrounding tissue from a “tissue” that includes a tumor and surrounding
tissue. Claim 17 also recites “progressively sectioning the tissue block into a
plurality of sections.” See Appeal Br. 26 (Claims Appendix).
Independent claim 22 similarly recites “selecting a selected tissue
block” and “removing the selected tissue block.” Claim 22 also recites
“progressively sectioning regions of the selected tissue block into a plurality
of sections.” See Appeal Br. 27–28 (Claims Appendix).
Independent claim 24 recites “isolating a tissue sample,” then
“selecting and isolating a selected tissue block from the tissue sample.”
Claim 24 also recites “progressively sectioning the tissue block to obtain a
plurality of tissue sections.” See Appeal Br. 29 (Claims Appendix).
As with the rejection for anticipation, the Examiner interprets
“selecting and removing a tissue block” (with respect to claim 1), “selecting
and collecting . . . [a] tissue block” (with respect to claim 17), “selecting and
removing a selected tissue block” (with respect to claim 22), and “selecting
and isolating a selected tissue block” (with respect to claim 24) to read on
Czerniak’s disclosure that “the bladder was opened longitudinally along the
anterior wall and pinned down to a paraffin block.” Final Action 10, 15, 22,
28.
In addition, the Examiner interprets the step—recited in each of
claims 1, 17, 22, and 24—of “progressively sectioning” a tissue block to
read on Czerniak’s disclosure that “single histologic sections were prepared
from each 1 x 2 cm tissue sample . . . wherein slicing one section from a
tissue sample produces two sections.” Final Action 10, 15, 22, 28.
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Thus, each of the rejections under 35 U.S.C. § 103 relies on the same
claim interpretation and the same disclosures in Czerniak that are discussed
above with regard to the rejection for anticipation. For the same reasons
discussed previously, we conclude that the Examiner’s interpretation of the
above-quoted limitations is unreasonably broad, and the cited passages in
Czerniak do not meet the claim limitations.
The Examiner has not pointed to any disclosure in Gui, Tabor,
Richards, Doyle, Guo, or Ukai that would make up for the deficiencies in
Czerniak. See Final Action 12–14, 17–19, 24–25, 30. We therefore reverse
all of the rejections under 35 U.S.C. § 103.
CONCLUSION
The rejections under 35 U.S.C. §§ 112(a) and 112(b) are affirmed.
The rejection under 35 U.S.C. §§ 102(a)(1) and 102(a)(2), and all of the
rejections under 35 U.S.C. § 103, are reversed.
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DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
21 112(a) Written Description 21
1, 15, 16,
25
112(b) Indefiniteness 1, 15, 16,
25

25 102(a)(1),
102(a)(2)
Czerniak 25
1, 15, 16 103 Czerniak, Gui, Tabor,
Richards, Doyle
1, 15, 16
17–19, 21 103 Czerniak, Gui, Tabor,
Richards, Doyle, Guo,
Ukai
17–19, 21
22 103 Czerniak, Gui, Doyle,
Guo, Ukai
22
24 103 Czerniak, Gui, Doyle 24
Overall
Outcome
1, 15, 16,
21, 25
17–19, 22,
24

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 IN PART