Ex Parte Kamath et al

Patent Trial and Appeal Board

Oct 31, 2018

13459958 (P.T.A.B. Oct. 31, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/459,958 04/30/2012
6147 7590 11/02/2018
GENERAL ELECTRIC COMPANY
GPO/GLOBAL RESEARCH
901 Main Avenue
3rd Floor
Norwalk, CT 06851
FIRST NAMED INVENTOR
Vidya Pundalik Karnath
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
251547-1 3840
EXAMINER
VALDEZ,PATRICKF
ART UNIT PAPER NUMBER
2611
NOTIFICATION DATE DELIVERY MODE
11/02/2018 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):
haeckl@ge.com
gpo.mail@ge.com
Lori.e.rooney@ge.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte VIDYA PUNDALIK KAMATH and
BRION DARYL SARACHAN
Appeal2017-004935
Application 13/459,958 1
Technology Center 2600
Before DONALD E. ADAMS, MICHAEL J. FITZPATRICK, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for displaying expression levels of one or more biomarkers in a field of view
of a biological tissue, which have been rejected as obvious. 2 We have
jurisdiction under 35 U.S.C. § 6(b ).
1 Appellants identify the real party in interest as the General Electric
Company. (Appeal Br. 2.)
2 We note that the subject matter of this application is similar to that of
Application 13/460,100 (Appeal Br. 2), which is the subject of Appeal No.
2017-004722, the claims of which were rejected as being directed to patent
ineligible subject matter and as obvious. In a decision issued simultaneously
herewith, we affirm the rejections of the claims on appeal in Appeal No.
2017-004 722, as being both directed to patent ineligible subject matter and
as obvious.
Appeal2017-004935
Application 13/459,958
We affirm.
STATEMENT OF THE CASE
"Examination of tissue specimens that have been treated to reveal the
expression of biomarkers is a known tool for biological research and clinical
studies." (Spec. 1.) "Commonly the treated tissue is examined with digital
imaging and the level of different signals emanating from different
biomarkers can consequently be readily quantified." (Id.)
A technique has further been developed which allows testing a
given tissue specimen for the expression of numerous
biomarkers. Generally, this technique involves staining the
specimen with a fluorophore labeled probe to generate a signal
for one or more probe bound biomarkers, chemically bleaching
these signals, and re-staining the specimen to generate signals
for some further biomarkers.
(Id.) "Digital images of the specimen are collected after each staining step."
(Id.) The claimed invention "leverage[ s] multiplexed biomarker images that
are generated through known techniques, such as a staining-bleaching-
restaining" (id. at 13), "allow[ing] users [of a graphical interface] to review
complex image and analysis data corresponding to multiple patients,
multiple tissue fields-of-view and/or multiple biomarker data in a structured
yet flexible and user-friendly manner" (id. at 19--20).
Claims 1-25 are on appeal. Claim 1 is representative and reads as
follows:
1. A computer-implemented method for displaying
expression levels of one or more biomarkers in a field of view
of a biological tissue, the method comprising:
rendering a graphical user interface on a visual display
device;
rendering, on the graphical user interface, a field of view
selection component allowing a user to select a field of view
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within a set of registered multiplexed biomarker images
capturing expression of a plurality of biomarkers in the same
sample of biological tissue, wherein the multiplexed biomarker
images are generated from the same sample of the biological
tissue by staining, bleaching, and restaining the same sample of
biological tissue;
receiving user input, at the field of view selection
component of the graphical user interface, selecting a respective
field of view common to each of the multiplexed cells and
corresponding to a subset of cells within the multiplexed
biomarker images;
receiving user input, at the graphical user interface,
selecting a first biomarker, assigning a first color to represent
expression levels of the first biomarker, selecting a second
biomarker, and assigning a second color to represent expression
levels of the second biomarker, wherein the first color and
second color are computer-generated and are independent of a
stain color used to stain one or both of the first biomarker or the
second biomarker;
in response to the user input, rendering in an overlaid
manner on the graphical user interface, a first image of the
selected field of view corresponding to the subset of cells in
which the expression levels of the first biomarker are
represented on a pixel-by-pixel basis using different intensities
of the first color to correspond to different expression levels of
the first biomarker, and a second image of the selected field of
view corresponding to the subset of cells in which the
expression levels of the second biomarker are represented on a
pixel-by-pixel basis using different intensities of the second
color to correspond to different expression levels of the second
biomarker; and
sending instructions to store, on a storage device, the
selected first color in association with the first biomarker to
indicate that expression levels of the first biomarker are to be
represented in the first color, and the selected second color
setting in association with the second biomarker to indicate that
expression levels of the second biomarker are to be represented
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in the second selected color; such that the selected first color
will be automatically selected in response to receiving user
input selecting the first biomarker and the selected second color
will be automatically selected in response to receiving user
input selecting the second biomarker.
(Appeal Br. 33-34.)
The following grounds of rejection by the Examiner are before us on
review:
Claims 1, 11, 12, 18, and 20-25 under 35 U.S.C. § I03(a) as
unpatentable over Younes, 3 imageJ, 4 Sarachan, 5 Kincaid, 6 and Kapelner. 7
Claim 2 under 35 U.S.C. § I03(a) as unpatentable over Younes,
imageJ, Sarachan, Kincaid, Kapelner, and Mayer. 8
Claim 3 under 35 U.S.C. § I03(a) as unpatentable over Younes,
imageJ, Sarachan, Kincaid, Kapelner, and Weybrew. 9
Claim 4 under 35 U.S.C. § I03(a) as unpatentable over Younes,
imageJ, Sarachan, Kincaid, Kapelner, Mayer, and Weybrew.
3 Younes et al., US 8,693,743 Bl, issued Apr. 8, 2014.
4 Tiago A. Ferreira & Wayne Rasband, The ImageJ User Guide Version
1.43 (2010), https://www.iib.uam.es/portal/documents/75233/75263/
Image+ J+user-guide.pdf/2ef41251-249e-4f86-a8c7-bfdl 792988d3
("imageJ").
5 Sarachan et al., US 2011/0091091 Al, published Apr. 21, 2011.
6 Kincaid, US 2010/0128988 Al, published May 27, 2010.
7 Adam Kapelner et al., Gemldent 1.0 user manual, GEMIDENT 2-26 (2007),
https://github.com/kapelner/Gemldent/raw/master/GemManualv2.pdf
("Kapelner").
8 Mayer, US 2007/0128899 Al, published June 7, 2007.
9 Weybrew et al., US 2008/0143737 Al, published June 19, 2008.
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Claims 5 and 6 under 35 U.S.C. § I03(a) as unpatentable over
Younes, imageJ, Sarachan, Kincaid, Kapelner, and Holmes. 10
Claims 7 and 8 under 35 U.S.C. § I03(a) as unpatentable over
Younes, imageJ, Sarachan, Kincaid, Kapelner, and Wang. 11
Claims 9 and 10 under 35 U.S.C. § I03(a) as unpatentable over
Younes, imageJ, Sarachan, Kincaid, Kapelner, and Al-Kofahi. 12
Claims 13-16 under 35 U.S.C. § I03(a) as unpatentable over Younes,
imageJ, Sarachan, Kincaid, Kapelner, and Bousamra. 13
Claim 17 under 35 U.S.C. § I03(a) as unpatentable over Younes,
imageJ, Sarachan, Kincaid, Kapelner, and Carpenter. 14
Claim 19 under 35 U.S.C. § I03(a) as unpatentable over Younes,
imageJ, Sarachan, Kincaid, Kapelner, and Jones. 15
DISCUSSION
Obviousness
The Examiner finds that Younes teaches a computer-implemented
method for displaying expression levels of one or more biomarkers in a
10 Susan Holmes et al., An Interactive Java Statistical Image Segmentation
System: Gemident, 30(10) J. of Statistical Software 1-20 (2009).
11 Quanli Wang et al., Image segmentation and dynamic lineage analysis in
single-cell fluorescence microscopy, 77(1) Cytometry A 101-110, (2010).
12 Yousef Al-Kofahi et al., Cell-based quantification of molecular
biomarkers in histopathology specimens, 59 Histopathology 40-54 (2011).
13 Bousamra et al., US 2012/0286953 Al, published Nov. 15, 2012.
14 Anne E. Carpenter & Thouis R. Jones, CellProfilerâ„¢ cell image analysis
software, CellProfiler TM (2008), http://d1zymp9ayga15t.cloudfront.net
/ content/Documentation/ cp l_manual_971 7. pdf.
15 Thouis R. Jones et al., Cell Profiler Analyst: data exploration and
analysis software for complex image-based screens, 9:482 BMC
Bioinformatics 1-16 (2008).
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biological tissue sample in a field of view using a graphical user interface
(GUI). (Final Action 3---6.) The Examiner explains that Younes discloses
rendering two images from two thin layers that are proximate each other in a
tissue sample and have been stained for different biomarkers and overlaying
them to observe co-expression ofbiomarkers on a per-cell basis. (Ans. 5-7.)
The Examiner notes that Younes teaches that the co-expression analysis can
be meaningfully performed to the extent that the single biomarker
expression "a" and single biomarker expression "b" intersect the same cell.
(Id. at 7.) Younes further teaches observing in a selected field of view the
different intensities of the biomarkers, which correspond with expression
level of the biomarker. (Id. at 5---6.) The Examiner acknowledges that
Younes does not teach the multiplexed biomarker images are generated from
the same sample of the biological tissue by staining, bleaching, and
restaining (Final Action 7) or expressly teach that the field of view selection
component provides for a user to select a field of view within a set of
registered multiplexed images or that the field of view selection component
of the GUI receives user input selecting a field of view that is common to
each of the multiplexed images (id. at 6). The Examiner contends that these
features would have been obvious to one of ordinary skill in the art in light
of the teachings of Sarachan and imageJ. (Id. at 6-7.) The Examiner
explains that imageJ explicitly "discloses the well-known concepts of
'rendering in an overlaid manner a first image and a second image on a
graphical user interface."' (Ans. 6.) ImageJ discloses providing a set of
registered images in a stack and allowing a user to display a selected field of
view within the stacked images. (Final Action 6.) The Examiner contends
that the implicit selection of an image from a stack in Younes would have
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been obvious in light of the well-known use of such technology and would
provide a user with a quick and efficient cycle through the stack of images to
select a particular one. (Id.)
With respect to providing a set of images in which a single tissue
sample has been stained, imaged, bleached, and then restained and imaged to
provide the set of images, the Examiner notes that Sarachan teaches such a
process was known in the art. (Final Action 7.) Sarachan explains that in
the process the images are registered to the sample so as to allow the images
to be grouped and sequentially overlaid for analysis. (Id.) The Examiner
explains that it would have been obvious to one of ordinary skill in the art to
use Sarachan's staining, bleaching, and restaining methodology to generate
the images to be analyzed according to the Younes method. (Id.) The
Examiner notes that one of ordinary skill in the art would have been
motivated to use that process of image collection for a biological tissue
sample in order to "to make the most efficient use of biological tissue
samples that may be rare and/or extremely difficult to obtain." (Id.)
The Examiner relies on Kincaid's disclosure for the obviousness of
assigning colors to represent expression levels of a biomarker to be applied
virtually in the field of cellular images viewed digitally. (Final Action 7-8.)
The Examiner concludes that it would have been obvious to adopt this in the
Younes process in order to provide for visually easy to distinguish attributes
in the digital per cell biomarker analysis described by Younes as modified
by Sarachan. (Id. at 9.) The Examiner relies on Kapelner for the
obviousness of sending the instructions to store the selected color
associations as recited in the claim. (Id.) The Examiner explains that
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providing such a feature would have been obvious to one of ordinary skill in
the art to improve the user convenience of the GUI. (Id. at 10.)
We agree with the Examiner's factual findings and conclusion that
claim 1 would have been obvious to one of ordinary skill in the art at the
time the invention was made.
Appellants' disagreement with the Examiner's rejection is based on
unwarranted narrow interpretations of the references. Appellants contend
that Younes teaches away from using the Sarachan staining, bleaching, and
restaining process. According to Appellants, this is so because (1) Younes is
directed to obtaining expression profiles from different tissue samples each
stained once with a single biomarker, which images thereof are stacked and
analyzed to obtain "some degree" of co-expression profile per-cell (Reply
Br. 3---6; see also Appeal Br. 16) and (2) Younes states:
"[i]n one or more embodiments of the invention, inherent error
associated with tagging multiple biomarkers on the same
sample is eliminated or minimized by first tagging biomarkers
separately on separate slices, and then performing the co-
expression analysis on a per-cell basis." Younes col. 4, lines
49-53.
(Reply Br. 7; Appeal Br. 25.) We do not find Appellants' argument
persuasive for the reasons explained by the Examiner. In particular, we
agree with the Examiner that Younes does not teach away from the Sarachan
process for collecting images from a single sample for analysis where that
single sample has been stained for biomarkers, imaged, bleached and then
restained and imaged again. (Ans. 12.) It is certainly true that Younes
teaches there is inherent error in tagging multiple biomarkers on the same
sample, but such a concern is likely because multiple biomarker stains on the
same tissue sample at the same time before imaging could interfere with one
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another. (Id.) Younes' solution to avoid the interference problem is to stain
different slices differently and then to stack those slices and analyze whether
the multiple stains are in one cell or not. But Younes does not counsel
against using another solution that would avoid biomarker interference.
Such a process is described by Sarachan.
In addition, Younes explains that the different stains on different
slices process is only useful in a per-cell biomarker analysis when the two
slices stained have intersected the same cell. (Younes 4:37--48, 7:25-33,
8:36-60, 11-13 ( describing generally cell-based expression analysis in an
aligned stack), 14--15 (describing a specific example of cell-based
expression analysis in an aligned stack).) Younes describes an involved
process to perform the requisite alignment when different samples are
stained to ensure the analysis of the different tissue samples provides for a
biomarker analysis on a per-cell basis. (See, e.g., Younes 11-15.) As the
Examiner explains, the Sarachan process ensures a simpler per-cell analysis
for expression ofbiomarker a and b because the same tissue sample with
different staining is imaged, and thus, the "complex, computationally
intensive steps requiring the registration (i.e. warping and/or alignment
calculations to align spatial locations of cellular structures) of tissue sample
images would not be required." (Ans. 12.) We agree, and do not find
persuasive Appellants' argument that "[t]here is no indication that staining
the same sample with multiple biomarkers would in any way improve the
co-expression analysis taught in the Younes reference" (Reply Br. 9).
Thus, while Younes does not teach a staining, bleaching, staining
process, we agree with the Examiner that one of ordinary skill in the art
would have found it obvious to modify the Younes process to include this
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well-known image collection process described in Sarachan to analyze
biomarkers on a per-cell basis.
Also, Appellants contend that Younes cannot be modified in the way
the Examiner suggests because the "goal" of the Younes reference "is
statistical co-expression profiles at the per-cell level." (Reply Br. 6; Appeal
Br. 17, 20.) While Younes does contemplate statistical profiles ( e.g.,
Younes 13:6-17, 13:30-50), Younes also teaches visually evaluating
biomarkers in individual cells (e.g., id. at 13:50-65 (
the above described categories of expression may be color
coded so that cells within each category are colored on the
captured/processed images enabling the operator to examine
individual cells in regard to their physical location within the
tissue sample. . . . In one particular embodiment of this color
correlation, the displayed colors could be user controlled such
that certain combinations or expressions can be turned on and
off.
Further, in one or more embodiments of the invention, a
user may interactively select different combinations of
biomarkers of interest. The display may dynamically update
the associated spatial rendering of correlated cells. The spatial
rendering may use different colors to convey information in an
effective manner. Furthermore, selected biomarker expression
information may be displayed ... on the captured image
directly ...
the display may allow the operator to select the biomarker that
mediates action of the least toxic and most effective drug, then
selecting all cells that are negative and to indicate what
percentage of cells are positive for the target for the next drug
of choice.))
Thus, even if Younes is generally "directed to generating a statistical report"
and "a modification of the teachings of the Younes reference is unnecessary"
in that context (Reply Br. 9), Younes, nevertheless, can reasonably be
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understood to describe visualizing biomarkers on images in a display on a
per-cell basis. And in that context, we do not find Appellants' contentions
of the modification that the Examiner urges would have been obvious to
have been considered "unnecessary."
Appellants contend that Younes "does not teach rendering images in
an overlaid manner." (Reply Br. 11; see also generally Appeal Br. 16-20.)
We disagree. As the Examiner pointed out (Final Action 5; Ans. 5), Younes
states:
FIG. 9 shows how the processing may be performed to stack or
overlay the images on each other to identify the co-expression
relationships in accordance with one or more embodiments of
the invention
(Younes 8:57-60);
During the computerized analysis, the software overlays the
tissue sample layers to identify the co-expression relationship
between biomarker A and biomarker B
(id. at 15:22-25);
The co-expression results may be displayed in many different
forms. . . . Further, the above described categories of
expression may be color coded so that cells within each
category are colored on the captured/processed images enabling
the operator to examine individual cells in regard to their
physical location within the tissue sample
(id. at 13:30-55); and
The non-transitory computer readable medium of claim 9,
wherein the biomarker co-expression profile is displayed as a
graphical image.
(Id. at 20:37-39 (claim 19).) Thus, we agree with the Examiner that Younes
can reasonably be understood to describe overlaying images to visually
observe the biomarkers.
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Moreover, as the Examiner also noted, even if Younes did not
expressly teach overlaying the images, such is a well-known concept as
described in imageJ, that one of ordinary skill in the art would have found
obvious to incorporate in Younes to provide for the visual display of the co-
expression profile that Younes teaches is desirable. (Ans. 6.) Such is also
manifestly obvious from the teachings of Sarachan, which indicates that the
ability to overlay images of the same fields of view having different
biomarkers allows for "biologists and oncologists to provide cytological
context to biomarker expression." (Sarachan ,r,r 9, 10, 50, 51, 55, 56.)
Consequently, for the reasons discussed above, we sustain the
Examiner's rejection of claim 1 under 35 U.S.C. § 103(a) as being obvious
over Younes, imageJ, Sarachan, Kincaid, and Kapelner.
Claims 11, 12, 18, and 20-25 have not been argued separately and,
therefore, fall with claim 1. 37 C.F.R. § 4I.37(c)(l)(iv).
Additional Grounds of Rejection
Appellants' arguments as to the Examiner's remaining rejections
relying on additional references, enumerated 2-10 by Appellants, rely solely
on the arguments made regarding claim 1. (See Appeal Br. 27-31.) For the
reasons discussed with respect to claim 1, we sustain the Examiner's
rejection with respect to each the additional grounds of rejection 2-10 made
by the Examiner.
SUMMARY
We affirm the rejection of claims 1, 11, 12, 18, and 20-25 under 35
U.S.C. § 103(a) as unpatentable over Younes, imageJ, Sarachan, Kincaid,
and Kapelner.
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We affirm the rejection of claim 2 under 35 U.S.C. § 103(a) as
unpatentable over Younes, imageJ, Sarachan, Kincaid, Kapelner, and Mayer.
We affirm the rejection of claim 3 under 35 U.S.C. § 103(a) as
unpatentable over Younes, imageJ, Sarachan, Kincaid, Kapelner, and
Weybrew.
We affirm the rejection of claim 4 under 35 U.S.C. § 103(a) as
unpatentable over Younes, imageJ, Sarachan, Kincaid, Kapelner, Mayer, and
Weybrew.
We affirm the rejection of claims 5 and 6 under 35 U.S.C. § 103(a) as
unpatentable over Younes, imageJ, Sarachan, Kincaid, Kapelner, and
Holmes.
We affirm the rejection of claims 7 and 8 under 35 U.S.C. § 103(a) as
unpatentable over Younes, imageJ, Sarachan, Kincaid, Kapelner, and Wang.
We affirm the rejection of claims 9 and 10 under 35 U.S.C. § 103(a)
as unpatentable over Younes, imageJ, Sarachan, Kincaid, Kapelner, and Al-
Kofahi.
We affirm the rejection of claims 13-16 under 35 U.S.C. § 103(a) as
unpatentable over Younes, imageJ, Sarachan, Kincaid, Kapelner, and
Bousamra.
We affirm the rejection of claim 17 under 35 U.S.C. § 103(a) as
unpatentable over Younes, imageJ, Sarachan, Kincaid, Kapelner, and
Carpenter.
We affirm the rejection of claim 19 under 35 U.S.C. § 103(a) as
unpatentable over Younes, imageJ, Sarachan, Kincaid, Kapelner, and Jones.
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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
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