Ex Parte McCulloch

Patent Trial and Appeal Board

Oct 31, 2018

13252078 (P.T.A.B. Oct. 31, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/252,078 10/03/2011
6147 7590 11/02/2018
GENERAL ELECTRIC COMPANY
GPO/GLOBAL RESEARCH
901 Main Avenue
3rd Floor
Norwalk, CT 06851
FIRST NAMED INVENTOR
Colin Craig McCulloch
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.
250530-4/120718-00504 6421
EXAMINER
HARWARD, SOREN T
ART UNIT PAPER NUMBER
1631
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 COLIN CRAIG McCULLOCH
Appeal2017-002258
Application 13/252,078 1
Technology Center 1600
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
of analyzing tissue features, which have been rejected as being directed to
patent ineligible subject matter and as obvious. 2 We have jurisdiction under
35 U.S.C. § 6(b).
1 Appellant identifies 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 13/252,069, which is the subject of Appeal No. 2017-008682
and of Application 13/252,072, which was the subject of Appeal No. 2016-
001180. In Appeal No. 2016-001180, the Board affirmed the Examiner's
rejection of the claims as being both directed to patent ineligible subject
matter and as obvious. In a decision issued simultaneously herewith, we
affirm the rejection of the claims on appeal in Appeal No. 2017-008682, as
being directed to patent ineligible subject matter.
Appeal2017-002258
Application 13/252,078
We affirm.
STATEMENT OF THE CASE
Studying tissue specimens using labelled antibodies or antibody
surrogates as biomarkers is well known, including testing "for the expression
of numerous biomarkers." (Spec. ,r,r 3, 5.) "The techniques of tissue
treatment and examination have been refined so that the level of expression
of a given biomarker in a particular cell or even a compartment of the given
cell such as the nucleus, cytoplasm or membrane can be quantitatively
determined." (Id. ,r 4.) "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.) Appellant's
Specification explains that
[ t ]he invention relates generally to analyzing and visualizing the
expression of biomarkers in individual cells, wherein the cells
are examined in situ in their tissue of origin, to identify and
understand patterns of expression that have an association with
a diagnosis, a prognosis, or a response to treatment of a
condition or a disease.
(Spec. ,r 2.)
Claims 1-13, 15, 18-33, 35, 38--44, and 47 are on appeal. Claim 1 is
representative and reads as follows:
1. A method of analyzing tissue features based on multiplexed
biometric image data comprising:
storing a data set using a storage device, the data set
comprising cell profile data comprising multiplexed biometric
images capturing the expression of a plurality of biomarkers
with respect to a plurality of fields of view, wherein said
plurality of biomarkers comprises a plurality of morphological
biomarkers and a plurality of non-morphological biomarkers,
and in which individual cells are delineated and segmented into
compartments, wherein
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the cell profile data is generated from a plurality of tissue
samples drawn from a cohort of patients having a commonality;
and
the data set further comprising an association of the cell
profile data with at least one piece of meta-information
including a field of view level assessment or a patient-level
assessment related to the commonality;
calculating using a processor at least one cell feature
based on the cell's expression of each of the plurality of
biomarkers, wherein the at least one cell feature comprises a
ratio based on a respective concentration level of each
biomarker between cell compartments for a respective cell;
calculating using the processor a first and second
moment for each of the plurality of fields of view from each of
the at least one cell feature wherein the first moment is mean
and wherein the second moment is standard deviation;
grouping using the processor the field of view level
assessments and examining the plurality of combinations of
attributes for an association with the grouped field of view level
assessment related to the commonality;
examining using the processor a plurality of
combinations of attributes comprising the calculated first and
second moments for an association with the at least one piece of
meta-information including the field of view level assessment
or the patient-level assessment related to the commonality;
ordering the plurality of attributes according to a variable
importance of the plurality of attributes;
selecting using the processor one of the plurality of
combinations of attributes comprising a predictive combination
of attributes based on a comparison of the performance of at
least one model of the plurality of combinations of attributes
and the variable importance of the plurality of attributes,
wherein the predictive combination eliminates a portion of the
plurality of attributes based on the variable importance and the
at least one piece of meta-information including a field of view
level assessment or a patient-level assessment related to the
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cohort of patients based on a performance metric of a pre-
defined threshold; and
providing an indication ofi3J related to the tissue samples.
(Appeal Br. 16-17.)
The following grounds of rejection by the Examiner are before us on
review:
Claims 1-13, 15, 18-33, 35, 38--44, and 47 under 35 U.S.C. § 101 as
being directed to non-statutory subject matter.
Claims 1-13, 15, 18-33, 35, 38--44, and 47 under 35 U.S.C. § I03(a)
pre-AIA as being unpatentable over Hunter, 4 Linke, 5 CRC, 6 and Pudil. 7
3 The claim appears to be missing one or more terms. It is not clear what
indication is being provided. Nevertheless, it appears that the Examiner
treated this last limitation as being directed to providing an indication of a
diagnosis, a prognosis, or a response to treatment of a condition or a disease.
See Final Action 6-7 (noting in the art rejection of the claims that Hunter
and Linke are both directed to clinical diagnoses based on tissue sample
analyses). We analyze the claims as if this were the limitation.
4 Hunter et al., US 2008/0144895 Al, published June 19, 2008.
5 Linke et al., US 2006/0275844 Al, published Dec. 7, 2006.
6 CRC Press LLC, Standard Mathematical Tables and Formulae (Daniel
Z willinger (ed.) 1996).
7 P. Pudil et al., Floating Search Methods In Feature Selection, Pattern
Recognition Letters, 1119-25 (1994).
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DISCUSSION
I
Patent Ineligible Subject Matter
The Examiner finds that the method of claim 1 and system of claim 21
are claims directed to an abstract idea that fail to meet the standard for
statutory eligibility because their central concept is the diagnostic data
processing algorithm that correlates cellular features with patient data.
(Final Action 3--4.) The Examiner notes that the claims recite using generic
structures that perform well-understood, routine, and conventional functions
by those of skill in the art prior to the invention. (Id.)
We agree with the Examiner's conclusion that the method of claim 1
and system of claim 21 are patent ineligible abstract ideas.
Section 101 provides that "[ w ]hoever invents or discovers any new
and useful process, machine, manufacture, or composition of matter, or any
new and useful improvement thereof, may obtain a patent therefor." 35
U.S.C. § 101. In Alice, the Supreme Court articulated a two-step test for
examining patent eligibility under § 101. Alice Corp. Pty. Ltd. v. CLS Bank
Int'!, 134 S. Ct. 2347 (2014). Step one involves determining whether the
claims at issue are directed to a patent ineligible concept, and step two,
reached only if the determination in step one is yes, considers the elements
of each claim both individually and "as an ordered combination" to
determine whether additional elements "transform the nature of the claim"
into a patent eligible application. Id. at 2355 (internal quotation marks and
citation omitted).
Appellant disagrees with the Examiner's characterization of the
claims, noting that they "are directed to processing of image data of
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multiplexed biometric ... [data]" as opposed to "an algorithm that correlates
cellular features with patient data." (Appeal Br. 9.) Appellant contends that
in light of this, the Examiner's rejection is in error because "image
processing claims have been found to be patentable under§ 101 ... [and] do
no fall within a judicial exception." (Id.) We do not find Appellant's
argument persuasive.
Appellant's characterization of the claims under step one of Alice fails
to examine the claims as a whole. See SAP Am., Inc. v. Investpic, LLC, 898
F.3d 1161, 1167 (Fed. Cir. 2018). While it is true that Appellant's claim 1
involves an examination of image data, the steps involved concern
manipulating stored data and analyzing it to identify a feature contained
within it without more. In particular, the steps require storing the images,
using a computer processor to extract information from the stored data
concerning cellular features that are within the data set and to correlate the
information using mathematical concepts, using the processor to examine
the newly correlated information and to group it, and then using the
processor to reassess the information using a pre-defined threshold and
mathematical modeling, and providing some "indication ... related to the
tissue samples." The system recited in claim 21 is similar. In addition to
reciting a process that performs the data manipulation and analysis noted
above, it recites a camera device that captures the multiplexed biometric
images that are then stored and a visual display device. As the Examiner
explained, when considered as a whole, the method and system both concern
a diagnostic data processing algorithm that manipulates stored data for
identification purposes.
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"The Supreme Court has not 'delimit[ed] the precise contours of the
'abstract ideas' category."' Content Extraction & Transmission LLC v.
Wells Fargo Bank, Nat'! Ass 'n, 776 F.3d 1343, 1346 (Fed. Cir.
2014) (quoting Alice, 134 S. Ct. at 2357). However, our reviewing Court
has explained that "[i]nformation as such is an intangible," and thus,
abstract, and "collecting information, including when limited to particular
content (which does not change its character as information), [i]s within the
realm of abstract ideas." Electric Power Group, LLC v. Alstom S.A., 830
F.3d 1350, 1353 (Fed. Cir. 2016) (citing cases). So, too, is "analyzing
information ... by mathematical algorithms, without more." Id. at 1354
(citing cases, including Parker v. Flook, 437 U.S. 584 (1978), and
Gottschalkv. Benson, 409 U.S. 63 (1972)). Claim 1 is directed at abstract
ideas under those principles.
The system for analyzing tissue features of claim 21 is as well. The
focus of claim 21 is not to any improved display device, camera, or storage
device, nor is it directed to an improvement in the way computers work.
Rather, it, too, is focused on the selection and mathematical analysis of
information, which is followed by display of results. Thus, the focus of
claim 21 is not on an improvement in computers as tools, but on abstract
ideas that use computers as tools. See SAP, 898 F.3d at 1167---68 (noting that
claims to an improvement in a mathematical technique with no improved
display mechanism were abstract as compared to those in McRO, Inc. v.
Bandai Namco Games America Inc., 837 F.3d 1299 (Fed. Cir. 2016) which
included a "claimed improvement ... [as] to how the physical display
operated (to produce better quality images)" in addition to having
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"specificity required to transform a claim from one claiming only a result to
one claiming a way of achieving it").
Appellant's general argument that image processing claims as a class
do not fall within a judicial exception (Appeal Br. 9) is simply incorrect.
While it is true that a process involving image analysis via computers was
found patent eligible in Research Corp. Tech. v. Microsoft Corp., 627 F.3d
859 (Fed. Cir. 2010), the claims at issue in that case involved an
improvement to computer technologies ( as compared to the prior art, the
"inventive mask produce[ d] higher quality halftone images while using less
processor power and memory space," Research Corp., 627 F.3d at 865, and
the method, "which required the manipulation of computer data structures
(the pixels of a digital image and the mask) and the output of a modified
computer data structure ( the halftoned image), was dependent upon the
computer components required to perform it." Bancorp Servs., L.L. C. v. Sun
Life Assur. Co. of Canada (US.), 687 F.3d 1266, 1279 (Fed. Cir. 2012)
( distinguishing claims on appeal from those in Research Corp). The claims
were not deemed patent eligible simply because they were an improvement
in the processing of information (Reply Br. 2), which is what the present
claims are alleged to achieve. Collecting and processing information
without more is within the realm of abstract ideas, as explained above.
The claims at issue here, while they may improve the processing of
the multiplexed images, do not improve computer technologies, see, e.g.,
McRO, 837 F.3d 1299 (improvement in how a physical display operated),
Finjan, Inc. v. Blue Coat Sys., Inc., 879 F.3d 1299, 1305 (Fed. Cir. 2018)
( claims were directed to employing a new kind of file that enables a
computer security system to do things it could not do before), or recite steps
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or rules that solve a technological problem in the use of computers in a
particular way, see, e.g., Enfish, LLC v. Microsoft Corp., 822 F.3d 1327,
1335-36 (Fed. Cir. 2016); BASCOM Glob. Internet Servs., Inc. v. AT&T
Mobility LLC, 827 F.3d 1341, 1348--49 (Fed. Cir. 2016)). Rather, as
discussed above, they merely use computers as a tool to manipulate stored
data and analyze it without more.
Consequently, we agree with the Examiner that the method and
system claims at issue are directed to an abstract idea: analyzing collected
data using various mathematical concepts, i.e., algorithms, and organizing it
into a new form.
We additionally, agree with the Examiner that the limitations of the
claim that are in addition to the abstract idea "amount to no more than mere
instructions to implement the algorithm on a generic computer ( as in claim 1
and its dependents), or generic computer or electronic structures that
perform well-understood, routine, and conventional activities." (Final
Action 3.) As explained in Appellant's Specification "[ e ]xamination of
tissue specimens that have been treated to reveal the expression of
biomarkers is a known tool for biological research and clinical studies."
(Spec. ,r 3 .) "Commonly the treated tissue is examined with digital imaging
and the level of different signals emanating from different biomarkers" is
"readily quantified" including by examining multiple images and to identify
patterns. (Id. ,r,r 4--14.) The known prior art processes include using
computers to assist in storing collected information about the tissue
specimen including the segmentation of "individual cell units and their
subcellular compartments (including membrane, cytoplasm and nucleus)"
(Id. ,r 9), "grouping ... cells together which have similar biomarker
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expression attributes" (Id. ,r,r 10-11), which grouping "could be examined to
identify any cell attribute which is associated with the diagnoses or
prognoses of a given condition or disease or with the response to a given
therapy for a given condition or disease," as well as "generat[ing] various
expression profiles that are then overlaid on an image of the tissue of
interest." (Id. ,r,r 7, 11.)
In its Appeal Brief, Appellant does not contest this, but rather
contends that the Examiner erred by not conducting a "Streamlined
Analysis." (Appeal Br. 9-11.) According to Appellant, if such an analysis
had been conducted, it would be seen that "the claims do not tie up an entire
judicial exception" because "there is no attempt to tie up an entire algorithm
for general use" (Appeal Br. 9-11), as the claims are "within the context of
analysis of biological images" (Reply Br. 4
( claims 1 and 21 recite the use of a particular type of data,
multiplexed biometric images that capture the expression of
biomarkers. The claims at issue are within the context of
analysis of biological images and the recited use is clearly
defined and limited in scope. As such, there is no attempt to tie
up an entire algorithm for general use.)).
We do not find Appellant's argument persuasive. The question of
import under a section 101 analysis is whether the Examiner properly made
a determination as to whether the claims were directed to a judicial
exception, e.g., an abstract idea, and a determination as to whether there are
additional limitations considered individually and together that establish the
claims are directed to something significantly more than the judicial
exception. We find the Examiner carried out an appropriate analysis of the
claims under 35 U.S.C. § 101.
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As to Appellant's argument that the claims are limited to a particular
field in which to apply the algorithm, we note that "merely limiting the field
of use of the abstract idea to a particular ... environment does not render the
claims any less abstract." Affinity Labs of Tex., LLC v. DIRECTV, LLC, 838
F.3d 1253, 1259 (Fed. Cir. 2016).
Without additional limitations, a process that employs
mathematical algorithms to manipulate existing information to
generate additional information is not patent eligible. "If a claim
is directed essentially to a method of calculating, using a
mathematical formula, even if the solution is for a specific
purpose, the claimed method is nonstatutory." Parker v.
Flook, 437 U.S. 584, 595 ... (1978) (internal quotations
omitted).
Digitech Image Techs., LLC v. Elecs.for Imaging, Inc., 758 F.3d 1344, 1351
(Fed. Cir. 2014). Indeed, "the absence of complete preemption does not
demonstrate patent eligibility." Ariosa Diagnostics, Inc. v. Sequenom, Inc.,
788 F.3d 1371, 1379 (Fed. Cir. 2015). Where a patent's claims are deemed
only to disclose patent ineligible subject matter under the two-step
framework, as they are in this case, preemption concerns are fully addressed
and made moot. Id.; see also Intellectual Ventures I LLC v. Symantec Corp.,
838 F.3d 1307, 1321 (Fed. Cir. 2016) ("A narrow claim directed to an
abstract idea, however, is not necessarily patent-eligible .... "); OIP Techs.,
Inc. v. Amazon.com, Inc., 788 F.3d 1359, 1362-63 (Fed. Cir. 2015) ("[T]hat
the claims do not preempt all ... [inventions in the field] or may be limited
to [ certain processes in the field] do[ es] not make them any less abstract.").
The mere fact that the claims are directed to systems and methods for
analysis of biological images, thus, is insufficient to overcome the
Examiner's rejection of the claims on appeal under 35 U.S.C. § 101.
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In its Reply Brief, Appellant asserts for the first time, that the claims
recite unconventional steps that "confine the claims to a particular useful
application" and, thus, "qualify" them as directed to patent eligible subject
matter. (Reply Br. 3.) In particular, Appellant states:
none of the cited art of record, as indicated below, appears to
teach calculating a first and second moment for each of the at
least one cell feature, wherein the first moment is mean and
wherein the second moment is standard deviation, and wherein
the at least one cell feature comprises a ratio based on a
respective concentration level of each biomarker between cell
compartments for a respective cell, claims 1 and 21 recite at
least limitations other than what is well-understood, routine,
conventional activity in the field as well as unconventional
steps.
Id. Appellant further argues in the Reply Brief that because claim 21
"recites a particular machine" for capturing multiplexed biometric images
that is not simply a generic digital camera, it recites something that
"amounts to significantly more and therefore renders this claim eligible
under 35 U.S.C. § 101." (Id. at 4.) We do not find these arguments
persuasive. First, "the reply brief [is not] an opportunity to make arguments
that could have been made in the principal brief on appeal to rebut the
Examiner's rejections, but were not." Ex parte Borden, 93 USPQ2d 1473,
1474 (BPAI 2010) (informative). As stated in Ex parte Borden,
consideration by the Board of new arguments presented for the first time in
the Reply Brief that could have been presented earlier would "vitiate the
force of the requirement in Board Rule 3 7 ( c )( 1 )( vii) that ' [ a ]ny arguments or
authorities not included in the brief ... will be refused consideration by the
Board, unless good cause is shown."' Id. Appellant has not demonstrated
any specific Examiner findings presented for the first time in the Answer
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necessitating this specific new argument in rebuttal in the Reply Brief. Nor
do we find any substantial differences in the Examiner's initial findings and
the Examiner's findings stated in the Answer that would warrant the new
arguments presented in the Reply Brief for the first time.
Second, the search for an inventive concept is distinct from
demonstrating novelty. See, e.g., SAP, 898 F.3d at 1162 (citing Synopsys,
Inc. v. Mentor Graphics Corp., 839 F.3d 1138, 1151 (Fed. Cir. 2016) ("[A]
claim for a new abstract idea is still an abstract idea. The search for a § 101
inventive concept is thus distinct from demonstrating§ 102 novelty.")).
Appellant relies on the calculation of a mean, standard deviation, and a ratio
as being unconventional steps in the analysis of the tissue. (Reply Br. 3.)
However, those steps are simply mathematical calculations which are
abstract ideas. An innovation that consists of using particular ineligible
subject matter, such as the mathematical calculations that Appellant points to
here in organizing the information into a new form, is insufficient to
establish that the claims at issue are directed to a patent-eligible application
of an abstract idea. SAP, 898 F.3d at 1162 ("an advance ... [that] lies
entirely in the realm of abstract ideas, with no plausibly alleged innovation
in the non-abstract application realm ... is ineligible for patenting"); see
also Synopsys, 839 F.3d at 1152 ("To the extent the Asserted Claims add
anything to the abstract idea (i.e., translating a functional description of a
logic circuit into a hardware component description of the logic circuit), it is
the use of assignment conditions as an intermediate step in the translation
process .... But, given that the claims are for a mental process, assignment
conditions, which merely aid in mental translation as opposed to computer
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efficacy, are not an inventive concept that takes the Asserted Claims beyond
their abstract idea.").
The fact that claim 21 requires the use of a specialized camera to
obtain the multiplexed biometric images is also insufficient to establish that
claim is directed to a patent-eligible application of an abstract idea.
Irrespective of the camera being a "specialized camera" and not simply any
digital camera, the use of such specialized cameras is conventional in
obtaining and analyzing cellular data from biomarker stained tissue as
explained in Appellant's Specification. (Spec. ,r,r 4--14.)
Consequently, for all of the reasons discussed above, we sustain the
Examiner's rejection of claims 1 and 21 under 35 U.S.C. § 101 as being
directed to non-statutory subject matter.
Claims 2-13, 15, 18-20, 22-33, 35, 38--44, and 47 have not been
argued separately and, therefore, fall with claims 1 and 21, respectively. 37
C.F.R. § 4I.37(c)(l)(iv).
II
Obviousness
The Examiner finds that Hunter teaches imaging biological material in
multiple optical channels where the plasma membrane and nucleus have
been differentially stained and then segmenting the images and calculating
various morphological biomarkers from the segmented image and that these
markers can be indicative of cancer. (Final Action 6.) The Examiner further
finds that Hunter teaches that one such biomarker can be "a ratio of
intensities between different compartments of an individual cell." (Id.) The
Examiner finds that Hunter teaches that the method can be performed using
a computer system that can include a digital camera. (Id.)
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The Examiner finds that Linke teaches obtaining tissue samples from
groups of patients, such as cancer patients, where each group has a common
characteristic, such as clinical outcome, or disease group versus control
group, and assaying the samples through biomarker analysis of one or more
polypeptides that employs imaging and quantifying the amounts of
polypeptides, which may be considered non-morphological markers. (Id.)
The Examiner finds that Linke teaches training a classifier to map selected
critical inputs, such as the biomarker quantities, clinicopathological
information and histological biomarkers, and outputs such as clinical
outcome. (Id.) The Examiner notes that Linke teaches that the input data
can be pre-processed and transformed, such as by calculation of mean data
and covariance matrices. (Id. at 6-7.) The Examiner explains that the
diagonal entries of the covariance matrix are a "second moment." (Id. at 7.)
The Examiner further explains that Linke teaches a subset of features can be
selected, based on, e.g., rank order where lowest-ranked features are
eliminated, and evaluated, which gives "the best classification results." (Id.)
The Examiner notes further, that Linke describes, subsequent to
classification, displaying a probability estimate of a clinical diagnosis of a
patient. (Id.) The Examiner notes that Linke teaches that a computer can be
used in performing the methods. (Id.)
According to the Examiner, one of ordinary skill in the art would have
found it obvious to combine the method of Hunter with Linke in cancer
diagnosis as both are concerned with using histological biomarkers in
assessing cancer and would readily predict that combination would result in
"a method that derives morphological and non-morphological biomarkers
from segmented fluorescence microscopy images, selects the best predictive
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biomarkers, and classifies the tissue sample based on those features." (Id. at
9.) The Examiner recognizes the combination does not explicitly teach
calculating a standard deviation of biomarker data, but that such would have
been an obvious statistical measure of the data in the Hunter/Linke
combined method of characterizing the distribution of biomarkers (id. at 7)
as evidenced by the CRC which teaches the mean, standard deviation, and
skewness are useful measures for characterizing distributions of variables
(id. at 9--10).
Appellant contends that the Examiner has failed to establish a prima
facie case of obviousness because Hunter does not disclose that the intensity
ratio that is measured is a measure taken for each cell rather than a global
measure of the tissue, and even if it did, that Hunter does not disclose
calculating first and second moments for such a measure. (Appeal Br. 14;
Reply Br. 5.) Appellant further argues that the combination of Linke and
CRC with Hunter does not disclose "the recited first and second moments of
a cell feature including a ratio biomarker expression between compartments"
because Linke "discloses determining mean and standard deviation for
biomarker expression alone, and not for any cell feature based on a ratio of
biomarker expression" and that "the Examiner's reliance on a general text
related to mathematical formulas [ for first and second moments] indicates
that the relied-upon features of these references are part of a hindsight
analysis." (Id.; see also Reply Br. 5-7 (noting that Linke "does not disclose
any ratio ofbiomarker expression between compartments").)
We do not find Appellant's arguments persuasive. We do not agree
with Appellant that Hunter is concerned solely with general identification of
membranes in a tissue image. (Appeal Br. 14.) Table 1 of Hunter indicates
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that measurement of cell dimensions and cell count are contemplated. This
indicates that Hunter is concerned with identification of individual cells.
Moreover, we agree with the Examiner (Ans. 6) that Hunter's teaching of
using an enhanced membrane mask in combination with CELL IDs to
analyze median intensity ratios reasonably conveys to one of ordinary skill
in the art that the intensity measure is a per cell measure in cell
compartments such as the membrane, cytoplasm, and nucleus. (Hunter ,r 40
and Table 1.) That is because the enhanced membrane mask segments
individual cells, which individual cells have been given a CELL ID. As the
Examiner notes, "there would be no purpose to using the membrane mask
nor the cell IDs" "if the intensity ratios were 'global measurements'." (Ans.
6.) Thus, even though Hunter does not specifically state that the measure of
median intensity ratio is for each respective cell (Reply Br. 6), we agree with
the Examiner that such is the import of the disclosure of Hunter (Ans. 6).
Regarding Appellant's argument as to the non-obviousness of
determining a first and second moment of a cell feature including a ratio
biomarker expression between compartments, we note that Appellant is
arguing that neither Hunter nor Linke independently teaches this limitation.
However, the rejection was based on what the combination of references
would have suggested to one of ordinary skill in the art. "Non-obviousness
cannot be established by attacking references individually where the
rejection is based upon the teachings of a combination of references ....
[The reference] must be read, not in isolation, but for what it fairly teaches
in combination with the prior art as a whole." In re Merck & Co., Inc., 800
F .2d 1091, 1097 (Fed. Cir. 1986). The Examiner's position is that Hunter
teaches determining the claimed ratio and Linke is relied upon for teaching
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the obviousness of the statistical analyses of collected data for collected
biomarker data in general (Ans. 6) which could also be applied to the ratio
that Hunter teaches to collect. The Examiner further relies on the CRC only
to explain that means and variances are "useful descriptive statistics of sets
of data" that would have been obvious for one of ordinary skill in the art to
have used in the Hunter/Linke combination. (J d.) We agree with the
Examiner's analysis.
Thus, Appellant has not established error in the Examiner's rejection
of claims 1 and 21 under 35 U.S.C. § 103(a) being unpatentable over Hunter,
Linke, CRC, and Pudil.
Claims 2-13, 15, 18-20, 22-33, 35, 38--44, and 47 have not been
argued separately and, therefore, fall with claims 1 and 21, respectively. 3 7
C.F.R. § 4I.37(c)(l)(iv).
SUMMARY
We affirm the Examiner's rejection of claims 1-13, 15, 18-33, 35,
38--44, and 47 under 35 U.S.C. § 101 as being directed to non-statutory
subject matter.
We affirm the Examiner's rejection of claims 1-13, 15, 18-33, 35,
38--44, and 47 under 35 U.S.C. § 103(a) pre-AIA as being unpatentable over
Hunter, Linke, CRC, and Pudil.
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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