Ex Parte Krutzik et al

Patent Trial and Appeal Board

Apr 19, 2017

13175566 (P.T.A.B. Apr. 19, 2017)

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.
13/175,566 07/01/2011 Peter O. Krutzik STAN-447DIV 2835
77974 7590 04/21/2017
Stanford University Office of Technology Licensing
Bozicevic, Field & Francis LLP
201 REDWOOD SHORES PARKWAY
SUITE 200
REDWOOD CITY, CA 94065
EXAMINER
CHEN, STACY BROWN
ART UNIT PAPER NUMBER
1648
NOTIFICATION DATE DELIVERY MODE
04/21/2017 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):
docket@bozpat.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte PETER O. KRUTZIK and GARRY NOLAN1
Appeal 2015-004805
Application 13/175,566
Technology Center 1600
Before FRANCISCO C. PRATS, TAWEN CHANG, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
NEWMAN, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to a kit for
detecting characteristics of interest on cells. The Examiner entered final
rejections for obviousness.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part.
1 Appellants identify the Real Party in Interest as Board of Trustees of the
Leland Stanford Junior University. App. Br. 3.
Appeal 2015-004805
Application 13/175,566
STATEMENT OF THE CASE
Background
The Specification discloses
multiplex cellular assays that employ Detectable Cell Barcodes
(DCB). In certain embodiments, different cell samples are
labeled with different amounts of a DCB marker, e.g., by
treatment with different concentrations of a DCB label that
binds to a cell (e.g., a cell-reactive form of a fluorophore or a
cell-reactive molecular mass marker). This gives each sample a
unique signature upon analysis (e.g., flow cytometric detection
and/or mass spectrometer analysis). In certain embodiments,
cell samples are coded with more than one DCB marker (e.g.,
DCB markers having distinct detection characteristics). In
these embodiments, the number of different DCB signatures
available increases geometrically because of multiplexing of
DCB intensity with DCB detection characteristic (for example,
using different channels on the flow cytometer). DCB allows
the multiplex analysis of hundreds to thousands of samples (or
more) in a single reaction tube, which significantly reduces
re [a] gent consumption, improves the throughput of
experiments, and eliminates potential sample to sample
variability.
Spec. 13.
“As used herein, ‘detectable cell barcode marker’ or ‘DCB marker’ or
‘DCB label’, or grammatical equivalents thereof, is meant a moiety that can
label a cell upon contact in a suitable buffer, either covalently or non-
covalently.” Id. at 120.
2
Appeal 2015-004805
Application 13/175,566
The Claims
Claims 22, 24—26, 29-47, and 49-53 are on appeal. Sole independent
claim 22 is illustrative and reads as follows, with the relevant claim
limitation emphasized:
22. A kit comprising:
(a) a first aliquot of a first amount of a detectable cell
barcode (DCB) label comprising a detectable moiety, wherein
the DCB label binds to a cell of a cell sample; and
(b) a second aliquot of a second amount of the DCB label
that is identical to the DCB label in the first amount, wherein
the second amount is different than the first amount.
App. Br. (Claims App’x.) 32.
The Issues
The following rejections are before us to review:
Claims 22, 24, 25, and 30—52 are rejected under pre-AIA 35 U.S.C.
§ 103(a) as being unpatentable over Archer.2
Claims 26 and 29 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Archer and Gordon.3
Findings of Fact
FF1. The Specification provides:
As used herein, “detectable cell barcode marker” or
“DCB marker” or “DCB label”, or grammatical equivalents
thereof, is meant a moiety that can label a cell upon contact in a
suitable buffer, either covalently or non-covalently. ... In
certain embodiments, a DCB marker is functionalized to bind
2 US 2005/0069962 Al, published March 31, 2005 (“Archer”)
3 US 5,486,452, issued January 23, 1996 (“Gordon”)
3
Appeal 2015-004805
Application 13/175,566
reversibly to a cell, e.g., attached to an antibody that binds to an
antigen on/in a cell. Types of detectable characteristics for DCB
labels/markers include, but are not limited to, fluorescence
emission, molecular mass, catalytic activity, or other detectable
characteristic. Virtually any distinct characteristic of a DCB
label that is detectable (e.g., by flow cytometry, mass
spectrometry, etc.) [] can be used.
Spec. 120.
FF2. Archer discloses:
The present invention provides labeling reagents and
methods for labeling primary antibodies and for detecting a
target in a sample using an immuno-labeled complex that
comprises a target-binding antibody and one or more labeling
reagents. The labeling reagents comprise monovalent antibody
fragments or non-antibody monomeric proteins whereby the
labeling proteins have affinity for a specific region of the target­
binding antibody and are covalently attached to a label.
Archer 112.
FF3. Archer discloses:
The labeling steps of the target-binding antibody are
optionally repeated to form a panel of subsets, these immuno-
labeled complex subsets may be used individually or pooled
wherein each subset is distinguished from another subset by i)
the target-binding antibody, or ii) a ratio of label to labeling
reagent, or iii) a ratio of labeling reagent to the target-binding
antibody or iv) by a physical property of the label. Thus, it is
appreciated that a wide range of subsets can be formed wherein
the subsets can be used individually to detect a target in a
sample or pooled to simultaneously detect multiple targets in a
sample. The simultaneous detection of multiple targets in a
sample is especially useful in methods that utilize flow
cytometry or methods that immobilize a population of cells or
tissue on a surface.
4
Appeal 2015-004805
Application 13/175,566
Archer 114.
FF4. Archer discloses:
The methods for determining a target in a sample using
immuno-labeled subsets comprises forming a subset of
immuno-labeled complexes, as described above, contacting a
sample with said immuno-labeled complexes, incubating the
sample for a time sufficient to allow the immunolabeled
complex to selectively bind to a desired target, and illuminating
the immuno-labeled complex whereby the target is detected.
The sample is any material that may contain a target and
typically comprises a population of cells, cellular extract,
subcellular component, proteins, peptides, tissue culture, tissue,
a bodily fluid, or a portion or combination thereof. When
multiple targets are detected a pooled subset of immuno-labeled
complexes are formed and incubated with the sample or
individual subsets are add[ed] sequentially to a sample.
Archer 115.
FF5. Archer discloses that “[t]he term ‘label’ as used herein refers to a
chemical moiety or protein that retains [its] native properties (e.g. spectral
properties, conformation and activity) when attached to a labeling reagent
and used in the present methods.” Archer 144. Archer discloses multiple
suitable labels with detection methods in the remainder of this paragraph.
Id.
FF6. Archer discloses that a “target-binding antibody . . . refers to an
antibody that has affinity for a discrete epitope or antigen.” Archer 1 55.
5
Appeal 2015-004805
Application 13/175,566
FF7. Archer discloses:
The labeling reagent and the methods of the present
invention provide for detection of one or multiple targets in a
sample. Multiple targets are detected when either pooled
subsets of immuno-labeled complexes or a panel of subsets that
are sequentially added to a sample. The subset of immuno-
labeled complexes begins with labeling reagent subsets wherein
a labeling reagent subset is distinguished by the ratio of label to
labeling reagent or by the physical characteristics of the label.
The discrete labeling reagents subsets are added to the target­
binding antibodies wherein the affinity of the antibody and ratio
of labeling reagent to target-binding antibody determines the
subsets of immunolabeled complexes. This results in an infinite
number of immuno-labeled complex subsets that are
distinguished by i) the target-binding antibody, or ii) a ratio of
label to labeling reagent, or iii) a ratio of labeling reagent to the
target binding antibody or iv) by a physical property of the
label. These subsets can be used individually in a method of the
present invention to detect a single or multiple targets in a
sample or pooled and used to simultaneously detect multiple
targets in a sample. These pooled subsets allow for not only
detection but also identification and quantitation of the targets.
Archer 158.
FF8. Archer discloses:
When the sample contains cellular nucleic acids (such as
chromosomal or plasmid-bome genes within cells, RNA or
DNA viruses or mycoplasma infecting cells, or intracellular
RNA) or proteins, preparation of the sample involves lysing or
permeabilizing the cell, in addition to the denaturation and
neutralization already described. Cells are lysed by exposure to
agents such as detergent (for example sodium dodecyl sulfate,
Tween, sarkosyl, or Triton), lysozyme, base (for example
sodium, lithium, or potassium hydroxide), chloroform, or heat.
6
Appeal 2015-004805
Application 13/175,566
Cells are permeabilized by conventional methods, such as by
formaldehyde in buffer.
Archer 1149.
FF9. Archer discloses:
The optical response is optionally detected by visual
inspection, or by use of any of the following devices: CCD
camera, video camera, photographic film, laser-scanning
devices, fluorometers, photodiodes, quantum counters,
epifluorescence microscopes, scanning microscopes, flow
cytometers, fluorescence microplate readers, or by means for
amplifying the signal such as photomultiplier tubes. Where the
sample is examined using a flow cytometer, examination of the
sample optionally includes sorting portions of the sample
according to their fluorescence response.
Archer 1154.
FF10. Gordon discloses:
the invention relates to kits comprising besides the described
devices in the form of the solid supports also trays and other
hardware suitable for processing the solid supports in the
assays, as well as prepared reagents in dry form, such as
predetermined amounts of carrier serum, indicator antibodies,
peroxidase substrates, etc. Such kits are e.g. in the form of
outfits including the devices of the invention, for instance in the
form of nitrocellulose sheets or strips, and any of the above
mentioned accessories. In particular, trays may take the form of
multicavity plastic trays.
Gordon 15:39-49.
7
Appeal 2015-004805
Application 13/175,566
Analysis
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art, as stated in the Final Action 2—84 and
Answer 2—11, and agree that the rejected claims are obvious over Archer or,
in the case of claims 26 and 29, Archer and Gordon, with the exception of
claim 36 (addressed below). We provide certain findings of fact only for
emphasis as we address Appellants’ arguments below.5
Group I6
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that Archer suggests a kit
comprising two different amounts of a “DCB label” for detecting a
characteristic of interest on a cell?
Appellants argue claims 22, 24, 25, 30-47, and 49—53 are directed to
“a kit with a first and a second aliquot of a DCB label that binds to a cell,
wherein the amounts of the first and second aliquots are different.” App.
Br. 9 (emphasis original). We select claim 22 as representative of the claims
subject to this ground of rejection. 37 C.F.R. § 41.37(c)(iv).
4 Examiner’s Final Action, May 29, 2014. (“Final Act.”)
5 Appellants argue the claims in “groups” of their own creation, and not as
they were rejected. See App. Br. 7—8, discussing groups. For clarity, we
address the arguments using the same grouping applied by Appellants and in
the order addressed. In doing so, we take no position on the subject matter
of the groupings, and cross-refer to the Examiner’s rejection for each group.
6 All rejections in Group I relate to the Examiner’s obviousness rejection
based on Archer alone.
8
Appeal 2015-004805
Application 13/175,566
Appellants argue the Examiner has not provided any evidence that
Archer teaches or suggests the claim limitations of a “kit comprising a DCB
label as claimed,” or “providing two different amounts of the same DCB
label as claimed” and that the labeling reagent of Archer cannot be a DCB
label because the Examiner acknowledges it is not. App. Br. 9-10.
Appellants argue that because the Examiner “recognizes that Archer does
not specifically suggest kits comprising labels (without the rest of the
labeling reagent complex),” the Examiner has “not provided a reference that
teaches or suggests a kit comprising a DCB label, much less different
amounts of the same DCB label, as claimed. As such, regardless of
motivation, the Examiner has not cited a reference that teaches or suggests
all the limitations of the claims.” App. Br. 11 (emphasis added).
The Examiner responds to acknowledge the precise kit as claimed is not
disclosed, but argues that using a DCB label as defined by Appellants or
different amounts of the label in a kit “would have been obvious
modifications to Archer’s teachings.” Ans. 6.
Appellants, in reply, argue “the only kits taught by Archer are ones that
include a labeling reagent, and not just a label. As agreed to by the
Examiner, Archer’s labeling reagents are not DCB labels of the presently
claimed kits.” Reply Br. 3.
We are not persuaded that Appellants have identified error in the
Examiner’s rejection over Archer. While the Examiner acknowledges that
the labeling reagent of Archer alone is not a “label,” it need not be in order
to disclose or suggest the limitations of claim 22.
9
Appeal 2015-004805
Application 13/175,566
Archer discloses use of a label attached to a labeling reagent to form a
“labeling solution” or an “immune-labeled complex”. FF 2—5. As noted by
the Examiner, this enables the label to be functionalized to bind to the target
moiety. Ans. 3.
The Specification defines a DCB label as “a moiety that can label a cell
upon contact in a suitable buffer, either covalently or non-covalently.” FF 1.
Accordingly, Archer’s use of a label within a labeling solution is identical to
the disclosed function a DCB. It is not necessary for Archer’s “label” to
exclude other elements such as a bound antibody, forming an immune-
labeled complex, because Appellants’ claim uses the open-ended
“comprising.” See Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501 (Fed.
Cir. 1997) (“‘Comprising’ is a term of art used in claim language which
means that the named elements are essential, but other elements may be
added and still form a construct within the scope of the claim.”). Therefore,
a labeling solution as disclosed and used by Archer (e.g., label conjugated to
antibody) reads on the DCB label of claim 22.
We are also not persuaded that Archer’s failure to disclose a kit
containing two different amounts of label alone renders the rejection over
Archer in error. Archer discloses the use of different amounts of labeling
reagent for use in differentiating between multiple targets by using
“immune-labeled subsets [that] comprise a different target-binding antibody
but differ in the label and ratio of label.” Archer 1132. Archer discloses
that subsets may be constructed as follows, with the following benefits:
The first subset comprises a fluorophore label that emits red-
fluorescent light, a second subset comprises a fluorophore label
10
Appeal 2015-004805
Application 13/175,566
that emits green fluorescent light, a third subset comprises a
ratio of 1: 1 red to green fluorophore label; a fourth subset
comprises a ratio of 2:1 red to green fluorophore label and a
fifth subset comprises a ratio of 1:2 red to green fluorophore
label. These subsets allow for the simultaneous detection offive
targets in a sample. This aspect of the present invention is
particularly important due to the limited range of fluorophores
available wherein the labeling reagents can be utilized to
increase the number of targets that can be detected at one time.
One of skill in the art can appreciate that these subsets could be
expanded by altering the ratio of label to labeling reagent
instead of just the ratio of labeling reagent to target-binding
antibody. This same methodology can also be applied to a
single fluorophore label wherein the ratios are altered and a
target is detected based on the intensity of the signal instead of
the color and the ratio of the color to another color.
Archer^ 132 (emphasis added).
The ease of formation of the complex permits rapid
optimization of the complex and assessment of the effect of
variation in experimental parameters. A particularly unique
advantage of the invention is that the stoichiometry of the
complex is easily adjusted to provide complexes with different
ratios of labeling reagent to target binding antibody, and thus
there is control over the ultimate detectability of the target in
the sample. Complexes that have been labeled with the same
dye but at different molar ratios can be separately detected by
the differences in their intensities.
Archer 1112 (emphasis added).
These disclosures — in particular, the italicized portions — inform the
skilled artisan that the labeling complex can be used to detect different
signals within the same sample based on intensity differences.
Archer further discloses kits for labeling targets:
11
Appeal 2015-004805
Application 13/175,566
A preferred kit of the present invention comprises: a) a
labeling solution comprising a labeling reagent that is
independently attached to one or more labels and b) a solution
comprising a capture reagent. . . . The labeling solution is either
a homogenous mixture of labeling reagents or comprises a
pooled subset of labeling reagents. Alternatively the kit
comprises a panel of labeling reagent subsets that can be used
to make a subset of immuno-labeled complexes.
Archer 1158.
In light of these teachings, we agree with the Examiner that
it would have been obvious to have prepared aliquots of various
amounts of the label itself... in a kit prior to it being further
processed to be attached to the monovalent antigen . . . along
with any buffers or other reagents that would be of use ... to
functionalize the label for customization purposes.
Ans. 4.
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Inti Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability.” Id. at 417.
During oral argument, Appellants’ counsel and inventor Dr. Garry
Nolan argued that the disclosure above and other relevant disclosures in
Archer do not render claim 22 obvious. Appellants argued:
None of what Archer is talking about has anything to do with
merging of wells, or merging and then subsequently
deconvoluting those wells .... So that you can basically mix
all of the wells, treat them as one, increase the statistical
inferences that you can get from it and then deconvolute later.
12
Appeal 2015-004805
Application 13/175,566
Hearing transcript 24:14—18. Appellants also argued that “[Archer is]
different because of the labeling reagents. So the dyes are not on their own.
They’re conjugated to a labeling reagent at this point.” Id. at 25:7—9.
Appellants further argued: “So [Archer is] able to detect, let’s say, one of
five different [cell] types in that, but that is not one of five different samples.
A sample contains multiple target cell types, right. They are not teaching the
ability to distinguish samples.” Id. at 29:4—8.
Based on these alleged distinguishing characteristics, Appellants
argue “there is nothing in Archer that would lead you to make two
concentrations, two amounts of the dye unconjugated to an antibody . . .
They don’t have kits that contain dyes. Dyes are not a central part of their
invention.” Id. at 21:12—17. See also App. Br. 10-12 and Reply Br. 3.
These arguments are unpersuasive. Claim 22 does not require
“merging of wells, or merging and then subsequently deconvoluting those
wells,” or the “ability to distinguish samples.” See Super Guide Corp. v.
DirecTV Enters., Inc., 358 F.3d 870, 875 (Fed. Cir. 2004). (“Though
understanding the claim language may be aided by the explanations
contained in the written description, it is important not to import into a claim
limitations that are not a part of the claim.”). Claim 22 requires a kit with
aliquots of a DCB label of two different amounts, nothing more. As
discussed above, that label can include an antibody binding to a cell due to
the definition of “DCB” in the Specification. Further, because claim 22
employs the open form “comprising,” a “DCB label” does not exclude
antibody conjugated to the label, forming an immune-labeled complex.
13
Appeal 2015-004805
Application 13/175,566
Appellants next argue that the Examiner has not provided “any
disclosure from Archer that supports the Examiner’s assertion that the ability
of an end user to choose the target-binding antibody is desired.” App. Br.
12.
Appellants assert that “the labeling reagents suggested by Archer
already allows for the customization described by the Examiner,” therefore
there is no motivation to “modify the kit of Archer to include unbound
label.” Id.
This argument is unpersuasive because “[i]n determining whether the
subject matter of a patent claim is obvious, neither the particular motivation
nor the avowed purpose of the patentee controls. . . . [A]ny need or problem
known in the field of endeavor at the time of invention and addressed by the
patent can provide a reason for combining the elements in the manner
claimed.” KSR, 550 U.S. at 419-20.
Appellants next argue that “modifying the kit of Archer to include
various amounts of the label itself would render the kit inoperable for its
intended purpose of rapidly labeling the target-binding antibody.” App. Br.
13. According to Appellants, “time consuming steps [] would be
necessitated if unbound label were included in the kit as proposed by the
Examiner.” Id.
This argument is unpersuasive because, as discussed above, the
“label” of claim 22 can be provided as an immune-labeled complex, which
would remove many if not all of the “time consuming steps.” Moreover,
even if the label were prepared separately to permit additional
customization, “‘[t]he fact that the motivating benefit comes at the expense
14
Appeal 2015-004805
Application 13/175,566
of another benefit. . . should not nullify its use as a basis to modify the
disclosure of one reference with the teachings of another. Instead, the
benefits, both lost and gained, should be weighed against one
another.’” Medichem S.A. v. Rolabo S.L., 437 F.3d 1157, 1165 (Fed. Cir.
2006) (quoting Winner Int 7 Royalty Corp. v. Wang, 202 F.3d 1340, 1349 n.8
(Fed. Cir. 2000)). In sum, Appellants have not persuasively demonstrated
that the skilled artisan seeking the benefit of customization would be
deterred by the noted additional steps, which are all known to the skilled
artisan. We affirm the rejection of claim 22. Claims 24, 25, 31-32, 35, 37,
45, 50, and 52 were not argued separately, and fall with claim 22.
Group IV7
Appellants argue the rejection of claims 30, 38, 42, and 49 also should
be reversed because “the claimed kit comprising multiple distinct DCB
labels is not taught or suggested by the cited reference.” App. Br. 17
(emphasis original). Appellants argue that paragraph 58 of Archer, cited by
the Examiner as the basis for the rejection, does not “discuss multiple
distinct labels.” Id.
We are not persuaded. In addition to the teachings discussed above,
paragraph 58 of Archer discloses that
[mjultiple targets are detected when either pooled subsets of
immuno-labeled complexes or a panel of subsets [] are
sequentially added to a sample. The subset of immuno-labeled
complexes begins with labeling reagent subsets wherein a
7 All rejections in Group IV relates to the Examiner’s obviousness rejection
based on Archer alone.
15
Appeal 2015-004805
Application 13/175,566
labeling reagent subset is distinguished by the ratio of label to
labeling reagent or by the physical characteristics of the label.
Accordingly, Archer teaches that a subset of immune-labeled complexes for
use in distinguishing the physical properties (e.g., physical characteristics) of
the targets is a subset made with multiple labels of different physical
properties. See FF3, discussing immuno-labeled complex subsets.
Therefore, we agree with the Examiner that generation of a kit containing
multiple distinct labels is obvious over Archer. The rejection of claims 30,
38, 42, and 49 is affirmed.
Group V8
Claim 36 recites an additional element wherein the DCB label
comprises a mass label. The Specification discloses that “molecular mass
labels have distinguishable masses that can be differentially detected by
mass spectrometry.” Spec 194.
The Examiner finds the following disclosure of Archer discloses a
label comprising a mass label: “[t]he label can be a chemiluminescent
substance, where the output signal is generated by chemical modification of
the signal compound; a metal containing substance; or an enzyme.”
Archer 144.
Appellants argue this disclosure does not teach a mass label because
Archer does not “disclose that the metal containing substance can be
distinguished by mass.” App. Br. 18—19.
8 The rejection in Group V relates to the Examiner’s obviousness rejection
based on Archer alone.
16
Appeal 2015-004805
Application 13/175,566
We are persuaded that the Examiner has not established that simply
because an output signal of a label is generated by a “metal containing
substance,” that the label would function as a mass label to permit
differential detection by mass spectrometry. Accordingly, we reverse the
rejection of claim 36.
Group VI9
Claim 43 recites an additional element wherein the kit “includes a
third aliquot of a third amount of the DCB label, where the third amount is
different from the first and second amounts.”
Appellants argue Archer does not disclose at least three different
aliquots for the same reasons it does not disclose at least two different
amounts, as Appellants previously argued. App. Br. 19-20.
We are not persuaded. As discussed above, Archer discloses the use
of multiple immune labeling complexes (e.g., Archer | 58). In light of these
findings, we affirm the rejection of claim 43.
Group VII10
Claim 44 recites an additional element wherein “the DCB label is
functionalized to bind non-covalently to the cell.”
Appellants argue that Archer does not teach this limitation and that
the Examiner has not identified any teaching of Archer for this element.
App. Br. 20. Rather, Appellants argue “the Examiner has asserted that the
9 The rejection in Group VI relates to the Examiner’s obviousness rejection
based on Archer alone.
10 The rejection in Group VII relates to the Examiner’s obviousness rejection
based on Archer alone.
17
Appeal 2015-004805
Application 13/175,566
label of Archer covalently attaches to its target.” Id. at 20—21 (emphasis
original).
The Examiner responds:
Archer’s labeling reagent comprises a label. The label is a
detectable moiety. The label itself. . . qualifies as a DCB label
[which is] then covalently attached to a monovalent antigen
fragment or non-antibody monomeric protein via a reactive
group, such as succinimidyl esters, for example, [], which then
binds to a target binding antibody, forming a complex, which
will in turn bind to an antigen of interest on a cell. . . Thus,
Archer’s label is functionalized to bind non-covalently to a cell
when the target-binding antibody of the complex binds to an
antigen of interest on a cell (i.e., non-covalent).
Ans. 9.
Appellants respond that “the Examiner has already acknowledged that
a labeling reagent is not the same as a DCB label of the claimed kit” and
therefore the above comments are inapplicable. App. Br. 21. Appellants do
not provide evidence or other argument regarding this rejection.
We are not persuaded because, as discussed above, the immune-
labeled complex of Archer meets the limitation of “DCB label” of claim 22.
Accordingly, we affirm the rejection of claim 44.
18
Appeal 2015-004805
Application 13/175,566
Group VIII11
Claims 46 and 47 recite the additional element that the kit comprises
“a buffer for labeling the cell of the cell sample with the DCB label, wherein
the buffer comprises a cell permeabilizing reagent.”
Appellants argue that “the Examiner has at no point provided
evidence that Archer teaches or suggests a kit comprising a buffer, wherein
the buffer comprises a cell permeabilizing reagent.” App. Br. 22
(emphasis original).
Examiner responds that “cell permeabilization agents, such as
Tween® or Triton®, among others [] are disclosed, as well as formaldehye
in buffer. Cell permeabilization agents are not likely to be used at 100%
concentration, rather, in a buffer.” Ans. 9-10; FF 8. Appellants do not
respond to this point or provide evidence that cell permeabilization agents
are not used with a buffer. Without evidence, we are not persuaded that the
Examiner has erred in rejecting claims 46 and 47 in light of Archer’s
disclosure of the use of cell permeabilization agents, which the skilled
artisan would recognize are commonly used with buffers. In re Geisler, 116
F.3d 1465, 1469 (Fed. Cir. 1997) (citing In re Antonie, 559 F.2d 618, 620
(CCPA 1977)). We affirm the rejection of claims 46 and 47.
11 The rejections in Group VIII relate to the Examiner’s obviousness
rejection based on Archer alone.
19
Appeal 2015-004805
Application 13/175,566
Group IX12
Claim 51 recites the additional element that the kit comprises “DCB
labeling control beads that bind the DCB label.”
Appellants argue:
not only does Archer not discuss control beads, but Archer does
not provide any teaching or suggestion to include control
beads that bind the DCB label... it is the immune-labeled
complex of Archer, not the label itself, that will be used to bind
the target.
[Cjontrol beads that bind the DCB label would not find use in
preparing an immuno-labeled complex (which is made by
mixing labeling reagent and the target binding antibody) or
detecting a target in the sample (which involves binding of the
immune-labeled complex).
App. Br. 24
As noted by the Examiner, “Archer discloses fixed cells and
fluorescent beads in paragraph [0150].” Ans. 10. Archer teaches that these
beads may be used for immobilization of the target materials, the immune-
labeled complex. Archer 1150. See also Archer 1134 (“Traditionally
targets identified using flow cytometry used either directly labeled primary
antibody or labeled microspheres that were covalently attached to a primary
antibody wherein the microsphere is the label. Examples include the
fluorescent encapsulated microsphere beads sold by Luminex.”).
12 The rejection in Group II relates to the Examiner’s obviousness rejection
based on Archer alone.
20
Appeal 2015-004805
Application 13/175,566
Appellants acknowledge that Archer discloses beads used to bind the
immune-labeled complex, which, as we have discussed above, meets the
limitation of a “DCB label.” App. Br. 23. Accordingly, we are not
persuaded that Archer fails to disclose the use of beads bound to a label.
Regarding whether Archer renders the use of beads as controls
obvious, the Examiner proposes that 1)
Using these components as controls would be an obvious
modification given the nature of performing detection assays
and the need to confirm the integrity of the reagents; and 2) the
skilled artisan would find it obvious to use the disclosed beads
as controls to bind any free DCB label (i.e., not fully
functionalized label) in an assay to improve results.
Final Act. 5; Ans. 10.
Appellants do not respond to this point or provide evidence why the
Examiner’s proposed uses would not be considered obvious by the skilled
artisan. Without evidence, we are not persuaded that the Examiner has erred
in rejecting claim 51 in light of Archer’s disclosure of the use of beads to
bind to the immune-label complex, which the skilled artisan would
recognize have uses in confirming the integrity of reagents and to bind free
label to improve results. In re Geisler, 116 F.3d at 1469. We affirm the
rejection of claim 51.
21
Appeal 2015-004805
Application 13/175,566
Group X13
Claim 53 recites the additional element that the kit comprises a
“computer readable medium comprising data analysis software configured
specifically to automatically deconvolute DCB data.” App. Br. 25.
Appellants argue that the Examiner’s rejection evidences a
misunderstanding of the software configured to deconvolute DCB data,
which is a “process, whether performed manually or in an automated system,
by which the detected DCB of each cell is used to determine from which
original sample it was derived.” Id. at 25. Appellants argue Archer does not
teach or suggest the underlying use of a DCB label to bind to a cell, or
sorting those cells into samples of origin, based on the DCB data, and
therefore cannot teach a kit modified to contain software to perform the
deconvolution. Id.
The Examiner responds that “[cjomputer readable medium
comprising data analysis configured specifically to automatically analyze
Archer’s labels is equivalent to deconvoluting DCB data and is a necessary
feature of any flow cytometer or other automated reader.” Ans. 10 (citing
Archer 1154); FF 9.
Appellants do not respond to this point or provide evidence why
Archer’s disclosure “[wjhere the sample is examined using a flow
cytometer, examination of the sample optionally includes sorting portions of
the sample according to their fluorescence response” does not disclose the
13 The rejection in Group X relates to the Examiner’s obviousness rejection
based on Archer alone.
22
Appeal 2015-004805
Application 13/175,566
same deconvolution as exemplified in their Specification (see Specification
5—6, disclosing use of “fluorescence-based detectable cell barcodes” that
are “deconvoluted back to the original samples based on their FCB
signature”).
As discussed above, the labeling complex of Archer meets the
limitations of a “DCB label.” Archer teaches binding of the labeling
complex to a cell and sorting of those samples by flow cytometer analysis.
FF 9. Moreover, “[i]t can be obvious to adapt a known product “using
modem electronic components in order to gain the commonly understood
benefits of such adaptation, such as decreased size, increased reliability,
simplified operation, and reduced cost.” Leapfrog Enterprises, Inc. v.
Fisher-Price, Inc., 485 F.3d 1157, 1161 (Fed. Cir. 2007). Accordingly, we
are not persuaded that Archer fails to teach or suggest a computer readable
medium comprising data analysis software configured specifically to
automatically deconvolute data obtained through use of a DCB label. We
affirm the rejection of claim 53.
Group II14
The additional element of claim 26 recites that the DCB label in the
kit is in a dry composition.
Appellants argue that the combination of Archer and Gordon does not
teach all elements of the claim. App. Br. 26. Appellants rely on their
previous arguments with regard to the defects of Archer and argue Gordon
14 The rejection in Group II relates to the Examiner’s obviousness rejection
based on Archer and Gordon.
23
Appeal 2015-004805
Application 13/175,566
does not overcome the deficiencies because it “is cited solely for teaching
reagents in dry composition and multi-well format.” Id. This argument is
not persuasive as the rejection is based on the combination of Archer and
Gordon. See In re Keller, 642 F.2d 413, 426 (CCPA 1981) (finding “one
cannot show nonobviousness by attacking references individually where, as
here, the rejections are based on combinations of references” (citations
omitted)).
Appellants further argue Gordon does not teach kits comprising DCB
labels or that the labels of Archer “would be suitable or desirable to provide
in dry form.” Id. at 27.
The Examiner responds that no such disclosure would be necessary to
the skilled artisan because
it would have been obvious to have used this type of pre­
packaging with a reasonable expectation of success, the
motivating factor being convenience (e.g., transport and storage
parameters), as described in Gordon. The same principle would
apply to the liquid form in situations where drying is necessary
or desirable. In light of the teachings of Gordon, one would
have been motivated to modify Archer's embodiments for at
least the sake of convenience and marketing.
Ans. 11.
The Examiner has the better position. Gordon discloses kits provided
in a form for easy use by the skilled artisan, including “trays and other
hardware suitable for processing the solid supports in the assays, as well as
prepared reagents in dry form.” FF10. Appellants’ own disclosure is
strikingly similar: “[t]he one or more DCB labels can be provided in the kit
in any convenient form, including as dry reagents (e.g., lyophilized) or in a
24
Appeal 2015-004805
Application 13/175,566
liquid buffer (e.g., as a suspension, dissolved, etc.).” Spec. 199. One of
skill in the art would readily recognize that providing kit reagents in dry
form is, as Appellants’ Specification recognizes, “convenient” and therefore
desirable. We affirm the rejection of claim 26.
Group III15
The additional element of Claim 29 is a kit wherein the first and
second aliquots of the DCB label are provided in a multi-well strip or multi­
well plate.
Appellants argue that Archer does not disclose a “kit comprising DCB
label provided in a multi-well strip or multi-well plate” and that the
Examiner failed to identify “a location in Gordon or a quote thereof
supporting the assertion that Gordon expresses the above motivation.” App.
Br. 25 (emphasis original).
These arguments are not persuasive as the rejection is based upon a
combination of Archer and Gordon, not either reference alone. See In re
Keller, 642 F.2d at 426). In addition, the reference to multi-well plates is at
Gordon 15:39-55, as identified by the Examiner in the Final Action at page
8.16
15 The rejection in Group III relates to the Examiner’s obviousness rejection
based on Archer and Gordon.
16 “Gordon discloses kits for immunological analysis comprising test trips,
reagents in dry form, pre-weighted aliquots of reagents and multi-cavity
plastic trays (see Gordon, col. 15).” Final Act. 8 (emphasis added).
25
Appeal 2015-004805
Application 13/175,566
Appellants further argue, but provide no evidence, that “packaging the
label of Archer in multi-well strips would not improve transport or storage
parameters.” Id. at 28. Without evidence, this argument is unpersuasive. In
re Geisler, 116 F.3d at 1469.
Appellants next argue:
the multi-well strips of Gordon enable reagents to be
simultaneously administered with special resolution to the
solid-phase immune-assay described in the Abstract of Gordon
(see for example, Figure 1). However, Archer does not share
this motivation with regard to the packaging of multiple labels,
as each label would have to be separately used to form a
labeling reagent, such as by addition to a column (see, for
example, paragraph [0022] and Figure 7 of Archer).
App. Br. 28.
We are not persuaded. As previously addressed, even if the skilled
artisan needed to take additional steps to prepare to use the claimed kit, the
benefits of doing so would be weighed by the artisan against potential
drawbacks. Medichem S.A., 437 F.3d at 1165. In addition, the multi-well
plate would still be useful once the components such as the labeling reagents
were prepared, due to its compact size and the ease of administration.
Appellants have not persuasively demonstrated that the skilled artisan
seeking these benefits would be deterred by the noted additional steps,
which may be necessary based on the targets to be detected. We affirm the
rejection of claim 29.
26
Appeal 2015-004805
Application 13/175,566
SUMMARY
We affirm the rejection of claims 22, 24—26, and 29-35, 37-47, and
49—53. We reverse the rejection of claim 36
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-IN-PART
27