Ex Parte Farrow

Board of Patent Appeals and Interferences

Sep 1, 2010

10601378 (B.P.A.I. Sep. 1, 2010)

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.
10/601,378 06/23/2003 David Farrow SMB-004 7906
22463 7590 09/01/2010
SMART & BIGGAR
438 UNIVERSITY AVENUE
SUITE 1500, BOX 111
TORONTO, ON M5G 2K8
CANADA
EXAMINER
SKOWRONEK, KARLHEINZ R
ART UNIT PAPER NUMBER
1631
MAIL DATE DELIVERY MODE
09/01/2010 PAPER
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.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte DAVID FARROW
__________

Appeal 2010-002895
Application 10/601,378
Technology Center 1600
__________

Before ERIC GRIMES, LORA M. GREEN, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134 involving claims to methods
of detecting analyte particles in a fluid. The Examiner has rejected the
claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.

1 The two-month time period for filing an appeal or commencing a
civil action, as recited in 37 C.F.R. § 1.304, or for filing a request
for rehearing, as recited in 37 C.F.R. § 41.52, begins to run from
the “MAIL DATE” (paper delivery mode) or the
“NOTIFICATION DATE” (electronic delivery mode) shown on
the PTOL-90A cover letter attached to this decision.
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Statement of the Case
The Claims
Claims 1-5, 7, 8, and 22-29 are on appeal. Claim 1 is
representative. Claim 1 reads as follows:
1. A method for detecting the presence of an
analyte particle in a fluid, said method comprising,
sequentially:
filtering a sample of said fluid from a first
chamber to a second chamber through a filter sized to
pass said analyte particle and particles smaller than
said analyte particle, retaining in said first chamber
particles in said sample larger than said analyte
particle thereby forming in said second chamber a
filtered sample;
adding to said filtered sample in said second
chamber a reagent that specifically interacts with said
analyte particle to form a reagent-analyte particle
complex that is larger than said analyte particle;
filtering said filtered sample from said second
chamber through a filter sized to pass particles that are
smaller than said reagent-analyte particle complex
thereby forming in said second chamber a further
filtered sample;
testing said further filtered sample in said
second chamber for the presence of residual particles,
wherein the presence of said residual particles
identifies the presence of said reagent-analyte particle
complex in said second chamber, and wherein the
presence of said-analyte particle complex is indicative
of the presence of said analyte particle in said fluid
and wherein the absence of said reagent-analyte
particle complex in said second chamber is indicative
of the absence of said analyte particle in said fluid.
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The prior art
The Examiner relies on the following prior art references to show
unpatentability:
Piesold et al. WO 01/85341 A1 Nov. 15, 2001
Petersen et al. US 2002/0042125 A1 Apr. 11, 2002
Bernhardt et al. US 6,391,657 B1 May 21, 2002
Chou et al. US 2004/0072278 A1 Apr. 15, 2004

Tullis et al., HIV affinity hemodialysis as a treatment for AIDS, AM.
CLINICAL LABORATORY 22-23 (2001).

The issues
A. The Examiner rejected claims 1-5, 7, 8, and 22-29 under 35 U.S.C. §
103(a) as obvious over Tullis, Bernhardt, Petersen and Piesold (Ans. 3-7).
B. The Examiner rejected claims 1-5, 7, 8, and 22-29 under 35 U.S.C. §
103(a) as obvious over Chou, Bernhardt, and Piesold (Ans. 7-11).
A. 35 U.S.C. § 103(a) over Tullis, Bernhardt, Petersen, and Piesold
The Examiner finds it “obvious to modify the filter of Tullis et al.
using the CD4 reagent of Bernhardt et al. with the microfluidics device of
Piesold because Piesold shows the device provides a beneficial enhancement
in the feasibility of miniaturizing experiments and assays” (Ans. 6).
Appellant contends that “none of the cited references provide the step
of testing for the presence of residual particles within the chamber in which
a reagent-analyte particle complex is formed” (App. Br. 8). Appellant
contends that:
In order to relate Piesold to the invention as claimed in
present claim 1 as the Examiner has done would require
modification of the device in Piesold in such a manner as to
destroy the purpose or function of the Piesold device, i.e. to
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reverse the flow backwards through the device in Piesold,
destroying the function of filter 4 for trapping particle beads
6 within reaction chamber 10 (since there would be nothing
stopping the beads from flowing out inlet 2).

(App. Br. 17). Appellant contends that the “four references in combination
do not disclose, describe or suggest testing for the presence of a residual
particles within a chamber of the device in which a reagent-analyte particle
complex is formed” (App. Br. 17).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that Tullis, Bernhardt, Petersen, and
Piesold render claim 1 obvious?
Findings of Fact
1. Tullis teaches that “[b]lood from the patient is pumped through
the hollow fibers, each of which has multiple submicron-sized pores to allow
passage of the virus and simultaneously prevent preformed blood elements
from exiting the fiber” (Tullis 22, col. 1-2).
2. Tullis teaches that “[d]uring transit, the virus is transported by a
combination of diffusion and convection through the pores and into the extra
fiber space which is filled with a matrix comprising antiviral antibodies
covalently coupled to a beaded agarose or silica solid support” (Tullis 22,
col. 2).
3. Tullis teaches that the “concentration of HIV was measured by
real-time PCR and confirmed by p24 enzyme linked immunosorbent assay
(ELISA) both directly in virus concentrated from plasma and RNA extracts
from virus trapped on the column” (Tullis 23, col. 1).
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4. Bernhardt teaches “the removal of viruses from aqueous
solutions, as a rule protein solutions, by ultrafiltration” (Bernhardt, col. 1, ll.
4-5). Bernhardt teaches that in “the most general form, the present invention
makes it possible to increase the size of any constituents of an aqueous
solution by binding to high molecular weight ligands to such an extent that
separation is then possible from the now smaller constituents in a filtration
step” (Bernhardt, col. 2, ll. 25-29).
5. Bernhardt teaches that the “viruses to be removed are increased
in size by binding to high molecular weight ligands, preferably specific
antibodies . . . to such an extent that they can be held back by filtration”
(Bernhardt, col. 2, ll. 11-18).
6. Bernhardt teaches that CD4 is a ligand which can be used to
bind and retain HIV (see Bernhardt, col. 2, ll. 30-50).
7. Figure 2 of Piesold is reproduced below:

“Figure 2 shows schematically a plan view of an embodiment of an
apparatus” (Piesold 6, l. 3).
8. Piesold teaches “a reaction apparatus comprising a porous
reaction chamber for trapping one or more particles therein and a reaction
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monitoring means arranged to monitor the particles trapped in the reaction
chamber; wherein the reaction chamber is arranged so as substantially to
correspond in shape to the reaction monitoring means” (Piesold 3, ll. 25-28).
9. Piesold teaches that while “preferred applications of the
invention are for reactions in which an analyte is immobilised on a bead of
some sort, it will be appreciated that apparatus in accordance with the
invention may also be used in applications not involving beads – e.g. cell-
cell separations, cell deformability tests and particle filtration” (Piesold 2, l.
31 to 3, l. 3).
10. Piesold teaches a DNA sequencing method in which
“[b]iotinylated inner PCR product was immobilized onto the streptavidin
coated beads” (Piesold 13, ll. 11-12).
11. Piesold teaches that “[s]ince the sample flow-through does not
displace the beads or their surface functional groups multi-step reactions can
be implemented at one location in the microfabricated device, facilitating
optical detection” (Piesold 12, ll. 22-25).
12. The Examiner finds that “Peterson et al. show an injection
molded plastic filtration device . . . Peterson et al. teach the device has a
solid support for capturing a desired analyte” (Ans. 6).
Principles of Law
The Examiner has the initial burden of establishing a prima facie case
obviousness under 35 U.S.C. § 103. In re Oetiker, 977 F.2d 1443, 1445
(Fed. Cir. 1992).
“[R]ejections on obviousness grounds cannot be sustained by mere
conclusory statements; instead, there must be some articulated reasoning
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with some rational underpinning to support the legal conclusion of
obviousness.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007).

Analysis
While some of the elements of Claim 1 are individually found in the
cited prior art references, the Examiner has not clearly demonstrated that the
references disclose multiple filtration steps in which a sample is filtered and
then the filtrate is further filtered to remove components. Also the Examiner
has not provided a reason to combine these scattered teachings in the manner
claimed by Appellant. That is, the Examiner relies on the PCR and ELISA
testing by Tullis to satisfy the step in Claim 1 of “testing said further filtered
sample in said second chamber”, but these tests are not performed in the
second chamber, but rather are performed on material which is removed
from the column and would not be in the chamber (FF 1-3). Bernhardt has
no interest in testing for viruses, but rather is interested in removing viruses
from solutions using the capture moieties (FF 4-6). Petersen was not relied
upon for this element (FF 12).
While Piesold does teach detection of material in a chamber in the
context of a DNA sequencing method (FF 10-11), Piesold also does not
suggest trapping the analyte with a specific reagent in the second chamber
(FF 10). In Piesold’s DNA sequencing example, the analyte is the bead
bound single stranded PCR amplified DNA after annealing to a primer, and
no capture occurs in the chamber (FF 10).
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We therefore agree with Appellant that “there is no reason that a
skilled person would be motivated to combine Tullis, Bernhardt, Petersen
and Piesold to arrive at the present method of claim 1” (App. Br. 18).
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that Tullis, Bernhardt, Petersen, and Piesold render claim 1 obvious.
B. 35 U.S.C. § 103(a) over Chou, Bernhardt, and Piesold
The Examiner finds:
It would have been obvious to one of ordinary skill in the art
at the time the invention was made to modify the differential
microfluidics particle filtering system of Chou et al. with the
formation of CD4-HIV complexes for the purpose of
increasing the HIV particle size of Bernhardt et al. because
Bernhardt et al. show that by forming a reagent-particle
complex increased filtration rates can be obtained. It would
have been further obvious to use CD4 as the HIV complex-
forming reagent because Chou et al. teach that CD4 is the
primary receptor for HIV. It would also have been further
obvious to modify the filtration device of Bernhardt et al.
with the microfluidics system of Chou et al. because Chou et
al. teach the microfluidics system has the advantages of
improved speed, accuracy, safety, and cost. It would have
been further obvious to modify the microfluidics filtering
system of Chou et al. using the CD4 reagent of Bernhardt et
al. with the microfluidics device of Piesold because Piesold
shows the device provides a beneficial enhancement in the
feasibility of miniaturizing experiments and assays. It would
have been further obvious to modify the microfluidics
filtering system of Chou et al. using the CD4 reagent of
Bernhardt et al. with the microfluidics device design of
Piesold because the application of differential filtering was
known in the art at the time of invention as demonstrated by
Bernhardt et al. One of ordinary skill in the art would have
been capable of applying differential filtering to the device
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of Piesold that was ready for improvement and the results
would have predictable to one of ordinary skill the art.

(Ans. 10-11).
Appellant contends that “Chou and Bernhardt together in view of
Piesold reveals that the new three-reference combination does not disclose,
describe or suggest testing for the presence of residual particles within the
chamber in which a reagent-analyte particle complex is formed, as claimed
in currently pending claim 1” (App. Br. 23). Appellant contends that the
filtering arrangement of Chou
does not suggest or provide an intervening step that involves
making the apparent size of the analyte larger based on a
specific interaction following a first filtration step, a
subsequent second filtration step and then testing for the
presence of residue remaining within the chamber in which a
reagent-analyte complex is formed, as required by present
claim 1.

(App. Br. 25). Appellant contends that “Piesold does not mention addition
of reagent, formation of a reagent-analyte complex, filtration of particles
smaller than the complex and testing for the presence of a residue within the
chamber in which the complex is formed, as required by pending claim 1”
(App. Br. 26).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that Chou, Bernhardt, and Piesold render
claim 1 obvious?

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Findings of Fact
13. Chou teaches that “[v]iruses may be manipulated and/or
analyzed as particles in microfluidic systems . . . Exemplary viruses may
include HIV” (Chou 8 ¶ 0167).
14. Chou teaches “size-selective channels may retain particles that
are too large to enter the channels. (Size-selective channels also may be
referred to as filter channels, micro channels, or particle-restrictive or
particle-selective channels.)” (Chou 11 ¶ 0214).
15. Chou teaches that
input particles may have a common size, such as cells from
a homogeneous cell population, or they may have a range of
sizes, such as cells from blood. In some embodiments, the
diameter of filter channel 616 allows size-selective retention
of a single particle. For example, the diameter may be large
enough to receive certain particles in a heterogeneous
particle population, such as red blood cells, but small
enough to exclude others, such as white blood cells.

(Chou 30 ¶ 0461).
16. Chou teaches that “[c]ell combs also can be cascaded so that
objects of different sizes are filtered out at different stages” (Chou 31 ¶
0468).
17. Chou teaches “microfluidic systems for sorting and analyzing
heterogeneous populations of particles, particularly cells, based on
differences in particle size” (Chou 47 ¶ 0655).
18. Chou teaches that “the system may be modified to include a
serial set of retention mechanisms . . . Each successive mechanism may have
a reduced diameter of channel . . . With this arrangement, larger particles are
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retained earlier in the series of mechanisms, whereas smaller particles are
retained later in the series” (Chou 47 ¶ 0660).
19. Chou teaches that “[p]articles retained in the retention
mechanism . . . may be treated and analyzed. Particles may be treated by
exposing them to desired reagents . . . Systems . . . may enable on-chip
staining and washing, eliminating any need for multiple pipeting and/or
centrifugation steps” (Chou 47 ¶ 0661).
20. Chou teaches that “characteristics of particles may be detected
or otherwise detected while the particles are relatively stationary, such as
when localized in chamber” (Chou 47 ¶ 0662).
Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l 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. Moreover, an “[e]xpress suggestion to substitute
one equivalent for another need not be present to render such substitution
obvious.” In re Fout, 675 F.2d 297, 301 (CCPA 1982). As noted by the
Court in KSR, “[a] person of ordinary skill is also a person of ordinary
creativity, not an automaton.” KSR at 421.
Analysis
Claim 1
Chou teaches detection of analyte particles in fluids (FF 13). Chou
teaches “to include a serial set of retention mechanisms . . . Each successive
mechanism may have a reduced diameter of channel . . . With this
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arrangement, larger particles are retained earlier in the series of mechanisms,
whereas smaller particles are retained later in the series” (Chou 47 ¶ 0660;
FF 18). Thus, Chou teaches a series of chambers in which the sample is
filtered to retain large particles in the first chamber and forming the filtered
sample in a second chamber, which is then itself filtered and larger particles
are retained in the second chamber and smaller particles flow further through
the device (FF 16-18). Chou teaches that “[c]ell combs also can be cascaded
so that objects of different sizes are filtered out at different stages” (Chou 31
¶ 0468; FF 16).
Chou teaches that “characteristics of particles may be detected or
otherwise detected while the particles are relatively stationary, such as when
localized in chamber” (Chou 47 ¶ 0662; FF 20).
The Examiner acknowledges that Chou does not “show the formation
of a reagent-particle complex that is separated from particles smaller than
the complex” (Ans. 8). However, the Examiner relies on Bernhardt to teach
that the “viruses to be removed are increased in size by binding to high
molecular weight ligands, preferably specific antibodies . . . to such an
extent that they can be held back by filtration” (Bernhardt, col. 2, ll. 11-18;
FF 5).
We agree with the Examiner that “Bernhardt et al. show the formation
of analytes reagent complexed that are larger than a selected pore size, and
Chou et al. and Bernhardt et al. show embodiments directed to the analysis
of blood for particular analyte particles” (Ans. 15).
Appellant contends that “Chou and Bernhardt together in view of
Piesold reveals that the new three-reference combination does not disclose,
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describe or suggest testing for the presence of residual particles within the
chamber in which a reagent-analyte particle complex is formed, as claimed
in currently pending claim 1” (App. Br. 23).
We are not persuaded. Chou is expressly interested in separating
virus particles into a “residual” chamber for detection after size separation
and Chou teaches detecting these particles (FF 13-20). Bernhardt teaches a
method of retaining virus particles into a particular chamber by adding a
component to increase the size of the particles (FF 4-6). Consistent with
KSR, the “combination of familiar elements according to known methods is
likely to be obvious when it does no more than yield predictable results.”
KSR at 416. Here, Bernhardt teaches that in “the most general form, the
present invention makes it possible to increase the size of any constituents of
an aqueous solution by binding to high molecular weight ligands to such an
extent that separation is then possible from the now smaller constituents in a
filtration step” (Bernhardt, col. 2, ll. 25-29;FF 4).
We conclude that an ordinary practitioner, motivated by Chou to
retain some particles while excluding others (FF 14-16) would have
reasonably applied the method of Bernhardt to permit separation of particles
(FF 4-6).
Appellant contends that the filtering arrangement of Chou
does not suggest or provide an intervening step that involves
making the apparent size of the analyte larger based on a
specific interaction following a first filtration step, a
subsequent second filtration step and then testing for the
presence of residue remaining within the chamber in which a
reagent-analyte complex is formed, as required by present
claim 1.

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(App. Br. 25). Appellant contends that “Piesold does not mention addition
of reagent, formation of a reagent-analyte complex, filtration of particles
smaller than the complex and testing for the presence of a residue within the
chamber in which the complex is formed, as required by pending claim 1”
(App. Br. 26).
We are not persuaded. Both of these arguments do not address the
combined teachings of the prior art, but rather, separately argue the
references. However, the Examiner is relying upon the combination of
references, since “[o]ften, it will be necessary . . . to look to interrelated
teachings of multiple [references] . . . and the background knowledge
possessed by a person having ordinary skill in the art, all in order to
determine whether there was an apparent reason to combine the known
elements in the fashion claimed.” KSR Int’l Co. v. Teleflex Inc., 550 U.S.
398, 418 (2007). Here, we agree with the Examiner that the interrelated
teachings of Chou, Bernhardt, and Piesold together render claim 1 obvious,
since Bernhardt teaches the concept of adding a retention component and
Chou teaches size selection of particles into multiple chambers (FF 4-6, 13-
18).
Claims 22 and 26
Appellant relies upon overcoming the base rejection for claims 22 and
26, but also argues that “there is no reason or motivation to combine and
modify the cited references in order to arrive at a detection method for
detecting the presence of human immundodeficiency virus in a fluid as
claimed in present claim 22” (App. Br. 30). Appellant similarly argues that
claim 26 incorporates HIV detection (see App. Br. 31).
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We are not persuaded. Chou teaches that “[v]iruses may be
manipulated and/or analyzed as particles in microfluidic systems . . .
Exemplary viruses may include HIV” (Chou 8 ¶ 0167; FF 13). Thus, Chou
expressly teaches detection of HIV (FF 13) and Bernhardt teaches retention
of HIV using CD4 (FF 6).
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that Chou,
Bernhardt, and Piesold render claim 1 obvious.
SUMMARY
In summary, we reverse the rejection of claims 1-5, 7, 8, and 22-29
under 35 U.S.C. § 103(a) as obvious over Tullis, Bernhardt, Petersen and
Piesold.
We affirm the rejection of claims 1, 22, and 26 under 35 U.S.C. §
103(a) as obvious over Chou, Bernhardt, and Piesold. Pursuant to 37 C.F.R.
§ 41.37(c)(1)(vii)(2006), we also affirm the rejection of claims 2-5, 7, 8, 23-
25, and 27-29 as these claims were not argued separately.

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No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv)(2006).

AFFIRMED

alw

SMART & BIGGAR
438 UNIVERSITY AVENUE
SUITE 1500, BOX 111
TORONTO, ON M5G 2K8 CA CANADA