Ex Parte Knize et al

Board of Patent Appeals and Interferences

Dec 1, 2010

11378853 (B.P.A.I. Dec. 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.
11/378,853 03/16/2006 Mark G. Knize IL-11466 7536
24981 7590 12/01/2010
Lawrence Livermore National Security, LLC
LAWRENCE LIVERMORE NATIONAL LABORATORY
PO BOX 808, L-703
LIVERMORE, CA 94551-0808
EXAMINER
MARTIN, PAUL C
ART UNIT PAPER NUMBER
1657
MAIL DATE DELIVERY MODE
12/01/2010 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 MARK G. KNIZE, KRISTEN S. KULP,
and KUANG JEN J. WU
__________

Appeal 2010-008412
Application 11/378,853
Technology Center 1600
__________

Before CAROL A. SPIEGEL, TONI R. SCHEINER, 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 an
apparatus for analyzing cells. The Examiner 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 Specification teaches that the “invention relates to sample
preparation and more particularly to sample preparation of biological cells
for use with imaging mass spectrometry” (Spec. 1 ¶ 0002).
The Claims
Claims 1, 3, 5, and 6 are on appeal. Claim 1 is representative
of the argued claims. The remaining claims have not been argued
separately and therefore stand or fall together. 37 C.F.R. §
41.37(c)(1)(vii). Claim 1 reads as follows:
1. An apparatus for reliably and reproducibly
exposing the contents of a biological cell to an
analysis instrument, wherein said biological cell
has intracellular contents, comprising:
a sample handling unit, said sample
handling unit including
a first solid substrate with first substrate face
and
a second solid substrate with second
substrate face, wherein said first substrate face and
said second substrate face are opposed with an
unobstructed open space between said first
substrate face and said second substrate face and
wherein the biological cell is positioned between
said first substrate face and said second substrate
face in said open space, and
a framework with a mechanism for applying
a range of pressures to said first substrate face and
said second substrate face that can force said first
substrate face directly against said second substrate
face to entirely close said unobstructed open space,
said mechanism for applying a range of
pressures to said first substrate face and said
second substrate face operable to apply a release
pressure to the biological cell to release the
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intracellular contents of the biological cell and
reliably and reproducibly expose the intracellular
contents of the biological cell to the analysis
instrument, and
a pressure measuring device connected to
said sample handling unit for enabling said
framework to apply said release pressure to the
biological cell to release the intracellular contents
of the biological cell and reliably and reproducibly
expose the intracellular contents of the biological
cell to the analysis instrument.

The issues
A. The Examiner rejected claims 1, 3, and 5 under 35 U.S.C. § 103(a) as
obvious over Takamatsu2 and Malone3 (Ans. 4-6).
B. The Examiner rejected claims 1, 3, 5, and 6 under 35 U.S.C. § 103(a)
as obvious over Takamatsu, Malone, and Roddy4 (Ans. 6-7).
A. 35 U.S.C. § 103(a) over Takamatsu and Malone
The Examiner finds it obvious “to modify the apparatus of Takamatsu
et al. to include a pressure measuring device as taught by Malone et al.
because this would provide important data as to what pressures are required

2 Takamatsu et al., On the mechanism of cell lysis by deformation,
38 J. BIOMECHANICS 117-124 (2005).
3 Malone et al., Effects of High Pressure on the Viability,
Morphology, Lysis, and Cell Wall Hydrolase Activity of
Lactococcus lactis subsp. cremoris, 68 APPLIED ENVIRONMENTAL
MICROBIOLOGY 4357-4363 (2002).
4 Roddy et al., Identification of Cellular Sections with Imaging
Mass Spectrometry Following Freeze Fracture, 74 ANALYTICAL
CHEMISTRY 4020-4026 (2002).
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to lyse the cells and at what pressures the appearance and degree of certain
morphologies occur” (Ans. 5).
Appellants note that “claim 1 includes the following claim limitations
. . . a mechanism for applying a range of pressures to said first substrate face
and said second substrate face that can force said first substrate face directly
against said second substrate face to entirely close said unobstructed open
space” (App. Br. 12-13). Appellants contend that in “the Takamatsu
reference a cell suspension is only deformed. Two glass beads are shown
positioned between the microslide and the cover glass. The two glass beads
prevent the microslide and the cover glass from contacting each other” (id. at
13).
Appellants also contend that the
Final Rejection does not establish a reasonable
expectation of success with the proposed
combination. There could be no combination of the
Primary Takamatsu reference and the Secondary
Malone reference that would provide a reasonable
expectation of success or that would show
Appellants’ invention of claims 1, 3, and 5. The
Takamatsu reference has no need to include
Applicants’ claim element, “a pressure measuring
device . . . ”
(id. at 15).
Appellants contend that the “Final Rejection does not provide an
explanation of how or why the Primary Takamatsu reference and the
Secondary Malone reference would or could be combined to produce the
missing claim limitations” (id.).
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The issue with respect to this rejection is: Does the preponderance of
the evidence of record support the Examiner’s conclusion that Takamatsu
and Malone render obvious the apparatus of claim 1?
Findings of Fact
1. Takamatsu teaches that a “mechanical device with two parallel
temperature-controlled stages was used to keep the two glass surfaces
parallel during the compression process and to ensure that the procedure was
performed at a precisely controlled temperature (Fig. 1)” (Takamatsu 118,
col. 2).
2. Figure 1 of Takamatsu is reproduced below:

“Fig. 1 Experimental technique for observation of deformed cells”
(Takamatsu 119, col. 1).
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3. Takamatsu teaches that the “cells became deformed between
the two flat surfaces and the distance between these surfaces was determined
from the known diameter of the glass beads. The glass plates with the
compressed cells were then placed under a microscope” (Takamatsu 118,
col. 2).
4. Takamatsu teaches that the “stage of the microscope was also
maintained at a controlled temperature. The phase-contrast and fluorescence
images observed using a 10x objective at the same position were recorded
using a digital camera” (Takamatsu 118, col. 2).
5. Malone teaches a study which “investigated the effects of high
pressure on the viability, structure, lysis, and cell wall hydrolase activity of
two L. lactis subsp. cremoris strains (MG1363 and SK11) in buffer
suspensions. This will provide a better understanding of the biochemical and
microbiological basis for changes that occur in pressure-treated cheeses”
(Malone 4357, col. 2).
6. Malone teaches that “the sample was pressure treated to a
pressure in the range of 100 to 800 MPa for 5 min at 25°C in a Quintus high-
pressure food processor” (Malone 4358, col. 1).
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
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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.” 550 U.S. at 421.
Analysis
Takamatsu teaches an apparatus with a sample handling unit, first and
second solid substrates with unobstructed faces opposed to one another, and
a framework for applying a range of pressures to the substrate faces (FF 1-
4). Malone teaches investigating the effects of pressure on cell lysis (FF 5).
Malone teaches that “the sample was pressure treated to a pressure in the
range of 100 to 800 MPa for 5 min at 25°C in a Quintus high-pressure food
processor” (Malone 4358, col. 1).
Applying the KSR standard of obviousness to the findings of fact, we
agree with the Examiner that it would have been obvious to include a
pressure sensor in the device of Takamatsu “as taught by Malone et al.
because this would provide important data as to what pressures are required
to lyse the cells and at what pressures the appearance and degree of certain
morphologies occur” (Ans. 5). Such a combination is merely a “predictable
use of prior art elements according to their established functions.” KSR, 550
U.S. at 417.
Appellants note that “claim 1 includes the following claim limitations
. . . a mechanism for applying a range of pressures to said first substrate face
and said second substrate face that can force said first substrate face directly
against said second substrate face to entirely close said unobstructed open
space” (App. Br. 12-13). Appellants contend that in “the Takamatsu
reference a cell suspension is only deformed. Two glass beads are shown
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positioned between the microslide and the cover glass. The two glass beads
prevent the microslide and the cover glass from contacting each other” (App.
Br. 13; also see Reply Br. 5-6).
We are not persuaded. Claim 1 is drawn to an apparatus, and not a
method of using that apparatus. The glass beads are added with
Takamatsu’s sample, and are not part of the device itself (FF 3). Use of a
different sample without the glass beads would permit the first and second
substrate faces of Takamatsu’s apparatus to close entirely, as required by
claim 1. See Catalina Marketing International, Inc. v. Coolsavings.com,
Inc., 289 F.3d 801, 810 (Fed. Cir. 2002) (“[D]isputed preamble language
does not limit Claim 1-an apparatus claim. To hold otherwise would
effectively impose a method limitation on an apparatus claim without
justification”).
Appellants also contend that the
Final Rejection does not establish a reasonable
expectation of success with the proposed
combination. There could be no combination of the
Primary Takamatsu reference and the Secondary
Malone reference that would provide a reasonable
expectation of success or that would show
Appellants’ invention of claims 1, 3, and 5. The
Takamatsu reference has no need to include
Applicants’ claim element, “a pressure measuring
device . . .”
(App. Br. 15).
We are not persuaded. Takamatsu teaches a device which permits
increasing the pressure and Malone teaches devices in which pressure is
measured. We agree with the Examiner that it would have been obvious to
include a means for measuring the pressure applied by Takamatsu’s device
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“because this would provide important data as to what pressures are required
to lyse the cells and at what pressures the appearance and degree of certain
morphologies occur” (Ans. 5), and there would have been a reasonable
expectation of success in adapting known pressure measuring devices of
Malone to known devices which apply pressure as in Takamatsu. Kubin
stated that “[r]esponding to concerns about uncertainty in the prior art
influencing the purported success of the claimed combination, this court [in
O’Farrell] stated: ‘[o]bviousness does not require absolute predictability of
success … all that is required is a reasonable expectation of success.”’ In
re Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009) (citing In re O’Farrell, 853
F.2d 894, 903-904 (Fed. Cir. 1988)).
Appellants contend that the “Final Rejection does not provide an
explanation of how or why the Primary Takamatsu reference and the
Secondary Malone reference would or could be combined to produce the
missing claim limitations” (App. Br. 15).
We are not persuaded. The Examiner provides a specific combination
which addresses the limitations of claim 1 (FF 1-6). Again, the Examiner
reasons it would have been obvious “to modify the apparatus of Takamatsu
et al. to include a pressure measuring device as taught by Malone et al.
because this would provide important data as to what pressures are required
to lyse the cells and at what pressures the appearance and degree of certain
morphologies occur” (Ans. 5). We agree with the reasoning of the
Examiner. The Examiner's reasoning for combining the references need not
disclose the same purpose as Appellants in order to establish obviousness
under 35 U.S.C. § 103. In re Dillon, 919 F.2d 688, 692-93 (Fed. Cir. 1990).
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Conclusion of Law
The preponderance of the evidence of record supports the Examiner’s
conclusion that Takamatsu and Malone render obvious the apparatus of
claim 1.
B. 35 U.S.C. § 103(a) over Takamatsu, Malone, and Roddy
The Examiner finds that the “teachings of Takamatsu et al. and
Malone et al. were discussed above. Neither Takamatsu et al. nor Malone et
al. taught an apparatus wherein the first solid and second solid substrates are
silicon or stainless steel” (Ans. 6). The Examiner finds that “Roddy et al.
teaches the use of two solid silicon wafers in a device for wherein an
aqueous solution of cells is positioned between the two wafers” (id.).
The Examiner finds it obvious
to modify mechanism for cell lysis by deformation
comprising a sample handling unit including a
cover glass and a slide glass as taught by
Takamatsu et al. to use two solid silicon substrates
as taught by Roddy et al. because both references
teach the use of solid silicon and glass substrates in
cell compression techniques to expose the contents
of biological cells to analysis.
(Ans. 7.)
Appellants reiterate the argument that in “the Takamatsu reference a
cell suspension is only deformed. Two glass beads are shown positioned
between the microslide and the cover glass. The two glass beads prevent the
microslide and the cover glass from contacting each other” (App. Br. 18).
Appellants also reiterate the argument that the “Takamatsu reference has no
need to include Applicants' claim element, ‘a pressure measuring device
connected to said sample handling unit . . .’” (App. Br. 21).
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We are not persuaded. As we have already noted, the claims are
drawn to an apparatus, not a method. The glass beads in Takamatsu are not
part of the apparatus, but rather are included in the sample which Takamatsu
analyzes. The apparatus itself does not include glass beads and would
therefore satisfy the claim limitation for two substrate faces which “entirely
close said unobstructed space” (see Claim 1). It is only in Takamatsu’s
application of the apparatus to a particular sample, not the apparatus itself,
that the glass beads are introduced (FF 1-4). As we noted, we agree with
the Examiner’s reason to incorporate a pressure measuring device (see Ans.
5).
SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C. §
103(a) as obvious over Takamatsu and Malone. Pursuant to 37 C.F.R. §
41.37(c)(1)(vii)(2006), we also affirm the rejection of claims 3 and 5, as
these claims were not argued separately.
We affirm the rejection of claim 6 under 35 U.S.C. § 103(a) as
obvious over Takamatsu, Malone, and Roddy.
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

Appeal 2010-008412
Application 11/378,853

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cdc

Lawrence Livermore National Security, LLC
LAWRENCE LIVERMORE NATIONAL LABORATORY
PO BOX 808, L-703
LIVERMORE, CA 94551-0808