Ex Parte Peltier

Patent Trial and Appeal Board

Jan 3, 2018

13636665 (P.T.A.B. Jan. 3, 2018)

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.
13/636,665 10/24/2012 Eric Peltier LAV0143.001APC 9949
20995 7590 01/05/2018
KNOBBE MARTENS OLSON & BEAR LLP
2040 MAIN STREET
FOURTEENTH FLOOR
IRVINE, CA 92614
EXAMINER
VISONE, THOMAS J
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
01/05/2018 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):
jayna.cartee@knobbe.com
efiling @ knobbe. com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ERIC PELTIER
Appeal 2017-001145
Application 13/636,665
Technology Center 1600
Before DEMETRA J. MILLS, JEFFREY N. FREDMAN, and
ROBERT A. POLLOCK, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to a process
for preparing and analyzing a plurality of cell suspensions. The Examiner
rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
Statement of the Case
Background
The invention relates to the preparation of cell suspensions for
cytological analysis. “To allow the analysis of a large number of samples
and at a fast processing rate, it is sought to automate the preparation of
samples for analysis and the actual analysis procedure” (Spec. 1:20-22).
1 Appellant identifies the Real Party in Interest as Novacyt (see App. Br. 3).
Appeal 2017-001145
Application 13/636,665
“Such automated equipment uses devices generating a certain numbers of
artefacts entailing in particular filter management and pressure problems
with changes in cell morphology and problems of filter mesh clogging with
debris” (id. 1:26—30).
The Claims
Claims 1—8, 24, and 25 are on appeal. Independent claim 1 is
representative and reads as follows:
1. A process for preparing and analyzing a plurality of cell
suspensions comprising the following successive steps:
(a) loading a plurality of sample containers on a platform,
each sample container comprising a cell suspension to be
analyzed;
(b) loading a plurality of analysis containers on the
platform;
(c) pipetting sample up and down in each of the sample
containers to break up cell clusters, wherein the cell clusters are
broken up by ejecting and fracturing the cell clusters against a
wall of the sample containers, thereby producing a cell
suspension;
(d) permitting cells in the cell suspension to settle in the
sample container for a predetermined time period, wherein a
gradient of cells of interest is established in the sample
containers; and
(e) selecting cells from each of the sample containers by
differential decanting comprising:
(i) at least one step of micro-mixing the cells in
each of the sample containers, wherein a volume of
solution is aspirated with a pipettor just above the bottom
of a decanting cone of the sample containers and then
reinjected at the same point to detach the cells from the
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Application 13/636,665
bottom of the decanting cone, thereby eliminating any
dead volume or residue of cells at the bottom of the
decanting cone, and
(ii) aspirating a volume of cells from a position in
the gradient of cells in each of the sample containers.
The Issues
A. The Examiner rejected claims 1—3, 7, 8, 24, and 25 under 35 U.S.C.
§ 103(a) as obvious over Peltier ’925,2 Barber,3 Ueno,4 John,5 Wakeman,6
Anderson ’343,7 Anderson ’884,8 Abilez,9 and Menzel10 (Final Act. 2—7).
B. The Examiner rejected claims 4 and 5 under 35 U.S.C. § 103(a) as
obvious over Peltier ’925, Barber, Ueno, John, Wakeman, Anderson ’343,
Anderson ’884, Abilez, Menzel, Peltier ’019,11 and Peltier ’68912 (Final Act.
7-8).
C. The Examiner rejected claim 6 under 35 U.S.C. § 103(a) as obvious
over Peltier ’925, Barber, Ueno, John, Wakeman, Anderson ’343, Anderson
’884, Abilez, Menzel, and Peltier ’01813 (Final Act. 8—9).
2 Peltier, US 2010/0089925 Al, publ. Apr. 15, 2010 (“Peltier ’925”).
3 Barber et al., US 5,408,891, issued Apr. 25, 1995 (“Barber”).
4 Ueno et al., EP 527059 Al, publ. Feb. 10, 1993 (“Ueno”).
5 John, US 2004/0086484 Al, publ. May 6, 2004 (“John”).
6 Wakeman et al., Neural Progenitors, in Human Adult Stem Cells, Human
Cell Culture 7, 1—44 (J.R. Masters, B.0. Palsson, eds.) (2009) (“Wakeman”).
7 Anderson, US 2003/0059343 Al, publ. Mar. 27, 2003 (“Anderson ’343”).
8 Anderson, US 2002/0023884 Al, publ. Feb. 28, 2002 (“Anderson ’884”).
9 Abilez et al., US 2007/0238169 Al, published Oct. 11, 2007 (“Abilez”).
10 Menzel et al., US 6,174,678 Bl, issued Jan. 16, 2001 (“Menzel”).
11 Peltier, FR 2,922,019 Bl, publ. Apr. 10, 2009 (“Peltier ’019”).
12 Peltier, US 2010/0178689 Al, publ. July 15, 2010 (“Peltier ’689”).
13 Peltier, US 8,478,018 B2, issued July 2, 2013 (“Peltier ’018”).
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Application 13/636,665
A. 35 U.S.C. § 103(a) over Peltier ’925, Barber, Ueno, John, Wakeman,
Anderson ’343, Anderson ’884, Abilez, andMenzel
The Examiner finds Peltier ’925 teaches “analyzing a sample
comprising the use of reception plate comprising a plurality of pierceable
and self-sealing bottles or flasks . . . [that] can be used in conjunction with
an automated pipette” as “part of a larger analysis system” (Final Act. 2—3).
The Examiner acknowledges Peltier ’925 “does not teach transferring
a sample of cell suspension to a plurality of analysis containers”; does “not
teach the additional step of breaking up cell clumps or mixing the cells
suspension by pipetting”; and does “not teach the formation of a cellular
gradient and the subsequent aspiration, using a pipette, of a specific level of
the cellular gradient for analysis” (Final Act. 3—4).
The Examiner finds Barber teaches “cell suspensions, such as blood,
can be transferred from sample containers to, e.g., analysis containers
comprising one or more reagents though automated pipettes” (Final Act. 3).
The Examiner finds Wakeman teaches “breaking up cell clusters by
pipetting and gently triturating the cell clutters at a 45-degree angle against
the wall of a conical tube” {id. at 4). The Examiner finds Anderson ’884
teaches “sampling of specific gradient layers, using an automated pipette,
and depositing the layers into a separate container for analysis” (id. at 4).
The Examiner finds the combination obvious because it would “allow
for automated and rapid analysis of cell suspensions” (Final Act. 3); because
“Wakeman further teaches the pipetting method advantageously breaks up
large cell clusters” (id. at 4); and to “allow for layer specific sampling from
the cellular gradient for subsequent analysis” (id. at 5).
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Application 13/636,665
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that the cited prior art renders
claim 1 obvious?
Findings of Fact
1. The Specification teaches:
The « micro-mixing » step consists of aspirating a
volume of cytological solution just above the bottom of the
decanting cone of the bottle, for example at a distance of 2 mm,
the volume being between 20 pL and 200 pL e.g. 100 pL, then
the pipetting means 20 re-inject part of the sampled volume e.g.
50 pL, substantially at the same point to avoid a « dead volume
or residue » 100, i.e. to detach the cells from the bottom of the
decanting cone 56 via the injection force of the pipetting means
20 and to obtain highly localized replacing in suspension.
This « micro-mixing » step is optional and can be
replaced by a simple sampling step of a volume of cytological
solution.
(Spec. 14:16-24).
2. Peltier ’925 teaches loading a “plurality of flasks on a tray and
to insert the tray into a machine for carrying out filling or sampling of the
contents of the flasks. The flasks are held on the tray, which moves beneath
the machine or above which a machine comprising filling or sampling means
moves” (Peltier ’925 12).
3. Barber teaches: “Automated pipettors are employed on such
analyzers to transfer the patient samples and reagents as required for the
specified analysis ... to pipette and deliver one or more reagents from
reagent containers to the reaction cell, either with the same probe or with
one or more reagent delivery probes” (Barber 1:25—38).
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4. Ueno teaches “a method of agitating and sampling a liquid
specimen, comprising sucking specimen from a specimen container with a
pipette, discharging the sucked specimen so as to agitate the specimen, and
sampling the specimen with the pipette” (Ueno 2:33—35).
5. John teaches: “Disaggregate the clump by pipetting up and
down gently” (John 1228).
6. Wakeman teaches:
Resuspend the cell pellet in 2 mL fresh pre-warmed NB-B27
growth medium with a P1000 pipette and gently triturate at a
45-degree angle against the wall of the conical tube (6-8 times)
until large clusters are no longer visible and the solution has a
homogenous “milky” and “sandy” appearance (warning: do not
hold the pipette tip firmly against the tube or triturate with
excessive force to avoid shearing). It is important to thoroughly
break up the cell pellet, again gently, but thoroughly before re­
plating. To the cell suspension, add 2 mL of NB-B27 growth
medium, evenly mix the cells by simple trituration, and return
the entire contents of the tube to its original flask.
(Wakeman 16).
7. Anderson ’343 teaches “the formation of sets of gradients in
parallel. These are particularly useful for fractionation of cellular or
subcellular particles from biological samples” (Anderson ’343 11).
8. Anderson ’343 teaches:
The present invention involves a system for producing
liquid density gradients by using a series of liquids of
increasing density prepared by mixing a starting set of liquids
of differing density. This is performed using an automatic
microprocessor controlled system for pipetting and mixing the
liquids according to a set or adjustable computer program, and a
device for introducing aliquots of the series of liquids into
centrifuge tubes to produce a gradient. It is particularly
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desirable that uniformly sharp interfaces can be made between
the individual liquids in the gradients whether they are density
gradients or a different type of gradient.
(Anderson ’343 1 80).
9. Anderson’884 teaches
It should be understood that the pipette 6 may be
positioned above the float 1 by hand, by a manually operated
positioning device, or may be connected to a robotic device that
includes a feedback controller that includes means for
determining the location of the layers in the vessel 1, and the
relative position of the pipette 6 and the float 1 to provide an
accurate means for removing each layer or zone.
(Anderson ’884 145).
10. Abilez teaches “each tube for each well was centrifuged . . .
The supernatant of media and PBS was then suctioned . . . leaving the pellet
of cells intact at the bottom of the tube. . . . media was added . . . Pipetting
the cells up and down in each tube was used to break the cells apart” (Abilez
1149).
11. Menzel teaches
The cultures were made permeable by repeated pipetting up and
down (in place; lOx). At this time, a P-galactosidase assay was
initiated by using an automated pipetting device to carefully (so
as to not disturb the CHCI3 in the bottom of the microtiter plate
well).
(Menzel 19:60-66).
Principles of Law
“An examiner bears the initial burden of presenting a prima facie case
of obviousness.” In re Huai-Hung Kao, 639 F.3d 1057, 1066 (Fed. Cir.
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Application 13/636,665
2011). A proper § 103 analysis requires “a searching comparison of the
claimed invention — including all its limitations — with the teaching of the
prior art.” In re Ochiai, 71 F.3d 1565, 1572 (Fed. Cir. 1995).
Analysis
Appellant contends “the at least one micro-mixing step includes
aspirating a volume of solution just above the bottom of the decanting cone
of the bottle and then reinjecting it at the same point, not simply of pipetting
up and down at any location within the sample container” (App. Br. 10).
Appellant contends: “While the Abilez and Menzel references disclose
methods of pipetting cells up and down, they do not provide any suggestion
of the micro-mixing step as recited in the claims” (id.).
Appellants specifically contend “Abilez does not describe a micro­
mixing step, wherein a volume of solution is aspirated just above the bottom
of the decanting cone of the bottle or that it is reinjected at the same point”
and “Menzel does not describe a decanting cone or that a volume of solution
is aspirated just above the bottom of a decanting cone of a bottle” (App. Br.
11).
The Examiner responds “the prior art clearly recognizes the concept
of aspirating a volume of fluid from a culture vessel and reinjecting the fluid
back into the vessel to create sufficient force to detach cells from a surface
(which would include the bottom) of the vessel” (Ans. 10). The Examiner
finds “Appellant is applying a simple, rudimentary pipetting technique to a
specific application to remove cells from the bottom of conical tube in a
matter consistent with the prior art” (id.).
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Application 13/636,665
We find that Appellant has the better position. While we agree with
the Examiner that pipetting is a fundamental technique, including the use of
repeated pipetting to detach cells from the bottom of a container (FF 10),
claim 1 requires this “micro-mixing” step to be performed in a solution with
a gradient solution and performing a “differential decanting” as required by
step (e)(ii) that allows separate aspiration of different cell volumes. As
Appellants contend “the micro-mixing step eliminates any dead volume or
residue of cells at the bottom of the decanting zone, without disrupting the
gradient of cells established in step (d)” (Reply Br. 2). This absence of
disruption is required by step (e)(ii) in which cells are aspirated “from a
position in the gradient,” so the micro-mixing step cannot disrupt the
gradient or step (e)(ii) would not be possible.
The only reference which discusses mixing cells that are associated
with a gradient is Menzel,14 who performs a chloroform extraction that
mixes the cells with chloroform, allows the aqueous and chloroform phases
to separate, and then differentially decants the aqueous phase for a [3-
galactosidase assay (FF 11). However, Menzel’s process significantly
differs from that of the claim because Menzel does not performing the
mixing pipetting in an already formed gradient as required by claim 1 steps
(d) and (e), but rather Menzel pipets the cells and then allows a gradient to
form.
14 We recognize that both Anderson ’343 and Anderson ’884 discuss the use
of gradients with pipetting, but the Examiner does not identify teachings in
either for performing mixing with the pipets in already formed gradients (FF
7-9).
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Therefore, none of the cited prior art references provide any teaching
or suggestion to form a gradient with cells in suspension, perform a micro­
mixing of the cells at the bottom of the gradient but remain able to aspirate
cells from “a position in the gradient of cells” as required by claim 1.
“[Rejections on obviousness grounds cannot be sustained by mere
conclusory statements; instead, there must be some articulated reasoning
with some rational underpinning to support the legal conclusion of
obviousness.” KSRInt’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007).
We conclude that the Examiner has not satisfied the burden to present
a prima facie case of obviousness because no reason or evidence was
provided to explain why the particular order of the steps was obvious, in
which a gradient was first formed followed by repeated pipetting at the
gradient bottom that did not mix with sufficient effect to prevent aspiration
“of cells from a position in the gradient.”
Conclusions of Law
The evidence of record does not support the Examiner’s conclusion
that the cited prior art renders claim 1 obvious.
B.-C. 35 U.S.C. § 103(a)
These rejections rely upon the underlying obviousness rejection over
Peltier ’925, Barber, Ueno, John, Wakeman, Anderson ’343, Anderson ’884,
Abilez, and Menzel. Having reversed the rejection of claim 1, we also
necessarily reverse these obviousness rejections because the Examiner does
not identify where Peltier ’019, Peltier ’689, or Peltier ’018 suggest a
process as required by claim 1.
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Application 13/636,665
SUMMARY
In summary, we reverse the rejection of claims 1—3, 7, 8, 24, and 25
under 35 U.S.C. § 103(a) as obvious over Peltier ’925, Barber, Ueno, John,
Wakeman, Anderson ’343, Anderson ’884, Abilez, and Menzel.
We reverse the rejection of claims 4 and 5 under 35 U.S.C. § 103(a)
as obvious over Peltier ’925, Barber, Ueno, John, Wakeman, Anderson ’343,
Anderson ’884, Abilez, Menzel, Peltier ’019, and Peltier ’689.
We reverse the rejection of claim 6 under 35 U.S.C. § 103(a) as
obvious over Peltier ’925, Barber, Ueno, John, Wakeman, Anderson ’343,
Anderson ’884, Abilez, Menzel, and Peltier ’018.
REVERSED
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